tag:theconversation.com,2011:/id/topics/cannabinoids-12042/articlesCannabinoids – The Conversation2024-02-06T13:53:28Ztag:theconversation.com,2011:article/2220242024-02-06T13:53:28Z2024-02-06T13:53:28ZDanish dog owners are medicating their pets with unlicensed cannabis products – is it safe?<figure><img src="https://images.theconversation.com/files/573280/original/file-20240204-27-f7ceiz.jpg?ixlib=rb-1.1.0&rect=0%2C21%2C7184%2C4764&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/hand-giving-dog-cbd-oil-by-2192674331">24-K Production/Shutterstock</a></span></figcaption></figure><p>Medical cannabis, often in the form of cannabidiol (CBD) oil, is one of the most recent trends in the human health and wellness world. Unsurprisingly, this trend has made its way to our pets, with a recent study suggesting that <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0296698">38% of surveyed Danish dog owners</a> routinely gave their pets some form of cannabis product.</p>
<p>Because many people actively promote the use of CBD to support their own health and wellbeing, the use of <a href="https://www.bluecross.org.uk/advice/dog/health-and-injuries/cbd-for-dogs">CBD oil for pets</a> is attracting increased attention from vets and pet owners alike.</p>
<p>Previous studies suggest that <a href="https://www.veterinarycannabis.org/uploads/1/1/6/0/116053487/dog_owner_use___perceptions.pdf">80% of dog owners</a> in the US and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563876/">Canada</a> had bought cannabis products for their pet. While availability and regulatory differences might account for this variance, it is clear that cannabinoids are regularly being given to pets globally.</p>
<p>It is important to note that CBD doesn’t contain the psychoactive substance THC (tetrahydrocannabinol) that is responsible for some of the serious effects seen in pets after accidental ingestion of <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261909">cannabis and derivatives</a>, so its use won’t make your pet high or give them the munchies.</p>
<p>But, is CBD safe for our pets and could it be a useful addition to our pet’s healthcare regime? </p>
<h2>Can CBD help our pets?</h2>
<p>The use of CBD oil by people to support conditions such as <a href="https://doi.org/10.7326/M21-4520">chronic pain</a>, <a href="https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.13345">migraines</a>, <a href="https://doi.org/10.7812/TPP/18-041">anxiety</a> and <a href="https://doi.org/10.5167/uzh-197549">epilespy</a> has led many people to consider its use for their pets, who often suffer from similar conditions.</p>
<p>While anecdotal reports of the benefits of CBD use are typically positive, many studies have failed to find an <a href="https://www.ncbi.nlm.nih.gov/books/NBK425767/">effect</a>. This means that its value as a potential therapeutic aid remains poorly understood.</p>
<p>However, in line with increased interest in CBD to support human health, research is <a href="https://www.waltham.com/new-study-shows-cannabidiol-cbd-effective-reducing-stress-dogs">exploring potential</a> benefits for pets, too, with some interesting outcomes.</p>
<h2>Pet benefits</h2>
<p>CBD oil has been shown to significantly reduce the <a href="https://www.frontiersin.org/articles/10.3389/fvets.2023.1112604/full">signs of stress</a> in dogs during travel and separation – two areas of concern for many pet owners. </p>
<p>For dogs suffering from osteoarthritis, CBD oil resulted in <a href="https://www.frontiersin.org/articles/10.3389/fvets.2018.00165/full">increased activity and decreased pain scores</a>, as assessed by a vet. Indeed, <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0296698#pone.0296698.ref016">36% of respondents in the Danish study</a> indicated that they used cannabinoids for pain management in their pets. This group also reported <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0296698#pone.0296698.ref016">high perceived efficacy</a> of CBD in managing their dog’s pain.</p>
<p>For dogs with skin irritation as the result of allergy, CBD <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/vde.13077">reduced itching</a> but not skin damage or lesions. In the Danish study, <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0296698#pone.0296698.ref036">11% of respondents</a> reported using CBD to help their dog with allergies, and the perceived outcome was good.</p>
<p>While CBD is typically given as drops or oil added to food, hemp-based treats can also be used. Giving <a href="https://doi.org/10.3389/fvets.2020.569565">CBD-infused treats</a> to pets suffering from noise anxiety, however, failed to show a positive outcome.</p>
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<img alt="Hemp-based dog treats" src="https://images.theconversation.com/files/573281/original/file-20240204-17-mb9uh1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/573281/original/file-20240204-17-mb9uh1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/573281/original/file-20240204-17-mb9uh1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/573281/original/file-20240204-17-mb9uh1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/573281/original/file-20240204-17-mb9uh1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/573281/original/file-20240204-17-mb9uh1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/573281/original/file-20240204-17-mb9uh1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">CBD-infused treats won’t help with noise anxiety.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-macro-treat-dogs-green-hemp-1733258240">PRO Stock Professional/Shutterstock</a></span>
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<h2>CBD challenges</h2>
<p>In many countries, treating pets with CBD is <a href="https://www.bsavalibrary.com/content/chapter/10.22233/9781910443514.chap8#html_fulltext">not authorised or approved</a>. In the UK, only a vet can prescribe a <a href="https://www.bluecross.org.uk/advice/dog/health-and-injuries/cbd-for-dogs">human CBD preparation</a> for a pet.</p>
<p>Cannabidiol is considered a complementary medicine and vets advise that it should not be used <a href="https://www.bsavalibrary.com/content/chapter/10.22233/9781910443514.chap8#html_fulltext">in place of proven treatments</a>. CBD could also <a href="https://www.ejinme.com/article/S0953-6205(18)30004-9/fulltext">interact</a> with prescribed drugs in ways that aren’t currently known.</p>
<p>Toxicity reports are rare, and healthy dogs appear to tolerate long-term, <a href="https://www.frontiersin.org/articles/10.3389/fvets.2022.977457/full">daily doses of CBD</a>. However, side-effects such as <a href="https://www.frontiersin.org/articles/10.3389/fvets.2023.1204526/full">vomiting, diarrhoea, lethargy and difficulty moving</a> have been recorded in dogs. <a href="https://www.bsavalibrary.com/content/chapter/10.22233/9781910443514.chap8#html_fulltext">Side-effects</a> in cats include excess licking and salivation, pacing, vomiting and grimacing. We still don’t have good safety and efficacy data, and effective dose rates are unclear.</p>
<p>A significant challenge in being able to identify consistent outcomes in CBD use is the variability in quality, <a href="https://www.frontiersin.org/articles/10.3389/fvets.2023.1204526/full#ref26">preparations and potency</a> of the active ingredient. CBD can also be provided in <a href="https://www.mdpi.com/2076-2615/9/10/832">edible treats</a>, oils and supplements or as <a href="https://www.ingentaconnect.com/content/cvma/cjvr/2018/00000082/00000003/art00002">topical creams</a> to be applied to the skin. These all have different uses, making outcome comparisons tricky.</p>
<p>There is also the potential for <a href="https://www.mayoclinicproceedings.org/article/S0025-6196(19)30007-2/fulltext">mislabelling and contamination of CBD products</a>, and production and distribution regulation is <a href="https://www.mayoclinicproceedings.org/article/S0025-6196(19)30007-2/fulltext">poor</a>. This can make it difficult for pet owners to make informed, safe and effective choices for their pets.</p>
<p>While the use of CBD for pets appears to be common, the potential downsides and concerns do need to be considered. How much CBD can be safely administered to our pets for effective use across a range of conditions remains largely unknown. </p>
<p>If you are thinking about using CBD for your pet, always speak to your vet in the first instance – they will be able to <a href="https://vmd.blog.gov.uk/2022/06/28/can-i-buy-cbd-oil-cannabidiol-for-my-pet/">advise you</a> on the safest and most legally appropriate way to do so.</p><img src="https://counter.theconversation.com/content/222024/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jacqueline Boyd is affiliated with The Kennel Club (UK) through membership, as Chair of the Activities Health and Welfare Subgroup and member of the Dog Health Group. Jacqueline is a full member of the Association of Pet Dog Trainers (APDT #01583) and she also writes, consults and coaches on canine matters on an independent basis, in addition to her academic affiliation at Nottingham Trent University.</span></em></p>Thirty-eight per cent of Danish dog owners surveyed said they dosed canines with cannabis products.Jacqueline Boyd, Senior Lecturer in Animal Science, Nottingham Trent UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2187842023-12-12T19:53:39Z2023-12-12T19:53:39ZCanada owes its veterans new mental health tools: Access to psychedelic therapies is overdue<iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/canada-owes-its-veterans-new-mental-health-tools-access-to-psychedelic-therapies-is-overdue" width="100%" height="400"></iframe>
<p>The Canadian Senate Subcommittee on Veterans Affairs recently released a striking report entitled <a href="https://sencanada.ca/en/info-page/parl-44-1/veac-psychedelic-therapies/"><em>The Time is Now: Granting Equitable Access to Psychedelic Therapies</em></a>. </p>
<p>To address high rates of suicide and post-traumatic stress disorder (PTSD) among veterans, the report calls on Veterans Affairs Canada (VAC) to immediately implement “a robust research program funded by VAC and the Department of National Defence (DND) in partnership with Health Canada, the Canadian Institutes of Health Research, and all other relevant partners.”</p>
<p>With psychedelic research, Veterans Affairs Canada has a real chance to live up to its mandate “to provide exemplary, client-centred services and benefits that respond to the needs of veterans, our other clients and their families.” </p>
<p>As a psychedelics researcher with an interest in veteran health, I couldn’t be happier, especially with the Senate focus on timeliness, equity and access. </p>
<p>Not only is <a href="https://www.researchgate.net/publication/372244882_Knowledge_Synthesis_in_the_Science_of_Psilocybin_Scoping_Reviews_of_Clinical_and_Preclinical_Research">my PhD on the therapeutic application of psilocybin</a>, but my father was a veteran of the Canadian Forces, as is my brother and two uncles and both of my grandfathers. I grew up on Canadian Forces bases.</p>
<h2>Canada’s veterans</h2>
<p>Lt. Col. (ret’d) Jack Shore, my father, graduate of the <a href="https://www.btb.termiumplus.gc.ca/tpv2alpha/alpha-eng.html?lang=eng&srchtxt=APPRENTICE%20SOLDIER">Soldier Apprentice Program</a> and a United Nations Peacekeeper in the <a href="https://peacekeeping.un.org/sites/default/files/past/onucB.htm">Congo mission</a> of the early 1960s, passed away as I was working as a guest co-editor of a special edition of the <a href="https://jmvfh.utpjournals.press/toc/jmvfh/current"><em>Journal of Military, Veteran and Family Health</em></a>. The theme of the edition is “Therapeutic use of psychedelics, entheogens, entactogens, cannabinoids and dissociative anesthetics for military members and veterans.” </p>
<p>While my Dad rarely talked about his time in the Congo, he experienced what we would now recognize as moral injury, and most likely PTSD. These conditions directly shaped our family life and upbringing. That was before Sudan, Rwanda, the Yugoslav wars and Afghanistan.</p>
<p>My childhood on bases occurred in time of relative peace, but Canada has now had a few generations of soldiers experience active combat. </p>
<p>The <a href="https://patientsmedicalhome.ca/resources/best-advice-guides/best-advice-guide-caring-for-veterans/">629,000 veterans living in Canada have rates of depression, anxiety and substance use disorder that are higher than the civilian population</a>. <a href="https://doi.org/10.1002/jts.21956">One in seven is living with PTSD</a>. Veterans are <a href="https://www.mcgill.ca/maxbellschool/files/maxbellschool/ofha_veteran_homelessness_policy_brief_-_2023.pdf">two to three times more likely</a> to experience homelessness compared to the general population. </p>
<h2>Duty of care</h2>
<p>To veterans of the Canadian Forces and to their families, we owe a duty of care, and not just to provide services and access to novel treatments. We also have a duty to care enough to do the science well and to tackle the public policy challenges (including regulatory drug reform) necessary to provide Canadian veterans with effective care.</p>
<blockquote>
<p>“It is the Government of Canada’s duty to assure veterans that it is doing everything in its power, immediately, to respect its solemn commitment to support, at any cost, those who chose to defend us with honour.” — <a href="https://sencanada.ca/en/info-page/parl-44-1/veac-psychedelic-therapies/">The Subcommittee on Veterans Affairs, Senate of Canada</a> </p>
</blockquote>
<p>The role of the VAC includes paying for the cost of health-care benefits and other services for veterans through the <a href="https://www.canada.ca/en/treasury-board-secretariat/topics/benefit-plans/plans/health-care-plan.html">Public Service Health Care Plan</a> and supplemental treatment benefits. While this single-payer provider model has advantages, it relies heavily on VAC staff and managers to assess and approve plans of care. </p>
<p>Developing a psychedelics research program for veterans should be seen as a public health priority. It will most likely require an independent panel of experts and stakeholders, including veterans, to help shape the agenda in a timely manner for the VAC. </p>
<h2>Psychedelic therapies</h2>
<p><a href="https://cimvhr.ca/">The Canadian Institute for Military and Veteran Health Research</a> (CIMVHR), founded in 2010, is well positioned as the Canadian hub for military, veteran and family health research to provide the infrastructure to foster collaboration, ensure stakeholder engagement and work on the knowledge translation so necessary to rapidly developing the capacity and expertise of Canadian researchers.</p>
<p>We can build on the work of the U.S. Department of Veterans Affairs, which is <a href="https://clinicaltrials.gov/study/NCT05876481?term=Veteran&intr=Psilocybin&rank=1">currently conducting several psilocybin trials</a>, and the long-standing work of <a href="https://maps.org/">MAPS (Multi-disciplinary Association of Psychedelic Studies)</a> in advancing MDMA-assisted therapy for PTSD towards regulatory approval. We can also listen to the experts, such as Canada Health Research Chair in Mental Health Disparities Monnica Williams, who are calling for <a href="https://doi.org/10.1007/s11469-023-01160-5">greater equity and improved inclusion of BIPOC veterans and researchers</a>. </p>
<blockquote>
<p>“When we have tried everything in our toolbox but still cannot help our patients, it is truly time for some new tools.” —<a href="https://jmvfh.utpjournals.press/toc/jmvfh/9/5">Monnica Williams</a>, Canada Health Research Chair in Mental Health Disparities </p>
</blockquote>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-potential-of-psychedelics-to-heal-our-racial-traumas-218233">The potential of psychedelics to heal our racial traumas</a>
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</em>
</p>
<hr>
<p>Psychedelic ketamine appears to have <a href="https://doi.org/10.1192%2Fbjo.2021.1061">positive but short-lived outcomes</a> in the treatment of mood disorders, and ketamine clinics require evaluation given recent <a href="https://www.fda.gov/drugs/human-drug-compounding/fda-warns-patients-and-health-care-providers-about-potential-risks-associated-compounded-ketamine">FDA warnings</a> about risks of commercialized mental health telemedicine and take-home doses.</p>
<p>Ultimately, the Canadian public may want to reconsider the policy framework that still severely limits access to these promising compounds for researchers, clinicians and those in need. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/albertas-new-policy-on-psychedelic-drug-treatment-for-mental-illness-will-canada-lead-the-psychedelic-renaissance-195061">Alberta’s new policy on psychedelic drug treatment for mental illness: Will Canada lead the psychedelic renaissance?</a>
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</em>
</p>
<hr>
<p>Veterans have taken it upon themselves to support each other and to advocate for change. <a href="https://heroicheartsproject.org/">The Heroic Hearts Project</a> helps veterans access psychedelic therapies and has long championed the potential benefits of plant medicine ceremony.</p>
<p><a href="https://www.heroicheartsproject.ca/">Heroic Hearts Canada</a>, which aims to provide Canadian veterans with equitable access to safe, effective and affordable psychedelic therapies, has recently partnered with University of Calgary for some <a href="https://www.ucalgary.ca/research/participate/study/16168/are-you-veteran-canadian-armed-forces-have-you-investigated-working-psychedelics-legally">important observational research</a>.</p>
<h2>Faster progress to medical use</h2>
<p>The time lag from drug discovery to patient care is often decades, prompting the expression “<a href="https://doi.org/10.1186/s41231-019-0050-7">valley of death</a>” to refer to the gap between bench science and bedside care. </p>
<p>Given the real mental health needs of Canadian veterans, and the known limits on effectiveness for current standards of care, we must aim for quicker progress towards medical use, <a href="https://www.unodc.org/res/WDR-2023/WDR23_B3_CH2_psychedelics.pdf">as both the United States and Australia have done</a>. However, this progress must not be at the expense of safety and quality, and definitely not simply for commercialization. </p>
<p>Thought needs to be given to the development, evaluation and quality assurance of accessible programs for veteran-centred care, with Veterans’ voices at the table. It is time for more emphasis on psychedelics-related <a href="https://doi.org/10.1016/j.psychres.2019.04.025">implementation science</a>, the study of methods to promote the uptake (and identify barriers) of research findings into routine clinical use in order to improve effectiveness of health services.</p>
<p>There is <a href="https://healthsci.queensu.ca/source/Psychedelics%2520Research/Psychedelic%2520Medicine%2520Report%2520-%2520Final.pdf">robust and mounting evidence to support regulatory approval for MDMA and psilocybin-assisted therapies</a>. Their availability and uptake by clinicians and the public is only a matter of time. </p>
<h2>The need for more diverse research</h2>
<p>Research funds now are best allocated towards large Phase 3 trials that treat wider cross-sections of the veteran community, to begin to assess the safety and efficacy of interventions such as the naturally ocurring and culturally significant psychedelic compounds <a href="https://doi.org/10.1080/00952990.2023.2220874">ibogaine and 5-MeO-DMT</a> <a href="https://www.proquest.com/openview/2d897baa8a8203979eaf5ee7deb9037e/1?pq-origsite=gscholar&cbl=18750&diss=y">and ayahuasca</a>, and to invest in knowledge translation, program evaluation and training researchers and clinicians. </p>
<p>Apart from new biomedical research, it is time we recognized the widespread personal use of psychedelics, including among veterans, and develop safer use guidelines for psychedelics like those in place <a href="https://www.canada.ca/en/health-canada/services/substance-use/alcohol/low-risk-alcohol-drinking-guidelines.html">for alcohol</a> and <a href="https://doi.org/10.1007/BF03404169">cannabis</a>.</p>
<p>While the Senate report does not mention cannabis, it is worth noting that veterans in Canada have been <a href="https://dimensionsretreats.com/dimensions-retreats-algonquin-elevate-veterans-only/#:%7E:text=The%2520program%2520does%2520not%2520include,mind%252Dbody%2520practices%2520in%2520nature.">approved for treatment with cannabis-assisted therapy</a>. </p>
<p>This includes the use of <a href="https://doi.org/10.1177/0269881121997099">cannabis as a psychedelic</a> and mimics the <a href="https://doi.org/10.1007/s40429-021-00401-8">preparation-session-integration protocols</a> of psychedelic therapies. This intervention is also worth rapid evaluation and possible expansion. </p>
<p>Given the pressing needs of Canadian veterans and the limitations of our current tools, the need for research on psychedelic therapies, as well as for timely and equitable access, is urgent.</p><img src="https://counter.theconversation.com/content/218784/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ron Shore worked for, and consulted to Dimensions Health Centres in 2021 and 2022; he continues to own shares in the company.</span></em></p>One in seven Canadian veterans is living with PTSD. Developing a psychedelics research program for veterans should be a public health priority.Ron Shore, Research Scientist, Queen's Health Sciences and Assistant Professor, Department of Psychiatry, Queen's University, OntarioLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1982202023-02-22T12:54:26Z2023-02-22T12:54:26ZPeople produce endocannabinoids – similar to compounds found in marijuana – that are critical to many bodily functions<figure><img src="https://images.theconversation.com/files/510907/original/file-20230217-380-5ni8j3.jpg?ixlib=rb-1.1.0&rect=30%2C38%2C5077%2C3339&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A healthy endocannabinoid system is critical to the human body’s immune functions.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/older-hispanic-woman-lifting-weights-in-living-room-royalty-free-image/546825853?phrase=energy%20exercise&adppopup=true">Jose Luis Pelaez Inc/Digital Vision via Getty Images</a></span></figcaption></figure><p>Over the past two decades, a great deal of attention has been given to marijuana – also known as pot or weed. As of early 2023, marijuana has been <a href="https://www.usnews.com/news/best-states/articles/where-is-marijuana-legal-a-guide-to-marijuana-legalization">legalized for recreational use in 21 states</a> and Washington, D.C., and the use of <a href="https://www.mayoclinic.org/healthy-lifestyle/consumer-health/in-depth/medical-marijuana/art-20137855">marijuana for medical purposes</a> has grown significantly during the <a href="https://nap.nationalacademies.org/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids-the-current-state">last 20 or so years</a>. </p>
<p>But few people know that the human body naturally produces chemicals that are very similar to delta-9-tetrahydrocannabinol, or THC, the psychoactive compound in marijuana, which comes from the <a href="https://doi.org/10.3389/fpls.2016.00019"><em>Cannabis sativa</em> plant</a>. These substances are called endocannabinoids, and they’re <a href="https://doi.org/10.3390%2Fani9090686">found across all vertebrate species</a>. </p>
<p>Evolutionarily, the appearance of endocannabinoids in vertebrate animals predates that of <em>Cannabis sativa</em> by <a href="https://doi.org/10.1300/J175v02n01_04">about 575 million years</a>. </p>
<p>It is as if the human body has its own version of a marijuana seedling inside, constantly producing small amounts of endocannabinoids.</p>
<p>The similarity of endocannabinoids to THC, and their importance in maintaining human health, have raised significant interest among scientists to further study their role in health and disease, and potentially use them as therapeutic targets to treat human diseases.</p>
<p>THC <a href="https://doi.org/10.1038/sj.bjp.0706406">was first identified</a> in 1964, and is just one of more than 100 compounds found in marijuana that are <a href="https://www.cdc.gov/marijuana/health-effects/index.html">called cannabinoids</a>.</p>
<p><a href="https://doi.org/10.1016/j.tips.2015.02.008">Endocannabinoids were not discovered</a> until 1992. Since then, research has revealed that they are critical for many important physiological functions that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/">regulate human health</a>. An imbalance in the production of endocannabinoids, or in the body’s responsiveness to them, <a href="https://doi.org/10.1111%2Ffebs.12260">can lead to major clinical disorders</a>, including obesity as well as neurodegenerative, cardiovascular and inflammatory diseases. </p>
<p>We <a href="https://scholar.google.com/citations?user=jJVj3sUAAAAJ&hl=en">are immunologists</a> who have been <a href="https://scholar.google.com/citations?user=af7TahQAAAAJ&hl=en">studying the effects of marijuana cannabinoids and vertebrate endocannabinoids</a> on inflammation and cancer for more than two decades. <a href="https://doi.org/10.1016%2Fj.phrs.2009.03.019">Research in our laboratory</a> has shown that endocannabinoids <a href="https://theconversation.com/what-is-inflammation-two-immunologists-explain-how-the-body-responds-to-everything-from-stings-to-vaccination-and-why-it-sometimes-goes-wrong-193503">regulate inflammation</a> and other immune functions. </p>
<h2>What is the endocannabinoid system?</h2>
<p>A variety of tissues in the body, including brain, muscle, fatty tissue and immune cells, <a href="https://pubmed.ncbi.nlm.nih.gov/19675519/">produce small quantities of endocannabinoids</a>. There are <a href="https://doi.org/10.1016/j.phrs.2009.03.019">two main types of endocannabinoids</a>: anandamide, or AEA, and 2-arachidonoyl glycerol, known as 2-AG. Both of them can activate the body’s cannabinoid receptors, which receive and process chemical signals in cells. </p>
<p>One of these receptors, called CB1, is <a href="https://doi.org/10.3390%2Fijms19030833">found predominantly in the brain</a>. The other, called CB2, is <a href="https://doi.org/10.4155/fmc.09.93">found mainly in immune cells</a>. It is primarily through the activation of these two receptors that endocannabinoids control many bodily functions.</p>
<p>The receptors can be compared to a “lock” and the endocannabinoids a “key” that can open the lock and gain entry into the cells. All these endocannabinoid receptors and molecules together are referred to as the endocannabinoid system. </p>
<p>The cannabis plant contains another compound called cannabidiol, or CBD, which has <a href="https://theconversation.com/cbd-is-not-a-cure-all-heres-what-science-says-about-its-real-health-benefits-186901">become popular</a> for its medicinal properties. Unlike THC, CBD doesn’t have psychoactive properties because it <a href="https://doi.org/10.1146%2Fannurev-neuro-070815-014038">does not activate CB1 receptors in the brain</a>. Nor does it <a href="https://doi.org/10.1038/sj.bjp.0707442">activate the CB2 receptors</a>, meaning that its action on immune cells is independent of CB2 receptors. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Textbook illustration of the human endocannabinoid system, highlighting the role of CB1 and CB2 receptors." src="https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=960&fit=crop&dpr=1 600w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=960&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=960&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1206&fit=crop&dpr=1 754w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1206&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/511480/original/file-20230221-2556-95l7i5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1206&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Endocannabinoid receptors are found throughout most of the human body.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/human-endocannabinoid-system-vertical-royalty-free-illustration/1178997969">About time/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<h2>Role of endocannabinoids in the body</h2>
<p>The euphoric “high” feeling that people experience when using marijuana comes from THC activating the CB1 receptors in the brain. </p>
<p>But when endocannabinoids activate CB1 receptors, by comparison, they do not cause a marijuana high. One reason is that the body <a href="https://doi.org/10.1038/npp.2017.130">produces them in smaller quantities</a> than the typical amount of THC in marijuana. The other is that <a href="https://doi.org/10.1021%2Fcr0782067">certain enzymes break them down</a> rapidly after they carry out their cellular functions.</p>
<p>However, there is growing evidence that certain activities may release mood-elevating endocannabinoids. Some research suggests that the relaxed, euphoric feeling you get after exercise, called a “<a href="https://theconversation.com/the-runners-high-may-result-from-molecules-called-cannabinoids-the-bodys-own-version-of-thc-and-cbd-170796">runner’s high</a>,” results from the <a href="https://www.scientificamerican.com/article/new-brain-effects-behind-runner-s-high/">release of endocannabinoids</a> <a href="https://runningmagazine.ca/health-nutrition/new-study-confirms-endorphins-arent-the-cause-of-the-runners-high/">rather than from endorphins</a>, as previously thought.</p>
<p>The endocannabinoids <a href="https://doi.org/10.3390/ijms22179472">regulate several bodily functions</a> such as sleep, mood, appetite, learning, memory, body temperature, pain, immune functions and fertility. They control some of these functions by regulating nerve cell signaling in the brain. Normally, nerve cells communicate with one another at junctions called synapses. The endocannabinoid system in the brain regulates this communication at synapses, which explains its ability to affect a wide array of bodily functions. </p>
<h2>The elixir of endocannabinoids</h2>
<p>Research in our laboratory has shown that <a href="https://doi.org/10.1002/eji.201546181">certain cells of the immune system produce endocannabinoids</a> that can regulate inflammation and other immune functions through the activation of CB2 receptors.</p>
<p>In addition, we have shown that <a href="https://doi.org/10.1124/mol.108.047035">endocannabinoids are highly effective in lessening the debilitating effects of autoimmune diseases</a>. These are diseases in which the immune system goes haywire and <a href="https://medlineplus.gov/autoimmunediseases.html">starts destroying the body’s organs and tissues</a>. Examples include <a href="https://medlineplus.gov/multiplesclerosis.html">multiple sclerosis</a>, <a href="https://doi.org/10.1124/mol.108.047035">lupus</a>, <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/hepatitis">hepatitis</a> and <a href="https://www.niams.nih.gov/health-topics/arthritis">arthritis</a>. </p>
<p>Recent research suggests that migraine, fibromyalgia, irritable bowel syndrome, post-traumatic stress disorder and bipolar disease are all <a href="https://doi.org/10.1089/can.2016.0009">linked to low levels of endocannabinoids</a>.</p>
<p>In a 2022 study, researchers found that a defect in a gene that helps produce endocannabinoids causes <a href="https://doi.org/10.1038/s41467-022-31168-9">early onset of Parkinson’s disease</a>. Another 2022 study linked the same gene defect to <a href="https://doi.org/10.1093/brain/awac223">other neurological disorders</a>, including developmental delay, poor muscle control and vision problems. </p>
<p>Other research has shown that people with a defective form of CB1 receptors <a href="https://doi.org/10.1371/journal.pone.0187926">experience increased pain sensitivity</a> such as migraine headaches and suffer from sleep and memory disorders and anxiety. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=495&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=495&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=495&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=622&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=622&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510714/original/file-20230216-14-6r2f4a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=622&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The endocannabinoid system – consisting of the endocannabinoids and the cannabinoid receptors – regulates nerve cell communication at the synapse, thereby playing a role in a variety of bodily functions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/endocannabinoid-system-royalty-free-illustration/1392987232?phrase=endocannabinoid%20system&adppopup=true">Carolina Hrejsa, CMI/iStock/Getty Images Plus via Getty Images</a></span>
</figcaption>
</figure>
<h2>The likeness between marijuana and endocannabinoids</h2>
<p>We believe that the medicinal properties of THC may be linked to the molecule’s ability to compensate for a deficiency or defect in the production or functions of the endocannabinoids. </p>
<p>For example, scientists have found that people who experience certain types of chronic pain may have <a href="https://doi.org/10.3390/molecules27144662">decreased production of endocannabinoids</a>. People who consume marijuana for medicinal purposes <a href="https://www.nationalacademies.org/news/2017/01/health-effects-of-marijuana-and-cannabis-derived-products-presented-in-new-report">report significant relief from pain</a>. Because the THC in marijuana <a href="https://dx.doi.org/10.1001/jama.2018.16202">is the cannabinoid that reduces pain</a>, it may be helping to compensate for the decreased production or functions of endocannabinoids in such patients. </p>
<p>Deciphering the role of endocannabinoids is still an emerging area of health research. Certainly much more research is needed to decipher their role in regulating different functions in the body. </p>
<p>In our view, it will also be important to continue to unravel the relationship between defects in the endocannabinoid system and the development of various diseases and clinical disorders. We think that the answers could hold great promise for the development of new therapies using the body’s own cannabinoids.</p><img src="https://counter.theconversation.com/content/198220/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prakash Nagarkatti receives funding from the National Institutes of Health and the National Science Foundation. </span></em></p><p class="fine-print"><em><span>Mitzi Nagarkatti receives funding from National Institutes of Health. </span></em></p>A THC-like substance that occurs naturally in humans and other vertebrates helps maintain immunity, memory, nerve function and more – and research suggests a lack of it can harm health.Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaMitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1869062022-11-02T12:29:49Z2022-11-02T12:29:49ZCannabis holds promise for pain management, reducing the need for opioid painkillers – a neuropharmacology expert explains how<figure><img src="https://images.theconversation.com/files/477967/original/file-20220808-82349-qkr00w.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5760%2C3325&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The cannabis plant produces both THC – the psychoactive component in marijuana – and the compound commonly known as CBD, which does not lead to a 'high.'</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/marijuana-leaves-background-royalty-free-image/1329249971?adppopup=true">Jena Ardell/Moment via Getty Images</a></span></figcaption></figure><p>Drug overdose deaths from opioids <a href="https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2021/20211117.htm">continue to rise in the U.S.</a> as a result of both the misuse of <a href="https://www.hhs.gov/opioids/about-the-epidemic/index.html">prescription opioids and the illicit drug market</a>. </p>
<p>But an interesting trend has developed: <a href="https://www.upmc.com/media/news/071221-drake-cannabisrcl">Opioid emergency room visits</a> drop by nearly 8% and <a href="https://doi.org/10.1007%2Fs11606-018-4782-2">opioid prescriptions</a> are modestly lower in <a href="https://www.usatoday.com/story/news/nation/2022/10/06/how-many-states-have-legalized-marijuana-cannabis-laws-unpacked/8200166001/">states where marijuana is legalized</a>. </p>
<p>Marijuana is produced by the cannabis plant, which is native to Asia but is now grown throughout the world. Individuals use marijuana for both its psychoactive, euphoria-inducing properties and its ability to <a href="https://doi.org/10.1002/j.1552-4604.1975.tb02348.x">relieve pain</a>. </p>
<p>Chemicals produced by the cannabis plant are commonly known as cannabinoids. The <a href="https://www.nccih.nih.gov/health/cannabis-marijuana-and-cannabinoids-what-you-need-to-know">two primary cannabinoids</a> that occur naturally in the cannabis plant are THC – the psychoactive compound in marijuana – and CBD, which does not cause the sensation of being high.</p>
<p>Many <a href="https://doi.org/10.1377/hlthaff.2018.05266">marijuana users say</a> they take it to treat pain, suggesting that readily available cannabinoids could potentially be used to offset the use of opioids such as morphine and oxycodone that are commonly used in pain treatment. A safer, natural alternative to opioid painkillers would be an important step toward <a href="https://www.cdc.gov/drugoverdose/epidemic/index.html">addressing the ongoing opioid epidemic</a>. </p>
<p>Intriguingly however, research suggests that cannabis use could also lessen the need for opioids directly by interacting with the body’s own natural <a href="https://doi.org/10.1097/j.pain.0000000000002527">opioid system</a> to produce similar pain-relief effects.</p>
<p>I am <a href="https://pharmacology.uw.edu/team-member/benjamin-land/">a neuropharmacology scientist</a> who <a href="https://scholar.google.com/citations?user=dux-xtoAAAAJ&hl=en">studies both opioids and cannabinoids</a> as they relate to pain treatment and substance abuse. My research focuses on the development of drug compounds that can provide chronic pain relief without the potential for overuse and without the tapering off of effectiveness that often accompanies traditional pain medications.</p>
<h2>How opioids work</h2>
<p>Our bodies have their own built-in opioid system that can aid in managing pain. These opioids, <a href="https://www.health.harvard.edu/mind-and-mood/endorphins-the-brains-natural-pain-reliever">such as endorphins</a>, are chemicals that are released when the body experiences stress such as strenuous exercise, as well as in response to pleasurable activities like eating a good meal. But it turns out that humans are not the only organisms that can make opioids. </p>
<p>In the 1800s, scientists discovered that <a href="https://www.history.com/topics/crime/history-of-heroin-morphine-and-opiates#">the opioid morphine</a> – isolated from opium poppy – was highly effective at relieving pain. In the last 150 years, scientists have developed additional synthetic opioids like hydrocodone and dihydrocodeine that also provide pain relief.</p>
<p>Other opioids like heroin and oxycodone are very similar to morphine, but with small differences that influence how quickly they act on the brain. Fentanyl has an even more unique chemical makeup. It is <a href="https://www.dea.gov/factsheets/fentanyl">the most powerful opioid</a> and is the culprit behind the <a href="https://theconversation.com/what-is-fentanyl-and-why-is-it-behind-the-deadly-surge-in-us-drug-overdoses-a-medical-toxicologist-explains-182629">current surge in drug overdoses and deaths</a>, <a href="https://www.uclahealth.org/news/adolescent-drug-overdose-deaths-rose-exponentially-first">including among young people</a>.</p>
<p>Opioids, whether naturally produced or synthetic, produce pain relief by binding to specific receptors in the body, which are proteins that act like a lock that can only be opened by an opioid key.</p>
<p>One such receptor, <a href="https://doi.org/10.1124%2Fpr.112.007138">known as the mu-opioid receptor</a>, is found on pain-transmitting nerve cells along the spinal cord. When activated, mu-receptors tamp down the cell’s ability to relay pain information. Thus, when these opioids are circulating in the body and they reach their receptor, stimuli that would normally cause pain are not transmitted to the brain.</p>
<p>These same receptors are also found in the brain. When opioids find their receptor, the brain releases <a href="https://www.health.harvard.edu/mind-and-mood/feel-good-hormones-how-they-affect-your-mind-mood-and-body">dopamine – the so-called “feel-good” chemical</a> – which has its own receptors. This is in part why opioids can be highly addicting. Research suggests that these receptors drive the <a href="https://doi.org/10.1016/j.biopsych.2019.05.023">brain’s reward system</a> and promote further drug-seeking. For people who are prescribed opiates, this creates the potential for abuse. </p>
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<figcaption><span class="caption">Opioid drugs, which include heroin, oxycodone and fentanyl, are highly addictive.</span></figcaption>
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<p>Opioid receptors are dynamically regulated, meaning that as they get exposed to more and more opioids, the body adapts quickly by deactivating the receptor. In other words, the body needs more and more of that opioid to get pain relief and to produce the feel-good response. This process is known as tolerance. The drive to seek more and more reward paired with an ever-increasing tolerance is what leads to the potential for overdose, which is why opioids are generally not long-term solutions for pain. </p>
<h2>The potential of THC and CBD for pain treatment</h2>
<p>Both THC and CBD have been shown in <a href="https://doi.org/10.2174/157015906778019527">numerous</a> <a href="https://pubmed.ncbi.nlm.nih.gov/20073408/">studies</a> to lessen pain, though – importantly – they differ in which receptors they bind to in order to produce these effects.</p>
<p>THC binds to cannabinoid receptors that are located throughout the central nervous system, producing a variety of responses. One of those responses is the high associated with cannabis use, and another is pain relief. Additionally, THC is believed to reduce inflammation in a manner <a href="https://theconversation.com/how-do-painkillers-actually-kill-pain-from-ibuprofen-to-fentanyl-its-about-meeting-the-pain-where-its-at-173804">similar to anti-inflammatory drugs like ibuprofen</a>. </p>
<p>In contrast, CBD appears to bind to <a href="https://doi.org/10.1111/bcpt.13710">several distinct receptors</a>, and many of these receptors can play a role in pain reduction. Importantly, this occurs without the high that occurs with THC. </p>
<p>Because they target different receptors, THC and CBD may be more effective working in concert <a href="https://doi.org/10.3390/ijms23158649">rather than alone</a>, but more studies in <a href="https://doi.org/10.2217/pmt-2020-0110">animal models and humans are needed</a>.</p>
<p>Cannabinoids may also be helpful for other conditions as well. Many studies have demonstrated that cannabinoid drugs approved for medical use are effective for pain and other symptoms like <a href="https://www.ninds.nih.gov/health-information/disorders/spasticity#">spasticity</a>, nausea and <a href="https://doi.org/10.1186/s12916-022-02459-1">appetite loss</a>.</p>
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<figcaption><span class="caption">The opioid crisis: Painkillers are killing us.</span></figcaption>
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<h2>Moving pain research forward</h2>
<p>Along with the pairing of THC and CBD, researchers are beginning to explore the use of those two cannabinoids together with existing opioids for pain management. This research is being done in <a href="https://doi.org/10.1038/s41386-022-01322-4">both animal models and humans</a>. </p>
<p>These studies are designed to understand both the benefits – pain relief – and risks – primarily addiction potential – of co-treatment with cannabinoids and opioids. The hope would be that THC or CBD may lower the amount of opioid necessary for powerful pain relief without increasing addiction risk.</p>
<p>For example, one study tested the <a href="https://doi.org/10.1038/s41386-018-0011-2">combination of smoked cannabis and oxycontin</a> for pain relief and reward. It found that co-treatment enhanced pain relief but also increased the pleasure of the drugs. This, as well as a limited number of other <a href="https://doi.org/10.1038/s41386-022-01322-4">studies</a>, suggests there may not be a net benefit.</p>
<p>However, many more studies of this type will be necessary to understand if cannabinoids and opioids can be safely used together for pain. Still, using cannabinoids as a substitution for opioids remains a promising pain treatment strategy. </p>
<p>The next decade of research will likely bring important new insights to the therapeutic potential of cannabinoids for chronic pain management. And as <a href="https://www.politico.com/news/2022/08/03/cannabis-legalization-efforts-across-the-states-00049224">marijuana legalization continues to spread</a> across the U.S., its use in medicine will undoubtedly grow exponentially.</p><img src="https://counter.theconversation.com/content/186906/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Benjamin Land receives funding from the NCCIH for cannabinoid work distinct from opioids, and has received cannabinoid related funding from the University of Washington Addiction and Drug Abuse Institute and SCAN Design Foundation.</span></em></p>Studies suggest that marijuana and CBD use might help relieve chronic pain while also reducing a patient’s need for opioids.Benjamin Land, Research Associate Professor of Pharmacology, School of Medicine, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1769632022-07-27T12:00:00Z2022-07-27T12:00:00ZNature is the world’s original pharmacy – returning to medicine’s roots could help fill drug discovery gaps<figure><img src="https://images.theconversation.com/files/475941/original/file-20220725-19-fgfrya.jpg?ixlib=rb-1.1.0&rect=98%2C165%2C1986%2C1237&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Around 75% of antibiotics, including penicillin and amphotericin B, are derived from natural products.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/directly-above-shot-of-pills-on-leaf-royalty-free-image/1004440852">Aphiwat Chuangchoem/EyeEm via Getty Images</a></span></figcaption></figure><p>While humans evolved over a period of approximately <a href="https://humanorigins.si.edu/education/introduction-human-evolution">6 million years</a>, breakthroughs in modern medicine as we know it today got going only in the <a href="https://www.medicalnewstoday.com/articles/323538">19th and 20th centuries</a>. So how did humans successfully survive through millions of years of diseases and illnesses without modern drugs and treatments?</p>
<p>This was a question I came to wonder about when the COVID-19 pandemic reached my family in India in April 2020, when there was very limited access to vaccines and treatments. All of my years working as a <a href="https://scholar.google.com/citations?user=8_T1ueYAAAAJ&hl=en">biomedical scientist</a>, requiring empirical evidence and formal safety testing before using a treatment, took a back seat as I scrambled for potential therapies from any sources I could find, be it scientific papers or folklore. I was ready to try any experimental or traditional medicine that might have a chance at helping my dad.</p>
<p>Luckily, my dad recovered. I can’t say for sure if any of the traditional medicines we used actually helped him recover. But as someone whose entire scientific career has focused on discovering new drugs from chemical compounds found in nature, I wondered if there was a molecule in the traditional medicines we used that could be isolated and optimized to treat COVID-19.</p>
<p>Scientists like me have been looking for new drugs for various diseases by purifying existing compounds in nature instead of synthesizing completely new ones in the lab. From <a href="https://doi.org/10.1021/acs.jnatprod.0c00968">COVID-19</a> to <a href="https://doi.org/10.1007/978-3-319-78538-7_17">antibiotic resistance</a>, I believe that past successes and new technologies point to the tremendous potential of developing new drugs from natural products.</p>
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<figcaption><span class="caption">Early drug development involved searching for plants with medicinal properties. Scientists have since been able to isolate the active ingredients bestowing medicinal properties on natural products, such as the morphine in poppies.</span></figcaption>
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<h2>The natural product advantage</h2>
<p>Humans have coevolved with the rest of nature over time, and obtaining medicine is perhaps one of the most important interactions people continue to have with the natural world. DNA analyses have shown that <a href="https://doi.org/10.1038/nature21674">early humans may have treated dental abscesses</a> with poplar, containing the active ingredient of aspirin, and <em>Penicillium</em> mold, containing the antibiotic penicillin.</p>
<p>Researchers call the molecules like the ones that give poplar and <em>Penicillium</em> their biological effects <a href="https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Basic_Principles_of_Organic_Chemistry_(Roberts_and_Caserio)/30%3A_Natural_Products_and_Biosynthesis">natural products</a> because they are produced by living organisms such as microbes, fungi, corals and plants. These natural products have evolved to be <a href="https://doi.org/10.1002/1521-3773(20020816)41:16%3C2878::AID-ANIE2878%3E3.0.CO;2-B">structurally “optimized</a>” to serve particular biological functions, primarily to <a href="https://pubs.rsc.org/en/content/articlelanding/2015/np/c4np00150h">deter predators or gain a survival advantage</a> in a particular environment and over other competitors.</p>
<p>Because natural products are already made to function in living creatures, this makes them especially attractive as a source for drug discovery. While proteins may look different in different organisms, many have <a href="https://doi.org/10.1073/pnas.95.18.10396">similar structural features and functions</a> across species. This can help ease the search for related proteins that work in people.</p>
<h2>Natural product hall of fame</h2>
<p>Natural products derived from microbes and plants are the biggest resource for drug discovery for modern medicine. Case in point, the discovery of the antibiotic <a href="https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html">penicillin</a> in 1940 from <em>Penicillium</em> mold allowed doctors to treat previously fatal infections and started the era of antibiotics. </p>
<p>As of September 2019, <a href="https://doi.org/10.1021/acs.jnatprod.9b01285">over 50%</a> of currently available FDA-approved drugs are either directly or indirectly derived from natural products. One of the best-selling drugs of the past two decades, atorvastatin (Lipitor), an anti-cholesterol drug, is derived from a compound produced by the fungus <a href="https://doi.org/10.1038/nm1008-1050"><em>Penicillium citrinum</em></a>. From 1992 to 2017, atorvastatin sales in the U.S. totaled <a href="https://www.fiercepharma.com/pharma/from-old-behemoth-lipitor-to-new-king-humira-u-s-best-selling-drugs-over-25-years">US$94.67 billion</a>.</p>
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<figcaption><span class="caption">Penicillin revolutionized medicine.</span></figcaption>
</figure>
<p>Other prominent examples of drugs derived from natural products currently used today include the anti-fungal <a href="https://doi.org/10.1378/chest.54.Supplement_1.296">amphotericin B</a>, isolated from the soil bacteria <em>Streptomyces nodosus</em>, the chemotherapy <a href="https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/camptothecintaxol.html">taxol</a>, isolated from the bark of the Pacific yew tree, and the immunosuppressant <a href="https://doi.org/10.1016/S0269-915X(98)80100-6">cyclosporin</a>, isolated from the fungus <em>Tolypocladium inflatum</em>.</p>
<p>I believe that undiscovered treatments for a wide range of diseases are lying right under our noses in natural products. In January 2021, the FDA approved <a href="https://www.lupus.org/resources/lupkynis-voclosporin-what-you-need-to-know">voclosporin (Lupkynis)</a>, isolated from the fungus <a href="https://mycocosm.jgi.doe.gov/Tolinf1/Tolinf1.home.html"><em>Tolypocladium inflatum</em></a>, to treat lupus. Recently, researchers have been looking into <a href="https://doi.org/10.1126/sciadv.abi6110">cannabidiol</a> and other <a href="https://doi.org/10.1021/acs.jnatprod.1c00946">cannabinoid compounds</a> as a potential way to prevent or treat COVID-19. The FDA has not authorized any drug containing CBD for COVID-19 yet.</p>
<h2>Challenges in natural product discovery</h2>
<p>Researchers are increasingly able to use new <a href="https://doi.org/10.1038/s41573-020-00114-z">screening technologies and methods</a> to isolate previously unidentified natural products. Screening for natural products typically involves looking through a large library of extracts from natural sources. The <a href="https://www.lsi.umich.edu/science/centers-technologies/natural-products-discovery-core">Natural Product Drug Discovery Core</a>, which I co-founded with my colleague <a href="https://scholar.google.com/citations?user=g9dFOKIAAAAJ&hl=en">David Sherman</a> at the University of Michigan, for example, searches for potential drug targets in a library containing around 50,000 natural product extracts that each contain 30 to 50 molecules to test.</p>
<p>However, discovering natural product-based drugs is not without challenges. <a href="https://doi.org/10.1073/pnas.1614680114">Since the 1980s</a>, natural products have fallen out of favor because of a number of challenges. These include difficulty accessing expensive screening methods, and limitations in technology that isn’t able to fully analyze the complexity of natural products. There are also <a href="https://doi.org/10.1007/s11101-014-9367-z">ecological and legal considerations</a>, such as accessing samples sustainably and maintaining biodiversity. Pharmaceutical companies have <a href="https://doi.org/10.1002/0471141755.ph0911s46">reduced their natural product-based drug discovery programs</a>, and <a href="https://doi.org/10.1093/ofid/ofaa001">federal funding</a> is also in short supply due to limited profitability.</p>
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<figcaption><span class="caption">As antibiotic resistance grows, developing new drugs and using current ones more responsibly becomes even more imperative.</span></figcaption>
</figure>
<h2>Finding new drugs in nature</h2>
<p>New drugs are often necessary for unprecedented health emergencies like COVID-19. They are also needed for a health emergency that began long before the pandemic – antibiotic resistance. </p>
<p>A <a href="https://apps.who.int/iris/handle/10665/258965">September 2017 report</a> from the World Health Organization reaffirmed that antibiotic resistance is a global health emergency that will seriously jeopardize progress in modern medicine. If current antibiotics lose their effectiveness, <a href="https://www.cdc.gov/drugresistance/about.html">common medical interventions</a> such as cesarean sections and cancer treatments may become incredibly risky. Transplantation could become virtually impossible. Antibiotic-resistant microbes were the direct cause of roughly <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">1.27 million deaths in 2019</a>. Treating just six of the 18 microbes that pose an antibiotic resistance threat is estimated to cost <a href="https://www.cdc.gov/drugresistance/solutions-initiative/stories/partnership-estimates-healthcare-cost.html">over $4.6 billion annually</a> in the U.S. alone. The <a href="https://www.cdc.gov/media/releases/2022/s0712-Antimicrobial-Resistance.html">COVID-19 pandemic has reversed prior progress addressing this issue</a>, with a 15% increase in antimicrobial-resistant infections from 2019 to 2020. In contrast, antimicrobial-resistant infections had fallen by 27% from 2012 to 2017. Among the likely causes of this backslide were increases in antibiotic use, difficulty following infection control guidelines and longer hospital stays.</p>
<p>As of recent estimates, <a href="https://doi.org/10.1038/ja.2017.30">roughly 75%</a> of approved antibiotics are derived from natural products. There are <a href="https://doi.org/10.1038/s41586-022-04862-3">thousands of microorganisms in the ocean</a> left to explore as potential sources of drug candidates, not to mention all the ones on land. In the search for new drugs to combat antibiotic resistance, natural products may still be the way to go.</p><img src="https://counter.theconversation.com/content/176963/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ashu Tripathi receives funding from the National Institute of Health and UM Biological Sciences Initiative. He is affiliated with the American Society of Pharmacognosy, Association of Biomolecular Resources Facilities, and Society of Industrial Microbiology and Biotechnology. </span></em></p>With the dual threats of antibiotic resistance and emerging pandemics, finding new drugs becomes even more urgent. A trove of medicines may be lying under our nose.Ashu Tripathi, Director, Natural Product Discovery Core; Assistant Professor/ Research of Medicinal Chemistry, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1738042022-06-24T11:52:20Z2022-06-24T11:52:20ZHow do painkillers actually kill pain? From ibuprofen to fentanyl, it’s about meeting the pain where it’s at<figure><img src="https://images.theconversation.com/files/470376/original/file-20220622-11-ijs4h6.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A variety of pain-relieving drugs are available both over the counter and by prescription.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/senior-woman-looking-at-prescription-bottles-royalty-free-image/150684340">SelectStock/Vetta via Getty Images</a></span></figcaption></figure><p>Without the ability to feel pain, life is more dangerous. To avoid injury, pain tells us to use a hammer more gently, wait for the soup to cool or put on gloves in a snowball fight. Those with <a href="https://www.ncbi.nlm.nih.gov/books/NBK481553/">rare inherited disorders</a> that leave them without the ability to feel pain are unable to protect themselves from environmental threats, leading to broken bones, damaged skin, infections and ultimately a shorter life span.</p>
<p>In these contexts, pain is much more than a sensation: It is a protective call to action. But pain that is too intense or long-lasting can be debilitating. So how does modern medicine soften the call?</p>
<p>As a <a href="https://scholar.google.com/citations?user=Hn7sPk0AAAAJ&hl=en">neurobiologist</a> and an <a href="https://www.anesthesiology.pitt.edu/people/benedict-alter-md-phd">anesthesiologist</a> who study pain, this is a question we and other researchers have tried to answer. Science’s understanding of how the body senses tissue damage and perceives it as pain has progressed tremendously over the past several years. It has become clear that there are <a href="https://doi.org/10.1126/science.aaf8933">multiple pathways</a> that signal tissue damage to the brain and sound the pain alarm bell. </p>
<p>Interestingly, while the brain uses different pain signaling pathways depending on the type of damage, there is also redundancy to these pathways. Even more intriguing, these neural pathways morph and amplify signals in the case of <a href="https://doi.org/10.1097/j.pain.0000000000001384">chronic pain</a> and pain caused by <a href="https://doi.org/10.1152/physrev.00045.2019">conditions affecting nerves themselves</a>, even though the protective function of pain is no longer needed.</p>
<p>Painkillers work by tackling different parts of these pathways. Not every painkiller works for every type of pain, however. Because of the multitude and redundancy of pain pathways, a perfect painkiller is elusive. But in the meantime, understanding how existing painkillers work helps medical providers and patients use them for the best results.</p>
<h2>Anti-inflammatory painkillers</h2>
<p>A bruise, sprain or broken bone from an injury all lead to tissue <a href="https://my.clevelandclinic.org/health/symptoms/21660-inflammation">inflammation</a>, an immune response that can lead to swelling and redness as the body tries to heal. Specialized nerve cells in the area of the injury called <a href="https://www.verywellhealth.com/what-are-nociceptors-2564616">nociceptors</a> sense the inflammatory chemicals the body produces and send pain signals to the brain. </p>
<p>Common over-the-counter <a href="https://doi.org/10.1016/j.anclin.2017.01.020">anti-inflammatory painkillers</a> work by decreasing inflammation in the injured area. These are particularly useful for musculoskeletal injuries or other pain problems caused by inflammation such as arthritis. </p>
<p>Nonsteroidal anti-inflammatories like ibuprofen (Advil, Motrin), naproxen (Aleve) and aspirin do this by blocking an enzyme called <a href="https://www.ncbi.nlm.nih.gov/books/NBK549795/">COX</a> that plays a key role in a biochemical cascade that produces inflammatory chemicals. Blocking the cascade decreases the amount of inflammatory chemicals, and thereby reduces the pain signals sent to the brain. While acetaminophen (Tylenol), also known as paracetamol, doesn’t reduce inflammation as NSAIDs do, it also inhibits COX enzymes and has similar pain-reducing effects.</p>
<p>Prescription anti-inflammatory painkillers include other COX inhibitors, corticosteroids and, more recently, drugs that target and <a href="https://doi.org/10.1186/s10194-017-0807-1">inactivate the inflammatory chemicals</a> themselves.</p>
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<figcaption><span class="caption">Aspirin and ibuprofen work by blocking the COX enzymes that play a key role in pain-causing processes.</span></figcaption>
</figure>
<p>Because inflammatory chemicals are involved in other important physiological functions beyond just sounding the pain alarm, medications that block them will have side effects and potential health risks, including irritating the stomach lining and affecting <a href="https://doi.org/10.1161/01.hyp.0000116221.27079.ea">kidney function</a>. <a href="https://medlineplus.gov/ency/article/002123.htm">Over-the-counter medications</a> are generally safe if the directions on the bottle are followed strictly.</p>
<p><a href="https://www.verywellhealth.com/using-corticosteroids-for-pain-control-2564537">Corticosteroids</a> like prednisone block the inflammatory cascade early on in the process, which is probably why they are so potent in reducing inflammation. However, because all the chemicals in the cascade are present in nearly every organ system, long-term use of steroids can pose many health risks that need to be discussed with a physician before starting a treatment plan.</p>
<h2>Topical medications</h2>
<p>Many <a href="https://doi.org/10.1002/14651858.cd008609.pub2">topical medications</a> target nociceptors, the specialized nerves that detect tissue damage. Local anesthetics, like lidocaine, prevent these nerves from sending electrical signals to the brain. </p>
<p>The protein sensors on the tips of other sensory neurons in the skin are also targets for topical painkillers. Activating these proteins can elicit particular sensations that can lessen the pain by reducing the activity of the damage-sensing nerves, like the cooling sensation of menthol or the burning sensation of capsaicin.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/470369/original/file-20220622-23-iz2b69.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Hand holding small container of topical ointment" src="https://images.theconversation.com/files/470369/original/file-20220622-23-iz2b69.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/470369/original/file-20220622-23-iz2b69.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/470369/original/file-20220622-23-iz2b69.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/470369/original/file-20220622-23-iz2b69.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/470369/original/file-20220622-23-iz2b69.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/470369/original/file-20220622-23-iz2b69.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/470369/original/file-20220622-23-iz2b69.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Certain topical ointments, like menthol and capsaicin, can crowd out pain signals with different sensations.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/topical-ointment-royalty-free-image/1328896655">Photography By Tonelson/iStock via Getty Images</a></span>
</figcaption>
</figure>
<p>Because these topical medications work on the tiny nerves in the skin, they are best used for pain directly affecting the skin. For example, a <a href="https://doi.org/10.2147%2FJMDH.S106340">shingles infection</a> can damage the nerves in the skin, causing them to become overactive and send persistent pain signals to the brain. Silencing those nerves with topical lidocaine or an overwhelming dose of capsaicin can reduce these pain signals.</p>
<h2>Nerve injury medications</h2>
<p><a href="https://doi.org/10.1152/physrev.00045.2019">Nerve injuries</a>, most commonly from arthritis and diabetes, can cause the pain-sensing part of the nervous system to become overactive. These injuries sound the pain alarm even in the absence of tissue damage. The best painkillers in these conditions are those that dampen that alarm.</p>
<p><a href="https://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/in-depth/pain-medications/art-20045004">Antiepileptic drugs</a>, such as gabapentin (Neurontin), suppress the pain-sensing system by blocking electrical signaling in the nerves. However, gabapentin can also reduce nerve activity in other parts of the nervous system, potentially leading to sleepiness and confusion.</p>
<p><a href="https://www.mayoclinic.org/pain-medications/art-20045647">Antidepressants</a>, such as duloxetine and nortriptyline, are thought to work by increasing certain neurotransmitters in the spinal cord and brain involved in regulating pain pathways. But they may also alter chemical signaling in the gastrointestinal tract, leading to an upset stomach.</p>
<p>All these medications are prescribed by doctors.</p>
<h2>Opioids</h2>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/18443637/">Opioids</a> are chemicals found or derived from the opium poppy. One of the earliest opioids, morphine, was purified in the 1800s. Since then, medical use of opioids has expanded to include many natural and synthetic derivatives of morphine with varying potency and duration. Some common examples include codeine, tramadol, hydrocodone, oxycodone, buprenorphine and fentanyl.</p>
<p>Opioids decrease pain by activating the body’s endorphin system. <a href="https://www.ncbi.nlm.nih.gov/books/NBK470306/">Endorphins</a> are a type of opioid your body naturally produces that decreases incoming signals of injury and produces feelings of euphoria – the so-called “runner’s high.” Opioids simulate the effects of endorphins by acting on similar targets in the body.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/NDVV_M__CSI?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">While opioids can provide strong pain relief, they are not meant for long-term use because they are addictive.</span></figcaption>
</figure>
<p>Although opioids can decrease some types of acute pain, such as after surgery, musculoskeletal injuries like a broken leg or <a href="https://doi.org/10.1002%2F14651858.CD012592.pub2">cancer pain</a>, they are often ineffective for <a href="https://doi.org/10.1001/jama.2018.18472">neuropathic injuries and chronic pain</a>. </p>
<p>Because the body uses opioid receptors in other organ systems like the gastrointestinal tract and the lungs, side effects and risks include constipation and potentially fatal suppression of breathing. Prolonged use of opioids may also lead to <a href="https://www.merckmanuals.com/home/drugs/factors-affecting-response-to-drugs/tolerance-and-resistance-to-drugs">tolerance</a>, where more drug is required to get the same painkilling effect. This is why opioids can be addictive and are not intended for long-term use. All opioids are controlled substances and are carefully prescribed by doctors because of these side effects and risks.</p>
<h2>Cannabinoids</h2>
<p>Although cannabis has received a lot of attention for its potential medical uses, there <a href="https://doi.org/10.1002/phar.2115">isn’t sufficient evidence available</a> to conclude that it can effectively treat pain. Since the use of cannabis is <a href="https://www.investopedia.com/marijuana-legality-by-state-4844504">illegal at the federal level</a> in the U.S., high-quality clinical research funded by the federal government has been lacking. </p>
<p>Researchers do know that the body naturally produces <a href="https://doi.org/10.1038/npp.2017.204">endocannabinoids</a>, a form of the chemicals in cannabis, to decrease pain perception. Cannabinoids may also reduce inflammation. Given the lack of strong clinical evidence, physicians typically don’t recommend them over FDA-approved medications.</p>
<h2>Matching pain to drug</h2>
<p>While sounding the pain alarm is important for survival, dampening the klaxon when it’s too loud or unhelpful is sometimes necessary. </p>
<p>No existing medication can perfectly treat pain. Matching specific types of pain to drugs that target specific pathways can improve pain relief, but even then, medications can fail to work even for people with the same condition. More research that deepens the medical field’s understanding of the pain pathways and targets in the body can help lead to more effective treatments and improved pain management.</p><img src="https://counter.theconversation.com/content/173804/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rebecca Seal receives funding from National Institutes of Health</span></em></p><p class="fine-print"><em><span>Benedict Alter receives funding from National Institutes of Health, Foundation for Anesthesia Education and Research, and the International Anesthesia Research Society. </span></em></p>Different painkillers provide relief in different ways. The most effective medication is the one that best targets the type of pain you’re experiencing with minimal side effects.Rebecca Seal, Associate Professor of Neurobiology, University of PittsburghBenedict Alter, Assistant Professor of Anesthesiology and Perioperative Medicine, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1707962021-12-17T13:26:16Z2021-12-17T13:26:16ZThe ‘runner’s high’ may result from molecules called cannabinoids – the body’s own version of THC and CBD<figure><img src="https://images.theconversation.com/files/436228/original/file-20211207-172173-y26qwj.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5220%2C3453&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Exercise spurs the release of the body's natural cannabinoids, which have myriad benefits for mental health and stress relief.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/running-along-road-at-sunrise-in-iceland-royalty-free-image/578633163?adppopup=true">Luca Sage/Stone via Getty Images</a></span></figcaption></figure><p>Many people have experienced reductions in stress, pain and anxiety and sometimes even euphoria after exercise. What’s behind this so-called “runner’s high”? New research on the neuroscience of exercise may surprise you. </p>
<p>The “runner’s high” has long been attributed to <a href="https://doi.org/10.2519/jospt.1983.4.3.169">endorphins</a>. These are chemicals produced naturally in the body of humans and other animals after exercise and in response to pain or stress. </p>
<p>However, <a href="https://doi.org/10.1089/can.2021.0113">new research from my lab</a> summarizes nearly two decades of work on this topic. We found that exercise reliably increases levels of the body’s endocannabinoids – which are molecules that work to maintain balance in the brain and body – a process called “homeostasis.” This natural chemical boost may better explain some of the beneficial effects of exercise on brain and body. </p>
<p>I am a <a href="https://scholar.google.com/citations?user=S9ykvZUAAAAJ&hl=en">neuroscientist</a> at the Wayne State University School of Medicine. <a href="https://wsuthinklab.mystrikingly.com/">My lab</a> studies brain development and mental health, as well as the role of the endocannabinoid system in stress regulation and anxiety disorders in children and adolescents. </p>
<p>This research has implications for everyone who exercises with the aim of reducing stress and should serve as a motivator for those who don’t regularly exercise. </p>
<h2>Health benefits of exercise</h2>
<p><a href="https://doi.org/10.1097/HCO.0000000000000437">Several decades of research</a> has shown that exercise is beneficial for physical health. These studies find a consistent link between varying amounts of physical activity and reduced risk of <a href="http://dx.doi.org/10.1136/bjsports-2018-100393">premature death</a> and dozens of chronic health conditions, including <a href="https://doi.org/10.1007/s10654-015-0056-z">diabetes</a>, <a href="https://doi.org/10.1007/s40279-013-0065-6">hypertension</a>, <a href="https://doi.org/10.1016/j.jval.2018.06.020">cancer</a> and <a href="https://doi.org/10.3390/ijerph9020391">heart disease</a>.</p>
<figure class="align-center ">
<img alt="The marijuana plant cannabis." src="https://images.theconversation.com/files/436203/original/file-20211207-19-7n3tp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/436203/original/file-20211207-19-7n3tp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/436203/original/file-20211207-19-7n3tp8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/436203/original/file-20211207-19-7n3tp8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/436203/original/file-20211207-19-7n3tp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/436203/original/file-20211207-19-7n3tp8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/436203/original/file-20211207-19-7n3tp8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">While cannabinoids are produced in cannabis, the marijuana plant, they are also made in the human body.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/background-texture-of-marijuana-plants-outdoor-royalty-free-image/1258024915?adppopup=true">Iuliia Bondar/Moment via Getty Images</a></span>
</figcaption>
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<p>More recently – over about the past <a href="https://doi.org/10.3389/fpsyt.2014.00066">two decades</a> – mounting research shows that exercise is also <a href="https://theconversation.com/swimming-gives-your-brain-a-boost-but-scientists-dont-know-yet-why-its-better-than-other-aerobic-activities-164297">highly beneficial for mental health</a>. In fact, regular exercise is associated with lower symptoms of anxiety, depression, Parkinson’s disease and other common mental health or <a href="https://doi.org/10.1159/000223730">neurological problems</a>. Consistent exercise <a href="https://doi.org/10.1159/000350946">is also linked to</a> better cognitive performance, improved mood, lower stress and higher self-esteem. </p>
<p>It is not yet clear what is behind these mental health boosts. We do know that exercise has a variety of effects on the brain, including raising <a href="https://doi.org/10.1038/tp.2017.135">metabolism</a> and <a href="https://doi.org/10.3233/JAD-201456">blood flow</a>, promoting the formation of <a href="https://doi.org/10.3389/fnins.2018.00052">new brain cells</a> – a process called neurogenesis – and increasing the release of several chemicals in the brain. </p>
<p>Some of these chemicals are called neurotrophic factors, such as <a href="https://doi.org/10.1159/000223730">brain-derived neurotrophic factor</a>. BDNF is intricately involved in brain “plasticity,” or changes in activity of brain cells, including those related to <a href="https://doi.org/10.3389/fncel.2019.00363">learning and memory</a>.</p>
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<figcaption><span class="caption">From the Dana Foundation: “How Exercise Affects The Brain”</span></figcaption>
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<p>Scientists have also shown that exercise increases blood levels of endorphins, one of the body’s natural opioids. Opioids are chemicals that work in the brain and have a variety of effects, including <a href="https://doi.org/10.3389/fpain.2021.721357">helping to relieve pain</a>. Some <a href="https://doi.org/10.1093/cercor/bhn013">early research</a> in the 1980s contributed to the long-standing popular belief that this endorphin release is related to the euphoric feeling known as the runner’s high. </p>
<p>However, <a href="http://dx.doi.org/10.1136/bjsm.2004.011718">scientists have</a> <a href="https://doi.org/10.1073/pnas.1514996112">long questioned</a> the role of endorphins in the runner’s high sensation, in part because endorphins cannot cross into the brain through the <a href="https://doi.org/10.1101/cshperspect.a020412">blood-brain barrier</a>, which protects the brain from toxins and pathogens. So endorphins are not likely to be the main driver for the beneficial effects of exercise on mood and mental state.</p>
<p>This is where our research and <a href="http://dx.doi.org/10.1136/bjsm.2004.011718">that of others</a> points to the role of our body’s natural versions of cannabinoids, called endocannabinoids.</p>
<h2>The surprising role of endocannabinoids</h2>
<p>You <a href="https://www.healthline.com/health/cbd-vs-thc">may be familiar with</a> cannabinoids such as tetrahydrocannabinol – better known as THC – the psychoactive compound in cannabis (from the <em>Cannabis sativa L.</em> plant) that causes people to feel high. Or you may have heard of <a href="https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis">cannabidiol, commonly known as CBD, an extract of cannabis</a> that is infused in some foods, medicines, oils and many other products. </p>
<p>But many people do not realize that humans also create their own versions of these chemicals, called endocannabinoids. These are tiny molecules made of lipids – or fats – that circulate in the brain and body; “endo” refers to those produced in the body rather than from a plant or in a lab.</p>
<p>Endocannabinoids work on cannabinoid receptors <a href="https://doi.org/10.1073/pnas.0703472104">throughout the brain</a> and body. They cause a variety of effects, including pain relief, reduction of anxiety and stress and enhanced learning and memory. They also affect hunger, inflammation and <a href="https://dx.doi.org/10.1038%2Fnpp.2017.130">immune functioning</a>. Endocannabinoid levels can be influenced by food, time of day, exercise, obesity, injury, inflammation and stress. </p>
<p>It’s worth noting that one should not be tempted to forgo a run or bike ride and resort to smoking or ingesting cannabis instead. Endocannabinoids lack the unwanted effects that come with getting high, such as <a href="https://doi.org/10.1007/s00213-006-0508-y">mental impairment</a>.</p>
<h2>Understanding the runner’s high</h2>
<p>Studies <a href="https://doi.org/10.1016/j.psyneuen.2021.105173">in humans</a> and in <a href="https://doi.org/10.1073/pnas.1514996112">animal models</a> are pointing to endocannabinoids – not endorphins – as the star players in the runner’s high.</p>
<p>These elegant studies demonstrate that when opioid receptors are blocked – in <a href="https://doi.org/10.1016/j.psyneuen.2021.105173">one example</a> by a drug called naltrexone – people still experienced euphoria and reduced pain and anxiety after exercise. On the flip side, the studies showed that blocking the effects of cannabinoid receptors reduced the beneficial effects of exercise on euphoria, pain and anxiety. </p>
<p>While <a href="https://doi.org/10.1016/j.mhpa.2020.100366">several studies</a> <a href="https://doi.org/10.1007/s00421-012-2495-5">have shown</a> that exercise increases the levels of endocannabinoids circulating in the blood, some have reported inconsistent findings, or that different endocannabinoids produce <a href="https://doi.org/10.3389/fnbeh.2018.00269">varying effects</a>. We also don’t know yet if all types of exercise, such as cycling, running or resistance exercise like weightlifting, produce similar results. And it is an open question whether people with and without preexisting health conditions like depression, PTSD or fibromyalgia experience the same endocannabinoid boosts.</p>
<p>To address these questions, an undergraduate student in my lab, Shreya Desai, led a <a href="https://doi.org/10.1089/can.2021.0113">systematic review and meta-analysis</a> of 33 published studies on the impact of exercise on endocannabinoid levels. We compared the effects of an “acute” exercise session – like going for a 30-minute run or cycle – with the effects of “chronic” programs, such as a 10-week running or weightlifting program. We separated them out because different levels and patterns of exertion could have very distinct effects on endocannabinoid responses.</p>
<p>We found that acute exercise consistently boosted endocannabinoid levels across studies. The effects were most consistent for a chemical messenger known as anandamide – the so-called <a href="https://doi.org/10.1126/science.1470919">“bliss” molecule</a>, which was named, in part, for its positive effects on mood.</p>
<p>Interestingly, we observed this exercise-related boost in endocannabinoids across different types of exercise, including running, swimming and weightlifting, and across individuals with and without preexisting health conditions. Although only a few studies looked at intensity and duration of exercise, it appears that moderate levels of exercise intensity – such as cycling or running – are more effective than lower-intensity exercise – like walking at slow speeds or low incline – when it comes to raising endocannabinoid levels. This suggests that it is important to keep your heart rate elevated – that is, between about 70% and 80% of age-adjusted maximum heart rate – for at least 30 minutes to reap the full benefits. </p>
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<p>There are still a lot of questions about the links between endocannabinoids and beneficial effects from exercise. For example, we didn’t see consistent effects for how a chronic exercise regimen, such as a six-week cycling program, might affect resting endocannabinoid levels. Likewise, it isn’t yet clear what the minimum amount of exercise is to get a boost in endocannabinoids, and how long these compounds remain elevated after acute exercise. </p>
<p>Despite these open questions, these findings bring researchers one step closer to understanding how exercise benefits brain and body. And they offer an important motivator for making time for exercise during the rush of the holidays.</p><img src="https://counter.theconversation.com/content/170796/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr. Marusak is funded, in part, by the National Institutes of Mental Health (K01MH119241).</span></em></p>A growing body of research points to the body’s natural cannabinoid system as the primary driver behind the runner’s high – and the mental health boost and stress relief following exercise.Hilary A. Marusak, Assistant Professor of Psychiatry and Behavioral Neurosciences, Wayne State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1699982021-11-21T13:20:58Z2021-11-21T13:20:58ZIndica and sativa labels are largely meaningless when it comes to cannabis complexities<figure><img src="https://images.theconversation.com/files/432299/original/file-20211117-23-cj20ew.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C3376&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cannabis is a complex plant, ideally labelling of cannabis products should accurately reflect the combinations of psychoactive ingredients present in a strain.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/indica-and-sativa-labels-are-largely-meaningless-when-it-comes-to-cannabis-complexities" width="100%" height="400"></iframe>
<p>Indica and sativa are commonly used to describe cannabis strains, but what’s the difference between these two labels?</p>
<p>Almost <a href="https://www150.statcan.gc.ca/n1/pub/82-003-x/2020002/article/00002-eng.htm">half of all Canadians have tried cannabis at some point in their lives</a>. If you’re one of them, you’ve probably been confronted with the choice between buying strains labelled indica or sativa.</p>
<p>Some people are adamant that <a href="https://www.thrillist.com/lifestyle/nation/indica-vs-sativa-differences-in-effects-and-appearance">indica strains are sedative with earthy aromas</a>. In contrast, sativa strains are supposedly energizing with sweet aromas. However, the extent to which indica and sativa labels actually capture meaningful information is unclear.</p>
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<a href="https://theconversation.com/wheres-the-weed-branding-is-essential-for-cannabis-companies-87400">'Where's the weed?' Branding is essential for cannabis companies</a>
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<h2>Detailed strain analyses</h2>
<p>Our team of researchers at Dalhousie University worked with Bedrocan International, a Dutch medical cannabis company, to study hundreds of cannabis strains with indica and sativa labels. We measured the chemical compounds produced by each strain. This included not only the major psychoactive cannabinoids like THC and CBD but also the terpenes that give cannabis its distinctive aromas. We also measured the genetic profiles and were then able to examine the chemical and genetic differences between strains.</p>
<p>If labels describing cannabis strains do in fact represent two distinct groups of cannabis, then the differences should be reflected by chemical and genetic differences. Our study, published in <em>Nature Plants</em>, found that indica and sativa labels are largely meaningless. </p>
<p>It was frequently the case that <a href="https://doi.org/10.1038/s41477-021-01003-y">strains labelled indica were just as closely related to strains labelled sativa as they were to other strains labelled indica</a>.</p>
<p>An <a href="https://phytokeys.pensoft.net/article/46700/element/4/459">example that illustrates the inconsistent use of these labels</a> is that in 1999, a cannabis strain named “AK 47” won the <a href="https://www.cannabiscupwinners.com/winner-links/2-cool-cannabis-hemp-links/37-seeds-online.html">Sativa Cup</a> in the Cannabis Cup. The same strain went on to win the <a href="https://www.cannabiscupwinners.com/2015-12-03-14-51-30/high-times-cannabis-cup/cannabis-cup-2003.html">Indica Cup</a> in the same competition four years later.</p>
<p>Not only did we find that indica/sativa labelling is misleading, but so are the names given to strains. For example, we found that two strains both named “OG Kush” were more similar to other strains with different names than they were to one another. Overall, strain names are often not reliable indicators of a plant’s genetic identity and chemical profile.</p>
<h2>Broken telephone</h2>
<p>If you’ve ever played a game of telephone, you’ll know how easily words can get twisted. Usually by the end of the game, the words are completely different from when it started. The way in which indica and sativa have been used over the years is similar to a very long game of broken telephone. </p>
<p>At one point in time, indica and sativa may have been used to describe two distinct species of cannabis. Over time, the two species likely hybridized to the extent that most of the cannabis grown and consumed today is a mashup of the two ancestral lineages. However, the use of indica and sativa has persisted as vernacular labels and have today taken on new meaning to describe psychoactive effects, aromas and morphologies.</p>
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<a href="https://images.theconversation.com/files/432300/original/file-20211117-21-su2u95.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An older woman smokes a joint and smiles" src="https://images.theconversation.com/files/432300/original/file-20211117-21-su2u95.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/432300/original/file-20211117-21-su2u95.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/432300/original/file-20211117-21-su2u95.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/432300/original/file-20211117-21-su2u95.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/432300/original/file-20211117-21-su2u95.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/432300/original/file-20211117-21-su2u95.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/432300/original/file-20211117-21-su2u95.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">People consume cannabis for a variety of reasons, including recreational and therapeutic purposes.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<p>In certain cases, we found weak correlations between indica and sativa labels and a small number of the aromatic terpenes. Strains labelled indica tended to have higher amounts of <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/myrcene">the terpene myrcene</a>, which is thought to contribute to sedation and the <a href="https://cannabis.net/blog/history/what-does-it-mean-to-be-couchlocked">more intense “couch-lock” effect</a>.</p>
<p>On the other hand, strains labelled sativa had higher amounts of sweet and herbal terpenes, like farnesene and bergamotene. These findings echo what cannabis consumers have long said about the differences between the two labels. </p>
<p>We have a hunch that due to the absence of strict naming and pedigree tracking, producers have been assigning labels to cannabis based primarily on aroma. Considering the historically clandestine nature of cannabis breeding, it’s unsurprising that labelling would have been relegated to more subjective methods, like smell, rather than a more consistent system that reliably distinguishes strains.</p>
<h2>Improving labelling</h2>
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<span class="caption">After cannabis was legalized, a flood of cannabis strains and products entered the market, from consumables to oils and foodstuffs.</span>
<span class="attribution"><span class="source">(THE CANADIAN PRESS/Nathan Denette)</span></span>
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<p>As Canada moves into its third year of legalized cannabis consumption, there is a need to revamp how cannabis is labelled, and clearly communicate its effects. The current way we label and name cannabis strains appears to fall short of the labelling standards applied to other agricultural crops.</p>
<p>For instance, imagine walking into a grocery store and buying a crunchy Honeycrisp apple, only to realize when you got home that it was in fact a less crisp McIntosh apple. Unlike apples, cannabis produces psychoactive compounds — the inconsistency of these labels could be very frustrating. From a medical standpoint, improper labelling could lead to negative or undesirable health outcomes. </p>
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<a href="https://theconversation.com/give-cannabis-producers-more-packaging-and-labelling-flexibility-152727">Give cannabis producers more packaging and labelling flexibility</a>
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<p>Cannabis is an incredibly diverse crop that produces over <a href="https://doi.org/10.1371/journal.pone.0192247">one hundred aromatic</a> and psychoactive compounds with distinct aromas and effects. Adding to the complexity of cannabis compounds, research has also indicated the possibility of an “<a href="https://doi.org/10.1111/j.1476-5381.2011.01238.x">entourage effect</a>,” whereby terpenes interact with cannabinoids to mediate different psychoactive effects. </p>
<p>Reducing cannabis to two categories does little to capture this incredible versatility and potential. We are likely better off abandoning the use of the terms sativa and indica altogether, and instead labelling cannabis with the quantities of key compounds that have medicinal effects or are known to affect consumer preferences.</p><img src="https://counter.theconversation.com/content/169998/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sophie Watts receives funding through a Vanier Scholarship from the National Sciences and Engineering Research Council of Canada. Bedrocan International funded the research referenced in this article.</span></em></p>Cannabis labelling is often misleading. Labelling cannabis products with quantities of key compounds will help consumers make informed decisions.Sophie Watts, PhD student, Plant, Food and Environmental Sciences, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1538412021-01-28T20:07:35Z2021-01-28T20:07:35ZWeed withdrawal: More than half of people using medical cannabis for pain experience withdrawal symptoms<figure><img src="https://images.theconversation.com/files/380735/original/file-20210126-21-1fdxais.jpg?ixlib=rb-1.1.0&rect=54%2C0%2C5083%2C3065&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The use of cannabis, though safer than many other drugs, is not entirely without risk. </span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/MarijuanaSmallTowns/8e11f4e5d6524549aa9a41f43fb79e87/photo?Query=marijuana%20AND%20jars&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=122&currentItemNo=0">AP Photo/David Zalubowski, file</a></span></figcaption></figure><figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/380977/original/file-20210127-23-1y9tl5r.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/380977/original/file-20210127-23-1y9tl5r.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=255&fit=crop&dpr=1 600w, https://images.theconversation.com/files/380977/original/file-20210127-23-1y9tl5r.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=255&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/380977/original/file-20210127-23-1y9tl5r.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=255&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/380977/original/file-20210127-23-1y9tl5r.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=321&fit=crop&dpr=1 754w, https://images.theconversation.com/files/380977/original/file-20210127-23-1y9tl5r.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=321&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/380977/original/file-20210127-23-1y9tl5r.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=321&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>In stark contrast to the <a href="https://en.wikipedia.org/wiki/Reefer_Madness">overblown fears</a> portrayed during decades past, these days, most people <a href="https://doi.org/10.1016/j.ypmed.2017.07.008">think cannabis is relatively harmless</a>. While weed is indeed less dangerous than some other drugs, it is not without risks. </p>
<p>In a study published Jan. 5, my colleagues and I found that 59% percent of people using medical cannabis for chronic pain experienced <a href="https://doi.org/10.1111/add.15370">moderate to severe withdrawal symptoms</a> if they stopped ingesting weed for hours or days.</p>
<p>Most states in the U.S. have legalized cannabis for medical purposes and 15 have legalized it for recreational use. More people are using cannabis, <a href="https://doi.org/10.1001/jamainternmed.2019.7517">especially older adults</a>, and the <a href="https://doi.org/10.1016/j.ypmed.2017.07.008">perceived harms from weed use are steadily decreasing</a>. While many people report therapeutic benefits or enjoy recreational use of cannabis, it is important people understand the <a href="https://doi.org/10.1037/adb0000452">potential risks of cannabis use</a> too.</p>
<h2>What cannabis withdrawal looks like</h2>
<p>Cannabis withdrawal symptoms can include both physical and psychological experiences that emerge when someone <a href="https://doi.org/10.1097/01.yco.0000218592.00689.e5">comes down from being high or goes for a period of time without use</a>. </p>
<p>When people use cannabis regularly – such as daily or nearly daily – parts of the brain become reliant on cannabinoids, the <a href="https://doi.org/10.1111/bcp.13710">psychoactive chemicals in cannabis</a>. Cannabinoids are naturally produced in the body, but at a much lower level than is available in most cannabis products. Among those who don’t use weed for a period of several hours or days, cannabinoid levels drop and they <a href="https://doi.org/10.1007/s40429-017-0143-1">experience withdrawal symptoms</a>. These can including irritability, depressed mood, decreased appetite, sleep difficulties, a desire or craving to use cannabis, restlessness, anxiety, increased aggression, headaches, shakiness, nausea, increased anger, strange dreams, stomach pain and sweating. </p>
<p>Cannabis withdrawal symptoms usually go away within one to two weeks after use is stopped as the body <a href="https://doi-org.proxy.lib.umich.edu/10.1037/0021-843X.112.3.393">adjusts back to its own natural production of cannabinoids</a>. Unlike withdrawal from some psychoactive substances – such as alcohol – cannabis withdrawal is not life threatening or medically dangerous. But it does exist. Cannabis withdrawal can also be quite unpleasant and people can end up continuing their cannabis use – even when they want to cut back – just to avoid experiencing withdrawal.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/380740/original/file-20210126-23-giekg0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A man inhales marijuana smoke from a glass bong in a room with other people around." src="https://images.theconversation.com/files/380740/original/file-20210126-23-giekg0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/380740/original/file-20210126-23-giekg0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=405&fit=crop&dpr=1 600w, https://images.theconversation.com/files/380740/original/file-20210126-23-giekg0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=405&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/380740/original/file-20210126-23-giekg0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=405&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/380740/original/file-20210126-23-giekg0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=509&fit=crop&dpr=1 754w, https://images.theconversation.com/files/380740/original/file-20210126-23-giekg0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=509&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/380740/original/file-20210126-23-giekg0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=509&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Regular use of cannabis can result in dependency and withdrawal when a person stops using cannabis.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/EndOfSmoking/0de2dc43b88b4467b075f5e42f86bbac/photo?Query=smoking%20AND%20marijuana&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=334&currentItemNo=10">AP Photo/Ted S. Warren</a></span>
</figcaption>
</figure>
<h2>How common are withdrawal symptoms?</h2>
<p>To figure out how common withdrawal symptoms are, over two years, my colleagues and I repeatedly surveyed 527 people who were using medical weed for chronic pain. We found that 59% of people who use medical cannabis for chronic pain <a href="https://doi.org/10.1111/add.15370">had moderate to severe withdrawal symptoms</a>. The most common symptoms were sleep difficulties, irritability and anxiety.</p>
<p>We also found that cannabis withdrawal symptoms were more severe in younger people, people with mental health problems, people who had a longer history of cannabis use and people who used more frequently or in larger amounts. Additionally, we found that smoking cannabis – rather than eating or topically applying it – was correlated with worse withdrawal symptoms. </p>
<p>Our team also looked at how people’s withdrawal symptoms changed over time. Most continued to experience the same severity of withdrawal symptoms any time they stopped ingesting cannabis over the two years of the study, but about 10% – particularly younger people – got worse over time. As with most dependency-forming substances, reducing the frequency or amount of cannabis use may help to alleviate these symptoms. </p>
<p>Our study looked at people who use medical cannabis only for pain. But in another recent meta-analysis that included both recreational and medical use, researchers found that <a href="https://doi.org/10.1001/jamanetworkopen.2020.2370">47% of frequent cannabis users experience withdrawals</a>. </p>
<p>Cannabis may not be the demon drug from <a href="https://www.imdb.com/title/tt0028346/">“Reefer Madness,”</a> but neither is it a wonder–plant with limitless upsides and no downsides. As cannabis use <a href="https://doi.org/10.1080/00952990.2019.1569668">increases across the U.S.</a>, it’s important for people to understand that regular use can lead to withdrawals, and to know what those symptoms are.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/153841/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lara Coughlin receives funding from the National Institute on Alcohol Abuse and Alcoholism. </span></em></p>Weed, though far less dangerous than many other drugs, is not entirely without risk. Some 59% of people treating pain with medical cannabis experience moderate to severe withdrawal symptomsLara Coughlin, Assistant Professor of Psychiatry, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1496122020-11-17T20:00:02Z2020-11-17T20:00:02ZCBD sales are soaring, but evidence is still slim that the cannabis derivative makes a difference for anxiety or pain<figure><img src="https://images.theconversation.com/files/369455/original/file-20201115-13-1k9f1pk.jpg?ixlib=rb-1.1.0&rect=0%2C43%2C4792%2C2953&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Hundreds of CBD products – including gummies – are now on the market.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/gummies-from-medical-mary-are-on-display-at-the-6th-annual-news-photo/1171381576?adppopup=true">Frederic J. Brown via Getty Images</a></span></figcaption></figure><p>Many people have turned to <a href="https://doi.org/10.1080/10550887.2020.1811455">cannabis</a> and its derivatives as they search for pandemic relief, and one of the most widely available ones is CBD. It is also legal. You can buy oils, tinctures, capsules, gummies, cosmetics and even <a href="https://nordicbotanics.com/product/cbd-toilet-paper/">toilet paper</a> said to contain the molecule. <a href="https://www.marthastewart.com/7985856/martha-stewart-canopy-growth-cbd">Martha Stewart has a line of CBD products</a>, and some companies are marketing CBD products for holiday gifts. And, you can even buy CBD products for your pet.</p>
<p>An investment bank has estimated that this <a href="https://www.nytimes.com/2020/05/23/sunday-review/coronavirus-cbd-oil.html">market will be worth US$16 billion by 2025</a>, even though many of the products that allegedly contain CBD may <a href="https://www.fda.gov/news-events/public-health-focus/warning-letters-and-test-results-cannabidiol-related-products">not contain any CBD all</a>. And, if they do, the amount often is far less than the amount stated on the product bottle or box.</p>
<p>The CBD craze started in 2018, after the U.S. Food and Drug Administration <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms">approved</a> Epidiolex, the first drug containing CBD, used to treat two rare and severe types of childhood epilepsy. Since that approval, research on the possible medical applications of CBD has risen sharply.</p>
<p>But while the ads boasting its benefits are ubiquitous, there is still much we scientists don’t know, including <a href="https://theconversation.com/no-cbd-is-not-a-miracle-molecule-that-can-cure-coronavirus-just-as-it-wont-cure-many-other-maladies-its-proponents-claim-132492">whether CBD can actually reduce stress and anxiety</a>. </p>
<p>That said, <a href="https://scholar.google.com/citations?user=S9ykvZUAAAAJ&hl=en">as a neuroscientist</a> who studies childhood anxiety disorders and the neurobiology of stress and anxiety, I am encouraged by some of the preliminary research. For example, pre-clinical studies show that CBD can reduce fear and anxiety-related behaviors in <a href="https://pubmed.ncbi.nlm.nih.gov/2162942/">mice</a>. Neuroimaging studies in humans show that CBD can reduce activity in the <a href="https://pubmed.ncbi.nlm.nih.gov/19124693/">amygdala and anterior cingulate cortex</a>, brain regions associated with stress and anxiety. Yet more research must take place before we can be certain.</p>
<figure class="align-center ">
<img alt="CBD products can be found all across the U.S." src="https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Early evidence suggests CBD could help with inflammation and some arthritic conditions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/various-wellness-products-containing-full-spectrum-news-photo/1266349533?adppopup=true">Smith Collection/Gado via Getty Images</a></span>
</figcaption>
</figure>
<h2>What is CBD?</h2>
<p>CBD is only one of more than 100 cannabinoids and other molecules found in the marijuana plant (<em>Cannabis Sativa</em>). Cannabinoids are known as signaling molecules: They interact with other molecules in the body, including the brain. For example, THC, the plant’s most abundant cannabinoid, interacts with brain receptors to cause the “high” feeling. Cannabinoids can also impact the immune system; this may help alleviate inflammation, arthritic conditions and neuropathic pain. </p>
<p>CBD, the plant’s second most abundant cannabinoid, does not contain THC, and therefore does not have psychoactive effects. There is no high. CBD also doesn’t seem to bind strongly with typical cannabinoid receptors. Instead, it interacts with other signaling molecules <a href="https://doi.org/10.1002/prp2.682">in the brain and throughout the body</a>. For example, CBD may act on the serotonin system, particularly serotonin <a href="https://doi.org/%2010.1097/j.pain.0000000000001386">5-HT1A receptors</a>, which are involved in signaling pathways that regulate pain, depression and anxiety.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573017/">Evidence suggests</a> that CBD may interact with the body’s own natural cannabinoid system – the endocannabinoid system – to boost levels of anandamide, the <a href="https://www.sciencedirect.com/topics/neuroscience/anandamide">“bliss molecule,”</a> our body’s natural version of THC, perhaps changing the way people think and feel. And CBD may act with the body’s natural <a href="https://pubmed.ncbi.nlm.nih.gov/33169541/">opioid system</a>. This would explain some of the reported pain-relieving qualities. Yet with all of these potential effects, we still don’t understand how CBD works to alleviate pain, anxiety, inflammation and even epilepsy, the only disorder for which a drug containing CBD has been FDA-approved. </p>
<p>In medicine, to see if something works, a randomized placebo-controlled trial is the gold standard. <a href="https://clinicaltrials.gov/ct2/results?cond=anxiety&term=cbd&cntry=&state=&city=&dist=">Several clinical trials</a> are underway to see if CBD works for anxiety, COVID-19-induced stress, and for the treatment of anxiety disorders – worldwide, the <a href="https://doi.org/10.1017/S1121189X00001421">most common mental disorder</a>. There are several <a href="https://www.nami.org/About-Mental-Illness/Mental-Health-Conditions/Anxiety-Disorders">types of anxiety</a> disorders, including generalized anxiety, which relates to excess worrying about everyday life, and social anxiety disorder, which includes intense fear around social interactions. Symptoms of anxiety can also vary, including feeling tense, irritable or jumpy, and also feeling that your heart is racing, sweating, headaches, stomachaches and insomnia. </p>
<p>Recent studies show that COVID-19 has exacerbated some already existing mental health problems. And, even for people without a history of mental health problems, <a href="https://doi.org/10.1016/S2215-0366(20)30462-4">a COVID-19 diagnosis increases</a> the risk of anxiety and other psychiatric disorders. </p>
<p>Preliminary and recent studies on the potential for CBD to reduce stress and anxiety <a href="https://doi.org/10.1089/can.2019.0052">are promising</a>. <a href="https://doi.org/10.1038/npp.2011.6">Two small preliminary studies</a>, for instance, tested whether CBD reduced anxiety in individuals with social anxiety disorder and in healthy volunteers. A public speaking test was simulated; those given CBD reported lower anxiety compared to those given a placebo (sugar pill). But we must wait for results of larger clinical trials to know if CBD works, and under what conditions. </p>
<figure class="align-center ">
<img alt="Dozens of food products laced with marijuana or CBD are on the market." src="https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dozens of marijuana or CBD-laced food products are now available.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/marijuana-brownies-royalty-free-image/1185895952?adppopup=true">Lauri Patterson via Getty Images</a></span>
</figcaption>
</figure>
<h2>Popularity outpaces science</h2>
<p>In November, voters in four states – Arizona, Montana, New Jersey and South Dakota – <a href="https://www.cnbc.com/2020/11/04/voters-chose-to-legalize-tax-recreational-marijuana-in-these-4-states.html">voted</a> to join 11 other states to legalize recreational cannabis use in the U.S. But the rise in legalization and decriminalization of cannabinoids, along with their widespread popularity, significantly outpaces the science. There is more research today on the potential medical applications of cannabinoids than ever before – including $196 million from the <a href="https://report.nih.gov/categorical_spending.aspx">National Institutes of Health</a>, along with $31 million on CBD in the year 2020.</p>
<p>Still, this is a relatively new area of medical research. CBD was discovered in 1940; the body’s own endocannabinoid system wasn’t discovered until 1992. This is shocking given that humans have been using cannabis and cannabis-based products for thousands of years. Evidence suggests medical use of cannabis dates back to ancient times, including around 2700 B.C., when Emperor Shen Nung – known as the father of Chinese medicine – was exploring cannabis use to treat over 100 different ailments, including <a href="https://books.google.com/books?hl=en&lr=&id=1AWGDhIOvk0C&oi=fnd&pg=PA35&dq=History+of+Therapeutic+Cannabis&ots=a3wpiboMDk&sig=sKYx899iOcrohVJjx4GoO_Cve3s#v=onepage&q=History%20of%20Therapeutic%20Cannabis&f=false">gout, rheumatism and malaria</a>.</p>
<p>But today, doctors, nurses and other medical providers are <a href="https://doi.org/10.1001/jamainternmed.2019.1529">generally not well prepared</a> to answer patients’ questions about potential risks, benefits and applications. This may be because cannabis and CBD are not a part of standard medical education. For example, a 2017 survey of medical residents and fellows in St. Louis found that 84.9% reported receiving no medical education about cannabis. </p>
<p>Government restrictions also contribute to the lag. Cannabis is still illegal at the federal level. In 2016, the U.S. Drug Enforcement Administration <a href="https://www.deadiversion.usdoj.gov/schedules/marijuana/Maintaining%20Marijuana%20in%20Schedule%20I%20of%20the%20Controlled%20Substances%20Act.pdf">affirmed</a> its classification of cannabis as a Schedule I drug. That put it in the same category as deadly and addictive drugs: opioids (like heroine and oxycodone). This is in stark contrast to research that shows cannabis is relatively safe and with a low potential for abuse. But because of this federal classification, scientific and medical study of cannabis is tightly regulated. Researchers need a special license from the DEA to study it. Physicians may also feel poorly trained because more and higher-quality research is needed before they make <a href="https://doi.org/10.1001/jamainternmed.2019.1529">recommendations</a> to their patients. </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>Researching CBD and other cannabis derivatives is also difficult. CBD products are currently unregulated by the U.S. Food and Drug Administration. This means CBD is not considered a dietary supplement, and marketed CBD products cannot make any health-related claims. This also means there’s no oversight on what’s in CBD products, which is why they are <a href="https://doi.org/10.1001/jama.2017.11909">frequently mislabeled</a>. This creates a “Wild West” environment for consumers. </p>
<p>So should you try CBD for stress and anxiety? The bottom line: It’s too early to tell. Those CBD gummies might just be an expensive placebo. In the meantime, turn to <a href="https://www.ajpmonline.org/article/S0749-3797(19)30246-6/fulltext">evidence-based treatments</a> for stress and anxiety relief – like good old-fashioned exercise.</p><img src="https://counter.theconversation.com/content/149612/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr. Marusak is supported, in part, by grants from the National Institute of Mental Health. </span></em></p>The jury’s still out on whether or not CBD relieves stress and anxiety.Hilary A. Marusak, Assistant Professor, Wayne State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1253702019-11-05T16:40:45Z2019-11-05T16:40:45ZCannabis shows potential for treating PTSD: New study<figure><img src="https://images.theconversation.com/files/298384/original/file-20191023-119409-ujvfo1.jpg?ixlib=rb-1.1.0&rect=16%2C133%2C2674%2C1888&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Research shows that cannabis use by people living with post-traumatic stress disorder may reduce their likelihood of depression and suicide.</span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Ryan Remiorz</span></span></figcaption></figure><p>Post-traumatic stress disorder (PTSD), a psychiatric condition linked to surviving or witnessing a traumatic life event, will <a href="https://doi.org/10.1192/bjp.bp.115.176628">affect around one in 10 Canadians</a> at some point in their lives. PTSD can cause <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181836/">agitation, flashbacks, impaired concentration and memory, insomnia and nightmares</a> and these symptoms can increase the risk of substance abuse and dependence, depression and suicide.</p>
<p>Many patients <a href="https://doi.org/10.4088/JCP.15m09932">struggle to find adequate symptom relief</a> from <a href="https://www.nejm.org/doi/full/10.1056/NEJMra1612499">conventional treatments for PTSD</a> including anti-depressant or anti-psychotic medications and psychological treatments such as trauma-focused cognitive behavioural therapy. </p>
<p>Unsurprisingly, many turn to alternative ways of coping — such as medical cannabis use. This is especially evident in the dramatic rise in number of <a href="https://www.veterans.gc.ca/eng/about-vac/research/research-directorate/publications/reports/cmp2018">Canadian military veterans receiving government reimbursement for medical cannabis</a>, with <a href="http://publications.gc.ca/collections/collection_2019/sen/yc33-0/YC33-0-421-26-eng.pdf">PTSD as a common reason</a> for use.</p>
<p>The results of clinical trials testing <a href="https://clinicaltrials.gov/ct2/show/results/NCT02517424?view=results">cannabis as a PTSD treatment are pending</a>. Previous research has linked cannabis use with <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029083/">poorer mental health in PTSD patients</a>, but it’s unclear whether cannabis exacerbates PTSD symptoms, or if patients with worse symptoms are simply self-medicating more. Much of the existing evidence for cannabis as a PTSD treatment comes from <a href="https://doi.org/10.3109/00952990.2013.821477">patient reports of success</a>.</p>
<p>As epidemiologists and substance use researchers, we have been exploring the relationship between cannabis and PTSD using readily available <a href="http://www23.statcan.gc.ca/imdb/p2SV.pl?Function=getSurvey&SDDS=5015">Statistics Canada mental health data</a>. </p>
<p>In <a href="https://journals.sagepub.com/doi/full/10.1177/0269881119882806">a recent study, published in the <em>Journal of Psychopharmacology</em></a>, we found that PTSD increased the risk of major depressive episodes among Canadians who didn’t use cannabis by roughly seven times, and suicidal ideation by roughly five times. But, among Canadians who did use cannabis, PTSD was not statistically associated with either outcome.</p>
<h2>How cannabis works in the body</h2>
<p>Substance use, <a href="http://dx.doi.org/10.1037/adb0000110">including cannabis use</a>, is common among trauma survivors. It’s easy to write off the drug as just a tool to briefly escape negative feelings, at the risk of worsening longer-term symptoms. However, the relationship between cannabis and PTSD is more complex than it appears on the surface.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/298380/original/file-20191023-119414-fvaup7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/298380/original/file-20191023-119414-fvaup7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/298380/original/file-20191023-119414-fvaup7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/298380/original/file-20191023-119414-fvaup7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/298380/original/file-20191023-119414-fvaup7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/298380/original/file-20191023-119414-fvaup7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/298380/original/file-20191023-119414-fvaup7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A marine veteran shows support for cannabis for PTSD sufferers, outside the state capitol in Des Moines, Iowa, in 2015.</span>
<span class="attribution"><span class="source">(Michael Zamora/The Des Moines Register via AP)</span></span>
</figcaption>
</figure>
<p>Our bodies naturally produce molecules called <a href="https://doi.org/10.1016/j.biopsych.2015.07.028">endogenous cannabinoids that fit into special cannabinoid receptors</a> throughout the brain and body. This endocannabinoid system is involved in <a href="https://doi.org/10.1016/j.amjmed.2006.11.013">stabilizing bodily processes</a>, including regulating many functions of the brain that tend to be affected after traumatic experiences, such as <a href="https://doi.org/10.1002/dta.1377">fear, memory and sleep</a>.</p>
<p><a href="https://www.cpha.ca/sites/default/files/uploads/resources/cannabis/cannabasics-2018-fact-sheets-e.pdf">Certain components of the cannabis plant</a>, including the well-known molecules tetrahydrocannabinol (THC, the component of cannabis that produces the high) and cannabidiol (CBD, the component of cannabis that won’t get you high, but has potential for treating <a href="https://doi.org/10.1016/S1474-4422(15)00379-8">epilepsy</a>, <a href="https://doi.org/10.1016/j.bmc.2015.01.059">inflammation</a>, <a href="https://doi.org/10.1111/j.1476-5381.2010.01176.x">nausea</a> and <a href="https://doi.org/10.1007/s13311-015-0387-1">anxiety</a>) are also cannabinoids because of their structural similarity to endogenous cannabinoids. </p>
<p>Even though THC and CBD aren’t naturally produced in our bodies, <a href="https://doi.org/10.1016/j.mayocp.2019.01.003">they can interact with the endocannabinoid system to influence a number of biological processes.</a></p>
<p>Research is still uncovering if and how cannabis works within the body to affect the course of PTSD. Brain imaging research suggests that patients with PTSD have an <a href="https://doi.org/10.1038/mp.2013.61">abundance of cannabinoid receptors</a> but produce few <a href="https://doi.org/10.1016/j.psyneuen.2013.08.004">endogenous cannabinoids</a> to lock into them, meaning that supplementing the body with plant-based cannabinoids like THC might help some brain processes function as normal.</p>
<h2>Reduced depression and suicide</h2>
<p>Roughly one in four individuals with PTSD in the Statistics Canada survey data that we analyzed used cannabis, compared to about one in nine in the general population. </p>
<p>In our study, we used statistical models to quantify the relationship between having PTSD and recently experiencing a major depressive episode or suicidal ideation. We hypothesized that if cannabis helped mitigate symptoms of PTSD, we’d see a much weaker association between PTSD and these indicators of mental distress in the cannabis-using population.</p>
<p>Indeed, exploring the associations in this way while controlling for other factors (such as sex, age, income, other substance use, other mental health problems) supported our hypothesis. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/298386/original/file-20191023-119414-1uvqjxv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/298386/original/file-20191023-119414-1uvqjxv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/298386/original/file-20191023-119414-1uvqjxv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/298386/original/file-20191023-119414-1uvqjxv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/298386/original/file-20191023-119414-1uvqjxv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/298386/original/file-20191023-119414-1uvqjxv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/298386/original/file-20191023-119414-1uvqjxv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A customer sniffs a display sample of marijuana at Evergreen Cannabis, in Vancouver, B.C.</span>
<span class="attribution"><span class="source">(AP Photo/Elaine Thompson)</span></span>
</figcaption>
</figure>
<p>In a follow-up analysis of the 420 individuals in the sample who had PTSD, we categorised cannabis use into “no use,” “low-risk use” and “high-risk use” (meaning that they screened positive for cannabis abuse or dependence). </p>
<p>We found that low-risk cannabis users were actually less likely than non-users to develop a major depressive episode or to be suicidal, though there was a trend towards increased risk of both outcomes for the high-risk users.</p>
<h2>A promising new signal</h2>
<p>People with PTSD are more likely to experience depression and suicidal ideation. However, our findings suggested that these indicators of mental health were improved when they were engaging in lower-risk cannabis use.</p>
<p>Our study has a number of limitations that prevent us from being able to understand whether cannabis is what’s causing the reduced association between PTSD, depression and suicide. </p>
<p>For example, our data captures information covering participants’ experiences from the previous year, meaning we can’t actually decipher what came first: the cannabis use, the PTSD or the major psychological episodes. </p>
<p>We didn’t have detailed information about how participants used cannabis: for example, the type and dose of cannabis they used, how often they used it or how they consumed it. These details will be crucial to future research in this area.</p>
<p>Our study’s strength comes from its ability to describe patterns of PTSD symptoms and cannabis use in a large sample that’s considered to be representative of the Canadian population. Although our findings suggest that cannabis could be of possible therapeutic use in the treatment of PTSD, cannabis use is not without risks, including the development of <a href="https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/health-effects/addiction.html">cannabis use disorder</a>. </p>
<p>We’ve uncovered a promising new signal on the potential of cannabis-based therapies, but we look forward to much work ahead in understanding how they might fit into PTSD and mental health treatment more broadly.</p>
<p>[ <em>Deep knowledge, daily.</em> <a href="https://theconversation.com/ca/newsletters?utm_source=TCCA&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/125370/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephanie Lake receives doctoral funding from the Canadian Institutes of Health Research and the Pierre Elliott Trudeau Foundation. She is affiliated with Canadian Students for Sensible Drug Policy. </span></em></p><p class="fine-print"><em><span>M-J Milloy is supported by a Canadian Institutes of Health Research New Investigator Award, a Michael Smith Foundation for Health Research Scholar Award, and the National Institutes of Drug Abuse. His institution has received an unstructured gift to support his research from NG Biomed, Ltd, an applicant to the Canadian federal government for a license to produce medical cannabis. He is the Canopy Growth Professor of cannabis science at the University of British Columbia, a position created by an unstructured gift to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia's Ministry of Mental Health and Addictions. </span></em></p>Cannabis use is common among trauma survivors, and may improve some of the symptoms of those with PTSD.Stephanie Lake, PhD student in Population and Public Health, University of British ColumbiaM-J Milloy, Research Scientist, BC Centre on Substance Use and Assistant Professor in the Division of AIDS, Department of Medicine, University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1207502019-07-30T01:45:16Z2019-07-30T01:45:16ZPotential cost to patient safety as NZ debates access to medicinal cannabis<figure><img src="https://images.theconversation.com/files/285966/original/file-20190729-43114-ku8ahq.jpg?ixlib=rb-1.1.0&rect=50%2C117%2C5557%2C3589&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The New Zealand government is introducing a scheme for regulating medicinal cannabis.</span> <span class="attribution"><span class="source">from www.shutterstock.com</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Cannabis-based products will be allowed to bypass usual processes required for medicines in New Zealand and go directly onto the market without any proof of safety or effectiveness. This unprecedented proposal is contained in the government’s <a href="https://www.health.govt.nz/system/files/documents/publications/medicinal-cannabis-scheme-consultation-document.pdf">consultation document</a> on giving greater access to medicinal cannabis. </p>
<p>The government is introducing a <a href="https://www.newshub.co.nz/home/politics/2019/07/exclusive-further-details-of-government-s-medicinal-cannabis-scheme-revealed.html">scheme for regulating medicinal cannabis</a>. The consultation covers proposed licensing, cultivation, manufacturing and product standards, and a prescription and enforcement regime.</p>
<p>The key driver for this seems to be that people currently access cannabis through the illegal recreational market. But even if there is no doubt that a regulated market would provide a safer environment for access, we argue that there could be a potential cost to patient safety. </p>
<h2>From trial to market</h2>
<p>The usual market pathway for a drug in New Zealand is the development and manufacture to good manufacturing practice (<a href="https://www.medsafe.govt.nz/regulatory/Guideline/NZGMPCodePart1Intro.asp">GMP</a>) standards. This ensures each batch has the same amount of active ingredient and is free from contaminants. </p>
<p>Companies then run clinical trials, first on small groups of healthy subjects to establish the compound is safe and to understand how it behaves in the body. This information is essential to ascertain dosage. </p>
<p>Finally, the medicine moves into “efficacy” trials. This is the first time it is given to patients. These trials confirm safety and, importantly, establish effectiveness. The data are then presented to the medical regulatory body <a href="https://www.medsafe.govt.nz/">Medsafe</a>, which decides if the drug can be prescribed.</p>
<p>Current medicinal cannabis regulations suggest bypassing all these processes and moving straight from manufacture to prescription. Whether or not manufacture needs to be to GMP standards is one of the consultation questions. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/legal-highs-arguments-for-and-against-legalising-cannabis-in-australia-95069">Legal highs: arguments for and against legalising cannabis in Australia</a>
</strong>
</em>
</p>
<hr>
<h2>What are cannabinoids</h2>
<p>Cannabis, like all plants, contains a wide array of different chemicals. Of these, <a href="https://www.ncbi.nlm.nih.gov/pubmed/28120229">phytocannabinoids</a> generate most interest. The most highly expressed cannabinoids in dried plant material are Δ9-tetrahydrocannabinol (<a href="https://www.ncbi.nlm.nih.gov/pubmed/30689342">THC</a>) and cannabidiol (<a href="https://www.ncbi.nlm.nih.gov/pubmed/30730563">CBD</a>), but at least 100 other cannabinoids are present, many in vanishingly small quantities. </p>
<p>THC is the main psychoactive component of the plant, known to generate a “<a href="https://www.ncbi.nlm.nih.gov/pubmed/30689342">high</a>” or sense of euphoria. Its <a href="https://www.drugabuse.gov/publications/research-reports/marijuana/how-does-marijuana-produce-its-effects">mechanism of action within the human body is well understood</a>. It mimics the body’s natural cannabinoids (endocannabinoids) to bind to and <a href="https://www.ncbi.nlm.nih.gov/pubmed/28120231">activate specific proteins in the brain</a>. The endocannabinoid system is involved in lots of different physiological processes, including memory formation, appetite, pain regulation and inflammation. THC can therefore alter these functions.</p>
<p>There is nothing unusual about a plant compound interacting with human proteins. A large number of drugs are originally from plants. This includes morphine, which comes from opiate poppies and mimics the body’s own opiates, the endorphins. </p>
<p>In contrast to THC, CBD does not produce a high and is often described as not-psychoactive. But this is a mistake as it clearly <a href="https://www.ncbi.nlm.nih.gov/pubmed/28412918">alters activity within the brain</a>. It is better described as a non-intoxicating cannabinoid. The mechanism by which CBD produces responses in the body are not well understood. </p>
<p>A <a href="https://www.ncbi.nlm.nih.gov/pubmed/26264914">recent review of scientific literature</a> described more than 65 discrete molecular targets that might interact with CBD, but concluded that it probably isn’t acting within the endocannabinoid system at all. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/cannabis-and-psychosis-what-is-the-link-and-who-is-at-risk-95368">Cannabis and psychosis: what is the link and who is at risk?</a>
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</em>
</p>
<hr>
<h2>Cannabinoids as medicines</h2>
<p>There is a commonly held idea that cannabis doesn’t lend itself to being treated as a typical medicine because it is the combination of different chemicals that produces the desired effects. But there is <a href="https://www.ncbi.nlm.nih.gov/pubmed/31084880">little scientific evidence</a> to support this. </p>
<p>Many plants have medically useful compounds and these, without fail, have been isolated, either by extraction from the plant or chemical synthesis. They form the basis of medicines such as morphine, codeine, aspirin and pseudoephidrine to name but a few. This same approach has been used for cannabis. Marinol (dronabinol) is synthetic THC, Nabilone is a synthetic THC derivative, Sativex is a plant extract blending two plant varieties, one high THC, one high CBD.</p>
<p>Sativex is <a href="https://medsafe.govt.nz/profs/RIss/Sativex.asp">approved by Medsafe</a> in New Zealand to treat muscle spasms related to multiple sclerosis and through the medicinal cannabis access scheme for other diseases. Although not yet approved for distribution in New Zealand, the pharmaceutical grade CBD product, Epidiolex recently became <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms">the first FDA-approved plant derived cannabinoid medication</a>. </p>
<p>All of these products have been through clinical trials to establish their safety and efficacy. They come with clear recommendations on dosage, likely adverse effects and indications on their likely effectiveness in given conditions. This means the doctor and the patient can genuinely make an informed decision about risks versus potential benefits. </p>
<p>This information also highlights potential drug-drug interactions. For example, clinical trials on Epidiolex for paediatric epilepsy highlighted that, at effective doses, CBD changes how other anti-epileptic medications are processed in the body, sometimes increasing them to toxic levels. </p>
<h2>Equity issues</h2>
<p>If we already have data for these existing medicines, why don’t we just manufacture a similar product but market it more cheaply? This is a model New Zealand has already adopted for <a href="https://www.pharmac.govt.nz/assets/factsheet-generic-meds.pdf">generic medicines</a>, essentially copies of original medicines for which the <a href="https://www.pharmac.govt.nz/about/">drug-funding agency PHARMAC</a> can negotiate cheaper pricing. </p>
<p>But even these medicines require early clinical testing. The manufacturer must test their medicine in people and prove that it is processed by the body in the same way as the established medicine before it can be prescribed. Even following these rigorous tests, differences can remain which make the copy of the drug less acceptable to a patient, such as was seen recently when <a href="https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=12002918">PHARMAC swapped the antidepressant EFFexor-XR for Enlafax-XR</a>. </p>
<p>The consultation document also raises the question of equity, both in terms of equity to access cannabis products and equity to enter the market as a manufacturer. There is an expectation that requiring cannabis derived medicines to meet Medsafe standards would <a href="https://www.newsroom.co.nz/2019/07/11/676984/cautious-optimism-over-proposed-medicinal-cannabis-scheme">push costs to prohibitive levels</a>. But data from the <a href="https://www.cfpc.ca/uploadedFiles/CPD/Cannabinoid_Guidelines_One-Pager.pdf">Canadian College of Family Physicians</a> suggest pricing in Canada is very similar between dried plant materials and pharmaceutical grade products. </p>
<p>Regardless, do any of these considerations outweigh patients’ right to safe, and proven effective medicine? Or doctors’ right to make a fully informed decision before writing a prescription?</p>
<p>New Zealand’s <a href="https://www.nzdoctor.co.nz/article/undoctored/budget-2019-health-32-billion-under-funded-200910">limited health care budget</a> already strains to keep up with demand. The lack of public funding for <a href="https://www.noted.co.nz/health/health/cancer-cost-the-great-disparity-between-treatment-for-rich-and-poor/">expensive but proven cancer medications</a> is just one example. How can we justify spending any of this budget on access to and regulatory control of products that don’t meet our standards, when we can’t afford to fund medicines that do? These are questions that should be answered before we add untested cannabis-based products into our health care system.</p><img src="https://counter.theconversation.com/content/120750/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michelle Glass is affiliated with the Medicinal Cannabis Advisory Group.
John Ashton is patient ambassador for Lung Foundation New Zealand</span></em></p><p class="fine-print"><em><span>John Ashton is affiliated with Lung Foundation NZ and is Chair of the EACD </span></em></p>There is no doubt a regulated market for access to medicinal cannabis is safer, but if cannabis-based products were allowed to bypass efficacy trials, there’s a potential cost to patient safety.Michelle Glass, Professor of Pharmacology, University of OtagoJohn Ashton, Associate Professor, University of OtagoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1054722018-10-24T18:43:51Z2018-10-24T18:43:51ZLiverwort could have medicinal benefits of cannabis THC – without the high<figure><img src="https://images.theconversation.com/files/241707/original/file-20181022-105767-2xl2c9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Radula complanata, a cannabinoid moss.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/radula-complanata-cannabinoid-moss-1036077001?src=lzoCMh01u070vQjk66JnAQ-1-0">Henri Koskinen/Shutterstock</a></span></figcaption></figure><p>Most of us know that the cannabis plant produces compounds that react with the human body. That’s because we have our own system that makes similar compounds, cannabinoids, that have a wide range of actions from appetite control to immune function. Cannabis contains <a href="https://www.livescience.com/24553-what-is-thc.html">a cannabinoid called THC</a> that interacts with the brain, resulting in euphoria and relaxation, as well as increased hunger and anxiety. It was long thought that there was no other natural source of cannabinoids – and along with a long list of supposed medical uses the mythical power of cannabis, and the psychoactive properties of THC, has grown. </p>
<p>But as it turned out, another plant contains something similar: a compound that has the structural hallmarks for it to act on the brain in a similar way to THC. The discovery of this lost twin, called <em>cis</em>-PET (perrottetinene), or PET, was tucked away in specialist chemistry journals in papers published in <a href="https://www.sciencedirect.com/science/article/pii/S0031942200903716">1994</a> and <a href="http://cpb.pharm.or.jp/cpb/200210/c10_1390.pdf">2002</a>, with no subsequent research confirming its biological activity. But in a new study, published in Science Advances, a group of Swiss scientists have delved into the mechanism by which PET may be acting on the brain.</p>
<p>The particular liverwort in question, <em>Radula</em>, is endemic to New Zealand and Tasmania and is <a href="https://www.radionz.co.nz/programmes/from-zero/story/201822571/from-zero-how-did-we-get-here">used as a herbal medicine</a> by the Maori people. Preparations using this plant are also sold as a THC-like legal high on the internet.</p>
<p>But while similar to THC, does PET actually produce the same effects that THC does at a cellular and molecular level? Does it mimic the physiological effects? And is it different in ways that could give it therapeutic advantage or disadvantage? Some 24 years after its first discovery, the team of chemists and biochemists behind the new study have teased some of the answers out. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/242034/original/file-20181024-48706-6d1rv2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/242034/original/file-20181024-48706-6d1rv2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/242034/original/file-20181024-48706-6d1rv2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/242034/original/file-20181024-48706-6d1rv2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/242034/original/file-20181024-48706-6d1rv2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/242034/original/file-20181024-48706-6d1rv2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/242034/original/file-20181024-48706-6d1rv2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Delivery of THC through smoking cannabis.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/preparing-rolling-marijuana-cannabis-joint-drugs-790174744?src=-mq1Qvxua6_NLsvJS83gig-1-44">guruXoX/Shutterstock</a></span>
</figcaption>
</figure>
<p>Their research was no mean feat. It required a new synthesis method to produce enough PET to do meaningful experiments. Once this was achieved, the researchers looked at two mirror versions of the two compounds, <em>cis</em> (the version found in the liverwort) and <em>trans</em> (a version they artificially created in the lab). In chemistry, the <em>cis</em> and <em>trans</em> terms tell us which side of the carbon chain the functional groups are (the bit of the molecule that does the work). The researchers wanted to find out if these two versions of PET were able to interact with <a href="https://www.ncbi.nlm.nih.gov/pubmed/18426493">the two receptors</a> found in humans that mediate the psychoactive effects of cannaboids – CB1, the receptor that produces the “high” effect from THC, and CB2 – in the same way as THC (how strongly they bound and how much is needed to produce an effect).</p>
<p>The researchers found intriguing similarities between the two versions in PET and THC. For both PET and THC, the <em>trans</em> versions (the abundant THC version found in cannabis and the lab-synthesised version found in liverwort) bound to the CB1 receptor better than the <em>cis</em> versions.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/242151/original/file-20181024-71035-s325s.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/242151/original/file-20181024-71035-s325s.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=192&fit=crop&dpr=1 600w, https://images.theconversation.com/files/242151/original/file-20181024-71035-s325s.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=192&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/242151/original/file-20181024-71035-s325s.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=192&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/242151/original/file-20181024-71035-s325s.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=241&fit=crop&dpr=1 754w, https://images.theconversation.com/files/242151/original/file-20181024-71035-s325s.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=241&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/242151/original/file-20181024-71035-s325s.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=241&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">THC and PET side by side.</span>
<span class="attribution"><a class="source" href="https://www.researchgate.net/figure/Structures-of-similar-cannabinoids-in-Radula-marginata-Perrottetinene-and-Cannabis_fig3_318013755">Oliver Kayser</a></span>
</figcaption>
</figure>
<p>What’s interesting about this is that while the levels of cis-PET found in the liverwort plant are too low to produce the “high” effects produced by THC (hence why smoking PET won’t produce a high), it could explain why PET might still have a medicinal effect (similar to the effect produced by <a href="https://www.sciencedirect.com/science/article/pii/S037687161730220X">lower dose THC</a>). However, any methods to extract and concentrate the liverwort compound could lead to the same problems as THC.</p>
<p>But what about CB2, the other cannabinoid receptor? This receptor plays a role in immune responses. Here the Swiss scientists found that the <em>cis</em> versions of both THC and PET bound this receptor better than the <em>trans</em> versions. The implications of this are yet to be explored, but it again hints at a potential medicinal benefit worth exploring further.</p>
<p>The authors of the study then went on to test whether the binding of the CB1 receptors in the brains of mice had the same recognisable THC effects. Usually when THC binds with this receptor it produces four key effects: reduced body temperature, muscle rigidity, reduced movement and decreased sensitivity to pain. In this behavioural test, all four effects were also achieved in the mice using <em>cis</em>-PET, albeit in a much bigger amount. </p>
<p>But there was one notable difference. Inflammation in the brain is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081099/">mediated by molecules</a> called prostaglandins that can be derived from metabolic pathways involving our own body cannabinoids or plant-derived <em>trans</em>-THC. In contrast, the production of these mediators was reduced by <em>cis</em>-PET. It remains to be seen whether this is a good thing or a bad thing.</p>
<p>So while the study is just a start in understanding the mechanisms and effects of PET on the brain, there’s much we still don’t know. What we do know now, however, is that the levels of PET that are found in the natural liverwort plant are too low to produce the recognised effects of THC, so smoking it is unlikely to lead to a high. But it is also interesting that this compound could well have medicinal benefits without the high – one of the key reasons that THC has previously been dismissed as a medicine. Illegal trading and cultivation has confounded much meaningful clinical research, but this is changing and this new compound will add to the treasure trove of plant-derived cannabinoids that we still have much to understand.</p><img src="https://counter.theconversation.com/content/105472/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Karen Wright has received funding from Wellcome Trust, Novartis, Peel Trust, BBSRC and MRC.</span></em></p>Radula liverwort shares an intriguing similarity to cannabis – researchers are working out what it does to the brain.Karen Wright, Lecturer in Biomedical and Life Sciences, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1033602018-09-19T10:43:17Z2018-09-19T10:43:17Z‘Legal highs’ may be more dangerous than traditional drugs of abuse<figure><img src="https://images.theconversation.com/files/237070/original/file-20180919-158234-tgidac.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1023688015?src=Ta8hDAOycpEPHYMo_6bQ_w-1-12&size=huge_jpg">Shutterstock</a></span></figcaption></figure><p>Novel psychoactive substances (NPS), or “legal highs”, have had various definitions but can simply be thought of as new drugs of abuse. Some may be entirely new, some may be designed to mimic existing drugs, some are based on psychoactive plants and some are medicines. </p>
<p>In the UK, most were legal up until the 2016 Psychoactive Drugs Act, which has effectively banned all drugs which have a psychoactive effect, except alcohol, nicotine, caffeine and drugs used for medicinal purposes. Despite this, they remain widely, albeit illegally, available.</p>
<p>Drug users are a heterogeneous group: many have continued to use traditional drugs of abuse, such as cocaine and heroin, but others have embraced legal highs. It was estimated in 2014 that <a href="https://www.theguardian.com/society/2014/oct/05/-sp-drug-use-is-rising-in-the-uk-but-were-not-addicted">nearly half of all drug users</a> in the UK have taken an NPS. </p>
<p>The reasons for their popularity include the misconception that because they were once legal they are safe, the ease of obtaining them, and a subset of drug abusers who are “novelty seekers” and want to try something new and exciting. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/236933/original/file-20180918-158219-4zntcl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/236933/original/file-20180918-158219-4zntcl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/236933/original/file-20180918-158219-4zntcl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/236933/original/file-20180918-158219-4zntcl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/236933/original/file-20180918-158219-4zntcl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/236933/original/file-20180918-158219-4zntcl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/236933/original/file-20180918-158219-4zntcl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Are synthetic cannabinoids like Spice worse than the real thing?</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Synthetic_cannabinoids#/media/File:USMC-100201-M-3762C-001.jpg">Damany S. Coleman/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>Prior to 2016, NPS were typically banned as individual drugs or more recently, as groups of <a href="https://www.gov.uk/government/news/legal-highs-to-be-banned-under-temporary-power">chemically related compounds</a>. This led to the synthesis and marketing of an NPS to take the place of the banned substance, while the novelty seekers also drove a market for new drugs.</p>
<p>Unfortunately, we now have close to <a href="http://www.emcdda.europa.eu/system/files/publications/8585/20181816_TDAT18001ENN_PDF.pdf">700 NPS</a> and this has exacerbated the health risk because, with a new drug, users are unsure how to take it safely and healthcare workers will also know very little about the drug, making effective treatment difficult. A legal high user in A&E might be reliant on medical staff who only have a packet of powder with an unhelpful street name such as “Ivory Wave” to go on.</p>
<p>We’re familiar with the side effects that come from long-term abuse of traditional drugs. Ketamine can lead to <a href="https://www.ncbi.nlm.nih.gov/pubmed/21777321">bladder problems and incontinence</a>, amphetamines can <a href="https://www.sciencedirect.com/science/article/pii/S0301008215001008">kill nerve cells</a> in a process called neurotoxicity, cannabis can increase the risk of developing <a href="https://www.frontiersin.org/articles/10.3389/fpsyt.2014.00054/full">schizophrenia-like symptoms</a>, MDMA may lead to <a href="https://www.sciencedirect.com/science/article/pii/S0002914907014634">heart valve problems</a> and numerous drugs lead to addiction.</p>
<p>The mechanisms underlying these problems are largely known and so we can predict the long-term problems of NPS use.</p>
<h2>How legal highs affect the body</h2>
<p>Synthetic cannabinoids were developed as a legal alternative to cannabis. The main psychoactive compound in cannabis is THC, which activates a cannabinoid receptor protein called CB1.</p>
<p>Spice or K2 has been found to be made up of a variety of synthetic cannabinoids, which are often <a href="https://www.sciencedirect.com/science/article/pii/S0028390815301817">more than ten times as potent</a> at the CB1 receptor. </p>
<p>The same dose of Spice will have a much bigger effect than the same dose of THC and long-term users of spice may therefore have a greater chance of developing schizophrenia than cannabis users. </p>
<p>Animal studies have long shown that amphetamine compounds can cause neurotoxicity, and may mean long-term amphetamine abusers have <a href="https://www.sciencedirect.com/science/article/pii/S0165017301000546">persistent dysfunction</a> in their brain dopamine systems. </p>
<p>Dopamine is not only the “reward” chemical in the brain, but is also critical to movement. Parkinson’s patients have part of their brain dopamine system destroyed, leading to problems initiating movement. More recently, studies have found long-term amphetamine users have a <a href="https://www.sciencedirect.com/science/article/pii/S0376871614018948">greater chance of developing Parkinson’s disease</a>, confirming what we’d already seen with animals.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/237075/original/file-20180919-158213-1bjkuqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/237075/original/file-20180919-158213-1bjkuqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=490&fit=crop&dpr=1 600w, https://images.theconversation.com/files/237075/original/file-20180919-158213-1bjkuqj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=490&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/237075/original/file-20180919-158213-1bjkuqj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=490&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/237075/original/file-20180919-158213-1bjkuqj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=616&fit=crop&dpr=1 754w, https://images.theconversation.com/files/237075/original/file-20180919-158213-1bjkuqj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=616&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/237075/original/file-20180919-158213-1bjkuqj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=616&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">3D image of a brain - red areas denote damage due to Parkinson’s.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/brain-degenerative-diseases-parkinsons-alzheimers-3d-616016804?src=9uyETuUW8gRrRNgnlY-rjw-1-26">Shutterstock</a></span>
</figcaption>
</figure>
<p><a href="https://www.vice.com/en_uk/article/9aa53a/the-story-of-mephedrone-the-party-drug-that-boomed-and-went-bust">One of the most popular</a> NPS since 2008 has been mephedrone, also known as MCAT or meow meow. Mephedrone is a synthetic drug, similar to the plant-based chemical cathinone. It is a stimulant, like amphetamine, and has a very <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1369-1600.2011.00384.x">similar effect in rats and mice</a> and could also leave users with a greater chance of developing Parkinson’s.</p>
<p>Examples abound of NPS which might be more dangerous than the drugs they were developed to replace. Desoxypipradrol (Ivory Wave) may be <a href="https://www.gov.uk/government/publications/acmd-report-on-desoxypipradrol">more likely to lead to psychosis than cocaine</a>. Benzofury, an MDMA-like drug, may also <a href="http://clok.uclan.ac.uk/18222/1/5APB%20in%20press.pdf">cause heart valve problems</a>, Mexxy (methoxetamine) a ketamine-like drug may also <a href="https://www.tandfonline.com/doi/abs/10.3109/15563650.2014.892605?journalCode=ictx20">cause bladder problems</a>. </p>
<p>Adding the relative ignorance among users and healthcare professionals about how to take these new drugs safely and how to treat overdoses, it’s clear that “legal highs” are anything but a safe substitute for traditional drugs of abuse.</p><img src="https://counter.theconversation.com/content/103360/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Colin Davidson receives funding from the European Union (EU Madness project) and the US NIH NIDA (National Institute on Drug Abuse) </span></em></p>We’ve got better at managing the health risks of traditional drugs of abuse, but novel psychoactive substances, or ‘legal highs’, are a dangerous unknown.Colin Davidson, Professor of Neuropharmacology, University of Central LancashireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/816032017-08-13T23:17:38Z2017-08-13T23:17:38ZLegal weed: An accidental solution to the opioid crisis?<figure><img src="https://images.theconversation.com/files/180476/original/file-20170801-28766-1erdw7h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There is growing evidence for the use of cannabis in treating opioid addiction.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>It’s hard to go a day in Canada without hearing about at least one of two types of drugs – but for vastly different reasons. One class of drug — opioids — <a href="https://www.thestar.com/news/canada/2017/04/19/death-toll-reaches-almost-4-a-day-in-overdose-crisis-in-bc-coroner.html">kills four people a day in British Columbia</a>. The other — cannabis — will be legal for adult purchase and consumption <a href="https://www.canada.ca/en/health-canada/news/2017/04/canada_takes_actiontolegalizeandstrictlyregulatecannabis.html">by this time next year.</a></p>
<p>The opioid overdose epidemic is Canada’s gravest public health crisis since the emergence of HIV in the 1980s. With its roots in the over-prescription of high-potency painkillers, sparked by the contamination of the illicit drug supply with fentanyl and related drugs, the crisis has reached across demographic divides. Experts agree on the need for creative responses based in scientific evidence. </p>
<p>Could cannabis legalization be a part of this solution? Increasingly, this is what the latest scientific research indicates. </p>
<h2>Fatal overdoses</h2>
<p>The opioid crisis is a product of the medical system’s <a href="https://theconversation.com/how-to-fix-canadas-opioid-crisis-it-starts-with-pain-and-the-prescription-pad-78512">over-reliance on opioids</a> for pain relief. Almost <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298051/">one in five Canadians</a> live with some form of chronic pain. Twenty years ago, pharmaceutical companies began to develop <a href="https://theconversation.com/oxycontin-how-purdue-pharma-helped-spark-the-opioid-epidemic-57331">slow-release formulations of opioids</a> (e.g. OxyContin) and marketed them as safe and effective medications for the treatment of chronic non-cancer pain. </p>
<p>We know now that these drugs carry an extremely high risk of dependence and fatal overdose. Despite this, <a href="https://www.theglobeandmail.com/news/national/sales-of-opiod-drug-prescriptionsskyrocketing/article26008639/">more than 20 million opioid prescriptions</a> are filled each year in Canada. Drug overdoses are now the <a href="https://www.nytimes.com/interactive/2017/06/05/upshot/opioid-epidemic-drug-overdose-deaths-are-rising-faster-than-ever.html">leading cause of death</a> among Americans under the age of 50. And prescription opioids are involved in <a href="https://www.cdc.gov/drugoverdose/data/overdose.html">nearly half</a> of these deaths. It is also becoming apparent that opioids might be less effective than initially thought in treating certain types of chronic non-cancer pain (<a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006146.pub2/abstract;jsessionid=F7C9469935C456F6BDD34331871E1FEA.f03t01?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+01st+July+from+03.00-09.00+EDT+and+on+Sunday+2nd+July+">e.g. neuropathic pain</a>).</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/180478/original/file-20170801-5515-q7tbo9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/180478/original/file-20170801-5515-q7tbo9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/180478/original/file-20170801-5515-q7tbo9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/180478/original/file-20170801-5515-q7tbo9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/180478/original/file-20170801-5515-q7tbo9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/180478/original/file-20170801-5515-q7tbo9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/180478/original/file-20170801-5515-q7tbo9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Canada will soon be the first country in the G-20 to legalize cannabis for non-medicinal purposes.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Cannabis, derived from the Cannabis sativa plant, contains several compounds. These include tetrahydrocannabinol (THC, the primary psychoactive component of cannabis) and cannabidiol (CBD). Beyond the well-known psychoactive effects of cannabinoids, new research has shown that they also interact with <a href="https://academic.oup.com/bja/article-lookup/doi/10.1093/bja/aen119">systems in the body involved in the regulation of pain</a>. </p>
<p>This discovery has led researchers to investigate the potential for cannabis to treat various pain conditions for which opioids are currently first- or second-line therapies. High-quality clinical research involving cannabis has been <a href="https://www.theatlantic.com/politics/archive/2014/06/its-hard-to-study-marijuanas-medical-benefits-when-its-illegal/373603/">stunted by its prohibited legal status</a>. But a recent <a href="https://link-springer-com.ezproxy.library.ubc.ca/article/10.1007%2Fs11481-015-9600-6">review of clinical studies</a> involving cannabis-based medicines (including smoked or vapourized cannabis) found strong evidence for relief of chronic non-cancer pain.</p>
<h2>Ground-breaking findings</h2>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/15731502">The substitution effect</a> is an idea from behavioural economics that describes how the use of one product might decrease when the availability of another increases. Substance use researchers have recently <a href="http://www.tandfonline.com/doi/abs/10.3109/16066359.2012.733465">adapted this theory</a> to understand the substitution potential between cannabis and opioids. In other words, does the use of opioids decrease with increasing access to cannabis?</p>
<p><a href="https://archinte.jamanetwork.com/article.aspx?doi=10.1001/jamainternmed.2014.4005">In a landmark 2014 study</a>, a team of researchers analzyed data from across the United States over a 10-year period. They found that states that had legalized medical cannabis saw 25 per cent fewer opioid-related deaths compared to states where medical cannabis remained illegal. </p>
<p>These findings broke ground for others in the field to find associations between U.S. medical cannabis laws and reduced state-level estimates of <a href="http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2016.303426?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed">opioid use</a> and <a href="http://www.nber.org/papers/w21345">dependence</a>. But, because these population-level studies cannot observe <a href="http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2210572">individual-level changes in cannabis and opioid use</a>, a closer look at these trends among different sub-populations of people affected by the opioid crisis is needed.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/180488/original/file-20170801-11176-1lbxy6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/180488/original/file-20170801-11176-1lbxy6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/180488/original/file-20170801-11176-1lbxy6y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/180488/original/file-20170801-11176-1lbxy6y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/180488/original/file-20170801-11176-1lbxy6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/180488/original/file-20170801-11176-1lbxy6y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/180488/original/file-20170801-11176-1lbxy6y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Legalizing cannabis will enable researchers to investigate the clinical and public health impacts of the drug.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Not surprisingly, findings from surveys conducted among patients using medical cannabis across North America demonstrate a clear preference for cannabis over opioids. For example, roughly one-third of a sample of patients enrolled in Health Canada’s Marihuana for Medical Purposes Regulations (MMPR) program in B.C. <a href="http://www.sciencedirect.com/science/article/pii/S0955395917300130">report substituting cannabis for prescription opioids.</a></p>
<p>For chronic pain patients, this substitution effect appears even more pervasive, with cannabis substitution occurring in roughly <a href="http://www.sciencedirect.com/science/article/pii/S1526590016005678?via%3Dihub">two-thirds</a> of a sample of former prescription opioid patients in Michigan who started using medical cannabis. </p>
<p><a href="http://online.liebertpub.com/doi/full/10.1089/can.2017.0012">In the most recent study</a>, 80 per cent of medical cannabis patients in California reported that taking cannabis alone was more effective at treating their medical condition than taking cannabis with opioids. More than 90 per cent agreed they would choose cannabis over opioids to treat their condition if it were readily available.</p>
<h2>Illicit opioid use</h2>
<p>But what about the relationship between cannabis and opioids among some of those most affected by the opioid crisis — people with long-term experience using illicit opioids?</p>
<p>Untreated pain and substance use have a high degree of overlap. Pain was reported by almost half of people who inject drugs surveyed in a recent <a href="https://substanceabusepolicy.biomedcentral.com/articles/10.1186/s13011-017-0112-7">San Francisco study.</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962749/">Research from our colleagues in Vancouver</a> found that under-treatment of pain in this population is common. It results in self-management of pain by obtaining heroin or prescription opioids on the street.</p>
<p>This means there could be a role for cannabis even among individuals with extensive experience using illicit opioids. <a href="http://www.sciencedirect.com/science/article/pii/S0376871615002501?via%3Dihub">A study from California</a> of people who inject drugs found that those who used cannabis used opioids less often. It’s still unclear if this difference is directly due to cannabis use and more research is needed.</p>
<h2>Potential as anxiety treatment</h2>
<p>Even without chronic pain, cannabis may prove an effective alternative among individuals wanting to reduce or stop their opioid use. There is growing evidence for the use of cannabis in treating opioid addiction. CBD, the non-psychoactive component of cannabis, is known to interact with <a href="https://link.springer.com/article/10.1007%2Fs13311-015-0387-1">several receptors involved in regulating fear and anxiety-related behaviours</a>. It shows potential for the treatment of several anxiety disorders. </p>
<p>Research is also investigating CBD’s role in modulating cravings and relapses — behaviours that are tightly linked to anxiety — among individuals with opioid addiction. <a href="https://link.springer.com/article/10.1007%2Fs13311-015-0373-7">Recent preliminary studies</a> suggest that CBD reduces opioid cravings. A <a href="https://clinicaltrials.gov/ct2/show/NCT02539823?lead=Hurd&cntry1=NA%3AUS&rank=1">larger clinical trial</a> is now underway in the United States.</p>
<h2>A bold response?</h2>
<p>Canada will soon be the first country in the G-20 to introduce a legal framework regulating the use of cannabis by adults for non-medical purposes. This will create a country-wide natural experiment for the world to observe. Legalizing cannabis will break down traditional barriers to understanding the clinical and public health impacts of the drug. </p>
<p>This massive drug policy change could not come at a more desperate time. By increasing access to the drug for therapeutic and recreational purposes, we will have the opportunity to investigate substitution effects within different populations of people who use opioids.</p>
<p>Protection of youth and removal of organized crime aside, the Cannabis Act may just be the unintentionally bold government response to the opioid crisis that our country so desperately needs.</p><img src="https://counter.theconversation.com/content/81603/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephanie Lake is supported by funding from the Canadian Institutes of Health Research and the Pierre Elliott Trudeau Foundation. She is affiliated with Canadian Students for Sensible Drug Policy. </span></em></p><p class="fine-print"><em><span>M-J Milloy is supported by funding from the United States National Institute on Drug Abuse, the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research. His institution has received an unstructured gift from NG Biomed Ltd., a private firm seeking a licence to produce medical cannabis, to support him.</span></em></p>As Canada moves towards legalization of cannabis in 2018, there is growing evidence of the drug’s potential to treat opioid addiction itself, as well as the chronic pain that often drives it.Stephanie Lake, PhD student in Population and Public Health, University of British ColumbiaM-J Milloy, Research Scientist, BC Centre on Substance Use and Assistant Professor in the Division of AIDS, UBC Department of Medicine, University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/770462017-05-16T06:37:24Z2017-05-16T06:37:24ZNAFTA’s biggest loser: the US, after Canada and Mexico get rich trading marijuana<p>The president of the United States, Donald Trump, prides himself on his business acumen. But his protectionism may get America a truly bad deal when it comes to North America’s next big market: marijuana.</p>
<p>Fulfilling a <a href="http://www.cbc.ca/news/politics/trudeau-pot-marijuana-legalization-timeline-1.3252088">campaign promise</a>, on April 13 Canadian Prime Minister Justin Trudeau presented a bill to <a href="http://www.parl.gc.ca/HousePublications/Publication.aspx?Language=E&Mode=1&DocId=8894959">legalise</a> cannabis for recreational uses (<a href="http://laws-lois.justice.gc.ca/eng/regulations/SOR-2016-230/index.html">medical marijuana</a> has been legal in the country since 2001).</p>
<p>Two weeks later, Mexico’s Congress followed suit, passing a bill <a href="http://gaceta.diputados.gob.mx/PDF/63/2017/abr/20170428-II.pdf">to authorise</a> cannabis use for medical and scientific purposes.</p>
<p>Two of three North American countries are now well positioned to unlock an industry that, according to <a href="https://www.forbes.com/sites/debraborchardt/2017/02/22/marijuana-industry-projected-to-create-more-jobs-than-manufacturing-by-2020/#418afe923fa9">Forbes</a> magazine, was worth an estimated US$7.2 billion in 2016 and is projected to grow at a compound annual rate of 17%. </p>
<p>In the US, on the other hand, a protectionist administration has threatened to <a href="https://www.nytimes.com/2017/03/30/business/nafta-trade-deal-trump.html?_r=0">withdraw from the “terrible” North American Free Trade Agreement</a> (NAFTA) and actively relaunched <a href="https://theconversation.com/what-does-donald-trump-think-about-drugs-70844">the US drug war</a>. It looks like America’s businessman president may allow his country to miss out on the cannabis boom.</p>
<h2>Prohibition is a commercial disaster</h2>
<p>Medical marijuana research is a growth industry. Cannabinoids, a main (non-psychoactive) chemical component in marijuana, hold significant prospects for development in the <a href="https://www.vice.com/es_mx/article/la-oportunidad-desperdiciada-por-mexico-ser-una-potencia-en-la-industria-farmaceutica-cannabica">pharmaceutical industry</a>, as potentially does tetrahydrocannabinol (THC), the ingredient that makes users feel high.</p>
<p>Marijuana has been scientifically proven to soothe the effects of <a href="https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#link/_40_toc">chemotherapy</a>, treat <a href="http://jamanetwork.com/journals/jamaophthalmology/fullarticle/264203">glaucoma</a> and ease some <a href="http://www.drugandalcoholdependence.com/article/S0376-8716%2814%2901975-9/abstract">chronic pain</a>. But <a href="http://jamanetwork.com/journals/jama/fullarticle/2338251">many fields of inquiry remain untapped</a>, thanks in large part to stringent US laws that classify cannabis <a href="https://www.dea.gov/druginfo/ds.shtml">as a Schedule I drug</a>. That’s the most tightly restricted category, reserved for substances with “no currently accepted medical use.”</p>
<p>Pharmaceutical companies are keen to further disprove that thesis, knowing they will soon be able to patent cannabis-based medicines in both <a href="http://www.altonivel.com.mx/55156-empresas-de-marihuana-ponen-la-mira-en-mexico-para-invertir/">Mexico</a> and <a href="http://www.bbc.com/news/world-us-canada-38083737">Canada</a>. Patients and doctors, too, have pleaded for restrictions on medical marijuana research in the US <a href="https://www.forbes.com/sites/cjarlotta/2015/06/30/more-rearch-on-cannabinoids-for-medical-use-needed-study-finds/#165df279eb48">to be eased</a>.</p>
<p>In the US, eight states and Washington, DC, have also <a href="https://theconversation.com/marijuana-legalization-big-changes-across-country-67415">legalised</a> recreational marijuana. A <a href="http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx">total</a> of 29 states plus the nation’s capital have legal medical cannabis. </p>
<p>But US Attorney General Jeff Sessions (who has <a href="https://www.justice.gov/opa/speech/attorney-general-jeff-sessions-delivers-remarks-efforts-combat-violent-crime-and-restore">declared</a> that he “rejects the idea that America will be a better place if marijuana is sold in every corner store”) and Homeland Security chief John Kelly (who has <a href="https://theconversation.com/why-are-politicians-still-referring-to-marijuana-as-a-gateway-drug-39348">erroneously</a> called marijuana a “<a href="http://www.nbcnews.com/politics/politics-news/homeland-sec-kelly-marijuana-dangerous-gateway-drug-n747901">dangerous gateway drug</a>”) consistently overlook this fact.</p>
<p>The Trump administration is determined to revamp prohibitionist policies. In a radical rollback of Barack Obama’s <a href="https://www.washingtonpost.com/world/national-security/obama-grants-final-330-commutations-to-nonviolent-drug-offenders/2017/01/19/41506468-de5d-11e6-918c-99ede3c8cafa_story.html?utm_term=.8c3d8055b963">compassionate approach</a> to nonviolent drug offenders, Sessions has actually <a href="http://edition.cnn.com/2017/05/12/politics/sessions-criminal-charging-memo/">ordered federal prosecutors</a> to charge suspects of any drug-related crime with the “most serious, readily provable offence”, or whichever crime entails the harshest punishment.</p>
<p>This move will have well-documented implications for law enforcement. In 2015, marijuana arrests outweighed those made for all violent crimes combined, including murder and rape, 574,000 to 505,681, according to the NGO <a href="https://www.hrw.org/report/2016/10/12/every-25-seconds/human-toll-criminalizing-drug-use-united-states">Human Rights Watch</a>. </p>
<p>Now America’s drug war will have commercial consequences too. In the US, the National Institute on Drug Abuse has developed research mainly on the <a href="https://www.drugabuse.gov/drugs-abuse/marijuana/marijuana-cannabinoid-research-nida">negative</a> effects of cannabis, only marginally considering its potential medical uses.</p>
<p>Medical trials conducted on human beings require permission from <a href="http://www.businessinsider.com/difficulty-of-study-medical-marijuana-2013-8?IR=T">several federal agencies</a>, including the Department of Health and Human Services, the Food and Drug Administration, and, when it comes to illegal substances, the Drug Enforcement Agency. That makes getting clearance for cannabis trials unduly complicated.</p>
<p>The inconsistencies between federal and state legislation also discourage research because they do not offer a secure legal ground for <a href="https://www.law.cornell.edu/uscode/text/35/101">patenting</a> cannabis-based medicines. Potential investors in medical cannabis are forced to <a href="https://news.vice.com/article/a-patent-for-cannabis-plants-is-already-a-reality-and-more-are-expected-to-follow">consider</a> not only corporate competition but also criminal prosecution.</p>
<p>Likewise, because budding American cannabis producers struggle to access <a href="http://www.economist.com/news/finance-economics/21720501-investors-can-gain-exposure-budding-industry-set-profit-canadian">investment funding</a>, the industry’s growth potential remains stunted.</p>
<h2>Outsmarting Trump</h2>
<p>If all of this sounds bad for American investors and patients, it’s good news for Mexico and Canada.</p>
<p>The Mexican medical marijuana bill <a href="http://www.gob.mx/cms/uploads/docs/Iniciativa_Marihuana.pdf">championed</a> by President Enrique Peña, who is not a bold politician, is quite limited. It emerged in response to <a href="https://news.vice.com/article/an-8-year-old-girl-just-became-mexicos-first-medical-marijuana-patient">the story of Grace</a>, a profoundly epileptic eight-year-old girl for whom cannabis oil, illicitly administered by her desperate mother, proved a literal lifesaver. </p>
<figure>
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<figcaption><span class="caption">The story of eight-year-old Grace won Mexican hearts.</span></figcaption>
</figure>
<p>By removing from cannabis the legal label of “<a href="http://internacional.elpais.com/internacional/2017/04/29/mexico/1493419178_321134.html">forbidden plant</a>”, the law will enable it to be used for medical or scientific purposes and permit the health ministry to conduct clinical research. </p>
<p>In legal terms, Mexican cannabis is now a <a href="http://mexico.justia.com/federales/codigos/codigo-civil-federal/libro-cuarto/primera-parte/titulo-primero/capitulo-i/#articulo-1793">commercial good</a> that falls under NAFTA’s purview. Medical cannabis is estimated to bring in between US$1 billion and US$2 billion to <a href="http://fortune.com/2016/02/02/medical-marijuana-mexico/">Mexico</a> over the next ten years. </p>
<p>Canada is making a bigger bet on marijuana. Once its cannabis-regulation bill <a href="http://time.com/4739145/justin-trudeau-canada-legalize-marijuana-pot-2018/">is implemented</a> in July 2018, it will become the <a href="http://www.montevideo.com.uy/contenido/Tras-Uruguay-Canada-se-convertira-en-el-segundo-pais-del-mundo-en-autorizar-el-cannabis-para-uso-recreativo-340341">second country</a> in the world to fully legalise marijuana, after Uruguay. It will <a href="https://www.nytimes.com/2017/04/13/world/canada/trudeau-marijuana.html?_r=0">stop short</a> of establishing an open market, though; provinces will decide where and how marijuana may be sold and priced, in conjunction with the federal government. </p>
<p>As in Mexico, Canadian cannabis will comprise a commercial good. Its medical <a href="https://www.statista.com/statistics/587568/estimated-medical-marijuana-market-size-canada/">marijuana market</a> is expected to be worth US$1 billion by 2020, while recreational marijuana <a href="https://www2.deloitte.com/content/dam/Deloitte/ca/Documents/Analytics/ca-en-analytics-DELOITTE%20Recreational%20Marijuana%20POV%20-%20ENGLISH%20FINAL_AODA.pdf">prospects</a> run as high as US$22.6 billion.</p>
<p>Once both countries’ systems are up and running, cannabis trading between Mexico and Canada can begin. The <a href="http://www.economist.com/news/finance-economics/21720501-investors-can-gain-exposure-budding-industry-set-profit-canadian">world’s first cannabis-focused exchange traded fund</a> has already opened on the Toronto Stock Exchange. </p>
<p>In theory, Canada and Mexico could also <a href="https://www.nafta-sec-alena.org/Home/Texts-of-the-Agreement/North-American-Free-Trade-Agreement?mvid=1&secid=3d71288c-7661-4fdb-8ab1-a6e3be74bdb6">trade</a> medical marijuana with dozens of US states. But given the current administration’s “<a href="https://www.whitehouse.gov/inaugural-address">America First</a>” motto, anti-Mexico rhetoric and fearmongering about drugs, that may prove difficult. </p>
<h2>The biggest losers</h2>
<p>The federal government is also forcing the US to miss out on something more valuable than profit: improving public health and social well-being. </p>
<p>Drugs in general and cannabis, in particular, can do harm if misused. But they are <a href="https://www.thefix.com/kofi-annan-war-drugs-more-dangerous-drugs-themselves">far less dangerous than the drug war</a> itself. After all, the <a href="https://www.theguardian.com/society/2015/mar/12/legal-marijuana-edibles-policy-studies">health risks</a> associated with legal cannabis can be prevented by strict packaging and labelling guidelines.</p>
<p>For Canada, which has long been <a href="https://www.canada.ca/en/services/policing/justice/legalization-regulation-marijuana.html">progressive</a> in its drug policy, cannabis legalisation should continue to reduce the harm created by the illicit drug trade. </p>
<p>Mexico’s bill has more radical implications for health and public safety. An average of <a href="https://www.opendemocracy.net/daniel-joloy/ten-years-of-militarised-drug-policies-in-mexico-more-violence-and-human-rights-violati">51 people die</a> every day in the country’s violent drug war. That’s so many homicides that male <a href="https://www.theguardian.com/world/2016/jan/06/mexico-men-life-expectancy-drug-war-murder">life expectancy</a> has actually dropped by more than half a year since 2010. </p>
<p>For many Mexicans, the revenue from medical marijuana is less important than the possibility of rolling back the <a href="https://theconversation.com/a-decade-of-murder-and-grief-mexicos-drug-war-turns-ten-70036">deadly drug war</a>. The country’s timid steps towards legalising medical marijuana have begun a critical process of democratic deliberation around <a href="https://theconversation.com/mexicos-military-is-a-lethal-killing-force-should-it-really-be-deployed-as-police-75521">using the military</a> for law enforcement in the war on drugs.</p>
<p>As for the US, it needn’t miss out. If only to keep America from falling behind Canada and Mexico, a scenario that would haunt its president, Trump could take action to improve the health, wealth and safety of his people. And that, <a href="http://edition.cnn.com/2017/04/26/politics/donald-trump-nafta/">to use his own words</a>, would actually be a “fair deal for all”.</p><img src="https://counter.theconversation.com/content/77046/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Luis Gómez Romero does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Mexico and Canada are about to turn medical cannabis into North America’s most lucrative new market.Luis Gómez Romero, Senior Lecturer in Human Rights, Constitutional Law and Legal Theory, University of WollongongLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/667742016-12-05T01:01:02Z2016-12-05T01:01:02ZCould a cannabis pill reduce chemotherapy-induced nausea and vomiting? Here’s how we find out<p>For some cancer patients undergoing chemotherapy, the thought of joining their loved ones for a meal can be, quite literally, sickening. Nausea and vomiting due to chemotherapy can cause devastating physical side effects and wreck a patient’s social and family life.</p>
<p>Patients say they find it difficult to manage the expectations of well-meaning family members and friends who want to “feed them up”, when their favourite foods become tasteless.</p>
<p>We need to do more to make chemotherapy as comfortable as possible for patients.</p>
<p>That’s why our research team at <a href="http://www.mylifehouse.org.au/">Chris O’Brien Lifehouse</a> in Sydney is about to embark on the largest and most definitive Randomised Controlled Trial ever in the world of medicinal cannabis for the prevention of chemotherapy-induced nausea and vomiting. With the help of more than 300 patients from several NSW hospitals, we hope to learn more over the next few years about how effective medicinal cannabis may or may not be for preventing chemotherapy-induced nausea and vomiting.</p>
<h2>New strategies for an old problem</h2>
<p>Cancer kills more Australians than any other disease. Almost half the 100,000 people diagnosed each year will be offered chemotherapy as an integral part of their treatment. While there have been significant advances in anti-nausea drugs over the past decade, more than one-third of patients receiving potent intravenous chemotherapy still suffer from nausea or vomiting.</p>
<p>Our team includes leading Australian researchers from Chris O'Brien Lifehouse, the University of Sydney and Royal Prince Alfred Hospital, specialising in cancer, addiction medicine and clinical toxicology.</p>
<p>We’re hoping to determine if giving patients an oral capsule of medicinal cannabis reduces nausea and vomiting during and after intravenous chemotherapy for cancer.</p>
<h2>Jury still out</h2>
<p>The jury is still out on the ability of cannabis and cannabis-derived medicines to treat a range of debilitating illnesses – and how to do it safely and effectively.</p>
<p>Despite dozens of trials internationally, the <a href="http://www.cochrane.org/CD009464/GYNAECA_cannabis-based-medicine-nausea-and-vomiting-people-treated-chemotherapy-cancer">evidence</a> is unconvincing. Some <a href="http://www.cochrane.org/CD009464/GYNAECA_cannabis-based-medicine-nausea-and-vomiting-people-treated-chemotherapy-cancer">research</a> failed to compare cannabis medicine against the best standard treatment of today. Some research had design flaws, such as failure to adequately account for the placebo effect, inappropriate dosing, small sample sizes and poor documentation of side effects and harms.</p>
<p>There remain many potentially valid reasons to use medicinal cannabis products. But we still don’t know how best to formulate and administer the drug, how well it might work, how safe it is and what the long-term side effects could be.</p>
<p>This is not to say medicinal cannabis for therapeutic use is a pipe dream – we just need to do the work first, and do it properly. And that takes time.</p>
<h2>A scientific approach</h2>
<p>However, using a scientific approach will give the best hope for patients and their families. It will give us better understanding of side effects and ideal dosages.</p>
<p>Producers of medicinal cannabis products will be encouraged to develop the most suitable formulations, delivery methods, and cannabinoid content.</p>
<p>Australian regulatory and funding authorities will have the evidence they need to decide which formulations of medicinal cannabis should be approved for which conditions, so they can be made safely available to the patients who need them.</p>
<p>Clearly, more research needs to be done. NSW is doing groundbreaking research on the use of medicinal cannabis for treatment-resistant childhood epilepsy, palliative care and chemotherapy-induced nausea and vomiting.</p>
<p>Many of my patients do not use illegal cannabis preparations because they are concerned about breaking the law. But if we were to pursue broad legalisation, as opposed to a medical pathway based on scientific evidence, we would miss the opportunity to create a safe, secure supply of cannabis medicines.</p>
<p>These medicines could be supervised by qualified practitioners to maximise the benefit to patients and manage side effects, and could potentially be subsidised under the Pharmaceutical Benefits Scheme.</p>
<p>Many of the cannabinoid products available overseas have little quality control, testing or certification.</p>
<h2>Relaxed but not “stoned”</h2>
<p>The cannabis plant varies considerably depending on its type and how it is grown. The cannabis plant contains hundreds of compounds, more than 60 of which are cannabinoids. The main cannabinoids studied in trials are delta-9-tetrahydrocannabidiol (THC), and cannabidiol (CBD).</p>
<p>THC is the type of cannabis that can make people feel “stoned”, while cannabidiol can make people feel relaxed and can hopefully relieve nausea.</p>
<p>Older cannabis medicines, such as Dronabinol and Nabilone, are made of synthetic THC. They are still sometimes used overseas as last-line options for treating nausea and vomiting caused by chemotherapy, but they’re not very effective, and can cause a lot of side effects.</p>
<p>The oral capsule for our NSW government-funded study contains equal amounts of THC and CBD. We think this will be more effective and have fewer side effects.</p>
<p>We worked with the Canadian company <a href="https://www.tilray.ca/">Tilray</a>, which developed the capsule to our specifications. It aims to minimise THC levels that have mood-altering characteristics, which means our patients are less likely to get “stoned”.</p>
<p>The trial is building on a small <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997305/">Spanish study</a> which found that a spray form of cannabis medicine containing THC and CBD in equal amounts (not routinely available in Australia) seemed to dramatically reduce nausea and vomiting in cancer patients receiving chemotherapy. The results, which found a 50% reduction in the number of patients suffering these effects, seem too good to be true, and need to be repeated in a rigorous clinical trial using a capsule that is available in Australia.</p>
<p>The NSW clinical trials exploring the use of medicinal cannabis are very significant. We don’t want to repeat past mistakes, and we want the investment in time and money to be worthwhile.</p>
<p>We can’t predict the outcome. The trials could show a benefit of medicinal cannabis, but they could also show that medicinal cannabis doesn’t work or has overwhelming side effects.</p>
<p>We are hopeful that, at the very least, NSW patients will be given a clear, scientific basis upon which to make important decisions about their treatment in the future.</p><img src="https://counter.theconversation.com/content/66774/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Grimison is a medical oncologist from Chris O`Brien Lifehouse cancer hospital and The University of Sydney and is leading the research team for the NSW Government’s clinical trial into the role of cannabis-derived medicines in chemotherapy-induced nausea and vomiting. The University of Sydney and Chris O'Brien Lifehouse receives funding from NSW Health to conduct a clinical trial of cannabis for chemotherapy-induced nausea and vomiting, for whom Tilray have provided the study drug.</span></em></p>NSW is about to embark on the largest and most definitive clinical trial ever of medicinal cannabis for chemotherapy-induced nausea and vomiting.Peter Grimison, Medical oncologist from Chris O`Brien Lifehouse cancer hospital, Lead researcher NSW Government clinical trial into the role of cannabis-derived medicines in chemotherapy-induced nausea and vomiting, Clinical Associate Professor., University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/678382016-11-01T02:36:36Z2016-11-01T02:36:36ZUsing DNA to unlock the mysteries of cannabis and reduce the risk of dodgy ‘medical’ products<p>The federal government will now <a href="http://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2015-ley123.htm">accept licence applications</a> for groups wanting to grow cannabis locally for scientific and medical purposes.</p>
<p>Cannabis <a href="http://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2015-ley123.htm">remains an illegal drug</a> in Australia for recreational use and there no plans to change that. But the reforms are part of a broader effort to enable a sustainable supply of safe medicinal cannabis products to Australian patients.</p>
<p>There is limited high quality evidence on how cannabis medicines may help people suffering problems such as chemotherapy-induced nausea or paediatric epilepsy. New South Wales’ upcoming medicinal cannabis <a href="https://www.medicinalcannabis.nsw.gov.au/about">trials</a> aim to find out more about its therapeutic potential. </p>
<p>Against this background, plant scientists in Australia are working to understand better the chemical make up of this complex plant and the incredible variation within the species. </p>
<p>Many questions remain unanswered, underscoring the potential risks of black market products. The composition of these products may be unknown, or vary wildly between products or batches. They may also be laced with pesticides and heavy metals. </p>
<p>This lack of quality control and quality assurance is a significant public health concern, especially for vulnerable patients who may not necessarily have a medical professional helping guide their treatment choices.</p>
<h2>One species, hundreds of strains</h2>
<p>You may think you know what a cannabis plant looks like, but even experts are still learning about how one plant may differ from the next in its chemical profile.</p>
<p>The two most well-known compounds in a cannabis plant are the psychoactive tetrahydrocannabinol, or <a href="https://theconversation.com/au/topics/thc-29805">THC</a>, and the non-psychoactive cannabidiol, or CBD. THC is the compound that delivers the “high”, while CBD is believed to have a relaxing effect. THC and CBD are part of a group of compounds that scientists call “cannabinoids”.</p>
<p>On the spectrum of variation, there are some plants that are high in THC and some that are high in CBD. But even for these two cannabinoids, there is much more of a <a href="http://link.springer.com/article/10.1007/s10681-015-1585-y">continuum</a> than most people realise. </p>
<p>You may read on the internet that there are two main types of cannabis – indica and sativa – and that one is more or less medically beneficial than the other. But this terminology is not backed by strong evidence. </p>
<h2>Heavy metals, pesticides</h2>
<p>Many existing products available on the black market may promise miraculous results without any compelling scientific evidence, regulation or product quality assurance standards. Some of the tinctures, oils or floral buds available on the black market may also be badly contaminated by pesticides, heavy metals and germs. </p>
<p>Some of the research <a href="http://sydney.edu.au/news-opinion/news/2016/08/18/pioneering-study-of-cannabis-extracts-in-treating-epileptic-kids.html">underway</a> in Australia is investigating just how variable the amounts of active ingredients may be in some of these products.</p>
<h2>Tracing the history, mapping the present</h2>
<p>All forms of cannabis currently growing have been domesticated at some point in the past few thousand years.</p>
<p>We can now use state-of-the art DNA technologies and detailed information on cannabinoid chemistry to help trace the domestication history of hemp, hempseed, recreational and now medicinal forms of cannabis.</p>
<p>Our research aims to map the details of the wide range of cannabinoid compositional profiles that may be found in the different cultivated forms (also known as cultivars or “strains”). We want to help create a better way of assessing the amount of CBD and other cannabinoids in different cannabis strains. We are developing tools to distinguish between different cannabis cultivars by DNA and chemical profiling.</p>
<p>Our researchers are working with a collection of over 200 strains of cannabis cultivars collated by the firm Ecofibre (one of our research funders and collaborators). This collection represents a large proportion of the <a href="http://journal.frontiersin.org/article/10.3389/fpls.2016.01113/full">worldwide cannabis gene pool</a>.</p>
<h2>How to measure the dose?</h2>
<p>There is still no single standard way of measuring cannabinoid composition. That makes it hard to know the relative “dose” of THC or CBD or other compounds in any given plant.</p>
<p>There is an urgent need to develop and adopt nationally and internationally agreed standards for the benefit of all involved, be they regulators, cultivators, processors, dispensers, prescribers or patients. </p>
<p>Without a systematic framework it is very hard to understand how growers could cultivate cannabis with a consistent composition and yield, leading to a predicable dose. Scientists also still don’t know enough about the shelf-life of various forms of medicinal cannabis.</p>
<p>Our research team surveyed the available reliable and systematic scientific literature on what factors help drive variation in cannabinoid content in a plant.</p>
<p>We found that there is little high quality scientific evidence out there on this question, despite what you may read on the internet. Many websites make bold claims about the “evidence” on cannabis plant science but most of this material is poorly formalised or does not bear scrutiny in terms of valid statistical design.</p>
<h2>New research to answer old questions</h2>
<p>For cultivators and manufacturers there is a need to be able to ensure production cycles can be predictable throughout the year to meet demand. For pharmacists and prescribers there is a need to know more about a product’s shelf-life. Patients must have confidence in the consistency and traceability of product – from plant through to the processing and supply chain – and prescribers need to be able to predict with certainty what effect a product will have on a patient.</p>
<p>The effect that a cannabis product will have on a person is the result of complex interplay between the original plant’s genetic composition, and environmental factors during cultivation and processing.</p>
<p>For a medicinal cannabis cultivation and processing industry to work best, we need to understand better – in a systematic and reproducible way – the interaction between the genetic composition and the environmental factors that may determine the level of THC and CBD in a plant.</p><img src="https://counter.theconversation.com/content/67838/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Graham King receives funding at Southern Cross University from the company Ecofibre Industries Operations Pty Ltd and the Australian government. He is on the advisory council of the NSW Centre for Medicinal Cannabis Research and Innovation.</span></em></p>The Australian government will now accept licence applications for groups wanting to grow cannabis for scientific and medical purposes. But there’s still a lot we don’t know about this complex plant.Graham King, Director, Southern Cross Plant Science, Southern Cross UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/642002016-10-19T01:02:23Z2016-10-19T01:02:23ZWhat do we know about marijuana’s medical benefits? Two experts explain the evidence<p>Currently <a href="http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx">25 states and the District of Columbia</a> have medical cannabis programs. On Nov. 8, Arkansas, Florida and North Dakota will <a href="https://ballotpedia.org/Marijuana_on_the_ballot#tab=By_year">vote on medical cannabis ballot initiatives</a>, while Montana will vote on repealing limitations in its existing law.</p>
<p>We have no political position on cannabis legalization. We study the cannabis plant, also known as marijuana, and its related chemical compounds. Despite claims that cannabis or its extracts relieve all sorts of maladies, the research has been sparse and the results mixed. At the moment, we just don’t know enough about cannabis or its elements to judge how effective it is as a medicine.</p>
<p>What does the available research suggest about medical cannabis, and why do we know so little about it?</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/137992/original/image-20160915-30575-u4evpk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/137992/original/image-20160915-30575-u4evpk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/137992/original/image-20160915-30575-u4evpk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/137992/original/image-20160915-30575-u4evpk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/137992/original/image-20160915-30575-u4evpk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/137992/original/image-20160915-30575-u4evpk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/137992/original/image-20160915-30575-u4evpk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The jury is still out on marijuana’s medical benefits.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/thomashawk/15678197523/in/photolist-pTqRUp-mH2uWp-aPvv6T-6myypu-6C9Vi4-2vQBzS-93HVne-pXBbXq-72LvdS-8gsYdj-95YdUT-bofivq-anfnem-G7L87b-e1dnje-bJD1wp-9Aiq6u-9PgZiP-vbSL8j-78BUTU-mN4fb7-bFbDLM-6JBoNY-7D2v5P-aEW2Xp-fFSpRv-9o6CA2-oUsZYf-bezxmp-JHLyre-8ZYjVQ-93Zkad-fmz2DL-aEazkf-6B71oq-aP5pHt-4CkxjN-6ck9tu-9Q7Go5-bmvw9K-96ijCm-ccsJnC-pcKXYz-kYq7YM-5SEyeD-91G6rS-9o9F2o-9Aiqcw-aEZSWy-9gSMSC">Thomas Hawk/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>What are researchers studying?</h2>
<p>While some researchers are investigating smoked or vaporized cannabis most are looking at specific cannabis compounds, called cannabinoids.</p>
<p>From a research standpoint, cannabis is considered a “dirty” drug because it contains hundreds of compounds with poorly understood effects. That’s why researchers tend to focus on just one cannabinoid at a time. Only two plant-based cannabinoids, THC and cannabidiol, have been studied extensively, but there could be others with medical benefits that we don’t know about yet. </p>
<p>THC is the main active component of cannabis. It activates <a href="https://www.youtube.com/watch?v=jznQfMj9RWM">cannabinoid receptors</a> in the brain, causing the “high” associated with cannabis, as well as in the liver, and other parts of the body. The only <a href="https://www.drugabuse.gov/publications/drugfacts/marijuana-medicine">FDA-approved cannabinoids</a> that doctors can legally prescribe are both lab produced drugs similar to THC. They are prescribed to increase appetite and prevent wasting caused by cancer or AIDS.</p>
<p>Cannabidiol (also called CBD), on the other hand, doesn’t interact with cannabinoid receptors. It doesn’t cause a high. <a href="http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx">Seventeen states</a> have <a href="http://www.nbcnews.com/storyline/legal-pot/no-buzz-medical-pot-laws-prove-problematic-patients-lawmakers-n556196">passed laws</a> <a href="http://onlinelibrary.wiley.com/doi/10.1002/phar.1780/abstract">allowing access to CBD</a> for people with certain medical conditions.</p>
<p>Our bodies also produce cannabinoids, called endocannabinoids. Researchers are creating new drugs that alter <a href="http://www.ccic.net/index.php?id=4,0,0,1,0,0">their function</a>, to better understand how cannabinoid receptors work. The goal of these <a href="http://online.liebertpub.com/doi/pdfplus/10.1089/can.2016.0009">studies</a> is to discover treatments that can use the body’s own cannabinoids to treat conditions such as chronic pain and epilepsy, instead of using cannabis itself. </p>
<p>Cannabis is promoted as a treatment for many medical conditions. We’ll take a look at two, chronic pain and epilepsy, to illustrate what we actually know about its medical benefits.</p>
<h2>Is it a chronic pain treatment?</h2>
<p>Research suggests that some people with chronic pain <a href="http://www.sciencedirect.com/science/article/pii/S0304395902004001">self-medicate with cannabis</a>. However, there is limited human research on whether cannabis or cannabinoids effectively reduce chronic pain.</p>
<p><a href="http://dx.doi.org/10.1503/cmaj.091414">Research in people</a> suggest that certain conditions, such as chronic pain caused by <a href="http://dx.doi.org/10.1016/j.jpain.2012.10.009">nerve injury</a>, may respond to smoked or vaporized cannabis, as well as an <a href="http://www.cmcr.ucsd.edu/index.php/2015-11-20-20-52-15/pending-studies/16-a-randomized-cross-over-controlled-trial-of-dronabinol-and-vaporized-cannabis-in-neuropathic-low-back-pain">FDA-approved THC drug</a>. But, most of these studies rely on subjective self-reported pain ratings, a significant limitation. Only a few controlled <a href="http://dx.doi.org/10.1007/s11481-015-9600-6">clinical trials</a> have been run, so we can’t yet conclude whether cannabis is an effective pain treatment. </p>
<p>An alternative research approach focuses on drug combination therapies, where an experimental cannabinoid drug is combined with an existing drug. For instance, a <a href="http://dx.doi.org/10.1111/bph.13012">recent study</a> in mice combined a low dose of a THC-like drug with an aspirin-like drug. The combination blocked nerve-related pain better than either drug alone. </p>
<p>In theory, the advantage to combination drug therapies is that less of each drug is needed, and side effects are reduced. In addition, some people may respond better to one drug ingredient than the other, so the drug combination may work for more people. Similar studies have not yet been run in people.</p>
<h2>Well-designed epilepsy studies are badly needed</h2>
<p>Despite some sensational <a href="http://www.wuft.org/news/2016/09/14/pot-works-effectively-as-a-medicine-says-gainesvilles-first-marijuana-doc/">news stories</a> and widespread speculation on the internet, the use of cannabis to reduce epileptic seizures is supported more by <a href="https://www.ncbi.nlm.nih.gov/pubmed/11779037">research in rodents</a> than in people. </p>
<p>In people the evidence is much less clear. There are many <a href="https://dx.doi.org/10.1111/epi.12610">anecdotes</a> and surveys about the positive effects of cannabis flowers or extracts for treating epilepsy. But these aren’t the same thing as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911937/">well-controlled clinical trials</a>, which can tell us which types of seizure, if any, respond positively to cannabinoids and give us stronger predictions about how most people respond. </p>
<p>While CBD has gained interest as a potential treatment for seizures in people, the physiological link between the two is unknown. As with chronic pain, the few clinical studies have been done included very <a href="https://www.ncbi.nlm.nih.gov/pubmed/26976797">few patients</a>. Studies of larger groups of people can tell us whether only some patients respond positively to CBD.</p>
<p>We also need to know more about the cannabinoid receptors in the brain and body, what systems they regulate, and how they could be influenced by CBD. For instance, CBD may <a href="https://dx.doi.org/10.1111/epi.13060">interact</a> with anti-epileptic drugs in ways we are still learning about. It may also have different effects in a developing brain than in an adult brain. Caution is particularly urged when seeking to medicate children with CBD or cannabis products. </p>
<h2>Cannabis research is hard</h2>
<p>Well-designed studies are the most effective way for us to understand what medical benefits cannabis may have. But research on cannabis or cannabinoids is particularly difficult. </p>
<p>Cannabis and its related compounds, <a href="https://www.dea.gov/divisions/hq/2015/hq122315.shtml">THC and CBD</a>, are on <a href="https://www.dea.gov/druginfo/ds.shtml">Schedule I</a> of the Controlled Substances Act, which is for drugs with “<a href="https://www.dea.gov/druginfo/ds.shtml">no currently accepted medical use and a high potential for abuse</a>” and includes Ecstasy and heroin.</p>
<p>In order to study cannabis, a researcher must first request permission at the state and federal level. This is followed by a lengthy federal review process involving inspections to ensure high security and detailed record-keeping. </p>
<p>In our labs, even the very small amounts of cannabinoids we need to conduct research in mice are highly scrutinized. This regulatory burden discourages many researchers. </p>
<p>Designing studies can also be a challenge. Many are based on users’ memories of their symptoms and how much cannabis they use. Bias is a limitation of any study that includes <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745402/">self-reports</a>. Furthermore, laboratory-based studies usually include only moderate to heavy users, who are likely to have formed some tolerance to marijuana’s effects and may not reflect the general population. These studies are also limited by using whole cannabis, which contains many cannabinoids, most of which are poorly understood. </p>
<p>Placebo trials can be a challenge because the euphoria associated with cannabis makes it easy to identify, especially at high THC doses. People know when they are high. </p>
<p>Another type of bias, called <a href="http://www.apa.org/research/action/glossary.aspx?tab=5">expectancy</a> bias, is a particular issue with cannabis research. This is the idea that we tend to experience what we expect, based on our previous knowledge. For example, people <a href="https://dx.doi.org/10.1177/0269881116632374">report feeling more alert</a> after drinking what they are told is regular coffee, even if it is actually decaffeinated. Similarly, research participants may report pain relief after ingesting cannabis, because they believe that cannabis relieves pain. </p>
<p>The best way to overcome expectancy effects is with a <a href="http://www.ncbi.nlm.nih.gov/pubmed/22588253">balanced placebo</a> design, in which participants are told that they are taking a placebo or varying cannabis dose, regardless of what they actually receive. </p>
<p>Studies should also include objective, biological measures, such as blood levels of THC or CBD, or physiological and sensory measures routinely used in other areas of biomedical research. At the moment, few do this, prioritizing self-reported measures instead.</p>
<h2>Cannabis isn’t without risks</h2>
<p>Abuse potential is a concern with any drug that affects the brain, and cannabinoids are no exception. Cannabis is somewhat similar to tobacco, in that some people have great difficulty quitting. And like tobacco, cannabis is a natural product that has been selectively bred to have strong effects on the brain and is not without risk. </p>
<p>Although many cannabis users are able to stop using the drug without problem, <a href="https://www.nih.gov/news-events/news-releases/marijuana-use-disorder-common-often-untreated">2-6 percent</a> of users have <a href="http://online.liebertpub.com/doi/full/10.1089/can.2015.29004.rtd">difficulty quitting</a>. Repeated use, despite the desire to decrease or stop using, is known as <a href="https://www.drugabuse.gov/publications/research-reports/marijuana/available-treatments-marijuana-use-disorders">cannabis use disorder</a>. </p>
<p>As more states more states pass medical cannabis or recreational cannabis laws, the number of people with some degree of cannabis use disorder is also likely to increase. </p>
<p>It is too soon to say for certain that the potential benefits of cannabis outweigh the risks. But with restrictions to cannabis (and cannabidiol) loosening at the state level, research is badly needed to get the facts in order.</p><img src="https://counter.theconversation.com/content/64200/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steven Kinsey receives funding from the National Institutes of Health. </span></em></p><p class="fine-print"><em><span>Divya Ramesh does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>With restrictions to cannabis loosening at the state level, research is badly needed to get the facts in order.Steven Kinsey, Assistant Professor of Psychology, West Virginia UniversityDivya Ramesh, Research Associate, University of ConnecticutLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/606002016-09-23T15:33:47Z2016-09-23T15:33:47ZWhat is Spice and why is the drug so dangerous?<p>Synthetic cannabis, of which Spice is an example, is linked to serious health issues ranging from difficulties breathing to psychotic episodes. But, despite well-known issues, these drugs are still in demand and homeless people, particularly, are at risk of mental health issues from their use. So what exactly are these drugs made of and why do they cause such violent reactions.</p>
<p>Spice is not a single drug, but a range of laboratory-made chemicals that mimic the effects of tetrahydrocannabinol (THC), the main psychoactive component of cannabis. <a href="http://ki.se/en/research/spice-a-hundred-times-more-potent-than-cannabis">Research suggests</a> that Spice and other forms of synthetic cannabis are capable of producing much more intense and prolonged effects at much lower doses than natural cannabis. This is because, while the THC in natural cannabis only partially reacts with the body, synthetic cannabis reacts far more fully. </p>
<p>To understand the biology behind the intense reaction to Spice we need to look at the parts of the body’s central nervous system that react to cannabis – the cannabinoid receptors – and the chemical part of the drug that reacts with the body – the “agonist”. </p>
<p>While THC is a “partial agonist” (it only partially reacts with cannabinoid receptors), synthetic cannabis is often a “full agonist”. In this way, the more adverse effects observed with synthetic cannabis use stem from its ability to completely saturate and activate all of the body’s cannabinoid receptors at a lower dose. </p>
<p>Although the consequences of long-term regular use are not well defined, <a href="http://onlinelibrary.wiley.com/doi/10.1002/jcph.827/epdf">experts believe</a> that synthetic cannabis has the potential to develop, or cause a relapse of mental illness, especially if there is a family history of mental disorders.</p>
<h2>Where does Spice come from?</h2>
<p>In 2008, the first synthetic cannabinoid – which reacts with the body in the same way as cannabis – was identified on the recreational drug market. JWH-018 was an aminoalklindole originally developed by <a href="http://pubs.rsc.org/en/Content/ArticleLanding/2015/AN/C5AN00797F#!divAbstract">John Huffman of Clemson University</a> in the US and sold under the brand name: Spice. Aminoalkylindoles – the most common sub-family of synthetic cannabinoids –- are produced, in kilogram quantities, through quick and simple chemical reactions using legal substances. These substances are produced on a large-scale by chemical companies based in China and then shipped, as bulk powders, to Europe by air or sea. Once in Europe, the synthetic cannabinoids are mixed with (or sprayed onto) plant material using solvents such as acetone or methanol to dissolve the powders. The combination is then dried, packaged and sold as either incense or smoking mixtures. </p>
<p>JWH-018 is now a controlled substance in many countries under narcotics legislation. But the prevalence of next-generation synthetic cannabinoids – now known colloquially as Spice or Mamba – continue to be the largest group of new psychoactive substances (NPS) in common usage. As of December 2015, 14 different sub-families of cannabinoid agonists have been identified – indicating that there are potentially hundreds of these types of substances circulating via the internet and often across international borders.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/125590/original/image-20160607-7438-1yw2w1s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/125590/original/image-20160607-7438-1yw2w1s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125590/original/image-20160607-7438-1yw2w1s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125590/original/image-20160607-7438-1yw2w1s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125590/original/image-20160607-7438-1yw2w1s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125590/original/image-20160607-7438-1yw2w1s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125590/original/image-20160607-7438-1yw2w1s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Spice – a particular problem among the homeless.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&autocomplete_id=&search_tracking_id=Q1owmDE5ORIXMQV19XaSJg&searchterm=homeless%20london&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=301238456">Elena Rostunova/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Why is it so dangerous?</h2>
<p>Different brands of smoking mixtures can have very different effects, but the strength of a specific brand appears to owe more to the ratio of cannabinoids to chemically inactive plant material in the mixture, rather than the variation in the <a href="https://www.unodc.org/documents/scientific/NPS_2013_SMART.pdf">chemical structure of compounds</a> themselves. In other words, the specific type of chemical in the mixture is less important than how much chemical there is compared to what has been put in to provide bulk. </p>
<p>Due to the high potency of some synthetic cannabinoids, the amount needed for each “hit” can be as little as a few tens of milligrams (about the size of a match head). The intoxicating effects of more potent brands – such as Clockwork Orange, Pandora’s Box and Annihilation – can be quite overpowering. Some people experience difficulty breathing, rapid heart rate, and shakes and sweats, all of which can lead to a severe <a href="http://dx.doi.org/10.3109/15563650.2015.1110590">panic attacks</a>. At higher doses, balance and coordination can be severely affected. Users can experience a loss of feeling and numbness in their limbs, nausea, collapse and unconsciousness. </p>
<p>Continued use of synthetic cannabinoids can cause psychotic episodes, which in extreme cases can last for weeks, and may exacerbate existing mental-health illnesses in susceptible users. But most reports of severe mental health, addiction and acts of violence as a result of regular use tend to be among <a href="https://www.theguardian.com/society/2015/nov/07/cheap-spice-strengthens-grip-northern-towns-blackpool-synthetic-cannabinoid">prisoners and homeless people</a>. These groups are much more likely to report high rates of drug dependency, self-define as having addictive personalities and disclose a range of diagnosed mental-health issues including “dual diagnosis” (drug dependence and at least one mental-health disorder, or at least two personality or psychotic disorders) and existing offences for violence. </p>
<p>Because of the substantial risks of synthetic cannabinoids, many countries have already outlawed their production, possession and distribution. But it is unlikely that the “war on drugs” will show any sign of relenting, given the <a href="https://theconversation.com/fast-market-for-legal-highs-poses-challenge-for-scientists-17709">rapidly evolving nature</a> of the recreational drugs market and the lack of globalised drug-control legislation. Only by working collectively can scientists, medical professionals and law makers help to stem the flow of these dangerous compounds before they pose a serious threat to health of vulnerable groups in society.</p><img src="https://counter.theconversation.com/content/60600/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>New psychoactive substances, same problematic users.Oliver Sutcliffe, Senior Lecturer in Psychopharmaceutical Chemistry, Manchester Metropolitan UniversityRobert Ralphs, Reader in Criminology, Manchester Metropolitan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/625742016-08-01T07:25:04Z2016-08-01T07:25:04ZIs cannabis really getting stronger?<figure><img src="https://images.theconversation.com/files/131482/original/image-20160721-32600-1c3eqpv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&autocomplete_id=&searchterm=marijuana&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=246790006">Mr High Sky/Shutterstock</a></span></figcaption></figure><p>Cannabis continues to be the world’s favourite illicit drug with around 147m people <a href="http://www.who.int/substance_abuse/facts/cannabis/en/">using it</a> annually. However, there are fears that the drug is becoming <a href="http://www.dailymail.co.uk/health/article-3439625/Pot-getting-potent-Level-psychoactive-ingredient-cannabis-TRIPLED-20-years-experts-warn.html">increasingly potent</a> and that it could pose a public health risk. But how reliable is the evidence? And is it really getting stronger?</p>
<p>The debate about cannabis potency and harm is long running. In the UK, where there are <a href="http://bit.ly/29TzaED">2m annual users</a>, it predates the <a href="https://policypress.co.uk/evidence-versus-politics">2004 downgrading of cannabis classification</a> from class B to class C. But this episode demonstrated some of the issues with estimating the harms of the drug. Research conducted at the time highlighted how the relative harms of cannabis compared with other class B substances was one of the factors behind the decision to reclassify. However, critics accused the government of ignoring emerging evidence that cannabis was becoming more potent and that it represented a serious public health problem. </p>
<p>Those more sympathetic to the change in classification questioned whether this interpretation of cannabis potency was accurate, highlighting how an alternative conclusion had been drawn from published research which suggested only modest changes in cannabis potency over the <a href="http://www.emcdda.europa.eu/attachements.cfm/att_33985_EN_Insight6.pdf">20 to 30 years</a> prior to 2004.</p>
<p>Others, meanwhile, questioned the relevance of potency evidence, pointing to a shortage of studies looking at the consumption of cannabis in a natural setting and how users may well be smoking higher strength strains, but that they could be <a href="http://onlinelibrary.wiley.com/doi/10.1111/add.12634/abstract?userIsAuthenticated=false&deniedAccessCustomisedMessage=">“titrating” their doses as a consequence</a>, for example, by taking smaller puffs.</p>
<p>The debate over potency is not helped by politicians referring to the “<a href="http://news.bbc.co.uk/1/hi/uk_politics/7372876.stm">lethal quality</a>” of today’s cannabis and although the evidence is inconclusive, there is widespread acceptance that strains of cannabis are stronger than in previous decades. </p>
<p>To date, most assessments of cannabis potency have focused on increasing levels of <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2008.02230.x/full">tetrahydrocannabinol (THC)</a>. But this doesn’t provide the full story. Cannabis contains hundreds of compounds, some of which interact with each other. For example, THC helps the user get high, but another compound, cannabidiol (CBD), can counter this by reducing unpleasant feelings such as anxiety. So it is the balance between THC and CBD over time that is important. </p>
<p>It would seem that many cannabis producers have competed to incrementally increase THC levels while selectively breeding out the more <a href="http://onlinelibrary.wiley.com/doi/10.1111/add.13207/full">protective cannabinoids</a>. Seizures from the US Drug Enforcement Administration show how this ratio has changed in America over the <a href="http://bit.ly/2ap8HR3">last 20 years</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/131158/original/image-20160719-7910-1rfnhg9.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/131158/original/image-20160719-7910-1rfnhg9.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/131158/original/image-20160719-7910-1rfnhg9.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=386&fit=crop&dpr=1 600w, https://images.theconversation.com/files/131158/original/image-20160719-7910-1rfnhg9.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=386&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/131158/original/image-20160719-7910-1rfnhg9.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=386&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/131158/original/image-20160719-7910-1rfnhg9.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=485&fit=crop&dpr=1 754w, https://images.theconversation.com/files/131158/original/image-20160719-7910-1rfnhg9.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=485&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/131158/original/image-20160719-7910-1rfnhg9.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=485&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">CBD / THC ratio over time.</span>
<span class="attribution"><span class="source">ElSohly et al 2016</span></span>
</figcaption>
</figure>
<p>This changing ratio was helped in the UK by the introduction of <a href="http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1997-01-01_1_page006.html">hydroponic techniques</a> in the 1980s for cultivating cannabis.</p>
<h2>Proxy problems</h2>
<p>Proxy measures of cannabis potency such as those based on home seizures of cannabis are <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1556-4029.2007.00603.x/full">widely used and quoted</a>. But we don’t know if the cannabis seized is a representative sample of the cannabis in circulation. Steve Rolles, senior policy analyst for Transform Drug Policy Foundation, describes it as “a massive data hole”.</p>
<p>Also, the quality and sophistication of the cannabis testing procedures, such as chromatography, used to analyse seizures has <a href="http://onlinelibrary.wiley.com/doi/10.1002/dta.1430/abstract">improved over recent decades</a>. But this means seminal and widely quoted research is outdated and less relevant.</p>
<p>Another factor to consider is how much cannabis is consumed in the average joint. A recent analysis of over 10,000 cannabis transactions carried out in the US between 2000 and 2010, estimated that the <a href="http://www.sciencedirect.com/science/article/pii/S0376871616301508">average joint</a> contains 0.3g. This is significantly lower than the previous estimates of 0.75 to 1g. </p>
<p><a href="http://onlinelibrary.wiley.com/doi/10.1111/add.12508/abstract?userIsAuthenticated=false&deniedAccessCustomisedMessage=">Other factors</a> that influence the strength of the hit are how deeply you inhale and how long you hold the smoke in your lungs.</p>
<p>The method used to ingest the drug also influences a user’s experience, such as eating, vaping or smoking. Dose can be increased by using a bong whereby a greater quantity of the drug is inhaled in one go compared to a single hit on a joint. Higher potency concentrates known as “dabs” have the potential to <a href="http://pediatrics.aappublications.org/content/136/1/1?utm_source=highwire&utm_medium=email&utm_campaign=Pediatrics_etoc">alter the level of intoxication</a> .</p>
<p>Research gathered from a subset of cannabis users creates ill informed policy, <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2010.03139.x/abstract">threatening the credibility of public health messages</a>. </p>
<h2>Why any of this matters</h2>
<p>Without any quality assurance system such as the one recently introduced <a href="http://www.economist.com/news/britain/21702624-revellers-get-chance-see-if-their-illegal-drugs-are-what-they-claim-be-cocaine-or">at a festival</a>, it is likely that younger users – who haven’t been using cannabis for long – are the most vulnerable to variations in cannabis potency.</p>
<p>There are public health implications. Cannabis users have to rely on their own knowledge when deciding on the dosage to achieve the desired high. A regulated market such as the one in <a href="http://www.tdpf.org.uk/blog/cannabis-regulation-colorado-early-evidence-defies-critics">Colorado</a> could mean users are able to make better decisions and, in turn, reduce the rate of people needing treatment services where <a href="http://www.tandfonline.com/doi/abs/10.3109/09687637.2015.1090398">cannabis is the primary problem</a> .</p>
<p>The government should regulate cannabis products to make them safer, enabling consumers to make more informed choices. It should create opportunities for targeted education and harm reduction, and employ other evidence-based health interventions.</p>
<p>The science underpinning the cannabis potency story is problematic. With so many people using cannabis, it can’t be acceptable to continue with a system where basic information about this product’s strength and purity are obscure. It is time for a national survey of cannabis that not only provides information about the strength of cannabis but how exactly it is consumed, too.</p><img src="https://counter.theconversation.com/content/62574/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Hamilton is affiliated with Alcohol Research UK. </span></em></p><p class="fine-print"><em><span>Mark Monaghan does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>147m people used the drug last year. We need to know much more about it.Ian Hamilton, Lecturer in Mental Health, University of YorkMark Monaghan, Lecturer in Crimimology and Social Policy, Loughborough UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/478962015-11-05T11:11:29Z2015-11-05T11:11:29ZLabs make new, dangerous synthetic cannabinoid drugs faster than we can ban them<p>XLR-11, PB-22, AB-FUBINACA, MAB-CHMINACA, 5F-AMB. These are the cryptic and sometimes unpronounceable names of the most dangerous drugs you’ve never heard of. They are responsible for kidney injury, psychosis, seizures, coma and death.</p>
<p>For instance, AB-FUBINACA was responsible for a spate of recent <a href="http://www.nytimes.com/2015/05/23/nyregion/federal-drug-charges-for-wesleyan-students-in-overdoses.html">poisonings at Wesleyan University</a>. And MAB-CHMINACA was associated with more than 100 <a href="http://new.dhh.louisiana.gov/index.cfm/newsroom/detail/3161">hospitalizations in Baton Rouge</a>. Neither of these drugs were known to the scientific community until late last year.</p>
<p>These drugs are synthetic cannabinoids – several of the hundreds that have been identified as new “designer drugs” in the past five years. More than 150 were reported in 2013 alone, according to the <a href="https://www.unodc.org/documents/scientific/Global_SMART_Update_13_web.pdf">United Nations Office on Drugs and Crime (UNODC)</a>. And police, doctors, scientists and lawmakers are all struggling to identify these new drugs as they hit the streets. </p>
<h2>What <em>are</em> synthetic cannabinoids?</h2>
<p>Synthetic cannabinoids are molecules designed to mimic the effects of tetrahydrocannabinol, or THC. Like THC, these synthetic cannabinoids target the cannabinoid type 1 receptor (CB1R) in the brain, which is responsible for the psychoactive effects of THC in cannabis.</p>
<p>Although these products are sometimes called “synthetic cannabis” or “fake pot,” both terms are wrong and misleading. They are called cannabinoids not because they are like cannabis, but because they interact with cannabinoid receptors in the brain and elsewhere in the body.</p>
<p>These molecules <em>look</em> chemically different from those found in cannabis, and have very different effects in laboratory tests, and on their users, than actual cannabis does.</p>
<p>These synthetic drugs are manufactured in <a href="http://www.theguardian.com/society/2015/may/01/chinese-labs-legal-highs-west-drugs">clandestine labs</a> (mostly in China) for export around the globe. They are usually sprayed onto dry herbs for smoking, and sold inexpensively in foil packets with constantly changing brand names like Spice, K2, Black Mamba, Cloud Nine, Maui Wowie, Mr Nice Guy and countless others. There are literally hundreds of individual products that are known to law enforcement. The brands change as frequently as the drugs themselves.</p>
<p>Underground chemists tweak the structures of these molecules using tricks similar to those employed in the pharmaceutical industry. Unlike Big Pharma, where the goal is to create safer medicines, synthetic cannabinoid designers want to ensure their products evade prohibition but still get their customers “high.” As molecules are identified and banned, drug labs reformulate their products to stay a step ahead. Consumers can never be sure of exactly what drug (or combination of drugs) they are using.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/100653/original/image-20151103-16532-3x9xk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/100653/original/image-20151103-16532-3x9xk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/100653/original/image-20151103-16532-3x9xk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=414&fit=crop&dpr=1 600w, https://images.theconversation.com/files/100653/original/image-20151103-16532-3x9xk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=414&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/100653/original/image-20151103-16532-3x9xk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=414&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/100653/original/image-20151103-16532-3x9xk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=520&fit=crop&dpr=1 754w, https://images.theconversation.com/files/100653/original/image-20151103-16532-3x9xk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=520&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/100653/original/image-20151103-16532-3x9xk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=520&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Dangerous highs.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/rclarkeimages/19688210679/in/photolist-vZMe7g-9siRYW-9FW4gT-9vGgur">raymondclarkeimages/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>Synthetic cannabinoids are getting stronger and more dangerous</h2>
<p>As part of a group of researchers from Australia, New Zealand and the United States, we studied the ability of several synthetic cannabinoids that were commonly available in the past few years to elicit a response from CB1R – the cannabinoid receptor in the brain.</p>
<p>The synthetic cannabinoids we tested that were commonly available during 2011-2013 were <a href="http://dx.doi.org/10.1021/acschemneuro.5b00107">several times as potent as THC</a>. But the latest drugs from 2014-2015 were <a href="http://dx.doi.org/10.1021/acschemneuro.5b00112">up to 700 times more potent</a>. In these tests most synthetic cannabinoids fully activated CB1R. THC, on the other hand, does not fully activate the receptor. This difference may account for the greater toxicity of these synthetic cannabinoids.</p>
<p>Serious illnesses due to cannabis are exceedingly rare, while those due to synthetic cannabinoid use are becoming more common. A <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6422a5.htm">recent report</a> by the Centers for Disease Control and Prevention stated that there were 3,572 calls to poison centers in the United States in the first half of this year due to synthetic cannabinoids, a 229% increase from the same period in 2014. More concerning is the fact that <a href="http://dx.doi.org/10.1056/NEJMp1505328">clusters of synthetic cannabinoid overdose</a> are associated with the newest drugs. </p>
<p>Thousands of people wound up in emergency rooms as a result of outbreaks in <a href="http://www.adph.org/news/assets/150423b.pdf">Alabama</a>, <a href="http://msdh.ms.gov/msdhsite/_static/resources/6307.pdf">Mississippi</a>, and <a href="http://www.nytimes.com/2015/04/25/health/surge-in-hospital-visits-linked-to-a-drug-called-spice-alarms-health-officials.html">New York</a> in April and May alone. Some of these cases were linked to MAB-CHMINACA, but others are likely due to synthetic cannabinoids so new they have not been identified.</p>
<p>Deaths due to synthetic cannabinoids have been climbing steadily as new variants emerge. During the <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6439a7.htm">Mississippi outbreak in April</a> alone there were nine deaths associated with synthetic cannabinoid use.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/100655/original/image-20151103-16502-qglk8p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/100655/original/image-20151103-16502-qglk8p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/100655/original/image-20151103-16502-qglk8p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/100655/original/image-20151103-16502-qglk8p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/100655/original/image-20151103-16502-qglk8p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/100655/original/image-20151103-16502-qglk8p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/100655/original/image-20151103-16502-qglk8p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Synthetic cannabinoids have been linked to poisonings and death.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/chelsea_nj/5586889117/in/photolist-vZMe7g-9siRYW-9FW4gT-9vGgur">Szapucki/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>The DEA can’t keep up with synthetic cannabinoids</h2>
<p>In 2012, President Obama signed into law the <a href="https://www.govtrack.us/congress/bills/112/s3187/text">Synthetic Drug Abuse Prevention Act (SDAPA)</a>, which amended the Controlled Substances Act (CSA) of 1970 to place “cannabimimetic agents” – substances that mimic the effects of cannabis – into <a href="http://www.dea.gov/druginfo/ds.shtml">Schedule I</a>, the most restrictive regulatory category. Schedule I covers drugs like heroin, LSD and actual cannabis. SDAPA designated several specific synthetic cannabinoids, as well as five chemical classes of cannabinoid molecules, as Schedule I substances. But none of the newest synthetic cannabinoids are explicitly covered by SDAPA.</p>
<p>As chemists modify structures to avoid prohibition, the Drug Enforcement Administration (DEA) adds more synthetic cannabinoids to Schedule I. Since January 2013, the DEA has exercised emergency scheduling powers five times to place a total of 25 synthetic cannabinoids into Schedule I. Keep in mind that more than 150 new synthetic cannabinoids were reported by UNODC in 2013.</p>
<p>Once a specific synthetic cannabinoid is placed into Schedule I, related molecules may be considered illegal due to a 1986 amendment to the CSA called the <a href="http://www.gpo.gov/fdsys/pkg/STATUTE-100/pdf/STATUTE-100-Pg3207.pdf">Controlled Substance Analogue Enforcement Act</a> (also called the Federal Analogue Act). The act allows any substance which is “substantially similar” to a Schedule I chemical to be treated as such. But in each instance that similarity needs to be demonstrated in a court of law – which can be a slow process. In effect, that means chemists can modify molecular structures faster than the government can demonstrate that they are illegal or add them to Schedule I.</p>
<p>For instance, a notice of intent to move MAB-CHMINACA, the drug tied to hospitalizations in Baton Rouge and elsewhere, to Schedule I was <a href="https://www.federalregister.gov/articles/2015/09/16/2015-23198/schedules-of-controlled-substances-temporary-placement-of-the-synthetic-cannabinoid-mab-chminaca">filed last month</a>. MAB-CHMINACA, a derivative of AB-FUBINACA, only appeared after AB-FUBINACA was placed in Schedule I <a href="https://www.federalregister.gov/articles/2014/01/10/2014-00217/schedules-of-controlled-substances-temporary-placement-of-four-synthetic-cannabinoids-into-schedule">last year</a> – and that is probably no coincidence.</p>
<h2>Using a proactive approach to combat synthetic cannabinoids</h2>
<p>Perhaps it is time we stopped reactively banning new synthetic cannabinoids and considered more innovative regulatory approaches.</p>
<p>In the pharmaceutical industry, the patents for a drug typically include related “prophetic” structures, preventing competitors from making modified versions of the drug. Prophetic structures are molecules that have not actually been created yet, but could feasibly be prepared, and are predicted to have similar effects to the protected drug.</p>
<p>A <a href="http://www.texastribune.org/2015/08/25/animation-texas-crack-down-synthetic-marijuana/">law passed in Texas</a> on September 1 used a similar approach to prohibit more than 1,000 <em>potential</em> synthetic cannabinoids that are anticipated to appear in future based on trends observed now. This is a creative approach, but 1,000 is still a finite number. And the total number of chemically possible synthetic cannabinoids is larger still.</p>
<p>Proactive prohibition may slow the release of new synthetic cannabinoids. Or it could simply catalyze the release of increasingly elaborate and chemically diverse variants. If the past few years are anything to go by, 2016 will bring a new wave of unknown and untested synthetic cannabinoids, and more challenges for police, doctors, scientists and lawmakers.</p><img src="https://counter.theconversation.com/content/47896/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Samuel Banister receives funding from the Australian Research Council.</span></em></p><p class="fine-print"><em><span>Iain S. McGregor receives funding from the National Health and Medical Research Council of Australia, the Australian Research Council, and the Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney. </span></em></p><p class="fine-print"><em><span>Roy Gerona receives funding from the National Institute of Environmental Health Sciences, National Institute of Allergy and Infectious Diseases, US Environmental Protection Agency, California Environmental Protection Agency, Breast Cancer Fund, Sheepdrove Trust and Safe Food Institute.</span></em></p>Synthetic cannabinoids – drugs that mimic the psychoactive effect of cannabis – have been linked to injuries and deaths. And when one is banned, another rises to take its place.Samuel Banister, Postdoctoral Research Fellow, Stanford UniversityIain S McGregor, Professor of Psychopharmacology and NHMRC Principal Research Fellow, University of SydneyRoy Gerona, Assistant Professor, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/426532015-06-26T12:05:56Z2015-06-26T12:05:56ZWhy anti-cancer properties in cannabis must be investigated<figure><img src="https://images.theconversation.com/files/85533/original/image-20150618-23259-jtwklc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It's the compounds in the cannabis that researchers are interested in. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/100651935@N07/9587691917/in/photolist-fBeqM4-mDrXYV-o2PWRG-aiNzFS-b7NGPa-p7AQJP-dxsNDZ-7d8tyc-mZyaL2-cki8oA-7eca4L-bnsgZh-dcKxfS-bAn7KZ-nTQRHB-4AF96c-obbKiG-f3biiv-8vXAa4-qaC7ws-nfPu7B-nhSp4z-jmEjVP-sG2ZAd-53668o-5sUSSq-55Dv5a-bAWniH-nhMFPP-7d7htP-8tAPqc-btZ2Er-nfL3Ys-5sQsMX-cj3Mj-4NFV7i-pSLitb-sGeVAt-rKpQUo-jUQMx-nxJrnF-AQuAX-fvJ7-rKrSbC-od5WjP-57mxh8-sGgykf-pCVk-iKv2SS-jmEQHL">Don Goofy</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Cancer is a word that conjures up many images. It is a varied disease that affects many people and can leave families distraught. There are fortunately treatments for a large number of these cancers, which work by restricting tumour growth and inducing cell death. However, there are cancers which pose more of a challenge, and so finding new drugs that can fight these ones becomes even more important.</p>
<p>The methods for discovering and developing new drugs, or chemotherapies, simply fall into two camps. The more recent approach has been the design of drugs with a particular molecular target in mind. This is arguably best exemplified <a href="http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Biologicaltherapies/Cancergrowthinhibitors/Imatinib.aspx">by the drug imatinib</a>, notably used to eat leukaemia. After scientists understood that the BCR-ABL hybrid gene was the cause of a certain type of leukaemia it allowed them to develop pharmacological ways to specifically counteract it – by inhibiting the signals inside the cancer cell used to grow and divide. The drug that was born to much fanfare and arguably revolutionised drug development. </p>
<p>Continued improvements in the understanding of the mechanisms inside cells that are hijacked by cancer have helped to improve the way that compounds are designed and then tested clinically. Those that are able to restore the normal function of the signalling pathways disrupted by cancer are an attractive target for drug development. </p>
<p>At least three major pharmaceutical players are in a fight to <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086120/">negate the cancer-supporting action of AKT</a>, for example. This protein kinase – a key regulator of cell function – is a central player in determining cell proliferation and growth, and is intimately linked with a number of other cell communications systems that all work in unison to support a cancer developing. Its level is over-expressed in a number of cancers, and is linked to a poorer prognosis. Consequently, therapeutic interventions to counteract its effects are particularly attractive and potentially lucrative. </p>
<h2>Isolating the compound</h2>
<p>It was however, never like this. Before the mystery of cancer was opened up, drug discovery was empirical in nature. Through antiquity, a range of flora were said to cure ailments and, using these anecdotes as guides, active ingredients have been extracted, purified and improved. This has been successful, and a number of drugs now form normal members of the pharmacopeia, including aspirin, which was isolated from the white willow, and less familiar anti-cancer drugs such as etoposide, irinotecan and taxol, which were derived from mayapples, camptotheca trees and Pacific yews. There is no doubt of their value in treatment and they’ve been used successfully for over 40 years.</p>
<p>Then there is the cannabis plant. The putative medicinal property of cannabis has been known for some time; indeed, <a href="http://bjp.rcpsych.org/content/178/2/107.long">history records</a> show they were used to ease symptoms of gout, malaria and even childbirth. However, the fundamental issue with using cannabis in its whole form as a medicine is its psychoactive properties, so it would make sense to identify the important anti-cancer parts and remove the psychoactive components. Cannabinoids are these. They number around 80, with cannabidiol (CBD) and tetrahydrocannabinol (THC) the two lead medicinal candidates. However, unlike the mayapple and Pacific yew, their development has been seriously curtailed. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/85526/original/image-20150618-23246-evxdjl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/85526/original/image-20150618-23246-evxdjl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/85526/original/image-20150618-23246-evxdjl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/85526/original/image-20150618-23246-evxdjl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/85526/original/image-20150618-23246-evxdjl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/85526/original/image-20150618-23246-evxdjl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/85526/original/image-20150618-23246-evxdjl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Cannabis.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/martius/9679798517/in/photolist-fKnuRT-aH42Ca-65h518-aiNz65-fBeqM4-o2PWRG-aiNzFS-p7AQJP-mZyaL2-cki8oA-7eca4L-bnsgZh-dcKxfS-nTQRHB-obbKiG-f3biiv-mDrXYV-b7NGPa-dxsNDZ-7d8tyc-bAn7KZ-4AF96c-8vXAa4-qaC7ws-nfPu7B-nhSp4z-jmEjVP-53668o-5sUSSq-bAWniH-nhMFPP-7d7htP-8tAPqc-btZ2Er-nfL3Ys-5sQsMX-cj3Mj-4NFV7i-pSLitb-jUQMx-od5WjP-AQuAX-sG2ZAd-55Dv5a-sGeVAt-rKpQUo-nxJrnF-fvJ7-rKrSbC-57mxh8">M a n u e l</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>It’s likely that the widespread use of cannabis as a recreational drug <a href="https://theconversation.com/medical-breakthroughs-missed-because-of-pointless-drug-bans-15072">has affected research</a> into the potential in cannabis – and the result was death by association. I wonder how the early development of CBD and THC would have progressed if it was known by any other name.</p>
<h2>Chequered pasts</h2>
<p>Drugs with chequered pasts have found redemption; take the <a href="http://www.nature.com/nrc/journal/v4/n4/full/nrc1323.html">thalidomide story</a>. This drug was infamously linked to babies born with deformations; however, serendipitous observations of improvements in leprosy in a patient taking thalidomide in 1965 led to the discovery that it also had important effects on the immune system. Refinements to the chemistry of the drug were made and the result was a new family of drugs that are valuable tools <a href="https://theconversation.com/how-thalidomide-became-one-of-the-most-talked-about-drugs-in-cancer-therapy-32194">in anti-cancer research and treatment</a>.</p>
<p>The story emphasises the point that medicinal potential of drugs should be seen objectively and guided scientifically. Cannabinoids and cannabis are not the same thing – it’s just that cannabinoids are derived from cannabis. Cannabinoids possess anti-cancer properties, which they achieve through their fundamental interactions with proteins embedded in the signalling pathways in cells that are now seen as particularly interesting for research.</p>
<p>In addition to this direct anti-cancer action, cannabinoids also have the capacity to disrupt the ability of cancer to feed itself by a process called <a href="http://www.spandidos-publications.com/or/17/4/813">angiogenesis</a> as well as being able to modulate the immune system to make it more hostile towards cancer. Furthermore, CBD and THC appear to support the activity and efficacy of other <a href="http://mct.aacrjournals.org/content/10/1/90.long">chemotherapy drugs</a>. Indeed, we <a href="https://theconversation.com/how-cannabis-was-used-to-shrink-one-of-the-most-aggressive-brain-cancers-34038">recently showed</a> that the cancer-killing property of radiotherapy was dramatically enhanced when cannabinoids were used in combination with this treatment – certain forms of brain cancer were reduced to sizes that were difficult to detect. Taken together, all of these features show a profile with great anti-cancer potential.</p>
<p>However slow things have been, a sea-change has been occurring; there is a palpable sense that legislators are becoming open to the scientific evidence that suggests cannabinoids may possess <a href="http://www.drugabuse.gov/publications/drugfacts/marijuana-medicine">medicinal quality</a>. Clinical trials using various forms of cannabinoids are now taking place in a number of countries, and we all await the results of <a href="https://clinicaltrials.gov/ct2/results?term=cannabinoids+cancer&Search=Search">these studies</a>. </p>
<p>I hope to be able to change the answer that I give to patients who contact me to ask: “do you think I should be using cannabinoids for my cancer?” from the negative to the affirmative. My frustrating answer has always been it is too early to say, as promising laboratory data has not yet been confirmed by objective clinical studies. This is not a criticism of the drug development system, as convincing clinical trials are needed to ensure patients are given drugs that have been thoroughly tested to ensure the best chance of them fighting their disease.</p>
<p>The flip side of those who passionately shout for the “legalisation of cannabis” is that their call may inadvertently hamper the medical development of cannabinoids, which is a shame. My aim is to deliver a drug that can be used in patients with cancer. And for a headache, no one would suggest you chew on a white willow plant, especially when you could be taking an aspirin. The same is true of cannabis and cannabinoids.</p><img src="https://counter.theconversation.com/content/42653/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Wai Liu receives funding from GW Pharmaceuticals Ltd. to explore the effects/potentials of cannabinoids as an anticancer therapy.</span></em></p>The three Cs that have caused much controversy in research: cancer, cannabis and cannabinoids.Wai Liu, Senior Research Fellow, St George's, University of LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/343262014-11-27T14:59:24Z2014-11-27T14:59:24ZHype around cannabis as a treatment for cancer is undeserved<figure><img src="https://images.theconversation.com/files/65628/original/image-20141126-4231-1wpb5dp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Role of cannabis in medicine does not strengthen argument for legalisation.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/thomashawk/71149302/sizes/l/in/photolist-7hEd7-6P64Ue-aiNz65-mDrXYV-b7NGPa-shGPU-o2PWRG-aiNzFS-7WMW5Z-cki8oA-dxsNDZ-fBeqM4-aps23m-oxb3RP-7d8tyc-mZyaL2-8ABrDN-jLumTV-ajeHFT-7eca4L-5SnDiL-f3biiv-bAn7KZ-8vXAa4-9FukZn-53668o-dcKxfS-5sUSSq-7MUm4B-bAWniH-nhMFPP-7d7htP-btZ2Er-nfL3Ys-5sQsMX-b9nfB2-cj3Mj-8Ayn9K-4NFV7i-pSLitb-9PM4rX-jmEjVP-hUZrvD-5Gvt8q-hUYRp3-aH42Ca-65h518-9b9czu-naETDn-daB1Bx-4iy3XH/">Thomas Hawk</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>Cannabis has long been touted as containing chemicals that might work against cancer. A <a href="http://mct.aacrjournals.org/content/early/2014/11/12/1535-7163.MCT-14-0402.abstract">recent study</a> suggested that two chemicals found in cannabis, the cannabinoids CBD and THC, could act on an aggressive brain tumour called glioma, where only 10% of people live for five years after diagnosis. The research found that THC and CBD, combined with radiotherapy <a href="https://theconversation.com/how-cannabis-was-used-to-shrink-one-of-the-most-aggressive-brain-cancers-34038">were able to shrink</a>, but not completely eradicate, gliomas that were artificially implanted in mice.</p>
<p>The results provide useful scientific information, and may indeed improve the treatment of brain cancer patients eventually, after clinical trials and all the other regulatory hurdles that must be cleared before a new treatment can be used in patients. But despite considerable public interest, the data isn’t yet there to show that cannabinoids are an effective treatment option in cancer in humans.</p>
<p>Radiotherapy is currently, regrettably one of the best tools against brain cancer that oncologists currently have. As with many treatments, irradiating the brain often comes with debilitating long-term side effects and patients, scientists and oncologists will universally be hoping that future treatments come with a smaller burden. If the cannabinoids study is replicated in people with glioma, it may be that less radiation is needed to get the same therapeutic effect – a very welcome advance, but still a long way off being anywhere near certain.</p>
<h2>Cancer, cannabis and talk of cures</h2>
<p>THC, one of the cannabinoids used in the study, has in fact already been tested in glioma patients: eight years ago in a <a href="http://www.nature.com/bjc/journal/v95/n2/full/6603236a.html">clinical trial on nine patients</a>. This study achieved its main aim, which was to see if THC was tolerated in these patients without serious side effects, but all of the patients in the study ultimately died within the time expected if they had received no further treatment. Despite this, the study was cited under the heading “Cures Brain Cancer” <a href="http://www.wakingtimes.com/2013/07/27/34-medical-studies-proving-cannabis-cures-cancer/">on one of many websites</a> listing medical studies that prove “cannabis cures cancer.”</p>
<p>Research is ongoing into cannabinoids around the world, but as Emma Smith, senior science information officer at Cancer Research UK, told me: “Cannabinoids can have a range of different effects on cancer cells grown in the lab and animal tumours, but at the moment there isn’t good evidence from clinical trials to prove that they can safely and effectively treat cancer in patients.”</p>
<p>There are also many other promising – and potentially even more effective – avenues that scientists are exploring for glioma. For example, <a href="http://cancerres.aacrjournals.org/content/74/19/5364.long">work published in October</a> showed that treating glioma in mice with a “specific inhibitor” drug called alisertib, targeted against a protein called Aurora-A, prolonged the survival of mice with artificial brain tumours, similar to those in the cannabinoids study.</p>
<p>Alisertib is also <a href="http://clinicaltrials.gov/ct2/results?term=Alisertib+AND+cancer&Search=Search">already in human clinical trials</a> for a number of different cancer types, so arguably this research is a lot closer to potentially helping patients with glioma, as it is likely to have fewer hurdles to jump over before approval than treatments that are yet to prove themselves in trials. It would be great to hear more about potential treatments at a more advanced stage like this, but it is unlikely to result in the thousands of shares and likes on Facebook that cannabis invites. </p>
<h2>Cannabis isn’t that special</h2>
<p>So why are we not equally as excited about the numerous other promising preliminary experiments of a similar nature? It is not simply a question of us not hearing about them – cannabis is perceived as special and causes a stir every time a fairly preliminary piece of research comes out. And equally, why are large cancer charities such as Cancer Research UK frequently attacked and forced to dedicate a lot of resources and expertise to <a href="http://scienceblog.cancerresearchuk.org/2012/07/25/cannabis-cannabinoids-and-cancer-the-evidence-so-far/">debunking the myths surrounding cannabis</a> and for “blocking” cannabis research – <a href="http://www.cancerresearchuk.org/about-cancer/trials/a-study-looking-at-dexanabinol-for-advanced-cancer">despite part-funding a Phase I clinical trial</a> into a synthetic cannabinoid called <a href="http://www.cancer.gov/drugdictionary?cdrid=720043">dexanabinol</a>?</p>
<p>This, too, must come with some caution. <a href="http://www.cancerresearchuk.org/science/research/who-and-what-we-fund/browse-by-location/newcastle/newcastle-university/ruth-plummer-9380">Ruth Plummer</a>, professor of experimental cancer medicine at Newcastle University and clinical co-ordinator of the trial, said it was at an early stage with safe doses and potential side effects still being explored. “While some patients do seem to have benefited from treatment there is still a long way to go before these agents are established as standard treatments for patients.” </p>
<h2>The plant-based theory</h2>
<p>Supporters of cannabis as a cancer treatment claim that as the chemicals are plant-based, they are safer and less toxic than conventional chemotherapies. The very well established chemotherapy agents doxorubicin (originally from soil bacteria) and vincristine (originally from the Madagascan periwinkle plant) do both have side-effects, so this assumption is not supported by science. They have also been proved to work effectively only when purified and used in controlled doses – something that would need to be figured out from research if cannabinoids are to be a useful part of our arsenal against cancer. </p>
<p>A quick trawl of social media sites suggests that the most ardent of supporters of the “cannabis cures cancer” belief are often recreational users who believe that if cannabis does have utility in cancer treatment, it will provide strength to their pro-legalisation stance. This certainly hasn’t happened so far with a range of strong painkillers and sedatives that are frequently used in medicine but considered illegal without medical prescription – <a href="http://www.release.org.uk/law/list-controlled-drugs">morphine and temazepam</a> are two examples. It’s unlikely that this would be any different with any cannabis derivatives.</p>
<p>If cannabinoids do have a role to play in treating cancer, scientists and doctors will welcome the advances. Currently, however, none of the numerous studies into cannabis-chemicals have shown anything to justify the hype and almost evangelical belief that it is “the cure” generated by many supporters.</p><img src="https://counter.theconversation.com/content/34326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Victoria Forster does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Cannabis has long been touted as containing chemicals that might work against cancer. A recent study suggested that two chemicals found in cannabis, the cannabinoids CBD and THC, could act on an aggressive…Victoria Forster, Postdoctoral Research Associate in Cancer Research, Newcastle UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/308282014-08-26T20:48:00Z2014-08-26T20:48:00ZOld dope, new tricks: the new science of medical cannabis<figure><img src="https://images.theconversation.com/files/57256/original/xn4nnd8h-1408947119.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Somewhere in this much-incinerated plant lies valuable medicine: perhaps a treatment for cancer or an antidote to obesity.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/prensa420/11875638094">Prensa 420/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>Medicinal cannabis is back in the news again after a planned trial to grow it in Norfolk Island was blocked by the federal government last week. The media is ablaze with political rumblings and tales of public woe, but what does science have to say on the subject?</p>
<p>Well, <a href="http://archinte.jamanetwork.com/article.aspx?articleid=1898878">an article just published</a> in the prestigious journal JAMA Internal Medicine provocatively suggests that US states with medical cannabis laws have dramatically reduced opioid mortality rates.</p>
<p>So the science is clearly every bit as alive and kicking as the political bluster, but rests on firmer, less emotive grounds. This is what we know: somewhere in that much-incinerated plant lies valuable medicine – perhaps a treatment for cancer or an antidote to obesity.</p>
<p>In fact, cannabis science is one of the fastest moving frontiers in pharmacology and has accelerated by the realisation that we’re all already marinated in cannabis-like molecules (endocannabinoids) and their receptors. Endocannabinoids help regulate many physiological processes: mood, memory, appetite, pain, immune function, metabolism and bone growth to name a few (there are even cannabinoid receptors in sperm). </p>
<p>Consuming cannabis modulates this endocannabinoid system in many ways. And the effects can be benevolent, although sometimes problematic.</p>
<h2>Cannabis’ changing fortunes</h2>
<p>Humanity has used cannabis as medicine <a href="http://www.readcube.com/articles/10.1038/nrn2253">for thousands of years</a>; the current era of prohibition is a historical aberration. But murky politics has seen a plant that has been widely utilised for clothing, fuel, food, fibre and medication ostracised – from nautical rope to killer dope.</p>
<p>Now, the pendulum is swinging back. Cannabis is legal in two of the United States of America, and a prescribed medicine in a further 23. Many other countries are also rapidly revising their attitudes. </p>
<p>In 2013, the NSW parliament convened a <a href="http://www.parliament.nsw.gov.au/Prod/Parlment/committee.nsf/0/FDB7842246A5AB71CA257B6C0002F09B">medical cannabis inquiry</a>, the current NSW premier <a href="http://www.theage.com.au/victoria/campaign-to-legalise-medicinal-marijuana-gains-momentum-20140824-107rxp.html">Mike Baird</a> is a supporter, as is shock-jock <a href="http://www.northerndailyleader.com.au/story/2335532/radio-king-joins-marijuana-fight/">Alan Jones</a>.</p>
<p>But if we’re going to rediscover the therapeutic value of cannabis – and we probably should – then there’s much to be gained from examining recent developments in cannabinoid science.</p>
<p>Cannabis contains more than 120 different cannabinoid molecules. But, as far as we know, only one gets you stoned: THC. The plant contains a cornucopia of non-psychoactive, non-intoxicating THC cousins with emerging medicinal potential. </p>
<p>Their abbreviated names resemble a bad Scrabble hand: CBD, CBG, THC-V, CBC, and CBN to mention a few. These have the potential to heal without making you a paranoid, gormless grinner.</p>
<h2>Useful cousins</h2>
<p>Cannabidiol (CBD) is perhaps the most interesting of the lot: a non-intoxicating cannabinoid that is present in variable amounts in different cannabis samples and moderates the actions of THC in the brain. Smoking high-cannabidiol weed appears less likely to cause psychosis, paranoia and cognitive impairment than low-CBD varieties. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/57257/original/y9dk2cc9-1408947213.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/57257/original/y9dk2cc9-1408947213.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/57257/original/y9dk2cc9-1408947213.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/57257/original/y9dk2cc9-1408947213.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/57257/original/y9dk2cc9-1408947213.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/57257/original/y9dk2cc9-1408947213.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/57257/original/y9dk2cc9-1408947213.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Cannabidiol is bred out of street cannabis in Australia.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/dankdepot/5500915995">Dank Depot/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Cannabidiol given alone has <a href="http://psychcentral.com/news/2012/06/07/marijuana-compound-may-beat-antipsychotics-at-treating-schizophrenia/39803.html">antipsychotic effects</a> as efficacious as standard anti-psychotic drugs but with fewer side effects. It also has remarkable effects in treating intractable childhood epilepsy that cannot be treated with conventional anti-convulsants.</p>
<p>Cannabis plants appear genetically programmed to produce THC or CBD. But <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0070052">our recent analysis</a> shows cannabidiol is bred out of street cannabis in Australia. Bringing it back may maximise cannabis’ medicinal potential and lessen the adverse mental health consequences of smoking weed. </p>
<p>The cannabinoid molecule that causes the high from cannabis, THC, mostly exists in plants as non-psychoactive THC-A (more than 80% of plant THC is in the form of THC-A). Cannabis must be heated above 170 Celsius to transform THC-A into the psychoactive THC. This is why pleasure seekers smoke, bake or vaporise their weed.</p>
<p>THC-A is anti-inflammatory and neuroprotective, and if plant material is ingested without heating, for example by juicing, then non-psychoactive THC-A effects are maximised and intoxication minimised. This also reduces the long-term hazards involved in smoking. </p>
<p><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219532/">THC-V</a> is another non-psychoactive cannabinoid that may actually block cannabinoid receptors, reducing appetite and the tendency to store fat, and making it a potentially wonder treatment for obesity.</p>
<p>One cannabis-derived product is already approved in Australia; Sativex oral spray contains equal amounts of THC and CBD. Absorbed across the mucous membranes of the mouth, Sativex reduces muscle spasms in multiple sclerosis. The route of absorption gives low and steady levels of THC and CBD in blood, in contrast to the often-disorienting THC tsunami obtained with smoked cannabis. </p>
<p>In <a href="http://archpsyc.jamanetwork.com/article.aspx?articleid=1812720">our recent study</a>, cannabis users given high doses of Sativex in a Cannabis Replacement Therapy clinical trial could not discriminate it from placebo, and reported little intoxication.</p>
<h2>Rediscovering cannabis</h2>
<p>We now know that the right cannabinoids, prepared and administered appropriately, might deliver medical benefits while minimising intoxication. So there’s certainly no good scientific rationale for prosecuting those supplying high CBD strains, or preparations that maximise consumption of THC-A, THC-V or other non-psychoactive cannabinoids. </p>
<p>Indeed, blindly scheduling the bad-scrabble cannabinoids in the cannabis regulatory bracket limits future research.</p>
<p>Even THC is a legitimate target for ongoing medical research, particularly when dosed in forms that give slow and steady blood levels. </p>
<p>THC clearly has important therapeutic effects in <a href="http://www.neurology.org/content/82/17/1556">multiple sclerosis and pain</a>, in stimulating appetite in HIV or cancer patients, and even <a href="http://www.medicaljane.com/2014/07/11/israeli-study-orally-administered-tetrahydrocannabinol-thc-may-help-treat-ptsd/">for anxiety disorders, such as post-traumatic stress disorder</a>.</p>
<p>No medicine is perfect: opiates control pain but may be addictive and constipating; antidepressants lift mood but may numb you out and ruin your sex life; statins can lower your cholesterol but can cause muscle wastage. All drugs are poisons, it’s just a matter of the dose you’re taking.</p>
<p>Cannabis has its own positives and negatives, and the risks involved in its regular use, particularly during adolescence, <a href="http://www.nejm.org/doi/full/10.1056/NEJMra1402309">continue to be well ventilated</a>. But if we’re clever about our use, then it can be a most valuable therapeutic: a voyage of rediscovery is long overdue. </p>
<p><strong><em>We’re currently recruiting participants for two cannabinoid research studies in Sydney. The first is looking at regular, non-treatment seeking cannabis users to help us understand <a href="http://www.davidallsop.net/cannabis-and-pain-study.html">the role of the endocannabinoid system in pain perception</a>, while the other is recruiting people who need help with problematic cannabis use, examining the effects of <a href="http://www.davidallsop.net/exercise-study.html">daily exercise on endocannabinoid release and stored THC</a>.</em></strong></p><img src="https://counter.theconversation.com/content/30828/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David J. Allsop receives funding from NHMRC. GW Pharmaceutical provided Sativex for our study.</span></em></p><p class="fine-print"><em><span>Iain S. McGregor receives funding from NHMRC and ARC. GW Pharmaceutical provided Sativex for our study.</span></em></p>Medicinal cannabis is back in the news again after a planned trial to grow it in Norfolk Island was blocked by the federal government last week. The media is ablaze with political rumblings and tales of…David J. Allsop, Research Fellow in Psychopharmacology and Addiction Medicine at the School of Psychology, University of SydneyIain S McGregor, Professor of Psychopharmacology at the School of Psychology, University of SydneyLicensed as Creative Commons – attribution, no derivatives.