tag:theconversation.com,2011:/id/topics/ketamine-8311/articlesKetamine – The Conversation2024-01-12T16:12:10Ztag:theconversation.com,2011:article/2205172024-01-12T16:12:10Z2024-01-12T16:12:10ZFour street drugs that could pose the biggest threat to UK public health in 2024<figure><img src="https://images.theconversation.com/files/569021/original/file-20240112-25-j3jcoe.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4025%2C3017&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Xanax pills</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/muncie-indiana-united-states-june-5-1416893333">gremlinworks/Shutterstock</a></span></figcaption></figure><p>As with fashion and music, illicit drugs go through peaks and troughs of popularity. There are popular staples, such as cannabis, and more disruptive and transient substances, such as <a href="https://theconversation.com/meow-hear-this-mephedrone-is-a-curious-khat-2164">mephedrone</a>. As with <a href="https://youtu.be/Ja2fgquYTCg?si=AjGVwuw92NiEPnMS">clothing fashion</a>, the drugs that most people are able to buy are <a href="https://www.emcdda.europa.eu/publications/eu-drug-markets_en">determined by</a> the choices of designers, manufacturers and logistical operations, rather than consumers. </p>
<p>Predicting how the UK drug market may change in 2024 relies not only on recent trends in drug use but also on international developments. Geopolitical events in <a href="https://geographical.co.uk/news/myanmar-becomes-worlds-biggest-producer-of-opium">south-east Asia</a> or <a href="https://www.bbc.co.uk/news/world-latin-america-67912242">South America</a> are just as important as organised crime activity in cities such as London or Liverpool. We suggest that there are four types of drugs that will be of increasing concern in 2024. </p>
<h2>1. Opioids</h2>
<p>Heroin sold in the UK is primarily sourced from opium grown in Afghanistan. Any change in the <a href="https://theconversation.com/afghanistan-what-the-conflict-means-for-the-global-heroin-trade-165995">production and distribution</a> of opium has a direct effect on the <a href="https://theconversation.com/nitazenes-synthetic-opioids-more-deadly-than-fentanyl-are-starting-to-turn-up-in-overdose-cases-212589">UK heroin market</a>. </p>
<p>After seizing power in 2022, the Taliban announced a clampdown on opium farming in Afghanistan. While other growing regions have <a href="https://www.unodc.org/roseap/en/2023/12/southeast-asia-opium-survey-report-launch/story.html#:%7E:text=Bangkok%20(Thailand)%2C%2012%20December,Asia%20released%20in%20Bangkok%20today.">increased production</a>, this has not been at the level of the Afghan crop. </p>
<p>Large stockpiles of opium and heroin stored along trafficking routes have depleted. 2024 will see the impact of this. </p>
<p>The estimated number of people who use heroin has <a href="https://www.gov.uk/government/publications/opiate-and-crack-cocaine-use-prevalence-estimates/estimates-of-opiate-and-crack-use-in-england-main-points-and-methods">increased</a> over the past decade, with an estimated 341,032 current users in England. </p>
<p>This is a highly profitable market, and suppliers are adaptable and nimble in responding to changes like these. As a consequence of the shortfall in Afghan heroin production, new, highly potent <a href="https://www.bmj.com/content/383/bmj.p2421">synthetic opioids</a> have already emerged to fill the gap. These include the group of synthetic opiates known as <a href="https://theconversation.com/nitazenes-synthetic-opioids-more-deadly-than-fentanyl-are-starting-to-turn-up-in-overdose-cases-212589">nitazenes</a>, which have contributed to the <a href="https://theconversation.com/generation-x-hardest-hit-as-drug-deaths-rise-yet-again-in-england-and-wales-220064">record levels</a> of drug-related deaths recorded in 2023 in the UK. </p>
<p>Increased market penetration of these drugs could lead to a big rise in deaths in 2024. Worryingly, <a href="https://www.bbc.co.uk/news/uk-england-manchester-67777938">misselling</a> as other products and unintentional contamination of other non-opioid drugs could increase the harms further. Government and treatment services must act now to prepare for an increase in the supply of these drugs, as the costs of not doing so might lead to a <a href="https://www.sciencedirect.com/science/article/pii/S0955395923003614?via%3Dihub">“nightmare scenario”</a>. </p>
<h2>2. Cocaine</h2>
<p>Cocaine has never been purer, more affordable and more available to those <a href="https://www.theguardian.com/commentisfree/2023/dec/23/coke-consumption-uk-millennials-generation-x">who want it in the UK</a>. While <a href="https://www.ons.gov.uk/peoplepopulationandcommunity/crimeandjustice/articles/drugmisuseinenglandandwales/yearendingmarch2023">levels of use</a> have been relatively stable over the past 20 years, <a href="https://theconversation.com/generation-x-hardest-hit-as-drug-deaths-rise-yet-again-in-england-and-wales-220064">deaths and hospitalisations</a> have increased due the nature of the product on the market and increases in the frequency and length of use. </p>
<p>Unlike other class A drugs, such as heroin, there are few effective treatments, and users tend to be more socially integrated. This means that they are less likely to come into contact with police or present to treatment services. </p>
<p>They may not identify themselves as having a drug problem, despite the effect it may be having on their lives. When disposable income continues to be squeezed as it is in the current cost of living crisis, powder cocaine (as opposed to crack cocaine) is a drug that will continue to provide good “value for money”. Sadly, we predict yet another rise in poisonings and hospitalisations in 2024.</p>
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<img alt="Older man snorting coke." src="https://images.theconversation.com/files/569019/original/file-20240112-29-ke6q5v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/569019/original/file-20240112-29-ke6q5v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/569019/original/file-20240112-29-ke6q5v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/569019/original/file-20240112-29-ke6q5v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/569019/original/file-20240112-29-ke6q5v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/569019/original/file-20240112-29-ke6q5v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/569019/original/file-20240112-29-ke6q5v.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">
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<span class="caption">Cocaine users tend to be more ‘socially integrated’.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/old-male-writer-smoking-cigarette-2284921057">Elnur/Shutterstock</a></span>
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<h2>3. Ketamine</h2>
<p>Ketamine has been used in medicine as an anaesthetic for many years, and more recently as an <a href="https://theconversation.com/how-antidepressants-ketamine-and-psychedelic-drugs-may-make-brains-more-flexible-new-research-216025">antidepressant</a>. Taken recreational at lower doses, the drug <a href="https://www.talktofrank.com/drug/ketamine">induces</a> feelings of detachment and happiness. </p>
<p>This is another drug that has become increasingly <a href="https://bjgp.org/content/73/727/87">popular</a> because it is cheap, fast-acting and easy to get hold of. </p>
<p>Around <a href="https://news.sky.com/story/student-died-after-taking-ketamine-now-her-mother-wants-to-address-naivety-among-parents-13039959">3.8% of young people</a> (aged 16 to 24) report having used the drug. This has been steadily rising over the past decade. Police report that the weight of <a href="https://www.gov.uk/government/statistics/seizures-of-drugs-in-england-and-wales-financial-year-ending-2022/seizures-of-drugs-in-england-and-wales-financial-year-ending-2022">seizures</a> of ketamine that they made increased sharply from 187kg in 2021 to 1,837kg in 2022. Drug seizures are often used as a proxy for estimating levels of supply.</p>
<p>A range of problems can develop for those using ketamine in higher doses or over a longer period, ranging from mental health problems to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544340/">incontinence</a>. An overdose of the drug can prove to be fatal.</p>
<p>As with most illicit drugs, combining ketamine with alcohol <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323326/">increases</a> health risks. Sadly, it is the norm for people to use more than one drug at a time – including alcohol.</p>
<p>Given the widespread availability and <a href="https://www.timeout.com/uk/nightlife/how-ketamine-became-britains-go-to-party-drug">affordability</a> of ketamine in the UK, its use will continue to rise in 2024. Use is concentrated among younger people, many of whom won’t be aware of its potential for harm until it’s too late. </p>
<p>As with cocaine, there has been a distinct lack of health messaging, advice and support for people who use ketamine. Some youth organisations that have tried to do this have faced unhelpful <a href="https://www.thetimes.co.uk/article/how-ketamine-became-the-uks-hidden-campus-killer-9mp3pm6ht">national media backlash</a>. </p>
<h2>4. Benzodiazapines</h2>
<p>Benzodiazepines, more commonly known by brand names such as Valium and Xanax, have proved to be popular and dangerous in equal measure. While medical prescriptions have <a href="https://www.england.nhs.uk/2023/03/opioid-prescriptions-cut-by-almost-half-a-million-in-four-years-as-nhs-continues-crackdown/">fallen</a> in recent years illicit <a href="https://www.ons.gov.uk/peoplepopulationandcommunity/crimeandjustice/articles/drugmisuseinenglandandwales/yearendingmarch2023">demand</a> and supply has not. </p>
<p>Although doctors have been <a href="https://www.nice.org.uk/sharedlearning/benzodiazepine-hypnotics-deprescribing">encouraged</a> to reduce prescriptions for benzodiazepines, the black market has filled the gap in demand. Unlike legitimate supply, the illicit market has no quality control or reliable information on strength – both of which lead to deaths.</p>
<p>The rapid rise in deaths from <a href="https://www.sciencedirect.com/science/article/abs/pii/S0955395921004308">these drugs</a> in Scotland shows regional differences both in the use of drugs and the risks they pose. Reversing this trend in use and fatalities will prove to be difficult in 2024 as there are few signs of a change in demand for, or supply of these drugs.</p>
<h2>Can we prevent drug harms?</h2>
<p>It is not possible to entirely prevent all the harms relating to drug use and the drugs market, but they can be reduced. 2024 may see the emergence of new drugs or new ways of taking them, but what won’t change will be the continuation of more than 20 years of increasing drug-related harm. </p>
<p>In a year of a general election in the UK, there is the danger that drugs policy will be used for political point scoring – signalling to the electorate how tough on crime one party is, or how soft on crime their opponents are. Whatever the outcome of the election, unless there is a clear commitment to long-term investment in responses to drug use, new records will be set in drug-related deaths.</p><img src="https://counter.theconversation.com/content/220517/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Harry Sumnall receives and has received funding from public grant awarding bodies for alcohol and other drugs research, and consultation fees from (international) not-for-profit organisations, and government Ministries for consultation work. He is an unpaid member of the Scientific Advisory Board of the Mind Foundation.</span></em></p><p class="fine-print"><em><span>Ian Hamilton 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>Synthetic opioids called nitazenes are ones to watch in 2024.Ian Hamilton, Honorary Fellow, Department of Health Sciences, University of YorkHarry Sumnall, Professor in Substance Use, Liverpool John Moores UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2200322023-12-18T10:28:05Z2023-12-18T10:28:05ZMatthew Perry died of ‘acute effects of ketamine’ – what you need to know about the drug<figure><img src="https://images.theconversation.com/files/566151/original/file-20231217-18-qrp95.jpg?ixlib=rb-1.1.0&rect=14%2C9%2C3196%2C2123&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Matthew Perry</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/matthew-perry-disney-abc-television-group-101622553">s_bukley/Shutterstock</a></span></figcaption></figure><p>Millions of people worldwide were left devastated by the <a href="https://www.bbc.co.uk/news/world-us-canada-67252752">death this year of 54-year-old Matthew Perry</a>, the Friends star famous for bringing wise-cracking Chandler Bing to life. A global superstar, recently sober with an autobiography on the bestseller lists, it looked like his troubled past was behind him. So the world was especially shocked and saddened to learn of his untimely death by apparent drowning.</p>
<p>This week, <a href="https://me.lacounty.gov/2023/press-releases/cause-and-manner-of-death-determined-for-matthew-langford-perry/">medical officials in Los Angeles</a>, have confirmed that his drowning was more complex than initially suspected. Toxicology reports have indicated that two drugs were in Perry’s system at the time of his death. These were <a href="https://patient.info/medicine/buprenorphine-tablets-for-addiction-treatment-espranor-prefibin-subutex">buprenorphine</a>, a drug used to treat opioid drug addiction, and <a href="https://www.talktofrank.com/drug/ketamine">ketamine</a>, sometimes referred to as special K or horse tranquilliser.</p>
<p>Given Perry’s well-documented addiction issues to opioid painkillers, his use of buprenorphine was not a surprise. But why was he taking ketamine?</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010394/">Ketamine</a> works by acting on receptors in the brain and, since its synthesis in the 1960s, has been used in veterinary medicine and also as a surgical anaesthetic in humans. </p>
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<img alt="Medical person holding ampoules of ketamine" src="https://images.theconversation.com/files/566152/original/file-20231217-27-iahpre.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/566152/original/file-20231217-27-iahpre.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/566152/original/file-20231217-27-iahpre.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/566152/original/file-20231217-27-iahpre.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/566152/original/file-20231217-27-iahpre.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/566152/original/file-20231217-27-iahpre.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/566152/original/file-20231217-27-iahpre.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">Ketamine is used as an anaesthetic in humans.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/ketamine-dissociative-anesthetic-analgesic-used-anesthesia-2328562769">luchschenF/Shutterstock</a></span>
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<p>Following signs that ketamine might affect user mood, it was investigated for its potential role in treating <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999402/">depression and anxiety</a>. Today, users can be prescribed ketamine for these conditions, but usually only after other antidepressant and anti-anxiety medications have failed. </p>
<p>The medical officer in LA specified that Perry was being legally prescribed infusions of ketamine to treat depression and anxiety. They did note, however, that given the time since his last dose, it was unlikely that the ketamine in his bloodstream was from his prescribed infusions. No other reason was offered as to why he would have had ketamine in his system so close to the time of his death.</p>
<p>In addition to finding drugs in his body, Perry was also listed as having <a href="https://www.nhs.uk/conditions/coronary-heart-disease/">heart disease</a>. Ketamine can cause an <a href="https://www.talktofrank.com/drug/ketamine#the-risks">increase in blood pressure and heart rate</a>, so it is not surprising to hear from the medical examiner that: “At the high levels of ketamine found in his post-mortem blood specimens, the main lethal effects would be from both cardiovascular overstimulation and respiratory depression.”</p>
<p>Another contributing factor to Perry’s death was listed as drowning. So does ketamine make drowning more likely? </p>
<p>Ketamine can cause users to have issues with <a href="https://www.talktofrank.com/drug/ketamine#the-risks">coordination, and they may feel disorientated</a>. The combination of these effects while in water, can make a person’s reactions slower, putting them at risk of harm, so ketamine certainly could make drowning more likely.</p>
<p>Also, taking ketamine with other substances, like alcohol, can increase the risk of drowsiness. While Perry had a much-publicised issue with alcohol, his toxicology report indicated no alcohol in his system at the time of his death.</p>
<h2>Not the first</h2>
<p>Sadly, Perry is not the first Hollywood star to die by drowning under the influence of drugs. In 2012, global star <a href="https://www.bbc.co.uk/news/entertainment-arts-17483997">Whitney Houston died in a bathtub</a> after consuming marijuana, cocaine, and the benzodiazepine known as alprazolam (Xanax).</p>
<p>These stories remind us all of the dangers of substance abuse and the importance of seeking professional help for addiction issues. </p>
<p>Matthew Perry was a vocal advocate for more addiction support services, and since his death the <a href="https://matthewperryfoundation.org/">Matthew Perry Foundation</a> has been set up to help those struggling with the disease of addiction. </p>
<p>Perry said: “When I die, I don’t want Friends to be the first thing that’s mentioned, I want helping others to be the first thing that’s mentioned. And I’m going to live the rest of my life proving that.” </p>
<p>In the last years of his life, he did just that. But sadly, it seems that it will be in death that he will have the biggest impact on helping others to overcome their demons.</p><img src="https://counter.theconversation.com/content/220032/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Philip Crilly 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>Perry was being legally prescribed infusions of ketamine.Philip Crilly, Senior Lecturer in Pharmacy Practice and Digital Public Health, Kingston 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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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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<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>
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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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<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/2160772023-11-08T13:37:22Z2023-11-08T13:37:22ZKetamine can rapidly reduce symptoms of PTSD and depression, new study finds<figure><img src="https://images.theconversation.com/files/555141/original/file-20231022-23-svzzue.jpg?ixlib=rb-1.1.0&rect=0%2C10%2C6949%2C4615&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ketamine is an anesthetic that must be administered carefully and by a health care professional.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/professional-wearing-gloves-injecting-ketamine-in-a-royalty-free-image/1614335455?phrase=ketamine&adppopup=true">Jeniffer Fontan/iStock via Getty Images Plus</a></span></figcaption></figure><p>The <a href="https://www.dea.gov/factsheets/ketamine">drug ketamine</a> can reduce the symptoms of post-traumatic stress disorder, or PTSD, and symptoms of depression in patients as early as a day after injection. That is the key finding of my team’s new meta-analysis, <a href="https://doi.org/10.1177/10600280231199666">just published in the journal Annals of Pharmacotherapy</a>. </p>
<p>Ketamine is an anesthetic that is sometimes used as a substance of abuse but is increasingly being <a href="https://theconversation.com/ketamine-paired-with-looking-at-smiling-faces-to-build-positive-associations-holds-promise-for-helping-people-with-treatment-resistant-depression-190950">explored as a treatment</a> for a range of mental health conditions.</p>
<p>We analyzed <a href="https://doi.org/10.1177/10600280231199666">six randomized controlled trials</a> representing 259 patients with moderate to severe PTSD. In all trials, about half were injected with ketamine. The rest received either salt water or the <a href="https://doi.org/10.1002/jcph.2233">drug midazolam</a>, a benzodiazepine like <a href="https://www.webmd.com/drugs/2/drug-9824/xanax-oral/details">Xanax</a> that is also used as an anesthetic agent. </p>
<p>Patients receiving ketamine saw their PTSD symptoms reduced by about 25% both at one day and one week after therapy. But if patients received <a href="https://doi.org/10.1038/s41386-022-01266-9">repeated injections over four weeks</a>, PTSD symptoms declined by only 12%. Reduction of depression symptoms were more modest but still significant.</p>
<p>In most of these trials, patients only received a single shot; in the other two, they were given an injection at the same dose six or more times over two to four weeks. The benefits after the first injection were similar across studies, but it’s unclear how well additional doses of ketamine over time maintain these benefits. </p>
<p>Overall, the benefits of even a single ketamine injection occur rapidly, but are modest in magnitude. The best regimen to maintain these benefits by reinjecting ketamine has not been determined.</p>
<h2>Why it matters</h2>
<p>PTSD, a <a href="https://doi.org/10.1016/j.comppsych.2012.02.009">debilitating mental health disorder</a>, occurs when past trauma causes flashbacks, nightmares, depressed mood, anxiety and avoidance of activities that could trigger traumatic memories. Patients with PTSD are <a href="https://www.ptsd.va.gov/professional/treat/cooccurring/suicide_ptsd.asp">twice as likely to attempt suicide</a> than the general population. </p>
<p>About <a href="https://www.ptsd.va.gov/understand/common/common_adults.asp">13 million Americans have PTSD</a> in a given year, which translates to nearly 5% of the adult population. PTSD is caused by experiencing or witnessing a traumatic event. Many combat veterans have the disorder, as do survivors of physical assault, natural disasters, child abuse and sexual abuse. Those with moderate to severe disease cases lose an average of about three and a half days of work per month due to triggered symptoms or treatment for the illness. </p>
<p><a href="https://www.healthquality.va.gov/guidelines/MH/ptsd/VA-DoD-CPG-PTSD-Full-CPG.pdf">Trauma-focused psychotherapy</a> – techniques that help patients <a href="https://www.nctsn.org/sites/default/files/interventions/tfcbt_fact_sheet.pdf">recall, process and respond</a> to traumatic memories – is the treatment of choice for PTSD, but it <a href="https://www.ptsd.va.gov/professional/treat/txessentials/overview_therapy.asp">can take several weeks to see benefits</a>, and not all patients respond. </p>
<p>For these people, antidepressants such as <a href="https://www.apa.org/ptsd-guideline/treatments/medications">paroxetine, sertraline and venlafaxine</a> are recommended as alternatives, or as an addition to psychotherapy. </p>
<p>But like psychotherapy, these drugs may not work for a while – about <a href="https://pubmed.ncbi.nlm.nih.gov/35234292/">five to eight weeks</a> – unlike ketamine, which seems to begin working almost immediately. That said, the reduction in PTSD and depression symptoms over time following ketamine injection is about the same as what the traditional antidepressants provide once they take effect.</p>
<p>Because some people with severe PTSD may be experiencing suicidal thoughts, time is of the essence; they simply might not be able to wait for traditional options to begin working. Ketamine might be an effective bridge to immediately reduce patients’ symptoms until trauma-focused psychotherapy and other antidepressants can kick in. </p>
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<figcaption><span class="caption">Researchers agree that new treatments for PTSD patients are greatly needed.</span></figcaption>
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<h2>What still isn’t known</h2>
<p>The big unknown with using ketamine for PTSD and depressive symptoms is how often the injections are needed. The data simply is not robust enough to determine whether multiple doses maintain the effects better than simply using a single dose.</p>
<p>Ketamine costs around <a href="https://psychedelicspotlight.com/ketamine-therapy-how-much-does-it-cost-who-is-eligible/">US$800 per injection</a>, so knowing how much to administer each treatment and how many injections to give over time is important.</p>
<p>Importantly, ketamine can be abused. If purchased from <a href="https://doi.org/10.1177/10600280221092482">unlicensed pharmacies or online stores</a>, the ketamine product is not approved by the Food and Drug Administration. It may not have the correct dose, may have expired or might not even have any ketamine in it. Or, it may contain a substitute drug with a dangerous active ingredient, like the <a href="https://www.dea.gov/factsheets/lsd">synthetic street drug LSD</a>. Such fake products <a href="https://doi.org/10.1016/j.japh.2020.04.020">can harm or even kill patients</a></p>
<p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take on interesting academic work.</em></p><img src="https://counter.theconversation.com/content/216077/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>C. Michael White 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>The analysis shows that ketamine may start relieving symptoms of PTSD within one day, but it is still unclear how long the effects last and how many injections are needed to maintain benefits.C. Michael White, Professor of Pharmacy Practice, University of ConnecticutLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2116852023-08-17T13:16:40Z2023-08-17T13:16:40ZHow consciousness may rely on brain cells acting collectively – new psychedelics research on rats<figure><img src="https://images.theconversation.com/files/542999/original/file-20230816-31-hyq6mq.jpg?ixlib=rb-1.1.0&rect=123%2C113%2C3470%2C2581&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Psychedelics can help uncover consciousness. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/will-universe-remember-me-series-artistic-484612375">agsandrew/Shutterstock</a></span></figcaption></figure><p>Psychedelics are known for inducing <a href="https://theconversation.com/how-lsd-helped-us-probe-what-the-sense-of-self-looks-like-in-the-brain-57703">altered states of consciousness</a> in humans by fundamentally changing our normal pattern of sensory perception, thought and emotion. Research into the therapeutic potential of psychedelics <a href="https://theconversation.com/psychedelics-how-they-act-on-the-brain-to-relieve-depression-183320">has increased significantly</a> in the last decade. </p>
<p>While this research is important, I have always been more intrigued by the idea that psychedelics can be used as a tool to study the neural basis of human consciousness in laboratory animals. We ultimately share the same basic neural hardware with other mammals, and possibly some basic aspects of consciousness, too. So by examining what happens in the brain when there’s a psychedelically induced change in conscious experience, we can perhaps glean insights into what consciousness is in the first place.</p>
<p>We still don’t know a lot about how the networks of cells in the brain enable conscious experience. The dominating view is that consciousness somehow emerges as a collective phenomenon when the dispersed information processing of individual neurons (brain cells) is integrated as the cells interact.</p>
<p>But the mechanism by which this is supposed to happen remains unclear. Now our <a href="https://www.nature.com/articles/s42003-023-05093-6">study on rats</a>, published in Communications Biology, suggests that psychedelics radically change the way that neurons interact and behave collectively.</p>
<p>Our study compared two different classes of psychedelics in rats: the classic LSD type and the less-typical ketamine type (ketamine is an anaesthetic in larger doses). Both classes are known to induce psychedelic experiences in humans, despite acting on different receptors in the brain. </p>
<h2>Exploring brain waves</h2>
<p>We used electrodes to simultaneously measure electrical activity from 128 separate areas of the brain of nine awake rats while they were given psychedelics. The electrodes could pick up two kinds of signals: <a href="https://www.scientificamerican.com/article/what-is-the-function-of-t-1997-12-22/">electrical brain waves</a> caused by the cumulative activity in thousands of neurons, and smaller transient electrical pulses, called action potentials, from individual neurons.</p>
<p>The classic psychedelics, such as LSD and psilocybin (the active ingredient in magic mushrooms), activates a receptor in the brain (5-HT2A) which normally binds to <a href="https://my.clevelandclinic.org/health/articles/22572-serotonin#:%7E:text=Serotonin%20is%20a%20chemical%20that,blood%20clotting%20and%20sexual%20desire.">serotonin</a>, a neurotransmitter that regulates mood and many other things. Ketamine, on the other hand, works by inhibiting another receptor (NMDA), which normally is activated by <a href="https://my.clevelandclinic.org/health/articles/22839-glutamate">glutamate</a>, the primary neurotransmitter in the brain for making neurons fire. </p>
<p>We speculated that, despite these differences, the two classes of psychedelics might have similar effects on the activity of brain cells. Indeed, it turned out that both drug classes induced a very similar and distinctive pattern of brain waves in multiple brain regions. </p>
<p>The brain waves were unusually fast, oscillating about 150 times per second. They were also surprisingly synchronised between different brain regions. Short bursts of oscillations at a similar frequency are known to occur occasionally under normal conditions in some brain regions. But in this case, it occurred for prolonged durations.</p>
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<img alt="Brain waves on electroencephalogram EEG." src="https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=423&fit=crop&dpr=1 754w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=423&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=423&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">Brain waves on electroencephalogram EEG.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/brain-wave-on-electroencephalogram-eeg-epilepsy-575882314">Chaikom/Shutterstock</a></span>
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<p>First, we assumed that a single brain structure was generating the wave and that it then spread to other locations. But the data was not consistent with that scenario. Instead, we saw that the waves went up and down almost simultaneously in all parts of the brain where we could detect them – a phenomenon called <a href="https://www.nature.com/articles/35067550#:%7E:text=Phase%20synchronization%20refers%20to%20the,signals%20regardless%20of%20signal%20amplitude.">phase synchronisation</a>. Such tight phase synchronisation over such long distances has to our knowledge never been observed before.</p>
<p>We were also able to measure action potentials from individual neurons during the psychedelic state. Action potentials are electrical pulses, no longer than a thousandth of a second, that are generated by the opening and closing of ion channels in the cell membrane. The action potentials are the primary way that neurons influence each other. Consequently, they are considered to be the main carrier of information in the brain.</p>
<p>However, the action potential activity caused by LSD and ketamine differed significantly. As such, they could not be directly linked to the general psychedelic state. For LSD, neurons were inhibited – meaning they fired fewer action potentials – in all parts of the brain. For ketamine, the effect depended on cell type – certain large neurons were inhibited, while a type of smaller, locally connecting neurons, fired more. </p>
<p>Therefore, it is probably the synchronised wave phenomenon – how the neurons behave collectively – that is most strongly linked to the psychedelic state. Mechanistically, this makes some sense. It is likely that this type of increased synchrony has large effects on the integration of information across neural systems that normal perception and cognition rely on.</p>
<p>I think that this possible link between neuron-level system dynamics and consciousness is fascinating. It suggests that consciousness relies on a coupled collective state rather than the activity of individual neurons – it is greater than the sum of its parts.</p>
<p>That said, this link is still highly speculative at this point. That’s because the phenomenon has not yet been observed in human brains. Also, one should be cautious when extrapolating human experiences to other animals – it is of course impossible to know exactly what aspects of a trip we share with our rodent relatives. </p>
<p>But when it comes to cracking the deep mystery of consciousness, every bit of information is valuable.</p><img src="https://counter.theconversation.com/content/211685/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Pär Halje receives funding from The Crafoord Foundation, Royal Physiographic Society of Lund, Magnus Bergvall Foundation, Olle Engkvist Foundation, The Swedish Parkinson Foundation, Petrus and Augusta Hedlund Foundation, Thorsten and Elsa Segerfalk Foundation, The Swedish Society for Medical Research (SSMF), Fredrik and Ingrid Thuring Foundation and Åhlén Foundation.</span></em></p>We still don’t know a lot about how the networks of cells in the brain enable conscious experience.Pär Halje, Associate Research Fellow of Neurophysiology, Lund UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2095912023-07-14T02:06:30Z2023-07-14T02:06:30ZKetamine injections for depression? A new study shows promise, but it’s one of many options<figure><img src="https://images.theconversation.com/files/537183/original/file-20230712-29-dtpug1.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1000%2C666&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Psychedelics like ketamine affect chemical messengers in the brain.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/abstract-brain-fractal-background-digital-illustration-2212346843">Shutterstock</a></span></figcaption></figure><p>Ketamine might be better known as a recreational drug or anaesthetic. But there’s growing evidence for its use for people with hard-to-treat depression.</p>
<p>An Australasian study <a href="https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/efficacy-and-safety-of-a-4week-course-of-repeated-subcutaneous-ketamine-injections-for-treatmentresistant-depression-kads-study-randomised-doubleblind-activecontrolled-trial/FDBAEC51F0891B57F5B04C572D13DA17">out today</a> showed some positive results for people with treatment-resistant depression when they had ketamine injections.</p>
<p>But we don’t know if these effects are sustained in the long term, and there are other ways of delivering ketamine. There are also other treatment options for this type of depression.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-anaesthetic-and-recreational-drug-ketamine-could-be-used-to-treat-depression-81468">Weekly Dose: anaesthetic and recreational drug ketamine could be used to treat depression</a>
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<h2>What is ketamine?</h2>
<p>Ketamine has been used as a powerful <a href="https://www.nature.com/articles/s41593-022-01203-5">general anaesthetic</a> for more than 50 years.</p>
<p>It’s also an <a href="https://www.ncbi.nlm.nih.gov/books/NBK470357/">illicit drug</a> of abuse and is considered a psychedelic. Psychedelics dramatically alter some neurotransmitters (chemical messengers) in the brain <a href="https://pubmed.ncbi.nlm.nih.gov/36280799/">to create</a> a profound change in perception, mood and anxiety.</p>
<p>In early animal studies, ketamine led to increase in levels of certain brain chemicals, such as dopamine, by <a href="https://www.nature.com/articles/mp2017190">up to 400%</a>. This led researchers to trial ketamine in humans to see what would happen in our brains.</p>
<p>Now, doses of ketamine (at those lower than used as an anaesthetic) are being used to help treatment-resistant depression. That’s when someone has tried at least two antidepressants and shows no improvement.</p>
<p>It is usually prescribed under strict conditions and observation that mitigate some <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322816/">serious risks</a>, such as increased feelings about suicide in some people. So people need to be assessed and monitored not only during treatment, but afterwards.</p>
<p>But some clinicians have resisted using ketamine due to its potential to become a <a href="https://www.ranzcp.org/getmedia/75baa529-2b71-419f-993a-2ff64ede50fe/cm-use-of-ketamine-in-psychiatric-practice.pdf">drug of abuse</a>.</p>
<p>Ketamine is also used to treat other mental health disorders such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959757/">PTSD</a> (post-traumatic stress disorder).</p>
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Read more:
<a href="https://theconversation.com/hallucinations-in-the-movies-tend-to-be-about-chaos-violence-and-mental-distress-but-they-can-be-positive-too-204547">Hallucinations in the movies tend to be about chaos, violence and mental distress. But they can be positive too</a>
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<h2>How about this new study?</h2>
<p>The research involved <a href="https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12616001096448">multiple centres</a> across Australia and New Zealand and compared how well ketamine injected <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193034/">under the skin</a> compared with taking another drug in treating people with treatment-resistant depression.</p>
<p>The trial randomised the 184 study participants into different groups – some receiving ketamine, the rest the drug <a href="https://pubmed.ncbi.nlm.nih.gov/9258787/">midazolam</a>, twice a week over four weeks. Neither the study participants nor those assessing the results knew who had ketamine and who didn’t.</p>
<p>At the start of the study, all participants had a clinical depression score of at least 20 (moderate depression) using a particular scale known as the Montgomery-Asberg Depression Rating Scale.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Doctor in white coat putting hand on shoulder of patient" src="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.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">The study participants had moderate depression.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-psychiatrist-shakes-hands-encouragement-patient-2188082723">Shutterstock</a></span>
</figcaption>
</figure>
<p>The researchers then looked for a score of less than 11, indicating a shift from a depression to remission.</p>
<p>After four weeks, there was a big difference between people treated with ketamine (19.6% in remission) compared with midazolam (2%). Another, less-strict way of measuring outcomes is to look for a halving of the depression score. This had an even bigger difference (29% compared with 4%). </p>
<p>However, four weeks after the treatment had ended, there was only limited sustained improvement in symptoms in the ketamine group. This suggests treatment may be needed over a longer period.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/do-psychedelics-really-work-to-treat-depression-and-ptsd-heres-what-the-evidence-says-208857">Do psychedelics really work to treat depression and PTSD? Here's what the evidence says</a>
</strong>
</em>
</p>
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<h2>There are other options</h2>
<p>In the trial, ketamine was given via an injection under the skin, which is a low-cost and efficient option. But ketamine can also be delivered directly into the bloodstream via an intravenous drip. Neither of these two options are routinely available in Australia and New Zealand outside clinical trials.</p>
<p>A third option uses a <a href="https://www.nps.org.au/australian-prescriber/articles/esketamine-hydrochloride-for-treatment-resistant-depression">different form</a> of ketamine and comes in a <a href="https://www.spravato.com/">nasal spray</a> (approved for use in <a href="https://www.tga.gov.au/resources/auspmd/spravato">Australia</a> and New Zealand). </p>
<p>Each option delivers ketamine in different amounts, and research into how these work in practice, and how they compare, is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193034/">ongoing</a>.</p>
<p>There are also other drug and non-drug options for treatment-resistant depression. These include:</p>
<ul>
<li><p><a href="https://pubmed.ncbi.nlm.nih.gov/33834408/">transcranial magnetic stimulation</a>, which stimulates parts of the brain to improve mood</p></li>
<li><p><a href="https://www.ranzcp.org/events-learning/psychedelic-assisted-therapy">psilocybin</a>, another psychedelic drug that has just been given the go-ahead for use in Australia under strict conditions as part of <a href="https://theconversation.com/psychedelic-medicine-is-on-its-way-but-its-not-doing-shrooms-with-your-shrink-heres-what-you-need-to-know-208568">psychedelic-assisted therapy</a></p></li>
<li><p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429332/">psychotherapy</a> (talking therapy) such as cognitive behavioural therapy, <a href="https://www.psychologytoday.com/au/therapy-types/acceptance-and-commitment-therapy">acceptance and commitment therapy</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/29761488/">dialectical behaviour therapy</a></p></li>
<li><p>changing some lifestyle factors, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164235/">such as diet</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/28110494/">exercise</a>, or <a href="https://pubmed.ncbi.nlm.nih.gov/32985916/">practising mindfulness</a> meditation.</p></li>
</ul>
<h2>In a nutshell</h2>
<p>Serious consequences of depression include <a href="https://theconversation.com/suicide-rates-are-rising-with-or-without-13-reasons-why-lets-use-it-as-a-chance-to-talk-116434">suicide</a> or a lifetime of anguish. This latest research shows promising outcomes for people whose symptoms are harder to treat. But this option is not yet widely available outside a clinical trial. Only the ketamine nasal spray has been approved for use in Australia and New Zealand.</p>
<p>There are also other treatments. So if your existing treatment is not working for you, discuss this with your doctor who will explain what else is available.</p>
<hr>
<p><em>If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14. Beyond Blue provides the free resource <a href="https://www.beyondblue.org.au/docs/default-source/resources/bl0556-what-works-for-depression-booklet_acc.pdf?sfvrsn=fe1646eb_2">A guide to what works for depression</a>.</em></p><img src="https://counter.theconversation.com/content/209591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Musker 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>This latest research provides hope for people whose symptoms are harder to treat.Michael Musker, Enterprise Fellow (Senior Research Fellow/Senior Lecturer), University of South AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1931352022-10-26T14:08:29Z2022-10-26T14:08:29ZHow does ketamine help fight depressive beliefs?<figure><img src="https://images.theconversation.com/files/491306/original/file-20221024-5750-jrh41.jpg?ixlib=rb-1.1.0&rect=0%2C35%2C4728%2C3085&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A depressive episode traps the patient in a negative view of the world around them.</span> <span class="attribution"><span class="source">KieferPix/Shutterstock</span></span></figcaption></figure><p>Which factors determine what we believe about our world, ourselves, our past, and our future? Cognitive neuroscience suggests that our beliefs are dependent on brain activity, specifically on the way our brains process <a href="https://theconversation.com/lesprit-est-il-une-machine-predictive-introduction-a-la-theorie-du-cerveau-bayesien-173707">sensory information in order to make sense of our environment</a>.</p>
<p>These beliefs (defined as <em>probability estimates</em>) are central to our brain’s <a href="https://pubmed.ncbi.nlm.nih.gov/30483088/">predictive processing</a> function, which enables it to predict the probabilistic structure of the world around us. These predictions could even be the fundamental building blocks of <a href="https://pubmed.ncbi.nlm.nih.gov/36056173/">mental states</a>, such as perceptions and emotions.</p>
<p>Many psychiatric disorders, such as depression and schizophrenia, are characterised by irregular beliefs <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969668/">whose origins we still don’t fully understand</a>. But if we can identify the cerebral systems governing them, we could target those very areas in a bid to alleviate the pain associated to these illnesses.</p>
<h2>Decoding belief mechanisms in psychiatry</h2>
<p>This is one of the findings of our study recently published in the journal <a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2796906"><em>JAMA Psychiatry</em></a>. For this study, I explored with my team how the dissociative psychotropic, ketamine, affects mechanisms of <a href="https://plato.stanford.edu/entries/logic-belief-revision/">belief updating</a> (i.e., how we change our beliefs upon receiving information) in patients with treatment-resistant depression.</p>
<p>While traditional antidepressants take weeks to show any results, ketamine – an antagonist molecule that acts on the NMDA (N-methyl-D-aspartate) receptors – produces <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416968/">antidepressant effects</a> within hours. When administered, it also causes a <a href="https://pubmed.ncbi.nlm.nih.gov/24679390/">dissociative experience of depersonalisation</a> typically associated with a sensation of leaving the body (known as “autoscopy”).</p>
<p>Given that ketamine’s rapid action and unexpected dissociative effects make it a potentially worthwhile option for treating mental health problems, we are on a mission to unpack this mystery, at the crossroads between pharmacology and neuroscience.</p>
<h2>Cognitive-affective biases in depression</h2>
<p>According to the <a href="https://www.who.int/news-room/fact-sheets/detail/depression">World Health Organization</a>, depression affects approximately 280 million people in the world and 700 000 people die due to <a href="https://pubmed.ncbi.nlm.nih.gov/34753436/">suicide</a> every year. One of the most specific symptoms of depression is <a href="https://pubmed.ncbi.nlm.nih.gov/34916079/">depressive beliefs</a> (e.g., pessimism, self-deprecation, rejection, and feelings of failure), described as “mood-congruent” beliefs when their content matches the subject’s affective state.</p>
<p>By influencing the patient’s perception and action, these beliefs play a vital role in triggering the phenomenon of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241292/">negative auto-reinforcement</a>. For example, the belief that we have been rejected by our peers gradually makes us more withdrawn, which in turn reinforces feelings of worthlessness. Once this feedback loop has been closed, it can be difficult not to spiral downward.</p>
<p>Ever since the pioneering research of psychiatrist <a href="https://www.nytimes.com/2021/11/01/health/dr-aaron-t-beck-dead.html">Aaron Beck</a>, many studies have suggested that the ways in which information is encoded in belief networks according to their valence (i.e., their positive or negative nature) could be linked to the <a href="https://www.sciencedirect.com/science/article/abs/pii/S0005796719301950">emergence of depressive beliefs</a>.</p>
<p>This innovative research has shown that our brains are <a href="https://www.sciencedirect.com/science/article/pii/S0960982211011912">likelier to encode positive information</a>. Known as “affective bias”, this phenomenon is responsible for generating beliefs that are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467896/">slightly more positive than reality</a>. For instance, we tend to think we are more intelligent, more attractive, better drivers or better lovers than what is shown in statistical reality.</p>
<p>However, with depression, this <a href="https://pubmed.ncbi.nlm.nih.gov/23672737/">bias disappears or flips</a>, with patients taking in more negative-valence information that gradually generates gloomier beliefs about the world, themselves, or the future. This phenomenon of an inverted affective bias could well be key to understanding the origins of depressive beliefs.</p>
<h2>How ketamine acts on belief systems</h2>
<p>We launched our study on the back of a surprising clinical observation made at our unit at Paris’s Hôpital de la Pitié-Salpêtrière. When given ketamine as an antidepressant, patients with treatment-resistant depression reported feeling a strange sensation whereby their perspectives on the world seemed to have shifted, almost <a href="https://www.sciencedirect.com/science/article/abs/pii/S0013700621002244">as though their very point of view had been altered</a>.</p>
<p>The negative beliefs that they had been carrying for several months appeared to have faded. Some patients even expressed a feeling of foreignness, as if their thoughts belonged to someone else. Even more intriguingly, these changes appeared to result from the drug’s antidepressant effect, although we still don’t understand the causality of this.</p>
<p>In light of our patients’ accounts, we suspected that ketamine had affected the brain’s belief-updating mechanisms. In an effort to understand this phenomenon, we conducted an experiment intended to assess <a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2796906">ketamine’s influence on the ways we generate beliefs</a>, using pre- and post-treatment experimental task and <a href="https://www.nature.com/articles/nn.4238">computational modelling</a>.</p>
<p>Prior to the <a href="https://institutducerveau-icm.org/en/actualite/ketamine-and-depression-a-mechanism-of-the-antidepressant-effect-revealed/">ketamine administrations</a>, we asked patients and healthy subjects to assess their likelihood of experiencing 40 different future negative events (e.g., being bitten by a dog or having a car accident). After being informed of the actual occurrence risks in the general population, the two groups were again asked to assess the probability of these events occurring in their lives. Results show healthy subjects took into account new positive facts to update their beliefs, whereas this was not the case for depressed persons.</p>
<p>However, this changed only four hours after receiving the first ketamine dose: patients were far <a href="https://institutducerveau-icm.org/en/actualite/ketamine-and-depression-a-mechanism-of-the-antidepressant-effect-revealed/">less sensitive to negative information and recovered their ability to update their beliefs</a>. This meant the positive affective bias had been restored among patients with treatment-resistant depression. All the more surprisingly, this effect was directly linked to a reduction in depressive symptoms after one week, which suggests that these cognitive changes may even occur prior to clinical improvement.</p>
<h2>Avenues of future research</h2>
<figure class="align-right ">
<img alt="3D structure of a NMDA receptor" src="https://images.theconversation.com/files/490120/original/file-20221017-6684-ujmh1q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/490120/original/file-20221017-6684-ujmh1q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=747&fit=crop&dpr=1 600w, https://images.theconversation.com/files/490120/original/file-20221017-6684-ujmh1q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=747&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/490120/original/file-20221017-6684-ujmh1q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=747&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/490120/original/file-20221017-6684-ujmh1q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=939&fit=crop&dpr=1 754w, https://images.theconversation.com/files/490120/original/file-20221017-6684-ujmh1q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=939&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/490120/original/file-20221017-6684-ujmh1q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=939&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Ketamine molecules attach themselves to NMDA neuronal receptors, which play an important role in brain plasticity and predictive processing.</span>
<span class="attribution"><span class="source">C22H31NO2</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Further research is needed to understand the brain processes associated with these changes, but many clues point to the involvement of <a href="https://www.nature.com/articles/s41467-021-27876-3">NMDA receptor-mediated signalling</a>. These neuronal receptors contribute to the brain’s excitation-inhibition balance, and appear to be essential to <a href="https://pubmed.ncbi.nlm.nih.gov/23177956/">predictive processing</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/26726120/">brain plasticity</a>.</p>
<p>Ketamine’s direct action on the activity of these receptors may constitute a direct pharmacological pathway that regulates <a href="https://pubmed.ncbi.nlm.nih.gov/32818386/">predictive mechanisms</a>, which would explain the drug’s rapid-onset antidepressant effects and its dissociative properties. By controlling the way the brain uses its sensory building blocks to generate beliefs, ketamine could help change the mechanisms behind depressive symptoms.</p>
<p>These hypotheses open up numerous perspectives for developing treatments targeting brain processing, or for combining these molecules with <a href="https://pubmed.ncbi.nlm.nih.gov/34876279/">augmented psychotherapy</a>, protocols that focus specifically on belief systems. This goal is at the core of debates in so-called psychedelic medicine, particularly in treatment using <a href="https://pubmed.ncbi.nlm.nih.gov/35360137/">psilocybin</a>, a hallucinogenic molecule that also presents rapid antidepressant effects. Could theses researches help bring pharmacological and psychotherapeutic approaches together in psychiatry?</p>
<hr>
<p><em>This article is based on the results of <a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2796906">“Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression”</a>, a study that was recently published in the journal JAMA Psychiatry.</em></p>
<p><em>Translated from the French by Enda Boorman for <a href="http://www.fastforword.fr/en">Fast ForWord</a>.</em></p><img src="https://counter.theconversation.com/content/193135/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hugo Bottemanne ne travaille pas, ne conseille pas, ne possède pas de parts, ne reçoit pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'a déclaré aucune autre affiliation que son organisme de recherche.</span></em></p>Approximately 280 million people in the world suffer for depression. Despite this, the disorder remains poorly explained and is often difficult to treat. Ketamine could offer an innovative approach.Hugo Bottemanne, Psychiatre à la Pitié-Salpêtrière & chercheur à l'Institut du Cerveau - Sorbonne Université AP-HP, Sorbonne UniversitéLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1928552022-10-20T01:32:05Z2022-10-20T01:32:05ZAn entirely new illicit drug has been discovered by Australian chemists. Here’s how they did it<figure><img src="https://images.theconversation.com/files/490583/original/file-20221019-22-c1leoa.jpg?ixlib=rb-1.1.0&rect=42%2C5%2C3282%2C1989&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Malcolm McLeod/ANU</span>, <span class="license">Author provided</span></span></figcaption></figure><p>Imagine, if you will, a small plastic baggy containing a mixture of crystals and powder. </p>
<p>The person presenting it thinks “it might be ketamine?”, but admits the subjective effects are different to what they’re used to. How do we find out if it’s what they think it is? And what are the consequences if it isn’t?</p>
<p>This is a typical scenario for the people working at <a href="https://www.cahma.org.au/services/cantest/">CanTEST</a> – Australia’s first and only fixed-site, face-to-face drug checking service, located in Canberra.</p>
<p>And in this case, it led chemists to discover a drug never before seen in Australia, and with no associated clinical information from anywhere in the world.</p>
<h2>Identifying ‘chemical X’</h2>
<p>The identification of <a href="https://adf.org.au/drug-facts/new-psychoactive-substances/">new psychoactive substances</a> – drugs made to resemble established illicit drugs – presents a major challenge when pill-testing. Testing a chemical provides us with its “fingerprint” that will hopefully match one of the thousands stored in databases available to analysts.</p>
<p>But what happens when a fingerprint doesn’t provide a match and we have come across “chemical X”? </p>
<p>That brings us back to the original baggy of powder. </p>
<p>Patrick Yates, a PhD candidate from the Australian National University’s Research School of Chemistry, ran the sample through the first piece of equipment, the Fourier transform infrared (FTIR) spectrometer – a workhorse of many drug-checking programs around the world.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/pill-testing-really-does-reduce-the-risk-of-harm-for-drug-users-181778">Pill testing really does reduce the risk of harm for drug users</a>
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<p>FTIR works quickly and reliably – even at a <a href="https://en.wikipedia.org/wiki/Doof">bush doof</a> – as long as an electricity supply is available. It shines a laser on the sample, and the “reflection” (a measure of how the drug shakes and wiggles) is captured and compared to a database of more than 30,000 chemicals.</p>
<p>Patrick’s analysis didn’t confirm a ketamine match, but suggested it might be a relatively new ketamine analogue called <a href="https://www.sciencedirect.com/science/article/pii/S0379073820301894">2-fluorodeschloroketamine</a> (2-FDCK). However, Patrick’s trained intuition left him doubtful.</p>
<p>PhD student Cassidy Whitefield then turned to an instrument known as ultra-high performance liquid chromatography with photodiode array (UPLC-PDA), humming away in the corner at CanTEST. She ran lab-based standards through it, calibrating the machine to the ten most common drugs we see, including ketamine.</p>
<p>Chemical X had to “run a race” against a known sample, comparing it to already known compounds. The UPLC-PDA test takes about four minutes to run.</p>
<figure class="align-center ">
<img alt="A woman in a lab environment wearing blue gloves leans over a small grey machine" src="https://images.theconversation.com/files/490576/original/file-20221019-14-wsieks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/490576/original/file-20221019-14-wsieks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=411&fit=crop&dpr=1 600w, https://images.theconversation.com/files/490576/original/file-20221019-14-wsieks.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=411&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/490576/original/file-20221019-14-wsieks.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=411&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/490576/original/file-20221019-14-wsieks.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=516&fit=crop&dpr=1 754w, https://images.theconversation.com/files/490576/original/file-20221019-14-wsieks.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=516&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/490576/original/file-20221019-14-wsieks.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=516&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Cassidy Whitefield tests a sample by FTIR at CanTEST.</span>
<span class="attribution"><span class="source">Tracey Nearmy/ANU</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>While the sample appeared similar to the ketamine standard, Cassie’s trained eye saw something was off. The rate at which chemical X ran its race (known as the retention time) was similar, but its absorption of ultraviolet radiation was off.</p>
<p>Whatever was there was real, quite pure, and neither ketamine nor 2-FDCK.</p>
<h2>When in doubt, run more tests</h2>
<p>Ketamine is both an invaluable agent in the emergency and pre-hospital environment, and part of an emerging group of illicit drugs known as <a href="https://link.springer.com/referenceworkentry/10.1007/978-3-319-20790-2_124-2">arylcyclohexamines</a>. </p>
<p>In consultation with ANU chemistry professor Mal McLeod, the CanTEST team arrived at chemical X being “ketamine-like”.</p>
<p>The person who brought it in was advised the substance was <em>not</em> ketamine, and its identity could not be ascertained – our band of peer workers advised extreme caution in using it.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/forgotten-how-to-party-safety-tips-from-a-drug-and-alcohol-expert-170007">Forgotten how to party? Safety tips from a drug and alcohol expert</a>
</strong>
</em>
</p>
<hr>
<p>But that was not the end of the story for analytical chemists – the full inquisition was just beginning.</p>
<p>Next up, chemical X was subjected to a method called gas chromatography–mass spectrometry (GC-MS), meaning the sample was made to “run another race”, and was then smashed into pieces to further fingerprint it.</p>
<p>The GC-MS data correlated closely with a ketamine derivative known as <a href="https://www.naddi.org/glossary/fluorexetamine/">fluorexetamine</a>, but the presence of an isomer – two compounds with the same molecular formula but arranged differently – could not be ruled out.</p>
<figure class="align-center ">
<img alt="Blue-gloved hands shaving a small amount of white powder off a solid piece" src="https://images.theconversation.com/files/490584/original/file-20221019-15-3d9kv3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/490584/original/file-20221019-15-3d9kv3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=374&fit=crop&dpr=1 600w, https://images.theconversation.com/files/490584/original/file-20221019-15-3d9kv3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=374&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/490584/original/file-20221019-15-3d9kv3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=374&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/490584/original/file-20221019-15-3d9kv3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=469&fit=crop&dpr=1 754w, https://images.theconversation.com/files/490584/original/file-20221019-15-3d9kv3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=469&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/490584/original/file-20221019-15-3d9kv3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=469&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Identifying unknown drugs requires running small amounts of the substance through various testing instruments – from simple to incredibly advanced.</span>
<span class="attribution"><span class="source">ANU</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>It was time to bring out the big guns: a nuclear magnetic resonance spectrometer is a chemist’s Book of Runes. Answers can be found, but only by those few who can speak the language well.</p>
<p>Eventually, after a series of multi-dimensional tests, the team figured out there were four hydrogens next to each other around the aromatic ring, meaning it could <em>not</em> be fluorexetamine.</p>
<p>Chemical X could <em>only</em> be something called 2’-fluoro-2-oxo-phenylcyclohexylethylamine. And they had never seen this compound before.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/490782/original/file-20221020-21-3k6de3.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Four chemical structures arranged in a simple chart" src="https://images.theconversation.com/files/490782/original/file-20221020-21-3k6de3.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/490782/original/file-20221020-21-3k6de3.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=570&fit=crop&dpr=1 600w, https://images.theconversation.com/files/490782/original/file-20221020-21-3k6de3.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=570&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/490782/original/file-20221020-21-3k6de3.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=570&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/490782/original/file-20221020-21-3k6de3.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=717&fit=crop&dpr=1 754w, https://images.theconversation.com/files/490782/original/file-20221020-21-3k6de3.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=717&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/490782/original/file-20221020-21-3k6de3.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=717&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 chemical structures of ketamine, 2-fluorodeschloroketamine, fluorexetamine and ‘CanKet’ – 2’fluoro-2-oxo-PCE.</span>
<span class="attribution"><span class="source">Malcolm McLeod</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>From chemical X to ‘CanKet’</h2>
<p>It’s hard to emphasise what a phenomenal piece of work this was. We contacted our offsiders at the UN Office of Drug Control, the European Monitoring Centre for Drugs and Drug Addiction, as well as several well-positioned researchers in this space from around the world. None had seen the compound before.</p>
<p>Our colleagues at the ACT Government Analytical Laboratory wrote to their international peers; a global forum of forensic and analytical chemists reviewed their locally acquired data and provided information that supported our findings. </p>
<p>We have since found a single further report out of China from a forensically obtained analytical sample, where it was described by another name (2F-NENDCK). As 2’-fluoro-2-oxo-phenylcyclohexylethylamine is a bit of a mouthful, our team has taken to calling it CanKet, as in “Canberra ketamine”.</p>
<p>After this feat of chemical analysis, we are now able to identify CanKet with impunity. We still don’t know its full effects, but thanks to understanding its chemical composition, we have a better idea of what we’re dealing with.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/yes-we-can-do-on-the-spot-drug-testing-quickly-and-safely-73343">Yes, we can do on-the-spot drug testing quickly and safely</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/192855/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Caldicott has previously been a recipient of an NH&MRC Partnership Grant.
He is the Clinical Lead for Pill Testing Australia, and CanTEST.</span></em></p><p class="fine-print"><em><span>Malcolm McLeod is chemistry lead for Pill Testing Australia and the CanTEST Health and Drug Checking Service operated by Directions Health Services and supported the ACT Government. He was awarded a 2020 Churchill Fellowship to visit leading international drug checking services to rapidly improve the analytical chemistry capabilities in Australia.</span></em></p>What happens when drug testing experts come across a substance they have never seen before?David Caldicott, Senior lecturer, Australian National UniversityMalcolm McLeod, Associate Professor, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1909502022-09-22T18:08:48Z2022-09-22T18:08:48ZKetamine paired with looking at smiling faces to build positive associations holds promise for helping people with treatment-resistant depression<figure><img src="https://images.theconversation.com/files/485716/original/file-20220920-14233-xe0rz7.jpg?ixlib=rb-1.1.0&rect=10%2C0%2C6699%2C4476&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Some of the positive photos used in the study were similar to this one -- a group of smiling strangers.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/successful-business-team-taking-selfie-royalty-free-image/1132119295?adppopup=true">Luis Alvarez/DigitalVision via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>Simple computer exercises using positive words and images designed to boost self-worth can prolong the antidepressant effects of ketamine in people with depression. That’s what my research team and I found <a href="https://www.doi.org/10.1176/appi.ajp.20220216">in our new study</a>.</p>
<p>Over two decades ago, researchers serendipitously discovered that intravenous ketamine, a widely used anesthetic medication that has been <a href="https://doi.org/10.1111/j.1365-2044.2007.05298.x">shown to be safe</a> when administered under medical supervision, had <a href="https://doi.org/10.1016/s0006-3223(99)00230-9">rapid-acting antidepressant effects</a> when given at lower doses than is used for anesthesia. </p>
<p>Our study included 154 adult patients with depression. One-third received a single infusion of ketamine and returned a day later to begin four consecutive days – about 30 to 40 minutes total each day – of our novel digital exercises. That is, we showed them repeated pairings of self-related words and images – such as the letter “I” and photos of the patient – paired up repeatedly with positive cues. These include positive words like “good,” “sweet” and “lovable” as well as photos of strangers smiling.</p>
<p>We targeted this period of time within five days of ketamine because we expected ketamine would quickly help restore the brain’s healthy capacity to adjust and learn in response to the environment. The specific exercises we used were designed based on our prior work showing that, shortly after a ketamine infusion, thought patterns related to oneself <a href="https://doi.org/10.1002/da.22253">may become less “stuck”</a> and be more malleable, creating a window of opportunity to improve a person’s sense of self-worth.</p>
<p>The other two-thirds of patients went into one of our two control groups: those who received ketamine followed by a neutral, or placebo, version of computer training, and those who received a saline infusion followed by the real training exercises. </p>
<p>We found that after just a single intravenous infusion of ketamine, patients experienced relief from depression symptoms for at least one month as long as they were assigned to the group that completed the digital exercises within the first five days. Compared with those in the control saline group, both of the groups that received a ketamine infusion experienced substantial relief from depression on the first day, prior to any computer training. </p>
<p>However, whereas the control group who went on to receive the “sham” computer training began to experience the return of depression symptoms in the subsequent 1.5 weeks or so, the group that received ketamine followed by exposure to positive conditioning continued to report decreased depression severity all the way out to the last follow-up interview, one month after ketamine. </p>
<p>The people who got digital training in the absence of ketamine had very little relief from their depression.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/a1Y1ocyudjs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">More than 20 million U.S. adults and 4 million adolescents have had at least one major depressive episode, according to the National Institute of Mental Health.</span></figcaption>
</figure>
<h2>Why it matters</h2>
<p>Depression is a highly prevalent and disabling condition that exacts a staggering burden on patients, families and communities. </p>
<p>Globally, <a href="https://www.who.int/news-room/fact-sheets/detail/depression">an estimated 280 million people</a> experience depression. There are <a href="https://doi.org/10.7326/AITC202105180">numerous effective treatments</a> for depression, including <a href="https://www.nice.org.uk/guidance/ng222">antidepressant medications and psychotherapy</a>. </p>
<p>However, unfortunately, not all patients <a href="https://doi.org/10.1176/ajp.2006.163.11.1905">are helped by such treatments</a>. And accessing them initially, as well as maintaining them over the long haul can be challenging for many patients.</p>
<p>The discovery of ketamine’s rapid-acting antidepressant effects opened up a brand new possibility within psychiatry to begin relieving symptoms within a day. Conventional treatments typically take six to eight weeks to reach a therapeutic effect.</p>
<p>However, a key question is how to keep that relief going without relying solely on repeated ketamine infusions. These can be burdensome and costly for patients and health care systems, and it is important to consider <a href="https://doi.org/10.1176/appi.ajp.2014.13101434">possible risks</a>, such as the potential for drug misuse. </p>
<p>Our study is the first to demonstrate that the rapid effects of ketamine can be made more enduring with simple, portable and automated techniques that would be relatively easy to provide to patients in a wide range of settings. </p>
<h2>What’s next</h2>
<p>Our initial findings suggest the positive conditioning exercises tripled – at a minimum – the duration of ketamine’s effects. But we don’t yet know how much longer the relief from depressive symptoms may have continued. </p>
<p>Patients in our trial will continue to complete questionnaires about their depression symptoms for an entire year following the infusion, enabling us to gain an initial understanding of just how long this benefit may endure.</p>
<p>Ongoing research is exploring whether <a href="https://clinicaltrials.gov/ct2/show/NCT04578938">similar techniques might help ease suicidality</a>, in the hopes of providing relief in the midst of a suicidal crisis that is both immediate and enduring. Other future research may expand these techniques to additional common forms of psychological suffering, such as anxiety, disordered eating and more.</p><img src="https://counter.theconversation.com/content/190950/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rebecca Price receives funding from the National Institute of Mental Health.
Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report.</span></em></p>In a new study, a single infusion of the antidepressant – along with repeated exposure to positive imagery – significantly reduced symptoms in depressed patients in a clinical trial.Rebecca Price, Associate Professor of Psychiatry and Psychology, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1700072021-10-21T19:16:44Z2021-10-21T19:16:44ZForgotten how to party? Safety tips from a drug and alcohol expert<figure><img src="https://images.theconversation.com/files/427412/original/file-20211020-20-smslqk.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1000%2C666&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/fun-disco-559484653">Shutterstock</a></span></figcaption></figure><p>Cancelled dance parties, festivals and other events have shaped how Australians use alcohol and other drugs during the pandemic.</p>
<p>Now restrictions are easing, some people who have not used alcohol or other drugs recently may start to use them again, and need to be aware of their reduced tolerance.</p>
<p>Here’s what <a href="https://ndarc.med.unsw.edu.au/program/drug-trends">survey data</a> released today by the National Drug and Alcohol Research Centre, tell us about drug use and drug markets during the pandemic.</p>
<p>And here’s what to think about if your drug use during the pandemic has changed, and you’re about to head off to a party.</p>
<h2>Cocaine up, ecstasy down, alcohol stable</h2>
<p>Of the two yearly surveys released today, one relates to people who inject drugs such as heroin. The other relates to people who use ecstasy and other party drugs, who typically use drugs occasionally.</p>
<p>The group using ecstasy and other party drugs showed significant changes in drug use between 2020 and 2021. This variability is probably because this group tends to use in specific contexts and is more strongly influenced by access and opportunity.</p>
<p>More people used cocaine in 2021 than in 2020, continuing the upward trend in recent years. We don’t know why cocaine use has been increasing. But the frequency of cocaine use was very low at just a few days in the past six months. </p>
<p>Cocaine purity in Australia tends to be fairly low and has been <a href="https://www.acic.gov.au/sites/default/files/2020-09/Illicit%20Drug%20Data%20Report%202018-19_Internals_V10_Cocaine%20CH.pdf">decreasing</a>. So, although other data also show that cocaine has increased in popularity in the past few years, we haven’t seen a big increase in harms. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-cocaine-the-glamour-drug-of-the-70s-is-making-a-comeback-88639">Weekly Dose: cocaine, the glamour drug of the ’70s, is making a comeback</a>
</strong>
</em>
</p>
<hr>
<p>Fewer people used ecstasy in 2021; the frequency of use also decreased (from 12 days in the past six months in 2020 to seven days in 2021).</p>
<p>But this was not just because of closed venues or cancelled events. People surveyed said it was also harder to get. The closed international border has restricted importation of ecstasy and the chemicals used to make it. In the past year, ecstasy purity has reportedly decreased and the price increased.</p>
<p>More people said they used “magic mushrooms”, <a href="https://theconversation.com/weekly-dose-anaesthetic-and-recreational-drug-ketamine-could-be-used-to-treat-depression-81468">ketamine</a>, and non-prescribed pharmaceutical stimulants such as <a href="https://www.healthdirect.gov.au/medicines/brand/amt,30571011000036106/dexamphetamine-sulfate-sigma">dexamphetamine</a> and <a href="https://www.healthdirect.gov.au/medicines/brand/amt,17251000168101/ritalin">methylphenidate</a>. The frequency of use of these drugs was very low at just a few days in the past six months.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-anaesthetic-and-recreational-drug-ketamine-could-be-used-to-treat-depression-81468">Weekly Dose: anaesthetic and recreational drug ketamine could be used to treat depression</a>
</strong>
</em>
</p>
<hr>
<p>The rate of alcohol use was stable. This is in line with <a href="https://www.aihw.gov.au/reports/alcohol/alcohol-tobacco-other-drugs-australia/contents/impact-of-covid-19-on-alcohol-and-other-drug-use">other data</a> showing that, although alcohol use may have increased slightly in the early months of the pandemic, it stabilised after that. Spending on takeaway alcohol at bottle shops increased, but the opportunities to drink at pubs, bars and restaurants decreased.</p>
<p>The surveys are not intended to represent all people who use drugs, so should be interpreted alongside other sources.</p>
<h2>What might happen as restrictions ease?</h2>
<p>As festivals and dance parties start up again, some people may start to use these drugs again.</p>
<p>When you use a drug, including alcohol, regularly, your body gets used to having it in your system and you need to use more to get the same effect. This is known as “<a href="https://www1.health.gov.au/internet/publications/publishing.nsf/Content/drugtreat-pubs-front6-fa-toc%7Edrugtreat-pubs-front6-fa-secb%7Edrugtreat-pubs-front6-fa-secb-8%7Edrugtreat-pubs-front6-fa-secb-8-2">tolerance</a>”.</p>
<p>If you haven’t used a drug for a while, your tolerance may have decreased. You’ll need less to get the same effect. So if you start using the same amount as before you might unintentionally use too much and experience unwanted side effects, including overdose.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/427416/original/file-20211020-23-yoiztt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person at home holding small bag containing white powder" src="https://images.theconversation.com/files/427416/original/file-20211020-23-yoiztt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/427416/original/file-20211020-23-yoiztt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/427416/original/file-20211020-23-yoiztt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/427416/original/file-20211020-23-yoiztt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/427416/original/file-20211020-23-yoiztt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/427416/original/file-20211020-23-yoiztt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/427416/original/file-20211020-23-yoiztt.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"></a>
<figcaption>
<span class="caption">Taking a drug at home can be very different to taking it while dancing all night at a club.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/drug-addict-dealer-closing-bag-cocaine-1019419879">Shutterstock</a></span>
</figcaption>
</figure>
<p>If you have increased use during the pandemic, your tolerance may have increased, so the effects at your usual dose may be reduced. This can also lead to unintentional overdose because, although you don’t feel the effects, the drug may still be toxic at high enough doses.</p>
<p>The setting you use a drug in also changes the effects you might feel. So if you have been using ecstasy quietly at home during the pandemic you’ll have different effects to using it while dancing all night.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-does-mdma-kill-109506">How does MDMA kill?</a>
</strong>
</em>
</p>
<hr>
<h2>What can you do to use more safely?</h2>
<p>With changes in the market, the strength and purity of illicit drugs you used before the pandemic might also be different to those you have access to now.</p>
<p>If you can have your drugs checked to see what’s in them you can decide whether to still take them or not. The ACT government has announced funding for a <a href="https://www.canberratimes.com.au/story/6888821/pill-testing-site-could-be-coming-to-the-city-this-summer/">trial of a drug checking service</a>. New Zealand passed interim legislation to <a href="https://theconversation.com/after-the-last-summer-of-terrible-drugs-its-time-to-make-nzs-temporary-drug-checking-law-permanent-165612">make drug checking legal</a> last year. It’s due to finalise the full legislation at the end of this year to <a href="https://www.loc.gov/item/global-legal-monitor/2021-04-14/new-zealand-government-indicates-that-drug-checking-law-will-be-made-permanent/">make it permanent</a>.</p>
<p>If you don’t have access to a drug checking service, you should be extra cautious the first few times you use a drug again after a break:</p>
<ul>
<li><p><strong>“<a href="https://wearetheloop.org/crush-dab-wait">crush/dab/wait</a>”</strong>: take a quarter of a pill or a dab of powder at first then wait an hour or two to see the effects. You can always take more if wanted, but you can’t get it out of your system if you take too much</p></li>
<li><p><strong>avoid mixing drugs</strong>: the more drugs you take at the same time the more likely you are to have problems, like overdose. Some drugs reduce your ability to feel the effects of other drugs. For example stimulants can mask the effects of alcohol, then you can drink too much</p></li>
<li><p><strong>check what’s circulating</strong>: the <a href="https://www.health.nsw.gov.au/aod/public-drug-alerts/Pages/default.aspx">New South Wales</a> and <a href="https://www2.health.vic.gov.au/alcohol-and-drugs/drug-alerts">Victorian</a> governments regularly release alerts to the public about contaminants found in seized drugs or from hospital data. Other states also sometimes release alerts.</p></li>
</ul>
<p>Tolerance also applies to legal drugs like alcohol. If you’ve been drinking more during lockdown, your tolerance might have increased and you might drink more than you intended. You might not feel drunk, but your brain function may still be affected and you can still be over the legal limit for driving.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/427418/original/file-20211020-21-1rg745s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Man drinking beer about to grab car keys, friend holding back arm" src="https://images.theconversation.com/files/427418/original/file-20211020-21-1rg745s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/427418/original/file-20211020-21-1rg745s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/427418/original/file-20211020-21-1rg745s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/427418/original/file-20211020-21-1rg745s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/427418/original/file-20211020-21-1rg745s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/427418/original/file-20211020-21-1rg745s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/427418/original/file-20211020-21-1rg745s.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">If you’ve been drinking more in lockdown, you might feel OK but be impaired and still be over the limit.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/do-not-drink-drive-cropped-image-572252890">Shutterstock</a></span>
</figcaption>
</figure>
<p>If you have been drinking less, your tolerance may have decreased so a smaller amount of alcohol will affect you more than normal. So, if you drink the same amount as you did before the pandemic you might get drunk more quickly.</p>
<p>Start slowly, monitor the number of drinks you have and pay attention to how drunk you are feeling.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/getting-back-on-the-beers-after-lockdown-heres-what-you-should-know-140454">Getting back on the beers after lockdown? Here's what you should know</a>
</strong>
</em>
</p>
<hr>
<h2>How to get help</h2>
<p>If you’re worried about your own or someone else’s use of alcohol or other drugs call the National Alcohol and other Drug Hotline on 1800 250 015, free from anywhere in Australia.</p>
<p>If you want support to manage your drinking, <a href="https://hellosundaymorning.org/">Hello Sunday Morning</a> offers a free online support community where you can connect and chat with others who are actively changing their alcohol use.</p>
<p>You can also chat online with a counsellor at <a href="https://www.counsellingonline.org.au/">Alcohol & Drug Counselling Online</a>, join an online support group at <a href="https://smartrecoveryaustralia.com.au/">SMART Recovery</a> or talk to your GP about seeing a psychologist. You may be able to access support via <a href="https://www.digitalhealth.gov.au/initiatives-and-programs/telehealth">telehealth</a>.</p><img src="https://counter.theconversation.com/content/170007/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicole Lee works as a consultant in the alcohol and other drug sector and a psychologist in private practice. She has previously been awarded funding by Australian and state governments, NHMRC and other bodies for evaluation and research into drug prevention and treatment. She is a member of the Australian National Advisory Council on Alcohol and other Drugs and the board of directors of Hello Sunday Morning and The Loop Australia.</span></em></p>Now restrictions are easing, some people who have not used alcohol or other drugs recently may start to use them again, and need to be aware of their reduced tolerance.Nicole Lee, Professor at the National Drug Research Institute (Melbourne), Curtin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1605382021-05-17T06:00:36Z2021-05-17T06:00:36ZWhat is drink spiking? How can you know if it’s happened to you, and how can it be prevented?<figure><img src="https://images.theconversation.com/files/399935/original/file-20210511-21-wi5zfe.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5689%2C3789&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/colorful-cocktail-on-top-bar-italian-276150941">Shutterstock</a></span></figcaption></figure><p><a href="https://www.theage.com.au/national/victoria/it-was-terrifying-police-on-alert-amid-rise-in-reports-of-drink-spiking-20210331-p57fil.html">Recent media reports</a> suggest drink spiking at pubs and clubs may be on the rise.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1378112697171120128"}"></div></p>
<p>“Drink spiking” is when someone puts alcohol or other drugs into another person’s drink without their knowledge.</p>
<p>It can include:</p>
<ul>
<li><p>putting alcohol into a non-alcoholic drink</p></li>
<li><p>adding extra alcohol to an alcoholic drink</p></li>
<li><p>slipping prescription or illegal drugs into an alcoholic or non-alcholic drink.</p></li>
</ul>
<p><a href="https://www.police.nsw.gov.au/__data/assets/pdf_file/0005/81374/fact_sheet_drink_spiking_myths.pdf">Alcohol</a> is actually the drug most commonly used in drink spiking. </p>
<p>The use of other drugs, such as benzodiazepines (like Rohypnol), GHB or ketamine is relatively rare.</p>
<p>These drugs are colourless and odourless so they are less easily detected. They cause drowsiness, and can cause “blackouts” and <a href="https://pubmed.ncbi.nlm.nih.gov/27198055/">memory loss</a> at high doses.</p>
<p>Perpetrators may spike victims’ drinks to commit sexual assault. But <a href="https://www.aic.gov.au/sites/default/files/2020-05/national-project-on-drink-spiking-investigating-the-nature-and-extent-of-drink-spiking-in-australia.pdf">according to the data</a>, the most common type of drink spiking is to “prank” someone or some other non-criminal motive.</p>
<p>So how can you know if your drink has been spiked, and as a society, how can we prevent it?</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-ghb-a-party-drug-thats-easy-to-overdose-on-but-was-once-used-in-childbirth-73266">Weekly Dose: GHB, a party drug that's easy to overdose on but was once used in childbirth</a>
</strong>
</em>
</p>
<hr>
<h2>How often does it happen?</h2>
<p>We don’t have very good data on how often drink spiking occurs. It’s often not reported to police because victims can’t remember what has happened.</p>
<p>If a perpetrator sexually assaults someone after spiking their drink, there are <a href="https://theconversation.com/almost-90-of-sexual-assault-victims-do-not-go-to-police-this-is-how-we-can-achieve-justice-for-survivors-157601">many complex reasons</a> why victims may not want to report to police.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/almost-90-of-sexual-assault-victims-do-not-go-to-police-this-is-how-we-can-achieve-justice-for-survivors-157601">Almost 90% of sexual assault victims do not go to police — this is how we can achieve justice for survivors</a>
</strong>
</em>
</p>
<hr>
<p><a href="https://www.aic.gov.au/sites/default/files/2020-05/national-project-on-drink-spiking-investigating-the-nature-and-extent-of-drink-spiking-in-australia.pdf">One study</a>, published in 2004, estimated there were about 3,000 to 4,000 suspected drink spiking incidents a year in Australia. It estimated less than 15% of incidents were reported to police.</p>
<p>It found four out of five victims were women. About half were under 24 years old and around one-third aged 25-34. Two-thirds of the suspected incidents occurred in licensed venues like pubs and clubs.</p>
<p>According to an Australian study from 2006, <a href="https://pubmed.ncbi.nlm.nih.gov/16580243/">around 3%</a> of adult sexual assault cases occurred after perpetrators intentionally drugged victims outside of their knowledge.</p>
<p>It’s crucial to note that sexual assault is a moral and legal violation, whether or not the victim was intoxicated and whether or not the victim became intoxicated voluntarily.</p>
<h2>How can you know if it’s happened to you?</h2>
<p>Some of the <a href="https://adf.org.au/insights/drink-spiking/">warning signs</a> your drink might have been spiked include:</p>
<ul>
<li><p>feeling lightheaded, or like you might faint</p></li>
<li><p>feeling quite sick or very tired</p></li>
<li><p>feeling drunk despite only having a very small amount of alcohol</p></li>
<li><p>passing out</p></li>
<li><p>feeling uncomfortable and confused when you wake up, with blanks in your memory about what happened the previous night.</p></li>
</ul>
<p>If you think your drink has been spiked, you should ask someone you trust to get you to a safe place, or talk to venue staff or security if you’re at a licensed venue. If you feel very unwell you should seek medical attention.</p>
<p>If you believe your drink has been spiked or you have been sexually assaulted, contact the police to report the incident.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1369483648781672448"}"></div></p>
<h2>How can drink spiking be prevented?</h2>
<p>Most drink spiking occurs at licensed venues like pubs and clubs. Licensees and people who serve alcohol have a responsibility to provide a safe environment for patrons, and have an important role to play in preventing drink spiking.</p>
<p>This includes having clear procedures in place to ensure staff understand the signs of drink spiking, including with alcohol.</p>
<p>Preventing drink spiking is a collective responsibility, not something to be shouldered by potential victims.</p>
<p>Licensees can take responsible steps including:</p>
<ul>
<li><p>removing unattended glasses</p></li>
<li><p>reporting suspicious behaviour</p></li>
<li><p>declining customer requests to add extra alcohol to a person’s drink</p></li>
<li><p>supplying water taps instead of large water jugs</p></li>
<li><p>promoting responsible consumption of alcohol, including discouraging rapid drinking</p></li>
<li><p>being aware of “red flag” drink requests, such as repeated shots, or double or triple shots, or adding vodka to beer or wine.</p></li>
</ul>
<figure class="align-center ">
<img alt="Bartender pouring drinks" src="https://images.theconversation.com/files/400926/original/file-20210517-17-rfcblw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/400926/original/file-20210517-17-rfcblw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/400926/original/file-20210517-17-rfcblw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/400926/original/file-20210517-17-rfcblw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/400926/original/file-20210517-17-rfcblw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/400926/original/file-20210517-17-rfcblw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/400926/original/file-20210517-17-rfcblw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Bartenders should be wary of ‘red flag’ drinks requests like people asking for double or triple shots.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>A few <a href="https://adf.org.au/insights/drink-spiking/">simple precautions</a> everyone can take to reduce the risk of drink spiking include:</p>
<ul>
<li><p>have your drink close to you, keep an eye on it and don’t leave it unattended</p></li>
<li><p>avoid sharing beverages with other people</p></li>
<li><p>purchase or pour your drinks yourself</p></li>
<li><p>if you’re offered a drink by someone you don’t know well, go to the bar with them and watch the bartender pour your drink</p></li>
<li><p>if you think your drink tastes weird, pour it out</p></li>
<li><p>keep an eye on your friends and their beverages too.</p></li>
</ul>
<h2>What are the consequences for drink spiking in Australia?</h2>
<p>It’s a criminal offence to spike someone’s drink with alcohol or other drugs without their consent in all states and territories.</p>
<p>In some jurisdictions, there are specific drink and food spiking laws. For example, in <a href="http://classic.austlii.edu.au/au/legis/vic/consol_act/soa1966189/s41h.html">Victoria</a>, the punishment is up to two years imprisonment.</p>
<p>In other jurisdictions, such as Tasmania, drink spiking <a href="https://www.legislation.tas.gov.au/view/html/inforce/current/act-1924-069#JS1@GS176@EN">comes under broader offences</a> such as “administering any poison or other noxious thing with intent to injure or annoy”.</p>
<p>Spiking someone’s drink with an intent to commit a serious criminal offence, such as sexual assault, usually comes with very severe penalties. For example, this carries a penalty of up to 14 years imprisonment in <a href="http://www6.austlii.edu.au/cgi-bin/viewdoc/au/legis/qld/consol_act/cc189994/s218.html">Queensland</a>.</p>
<p>There are <a href="https://justice.nt.gov.au/__data/assets/pdf_file/0004/171850/drink-spiking-discussion-paper.pdf">some ambiguities</a> in the criminal law. For example, some laws aren’t clear about whether drink spiking with alcohol is an offence.</p>
<p>However, in all states and territories, if someone is substantially intoxicated with alcohol or other drugs it’s good evidence they <a href="https://www.monash.edu/__data/assets/pdf_file/0003/1092675/05_McNamara.pdf">aren’t able to give consent</a> to sex. Sex with a substantially intoxicated person who’s unable to consent may constitute rape or another sexual assault offence.</p>
<hr>
<p><strong><em>Getting help</em></strong></p>
<p><em>In an emergency, call triple zero (000) or the nearest police station.</em> </p>
<p><em>For information about sexual assault, or for counselling or referral, call 1800RESPECT (1800 737 732).</em></p>
<p><em>If you’ve been a victim of drink spiking and want to talk to someone, the following confidential services can help:</em></p>
<p><em>- Beyond Blue: 1300 22 4636</em></p>
<p><em>- Kids Helpline (5-25 year olds): 1800 55 1800</em></p>
<p><em>- National Alcohol and other Drug Hotline: 1800 250 015.</em></p>
<hr>
<p><em>This article has been amended to remove a reference to blood tests for criminal prosecution which may not be available across Australia.</em></p><img src="https://counter.theconversation.com/content/160538/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicole Lee works as a consultant in the alcohol and other drug sector and a psychologist in private practice. She has previously been awarded funding by Australian and state governments, NHMRC and other bodies for evaluation and research into alcohol and other drug prevention and treatment, and currently receives funds from the Australian Government, and several state and territory governments. She is a member of the Australian Government's Australian National Advisory Council on Alcohol and other Drugs, a member of the board of directors of Hello Sunday Morning and volunteers with The Loop Australia.</span></em></p><p class="fine-print"><em><span>Jarryd Bartle works as a consultant in the alcohol and other drug sector.</span></em></p>Preventing drink spiking is a collective responsibility, not something to be shouldered by potential victims.Nicole Lee, Professor at the National Drug Research Institute (Melbourne), Curtin UniversityJarryd Bartle, Sessional Lecturer, RMIT UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1487212020-12-21T13:05:44Z2020-12-21T13:05:44ZNew antidepressants can lift depression and suicidal thoughts fast, but don’t expect magic cures<figure><img src="https://images.theconversation.com/files/374930/original/file-20201214-20-vhn4py.jpg?ixlib=rb-1.1.0&rect=302%2C33%2C2899%2C1918&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Alleviating major depression for the long term involves more than just drugs.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/worried-woman-royalty-free-image/563853729">Rafa Elias via Getty Images</a></span></figcaption></figure><p>Depression is the <a href="https://www.who.int/news-room/fact-sheets/detail/depression">most common cause of disability</a> in the world. Chances are high that you or someone you know will experience a period when depression gets in the way of work, social life or family life. Nearly two in three people with depression will experience <a href="https://www.nimh.nih.gov/health/statistics/major-depression.shtml#part_155030">severe effects</a>.</p>
<p>As a <a href="https://scholar.google.com/citations?user=5DzjK7QAAAAJ&hl=en">psychiatrist</a> specializing in behavioral neuroscience, I help patients who suffer from mood disorders. Many have “<a href="http://doi.org/10.1016/s0193-953x(05)70283-5">treatment-resistant</a>” depression and are on a nearly constant search for relief. </p>
<p>There have been some exciting developments in treating depression recently, particularly new rapid-acting antidepressants. But it’s important to understand that these medications aren’t cure-alls.</p>
<p>The new treatments for depression <a href="https://www.nytimes.com/2019/03/05/health/depression-treatment-ketamine-fda.html">promise</a> to relieve distressing symptoms, including <a href="https://www.npr.org/sections/health-shots/2020/08/07/900272454/nasal-spray-is-a-new-antidepressant-option-for-people-at-high-risk-of-suicide">suicidal thinking</a>, faster than any previous treatment. They include ketamine, an anesthetic that is also abused as a street drug, and a derivative of ketamine called esketamine. These drugs have been shown to help relieve symptoms of depression <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534172/">within hours</a>, but each dose only works for a few days. <a href="https://doi.org/10.1080/15622975.2020.1836399">They also carry risks</a>, including the potential for drug abuse.</p>
<p>With the <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6932a1.htm">coronavirus pandemic taking a toll</a> on mental health, patients are looking for fast relief. Medication can help, but to effectively treat depression long term, with its mix of biological, psychological, social and cultural components, requires more than just drugs. </p>
<h2>Depression medications have evolved</h2>
<p>The early history of depression treatments focused on the psychological components of illness. The goal in the early 20th century was for a patient to understand unconscious urges established during childhood. </p>
<p><a href="http://library.law.columbia.edu/urlmirror/CJAL/14CJAL1/shock_i.htm">Biological treatments at the time</a> seem frightening today. They included insulin coma therapy and primitive, frequently misused versions of a modern lifesaving procedure – electroconvulsive therapy.</p>
<p>In the middle of the 20th century, medicines that affected behavior were discovered. The first medicines were sedatives and antipsychotic medicines. <a href="https://pubmed.ncbi.nlm.nih.gov/16433053/">Chlorpromazine</a>, marketed as “Thorazine,” led the way in the 1950s. In 1951, imipramine was discovered and would become one of the first antidepressants. The <a href="https://archive.fortune.com/magazines/fortune/fortune_archive/2004/06/28/374398/index.htm">“blockbuster”</a> antidepressant Prozac, a selective serotonin reuptake inhibitor, or SSRI, was approved in 1987. </p>
<figure class="align-center ">
<img alt="Man in therapy session." src="https://images.theconversation.com/files/374921/original/file-20201214-15-6n0f22.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/374921/original/file-20201214-15-6n0f22.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/374921/original/file-20201214-15-6n0f22.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/374921/original/file-20201214-15-6n0f22.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/374921/original/file-20201214-15-6n0f22.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/374921/original/file-20201214-15-6n0f22.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/374921/original/file-20201214-15-6n0f22.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 physician-patient relationship can help ensure all components of major depression are being addressed.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/youre-not-alone-royalty-free-image/1048189084">SolStock via Getty Images</a></span>
</figcaption>
</figure>
<p>It’s been over 30 years since we’ve seen a novel class of antidepressant medicine. That’s one reason rapid-acting antidepressants are exciting.</p>
<h2>What depression looks like inside the brain</h2>
<p>Medical treatments for depression affect certain processing cells in the brain area above your eyes and under your forehead. This area, called the prefrontal cortex, processes complex information including emotional expressions and social behavior. </p>
<p>Brain cells called neurons are chemically controlled by <a href="https://thebrain.mcgill.ca/flash/i/i_01/i_01_m/i_01_m_ana/i_01_m_ana.html">two opposing messenger</a> molecules, glutamate and gamma-amino-butyric acid (GABA). Glutamate works like a gas pedal and GABA is the brake. They tell the neurons to speed up or slow down.</p>
<p>Rapid-acting medicines for depression decrease the action of glutamate, the gas pedal. </p>
<p>Other treatments have been developed to rebalance GABA. A neurosteroid called <a href="https://doi.org/10.3389/fendo.2020.00236">allopregnanolone</a> affects GABA and applies the brake. Both allopregnanolone and esketamine have federal approval for treatment of depression, allopregnanolone <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-post-partum-depression">for postpartum depression</a> and esketamine for <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified">major depressive disorder and suicidal thinking</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/GnL4p-35Grg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<h2>Not so fast</h2>
<p>Around 2016-2017, young psychiatrists like myself were rushing to implement these novel antidepressant treatments. Our training supervisors said, “not so fast.” They explained why we should wait to see how studies of the new drugs turn out.</p>
<p>Several years before, the medical community experienced similar excitement over Vivitrol to treat opioid addiction. Vivitrol is a monthly injected form of naltrexone, an opioid-blocking medicine. </p>
<p>Clinical trials are executed in a highly controlled and clean environment, while the real world can be highly uncontrolled and very messy. Without risk reduction, education and psychosocial treatment, the potential <a href="https://www.vivitrol.com/important-safety-information">risks of medications like Vivitrol</a> can be magnified. Vivitrol can help reduce relapses, but isn’t a panacea on its own. The National Institute on Drug Abuse <a href="https://www.drugabuse.gov/publications/principles-drug-addiction-treatment-research-based-guide-third-edition/principles-effective-treatment">recommends integrated treatment</a> for addiction. </p>
<p>Treating depression may be <a href="http://doi.org/10.1176/appi.ajp.2015.15040476">similar</a>. Medication and psychological support together work better than either on its own.</p>
<h2>The risks</h2>
<p>In depression, the more treatments a person tries that don’t work, the less likely that person is to have success with the next treatment option. This was a main message of the largest clinical trial studying depression medications, the <a href="https://www.nimh.nih.gov/funding/clinical-research/practical/stard/index.shtml">National Institutes of Health-directed STAR-D study</a>, completed in 2006.</p>
<p>Providing a more effective option for patients who don’t respond to a first or second antidepressant may turn that STAR-D message on its head. However, when dealing with an illness that is affected by <a href="http://doi.org/10.2174/1570159x1304150831150507">external stress</a> like trauma and loss, treatment is more likely to succeed with both medication and psychological support. </p>
<p>A real-world treatment approach called the <a href="https://www.psychiatrictimes.com/view/can-we-salvage-biopsychosocial-model">biopsychosocial paradigm</a> accounts for the wide range of relevant biological, psychological and social components of mental illnesses. The patient and physician work together to process the patient’s problematic experiences, thoughts and feelings. </p>
<p>A hyperfocus on novel drugs may overlook the importance of addressing and monitoring all those components, which could mean problems surface in the future. Medications like opiates or other substances that provide rapid relief of physical or psychological pain can also be physically and psychologically addictive, and novel rapid-acting antidepressants <a href="http://doi.org/10.1177/0897190014525754">can have the same risks</a>.</p>
<p>Rapid-acting antidepressants can be powerful tools for treating major depression when used with other forms of therapy, but are they the answer? Not so fast.</p>
<p>[<em>Get facts about coronavirus and the latest research.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=coronavirus-facts">Sign up for The Conversation’s newsletter.</a>]</p><img src="https://counter.theconversation.com/content/148721/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicholas Mischel receives or has received funding from the American Heart Association, National Institutes of Health, and Wayne State University. He is employed by Wayne State University and member of the American Psychiatric Association, Society of Biological Psychiatry, North American Neuromodulation Society, the Clinical TMS Society, and the American Society of Ketamine
Physicians, Psychotherapists & Practitioners.</span></em></p>Drugs like ketamine can relieve depression symptoms, including suicidal thoughts, within hours, but they also carry risks that patients need to understand.Nicholas Mischel, Assistant Professor of Psychiatry and Behavioral Neurosciences; Director, Interventional Psychiatry and Neuromodulation Research Program, Wayne State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1492132020-11-04T14:04:28Z2020-11-04T14:04:28ZDepression, anxiety and heart disease risk all linked to single brain region<figure><img src="https://images.theconversation.com/files/367479/original/file-20201104-19-1poelhg.jpg?ixlib=rb-1.1.0&rect=8%2C8%2C5982%2C3979&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Over-activity in the brain's subgenual anterior cingulate cortex is likely to be one cause of depression and anxiety.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/puzzle-head-brain-concept-human-face-269726339">ESB Professional/ Shutterstock</a></span></figcaption></figure><p>Although depression and <a href="https://apps.who.int/iris/bitstream/handle/10665/254610/WHO-MSD-MER-2017.2-eng.pdf">anxiety</a> affect <a href="https://www.who.int/news-room/fact-sheets/detail/depression">millions of people</a> worldwide, there’s still much we don’t know about them. In fact, we still don’t fully understand which brain regions are involved in depression and anxiety, and how they differ between people with varying symptoms. Understanding how or why these differences occur is fundamental to developing better treatments. </p>
<p>So far, we know that part of the brain’s frontal lobe, the <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/prefrontal-cortex">prefrontal cortex</a>, often shows <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2522333/">activity changes</a> in people with depression and anxiety. Parts involved in cognition and regulating emotions are underactive, whereas other parts involved in emotion generation and internal bodily functions are over-active.</p>
<p>One key region shown to be over-active in people with depression and anxiety is the subgenual anterior cingulate cortex (sgACC), thought to be involved in emotional responses. However, neuroimaging studies only show correlation and don’t tell us that the over-activity causes any of the symptoms. But <a href="https://www.nature.com/articles/s41467-020-19167-0">our new research</a> has found over-activating the sgACC induces symptoms of depression and anxiety, highlighting causality. </p>
<p>For our study, we used marmosets (a type of primate) because their brain closely resembles a human’s brain. We found over-activity in this region causes several key features of mood and anxiety disorders, particularly how reactive they are to threat. Their reaction to threat is important, as patients with depression and anxiety tend to perceive and react to situations more negatively.</p>
<p>To over-activate sgACC, we implanted tiny hollow tubes – called cannulae – into the marmosets’ brains. We then infused small amounts of a drug into sgACC to increase excitability without damaging or disrupting function in other brain regions. We also implanted a small wireless device into an artery to measure blood pressure and heart rate.</p>
<p>But before over-activating sgACC, we trained the marmosets to associate a specific tone with the presence of a rubber snake, which marmosets find threatening. After learning this association, the marmosets exhibited fear and had higher blood pressure when hearing the tone. We then presented the tone without the snake to break this association. This allowed us to measure how quickly the marmosets could dampen their fear response with and without sgACC over-activation. </p>
<p>Without over-activation, marmosets gradually regulated their threat response within minutes when hearing the tone without the snake. But after over-activating sgACC, marmosets exhibited fearful behaviour and higher blood pressure for much longer. They also remained anxious around other types of threat (in the form of an unfamiliar human). This reaction showed they could no longer dampen down their threat responses. Being unable to regulate emotions is also seen in many patients with anxiety and depression.</p>
<figure class="align-center ">
<img alt="A marmoset sits on a tree branch looking at the camera." src="https://images.theconversation.com/files/367477/original/file-20201104-13-1qx3ayb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/367477/original/file-20201104-13-1qx3ayb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/367477/original/file-20201104-13-1qx3ayb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/367477/original/file-20201104-13-1qx3ayb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/367477/original/file-20201104-13-1qx3ayb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/367477/original/file-20201104-13-1qx3ayb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/367477/original/file-20201104-13-1qx3ayb.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 marmosets were more anxious around perceived threat.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/marmoset-tree-woods-300583817">nattanan726/ Shutterstock</a></span>
</figcaption>
</figure>
<p>These findings build on our <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344231/">earlier work</a> that showed over-activity of sgACC reduces anticipation and motivation for rewards, mirroring the anhedonia (inability to feel pleasure) seen in depression. This suggests sgACC over-activity can cause two of the core symptoms seen in depression – negative emotions (including anxiety) and lack of pleasure. </p>
<h2>Heart disease and depression</h2>
<p>Another outstanding question is why people with depression also have <a href="https://academic.oup.com/eurheartj/article/41/17/1687/5303703">increased risk of heart disease</a>. While there’s undoubtedly lifestyle and socioeconomic factors linking heart disease and depression, we wanted to test whether sgACC over-activity itself could disrupt cardiovascular function. We thought this region might be important because it’s connected to the brainstem, which regulates our heart rate and blood pressure.</p>
<p>We found that sgACC over-activity not only exaggerated marmosets’ blood pressure response to threat, it also increased heart rate and reduce heart rate variability even at rest. Heart rate variability is an important measure of how rapidly the heart can adapt to changes in the environment, especially cues which predict reward or punishment. </p>
<p>These changes mirror some of the cardiac dysfunction seen in <a href="https://academic.oup.com/eurheartj/article/41/17/1687/5303703#203097326">depression and anxiety</a>. The elevated heart rate and reduced heart rate variability suggests that over-activity in sgACC promotes the body’s “fight-or-flight” response, which – if lasting over long periods of time – puts the heart under extra strain and might explain the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800172/">increased incidence of heart disease</a>.</p>
<h2>Treatment response</h2>
<p>We also used brain imaging to investigate the other regions affected by sgACC over-activity in threatening situations. We saw increased activity in two key parts of the brain’s stress network, the amygdala and hypothalamus. By contrast, reduced activity was seen in parts of the lateral prefrontal cortex, which regulates emotional responses and is underactive in depression. These changes were very different to those seen following over-activation during a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344231/">rewarding situation</a>. </p>
<p>Knowing these differences may be key to us understanding which treatments will be most effective depending on the symptoms exhibited by a patient. This then led us to investigate why some people respond to antidepressants while others don’t. The most common type of antidepressants are selective serotonin re-uptake inhibitors (SSRIs). But <a href="https://pubmed.ncbi.nlm.nih.gov/17074942/">up to one-third</a> of people who take antidepressants are treatment resistant – meaning they don’t respond to them. New treatments are urgently needed for these people. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968361/">Ketamine</a> has shown some promise in successfully treating people with treatment resistant depression – and acts within hours to relieve symptoms. Previously, we had shown ketamine effectively <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344231/">treated anhedonia</a> after sgACC had been over-activated.</p>
<p>But in our recent study, we found that ketamine could not improve the elevated anxiety-like responses the marmosets displayed towards the unfamiliar human. This shows us different depression and anxiety symptoms react differently to different types of antidepressants or treatments. On one hand, anhedonia was reversed by ketamine, while anxiety was not.</p>
<p>But over-activation of sgACC is likely to be just one underlying cause of depression and anxiety. Others may have altered activity in different regions of the prefrontal cortex, which are also <a href="https://pubmed.ncbi.nlm.nih.gov/32958652/">linked to anxiety</a>. There’s still a long way to go before we have identified the different causes of depression and anxiety and which treatments can improve them. But our research shows that for some, targeting sgACC over-activity may be key in treating their symptoms.</p><img src="https://counter.theconversation.com/content/149213/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Angela Charlotte Roberts receives funding from the Medical Research Council and the Wellcome Trust</span></em></p><p class="fine-print"><em><span>Christian Wood and Laith Alexander 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>This brain region also shows how effective certain treatments will be.Laith Alexander, Academic Foundation Doctor, University of CambridgeAngela Charlotte Roberts, Professor of Behavioural Neuroscience, University of CambridgeChristian Wood, Postdoctoral Research Associate, Physiology and Pharmacology, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1460922020-09-21T06:04:47Z2020-09-21T06:04:47ZPTSD and psychoactive drugs: MDMA treatment shows potential, but others lack evidence<figure><img src="https://images.theconversation.com/files/358968/original/file-20200921-22-k4xxl2.jpg?ixlib=rb-1.1.0&rect=11%2C5%2C3822%2C2149&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shuterstock</span></span></figcaption></figure><p>Can psychoactive drugs be used to treat mental health problems? The idea has been around for years, and recently received some <a href="https://www.abc.net.au/triplej/programs/hack/proposal-to-treat-mental-illness-with-magic-mushrooms-and-mdma/12622680">attention</a> in the media.</p>
<p>Interest in the potential of drugs such as MDMA (scientific name 3,4-methylenedioxymethamphetamine), ketamine, psilocybin and LSD (lysergic acid diethylamide) has been growing among scientists and doctors, as well as the wider community. </p>
<p>However, there is still debate among experts about whether these drugs are safe and effective. In a <a href="https://www.tandfonline.com/doi/full/10.1080/02791072.2020.1817639">new study</a>, we reviewed the state of the evidence for using these drugs in the treatment of post-traumatic stress disorder (PTSD). </p>
<h2>How PTSD is treated now</h2>
<p>Up to 10% of people who are exposed to traumatic events such as a serious accident, physical assault, war, natural disaster, sexual assault or abuse will develop PTSD. Symptoms can include reliving the event through unwanted thoughts, flashbacks or nightmares; feeling wound up, having trouble sleeping, concentrating or being on the lookout for danger; and avoiding reminders of the event. These symptoms may last for years if left untreated. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-post-traumatic-stress-disorder-11135">Explainer: what is post-traumatic stress disorder?</a>
</strong>
</em>
</p>
<hr>
<p>Psychotherapies such as trauma-focused cognitive behavioural therapy (CBT) and eye movement desensitisation and reprocessing (EMDR) therapy are first-line treatments for PTSD. These types of treatments involve teaching patients to confront and come to terms with the painful memories, thoughts and images they have been avoiding. They also provide patients with tools to get back into the activities or places they have been avoiding, and to relax when they start to feel wound up.</p>
<p>While there is strong evidence showing these treatments are effective, not everyone responds to them. Psychoactive drugs are often touted as the solution to this problem. But does the science match the hype?</p>
<h2>What do we already know about psychoactive drugs for PTSD?</h2>
<p>Ketamine, MDMA, LSD and psilocybin have all been considered as potential treatments for PTSD:</p>
<ul>
<li><p>ketamine was developed as a general anaesthetic but is used recreationally because of its psychedelic and hallucinogenic properties. It acts mainly on the glutamergic system, which regulates large regions of the nervous system and has been implicated in the formation of traumatic memories and reduction of the stress response</p></li>
<li><p>MDMA is a synthetic compound and is typically the main constituent of “ecstasy”. It induces changes in human emotion and it is possible that MDMA, in combination with psychotherapy, can increase a person’s ability to access and process painful or negative emotions, and increase positive emotions and social interactions</p></li>
</ul>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/is-psychiatry-ready-for-medical-mdma-94105">Is psychiatry ready for medical MDMA?</a>
</strong>
</em>
</p>
<hr>
<ul>
<li><p>LSD is a hallucinogen that produces psychosensory changes and alters cognition, often increasing optimism and inducing a sense of well-being. By increasing prosocial behaviour, it may strengthen the alliance between therapist and patient and so increase the effectiveness of psychotherapy. It can also encourage catharsis and relaxation</p></li>
<li><p>psilocybin naturally occurs in “magic mushrooms” and, like LSD, it increases a person’s sense of optimism and well-being and reduces negative mood. It can also be associated with increased capacity for introspection, and <a href="https://journals.sagepub.com/doi/10.1177/0269881116675512">research studies</a> have found it can reduce levels of anxiety and depression in cancer patients.</p></li>
</ul>
<p>But do these drugs make a real difference in resolving PTSD symptoms? And are they any better than the treatments that we already have?</p>
<h2>What does the latest evidence say?</h2>
<p>To find out what the current evidence says, my colleagues and I at <a href="https://www.phoenixaustralia.org">Phoenix Australia</a> conducted a <a href="https://www.tandfonline.com/doi/full/10.1080/02791072.2020.1817639">systematic review</a> of the published research.</p>
<p>We found two <a href="https://pubmed.ncbi.nlm.nih.gov/29563072/">small</a> randomised <a href="http://www.actnjournal.com/article.asp?issn=2542-3932;year=2017;volume=2;issue=3;spage=80;epage=90;aulast=Pradhan">trials</a> in which ketamine was used in combination with psychotherapy to treat PTSD. Overall, we found ketamine shows some promise when compared with placebo, but future research is needed to investigate how ketamine, in combination with psychotherapy, stacks up against standard PTSD treatment.</p>
<p>The effect of using MDMA with psychotherapy was a little more encouraging, with <a href="https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(18)30135-4/fulltext">four</a> <a href="https://journals.sagepub.com/doi/10.1177/0269881110378371">small</a> <a href="https://journals.sagepub.com/doi/full/10.1177/0269881112464827">randomised</a> <a href="https://journals.sagepub.com/doi/full/10.1177/0269881118806297">trials</a> reporting positive effects in treating PTSD. We found MDMA currently has more promise than ketamine, based on the studies included in our review. It should be noted, though, that none of these four studies compared MDMA, in combination with psychotherapy, to a typical treatment for PTSD.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/358989/original/file-20200921-16-1n6sm9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358989/original/file-20200921-16-1n6sm9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358989/original/file-20200921-16-1n6sm9w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358989/original/file-20200921-16-1n6sm9w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358989/original/file-20200921-16-1n6sm9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358989/original/file-20200921-16-1n6sm9w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358989/original/file-20200921-16-1n6sm9w.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">Better known as the recreational drug ecstasy, MDMA may also play a valuable role in the treatment of PTSD and other mental health problems.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>The MDMA studies in the review found that improvements in clinician-rated PTSD symptoms, and in self-reported physical responses to stress, were “significantly greater” for those who received MDMA and psychotherapy compared to a placebo. A <a href="https://journals.sagepub.com/doi/10.1177/0269881112456611">small trial</a> showed that 17-74 months after MDMA and therapy was delivered, on average, improvements were still being felt.</p>
<p>Another <a href="https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(18)30135-4/fulltext">slightly larger trial</a> involved military veterans, firefighters and police officers with chronic PTSD, and found a significant reduction in the severity of symptoms. Out of 24 participants who completed a 12-month follow-up, 16 did not have a PTSD diagnosis.</p>
<p>We also looked for research on the use of LSD and psilocybin in PTSD treatment, and were surprised to discover no randomised controlled trials have been conducted.</p>
<h2>Where to from here?</h2>
<p>Attitudes towards psychoactive drugs for the treatment of PTSD are changing. Some proponents <a href="https://www.medicinenet.com/script/main/art.asp?articlekey=200991">suggest</a> they offer a “chemical safety net” for patients.</p>
<p>However, our review highlights the fact that, scientifically, this area is still in its infancy. There is a clear need for further high quality research, to provide us with a better understanding of these treatments, and how they might fit into treatment options for PTSD.</p><img src="https://counter.theconversation.com/content/146092/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tracey Varker receives funding from the Defence Health Foundation. </span></em></p>Drugs like MDMA, ketamine, LSD and psylocibin may help heal the wounds of trauma - but more research is needed.Tracey Varker, Senior research fellow, Phoenix Australia, Department of Psychiatry, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1179422019-06-04T13:48:25Z2019-06-04T13:48:25ZPsychedelic drugs: would you accept a prescription? It depends if you’ve tried them before<figure><img src="https://images.theconversation.com/files/277942/original/file-20190604-69051-1axiiqj.jpg?ixlib=rb-1.1.0&rect=33%2C55%2C7315%2C4847&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Would you put it up your nose?</span> <span class="attribution"><a class="source" href="https://www.imagenation.it/instantart">Shutterstock.</a></span></figcaption></figure><p>In countries such as the UK, US and Australia, strict laws and international conventions prohibiting the use of psychedelic drugs have made it almost impossible to research how these drugs work, and how they might be used to heal instead of harm – until recently. These barriers – together with cost, ethics committees, ideologically driven myths and stigma – have delayed research into a promising area of medicine. But things are changing for the better, as evidence and unmet need are at last being recognised. </p>
<p>In March 2019, the US <a href="https://www.fda.gov/home">Food and Drug Administration</a> (FDA) licensed a form of ketamine – esketamine – as a <a href="https://www.theverge.com/2019/3/11/18260297/esketamine-fda-approval-depression-ketamine-clinic-science-health">treatment for depression</a>. In low doses, ketamine <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011612.pub2/full">rapidly relieves depression</a> that is otherwise resistant to treatment. But regular doses of the drug are necessary to prevent relapse, so it’s administered as a nasal spray in a clinic, initially twice a week, then weekly or fortnightly.</p>
<p>This is good news. In cases where the first two or three antidepressants have failed, the chance of further drugs helping has hitherto been small – this new treatment could improve those odds. Its rapid effect is also welcome; for a long time, psychiatrists have bemoaned the slow effect of drugs such as Prozac – which can <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865459/">take two weeks</a> to start working – partly because there’s a chance that more rapid action could prevent suicide.</p>
<p>But the most revolutionary and disruptive consequence of the licensing of esketamine – the side effects of which <a href="https://www.ncbi.nlm.nih.gov/pubmed/28757132">include dissociation</a> – is that a new, previously illegal, field of medicine has suddenly, quietly, become legal: psychedelic-assisted psychotherapy. </p>
<p>This creates the possibility of combining established forms of psychotherapy with other drugs such as psilocybin (the psychedelic compound found in some varieties of mushroom), LSD and MDMA – all of which are in active development by pharmaceutical companies (Compass, Eleusis and MAPS respectively). </p>
<h2>Polarised opinion</h2>
<p>But even if we’re heading towards a new era, where psychedelics can make therapy more effective, these drugs still have their own stigma to shed. New data from the 2019 <a href="https://www.globaldrugsurvey.com/">Global Drug Survey</a> (GDS) offer an indication of how the public might react if psychedelic drugs were more widely available for mental disorders. Opinion is surprisingly polarised, between those who would actually prefer psychedelic psychotherapy and those who wouldn’t touch it.</p>
<p>In our study of more than 85,000 people, recruited as part of GDS2019, we looked at how acceptable people found different approaches to treating mental illness. As expected, people prefer talking to medication: 70% would be likely to accept talking therapies such as <a href="https://www.nhs.uk/conditions/cognitive-behavioural-therapy-cbt/">Cognitive Behavioural Therapy</a> (CBT), but only 40% said they would accept drugs – whether psychiatric or psychedelic. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/277934/original/file-20190604-69051-1has5we.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/277934/original/file-20190604-69051-1has5we.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=345&fit=crop&dpr=1 600w, https://images.theconversation.com/files/277934/original/file-20190604-69051-1has5we.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=345&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/277934/original/file-20190604-69051-1has5we.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=345&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/277934/original/file-20190604-69051-1has5we.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=434&fit=crop&dpr=1 754w, https://images.theconversation.com/files/277934/original/file-20190604-69051-1has5we.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=434&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/277934/original/file-20190604-69051-1has5we.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=434&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Ketamine in crystal form.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/3/30/Ketamine_Crystals.jpg">Coaster420/Wikimedia Commons.</a></span>
</figcaption>
</figure>
<p>Of those who had never taken psychedelics, almost 40% said that they would be unlikely to accept them as therapies, mainly because they were fearful of brain damage or a “bad trip”. Conversely, conventional antidepressants were unpopular with those with had taken psychedelics.</p>
<h2>A thorny problem</h2>
<p>This highlights a thorny dilemma for doctors and policy makers. If people’s responses to a hypothetical scenario in our survey are reflected in actual behaviour, then we can expect those with experience of illegal drug use to be over-represented in the early adopters of psychedelic therapies. This group may also differ in their openness to novel therapies and <a href="https://www.theguardian.com/society/2012/mar/15/truth-about-young-people-and-drugs">attitudes towards risk</a>. </p>
<p>A second, more urgent problem is that delays to legal access, caused by high costs, delays in drug licensing, or lack of availability via public health services could lead to more people treating themselves without medical supervision. It seems inevitable that untrained therapists will start appearing. The number of people self-treating with illegal ketamine and other psychedelics could even come to exceed the number accessing them through legitimate, supervised sources.</p>
<p>The biggest mistake would be to ignore the lessons of history. All too often, psychiatrists’ initial enthusiasm toward new treatments eventually lead to reactive backlash and reinforced stigma. For example, <a href="https://theconversation.com/opioid-epidemic-the-global-spread-explained-101649">the global spread</a> of the opioid epidemic began with a delay in data collection, failures to track doctor shopping (when people visit multiple doctors until they find one who will prescribe), lack of monitoring when people switched to stronger drugs and eventually the introduction of prohibition measures. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/opioid-epidemic-the-global-spread-explained-101649">Opioid epidemic – the global spread explained</a>
</strong>
</em>
</p>
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<p>At present, the drug licensing system means that companies are only responsible for tracking the side effects of their own drugs. The FDA has insisted on a risk mitigation plan for esketamine in the US – but it only tracks when people switch from ketamine (US$8 a dose) to esketamine (over US$600 a dose). So the real risks – which would arise from people switching from esketamine to ketamine, and from medical to illegal ketamine – will remain unquantified. </p>
<h2>Risks and rewards</h2>
<p>As it stands, there are many registries – often held by governments or pharmaceutical companies – which gather information about the drugs used to treat mental illness, but do not share it. But we think it would be better to bring this information together, and give people the chance to share their own experiences – whether they’re receiving treatment in a clinic, or insist on treating themselves.</p>
<p>Not only would this provide doctors and researchers with valuable data – it could also be an effective way to raise awareness about the risks of using drugs outside a clinical setting. People who treat themselves risk exacerbating psychotic disorders, engaging in dangerous behaviour and suffering acute cardiovascular effects like increased blood pressure. Within proper clinical settings, doctors can ensure there is appropriate patient screening, preparation, monitoring and follow up care, which can substantially mitigate these risks. </p>
<p>There’s still a chance for European and UK regulators to recognise the need to monitor people’s use of ketamine and other psychedelic drugs, as they begin to be licensed for medical use. Failure to involve patients and those who use drugs, and learn from their vast experience, is a historical error it would be wise to avoid. Patients’ experiences matter – now doctors need to give them a voice.</p><img src="https://counter.theconversation.com/content/117942/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>AW is the founder and owner of Global Drug Survey – an independent research organisation based in London. The Global Drug Survey receives ethics approval from UCL, University of NSW and University of Queensland. </span></em></p><p class="fine-print"><em><span>Rupert McShane has received remuneration for his work on advisory boards for Janssen, Sage and Eleusis.</span></em></p>Ketamine and other psychedelics are being licensed for medical use – two experts advise how to minimise harm for users.Adam Winstock, Honorary Clinical Professor, UCLRupert McShane, Associate Professor in Psychiatry, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1156972019-05-14T22:50:22Z2019-05-14T22:50:22ZKetamine: The illicit party psychedelic that promises to heal depression<figure><img src="https://images.theconversation.com/files/273668/original/file-20190509-183077-1whnt10.jpg?ixlib=rb-1.1.0&rect=83%2C330%2C2483%2C1521&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ketamine is effective for those who do not respond to traditional anti-depressants. It also shows promise for the treatment of PTSD and bipolar disorder. </span> <span class="attribution"><span class="source">(Unsplash/Kal Visuals)</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>It’s been 50 years in the making, but the anaesthetic and illicit party drug ketamine is now having a clinical comeback. New studies show that this commonly used anaesthetic can provide quick relief of core symptoms associated with severe depression, including <a href="https://www.cbc.ca/radio/april-13-2019-black-hole-imaged-a-new-tiny-human-rebuilding-coral-reefs-and-more-1.5093713/ketamine-works-its-magic-on-depression-by-stabilizing-the-brain-in-a-well-state-1.5093729">suicidal ideation</a>. </p>
<p>Amazingly, ketamine works within hours and its <a href="https://doi.org/10.1001/archpsyc.63.8.856">effects are maintained for at least one week</a>. Most strikingly, ketamine is effective in those patients who are <a href="https://doi.org/10.1176/appi.ajp.2013.13030392">resistant to ordinary antidepressants</a>, and they make up around <a href="https://doi.org/10.3310/hta18310">30 to 50 per cent of the depressed population</a>.</p>
<p>Now, efforts in <a href="https://doi.org/10.1111/pcn.12675">Mexico</a>, <a href="https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12616001096448">Australia</a>, <a href="https://doi.org/10.1016/j.psychres.2015.10.032">France</a>, <a href="https://doi.org/10.1016/j.biopsych.2018.02.1052">Canada</a> and the <a href="https://doi.org/10.1016/j.biopsych.2009.04.029">United States</a>, among others, are focusing on understanding exactly how ketamine does this, and to what extent it is safe and effective in a clinical setting. Together, these studies will increase our understanding of depression around the world and perhaps expand ketamine’s potential to treat other forms of mental illness as well.</p>
<p>The focus of <a href="https://www.uoguelph.ca/psychology/users/francesco-leri">our lab at the University of Guelph</a> is to understand how specific drugs, such as ketamine, work in the brain and influence behaviour. </p>
<p>My doctoral research, specifically, looks at <a href="https://www.researchgate.net/profile/Brett_Melanson2">the link between stress, inflammation and behaviour</a>. I am studying how ketamine influences behaviour and can reduce the effects of stress, and what this means for mood disorders, such as major depression.</p>
<h2>The first dissociative anaesthetic</h2>
<p>Initially, ketamine was developed as an alternative to the well-known, illegal party drug, phencyclidine (PCP). In the late 1950s, PCP was the focus of Parke-Davis pharmaceuticals for its use as an anesthetic. However, the drug came with <a href="https://doi.org/10.1097/ALN.0b013e3181ed09a2">uncomfortable side effects</a> such as delirium and a loss of feeling in the limbs, which lasted for several hours after the drug was taken.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/273394/original/file-20190508-183083-i63nor.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/273394/original/file-20190508-183083-i63nor.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/273394/original/file-20190508-183083-i63nor.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/273394/original/file-20190508-183083-i63nor.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/273394/original/file-20190508-183083-i63nor.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/273394/original/file-20190508-183083-i63nor.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/273394/original/file-20190508-183083-i63nor.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">Ketamine is known as the party drug Special K.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>To fix this issue, Cal Bratton of Parke-Davis encouraged scientists to look into possible ways to modify PCP, with a primary goal of reducing side effects. In 1962, the organic chemist, Calvin Stevens, made a PCP-like compound which he said had similar anaesthetic properties, with shorter acting psychoactive effects than PCP. </p>
<p>This compound, <a href="https://doi.org/10.1097/ALN.0b013e3181ed09a2">originally known as CI-581</a>, was eventually named <a href="https://doi.org/10.1097/EJA.0000000000000638">ketamine</a> based on the ketone and amine group that formed its chemical structure.</p>
<p>Followings its discovery, ketamine was then used in the first human trials in the mid-1960s which included testing on <a href="https://doi.org/10.1111/j.1365-2044.1990.tb14287.x">volunteer inmates of Jackson Prison</a> in Michigan, United States. </p>
<p>After consistent reports of feeling “disconnected” from the environment when given ketamine, it was classified as the first <a href="https://doi.org/10.1097/ALN.0b013e3181ed09a2">dissociative anesthetic</a>. </p>
<p>In the years after its initial testing, the effects of ketamine rapidly gained popularity around the globe, and the approval as a human anaesthetic was passed by the U.S. Food and Drug Administration (FDA) in 1970 — <a href="https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm">to be sold as Ketalar</a>.</p>
<h2>Unique antidepressant effect</h2>
<p>Recent studies describing ketamine’s antidepressant properties have led to a dramatic shift in how we view the drug and treat mental illness.</p>
<p>Typical antidepressants work by controlling levels of neurotransmitters in the brain known as monoamines, such as serotonin and norepinephrine. Ketamine’s antidepressant effect is unique, as it <a href="https://doi.org/10.1016/j.psychres.2014.10.028">modifies the activity of glutamate</a>, which is the main excitatory neurotransmitter in the brain and is not a monoamine.</p>
<p>One of the fascinating findings about ketamine is that it can rapidly reduce depressive symptoms in <a href="https://www.ncbi.nlm.nih.gov/books/NBK487457/pdf/Bookshelf_NBK487457.pdf">patients who do not respond to typical monoamine antidepressants</a>. This suggests the role of glutamate in depression.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/273667/original/file-20190509-183112-e1i9bo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/273667/original/file-20190509-183112-e1i9bo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/273667/original/file-20190509-183112-e1i9bo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/273667/original/file-20190509-183112-e1i9bo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/273667/original/file-20190509-183112-e1i9bo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/273667/original/file-20190509-183112-e1i9bo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/273667/original/file-20190509-183112-e1i9bo.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">The study of ketamine is opening new doors for treating mental illness.</span>
<span class="attribution"><span class="source">(Unsplash/Candice Picard)</span></span>
</figcaption>
</figure>
<p>In fact, studies have related ketamine’s antidepressant effect with its ability to maintain connections between neurons (or nerve cells) in the brain. These connections are known to continuously change in response to our environment, which is a process known as <em>plasticity</em>. Interestingly, the ability of these neurons to change connections highly relies on normal glutamate activity. </p>
<p>A combination of human and animal studies suggest that ketamine’s antidepressant effect may involve regulating glutamate levels to <a href="https://doi.org/10.4103/1673-5374.230288">strengthen these connections</a> and/or restore them <a href="https://www.bbrfoundation.org/event/brain-plasticity-effects-antidepressants-major-depression">back to a pre-stressed state</a>.</p>
<p>Further study of ketamine’s ability to restore these neural connections and how glutamate relates to mood disorders will surely open new doors for understanding mental illness.</p>
<h2>Nasal sprays and biomarkers</h2>
<p>Current research has shown positive effects of ketamine for other forms of mental illness as well, such as <a href="https://doi.org/10.4088/JCP.17m11634">post-traumatic stress disorder (PTSD)</a> and <a href="https://doi.org/10.9740/mhc.2017.01.016">bipolar disorder</a>. Though the results seem quite positive, more studies are required to validate their use beyond depression. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/273395/original/file-20190508-183103-1t9fg1i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/273395/original/file-20190508-183103-1t9fg1i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/273395/original/file-20190508-183103-1t9fg1i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/273395/original/file-20190508-183103-1t9fg1i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/273395/original/file-20190508-183103-1t9fg1i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=507&fit=crop&dpr=1 754w, https://images.theconversation.com/files/273395/original/file-20190508-183103-1t9fg1i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=507&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/273395/original/file-20190508-183103-1t9fg1i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=507&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A vial of ketamine.</span>
<span class="attribution"><span class="source">(AP Photo/Teresa Crawford)</span></span>
</figcaption>
</figure>
<p>Other studies using a <a href="https://doi.org/10.1176/appi.ajp.2018.18070834">repeated treatment method over several weeks</a> showed that ketamine can produce long-term reductions in symptoms of treatment-resistant depression, lending potential to its safety and effectiveness over longer periods of treatment.</p>
<p>Recently, the FDA has approved esketamine (ketamine’s “close cousin”) in the U.S., sold as <a href="https://www.cnn.com/2019/03/05/health/esketamine-depression-nasal-spray-fda-bn/index.html">Spravato</a> in the form of a nasal spray. Importantly, the spray is only prescribed to treatment-resistant patients who continue to take an oral antidepressant and can only be used under the supervision of a health-care provider.</p>
<p>Finally, studies are also looking into <a href="https://www.mayoclinic.org/medical-professionals/psychiatry-psychology/news/ketamine-research-focuses-on-mechanisms-of-action-and-biomarker-development/mac-20430311">biological markers that can predict response to treatment, also known as biomarkers</a>. If successful, this research would allow for more accurate and effective treatment delivery in the form of <a href="https://www.canbind.ca/research/why-and-how-we-study-depression/">personalised treatment plans</a>.</p>
<p>Increasing accessibility to ketamine treatment for depression will be the next major milestone for this drug. It is sure to provide effective relief for those who continue to experience treatment-resistant and severe depression.</p>
<p><br>
<br></p>
<p><em>The promise of ketamine for treating mood disorders only applies in a carefully monitored clinical setting. The street drug <a href="https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/ketamine">Special K can be addictive, put users at high risk and cause long-term psychological harm</a>.</em></p><img src="https://counter.theconversation.com/content/115697/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brett Melanson 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>Research shows that ketamine can produce long-term reductions in symptoms of treatment-resistant depression.Brett Melanson, PhD Student in Neuroscience and Applied Cognitive Science, University of GuelphLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1119662019-02-21T11:42:51Z2019-02-21T11:42:51ZFDA approves promising new drug, called esketamine, for treatment-resistant depression<figure><img src="https://images.theconversation.com/files/259990/original/file-20190220-148509-h4lja8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">One in 3 people with severe depression do not respond to treatment.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/depressed-man-sitting-head-hands-on-530048185?src=PfMH5Bu4fWJt4CrhKG_fHw-1-10">TZIDO SUN/Shutterstock.com</a></span></figcaption></figure><p><a href="https://www.nimh.nih.gov/research-priorities/research-initiatives/rapidly-acting-treatments-for-treatment-resistant-depression-rapid.shtml">Treatment-resistant depression</a> affects 1 in 3 of the <a href="https://www.nimh.nih.gov/health/statistics/major-depression.shtml">estimated 16.2 million adults in the U.S.</a> who have suffered at least one major depressive episode. For them, two or more therapies have failed and the risk of suicide is much greater. It’s a grim prognosis. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/259992/original/file-20190220-148523-1lu62x9.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/259992/original/file-20190220-148523-1lu62x9.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/259992/original/file-20190220-148523-1lu62x9.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=607&fit=crop&dpr=1 600w, https://images.theconversation.com/files/259992/original/file-20190220-148523-1lu62x9.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=607&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/259992/original/file-20190220-148523-1lu62x9.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=607&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/259992/original/file-20190220-148523-1lu62x9.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=762&fit=crop&dpr=1 754w, https://images.theconversation.com/files/259992/original/file-20190220-148523-1lu62x9.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=762&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/259992/original/file-20190220-148523-1lu62x9.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=762&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 chemical structure of esketamine.</span>
</figcaption>
</figure>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/259993/original/file-20190220-148533-93apic.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/259993/original/file-20190220-148533-93apic.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=606&fit=crop&dpr=1 600w, https://images.theconversation.com/files/259993/original/file-20190220-148533-93apic.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=606&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/259993/original/file-20190220-148533-93apic.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=606&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/259993/original/file-20190220-148533-93apic.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=761&fit=crop&dpr=1 754w, https://images.theconversation.com/files/259993/original/file-20190220-148533-93apic.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=761&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/259993/original/file-20190220-148533-93apic.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=761&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The chemical structure of ketamine.</span>
</figcaption>
</figure>
<p>There are few therapies for depression that resists treatment, which is why the FDA granted this new drug application <a href="https://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm">Fast Track</a> and Breakthrough Therapy status. On March 5, the Food and Drug Administration <a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm632761.htm">approved a new treatment called esketamine</a>. </p>
<p>On Feb. 12, 2019, I participated in the <a href="https://www.fda.gov/AdvisoryCommittees/Calendar/ucm630167.htm">FDA review of this drug</a>. Practically speaking, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Esketamine#section=2D-Structure">esketamine</a> is essentially the same as <a href="https://pubchem.ncbi.nlm.nih.gov/compound/3821#section=Top">ketamine</a>, which is a pain killer with hallucinogenic effects and used illegally. As a member of the Drug Safety and Risk Management Advisory Committee of the FDA, I voted with the majority of that panel 14-2, to approve esketamine only for people who have treatment-resistant depression.</p>
<p>For more than 20 years, <a href="http://anthropology.case.edu/faculty/lee-hoffer/">I have researched</a> illegal drug use and addiction. As a medical anthropologist, my work is oriented to understanding the perspectives and behaviors of people actively using illegal drugs. My research often involves fieldwork, which means participating in the lives of people as they go about their everyday routines. This has given me a personalized and practical outlook on illegal drug use. Many of the people I currently interview are heroin injectors who first started opioid use by misusing prescription drugs. </p>
<h2>Not a street drug</h2>
<p>But many drugs, especially those for the treatment of mental illness, have powerful effects on the central nervous system. How the drug is distributed and administered must minimize risk. What if the drug is addicting? </p>
<p>Some reports about esketamine have sensationalized this issue by referring to ketamine as a <a href="https://www.nbcnews.com/health/mental-health/new-depression-drug-related-ketamine-recommended-fda-panel-n970836">highly addictive street drug</a>. In my research, this is not true. First, <a href="https://nsduhweb.rti.org/respweb/homepage.cfm">ketamine use is rare</a>. The last time I interviewed a ketamine users was nearly 20 years ago and since its introduction in 1964, there have been <a href="http://www.monitoringthefuture.org">no significant trends or outbreaks</a> in its diversion or use. </p>
<p>Not all illegal drugs are sold “on the street.” Street drugs are staples of the illegal drug economy, which is run by drug trafficking organizations. Prescription opioids, heroin, cocaine, and marijuana are street drugs sold in open-air drug markets, where such markets exist. Hallucinogens and exotic, designer and other less popular drugs are rarely available in these settings. They simply do no appeal to enough users to make them profitable for drug traffickers to supply. Ketamine has always been in this second group. Why? </p>
<h2>Is it addictive?</h2>
<p>Ketamine is short-acting – between two and four hours – and produces euphoria, sustained pain relief and sedation mixed with powerful hallucinogenic effects. Taking this drug can be very unpleasant. Out-of-body experiences, time perception distortions, tunnel vision and dissociation are common. These effects limit the popularity of ketamine and make it difficult to use habitually. </p>
<p>A person can take heroin everyday and function. Ketamine is disruptive. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/260022/original/file-20190220-148509-1axr5uy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/260022/original/file-20190220-148509-1axr5uy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/260022/original/file-20190220-148509-1axr5uy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/260022/original/file-20190220-148509-1axr5uy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/260022/original/file-20190220-148509-1axr5uy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/260022/original/file-20190220-148509-1axr5uy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/260022/original/file-20190220-148509-1axr5uy.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">Esketamine is taken as a nasal spray.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/closeup-unrecognizable-woman-who-about-use-93785065?src=tAWHeLRQhRCZyjQNDBATgA-1-36">Kirill Linnik/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Another reason that ketamine isn’t popular on the street is that users do not have to keep using it to avoid withdrawal. There is no withdrawal syndrome associated with ketamine; when people stop using it, they do not get sick. This is actually a benefit, because fear of withdrawal is often a major motivation for the continuation of drug use. Unlike street drugs, its appeal is limited and its addiction liability is comparatively low. </p>
<p>On balance, the profile of ketamine is more like <a href="https://www.drugs.com/illicit/lsd.html">LSD</a> than cocaine or opioids. People do not get addicted. This does not mean that ketamine or esketamine is safe. Its access should be restricted and use monitored by a physician. The manufacturer is placing important restrictions on the drug. It will not be available at local pharmacies and never for take-home use. A person receiving the treatment, which was developed by Johnson & Johnson and delivered as a nasal spray, will be under observation and care of a health professional trained in the therapy. The drug will be given in an office or approved health center, and the patient will not be allowed to drive until the day after treatment. </p>
<p>Given its effectiveness and the proposed risk evaluation and mitigation strategy, the benefits outweigh the risks of esketamine for the treatment of depression that has not responded to other treatments. Like any new treatment, as manufacturers make this product available, monitoring it will be important to make sure the benefits outweigh the costs. People living with the misery of treatment-resistant depression need more options, and this drug should help.</p><img src="https://counter.theconversation.com/content/111966/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lee Hoffer receives funding from the National Institutes of Health, National Institute on Drug Abuse, to fund his research. </span></em></p>A safety committee convened by the FDA has declared esketamine safe for severe depression. But isn’t this drug the same as ketamine, an illegal street drug? A medical anthropologist explains.Lee Hoffer, Associate Professor of Anthropology; Professor of Psychiatry, Case Western Reserve 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/980712018-06-12T16:31:12Z2018-06-12T16:31:12ZMind molding psychedelic drugs could treat depression, and other mental illnesses<figure><img src="https://images.theconversation.com/files/222661/original/file-20180611-191959-1xq0kl3.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/image-illustration/cpu-mind-series-design-made-human-704693527">By agsandrew/shutterstock.com</a></span></figcaption></figure><p>It seems that psychedelics do more than simply alter perception. According to <a href="https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30755-1">the latest research</a> from my colleagues and me, they change the structures of neurons themselves.</p>
<p>My <a href="https://www.olsonlab.org/">research group</a> has been studying the effects of psychedelics on neuronal structure and function, and we found that these compounds cause neurons to grow. A lot. Many of these compounds are well-known and include lysergic acid diethylamide (LSD), psilocin (from magic mushrooms), <em>N,N</em>-dimethyltryptamine (DMT, from ayahuasca) and 3,4-methylenedioxymethamphetamine (MDMA, aka ecstasy).</p>
<p>These are among the most powerful drugs known to affect brain function, and <a href="http://dx.doi.org/10.1016/j.celrep.2018.05.022">our research</a> shows that they can alter the structure of the brain as well. Changes in neuronal structure are important because they can impact how the brain is wired, and consequently, how we feel, think and behave.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/v0g9jf6GqEE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>Prior to our study, there were relatively few compounds known to have such drastic and rapid effects on neuronal structure. One of those compounds was ketamine – a dissociative anesthetic and <a href="http://doi.org/10.1126/science.1190287">quite possibly the best fast-acting antidepressant</a> that we have available to us at the moment.</p>
<p>If you think of a neuron like a tree, then its dendrites would be the large branches, and its dendritic spines – which receive signals from other neurons – would be the small branches. Some of these small branches might have leaves, or synapses in the case of a neuron. In fact, neuroscientists often use terms like “arbor” and “pruning” much like a horticulturist would. When we grew neurons in a dish – which is not unlike growing a plant in a pot – and fed them psychedelic compounds, the neurons sprouted more dendritic branches, grew more dendritic spines, and formed more connections with neighboring neurons.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/222616/original/file-20180611-191971-1jg989x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/222616/original/file-20180611-191971-1jg989x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=448&fit=crop&dpr=1 600w, https://images.theconversation.com/files/222616/original/file-20180611-191971-1jg989x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=448&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/222616/original/file-20180611-191971-1jg989x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=448&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/222616/original/file-20180611-191971-1jg989x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=563&fit=crop&dpr=1 754w, https://images.theconversation.com/files/222616/original/file-20180611-191971-1jg989x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=563&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/222616/original/file-20180611-191971-1jg989x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=563&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The rainbow-colored neuron was treated with LSD, while the purple neuron was the control. LSD altered the structure of the neuron, allowing it to grow more branches and develop a more complex structure.</span>
<span class="attribution"><span class="source">Calvin Ly and Joanne Ly</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Rethinking depression</h2>
<p>Thanks to <a href="http://doi.org/10.1038/nm.4050">studies on ketamine, slow-acting antidepressants and chronic stress models of depression</a>, scientists now know that depression is not simply the result of a “chemical imbalance,” as pharmaceutical companies like to suggest. It is far more complicated and <a href="http://doi.org/10.1038/nm.4050">involves structural changes in key neural circuits that regulate emotion, anxiety, memory and reward</a>.</p>
<p>One of the hallmarks of depression is the <a href="http://doi.org/10.1016/j.ceb.2011.09.002">atrophy of neurons in the prefrontal cortex</a> – a region of the brain that controls anxiety and regulates mood among other things. Basically, these branches and spines shrivel up, disconnecting from other neurons in the brain. One hypothesis for why ketamine is so effective is because it can rapidly regrow the arbors and spines of these critical neurons.</p>
<p>Like ketamine, psychedelics have shown promise in the clinic for treating neuropsychiatric diseases. The DMT-containing herbal tea known as ayahuasca produces <a href="http://dx.doi.org/10.1590/1516-4446-2014-1496">fast-acting antidepressant effects within a day</a>, <a href="http://doi.org/10.1001/archgenpsychiatry.2010.116">psilocybin eases the anxiety of terminally ill cancer patients</a> and <a href="http://doi.org/10.1177/0269881112456611">MDMA can reduce fear in those suffering from post-traumatic stress disorder</a> (PTSD). Our <a href="https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30755-1">recent</a> <a href="http://doi.org/10.1021/acschemneuro.8b00134">papers</a> suggest the intriguing possibility that psychedelic compounds and ketamine might share a common therapeutic mechanism.</p>
<h2>Psychedelics vs. psychoplastogens</h2>
<p>Strictly speaking, a psychedelic is a “mind-manifesting” drug – a definition that’s open to interpretation. They tend to produce perceptual distortions or hallucinations by activating 5-HT2A receptors. Our research group has found that compounds typically regarded as psychedelics, like LSD and DMT, as well as those that are sometimes called psychedelics, like MDMA, and those that are not usually called psychedelics, like ketamine, are all capable of profoundly impacting neuronal structure. </p>
<p>Our group has coined the term “psychoplastogen” to refer to such compounds, and we believe that these molecules may hold the key to treating a wide variety of brain diseases.</p>
<p>Our studies on neurons grown in dishes, as well as experiments performed using fruit flies and rodents, have demonstrated that several psychoplastogens, including psychedelics and ketamine, encourage neurons to grow more branches and spines. It seems that all of these compounds work by activating mTOR – a key protein involved in cell growth.</p>
<p>The biochemical machinery that regulates mTOR activity is intricate. As we tease apart how psychedelics and other psychoplastogens turn on mTOR signaling, we might be able to engineer compounds that only produce the therapeutic effects on neuronal growth while bypassing pathways that lead to undesired hallucinations.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/222637/original/file-20180611-191962-b7cju8.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/222637/original/file-20180611-191962-b7cju8.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=253&fit=crop&dpr=1 600w, https://images.theconversation.com/files/222637/original/file-20180611-191962-b7cju8.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=253&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/222637/original/file-20180611-191962-b7cju8.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=253&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/222637/original/file-20180611-191962-b7cju8.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=318&fit=crop&dpr=1 754w, https://images.theconversation.com/files/222637/original/file-20180611-191962-b7cju8.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=318&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/222637/original/file-20180611-191962-b7cju8.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=318&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">This figure shows the effects of three psychedelics and one control (VEH) on cortical neurons. These neurons were treated for 24 hours before being visualized using super-resolution microscopy. The colors represent proteins found in specific locations of the neuron. Orange protrusions from the purple dendrite indicate dendritic spines.</span>
<span class="attribution"><span class="source">Ly et al.</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>The field has known for some time now that <a href="https://doi.org/10.3109/00952990.2016.1170135">psychedelics can produce lasting positive effects on brain function</a>, and it’s possible that these long-lasting changes result from the psychoplastogenic effects of these drugs. If true, this would suggest that psychoplastogens might be used to repair circuits that are damaged in mood and anxiety disorders.</p>
<h2>Panacea or poison?</h2>
<p>Many diseases, such as depression and anxiety disorders, are characterized by atrophy of dendritic branches and spines. Therefore, compounds capable of rapidly promoting dendritic growth, like psychedelics, have broad therapeutic potential. The number of papers demonstrating that psychedelics can produce therapeutic effects continues to grow every year.</p>
<p>However, we should temper our enthusiasm because we do not yet know all of the risks associated with using these drugs. For example, it’s possible that promoting neuronal growth during development could have negative consequences by interfering with the normal processes by which neural circuits are refined. We just don’t know, yet.</p>
<p>Similarly, it is unclear what effects psychoplastogens will have on the aging brain. It’s important to keep in mind that excessive mTOR activation is also associated with a number of diseases <a href="https://doi.org/10.1016/j.neuron.2014.07.040">including autism spectrum disorder</a> (ASD) and <a href="https://doi.org/10.2147/NDT.S75717">Alzheimer’s disease</a>.</p>
<p>To me, it’s obvious that we need to understand how these powerful compounds affect the brain, in both positive and negative ways, if we hope to fully comprehend the fundamental laws governing how the nervous system works and how to fix it when it doesn’t.</p><img src="https://counter.theconversation.com/content/98071/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David E. Olson receives funding from the NIH. </span></em></p>Psychedelic drugs have inspired great songs and works of art. But they may also have potential for treating disease like depression and PTSD by helping to regrow damaged regions of the brain.David E. Olson, Assistant Professor, Department of Chemistry; Department of Biochemistry & Molecular Medicine; Center for Neuroscience, University of California, DavisLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/939782018-04-01T20:28:40Z2018-04-01T20:28:40ZDrug use can have social benefits, and acknowledging this could improve rehabilitation<figure><img src="https://images.theconversation.com/files/212413/original/file-20180328-109207-i3y096.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Young people have reported cultural gains from drug use, such as strengthening social ties and gaining access to social networks.</span> <span class="attribution"><span class="source">from www.shutterstock.com</span></span></figcaption></figure><p>Illicit drug use is <a href="http://www.ijdp.org/article/S0955-3959(11)00089-2/fulltext">often framed</a> in terms of risk and antisocial or criminal behaviour. But drug use is often a highly social activity. For many people, the pleasure of using drugs is about social connection as much as it is about the physical effects. </p>
<p><a href="http://www.publish.csiro.au/sh/Fulltext/SH17151">A new study</a> aiming to understanding the social benefits of drug use may help us to improve responses to risky or harmful drug taking.</p>
<h2>Pleasure is not just physical</h2>
<p>Pleasure is an obvious part of drug use and the <a href="https://adf.org.au/insights/why-do-people-use-alcohol-and-other-drugs/">short-term physical benefits</a> are well known. Drugs can produce a “high”, give people energy, make them feel good, reduce stress and aid sleep.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-ghb-a-party-drug-thats-easy-to-overdose-on-but-was-once-used-in-childbirth-73266">Weekly Dose: GHB, a party drug that's easy to overdose on but was once used in childbirth</a>
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<p>The social benefits of drug use are more complex to quantify. But there are now numerous studies showing people use <a href="https://www.psychologicalscience.org/news/alcohol-is-a-social-lubricant-study-confirms.html">alcohol</a> or <a href="http://journals.sagepub.com/doi/abs/10.1177/009145090903600109">other drugs</a> in social settings such as bars, clubs and parties to enhance their interactions with others through increased confidence, greater sociability and less anxiety. For some people this leads to <a href="https://www.tandfonline.com/doi/pdf/10.1080/13676260600983668?needAccess=true">longer-term benefits</a> such as stronger bonds with friends.</p>
<p>This was shown in <a href="https://theconversation.com/what-do-young-people-gain-from-drug-use-18878">recent Australian studies</a> where young people reported cultural gains from drug use, such as strengthening social ties and gaining access to social networks that offered a form of cultural capital.</p>
<h2>The social benefits of drug use</h2>
<p>“<a href="https://www.racgp.org.au/download/documents/AFP/2010/August/201008frei_partydrugs.pdf">Party drugs</a>” are those which, as the name suggests, are generally used in a dance party or nightclub setting. This set of drugs often includes MDMA (ecstasy), cocaine, ketamine, gamma hydroxybutyrate (GHB), methamphetamine (speed) or crystal methamphetamine (crystal meth or ice). </p>
<p><a href="https://www.tandfonline.com/doi/abs/10.1080/16066350801983681">Studies</a> have shown people generally use party drugs to give them energy, help them socialise and have fun. </p>
<p>At La Trobe University, we recently conducted a <a href="http://www.publish.csiro.au/sh/Fulltext/SH17151">study</a> which explored party drug use – including use of crystal meth – among Australian gay and bisexual men who are living with HIV. Consistent with what we know about <a href="http://europepmc.org/abstract/med/12717048">party-drug use</a>, we found the men in our study almost always used party drugs socially – at nightclubs and dance parties or to facilitate sexual pleasure. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/212414/original/file-20180328-109175-mceyeq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/212414/original/file-20180328-109175-mceyeq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/212414/original/file-20180328-109175-mceyeq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/212414/original/file-20180328-109175-mceyeq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/212414/original/file-20180328-109175-mceyeq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/212414/original/file-20180328-109175-mceyeq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/212414/original/file-20180328-109175-mceyeq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/212414/original/file-20180328-109175-mceyeq.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 generally use party drugs to give them energy, help them socialise and have fun.</span>
<span class="attribution"><span class="source">Stephen Arnold Unsplash</span></span>
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<a href="https://theconversation.com/we-cant-eradicate-drugs-but-we-can-stop-people-dying-from-them-54636">We can't eradicate drugs, but we can stop people dying from them</a>
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<p>More surprisingly, we also found men who were occasional or regular users of party drugs reported significantly better social outcomes than non-users on a range of measures including a higher level of resilience, less experience of HIV-related stigma, and a greater sense of support from other people living with HIV as well as from their gay and bisexual friends. </p>
<p>This is important because all of these outcomes are strongly associated with <a href="https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-016-0154-z">greater emotional well-being</a> among people living with HIV. </p>
<p>We are not claiming this study shows drug-use (in any form) has a direct impact on longer-term well-being. It’s also possible people who are resilient and <a href="http://journals.sagepub.com/doi/abs/10.1177/0022146510395026">socially connected</a> are more likely than others to be part of social circles in which drug use is common. </p>
<p>But this study does encourage us to consider the social losses some people might encounter if they stop drug use. <a href="http://psycnet.apa.org/buy/1995-29052-001">Friendship, connection, intimacy</a> and sex are fundamental to humanity. If these are strongly tied to the social circles in which a person consumes drugs, their social and emotional well-being may suffer if they cease drug use. </p>
<p>For people living with HIV, who may have experienced <a href="https://www.tandfonline.com/doi/abs/10.1080/09540121.2011.613910">HIV-related stigma</a> or rejection by sexual partners, access to social and sexual networks in which they feel accepted may be part of the appeal of party drugs. </p>
<h2>How this can help responses to drug use</h2>
<p>Research that explores people’s social experiences of drug use can usefully inform harm minimisation or drug cessation programs. </p>
<p>While the physical effects of a drug may pose risks, the social settings in which drugs are consumed are not necessarily damaging or dangerous. In fact, they may be quite the opposite, providing a source of friendship, support and happiness for users.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-ecstasy-the-party-drug-that-could-be-used-to-treat-ptsd-55149">Weekly Dose: ecstasy, the party drug that could be used to treat PTSD</a>
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<p>It might be tempting to denounce this with the assertion that the potential health risks undermine any claims to benefit – or that friendships generated through drug use are not genuine. But sense of community and friendship has been successfully harnessed in drug and alcohol harm minimisation campaigns such as the “<a href="https://www.smh.com.au/lifestyle/life-and-relationships/schoolies-urged-to-look-after-their-mates-20171118-p4yx2r.html">Take Care of Your Mates</a>” campaigns directed toward young people. </p>
<p>Focusing on <a href="https://www.tandfonline.com/doi/pdf/10.1080/13691050600783320?needAccess=true">the social settings in which drug use occurs</a> may also be useful for strategies to reduce other risks. For example, <a href="http://www.starobserver.com.au/features/in-depth-features/heat-moment-chemsex-sex-venues/154631">campaigns</a> to promote safer sex among gay men who use crystal meth have focused on venues and parties where “sex on drugs” is common. </p>
<p>Understanding the potential social benefits of drug use may also enhance drug rehabilitation programs. Strategies to help people rebuild social ties, friendships and support networks could be important in supporting long term cessation of drug use.</p><img src="https://counter.theconversation.com/content/93978/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer Power receives funding for research from The Australian Department of Health and ViiV Healthcare. She has previously received funding from the Australian Research Council. Jennifer's research cited in this article was wholly funded by the Australian Department of Health. </span></em></p>A new study among gay and bisexual men living with HIV found those who were occasional or regular users of party drugs reported significantly better social outcomes than non-users.Jennifer Power, Senior Research Fellow at the Australian Research Centre in Sex, Health and Society, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/814682017-08-02T04:19:35Z2017-08-02T04:19:35ZWeekly Dose: anaesthetic and recreational drug ketamine could be used to treat depression<figure><img src="https://images.theconversation.com/files/180472/original/file-20170801-5515-ouj9td.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A small number of people, who probably use other party drugs, use ketamine recreationally. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p><a href="http://www.drugs.health.gov.au/internet/drugs/publishing.nsf/content/other4">Ketamine hydrochloride</a> is an anaesthetic that causes people to feel disconnected from their bodies. At low doses, they remain conscious and can talk but do not feel pain. At higher doses, ketamine is used to induce a trance-like state or sedate people with burns or other traumatic injuries. </p>
<p>The drug can be used to perform short operations, particularly on children who are allergic to other drugs. Vets also use ketamine as an anaesthetic.</p>
<p>A small number of people, usually those who also use other party drugs, use ketamine as <a href="https://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/TR.111.pdf">a recreational drug</a>. Recreational users are seeking the relaxed and disconnected feeling it causes, as well as hallucinogenic effects that change sight, sound and touch. People may take ketamine accidentally because it is sold as ecstasy or is mixed with ecstasy.</p>
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<a href="https://images.theconversation.com/files/180489/original/file-20170801-5515-1vekddk.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/180489/original/file-20170801-5515-1vekddk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/180489/original/file-20170801-5515-1vekddk.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=745&fit=crop&dpr=1 600w, https://images.theconversation.com/files/180489/original/file-20170801-5515-1vekddk.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=745&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/180489/original/file-20170801-5515-1vekddk.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=745&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/180489/original/file-20170801-5515-1vekddk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=937&fit=crop&dpr=1 754w, https://images.theconversation.com/files/180489/original/file-20170801-5515-1vekddk.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=937&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/180489/original/file-20170801-5515-1vekddk.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=937&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<p>In Australia, ketamine is a <a href="https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=pi&q=ketamine">Schedule 8</a> or controlled drug sold as Ketamine APOTEX, Ketalar or Ketamine-Claris. <a href="http://www.petplace.com/article/drug-library/library/prescription/ketamine-ketaset-vetalar-vetaket">For animals</a>, it’s sold as Ketaset, Vetalar and Vetaket. </p>
<p>Ketamine is produced as liquid in small bottles for medical use. The liquid is evaporated for recreational use to make a white powder that is snorted, swallowed, or dissolved in water and injected.</p>
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Read more:
<a href="https://theconversation.com/a-short-history-of-anaesthesia-from-unspeakable-agony-to-unlocking-consciousness-74748">A short history of anaesthesia: from unspeakable agony to unlocking consciousness</a>
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<h2>A brief history of ketamine</h2>
<p>Ketamine was <a href="http://www.cesar.umd.edu/cesar/drugs/ketamine.asp">discovered in 1962</a> and approved for use in the United States as a battlefield anaesthetic during the Vietnam war.</p>
<p>Calvin L. Stevens, a professor of chemistry at Wayne State University, made ketamine when he was <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126726/">conducting research on phencyclidine</a> – an anaesthetic also known as angel dust, which worked well but caused hallucinations in people as they woke up. <a href="https://www.ncbi.nlm.nih.gov/pubmed/27965560">Ketamine was named CI-581</a> and was one-tenth as strong as phencyclidine. </p>
<p>After research on animals, ketamine was tested on human prisoners in 1964 and 1965. Guenter Corssen, a professor of anaesthetics, <a href="http://journals.lww.com/anesthesia-analgesia/Citation/1971/05000/Computerized_Evaluation_of_Psychic_Effects_of.26.aspx">conducted experiments on CI-581</a> using prisoners who had volunteered. He found it was a fast-acting anaesthetic that wore off quickly. </p>
<p>Corssen reported that some of the men it was tested on had hallucinations. These included thinking they had died, their arms and legs had been cut off, or they had been to outer space. Some refused to continue in the research. Corssen was the first to call ketamine <a href="https://www.ncbi.nlm.nih.gov/pubmed/20693870">a dissociative anaesthetic</a>, meaning it causes you to feel disconnected from your body. </p>
<p>Ketamine is now on the World Health Organisation’s <a href="http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1">list of essential drugs</a> as an anaesthetic. Ketamine is complicated to make, so is not made illegally. Drug companies manufacture it for medical and veterinary treatment.</p>
<h2>Who uses ketamine?</h2>
<p>Ketamine started being used as a recreational drug in the 1970s because of its dissociative and hallucinogenic effects. But not many people use ketamine. <a href="http://www.aihw.gov.au/alcohol-and-other-drugs/data-sources/ndshs-2016/key-findings/?platform=hootsuite">Use in the past 12 months</a> is reported to be around 0.4% of the Australian population. Only 1.7% ever use ketamine in their lifetime. Lifetime use has doubled since 1999, suggesting greater availability of ketamine for those who want to try it. </p>
<p><a href="http://www.who.int/medicines/areas/quality_safety/4.3KetamineCritReview.pdf">Most people using ketamine</a> will be health or medical professionals who can get it in their workplace, or people in the dance club culture <a href="http://www.drugtrends.org.au/reports/2016-idrs-edrs-key-findings-drug-trends-conference-handout/">who are likely to use other drugs</a>.</p>
<h2>Effects and risks</h2>
<p><a href="http://www.who.int/medicines/areas/quality_safety/4.3KetamineCritReview.pdf">Studies conducted in the 1990s</a> found ketamine caused the same symptoms as schizophrenia – unusual thoughts, hallucinations, trouble explaining things (disorganised speech), emotional withdrawal and difficulty moving. </p>
<p>The effects of ketamine are <a href="http://steinhardt.nyu.edu/appsych/chibps/ketamine">related to the amount taken</a>. A dose of 1-2mg per kilogram of body weight produces an intense experience lasting about one hour. Effects start in less than five minutes if injected, or 30 minutes if swallowed. The effects last about one hour, with all effects wearing off after two to three hours.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/180490/original/file-20170801-12621-1g0a4w8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/180490/original/file-20170801-12621-1g0a4w8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/180490/original/file-20170801-12621-1g0a4w8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=966&fit=crop&dpr=1 600w, https://images.theconversation.com/files/180490/original/file-20170801-12621-1g0a4w8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=966&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/180490/original/file-20170801-12621-1g0a4w8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=966&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/180490/original/file-20170801-12621-1g0a4w8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1214&fit=crop&dpr=1 754w, https://images.theconversation.com/files/180490/original/file-20170801-12621-1g0a4w8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1214&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/180490/original/file-20170801-12621-1g0a4w8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1214&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">Ketamine has reportedly been used as a date rape drug.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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<p>Larger doses of ketamine cause an anaesthetic effect, or what recreational users refer to as a “K-hole”. A K-hole is generally reached when the user is nearly fully sedated and is described as similar to an out-of-body or near-death experience.</p>
<p><a href="http://www.cesar.umd.edu/cesar/drugs/ketamine.asp">High doses of ketamine</a> can cause breathing problems, muscle twitches, dizziness, slurred speech, nausea and vomiting. People may be injured because of problems with balance, numbness, muscle weakness and poor vision. Probably due to its anaesthetic properties, ketamine has been reported as a “date rape” drug.</p>
<p>There are few reports of overdose or death from ketamine. Dosage is controlled in medical settings according to body weight, and recreationally people tend to use less. The greatest risk is when ketamine is combined with alcohol or other central nervous system depressants, such as opioids or benzodiazepines, which can affect breathing and <a href="http://www.telegraph.co.uk/news/uknews/law-and-order/10633700/Ketamine-death-of-public-schoolgirl-an-act-of-stupidity-which-destroyed-family.html">cause death</a>.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-valium-the-safer-choice-that-led-to-dependence-and-addiction-59824">Weekly Dose: Valium, the 'safer choice' that led to dependence and addiction</a>
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<p>Ketamine-related deaths can be because of accidents while affected. An example would be <a href="https://www.maps.org/images/pdf/books/K-DreamsKJansenMAPS.pdf">drowning in a bath</a> after taking ketamine and losing consciousness.</p>
<h2>Possible future uses</h2>
<p>Even though it’s a nervous system depressant, ketamine stimulates circulation. This means it doesn’t cause low blood pressure like most anaesthetics, making it useful for <a href="https://www.ncbi.nlm.nih.gov/pubmed/1139377">treating people with head injuries</a>. </p>
<p>Ketamine has been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243034/">used as an antidepressant</a> for people with treatment-resistant depression. A low dose of ketamine is given intravenously, with patients reporting effects in two hours that lasted one or two weeks. Although the quality of the evidence supporting positive effects is generally low, initial studies have resulted in interest because ketamine works quickly and appears to <a href="https://www.ncbi.nlm.nih.gov/pubmed/28249076">work on different receptors</a> to traditional antidepressants.</p>
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Read more:
<a href="https://theconversation.com/special-k-ketamines-road-from-tranquilliser-to-possible-antidepressant-8766">Special K: ketamine's road from tranquilliser to possible antidepressant </a>
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<p>Ketamine is not approved for the treatment of depression, so this is an off-label use. From June this year a nasal-spray form of ketamine (<a href="http://adisinsight.springer.com/drugs/800037644">esketamine</a>) started clinical trials for treatment of depression.</p>
<p>Australia is conducting the world’s largest study of ketamine as a treatment for depression. A trial of regular ketamine injections <a href="https://www.blackdoginstitute.org.au/news/news-detail/2017/07/24/world-first-ketamine-trial-shows-promise-for-geriatric-depression">helped older people</a> with depression feel less depressed, with about half reporting no depression six months later. But the researchers are cautious about the results because only 16 people participated in the trial.</p>
<p>Another <a href="https://www.blackdoginstitute.org.au/news/news-detail/2016/08/16/world-s-largest-trial-of-ketamine-to-treat-depression-begins">trial is under way</a> with different age groups of people who have tried other treatments that have not reduced their depression.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/28249076">Evidence is still limited</a> on ketamine’s effect on depression, the side effects, length of time it is safe to use and if tolerance to the drug will become a problem for people who use it.</p><img src="https://counter.theconversation.com/content/81468/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julaine Allan has received funding from NHMRC, ARC, RIRDC and NSW Health to undertake research related to drug and alcohol use and treatment.</span></em></p>At higher doses ketamine is used to induce a trance-like state, sedate people with burns or other traumatic injuries, or as an anaesthetic to perform short operations.Julaine Allan, Senior Research Fellow, Charles Sturt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/645502016-09-21T05:35:23Z2016-09-21T05:35:23ZWeekly Dose: LSD – dangerous, mystical or therapeutic?<figure><img src="https://images.theconversation.com/files/137514/original/image-20160913-19269-rtw2nj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">LSD causes euphoria, increased body temperature and hallucinations where some or all of the senses are distorted.</span> <span class="attribution"><span class="source">from shutterstock.com</span></span></figcaption></figure><p>Lysergic acid diethylamide (LSD) is a synthetic chemical made from a substance found in a fungus that grows on rye and other grains, called <a href="https://en.wikipedia.org/wiki/Ergot">ergot</a>.</p>
<p>In 1943, Swiss scientist Albert Hofmann – who was interested in the medicinal properties of plants – <a href="http://www.drugscience.org.uk/drugs-info/lsd/">altered a molecule in the fungus</a> hoping to create something that would stimulate blood circulation. But by testing the compound on himself, he discovered <a href="http://www.maps.org/news-letters/v06n3/06346hof.html">he had created a hallucinogen</a> instead.</p>
<p>Today, LSD is an illicit substance used recreationally for its hallucinogenic effects.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/137902/original/image-20160915-30608-1574br2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/137902/original/image-20160915-30608-1574br2.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=870&fit=crop&dpr=1 600w, https://images.theconversation.com/files/137902/original/image-20160915-30608-1574br2.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=870&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/137902/original/image-20160915-30608-1574br2.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=870&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/137902/original/image-20160915-30608-1574br2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1093&fit=crop&dpr=1 754w, https://images.theconversation.com/files/137902/original/image-20160915-30608-1574br2.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1093&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/137902/original/image-20160915-30608-1574br2.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1093&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
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</figure>
<h2>How is it used?</h2>
<p>LSD is a white powder with no smell. A <a href="http://www.drugscience.org.uk/drugs-info/lsd/">tiny amount is mixed with liquid</a> and soaked into blotting paper, sugar cubes, gelatine squares and tiny pills called microdots; or squeezed out of a dropper and swallowed; or held under the tongue.</p>
<p>LSD takes 30 to 60 minutes <a href="http://www.druginfo.adf.org.au/drug-facts/lsd#references">to have an effect</a>, which is called a trip. A trip can last from four to 12 hours and is characterised by feelings of euphoria, increased body temperature and hallucinations, where some or all of the senses are distorted. Time may seem to pass slowly or quickly, colours are enhanced, smells are stronger and <a href="https://www.drugabuse.gov/publications/drugfacts/hallucinogens">thoughts are intense</a>. </p>
<p>A trip can be positive or negative. A bad trip can include overwhelming memories of traumatic experiences, increased anxiety, or fear of people or things in the environment. A person’s mood, the setting and the dose <a href="http://csp.org/psilocybin/HopkinsHallucinogenSafety2008.pdf">will influence the experience</a> of LSD.</p>
<h2>History of use</h2>
<p>During the 1950s and 1960s, LSD was used more for psychotherapy than recreation. Between 1950 and 1965, <a href="https://www.erowid.org/archive/rhodium/chemistry/lsdpatent.html">40,000 people were treated with LSD</a> (under the brand name Delysid) for alcoholism, depression, schizophrenia, autism and homosexuality.</p>
<p>In the United States, psychotherapists <a href="http://www.ncbi.nlm.nih.gov/pubmed/19040555">used low doses of LSD</a> to enhance the standard therapeutic process. In Europe, psychologists used higher doses to induce a mystical experience and emotional release, believing this would reduce anxiety and depression. </p>
<p>Scientific reports on the <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086777/">effectiveness of either approach</a> are limited. </p>
<p>Most LSD-assisted psychotherapy stopped when increased recreational use led to it being made <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086777/">illegal in the United States</a> in 1966. In <a href="https://extranet.who.int/iris/restricted/bitstream/10665/89509/1/WHA20.42_eng.pdf">1967, the World Health Organisation recommended</a> LSD become a controlled substance.</p>
<h2>How does it work?</h2>
<p>Limited research has been conducted into how LSD produces its psychoactive effects. One <a href="http://www.pnas.org/content/109/6/2138.full">study on psilocybin</a>, the hallucinogenic substance in magic mushrooms, found it led to decreased activity and connections in the brain, as well as causing changes in blood flow. The link to blood flow suggests Hofman’s theory about LSD affecting circulation could be true.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/138563/original/image-20160921-12483-1cq5cia.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/138563/original/image-20160921-12483-1cq5cia.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/138563/original/image-20160921-12483-1cq5cia.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=347&fit=crop&dpr=1 600w, https://images.theconversation.com/files/138563/original/image-20160921-12483-1cq5cia.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=347&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/138563/original/image-20160921-12483-1cq5cia.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=347&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/138563/original/image-20160921-12483-1cq5cia.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=436&fit=crop&dpr=1 754w, https://images.theconversation.com/files/138563/original/image-20160921-12483-1cq5cia.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=436&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/138563/original/image-20160921-12483-1cq5cia.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=436&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Limited research has been conducted into how LSD produces its psychoactive effects.</span>
<span class="attribution"><a class="source" href="https://pixabay.com/en/forest-abstract-colorful-forest-764924/#_=_">Pixabay</a></span>
</figcaption>
</figure>
<p>Other scientists have suggested LSD <a href="http://www.nature.com/npp/journal/v21/n1s/full/1395318a.html">affects the brain’s serotonin receptors</a> that regulate moods, appetite, sex drive and perception.</p>
<h2>It it dangerous?</h2>
<p>LSD is not <a href="http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0030437">physically addictive</a>. Tripping on a regular basis, and therefore relying on the drug to have a good time, can lead to psychological dependence.</p>
<p>There have been many reports of phenomena termed <a href="https://askthepsych.com/atp/2009/07/13/dealing-with-lsd-flashbacks/">acid flashbacks</a> – bouts of psychedelic-like perception long after the drug’s effects have work off. Although the flashback is frequently described by people who have used LSD, it has not been well researched or understood. </p>
<p>Except in the case of a pre-existing mental illness, there is <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063972">little evidence of LSD having a negative</a>, long-term impact on mental health. </p>
<p>The biggest risks associated with LSD are accidents and injuries during trips because of distorted perceptions and feelings of immortality that can lead to risk-taking behaviour.</p>
<p>Reports of overdose are rare. In 1973, <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1129381/">eight people were taken to hospital</a> after snorting several milligrams of a powder they thought was cocaine but was actually LSD. They passed out and were hospitalised with high temperatures, internal bleeding and vomiting; although all recovered within 12 hours.</p>
<p>However, a more powerful hallucinogenic sometimes sold as LSD – called 251-NBOMe, 251 or N-bomb – has caused a number of deaths around the world including in <a href="http://www.adelaidenow.com.au/news/south-australia/new-hallucinogenic-drug-25b-nbome-and-25i-nbome-led-to-south-australian-mans-bizarre-death/story-e6frea83-1226472672220">Australia</a>, both from overdose as well as <a href="https://theconversation.com/explainer-what-is-nbome-16950">accidents and injuries</a>. </p>
<h2>How many people use it?</h2>
<p>A <a href="http://www.aihw.gov.au/alcohol-and-other-drugs/ndshs/">survey found that in 2013</a>, around 1.3% of the Australian population, or 299,000 people over 14 years of age, had used a hallucinogen in the previous 12 months. This includes LSD and other drugs that cause hallucinations such as magic mushrooms. </p>
<p>The rate of use has not changed much over time, although it was <a href="http://www.aihw.gov.au/alcohol-and-other-drugs/ndshs/2013/data-and-references/">recorded as 3% of the population</a> in 1998.</p>
<h2>How much does it cost?</h2>
<p>The <a href="https://www.reddit.com/r/Drugs/comments/1dt26w/lsd_prices/?st=isjp00o3&sh=b2609aab">price of a single dose varies</a> between A$5 and A$25. An average dose is thought to be 0.001 of a gram, althoough 20 to 30 micrograms (a millionth of a gram) can produce an <a href="https://www.erowid.org/psychoactives/guides/handbook_lsd25.shtml#11">effect</a>.
Like most illicit drugs, the amount of LSD in a purchased dose is unknown.</p>
<h2>Other points of interest</h2>
<p>A controversial psychologist Timothy Leary was sacked from Harvard University for using LSD in experiments, and recreationally with students. </p>
<p>In response to supply restrictions, in 1967, Leary founded The League for Spiritual Discovery, a religion that claimed LSD as a holy sacrament that should be legal as a religious freedom. United States president at the time, Richard Nixon, <a href="http://www.nytimes.com/1996/06/01/us/timothy-leary-pied-piper-of-psychedelic-60-s-dies-at-75.html">called Leary the most dangerous man</a> in America. </p>
<p>Leary <a href="http://www.csp.org/chrestomathy/realms_of3.html">wasn’t the only one who believed</a> LSD caused religious or mystical experiences. Many people in the 1960s sought such experiences from LSD, and were sometimes called psychonauts.</p>
<p>Aldous Huxley, author of the dystopian novel Brave New World, regularly used and wrote about psychoactive substances such as LSD and mescaline, a cactus-obtained hallucinogen. He thought LSD was <a href="http://www.maps.org/news-letters/v06n3/06346hof.html">valuable for those who didn’t have a talent</a> for visionary experiences; the kinds necessary to produce great works of art.</p>
<p>Indeed, great artists such as The Beatles did a lot to popularise LSD; with their song Tomorrow Never Knows <a href="http://time.com/4435236/revolver-released-50-years-ago/">quoting directly from a book</a> co-authored by Timothy Leary.</p>
<p>Interest in the medical uses of hallucinogens continues. A 2014 study in Switzerland <a href="http://www.maps.org/research-archive/lsd/Gasser-2014-JMND-4March14.pdf">reported</a> participants’ anxiety was reduced following two LSD-assisted psychotherapy sessions.</p>
<p>In Australia, an anaesthetic called ketamine – which causes hallucinations – is being trialled to see if it helps people with <a href="http://www.blackdoginstitute.org.au/public/research/Usingketamineasanantidepressantwaysandmeans.cfm">depression</a>.</p><img src="https://counter.theconversation.com/content/64550/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julaine Allan has received funding from the NHMRC, ARC and RIRDC for the various research projects she has been involved with.</span></em></p>During the 1950s and 1960s, LSD was used more for psychotherapy than recreation. Between 1950 and 1965, many were treated with LSD for alcoholism, depression, schizophrenia, autism and homosexuality.Julaine Allan, Senior Research Fellow, Charles Sturt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/590612016-05-16T13:15:39Z2016-05-16T13:15:39ZKetamine: painkiller, party drug – and possibly next-generation antidepressant<figure><img src="https://images.theconversation.com/files/122715/original/image-20160516-15899-16p64io.jpg?ixlib=rb-1.1.0&rect=0%2C268%2C2560%2C1425&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ketamine crystals could help depression, too.</span> <span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/File:Ketamine_Crystals.jpg">michel1972</a></span></figcaption></figure><p>Ecstasy, methylenedioxy-methamphetamine or MDMA, is well known as a recreational drug today, but its first use was as a <a href="http://bjp.rcpsych.org/content/206/1/4">therapeutic aid</a> for couples attending marriage guidance counselling. LSD, the potent psychedelic popularised by the counter-cultural movements of the 1960s onwards, and <a href="https://www.theguardian.com/science/2016/may/17/magic-mushrooms-lift-severe-depression-in-clinical-trial">psilocybin</a>, found in hallucinogenic mushrooms, have also been studied for their potential in <a href="http://www.popsci.com/science/article/2013-04/new-science-lsd-therapy">treating post-traumatic stress, depression, and alcoholism</a>.</p>
<p><a href="https://theconversation.com/medical-breakthroughs-missed-because-of-pointless-drug-bans-15072">Strict drugs laws make it difficult to research</a> these psychoactive drugs, and clinical research typically lags behind the bold claims of advocates. Ketamine is another drug with a recent history of recreational use, but as it has a longstanding legal pharmaceutical use as an anaesthetic, it is available for research and has in recent years been examined for its anti-depressant effects.</p>
<p>Ketamine, originally called CI-581, was <a href="http://ketamine.com/history-of-ketamine/">first synthesised in 1962</a> and patented for use as an anaesthetic in humans and animals four years later. The drug was used as a battlefield anaesthetic by US forces during the Vietnam War, and is commonly used by vets as an animal tranquilliser.</p>
<p>On August 3, 1964, Edward Domino administered the first intravenous subanesthetic dose of ketamine to a human, <a href="http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1933174">remarking</a>: “I gradually increased the dose from no effect, to conscious but ‘spaced out’, and finally to enough for general anesthesia. Our findings were remarkable!”</p>
<p>From the beginning, clinicians noted that many who were given ketamine described strange experiences such as the feeling of floating in space and something akin to an out-of-body experience – described by today’s recreational users as the “<a href="http://ketamine.com/ketamine-street-names/what-is-a-k-hole-and-how-is-it-dangerous/">K-hole</a>”.</p>
<p>But in the past few years, ketamine has been reborn as an antidepressant. Trials consistently show that it reduces the symptoms of depression, often in the <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243034/">10-20%</a> who have failed to respond to other drug treatments, and in emergency situations, where ketamine can rapidly reduce <a href="http://www.psychiatrist.com/JCP/article/Pages/2016/aheadofprint/15m10056.aspx">suicidal thinking</a> possibly for up to three months. Ketamine has also proved to be a safe, effective and crucially, a rapid way to potentially reduce fear, depression, pain and suffering <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717203/">in the terminally ill</a>. </p>
<p><a href="http://www.ncbi.nlm.nih.gov/pubmed/25847818">Our own meta-analysis</a> of 21 published trials into antidepressant uses for ketamine leaves no doubt as to the drug’s efficacy as a rapid antidepressant, with consistent reports of considerable effects on tackling depressive symptoms. In people diagnosed with major depression, the benefit occurs within four hours following a single dose of the drug. A comparable pattern of responsiveness has also been found for people diagnosed with bipolar depression. By contrast, conventional antidepressants and psychotherapy may take weeks or months to produce any effect.</p>
<p>Such findings have led to ketamine being described as “<a href="http://science.sciencemag.org/content/338/6103/68.full">arguably the most important discovery in half a century</a>”. Despite its promise as an antidepressant, ketamine as a treatment has been slow to take off and met with scepticism. A <a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17998.html">new study published in Nature</a> now offers hope that the unpleasant side effects and hallucinogenic effects of ketamine may be bypassed as the team of researchers from the US have tried to pinpoint the underlying mechanism by which ketamine relieves depression. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/122714/original/image-20160516-15904-6ua3z3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/122714/original/image-20160516-15904-6ua3z3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=468&fit=crop&dpr=1 600w, https://images.theconversation.com/files/122714/original/image-20160516-15904-6ua3z3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=468&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/122714/original/image-20160516-15904-6ua3z3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=468&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/122714/original/image-20160516-15904-6ua3z3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=588&fit=crop&dpr=1 754w, https://images.theconversation.com/files/122714/original/image-20160516-15904-6ua3z3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=588&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/122714/original/image-20160516-15904-6ua3z3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=588&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">SSRI antidepressants such as Prozac bring unwelcome side effects.</span>
<span class="attribution"><span class="source">Michiel1972</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Bypassing side effects</h2>
<p>Ketamine belongs to a class of drugs that block cellular receptors for the neurotransmitter glutamate, an important chemical that is the brain’s chief means of activating neurons. Until now, it was proposed that ketamine’s antidepressant effects were produced by blocking N-methyl-D-aspartic acid (NMDA) glutamate receptors. However, questions about the mechanisms underpinning ketamine’s antidepressive effects remained unanswered. NMDA is largely involved in associative memory and learning, so the link with depression was unclear. Additionally, the beneficial effects of ketamine appear to persist long after the drug has been excreted from the body. </p>
<p>This study suggests that a chemical byproduct the body creates while breaking down ketamine may underpin its rapid antidepressant effect. The authors found that this byproduct, or metabolite, called (2R,6R)-hydroxynorketamine, is responsible for reversing depression-like behaviours in mice. But they found it didn’t elicit the anaesthetic, dissociative psychological effects, nor <a href="https://theconversation.com/classifying-ketamine-what-it-means-if-k-moves-from-c-to-b-21391">the damage to the bladder</a> that is associated with ketamine use. </p>
<p>If this study’s outcomes can be repeated in human subjects, it would mean a massive expansion of the potential uses for the drug, particularly as a treatment for depression. Because the effects of ketamine are relatively short-lived, concerns about side effects, building up a tolerance to the drug, and safety have so far proved a barrier to administering repeated doses of ketamine. This new study goes some way towards addressing those concerns.</p>
<p>The prospect of using ketamine or a derivative of it as an antidepressant is fascinating, especially comparing its effects to psychotherapy or those of common SSRIs antidepressants such as Prozac which can take weeks before antidepressant effects begin to take hold (and even <a href="http://www.sciencedirect.com/science/article/pii/S136466131400237X">increase depressive symptoms in the short term</a>). </p>
<p>But we should not race too far ahead. At present, the antidepressant effects of ketamine have not been examined beyond a two-week window, and this partly reflects the issue of side effects. Until these wrinkles are ironed out, there’s still more work to do before ketamine could emerge as a truly viable mainstream treatment for depression.</p><img src="https://counter.theconversation.com/content/59061/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Keith Laws 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>Ketamine may be the latest recreational drug to find a new legal use.Keith Laws, Professor of Cognitive Neuropsychology, University of HertfordshireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/218152014-01-22T06:47:45Z2014-01-22T06:47:45ZChina’s drug takers are chasing newer highs<figure><img src="https://images.theconversation.com/files/39580/original/gmpsxms8-1390319022.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Younger Chinese revellers are seeking new highs.</span> <span class="attribution"><span class="source">Ding Zhou</span></span></figcaption></figure><p>The close of 2013 saw <a href="http://www.chinasmack.com/2014/stories/3000-police-raid-chinese-meth-cooking-village-in-crackdown.html">a drugs bust</a> of cinematic proportions in China. </p>
<p>Part of Operation Thunder, more than 3,000 armed police with a cavalry of helicopters, motorboats and police dogs busted the village of Boshe’s drug rings, including 18 large gangs and 77 drug-production sites. They seized nearly three tonnes of methamphetamine, 260kg of ketamine and more than 23 tonnes of other raw drug material. </p>
<p>Boshe village and the surrounding city of Lufeng (in the south-eastern province of Guangdong) have long been notorious for drug manufacturing. In 2013 <a href="http://xmzk.xinminweekly.com.cn/News/Content/3195">more than 20%</a> of the families in Boshe were engaged in drug trafficking – directly or by proxy – and it provided a third of the crystal meth in China, up from 14% in 2010.</p>
<p>Synthetic drug manufacturing dens are not uncommon in China. China’s Ministry of Public Security destroyed 326 drug dens in 2012 across 22 Chinese provinces. Among the country’s ten largest narcotics cases in 2012, there were nine cases about manufacturing and trafficking of synthetic drugs. Shanwei and Huizhou cities, also in Guangdong province, and Chengdu city in Sichuan province in particular are making most of the crystal methamphetamine and ketamine in China. </p>
<p>Along with increasing numbers of new synthetic drugs being trafficked into the country from the neighbouring region – <a href="http://www.unodc.org/documents/wdr/WDR_2010/World_Drug_Report_2010_lo-res.pdf">Myanmar especially</a> – the size of the domestic production has been growing rapidly in recent years.</p>
<h2>Synthetic drug use up</h2>
<p>Methamphetamine <a href="https://theconversation.com/breaking-bad-and-crystal-meth-a-chemical-reaction-17477">is a stimulant</a> and gives users sensations including euphoria and alertness but it can also cause compulsive feelings <a href="http://www.independent.co.uk/voices/iv-drip/the-shocking-before-and-after-pictures-of-meth-addicts--warning-disturbing-images-8392937.html">and ravage</a> persistent users. Ketamine is an anaesthetic and it can give users an out of body experience, but over time can damage the kidneys <a href="http://www.bbc.co.uk/news/uk-14200961">and bladder</a>.</p>
<p>Coinciding with the rise in domestic production of synthetic drugs in China, the number of synthetic drug users has also risen sharply. This boom has resulted in more and more new abusers. </p>
<p>In China, drug users are required to register with the local police force. This information is collected in the Narcotics Control Bureau of the Ministry of Public Security. By the end of March last year 40% of registered users had used synthetic drugs, up from as low as 7% in 2005. Estimates also suggest that the majority (about 86%) are under the age of 18. In recent years, more and more Chinese youths select to use synthetic drugs and ice (another name for crystal meth) and <a href="https://theconversation.com/classifying-ketamine-what-it-means-if-k-moves-from-c-to-b-21391">ketamine</a> in bars, at karaoke and other places.</p>
<p>To face the rampant domestic manufacture of synthetic drugs and the rapid rise in users that has accompanied it, a number of steps need to be taken to reduce both the supply and demand.</p>
<h2>A three-step programme</h2>
<p>The Chinese government could give greater attention to reducing the domestic supply of synthetic drugs. China engages with and co-operates with its south-east Asian neighbours on the issue of <a href="http://www.unodc.org/documents/wdr/WDR_2010/World_Drug_Report_2010_lo-res.pdf">drug control</a>, as well as Pakistan, Afghanistan and Russia. </p>
<p>But, given the increase in domestic manufacturing of synthetic drugs, the Chinese government should enforce stricter measures. There are multiple stages where the manufacturing trade can be tackled, from clamping down in the trade of the drugs’ base ingredients <a href="http://www.bbc.co.uk/newsbeat/10353130">such as PMK</a>, to where they are manufactured and then trafficked. </p>
<p>The government should help find alternative economic options for people who manufacture synthetic drugs. Synthetic drugs offer a low cost and high profit business model to citizens. The rise in this illegal economy has come at the expense of the traditional economy of agriculture. Economic support and investment the local infrastructure could be an appropriate response.</p>
<p>Drug education programmes among young people could also be improved. Many young people in China lack awareness of the dangers involved in synthetic drug taking. Young users can feel “high” but not as though they are “addicts”. Their focus is on the entertainment part of taking drugs and there is an ignorance surrounding their long-term health effects. </p>
<p>The public perception of drug addiction was defined around opiates such as opium and heroin, and therefore it conceals the real risk of synthetic drugs. Opiates – though still used, particularly among an older generation – have had sufficient bad press to ensure that people are aware of the dangers and health risks.</p>
<p>To tackle the problem, the Chinese government should conduct targeted research and treatment programmes for synthetic drugs, redefine understanding of addiction beyond opiates and establish better definitions of synthetic drugs – what they are and what is in them.</p><img src="https://counter.theconversation.com/content/21815/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yong-an Zhang is affiliated with David Musto Center for Drug Policy Studies, Shanghai University.</span></em></p><p class="fine-print"><em><span>Shao-zhen Lin receives funding from MOE (Ministry of Education in China) Project of Humanities and Social Sciences (Project No.11YJC840026) and the Science Foundation of Huaqiao University (Project No.13SKBS108).</span></em></p>The close of 2013 saw a drugs bust of cinematic proportions in China. Part of Operation Thunder, more than 3,000 armed police with a cavalry of helicopters, motorboats and police dogs busted the village…Yong-an Zhang, Professor of History, Shanghai UniversityShao-zhen Lin, Associate professor of Sociology, Huaqiao UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/213912013-12-12T06:57:55Z2013-12-12T06:57:55ZClassifying Ketamine – what it means if K moves from C to B<figure><img src="https://images.theconversation.com/files/37483/original/xw3sxsbv-1386762295.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1024%2C722&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Except for medical reasons or if you're a horse.</span> <span class="attribution"><span class="source">The Justified Sinner</span></span></figcaption></figure><p>Sometimes it seems you’ve only got to turn around and there is another drug in the news. Now we are told that ketamine should be upgraded from being a Class C drug <a href="http://news.sky.com/story/1180432/ketamine-dangerous-drug-should-be-class-b">to a Class B drug</a>. Why does this matter?</p>
<p>Ketamine isn’t another “designer drug”, one that is made especially for people to use to obtain a “high”. Instead it was designed by chemists more than half a century ago for use as an anaesthetic. Somewhat ironically, its development followed concerns about the side-effects encountered with another anaesthetic, phencyclidine, better known as PCP or “angel dust”, which became a street drug of abuse, <a href="http://www.bbc.co.uk/radio1/advice/factfile_az/pcp">surfacing in Los Angeles</a> in the 1970s. </p>
<p>Ketamine is used both on humans and animals. It is a very effective anaesthetic and painkiller that has been used safely throughout that period. Unlike other anaesthetics, its use does not result in collapse of airways, which makes it very useful in the field, where it is difficult to administer oxygen, in situations such as battlefields or for victims of traffic accidents. </p>
<p>In low doses it can be used as a local anaesthetic and in some cases can be used alongside opiates as an effective painkiller. It has even put forward as a <a href="http://www.independent.co.uk/life-style/health-and-families/health-news/ketamine-a-cure-for-depression-8198396.html">potential treatment</a> for depression. It’s also the most common substance used to anaesthetise horses – hence it being popularly referred to as a horse tranquiliser.</p>
<h2>Psychotropic effects</h2>
<p>After ketamine came into medical use, it was found that some patients coming round from ketamine-induced anaesthesia experienced psychotropic effects, reporting “near-death” or “out of body” experiences as well as other strange sensations, like floating or flying – sometimes pleasant, sometimes unpleasant. People said they had experienced the feeling of being peaceful and detached from life, of travelling through a dark tunnel only to emerge into a world of light, and even of “seeing God”.</p>
<p>It was therefore not entirely surprising that ketamine was soon being abused in the US, just a few years after it was introduced. Some believe this was due to returning Vietnam veterans who had been treated with the drug. </p>
<p>It has been abused in the UK over the past 20 years – first in the dance scene in the 1990s – and the Home Office estimates that around <a href="http://www.bbc.co.uk/news/uk-25301908">120,000 people</a> now take it each year in England and Wales. The Independent Scientific Committee on Drugs has said recreational use of ketamine appeared to be a growing problem. Although it didn’t call for ketamine to be reclassified, the committee <a href="http://www.bbc.co.uk/news/uk-14200961">suggested in 2011</a> that the drug was wrongly classified as less harmful than ecstasy and cannabis. It is also of increasing concern in other areas of the world <a href="http://www.unodc.org/documents/wdr/WDR_2010/World_Drug_Report_2010_lo-res.pdf">such as Hong Kong</a>.</p>
<p>Drugs often take on street names and while ketamine is often just called “ket”, some refer to it as “special K” – but I certainly wouldn’t recommend it for breakfast.</p>
<h2>Difficult to manufacture</h2>
<p>Ketamine is a <a href="http://www.who.int/medicines/areas/quality_safety/4.3KetamineCritReview.pdf">difficult chemical to manufacture</a>, so there is no risk of it being made in illegal labs in peoples’ kitchens, as with methamphetamine. It seems the ketamine on the market may be obtained mainly from legal manufacturers (especially in Asia or from chemical companies in Europe.</p>
<p>There have been concerns about <a href="http://www.bbc.co.uk/newsbeat/25186316">ketamine abuse</a> for years. Fatalities have resulted, sometimes from combining it with stimulants, for example cocaine or ecstasy, sometimes from combining it with alcohol. </p>
<p>The complication that has recently gained publicity, first recognised about six years ago, is the potential damage caused to the kidneys and bladder. Ketamine-induced ulcerative cystitis <a href="http://www.ketaminebladdersyndrome.com/KBS/Welcome.html">is an emerging disease</a>. Early symptoms include blood in the urine and the need to urinate more frequently than usual, as well as incontinence. Some regular ketamine users have required surgery, sometimes even needing to have their <a href="http://www.bbc.co.uk/news/uk-14200961">bladders removed</a>, meaning that they will never again be able to urinate normally. This is not a problem with therapeutic use of ketamine.</p>
<p>These considerations weighed heavily on the Advisory Council on the Misuse of Drugs, which has suggested to the government that ketamine should be reclassified as a Class B drug, in the same classification as amphetamines, with penalties for its use of, potentially, several years in jail. </p>
<p>They have also suggested that restrictions might be introduced on legal medical use of ketamine, meaning it has to be kept under lock and key, which could present problems. When it comes to investigations into ketamine’s potential to treat depression, it’s in no one’s interest to make potentially important research even <a href="https://theconversation.com/medical-breakthroughs-missed-because-of-pointless-drug-bans-15072">more difficult</a>. </p>
<p>Still, the dangers of misuse have shown this is by no means a safe drug and this is what the government will now need to consider along with the size of the problem. This should involve good research into who takes it, how many take it and how much they take.</p><img src="https://counter.theconversation.com/content/21391/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Simon Cotton 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>Sometimes it seems you’ve only got to turn around and there is another drug in the news. Now we are told that ketamine should be upgraded from being a Class C drug to a Class B drug. Why does this matter…Simon Cotton, Senior Lecturer in Chemistry, University of BirminghamLicensed as Creative Commons – attribution, no derivatives.