tag:theconversation.com,2011:/africa/topics/weekly-dose-25844/articlesWeekly Dose – The Conversation2019-10-02T06:10:04Ztag:theconversation.com,2011:article/1245782019-10-02T06:10:04Z2019-10-02T06:10:04ZWeekly Dose: ranitidine, the heartburn medicine being recalled because of cancer-causing contamination<figure><img src="https://images.theconversation.com/files/295140/original/file-20191002-101488-5qo03y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ranitidine, which works by either neutralising acid or reducing the production of stomach acid, is available in a range of generic and brand name formulations.</span> <span class="attribution"><span class="source">Author photo</span></span></figcaption></figure><p>Ranitidine is a medicine used for the short-term treatment of heartburn. Available in supermarkets and pharmacies, a prescription is only needed when a higher dose of the medicine is required over a longer period of time. </p>
<p>Ranitidine (sold under brand names Zantac, Rani 2, and Ausran) is currently in the news because regulators have found that most formulations are contaminated with a chemical called NDMA, which is as a probable carcinogen. </p>
<p>The drug has been <a href="https://www.health.harvard.edu/blog/popular-heartburn-drug-ranitidine-recalled-what-you-need-to-know-and-do-2019092817911">recalled by the manufacturers</a> in some countries. Two generic brands – <a href="http://apps.tga.gov.au/PROD/SARA/arn-detail.aspx?k=RC-2019-RN-01455-1">Apotex Ranitidine</a> and <a href="http://apps.tga.gov.au/PROD/SARA/arn-detail.aspx?k=RC-2019-RN-01311-1">Sandoz Ranitidine</a> – have been recalled in Australia so far, with <a href="https://www.tga.gov.au/alert/ranitidine">more recalls likely</a>. </p>
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<h2>When was it developed?</h2>
<p>Ranitidine was first reported in the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2043664/pdf/brjpharm00670-0106.pdf">scientific literature in 1976</a>, and became available in 1981. </p>
<p>Peptic ulcer disease had been a significant health issue affecting millions of people around the world and at the time of ranitidine coming to market, approximately <a href="https://www.ncbi.nlm.nih.gov/pubmed/6378441">four million people</a> in the United States had active peptic ulcers, which resulted in 6,000 deaths per year.</p>
<p>At one stage, ranitidine, as sold under the Zantac brand name, was the <a href="https://www.ncbi.nlm.nih.gov/pubmed/10169076">best selling drug in the world</a>. </p>
<p>However, the drug is now off-patent (available in cheap generic formulations) and is included on the World Health Organisation’s (WHO) <a href="https://www.who.int/medicines/publications/essentialmedicines/18th_EML.pdf">list of essential medicines</a> as an anti-ucler medicine.</p>
<h2>How and why is it used?</h2>
<p>Antacids work by either neutralising acid or reducing the production of stomach acid.</p>
<p>Ranitidine reduces the amount of acid produced in the stomach and is part of a larger family of drugs called H2-histamine receptor antagonists.</p>
<p>It is a type of antihistamine, but not the type used for treating allergies. This is because the chemical <a href="https://medlineplus.gov/medlineplus-videos/histamine-the-stuff-allergies-are-made-of/">histamine</a>, although involved in allergic reactions, also stimulates the production of stomach acid. So blocking the effect of histamine also reduces the production of stomach acid. </p>
<p>Ranitidine is commonly used to relieve the symptoms of heartburn and indigestion but has also been used in the past to treat more serious conditions, such as peptic ulcers. </p>
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<img alt="" src="https://images.theconversation.com/files/295166/original/file-20191002-101479-4jq60i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/295166/original/file-20191002-101479-4jq60i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/295166/original/file-20191002-101479-4jq60i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/295166/original/file-20191002-101479-4jq60i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/295166/original/file-20191002-101479-4jq60i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/295166/original/file-20191002-101479-4jq60i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/295166/original/file-20191002-101479-4jq60i.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">Ranitidine reduces the amount of acid produced in the stomach.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1131953912?src=nxBHufddmHLG8QIOSiHXsg-1-16&size=huge_jpg">Dragana Gordic/Shutterstock</a></span>
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<p>In recent times, longer lasting medications called proton pump inhibitors, that are more effective at reducing acid production, have largely replaced ranitidine for more serious conditions. </p>
<p>The most common formulations of ranitidine sold in pharmacies are oral tablets. For those patients who have difficulty swallowing, the medicine is also available as effervescent tablets (fast dissolving in a glass of water) and as a pre-prepared oral liquid.</p>
<h2>What’s the link with cancer?</h2>
<p>Ranitidine is currently in the news after the Australian Therapeutic Goods Administration (TGA) <a href="https://www.tga.gov.au/alert/ranitidine">issued an alert</a> stating many formulations of the drug were contaminated with a chemical called <em>N</em>-nitrosodimethylamine, abbreviated as NDMA. This should not be confused with the illegal party drug <a href="https://www.healthdirect.gov.au/mdma-ecstasy">MDMA (ecstasy)</a>, which is a completely different chemical. </p>
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<p>Similar alerts have been issued by the US <a href="https://www.fda.gov/news-events/press-announcements/statement-alerting-patients-and-health-care-professionals-ndma-found-samples-ranitidine">Food and Drug Administration</a>, and <a href="https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/71029a-eng.php">Health Canada</a>.</p>
<p>Contamination of ranitidine formulations is a problem because the World Health Organisation lists NDMA as a <a href="https://www.who.int/water_sanitation_health/dwq/chemicals/ndmasummary_2ndadd.pdf">probable carcinogen</a>, meaning it may cause cancer. </p>
<p>But it’s important to note most people are exposed to NDMA as part of their normal lives. NDMA can be found in cooked and smoked meats, from smoking cigarettes, beer, and even some toiletry and cosmetic products. </p>
<p>It’s not clear how the ranitidine formulations have become contaminated with NDMA. A similar chemical, dimethylamine, is used in the synthesis of ranitidine, and it may be possible some NDMA is created when the drug is made. Alternatively, ranitidine may be broken down, producing NDMA, during storage. </p>
<p>It will be important to determine the source of the contamination if new formulations are to be made free from NDMA.</p>
<p>The response in many countries has been the recall of ranitidine formulations. In the United States, the companies Sandoz and Apotex have voluntarily withdrawn their brands from sale. In Canada, the government has asked companies to stop distributing the medicine. </p>
<p>On September 17, Australia’s <a href="https://www.tga.gov.au/alert/ranitidine">TGA said it anticipated a recall of ranitidine</a> and until then would be working with international regulators and companies to investigate the problem. The TGA also announced it was doing batch testing of products to determine the extent of the contamination in Australia. </p>
<p>Since that announcement two products have been recalled, <a href="http://apps.tga.gov.au/PROD/SARA/arn-detail.aspx?k=RC-2019-RN-01455-1">Apotex Ranitidine</a> and <a href="http://apps.tga.gov.au/PROD/SARA/arn-detail.aspx?k=RC-2019-RN-01311-1">Sandoz Ranitidine</a>, but further recalls and shortages may occur.</p>
<h2>What if you’re currently taking ranitidine?</h2>
<p>If the medicine works for you and you wish to keep taking it, there is <a href="https://www.tga.gov.au/alert/ranitidine">no immediate health risk</a>. The only issue is from long-term use and could mean a possible increase in your risk of cancer later in life. </p>
<p>If you do wish to stop taking ranitidine, your pharmacist or general practitioner will be able to recommend other heartburn medicines that may be effective for you.</p><img src="https://counter.theconversation.com/content/124578/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Associate Professor Wheate in the past has received funding from the ACT Cancer Council, Tenovus Scotland, Medical Research Scotland, Scottish Crucible, and the Scottish Universities Life Sciences Alliance. He is Fellow of the Royal Australian Chemical Institute and a member of the Australasian Pharmaceutical Science Association.</span></em></p><p class="fine-print"><em><span>Andrew Bartlett is a member of the Australian College of Pharmacy</span></em></p>Contamination with the chemical NDMA means long-term use of ranitidine may increase a person’s risk of cancer later in life.Nial Wheate, Associate Professor | Program Director, Undergraduate Pharmacy, University of SydneyAndrew Bartlett, Associate Lecturer Pharmacy practice, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1210972019-07-29T02:38:05Z2019-07-29T02:38:05ZWhat is Ligandrol, the drug swimmer Shayna Jack had in her system?<p>Australian freestyle swimmer Shayna Jack tested positive to the <a href="https://www.wada-ama.org/en/resources/science-medicine/prohibited-list-documents">banned substance</a> Ligandrol in <a href="https://theconversation.com/drafts/121097/edit#">late June</a>, before competing at the <a href="http://www.fina.org/event/18th-fina-world-championships">world swimming championships</a> in South Korea this month. </p>
<p>Jack said she <a href="https://7news.com.au/sport/swimming/shayna-jack-issues-new-statement-over-failed-drug-test-c-370056">did not knowingly take Ligandrol</a> but noted it could be found in contaminated supplements. </p>
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<p>Ligandrol can help repair and build muscles. While it has been studied as a treatment for cancer and other conditions where patients experience muscle weakness and wastage, it is banned for use by professional athletes. </p>
<p>So how long has this drug been around, and how does it work?</p>
<h2>History of Ligandrol</h2>
<p>Ligandrol, which is also known by the development codes LGD-4033 and VK5211 and the name Anabolicum, was initially developed by the company <a href="https://www.ligand.com/">Ligand Pharmaceuticals</a> in the United States. It was <a href="https://patentimages.storage.googleapis.com/19/a8/9e/13c920a3dad32f/WO2009082437A2.pdf">patented in 2009</a>. </p>
<p>The results of the first human clinical trial were published in 2013, where taking <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111291/">Ligandrol was found to increase muscle mass</a> without also putting on fat.</p>
<p>The drug rights have since been licensed to the company <a href="https://www.vikingtherapeutics.com/">Viking Therapeutics</a>. In 2018, it completed a clinical trial which examined <a href="http://ir.vikingtherapeutics.com/2018-10-01-Viking-Therapeutics-Presents-Results-from-Phase-2-Study-of-VK5211-in-Patients-Recovering-from-Hip-Fracture-in-Plenary-Oral-Presentation-at-ASBMR-2018-Annual-Meeting">Ligandrol for people aged over 65 who were recovering from a hip fracture</a>. The results showed patients who took Ligandrol significantly increased their muscle mass and could walk further than patients not on the drug.</p>
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<p>The drug has also been examined for <a href="https://reader.elsevier.com/reader/sd/pii/S2050052118301100?token=DE618D928D8A7ECDEDBA37D3BB4BBB726AFD01C434FC7DE90430B108A4883C4E0EBE70D6B84A52B46128CE84B2FB4DE6">other conditions</a>, including as a possible treatment for cancer-related weight loss, enlarged prostates, for patients who have a diminished function of testes and ovaries, and as a potential cure for breast cancer.</p>
<p>Ligandrol is still considered an experimental drug, and as such, is not approved for sale by the Australian Therapeutic Goods Administration (TGA).</p>
<h2>How Ligandrol works</h2>
<p>Ligandrol is taken orally as a tablet at doses between 0.5 and 2 milligrams. </p>
<p>The drug is what pharmacists call a <a href="https://www.ncbi.nlm.nih.gov/pubmed/30503797">selective androgen receptor modulator</a> (SARM). These drugs bind at specific sites on skeletal muscles. There, they initiate a cascade of processes which change the expression of different genes in the DNA of muscle cells. The end effect is an increase in the repair and growth of muscle.</p>
<p>This means Ligandrol works in a similar way to testosterone and anabolic steroids, although SARMs typically have fewer side effects. The typical side effects of anabolic steriods can include short-term aggression and violence, acne, and sleeping difficulties, and long-term effects such as damage to the liver and kidneys, depression, and high blood pressure.</p>
<p>In contrast, in clinical trials of patients taking Ligandrol, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111291/">the rate of side effects was similar to those in the placebo group</a> and included headache and dry mouth. While clinical trial participants on Ligandrol did have a higher rate of throat infections, it was concluded this was not due to the drug.</p>
<p>Ligandrol <a href="https://onlinelibrary.wiley.com/doi/10.1002/dta.2512">can be detected for up to 21 days</a> in the urine of those who take it.</p>
<h2>In the news</h2>
<p>Because Ligandrol can potentially be used to gain an advantage in competitive sports, the <a href="https://www.wada-ama.org/">World Anti-Doping Agency</a> (WADA) placed the drug on its <a href="https://www.wada-ama.org/en/resources/science-medicine/prohibited-list-documents">prohibited list</a>.</p>
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<p>Shayna Jack’s hypothesis that it must have entered her system through contaminated supplements is not without merit. The TGA regularly bans the import of supposedly natural supplements for <a href="https://www.tga.gov.au/overseas-weight-loss-products">weight loss</a>, <a href="https://www.tga.gov.au/alert/liangzern-dietary-supplements">erectile dysfunction</a>, and body building because they contain prescription-only medicines. </p>
<p>While there have been no instances of body building protein or sports supplements being adulterated with Ligandrol, there are reports of some <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/1541-4337.12173">dietary supplements being spiked with anabolic steroids</a> and similar drugs.</p>
<p>For safety and security, athletes should only use supplements from reputable brands bought from reliable stores in their home country. The risk of accidentally taking a banned substance is significant if an athlete buys supplements online.</p><img src="https://counter.theconversation.com/content/121097/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Associate Professor Wheate is a Fellow and Chartered Chemist of the Royal Australian Chemical Institute and a member of the Australasian Pharmaceutical Science Association.</span></em></p>Ligandrol is used to help repair and build mass and is banned for use by professional athletes because it can give a competitive advantage.Nial Wheate, Associate Professor | Program Director, Undergraduate Pharmacy, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1050472018-11-06T19:10:46Z2018-11-06T19:10:46ZWeekly Dose: quetiapine, the antipsychotic ‘sleeping pill’ linked to overdoses<figure><img src="https://images.theconversation.com/files/244024/original/file-20181106-74778-8bmdrw.jpg?ixlib=rb-1.1.0&rect=0%2C1055%2C4896%2C2198&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Quetiapine is increasingly prescribed a sleeping drug.</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/8cOib7pidak">Mink Mingle</a></span></figcaption></figure><p>Quetiapine is a drug designed to reduce hallucinations and delusions experienced by people with schizophrenia or bipolar disorder. </p>
<p>The most common brand name of quetiapine is Seroquel but it’s also known by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848462/">the slang names</a> quell, Suzi-Q, baby heroin and Q-ball. Q-ball refers to a combination of quetiapine and cocaine, or sometimes heroin. </p>
<p>Quetiapine was developed by the ICI chemical company in England and <a href="http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=4,879,288.PN.&OS=PN/4,879,288&RS=PN/4,879,288">patented in 1987</a>. Scientists were <a href="https://www.nps.org.au/australian-prescriber/articles/are-atypical-antipsychotics-advantageous-the-case-for">trying to find a drug</a> that would help reduce the symptoms of mental illnesses without the distressing side effects caused by the antipsychotics developed in the 1950s. </p>
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<h2>How does it work?</h2>
<p>Quetiapine works by attaching to the brain’s <a href="https://pubchem.ncbi.nlm.nih.gov/compound/5002#section=Top">dopamine receptors</a> and altering serotonin levels. </p>
<p><a href="https://link.springer.com/chapter/10.1007/7854_2015_424">Short-term effects</a> include feeling sleepy, a dry mouth, dizziness and low blood pressure when you stand up. These effects <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848462/">lasts about six hours</a>.</p>
<p>The product information for quetiapine includes a warning not to drink grapefruit juice while taking <a href="https://www.medicines.org.uk/emc/product/5495/pil">the medication</a> because it stops the drug being metabolised in the intestines and could <a href="http://www.epocrates.com/dacc/1301/DrugGrapefruitJuiceBMJ1301.pdf">increase the effects</a> of the drug. </p>
<p>Longer-term effects of quetiapine use include weight gain, high blood sugars and a greater risk of diabetes. </p>
<p>People who take quetiapine regularly will experience <a href="https://link.springer.com/chapter/10.1007/7854_2015_424">withdrawal</a> when they stop. Symptoms include nausea, insomnia, headache, diarrhoea, vomiting, dizziness and irritability. </p>
<h2>Use as a sleeping drug</h2>
<p>Quetiapine is often prescribed by doctors at low doses for things other than mental illness. This is mostly because the main side effect of it is making people <a href="https://www.nps.org.au/australian-prescriber/articles/are-atypical-antipsychotics-advantageous-the-case-for">feel sleepy</a>.</p>
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<p>As doctors have realised that benzodiazepines cause dependence when used regularly, other options to help people sleep or calm down have <a href="https://www.ncbi.nlm.nih.gov/pubmed/26648630">been sought</a> and quetiapine has filled the gap. </p>
<p>Doctors <a href="https://www.ncbi.nlm.nih.gov/pubmed/29712643">report prescribing quetiapine</a> because they were not sure about a patient’s mental health or they had a lot of personal problems.</p>
<p>War veterans are a group who have found quetiapine useful for sleeping. Soldiers first using it reported relief from nightmares and anxiety. Some said it was the first time since returning home from war that they had more than six hours sleep. </p>
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<img alt="" src="https://images.theconversation.com/files/244025/original/file-20181106-74769-t2cnx2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/244025/original/file-20181106-74769-t2cnx2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/244025/original/file-20181106-74769-t2cnx2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/244025/original/file-20181106-74769-t2cnx2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/244025/original/file-20181106-74769-t2cnx2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/244025/original/file-20181106-74769-t2cnx2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/244025/original/file-20181106-74769-t2cnx2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&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">Veterans shouldn’t bypass talking therapies.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/sO6yji4O_FI">Andrik Langfield</a></span>
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<p>However, several deaths related to quetiapine were <a href="https://web.archive.org/web/20130618114129/http:/www.marinecorpstimes.com/article/20100830/NEWS/8300315/Questions-loom-over-drug-for-sleepless-vets">reported in the United States</a>. </p>
<p>Concerns have also been expressed about prescribing quetiapine to Australian soldiers with post-traumatic stress disorder (PTSD) instead of providing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653966/">talking therapies</a>.</p>
<h2>Recreational use</h2>
<p>The reasons people use quetiapine recreationally are the same as for other drugs, for example, they like the effect, it enhances the effect of other drugs, or they want to <a href="https://www-ncbi-nlm-nih-gov.ezproxy.csu.edu.au/pubmed/25216812?dopt=Abstract">experiment</a>. </p>
<p>Other uses include managing the symptoms of withdrawal from other drugs, including helping with <a href="https://www.medscape.com/viewarticle/817961#vp_2">sleep</a>. </p>
<p><a href="https://www.thedailybeast.com/ambien-for-coke-heads">Drug information websites</a> describe quetiapine as good for the “comedown” because it <a href="http://www.bluelight.org/vb/archive/index.php/t-520226.html">puts people to sleep very quickly</a>. </p>
<p>People using amphetamines can regularly experience psychotic symptoms. Quetiapine has been recommended around networks of people who use drugs as helpful way to reduce those symptoms.</p>
<h2>Rising popularity</h2>
<p>Since 1997 when quetiapine was approved in the US, prescribing rates have increased dramatically all over the world. It’s the fifth-biggest selling prescription drug in the US, with sales over <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653966/">US$6 billion</a>.</p>
<p>In Norway, prescriptions for quetiapine have increased over time from 584 in 2004 to 8,506 <a href="https://link.springer.com/article/10.1007%2Fs00228-017-2281-8">in 2015</a>.</p>
<p>In 2010, AstraZeneca – the US pharmaceutical company that makes Seroquel – was <a href="https://www.justice.gov/opa/pr/pharmaceutical-giant-astrazeneca-pay-520-million-label-drug-marketing">fined US$520 million for promoting “off-label” uses of Seroquel</a> to doctors. </p>
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Read more:
<a href="https://theconversation.com/explainer-why-are-off-label-medicines-prescribed-44783">Explainer: why are off-label medicines prescribed?</a>
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<p>This means it was promoted for conditions it was not licensed to treat, such as anger management, anxiety, attention-deficit hyperactivity disorder (ADHD), dementia, depression, mood disorder, PTSD, and sleeplessness. </p>
<p>The company denied the allegations but had to <a href="https://www.genengnews.com/gen-news-highlights/astrazeneca-to-pay-520m-settlement-in-seroquel-lawsuit/78565333">pay the fine</a>. </p>
<h2>Overdose and dependence</h2>
<p>As prescribing of quetiapine has increased, so have <a href="https://www.abc.net.au/7.30/concerns-grow-over-top-selling-drugs-side-effects/5121068">reports of overdose and problems</a> with dependence on the drug. </p>
<p>A <a href="https://www.ncbi.nlm.nih.gov/pubmed/23350582">study of ambulance call outs</a> in Victoria found substantial increases in the number of calls for quetiapine overdoses and that <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/add.12395">most overdoses are in areas</a> with high prescribing rates.</p>
<p>The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444129/">United States Drug Abuse Warning Network</a> reported a 90% increase in quetiapine-related emergency department visits between 2005 and 2011. The people most at risk of overdose were those using other drugs and women.</p>
<p>Men in their mid-thirties are the largest group of non-medical <a href="https://link.springer.com/chapter/10.1007/7854_2015_424">quetiapine users</a> but it’s also common among some teens. A <a href="http://www.justicehealth.nsw.gov.au/publications/2015YPICHSReportwebreadyversion.PDF">NSW Justice Health report</a> found that 16% of 14- and 15-year-olds in juvenile justice centres had used quetiapine they weren’t prescribed.</p>
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Read more:
<a href="https://theconversation.com/explainer-what-is-seroquel-and-should-you-take-it-for-insomnia-42893">Explainer: what is Seroquel and should you take it for insomnia?</a>
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<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348850/">Studies of quetiapine misuse</a> have found most people are using other drugs as well – mostly benzodiazapienes or <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/add.12395">prescription opioids</a>. </p>
<p>A study of people in a substance treatment program found 96% of people had used quetiapine, which they got from doctors or family and friends.</p>
<p>A packet of 60 quetiapine tablets costs A$<a href="http://www.pbs.gov.au/medicine/item/8456C">22</a>-$<a href="http://www.pbs.gov.au/medicine/item/9202H-5458G-9204K-8456C-9205L-8580N-8458E-8457D-9203J">45</a> (A$6.40 concession). In 2015, the street value of one quetiapine <a href="https://link.springer.com/chapter/10.1007/7854_2015_424">tablet was reportedly A$5</a>.</p><img src="https://counter.theconversation.com/content/105047/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julaine Allan has received research funding from NSW Health, NHMRC, Australian Research Council and the Ian Potter Foundation. Julaine is affiliated with Lives Lived Well, a not for profit drug and alcohol treatment, research and training organisation. </span></em></p>Quetiapine is an antipsychotic drug to treat severe mental illness, but it makes people feel sleepy, so has also been used as a sleeping pill – by prescription and illicitly.Julaine Allan, Senior research fellow, Charles Sturt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/960052018-05-04T06:27:24Z2018-05-04T06:27:24ZWeekly Dose: ephylone, the dangerous designer stimulant found at Groovin the Moo<figure><img src="https://images.theconversation.com/files/217702/original/file-20180504-182160-db6oh8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Synthetic cathinones are sometimes sold as “bath salts” or “plant food”, but are intended to be snorted or swallowed for their psychoactive effects.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/782607532?src=Rn8NmLvH7jmO4U_M2b9hsw-2-69&size=huge_jpg">Shutterstock</a></span></figcaption></figure><p>Australia’s first pill testing service was successfully trialled on Sunday at the Groovin the Moo music festival in Canberra. The group <a href="http://www.health.act.gov.au/pilltesting">Safety and Testing and Advisory Service at Festivals and Events</a> tested 128 samples and <a href="http://www.abc.net.au/news/2018-04-30/groovin-the-moo-pill-testing-finds-lethal-product/9710112">identified 85 substances</a>, including paint, toothpaste, and a dangerous drug called ephylone.</p>
<p>While this is the first time ephylone has been detected in Australia, it has been growing in popularity in New Zealand. Festival drug testers from <a href="https://knowyourstuff.nz/2018/02/07/this-summers-crap-drug-n-ethylpentylone/">Know Your Stuff NZ</a> detected ephylone at every event they attended over summer. In March, <a href="https://www.police.govt.nz/news/release/police-issue-warning-about-n-ethylpentylone">13 New Zealanders were hospitalised</a> for ephylone overdoses and <a href="https://www.stuff.co.nz/national/crime/102124143/deadly-new-nethylpentylone-drug-ring-busted-as-police-seize-405k-luxury-cars-and-6kg-of-drugs-in-wellington-sting">police seized six kilograms of the drug</a> worth around NZD$600,000. </p>
<p>Ephylone was also responsible for deaths in <a href="https://www.news24.com/SouthAfrica/News/no-antidote-yet-for-killer-drugs-special-ingredient-20160414">South Africa</a> and the <a href="https://doi.org/10.1093/jat/bky025">the United States</a> in recent years.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-phenibut-the-russian-anti-anxiety-drug-linked-to-gold-coast-teens-overdoses-92339">Weekly Dose: phenibut – the Russian anti-anxiety drug linked to Gold Coast teens' overdoses</a>
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<h2>What type of drug is it?</h2>
<p>Ephylone, also known as <em>N</em>-ethylpentylone and beta-keto-1,3-benzodioxolyl-<em>N</em>-ethylbutanamine (bk-EBDP), is a so-called “new psychoactive substance”. It belongs to the growing class of designer stimulants termed synthetic cathinones. </p>
<p>Synthetic cathinones are sometimes sold as “bath salts” or “plant food”, but are intended to be snorted or swallowed for their psychoactive effects. </p>
<p>According to the <a href="https://www.unodc.org/wdr2017/field/Booklet_4_ATSNPS.pdf">United Nations Office on Drugs and Crime</a>, more than 140 individual cathinone derivatives have been identified as illicit drugs. </p>
<p>Although synthetic cathinones share a common chemical template, the potency, effects, and toxicity of these stimulants can vary enormously. Based on user reports of these substances, some synthetic cathinones produce experiences that are a mix between MDMA (ecstasy) and cocaine, while others are described as being similar to methamphetamine (ice).</p>
<h2>How was it developed?</h2>
<p>Ephylone was first described in a <a href="https://worldwide.espacenet.com/publicationDetails/biblio?CC=GB&NR=1085135&KC=&FT=E&locale=en_EP#">1967 patent</a> by the pharmaceutical firm Boehringer Ingelheim. It was originally designed to treat mild depression and fatigue, and researchers of the time showed that it produced stimulant activity in mice.</p>
<p>No formal scientific study of ephylone has occurred since then, so we can’t be certain about its effects in humans.</p>
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<strong>
Read more:
<a href="https://theconversation.com/flakka-is-a-dangerous-drug-but-it-doesnt-turn-you-into-a-zombie-69533">Flakka is a dangerous drug, but it doesn't turn you into a zombie</a>
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<p>The closest chemical cousins of ephylone, such as <a href="https://doi.org/10.1111/j.1476-5381.2012.02145.x">pentylone</a>, increase levels of the neurotransmitters (brain signalling molecules) dopamine, norepinephrine, and serotonin in cellular tests. Stimulants such as MDMA, cocaine, and methamphetamine can affect these three neurotransmitters to varying extents.</p>
<p>These neurotransmitters are highly involved in the processes underlying mood, arousal, appetite, and addiction. Modulation of the levels of these neurotransmitters in certain brain regions is key to the effects of stimulant drugs, but also clinically useful antidepressants and pharmaceuticals for attention deficit hyperactivity disorder (ADHD).</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/217705/original/file-20180504-153881-1ik3r5h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/217705/original/file-20180504-153881-1ik3r5h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/217705/original/file-20180504-153881-1ik3r5h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/217705/original/file-20180504-153881-1ik3r5h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/217705/original/file-20180504-153881-1ik3r5h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/217705/original/file-20180504-153881-1ik3r5h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/217705/original/file-20180504-153881-1ik3r5h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Ephylone producers similar effects to MDMA but is much stronger.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/489615511?size=medium_jpg">bbernard/Shutterstock</a></span>
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</figure>
<h2>What does it do?</h2>
<p>Although scientists have not yet investigated ephylone specifically, its chemical relative pentylone produces cocaine- and methamphetamine-like effects in rats lasting up to six hours. At higher doses, it causes <a href="https://dx.doi.org/10.1007%2Fs00213-014-3755-3">fatal seizures</a>. <a href="https://www.biorxiv.org/content/early/2017/07/21/166579">Rodent studies</a> also suggest that pentylone and related molecules are likely addictive.</p>
<p>Online user reports posted to the websites <a href="https://erowid.org/experiences/subs/exp_bkEBDP.shtml">Erowid</a> and <a href="https://www.reddit.com/r/researchchemicals/search?q=N-ethylpentylone">Reddit</a> describe the effects of ephylone as euphoric, stimulating, and mildly empathogenic (producing a feeling of emotional openness), similar to MDMA.</p>
<p>As with other stimulants, <a href="https://doi.org/10.1093/jat/bkx004">overdose of ephylone</a> can lead to overheating, dangerous changes to blood acidity, cardiotoxicity, and multiple organ failure.</p>
<h2>How is it sold?</h2>
<p>The active dose of ephylone is unknown, and it is often <a href="https://www.vice.com/en_au/article/vbbexd/all-the-dodgy-stuff-found-in-the-drugs-at-boomtown-this-year-safe-sesh">sold as MDMA</a>, which has a typical dosage of around 100 mg. </p>
<p>According to <a href="https://www.ecstasydata.org/results.php?start=0&search_field=substance&s=n-ethylpentylone">one pill testing website</a>, ephylone capsules have been found to contain anywhere from tens of milligrams to almost half a gram. The variability of ephylone dosages, and its misrepresentation as MDMA, increases the risk of overdose.</p>
<p>Although ephylone was only reported as an illicit drug for the <a href="http://www.emcdda.europa.eu/system/files/publications/4724/TDAN17001ENN_PDFWEB.pdf">first time in 2016</a>, it was the most common cathinone drug in the <a href="https://ndews.umd.edu/sites/ndews.umd.edu/files/ndews_synthetic-drug-threats-in-us-2018-update-jill-head.pdf">United States by 2017</a>, making up more than half of all synthetic cathinone seizures.</p>
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Read more:
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<p>Individual synthetic cathinones appear on the illicit drug market faster than we can comprehensively study them, and are often deceptively sold as other substances; a situation we have seen with other classes of designer drugs such as <a href="https://theconversation.com/labs-make-new-dangerous-synthetic-cannabinoid-drugs-faster-than-we-can-ban-them-47896">synthetic cannabinoids</a> and <a href="https://theconversation.com/fentanyl-and-other-synthetic-opioids-sold-as-counterfeits-in-deadly-new-trend-62814">fentanyl derivatives</a>. </p>
<p>As the recent success of pill testing at Groovin the Moo shows, <a href="https://www.theverge.com/2017/11/8/16619142/designer-drugs-k2-spice-synthetic-weed-ucsf-lab-dea">proactive approaches</a> to the identification and study of new designer drugs can empower governments to respond quickly and effectively to emerging threats while minimising harms to users.</p><img src="https://counter.theconversation.com/content/96005/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Samuel Banister receives funding from the Australian Research Council and the Brain and Mind Centre at The University of Sydney. </span></em></p><p class="fine-print"><em><span>Richard Kevin 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>Ephylone belongs to the growing class of designer stimulants called synthetic cathinones. The effects have been described as a mix between MDMA and cocaine, while others are more similar to ice.Samuel Banister, Team Leader in Medicinal Chemistry, University of SydneyRichard Kevin, Postdoctoral research associate, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/886392018-03-08T19:26:46Z2018-03-08T19:26:46ZWeekly Dose: cocaine, the glamour drug of the ’70s, is making a comeback<figure><img src="https://images.theconversation.com/files/199863/original/file-20171219-27554-4kqhyr.jpg?ixlib=rb-1.1.0&rect=331%2C840%2C5636%2C2916&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In Australia, cocaine is most commonly snorted.</span> <span class="attribution"><span class="source">Ralf Geithe/Shutterstock</span></span></figcaption></figure><p>Cocaine is derived from the <a href="http://anesthesiology.pubs.asahq.org/Article.aspx?articleid=1943164">leaves of the coca plant</a>, which is native to South America. For thousands of years, the leaves were used by the local inhabitants such as the Incas, who chewed or made them into a tea, because of the alertness and energy they provided. </p>
<p>German chemist Albert Niemann eventually isolated the active ingredient in 1859 and it was named cocaine. This <a href="https://www.wiley.com/en-au/Medical+Toxicology+of+Drug+Abuse:+Synthesized+Chemicals+and+Psychoactive+Plants-p-9780471727606">was the beginning</a> of the drug’s use as a medicinal and recreational substance in Western culture.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/209431/original/file-20180308-146666-lm97f3.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209431/original/file-20180308-146666-lm97f3.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/209431/original/file-20180308-146666-lm97f3.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=735&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209431/original/file-20180308-146666-lm97f3.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=735&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209431/original/file-20180308-146666-lm97f3.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=735&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209431/original/file-20180308-146666-lm97f3.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=924&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209431/original/file-20180308-146666-lm97f3.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=924&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209431/original/file-20180308-146666-lm97f3.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=924&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>How many people use it</h2>
<p>Cocaine is the second most commonly used illicit substance in Australia, after marijuana. Reports of <a href="https://www.aihw.gov.au/reports/illicit-use-of-drugs/ndshs-2016-key-findings/contents/illicit-use-of-drugs">cocaine use</a> in the 12 months to June 2017 more than doubled since 2004 – from 1% to 2.5% (or around 170,000 to 500,000 people). </p>
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Read more:
<a href="https://theconversation.com/weekly-dose-cannabis-has-been-used-medicinally-for-millennia-why-is-legalising-it-taking-so-long-56064">Weekly Dose: cannabis has been used medicinally for millennia, why is legalising it taking so long?</a>
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<p>The number of people who have ever used cocaine has had a similar percentage increase – from 4.7% in 2004 to 9% in 2016. Cocaine use <a href="https://www.aihw.gov.au/reports/illicit-use-of-drugs/ndshs-2016-key-findings/report-editions">has reached</a> a 15-year high.</p>
<h2>History and use over time</h2>
<p>Cocaine gained prominence in the 1880s. Sigmund Freud <a href="https://www.wiley.com/en-au/Medical+Toxicology+of+Drug+Abuse:+Synthesized+Chemicals+and+Psychoactive+Plants-p-9780471727606">broadly praised its uses</a>, including in overcoming morphine addiction and treating depression. </p>
<p>Viennese ophthalmologist Carl Koller performed the first operation using <a href="http://anesthesiology.pubs.asahq.org/Article.aspx?articleid=1943164">cocaine as an anaesthetic</a> on a patient with glaucoma, which led to its use as a local anaesthetic. </p>
<p>But, soon after, practitioners began reporting side effects. Cocaine doses were administered at such high concentrations that there were <a href="https://books.google.com.au/books/about/Drug_Use_in_America_Problem_in_Perspecti.html?id=2DFLI2ib-1oC&redir_esc=y">200 cases of intoxication</a> and 13 deaths (in around seven years) as a result.</p>
<p>At the 1912 <a href="https://www.unodc.org/unodc/en/frontpage/the-1912-hague-international-opium-convention.html">Hague International Opium Convention</a> cocaine (and heroin) was added to the drug control treaty as problematic substance. This sparked the introduction of new drug control laws relating to cocaine in various countries.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/209449/original/file-20180308-146703-1w320h6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209449/original/file-20180308-146703-1w320h6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/209449/original/file-20180308-146703-1w320h6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209449/original/file-20180308-146703-1w320h6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209449/original/file-20180308-146703-1w320h6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209449/original/file-20180308-146703-1w320h6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209449/original/file-20180308-146703-1w320h6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209449/original/file-20180308-146703-1w320h6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Crack cocaine is a solid, rock-like version of the drug which can be smoked.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
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<p>Cocaine use decreased after this, but later experienced a surge in popularity in the <a href="http://www.cesar.umd.edu/cesar/drugs/crack.asp">1970s</a>, peaking in the 1980s. During this time, cocaine was associated with celebrities, high rollers and glamorous parties.</p>
<p>Then a new, crystallised form of cocaine (crack cocaine) was developed. Crack cocaine is processed with ammonia or baking soda, producing a solid “rock” version of the drug which could be smoked. </p>
<p>Not only was crack cocaine more potent, but the effects of the drug (typically after smoking) were felt faster. It was also much cheaper, which allowed it to spread quickly into poorer communities. Its use <a href="http://www.columbia.edu/cu/ccbh/souls/vol1no1/vol1num1art4.pdf">became recognised</a> as an “epidemic” around 1985, which lasted for ten years. </p>
<h2>How it works</h2>
<p>The nervous system uses chemicals called <a href="https://qbi.uq.edu.au/brain/brain-physiology/what-are-neurotransmitters">neurotransmitters</a> to communicate. These move across the space between two nerve cells and bind to receptors on the receiving cell. </p>
<p>Neurotransmitters do different things. Dopamine, for instance, is involved in the reward system of the brain. It creates feelings of pleasure and contributes to motor control, reinforcement and motivation. </p>
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Read more:
<a href="https://theconversation.com/explainer-how-do-drugs-work-48665">Explainer: how do drugs work?</a>
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<p>The more neurotransmitters are present in the space between two cells, the more can bind to receptors and have a stronger effect. When the body no longer needs the neurotransmitter in its system, it gets reabsorbed into the cell that released it. This is called re-uptake. </p>
<p>One way to increase the level of a neurotransmitter in the brain is to prevent this re-uptake process from occurring. Cocaine inhibits the re-uptake of dopamine in the brain. The resulting increase in dopamine can cause heightened feelings of pleasure and well-being, among other effects.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/199869/original/file-20171219-27547-13r4z2k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/199869/original/file-20171219-27547-13r4z2k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/199869/original/file-20171219-27547-13r4z2k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/199869/original/file-20171219-27547-13r4z2k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/199869/original/file-20171219-27547-13r4z2k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/199869/original/file-20171219-27547-13r4z2k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/199869/original/file-20171219-27547-13r4z2k.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 coca plant, from which cocaine is derived, is native to South America.</span>
<span class="attribution"><span class="source">Olmez/Shutterstock</span></span>
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</figure>
<p>Some <a href="https://s3.amazonaws.com/academia.edu.documents/54130855/Goodman___Gilmans_The_Pharmacological_Basis_of_Therapeutics__12th_Edition.pdf">evidence suggests</a> cocaine also inhibits the uptake of the stimulant norepinephrine and the mood regulator serotonin.</p>
<p>Nerves also communicate through electrical signals. Cocaine inhibits electrical communication. In this way, it also works as an anaesthetic by blocking communication between peripheral nerve cells. Cocaine produces a numbing effect when applied to mucous membranes such as the mouth, throat and inside the nose. </p>
<h2>How much it costs</h2>
<p>The average price for cocaine is around A$300-$350 per gram. That’s A$50 more per gram than methamphetamine (ice). In 2017, <a href="https://www.globaldrugsurvey.com/">Australia ranked</a> as the <a href="https://www.smh.com.au/healthcare/global-drug-survey-2017-finds-australians-are-the-biggest-bong-users-pay-most-for-cocaine-20170523-gwb2jd.html">most expensive country</a> to buy cocaine.</p>
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<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-ice-and-speed-the-drugs-that-kept-soldiers-awake-and-a-president-young-61002">Weekly Dose: ice and speed, the drugs that kept soldiers awake and a president young</a>
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</p>
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<h2>How it’s used</h2>
<p>Cocaine is used primarily as a <a href="https://www.australianpolice.com.au/main-drug-index-section/cocaine-drug-info/">recreational drug</a>. In Australia it’s most commonly snorted. Injecting, swallowing and smoking are less common.</p>
<h2>How it makes you feel</h2>
<p>The <a href="http://www.health.gov.au/internet/publications/publishing.nsf/Content/drugtreat-pubs-modpsy-toc%7Edrugtreat-pubs-modpsy-2%7Edrugtreat-pubs-modpsy-2-3%7Edrugtreat-pubs-modpsy-2-3-pcoc">effects of cocaine</a> depend on the dose, form, method of use and what the cocaine is cut with. Cocaine is commonly taken in doses of between <a href="http://drug.addictionblog.org/cocaine-overdose-how-much-amount-of-cocaine-to-overdose/">10mg and 120mg</a>. A high lasts between 15-30 minutes and has a half-life (time required before 50% of the drug has left the user’s system) of one hour. </p>
<p>Lower doses will cause a person to experience increased heart rate, body temperature and blood pressure. Cocaine also <a href="https://trove.nla.gov.au/work/16095168?q&sort=holdings+desc&_=1513628574313&versionId=46498173">brings out feelings</a> of euphoria, confidence, giddiness, alertness and enhanced self-consciousness. </p>
<p>Higher doses can cause <a href="https://www.projectknow.com/research/cocaine-overdose/">additional effects</a> such as sleep deprivation, hyper-vigilance, anxiety and paranoia. </p>
<p>Some people who use cocaine may also experience tactile hallucinations. A common example of this is the <a href="http://psycnet.apa.org/doi/10.1176/ajp.135.3.309">feeling of bugs crawling</a> on the skin.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/209456/original/file-20180308-146661-j5uvfd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209456/original/file-20180308-146661-j5uvfd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/209456/original/file-20180308-146661-j5uvfd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209456/original/file-20180308-146661-j5uvfd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209456/original/file-20180308-146661-j5uvfd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209456/original/file-20180308-146661-j5uvfd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=425&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209456/original/file-20180308-146661-j5uvfd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=425&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209456/original/file-20180308-146661-j5uvfd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=425&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cocaine users can experience tactile hallucinations, such as the feeling of bugs crawling on their skin.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>Using cocaine over a long time or in binges may lead to depression, irritability, disturbances of eating and sleeping, and tactile hallucinations. </p>
<p>Cocaine is also very <a href="https://www.healthdirect.gov.au/cocaine">addictive</a>. Withdrawal symptoms last up to ten weeks.</p>
<p>Cocaine can cause severe heart and neurological issues, and even death, when taken in too large a quantity.</p>
<p>Recent data show that seven people died due to <a href="https://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/CokeMethDeaths_2013_Website_FINAL.pdf">cocaine overdose in 2013</a> in Australia. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/209457/original/file-20180308-146650-1gc94if.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/209457/original/file-20180308-146650-1gc94if.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/209457/original/file-20180308-146650-1gc94if.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=960&fit=crop&dpr=1 600w, https://images.theconversation.com/files/209457/original/file-20180308-146650-1gc94if.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=960&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/209457/original/file-20180308-146650-1gc94if.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=960&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/209457/original/file-20180308-146650-1gc94if.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1206&fit=crop&dpr=1 754w, https://images.theconversation.com/files/209457/original/file-20180308-146650-1gc94if.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1206&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/209457/original/file-20180308-146650-1gc94if.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1206&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cocaine used to be added to Coca-Cola.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<h2>Other points of interest</h2>
<p>In the 1880s in the US, cocaine was included in numerous medicines, and even in Coca-Cola. Coca-Cola had about <a href="https://www.sciencedirect.com/topics/neuroscience/coca">60mg of cocaine</a> in a 250ml bottle.</p>
<p>In <a href="https://www.pri.org/stories/2012-06-30/colombia-decriminalizes-cocaine-marijuana">Colombia</a>, <a href="https://www.loc.gov/law/help/decriminalization-of-narcotics/mexico.php">Mexico</a> and <a href="http://druglawreform.info/en/country-information/latin-america/peru/item/207-peru">Peru</a>, possessing small amounts of cocaine for personal use is decriminalised.</p>
<p>One of the more recent concerns about the resurgence of cocaine is the potentially deadly effect it has when cut with fentanyl, a <a href="https://www.businessinsider.com.au/fentanyl-cut-cocaine-causing-overdoses-2017-6?r=US&IR=T">potent opioid</a>. A number of recent drug overdoses in Sydney have been linked to heroin cut with fentanyl, highlighting its <a href="http://www.news.com.au/lifestyle/health/health-problems/the-drop-dead-drug-that-creates-zombies-tightens-its-grip/news-story/ddf9e269c84c7ec42dff126228023d41">deadly effects</a>. While this hasn’t yet become popular with cocaine, it very well could.</p>
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<strong>
Read more:
<a href="https://theconversation.com/princes-death-from-fentanyl-is-only-the-tip-of-the-global-overdose-iceberg-60441">Prince's death from fentanyl is only the tip of the global overdose iceberg</a>
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<p><em>A previous version of this article indicated the coca plant was native to Central America. This has now been corrected to South America.</em></p><img src="https://counter.theconversation.com/content/88639/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jason Ferris is the chief biostatistician for the Global Drug Survey, founded by Adam Winstock. He has received funding from National Health and Medical Research Council, The Australian Research Council, the Foundation for Alcohol Research and Education, Queensland Government, Australian & New Zealand Association of Oral & Maxillofacial Surgeons, Tasmanian Department of Health and Human Services, Criminology Research Grant, Victorian Law Enforcement Drug Fund, Department of Health and Ageing, VicHealth, Australian National Preventive Health Agency</span></em></p><p class="fine-print"><em><span>Barbara Wood and Stephanie Cook 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>Cocaine is the second most commonly used illicit substance in Australia, after marijuana.Jason Ferris, Associate Professor, The University of QueenslandBarbara Wood, Research Assistant, The University of QueenslandStephanie Cook, Research Assistant at the Institute for Social Science Research, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/923392018-02-26T08:59:38Z2018-02-26T08:59:38ZWeekly Dose: phenibut – the Russian anti-anxiety drug linked to Gold Coast teens’ overdoses<figure><img src="https://images.theconversation.com/files/207811/original/file-20180226-140187-ddqpd0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Phenibut was included in medical kits for Russian cosmonauts for its anti-anxiety and tranquilising properties.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Soyuz_TMA-18_Crew_in_front_of_the_capsule.jpg">Wikimedia Commons</a></span></figcaption></figure><p>Phenibut was initially developed in the 1960s in Russia as an anti-anxiety (anxiolytic) drug with <a href="https://www.ncbi.nlm.nih.gov/pubmed/11830761">cognitive enhancing properties</a>. It has since attracted a strong following of users in the “smart drug” market, with claims of boosting memory recall and exam performance. </p>
<p>Originally given to Soviet cosmonauts to combat anxiety and insomnia, the powdered drug is suspected to have played a role in the recent <a href="https://www.theguardian.com/australia-news/2018/feb/23/banned-anti-anxiety-drug-phenibut-may-have-caused-gold-coast-students-overdose">overdose of seven teenagers</a> at a Queensland private school.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207780/original/file-20180226-140184-11po93t.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/207780/original/file-20180226-140184-11po93t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/207780/original/file-20180226-140184-11po93t.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=870&fit=crop&dpr=1 600w, https://images.theconversation.com/files/207780/original/file-20180226-140184-11po93t.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=870&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/207780/original/file-20180226-140184-11po93t.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=870&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/207780/original/file-20180226-140184-11po93t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1093&fit=crop&dpr=1 754w, https://images.theconversation.com/files/207780/original/file-20180226-140184-11po93t.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1093&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/207780/original/file-20180226-140184-11po93t.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"></a>
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<h2>How it works</h2>
<p>Phenibut – <a href="https://www.thetreatmentcenter.com/resources/drug-slang/">also known as</a> pbut, noofen, party powder (or its scientific name β-phenyl-γ-aminobutyric acid and brand name Bifren) – is a psychotropic drug, which means it affects the user’s mental state. </p>
<p>The drug is similar in structure to a type of neurotransmitter known as neurotransmitter γ-aminobutyric acid (GABA), which plays a role in reducing excitability and anxiety, as well as enhancing euphoria and cognitive function. Phenibut binds to a <a href="https://www.sciencedirect.com/science/article/pii/S1471489205001852">specific subtype of the GABA receptor</a>, activating a similar reaction as GABA. </p>
<p>Animal studies <a href="https://www.ncbi.nlm.nih.gov/pubmed/11830761">have shown</a> that phenibut is able to penetrate the blood brain barrier. The blood-brain barrier is is an important mechanism that stops harmful toxins and bugs travelling through the blood stream and entering the brain. </p>
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Read more:
<a href="https://theconversation.com/explainer-what-is-the-blood-brain-barrier-and-how-can-we-overcome-it-75454">Explainer: what is the blood-brain barrier and how can we overcome it?</a>
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<p>Once phenibut reaches the brain the result is reduced anxiety and social inhibition. Because it depresses the central nervous system (like GABA), it is also used as a <a href="https://www.ncbi.nlm.nih.gov/pubmed/11830761">mood elevator and tranquiliser</a>.</p>
<p>Phenibut is structurally similar to the widely prescribed drug <a href="https://www.drugs.com/baclofen.html">baclofen</a> (Lioresal), which is available in Australia. Baclofen is prescribed as a muscle relaxant for patients with conditions such as multiple sclerosis.</p>
<h2>What is it used for?</h2>
<p>Phenibut can be used to treat anxiety, post-traumatic stress disorder, alcohol withdrawal syndrome and vestibular (balance) disorders such as vertigo. It is also <a href="https://www.ncbi.nlm.nih.gov/pubmed/26693960">used recreationally</a> in many countries including the United States, United Kingdom and Australia to reduce social anxiety and induce feelings of euphoria.</p>
<p>Animal studies <a href="https://www.sciencedirect.com/science/article/pii/S1043661815301225">also show it has potential</a> to improve brain function after a stroke. </p>
<p>Phenibut is <a href="https://www.ncbi.nlm.nih.gov/pubmed/26693960">not licenced</a> for use in the European Union, Australia or the United States due to safety concerns. In Australia specifically, the drug regulator, the Therapeutic Goods Administration (TGA) has <a href="https://www.tga.gov.au/book-page/23-phenibut">rejected 11 public submissions</a> for registration and states that phenibut “represents a significant risk of harm, including overdose”.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/207812/original/file-20180226-140217-78pliq.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/207812/original/file-20180226-140217-78pliq.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/207812/original/file-20180226-140217-78pliq.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=277&fit=crop&dpr=1 600w, https://images.theconversation.com/files/207812/original/file-20180226-140217-78pliq.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=277&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/207812/original/file-20180226-140217-78pliq.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=277&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/207812/original/file-20180226-140217-78pliq.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=348&fit=crop&dpr=1 754w, https://images.theconversation.com/files/207812/original/file-20180226-140217-78pliq.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=348&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/207812/original/file-20180226-140217-78pliq.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=348&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">In Russia, Phenibut is sold commercially.</span>
<span class="attribution"><a class="source" href="http://www.apteka0303.com.ua/notes.php?lek=1000374">Screenshot</a></span>
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<p>Although phenibut is commercially available in few countries around the world, aside from Russia, a <a href="https://www.ncbi.nlm.nih.gov/pubmed/26693960">recent study</a> showed that 48 unrelated internet suppliers sold phenibut from the United Kingdom, United States, China, Australia and Canada. In Russia and the Ukraine, it is commercially available as БИФРЕН® (Bifren) and <a href="https://www.ncbi.nlm.nih.gov/pubmed/24713208">daily doses</a> range from 500 to 2000 mg.</p>
<p>Phenibut was available as a powder in amounts ranging from 5 g to 1,000 kg and as capsules containing 200–500 mg in packs of between six and 360. </p>
<h2>How was was it developed?</h2>
<p>Phenibut was first synthesised in Russia in the 1960s by Vsevolod Vasilievich Perekalin and his associates at the Department of Organic Chemistry of the Herzen Pedagogical Institute in St Petersburg, Russia. In <a href="https://www.ncbi.nlm.nih.gov/pubmed/11830761">initial publications</a>, phenibut was known as phenigamma. </p>
<p>The drug <a href="https://www.ncbi.nlm.nih.gov/pubmed/661205">used to be included</a> in medical kits for cosmonauts on Russian space flights due to the reports of enhanced cognition and high tranquilising properties.</p>
<h2>Side effects</h2>
<p>Side effects of phenibut are generally linked to its central nervous system depressant effects, such as sedation and problems with breathing. </p>
<p>There is currently limited information about phenibut. But because it has <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604470/">similar pharmacological properties to baclofen</a> it’s likely to have similar side effects. </p>
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Read more:
<a href="https://theconversation.com/explainer-how-do-drugs-work-48665">Explainer: how do drugs work?</a>
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<p>These include gastrointesinal symptoms (nausea, vomiting, diarrhoea), central nervous system symptoms (insomnia, confusion, euphoria, depression, hallucinations), and visual disturbances and musculoskeletal symptoms (such as tremors).</p>
<p>Users of phenibut can also <a href="https://www.ncbi.nlm.nih.gov/pubmed/26693960">develop tolerance</a> within days, needing more of the drug to feel the same effects. This can increase the risk of adverse effects. Users may develop withdrawal effects, such as severe rebound anxiety and insomnia, when they stop taking the drug. </p>
<p>Despite phenibut not being registered or legally available in Australia, the TGA has received <a href="http://apps.tga.gov.au/PROD/DAEN/daen-report.aspx">three reports</a> of problems related to phenibut use in the past five years. These cases range from isolated symptoms of headaches, to a cluster of symptoms such as visual impairment, muscle spasms, palpitations and nausea/vomiting. </p>
<p><a href="https://sdtreatmentcenter.com/phenibut/">Signs of overdose</a> include: shallow irregular breathing; drowsiness and lethargy; increased sweating; decreasing blood pressure; nausea and vomiting; and lowering body temperature. </p>
<p>The reported adverse events of phenibut are just scratching surface of a largely unregulated online drug market with no standards of quality assurance. So for those students seeking the competitive edge, it looks like those extra marks are not worth it after all.</p><img src="https://counter.theconversation.com/content/92339/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Janet Cheung has received funding from the Fonds de recherche Nature et technologies (FRQNT), Quebec Canada</span></em></p><p class="fine-print"><em><span>Jonathan Penm 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>Phenibut is a central nervous system depressant, and is currently being investigated for its possible role in seven overdoses at a Queensland school.Janet Cheung, Lecturer in Pharmacology, University of SydneyJonathan Penm, Lecturer (Pharmacy), University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/835732017-10-09T03:30:13Z2017-10-09T03:30:13ZWeekly Dose: from laughing parties to whipped cream, nitrous oxide’s on the rise as a recreational drug<figure><img src="https://images.theconversation.com/files/185601/original/file-20170912-11519-yxycre.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nitrous oxide inhaled out of a balloon gives the user euphoric feelings. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>Nang is a slang name for the small metal cylinders usually used in whipped cream siphons. They are also called nossies or whippets. The cylinders have about eight grams of nitrous oxide in them that can be inhaled for a euphoric effect. </p>
<p>The <a href="https://www.globaldrugsurvey.com/past-findings/the-global-drug-survey-2016-findings/">2016 global drug survey</a> found nitrous oxide is the seventh most popular drug in the world excluding alcohol, tobacco and caffeine.</p>
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<a href="https://images.theconversation.com/files/185948/original/file-20170914-19487-ta5aw2.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/185948/original/file-20170914-19487-ta5aw2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/185948/original/file-20170914-19487-ta5aw2.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=739&fit=crop&dpr=1 600w, https://images.theconversation.com/files/185948/original/file-20170914-19487-ta5aw2.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=739&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/185948/original/file-20170914-19487-ta5aw2.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=739&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/185948/original/file-20170914-19487-ta5aw2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=929&fit=crop&dpr=1 754w, https://images.theconversation.com/files/185948/original/file-20170914-19487-ta5aw2.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=929&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/185948/original/file-20170914-19487-ta5aw2.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=929&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>Who uses nangs?</h2>
<p>Nang use seems to be increasing in Australia. An <a href="https://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/National_EDRS_%202016_FINALwith%20customs.pdf">annual national survey</a> of people who use ecstasy found a significant increase in the number of people also reporting recent nitrous oxide use from 26% of people surveyed in 2015 to 36% in 2016. But not much is known about how widespread nang use is. </p>
<p>The <a href="https://www.aihw.gov.au/reports/illicit-use-of-drugs/ndshs-2016-key-findings/data">Australian household drug survey</a> does not report nitrous oxide use specifically and does not list it in the range of pharmaceutical drugs or inhalants. A <a href="https://ndarc.med.unsw.edu.au/resource/just-laughing-matter-nitrous-oxide-use-among-group-regular-psychostimulant-users-melbourne">2013 survey</a> of 1,360 university students in New Zealand found 12% of the sample reported using nangs in the past year. The average number of bulbs used in one session ranged from two to six. </p>
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<a href="https://images.theconversation.com/files/185602/original/file-20170912-11519-1lia0dx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/185602/original/file-20170912-11519-1lia0dx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/185602/original/file-20170912-11519-1lia0dx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/185602/original/file-20170912-11519-1lia0dx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/185602/original/file-20170912-11519-1lia0dx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/185602/original/file-20170912-11519-1lia0dx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/185602/original/file-20170912-11519-1lia0dx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/185602/original/file-20170912-11519-1lia0dx.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">A survey of NZ university students found 12% had used nangs in the past year.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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<h2>How do they work?</h2>
<p>Nangs are cheap, legal and easy to get. A box of ten costs less than A$10 and they are stocked in supermarkets and service stations. <a href="https://www.erowid.org/chemicals/nitrous/nitrous_info7.shtml">To use them</a>, the cylinder is pierced and the gas released into a balloon, then inhaled. </p>
<p>A balloon is used because the gas is freezing and can <a href="https://www.ncbi.nlm.nih.gov/pubmed/8634126">burn the face and lips</a>. It takes <a href="https://ndarc.med.unsw.edu.au/resource/just-laughing-matter-nitrous-oxide-use-among-group-regular-psychostimulant-users-melbourne">about one minute</a> to feel an effect that lasts about one minute.</p>
<p>Nitrous oxide is a colourless gas used for pain relief in hospitals and dentistry. It’s a <a href="https://doi.org/10.1007/978-3-642-27772-6_341-2">dissociative anaesthetic</a>. This means that at low doses, it gives a sense of floating and separation from the body without causing unconsciousness. </p>
<p>The positive effects of nangs are reported as euphoria, a feeling of floating and heightened consciousness. <a href="https://adf.org.au/drug-facts/nitrous-oxide/">The negative effects</a> include nausea, vomiting, disorientation and lack of oxygen to the brain. Some people make strange sounds and movements while intoxicated.</p>
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<a href="https://images.theconversation.com/files/185603/original/file-20170912-11574-1k2ro13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/185603/original/file-20170912-11574-1k2ro13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/185603/original/file-20170912-11574-1k2ro13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=382&fit=crop&dpr=1 600w, https://images.theconversation.com/files/185603/original/file-20170912-11574-1k2ro13.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=382&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/185603/original/file-20170912-11574-1k2ro13.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=382&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/185603/original/file-20170912-11574-1k2ro13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=480&fit=crop&dpr=1 754w, https://images.theconversation.com/files/185603/original/file-20170912-11574-1k2ro13.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=480&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/185603/original/file-20170912-11574-1k2ro13.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=480&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">Canisters are very cheap.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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<p>Heavy users may get a vitamin B12 deficiency, because nitrous oxide inactivates <a href="https://www.ncbi.nlm.nih.gov/pubmed/10528308">B12 in the body</a>. The symptoms include numbness and tingling in toes and fingers. Difficulty walking may happen in serious cases, that lasts until B12 levels are increased. Some <a href="https://www.vice.com/en_au/article/gyy94j/meet-the-people-doing-far-more-nangs-than-you">regular users</a> have reported memory loss and trouble concentrating. <a href="http://www.tmz.com/2012/01/25/demi-moore-whip-its-nitrous-oxide-seizure/">Seizures</a> and collapse have also been reported, but usually when nangs are used in combination with other drugs.</p>
<h2>How was it developed?</h2>
<p><a href="https://web.archive.org/web/20141219051822/http://journals.lww.com/anesthesiology/citation/1941/07000/Technical_Development_of_Gas_Anesthesia.4.aspx">Nitrous oxide was synthesised</a> by an English chemist, Joseph Priestly, in 1722 and used as a recreational drug at laughing gas parties. It wasn’t used as an aid to surgery until 1844. </p>
<p>Manufacturers started using nitrous oxide for <a href="http://www.cnsproductions.com/pdf/Lynn.pdf">whipping cream</a> and making aerosols in 1869 and to <a href="http://boxwrench.net/NOS/iframe-test.htm">increase engine performance</a> in cars. An explosion in a Florida factory where nitrous oxide was made <a href="http://www.ada.org/en/publications/ada-news/2017-archive/august/nitrous-oxide-shortage-continues-after-2016-explosion">has reduced supplies in the USA</a>, including in <a href="https://dragillustrated.com/is-drag-racing-facing-a-nitrous-shortage/">whipped cream products</a>. </p>
<p>The word “<a href="http://www.urbandictionary.com/define.php?term=nang">nang</a>” as a name for small nitrous oxide cylinders appears to be Australian. It’s thought to come from Western Australia, and mimics the sound distortion people hear while intoxicated. Nang is also a <a href="https://en.wiktionary.org/wiki/nang">British slang</a> word for excellent or awesome.</p>
<h2>What are the long-term risks?</h2>
<p>Seventeen deaths in six years in the UK were reportedly caused by nitrous oxide, while the USA reports about <a href="http://www.bbc.com/news/uk-england-sussex-32494219">15 deaths per year</a>. Australia has not reported any. The long-term health risks associated with nitrous oxide use include B12 deficiency, brain damage from reduced oxygen, incontinence, depression and psychological dependence. </p>
<p>However, there are few reports of people using nangs for long periods of time. Nang use may be overlooked as a health risk because most people using them are likely to use other drugs as well. It’s also important to note that nitrous oxide is linked to climate change, so there are <a href="https://theconversation.com/meet-n2o-the-greenhouse-gas-300-times-worse-than-co2-35204">environmental risks too</a>. This gas is about 300 times more damaging than carbon dioxide to the atmosphere.</p><img src="https://counter.theconversation.com/content/83573/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julaine Allan has received funding from government and philanthropic agencies to conduct research related to drug and alcohol use.She is affiliated with Lives Lived Well and Lyndon, both NGO substance treatment, training and research organisations. </span></em></p>“Nangs” are cheap, legal and easy to get - but like most drugs, they are also highly dangerous.Julaine Allan, Senior Research Fellow, Charles Sturt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/828262017-08-31T01:51:27Z2017-08-31T01:51:27ZWeekly Dose: Gardasil 9, the vaccine that could soon protect against cervical cancer in fewer doses<figure><img src="https://images.theconversation.com/files/183928/original/file-20170830-23696-1ffj6mj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A new version of Gardasil, the HPV vaccine that protects against cervical cancer, has just been approved for listing on the Pharmaceutical Benefits Schedule.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/637851685?src=YkYHp0roOsC412pAJx7Mpg-1-15&size=medium_jpg">from www.shutterstock.com</a></span></figcaption></figure><p>Gardasil is a vaccine that protects against cervical and other cancers. It works by boosting the immune response against the types of <a href="http://www.ncirs.edu.au/assets/provider_resources/fact-sheets/human-papillomavirus-hpv-fact-sheet.pdf">human papillomavirus (HPV)</a> known to be behind most of these cancers.</p>
<p>Girls aged 12-13 have been receiving Gardasil as part of Australia’s <a href="http://www.health.gov.au/internet/main/publishing.nsf/content/cda-cdi3702i.htm">school-based immunisation program</a> since 2007. And from 2013, boys of the same age were also included in the program.</p>
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Read more:
<a href="https://theconversation.com/boys-should-also-get-the-hpv-vaccine-to-protect-themselves-from-oral-and-genital-cancers-58772">Boys should also get the HPV vaccine to protect themselves from oral and genital cancers</a>
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<p>The vaccine has been <a href="http://www.abc.net.au/news/2017-08-10/new-vaccine-may-nearly-eliminate-cervical-cancer/8793316">in the news recently</a> because the committee that advises the federal government on which medicines should be publicly funded has recommended a new version of Gardasil (Gardasil 9) <a href="http://www.pbs.gov.au/industry/listing/elements/pbac-meetings/pbac-outcomes/2017-07/positive-recommendations-2017-07.pdf">be subsidised</a>. It is likely to replace the original Gardasil in the school vaccination program from 2018. </p>
<p>Gardasil 9, as its name suggests, protects against nine types of HPV (five more than the existing Gardasil). Recent studies have also shown that if you vaccinate people under 15 <a href="http://jamanetwork.com/journals/jama/fullarticle/1682939">only two</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338934/">doses</a>, not three doses, are needed to achieve good immunity. This obviously has implications both for cost and convenience, and only two doses of Gardasil 9, 12 months apart, will be given in the new school program. Those older than 14 will still need three doses of the new vaccine. </p>
<p>While Gardasil 9 is <a href="https://www.tga.gov.au/auspar/auspar-human-papillomavirus-9-valent-vaccine">licensed for use in Australia</a>, it is not yet available, nor is it clear when it will be introduced in all states. However, it is already used in the US, New Zealand and Europe.</p>
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<a href="https://images.theconversation.com/files/183939/original/file-20170830-23702-1ufs7wz.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/183939/original/file-20170830-23702-1ufs7wz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/183939/original/file-20170830-23702-1ufs7wz.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=788&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183939/original/file-20170830-23702-1ufs7wz.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=788&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183939/original/file-20170830-23702-1ufs7wz.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=788&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183939/original/file-20170830-23702-1ufs7wz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=990&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183939/original/file-20170830-23702-1ufs7wz.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=990&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183939/original/file-20170830-23702-1ufs7wz.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=990&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>HPV: common, infectious and potentially deadly</h2>
<p><a href="http://www.sciencedirect.com/science/article/pii/S0042682213003565">Over 120 different types of HPV infect humans</a> and 15 of them, almost always sexually transmitted, are linked to cancers of the genital area and throat.</p>
<p>HPV is highly infectious and by age 50, <a href="https://www.cdc.gov/cancer/hpv/basic_info//">some 80% of sexually active people</a> will have picked up at least one type of genital HPV.</p>
<p>Most HPV infections settle within two years, but in a small number of people the virus secretes itself within the cell nucleus, evading the immune system and increasing the risk of future cancer. HPV contributes to almost all cancers of the cervix, vulva and vagina, and is also the trigger for many cancers of the anus and throat. </p>
<p><a href="http://www.who.int/mediacentre/factsheets/fs380/en/">Cervical cancer</a> is the fourth most common female cancer worldwide and the cause of about 270,000 deaths each year. <a href="http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/key-statistics-2">About 250</a> of those who die each year are Australian women.</p>
<h2>Gardasil</h2>
<p>The 1990s saw the development of the first HPV vaccine, Gardasil. The vaccine contains no infectious material. Instead, it contains four different <a href="https://www.ncbi.nlm.nih.gov/pubmed/20923267">virus-like particles</a>, identical to those in the protective capsule around HPV types 6, 11, 16 and 18. These are produced inside yeast cells. </p>
<p>Types 6 and 11 <a href="http://www.sciencedirect.com/science/article/pii/S0090825807005446?via%3Dihub">cause 90% of genital warts</a>, while types 16 and 18 are <a href="http://www.sciencedirect.com/science/article/pii/S0090825807005446?via%3Dihub">associated with around 70% of cervical cancers</a>.</p>
<p>Once injected, the virus-like particles generate a strong immune “memory”, providing protection from those particular HPV types in the future. Three injections were required over six months to ensure the best immune response.</p>
<p>It was recommended that age 12-13 was the best time for Gardasil vaccination for a number of reasons. Mainly because vaccination at this age is likely to be before their first sexual encounter (and HPV exposure). Also, the immune response tends to be <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm?s">stronger and more long-lasting</a> when the vaccine is given to pre-adolescents.</p>
<p>By 2011, only four years after the school-based vaccination program in Australia began, sexual health clinics were reporting a <a href="http://www.bmj.com/content/346/bmj.f2032.long">73% reduction</a> in genital warts in young heterosexual women and their male partners. And 2014 saw a <a href="https://www.mja.com.au/journal/2016/204/5/hpv-vaccine-impact-australian-women-ready-hpv-based-screening-program">significant drop</a> in the numbers of high-grade cervical pre-cancers in those under 30, while the figures for their older sisters remained stable. These high-grade changes are associated with a greater risk of cervical cancer later on. </p>
<h2>What does Gardasil 9 add?</h2>
<p><a href="https://www.tga.gov.au/auspar/auspar-human-papillomavirus-9-valent-vaccine">Gardasil 9</a> contains five more virus-like particles than the original vaccine and offers protection against HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58. </p>
<p>The <a href="http://onlinelibrary.wiley.com/doi/10.1002/ijc.30871/full">extra viral types</a> are responsible for another 20% of female genital cancers and the new vaccine could potentially increase the protection rate for cervical cancer to around 90%.</p>
<p>Women still need regular cervical screening but even fewer should find themselves facing further testing and treatment over time.</p>
<h2>Side-effects and controversies</h2>
<p>Neither Gardasil or Gardasil 9 is licensed for use during pregnancy. Vaccination should be delayed if the person is very unwell or has a high temperature; medical advice is recommended if the person is allergic to yeast or has had a severe reaction to a previous vaccine; and anyone who has the vaccine is recommended to sit for 15 minutes to reduce the risk of fainting.</p>
<p>Vaccines, and HPV vaccines in particular, have attracted a significant amount of <a href="http://www.sciencedirect.com/science/article/pii/S0264410X12004860">online concern</a> about their safety.</p>
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Read more:
<a href="https://theconversation.com/the-best-shot-at-overcoming-vaccination-standoffs-having-doctors-listen-to-not-shun-reluctant-parents-81592">The best shot at overcoming vaccination standoffs? Having doctors listen to – not shun – reluctant parents</a>
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<p>Gardasil 9 has been studied in more than <a href="https://www.tga.gov.au/sites/default/files/auspar-human-papillomavirus-9-valent-vaccine-170103-pi.pdf">13,000 females and males</a> before release overseas. Five people in those trials had significant side-effects such as tonsillitis, fever, allergy and asthma. The commonest side-effect (in more than 80% of people) was pain, redness and swelling at the injection site.</p>
<p>More than <a href="http://www.who.int/vaccine_safety/committee/GACVS_HPV_statement_17Dec2015.pdf">200 million doses</a> of the original Gardasil vaccine have been administered in over 100 countries worldwide with <a href="https://www.cdc.gov/vaccinesafety/vaccines/hpv/hpv-safety-faqs.html">over 10 million doses of Gardasil 9</a> given in the US alone in the past year.</p>
<p>Given those numbers, the problems reported have been few. Though ongoing safety monitoring is important, it would appear that for most young people <a href="https://www.cdc.gov/vaccinesafety/vaccines/hpv/hpv-safety-faqs.html#A1">the benefits of this new vaccine far outweigh the risks</a>.</p><img src="https://counter.theconversation.com/content/82826/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Terri Foran has worked in the past as a consultant and has developed educational material around contraception for Merck Sharpe and Dohme, the company which distributes Gardasil and Gardasil 9 in many countries. She has never been involved in any consultancy work relating to either of these vaccines. She has no association whatsoever with the Australian distributor of these vaccines. </span></em></p>A new version of the HPV vaccine Gardasil protects against nine types of the virus, and is already being used overseas.Terri Foran, Lecturer in the School of Women's and Children's Health, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/818932017-08-03T02:48:37Z2017-08-03T02:48:37ZWeekly Dose: methylprednisolone, a drug for treating inflammation but not rare kidney disease<figure><img src="https://images.theconversation.com/files/180649/original/file-20170802-11374-1dpcm62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Methylprednisolone, the corticosteroid that's used to treat serious asthma attacks, works by reducing inflammation.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/518348707?size=medium_jpg">from www.shutterstock.com</a></span></figcaption></figure><p>Methylprednisolone is a prescription drug used to treat conditions involving inflammation, like asthma, arthritis, gout, tendinitis, transplant rejection, allergic reactions, and the skin conditions eczema and psoriasis.</p>
<p>It’s in the news because doctors have been trialling the drug to see if it helped treat a rare kidney condition called IgA nephropathy, also known as <a href="http://kidney.org.au/cms_uploads/docs/rrc-iga-nephropathy.pdf">Berger’s disease</a>.</p>
<p>A study <a href="http://dx.doi.org/10.1001/jama.2017.9362">published this week</a> reported an international trial of oral methylprednisolone involving 262 patients (including Australians) was stopped early due to safety concerns. Although the drug resulted in an almost three fold lower risk of kidney failure, there was an almost five fold higher risk of serious infection. The researchers reported two patients had died from these trial-related infections.</p>
<p><a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1415463#t=article">Other clinical trials</a> have also reported higher rates of adverse effects, like serious infections, from oral use of methylprednisolone when treating IgA nephropathy.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/kidneys-are-amazing-for-all-they-do-be-sure-to-look-after-yours-30966">Kidneys are amazing for all they do, be sure to look after yours</a>
</strong>
</em>
</p>
<hr>
<p>However, for people prescribed the drug for other reasons side effects are rare. And methylprednisolone should not to be confused with similarly sounding medicines in the same drug family, like prednisolone or prednisone.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/180658/original/file-20170802-7559-8dnmh2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/180658/original/file-20170802-7559-8dnmh2.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=812&fit=crop&dpr=1 600w, https://images.theconversation.com/files/180658/original/file-20170802-7559-8dnmh2.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=812&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/180658/original/file-20170802-7559-8dnmh2.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=812&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/180658/original/file-20170802-7559-8dnmh2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1021&fit=crop&dpr=1 754w, https://images.theconversation.com/files/180658/original/file-20170802-7559-8dnmh2.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1021&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/180658/original/file-20170802-7559-8dnmh2.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1021&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Use and formulations</h2>
<p>Methylprednisolone is a type of <a href="http://www.medicinenet.com/corticosteroids-oral/article.htm">corticosteroid</a>, the same drug family containing hydrocortisone, dexamethasone, prednisone, prednisolone and triamcinolone.</p>
<p>Corticosteroids are not the same as <a href="https://www.drugabuse.gov/publications/drugfacts/anabolic-steroids">anabolic steroids</a>, which some athletes and body builders use illegally to build muscle and help performance.</p>
<p>Corticosteroids suppress inflammation and the immune system by <a href="https://www.yourgenome.org/facts/what-is-gene-expression">regulating how genes are expressed</a>.</p>
<p>In Australia, methylprednisolone is indicated for acute severe asthma, arthritis (including both rheumatoid and osteoarthritis), <a href="http://www.move.org.au/Conditions-and-Symptoms/Gout?gclid=CjwKCAjwzYDMBRA1EiwAwCv6JrreALKZbjLvlHyyzXDXWtCMQOCcowEcp8TXDGQdja2F9fdUaZrfMBoCAxMQAvD_BwE">gout</a> (an arthritis-like condition due to the build up of uric acid in the bloodstream), <a href="http://www.webmd.com/fitness-exercise/arthritis-tendinitis#1">tendinitis</a>, acute transplant rejection, and some autoimmune diseases, like allergies, <a href="https://www.allergy.org.au/patients/skin-allergy/eczema">eczema</a> and <a href="http://www.psoriasisxplained.com.au/psoriasis-app-page/?utm_source=Adwords&utm_medium=Advert&utm_campaign=launch&gclid=CjwKCAjwzYDMBRA1EiwAwCv6JjRBx5XwiFqZA1GsBO0BCy0UJxbKAu9WRRk1c54r0Dl0u6lQgUAp0hoCTS0QAvD_BwE">psoriasis</a>.</p>
<p>Methylprednisolone is also on the <a href="http://www.who.int/topics/essential_medicines/en/">World Health Organisation’s list of essential medicines</a> that:</p>
<blockquote>
<p>… satisfy the priority health care needs of the population. They are selected with due regard to public health relevance, evidence on efficacy and safety, and comparative cost-effectiveness.</p>
</blockquote>
<p>The most <a href="http://www.who.int/medicines/publications/essentialmedicines/20th_EML2017.pdf?ua=1">up-to-date list</a> published in March 2017 includes methylprednisolone for the treatment of acute lymphoblastic leukaemia. The list also includes the related drug, <a href="https://beta.nhs.uk/medicines/prednisolone/">prednisolone</a>, to treat different types of leukaemia and lymphoma.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-can-go-wrong-in-the-blood-a-brief-overview-of-bleeding-clotting-and-cancer-76400">What can go wrong in the blood? A brief overview of bleeding, clotting and cancer</a>
</strong>
</em>
</p>
<hr>
<p>While methylpredisolone is available in other countries in tablet form, in Australia it is only available by prescription as an injection or as skin cream or ointment. As an <a href="http://www.pharmexec.com/what-happens-when-product-loses-its-patent">off-patent</a> medicine, it is available from a variety of companies in different brands. </p>
<h2>Safety and side effects</h2>
<p>The <a href="https://amhonline.amh.net.au/">Australian Medicines Handbook</a> (subscription required) says side effects should be rare (have a rate less than 0.1%), the most common of which is liver toxicity. It is safe for women to use immediately after breastfeeding, but they should avoid using it within four hours before breastfeeding. This is because very small amounts of the drug can be transferred into the milk.</p>
<p><a href="https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2014-CMI-02603-1">Other side-effects</a> depend on the dose and the formulation used. When used on the skin, side effects can include: thinning of the skin, appearance of fine blood vessels, acne, infection of hair follicles, excessive or unwanted hair growth, redness around the mouth, skin discolouration and allergic skin reactions.</p>
<h2>In a nutshell</h2>
<p>Methylprednisolone is an effective and safe medicine for treating inflammatory and autoimmune conditions. Recent studies into its use for IgA nephropathy have indicated an unacceptably high risk of serious infection. </p>
<p>Despite this, you should not be at risk if you use the medication as directed and prescribed by your doctor. However, if you have any concerns, you should speak to your local pharmacist.</p><img src="https://counter.theconversation.com/content/81893/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr Wheate in the past has received funding from the ACT Cancer Council, Tenovus Scotland, Medical Research Scotland, Scottish Crucible, and the Scottish Universities Life Sciences Alliance. He is affiliated with the Royal Australian Chemical Institute.</span></em></p>A trial of methylprednisolone in kidney patients was halted recently because of safety concerns. But this doesn’t affect people taking the drug for asthma, arthritis or other inflammatory conditions.Nial Wheate, BPharm Coordinator and Senior Lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/769342017-05-03T04:22:05Z2017-05-03T04:22:05ZWeekly Dose: Kalydeco, the drug that treats the cause of cystic fibrosis, not just symptoms<figure><img src="https://images.theconversation.com/files/167444/original/file-20170502-17322-1f2k6hm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People with cystic fibrosis, Australia's most common inherited condition, have thick mucus, including on the lungs.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/396255907?src=OOFB-3qYwLVlctPd4ckqTw-1-16&size=medium_jpg">from www.shutterstock.com</a></span></figcaption></figure><p>Kalydeco (ivacaftor) is a drug used to treat <a href="http://www.cysticfibrosis.org.au/all/learn/">cystic fibrosis</a>, a disorder that affects many organs, particularly the lungs. Cystic fibrosis is Australia’s most commonly inherited disorder.</p>
<p>The drug has been <a href="http://www.smh.com.au/federal-politics/political-news/cystic-fibrosis-miracle-drug-among-turnbull-governments-310m-pbs-listing-20170430-gvvl0l.html">in the</a> <a href="http://www.theaustralian.com.au/news/latest-news/lifesaving-drugs-lose-hefty-pricetags/news-story/344e8dcc4fbb9f99b0a929a7f2a4cdd1">news</a> recently because, as of <a href="http://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2017-hunt040.htm">May 1</a>, 2017 a wider range of people are now eligible to receive it under the <a href="http://www.pbs.gov.au/pbs/home">Pharmaceutical Benefits Scheme</a> (PBS).</p>
<p>Before May 1, <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">more than 200</a> Australians over the age of six years were eligible for Kalydeco. <a href="https://www.vrtx.com/story/children-ages-2-5-gating-mutations-australia-be-provided-immediate-access-kalydeco-ivacaftor">Widening its subsidy</a> to certain younger patients aged two to five means <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">another 30</a> children can benefit. This accounts for <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">10 to 12%</a> of patients with cystic fibrosis.</p>
<p>Before PBS listing in 2014, patients and families needed to find A$300,000 per year to fund the drug. Now, for eligible patients, it is available for A$6.30 a script for concession-card holders and A$38.80 for general patients. But patients will still need to satisfy specific criteria (have specific gene mutations) to qualify.</p>
<h2>What is cystic fibrosis?</h2>
<p>Cystic fibrosis affects <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">one in 3,600</a> live births in Australia. It is caused by defects in a single gene, known as the cystic fibrosis transmembrane regulator (CFTR).</p>
<p>The gene has a critical role in controlling how chloride ions (salt) move in and out of cells via proteins called chloride channels. Too much salt and not enough water can lead to mucus becoming very thick and sticky, which can build up in the lungs (and other organs).</p>
<p>This sticky mucus clogs the tiny air passages in the lungs and traps bacteria. Repeated infections and blockages can cause irreversible lung damage, which is the most common cause of death in people with this condition.</p>
<p>Mucus can also cause problems in the pancreas, preventing the release of enzymes needed to digest food and so leading to nutrition problems.</p>
<p>Patients can also have liver disease, chronic sinus infections, diabetes and fertility problems due to this faulty gene.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=870&fit=crop&dpr=1 600w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=870&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=870&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1093&fit=crop&dpr=1 754w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1093&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.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"></a>
<figcaption>
<span class="caption">Kalydeco.</span>
</figcaption>
</figure>
<h2>How does Kalydeco work?</h2>
<p>The drug was discovered as part of a collaboration with Vertex Pharmaceuticals Inc in the USA and Cystic Fibrosis Foundation, US. It took more than 14 years to develop. </p>
<p>Until it became available, drug therapies for cystic fibrosis were less targeted and only aimed at reducing symptoms in an attempt to slow the disease. </p>
<p>Researchers have found more than 2,000 genetic mutations in the CFTR gene and each leads to a different defect in the chloride channels. Kalydeco is the first medicine to treat the underlying cause of cystic fibrosis in people with specific mutations in this CFTR gene. </p>
<p>It works by targeting certain abnormal chloride channels and opening them to allow chloride ions to move in and out of the cell. This leads to an increase in water levels in the airways helping to thin the mucus.</p>
<p>By keeping the airways well hydrated, mucus can be cleared from the airways, <a href="http://www.kalydeco.com/how-kalydeco-works">reducing the risk of lung infections and progressive lung damage</a>. The reduction in mucus also affects the pancreatic ducts, which in turn results in improvement in glucose levels reducing patients’ risk of cystic fibrosis-related diabetes. </p>
<p><a href="https://dx.doi.org/10.1056/NEJMoa0909825">Studies</a> <a href="https://dx.doi.org/10.1164/rccm.201301-0153OC">of drugs</a> <a href="https://dx.doi.org/10.1056/NEJMoa1105185">like Kalydeco</a>, which work to counter the effects of the faulty CFTR gene, suggest they increase the lifespan of people with cystic fibrosis and decrease the severity of illness. Treating the condition at an earlier stage in the progression of disease may also limit organ damage, reduce illness due to chest infections and improve respiratory-related quality of life. </p>
<h2>How do patients take it?</h2>
<p>In Australia, the medication is available on the <a href="https://www.pbs.gov.au/info/browse/section-100/s100-highly-specialised-drugs">Highly Specialised Drugs Program</a>, which means only doctors with experience in treating cystic fibrosis can prescribe it. The drug comes as a tablet or oral solution that patients take twice a day.</p>
<p>To increase the absorption of Kalydeco, patients take the medication with fatty foods such as butter, eggs, cheese, nuts, avocados, or whole milk.</p>
<h2>How about side-effects and interactions?</h2>
<p>Some patients have high levels of certain liver enzymes while on the drug (which might be a sign of a stressed liver) so doctors need to keep an eye on these. And some adolescents and children develop cataracts (clouding of the eye lens) while on the drug so need to have their eyes monitored.</p>
<p>Most common side effects include: headache, upper respiratory tract infection, stomach pain, diarrhoea, rash, nausea and dizziness. People should also not drive or operate machinery until they know how Kalydeco affects them.</p>
<p>Taking the drug with some antibiotics (like rifampicin and rifabutin); seizure medications (phenytoin, carbamazepine or phenobarbital); and the herbal supplement St John’s Wort can substantially decrease the effectiveness of Kalydeco.</p>
<p>Patients are also recommended to avoid taking it with grapefruit juice, grapefruits or Seville oranges because this makes them increasingly sensitive to it. Anti-fungal medications (ketoconazole, itraconazole, posaconazole, voriconazole or fluconazole), other antibiotics (such as clarithromycin or erythromycin) can also increase Kalydeco exposure, so if taking these medicines at the same time, patients need lower doses of the cystic fibrosis drug.</p>
<p>With the <a href="https://www.pbs.gov.au/medicine/item/10170G-10175M-11097C-11098D-11105L-11109Q">new PBS listing for Kalydeco</a>, younger patients have been provided access to the life-saving treatment aimed at addressing the underlying cause of cystic fibrosis, instead of only treating its symptoms.</p><img src="https://counter.theconversation.com/content/76934/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Odette Erskine is a sub-investigator for clinical trials conducted by Vertex Pharmaceuticals Inc, Australia. She does not receive any direct funding from the company.</span></em></p>Wider availability of the cystic fibrosis drug Kalydeco since May 1, 2017 means younger patients can now access it.Odette Erskine, Respiratory and Sleep Medicine Physician; Clinical Lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/739532017-03-14T19:13:09Z2017-03-14T19:13:09ZWeekly Dose: ayahuasca, a cautionary tale for tourists eager to try this shamanic brew<figure><img src="https://images.theconversation.com/files/160245/original/image-20170310-3687-1zwrk1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ayahuasca, a plant-based brew that gives people a psychedelic experience, can be fatal, especially when mixed with other drugs.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/jairinflas/11949826476/in/photolist-jcXZ5Y-9npKoi-aJaaBe-fozKoz-q1mwX6-q1eg1y-qhBnwa-9foD9i-q1n5cF-bcuDZa-qhLJce-qhBhUK-vTB8V-q1e4WQ-q1dutL-pm1WC6-q1mNUg-q1mBpc-pKhbBf-pm2iEr-aJaaKV-a1EpvL-qhLVaB-foQ2jA-foQ1F7-5KX4Jp-qhHSe9-foQ1Pf-q1evVU-q1ktaR-a1Epto-qhB4X2-qhLKgi-nWT44g-qfuT6G-qhAH6H-q1mUin-q1dBbd-cYDvm-pdg2i-72Atft-qfuhFu-qhACUM-qfuuQE-q1dP7C-d88dT7-cYhrw-q1mZ7a-qhB3Jv-q1dZoG">Jairo Galvis Henao/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>Last night’s ABC <a href="http://www.abc.net.au/foreign/">Foreign Correspondent</a> highlighted how Australians have been travelling to South America to seek the mystical experiences and healing properties of the plant brew ayahuasca.</p>
<p>Spiritual leaders known as <a href="https://en.oxforddictionaries.com/definition/shaman">shaman</a> have been using this brew for hundreds of years for healing and religious purposes. It’s prepared by boiling plants from the Amazon and reducing the brew. Either the shaman or the person who wants to be healed (or both) can drink it.</p>
<p>But the program shows the dangers of using such a powerful drug while overseas where there is little regulation over the retreats that offer it.</p>
<h2>What is ayahuasca?</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/160622/original/image-20170313-9624-ya80ep.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/160622/original/image-20170313-9624-ya80ep.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/160622/original/image-20170313-9624-ya80ep.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=704&fit=crop&dpr=1 600w, https://images.theconversation.com/files/160622/original/image-20170313-9624-ya80ep.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=704&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/160622/original/image-20170313-9624-ya80ep.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=704&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/160622/original/image-20170313-9624-ya80ep.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=885&fit=crop&dpr=1 754w, https://images.theconversation.com/files/160622/original/image-20170313-9624-ya80ep.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=885&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/160622/original/image-20170313-9624-ya80ep.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=885&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p>Ayahuasca has two main ingredients, both of which are needed for the drug to have its psychoactive effects.</p>
<p>One is a plant containing <a href="https://erowid.org/chemicals/dmt/dmt.shtml">dimethyltryptamine</a> (DMT), the same compound found in many plants, including <a href="https://en.wikipedia.org/wiki/List_of_Acacia_species_known_to_contain_psychoactive_alkaloids">Australia’s national floral emblem, the wattle</a>. Usually, if you eat or drink dimethyltryptamine, an enzyme in your stomach called <a href="https://en.wikipedia.org/wiki/Monoamine_oxidase">monoamine oxidase</a> quickly metabolises it into non-psychoactive chemicals. So, on its own, dimethyltryptamine has almost no psychoactive effect.</p>
<p>But among the millions of plants in the Amazon, shaman somehow realised mixing two plants could create a brew to provide a mystical experience and powerful visions. This second plant contains chemicals known as reversible monoamine oxidase inhibitors, which “neutralise” monoamine oxidase. So, dimethyltryptamine is free to be absorbed into the body, unaltered.</p>
<p>Dimethyltryptamine then activates the same receptors in the brain activated by psychedelic drugs like <a href="https://theconversation.com/weekly-dose-lsd-dangerous-mystical-or-therapeutic-64550">LSD</a> (lysergic acid diethylamide) and <a href="https://theconversation.com/shroom-to-grow-australias-missing-psychedelic-science-17344">psilocybin</a> (found in some mushrooms).</p>
<h2>What are its effects and risks?</h2>
<p>When you drink ayahuasca, the acute effects last about four hours. These include powerful perceptual changes users have reported can <a href="http://www.newyorker.com/magazine/2016/09/12/the-ayahuasca-boom-in-the-u-s">change a person’s view on life</a>.</p>
<p>But sometimes a person might feel they are dying or losing control of their mind. Common acute side-effects include vomiting and diarrhoea, which Amazonian shaman view as <a href="https://www.dmt-nexus.me/forum/default.aspx?g=posts&t=30502">spiritual purging</a>. Ayahuasca is hardly a “recreational drug”.</p>
<p>For a few hours after the acute effects wear off, people report being sedated, thanks to the various monoamine oxidase inhibitors in the brew; there are few documented cases of longer lasting negative side effects.</p>
<p>But if people with a serious mental illness such as schizophrenia or bipolar disorder use ayahuasca, their symptoms may worsen. So, it’s recommended people with such a pre-existing condition, or a predisposition to one, avoid it.</p>
<p>While there is a low chance of overdosing from ayahuasca due to its pungent flavour, high doses are linked with having strong changes in perception, which can be distressing.</p>
<p>Ayahuasca, however, carries with it a physiological risk. Monoamine oxidases have an important protective role in the body in defending the circulation from substances in the gut, either food or drugs. So, turning off these protective enzymes <a href="http://www.ayahuasca.com/science/foods-and-meds-to-avoid-with-maois/">exposes the body</a> to a variety of possible toxicological effects, like seizures, delirium, coma and collapse of the circulatory system. These effects, particularly in the context of other drugs, either illicit or medical, have the potential to be fatal. </p>
<p>As a consequence, there are <a href="http://www.ayahuasca.com/science/foods-and-meds-to-avoid-with-maois/">substantial numbers of drugs</a> that could have significant, even potentially lethal consequences if taken with ayahuasca, including medications for depression, high blood pressure, some complementary medicines, and illicit drugs, including cocaine and amphetamines.</p>
<p><a href="http://www.ayahuasca.com/science/foods-and-meds-to-avoid-with-maois/">Foods to avoid</a> for similar reasons include those that are aged, preserved, dried, fermented, pickled, cured (meats), rancid, old, out of date, overripe, or even slightly spoiled.</p>
<p>But the death reported by <a href="http://www.abc.net.au/foreign/">Foreign Correspondent</a> did not involve ayahuasca; it involved a brew of tobacco mixture touted as a body cleanse. In fact, most deaths associated with ayahuasca have been due to various plants, like tobacco or <a href="http://www.mensjournal.com/magazine/the-dark-side-of-ayahuasca-20130215">brugmansia</a>, added to the brew.</p>
<h2>Are there benefits?</h2>
<p>When drunk in a safe setting with the right intention, ayahuasca can have beneficial effects, with potential therapeutic effects attracting much <a href="https://books.google.com.au/books/about/The_Therapeutic_Use_of_Ayahuasca.html?id=h0_ABAAAQBAJ&source=kp_cover&redir_esc=y&hl=en">research</a> attention.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/7892432">Early research</a> found people who drank ayahuasca at a Brazilian church had decreased levels of depression compared to a matched control group. This was thought to be related to increased levels of serotonin, which researchers found among regular ayahuasca drinkers.</p>
<p>Meanwhile, a recent systematic review found it helped <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910400/">anxiety and depression</a>. There is also <a href="https://www.ncbi.nlm.nih.gov/pubmed/23627784">research</a> suggesting ayahuasca could treat addictive behaviours.</p>
<h2>Ayahuasca tourism</h2>
<p>Travelling overseas to drink ayahuasca is not new, with the Australian media reporting on ayahuasca tourism as early as <a href="http://www.news.com.au/travel/australians-flock-to-peru-for-8216spiritual-awakening8217/news-story/1f708f6d4075166aa75b164ff607a197">2013</a>. And in 2014, it was featured in <a href="http://www.hamishandandy.com/south-america-gap-year/">Hamish and Andy’s Gap Year South America</a>.</p>
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<figcaption><span class="caption">Hamish and Andy’s Gap Year South America showed the effects of ayahuasca.</span></figcaption>
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<p>Australia’s Department of Foreign Affairs and Trade <a href="http://smartraveller.gov.au/Countries/americas/south/Pages/peru.aspx">website warns</a> about ayahuasca tourism being a burgeoning industry in parts of Ecuador and Peru and while not illegal, there is no way to thoroughly vet ayahuasca tour operators. There have been reports of <a href="http://www.abc.net.au/news/2016-04-10/the-new-age-of-ayahuasca/7257244">assaults and people being robbed</a>, <a href="http://nymag.com/thecut/2017/01/sexual-assault-ayahuasca-tourism.html">rape</a> and <a href="http://www.smh.com.au/world/australian-owner-shocked-after-man-stabbed-to-death-at-peru-drug-retreat-20151221-glsxq8.html">murder</a> linked with it.</p>
<h2>Ayahuasca in Australia</h2>
<p>We don’t know how many people use ayahuasca in Australia, but a story on SBS in 2016 featured an <a href="http://www.sbs.com.au/news/thefeed/article/2016/06/13/australian-ayahuasca-debate">interview</a> with a local facilitator of ayahuasca ceremonies.</p>
<p>Although the active ingredient dimethyltryptamine is found in many Australian acacias, it remains an illegal drug in all states and territories. Drinking ayahuasca is therefore considered illegal. This perhaps explains why many Australians drink it overseas rather than in Australia.</p>
<p>An application to Australia’s drug regulator, the Therapeutic Goods Administration, last year to grant Australian members of some faiths the right to legally make and drink ayahuasca <a href="https://www.tga.gov.au/book-page/14-nn-dimethyltrypamine">was denied</a>, citing concerns about managing safety risks.</p><img src="https://counter.theconversation.com/content/73953/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephen Bright is vice president of Psychedelic Research in Science & Medicine (PRISM), a not-for profit organisation that facilitates research into the beneficial uses of psychedelic drugs (<a href="http://www.prism.org.au">www.prism.org.au</a>) </span></em></p><p class="fine-print"><em><span>David Caldicott receives funding from an NH&MRC Partnership Grant. He is affiliated with ATODA and Harm Reduction Australia, and is the Cinical Lead of the Australian Drug Observatory</span></em></p>Shaman have used the psychoactive effects of ayahuasca for spiritual and healing purposes for hundreds of years. But a new breed of tourist has discovered this plant-based drug.Stephen Bright, Senior Lecturer of Addiction, Edith Cowan UniversityDavid Caldicott, Emergency Medicine Consultant, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/732702017-03-09T02:56:24Z2017-03-09T02:56:24ZWeekly Dose: while the media panic about ice, we should worry about carfentanil<figure><img src="https://images.theconversation.com/files/158652/original/image-20170228-29942-5zatbp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Most people who take carfentanil think they're taking something else, usually heroin. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>While the <a href="https://theconversation.com/ice-wars-message-is-overblown-and-unhelpful-72719">media seem embroiled</a> in a <a href="http://www.huffingtonpost.com/christopher-j-ferguson/how-journalists-contribut_b_6213190.html">moral panic</a> about methamphetamine or “ice”, those of us who actually work with overdose patients are nervously watching out for a far more dangerous drug: carfentanil.</p>
<p>You may have heard of <a href="https://theconversation.com/weekly-dose-fentanyl-the-anaesthetic-that-may-have-been-used-as-a-chemical-weapon-on-chechen-rebels-62966">fentanyl</a>, a synthetic opioid similar to morphine, the drug derived from the opium poppy. Fentanyl is 50 to 100 times more potent than morphine, but there wouldn’t be a day that goes by where we don’t use it in the emergency department, mostly for pain relief. </p>
<p>Carfentanil is an ultra-potent synthetic version of this. Its only legitimate use is in veterinary practice for large animals such as elephants. Its distribution is restricted to veterinarians engaged in zoo and exotic animal practice, wildlife management programs, and researchers.</p>
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<h2>How does it work?</h2>
<p>The human body manufactures neuropeptides called endorphins. Opioids work by binding to endorphin receptors in the body, namely opioid receptors. </p>
<p>There are several types of receptors, all which, when activated, create slightly different effects - some make you feel good, or sleepy, or less anxious. </p>
<p>One, called the μ-receptor, is very good at mediating respiratory depression. And carfentanil can activate this receptor better than almost any other opiate.</p>
<h2>How was it developed?</h2>
<p>Developed in the mid-1970s as a large animal sedative (Wildnil), carfentanil is 10,000 times more potent than morphine. A lethal dose in humans is only 20 micrograms. That is the weight of ten snowflakes, or a single grain of pollen.</p>
<p>It is so potent that lab technicians require special protective equipment to analyse it, and have to have the antidote at the lab bench. It <a href="http://www.elephantcare.org/Drugs/carfenta.htm">takes only 10mg</a> to knock down a wild African elephant. An <a href="http://www.ajemjournal.com/article/S0735-6757(10)00117-8/abstract">unfortunate veterinarian</a> who merely splashed some on his eye while trying to sedate an elk required resuscitation.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-fentanyl-the-anaesthetic-that-may-have-been-used-as-a-chemical-weapon-on-chechen-rebels-62966">Weekly Dose: fentanyl, the anaesthetic that may have been used as a chemical weapon on Chechen rebels</a>
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<h2>What are its uses?</h2>
<p>Carfentanil has no therapeutic human application. And for most consumers who have ingested it, they have done so involuntarily, thinking it was another drug, usually heroin.</p>
<p>So why is it available? In the world of heroin, “quality” is frequently conflated with potency. A product that may be significantly “cut” can be dosed with minute quantities of fentanyl-like products to give the impression of enhanced value. By increasing the perceived “purity” of a shipment, you can increase its apparent value. </p>
<p>It’s particularly useful that the manufacture of carfentanil is entirely synthetic, and not reliant on the vagaries of crops in Afghanistan’s Helmand province, or border patrols in Herat Province. It’s far easier to smuggle a suitcase of an ultra-potent product globally than a shipping container of something more “dilute” and organic.</p>
<h2>Why should we be so concerned about it?</h2>
<p>The first epidemic of fentanyls and fentanyl-related compounds <a href="https://en.wikipedia.org/wiki/%CE%91-Methylfentanyl">dates back to the 1970s</a>. Between 2005 and 2007, another product, this time from Mexico, <a href="https://www.justice.gov/archive/ndic/pubs11/20469/index.htm">killed hundreds of Americans</a>. </p>
<p>Globally, we are now seeing a third wave of fentanyl-related deaths, dating from perhaps late 2013, far more serious than any that preceded it. There were over <a href="https://www.cdc.gov/mmwr/volumes/65/wr/mm6533a2.htm">5,000 deaths in the US alone in 2014</a>. Ohio state had <a href="https://www.cdc.gov/mmwr/volumes/65/wr/mm6533a3.htm">over 1,100 deaths in 2015 alone</a>. The figures for 2016 could be far greater still.</p>
<p>Those of us in the business of tracking down new illicit drugs in Australia have felt the malign presence of the fentanyls for a while now. We have been forewarned by our overseas colleagues - equally aghast at their escape into the open market. <a href="https://www.eventbrite.com.au/e/new-and-novel-psychoactive-substances-challenges-for-healthcare-workers-tickets-22756633704#">We predicted</a> the synthetic fentanyls would be a major issue for Australia in April 2016. </p>
<p>For about a year, we’ve been hearing reports of “heroin” overdoses that are no longer responding to standard doses of our normal opiate antidote, <a href="https://theconversation.com/weekly-dose-naloxone-how-to-save-a-life-from-opioid-overdose-63459">naloxone</a>. That is usually about 2mg, but in cases we suspect involved carfentanil and its close cousins, it can take ten times more to make someone breathe again.</p>
<p>In December, a carfentanil seizure was <a href="http://www.couriermail.com.au/news/carfentanil-deadly-tranquilliser-found-for-the-first-time-in-australia/news-story/21cf74b4e9d2fe46ec8263e60aee343a">reported in Sydney</a> - last month <a href="http://www.dailymail.co.uk/news/article-4233436/Queensland-Police-issue-warning-carfentanil-drug.html">another in Brisbane</a>. Like a lethal strain of flu, now it’s here, and all we can do is work furiously to prevent it becoming established. This involves engagement with the consumer community, an approach which doesn’t appear to be viewed favourably by Australian policy makers.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-naloxone-how-to-save-a-life-from-opioid-overdose-63459">Weekly Dose: Naloxone, how to save a life from opioid overdose</a>
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<p>In many ways, the fentanyl-related compounds connect many of the problems and solutions of modern drugs policy in Australia. Many are novel products, manufactured to pharmaceutical purity, as the global drug market mutates into something darker and less tangible. Their emergence has been catalysed by a Big Pharma peddled epidemic of opiates, <a href="https://www.theguardian.com/science/2016/may/25/opioid-epidemic-prescription-painkillers-heroin-addiction">coupled with a subsequent crackdown in availability</a>.</p>
<p>We have no meaningful toxicological early warning system that widely shares data in Australia - we rely on whispers. Consumers who overdose are unlikely to survive outside of a medically-supervised injecting centre, providing yet more pressure for the <a href="https://theconversation.com/why-australia-needs-drug-consumption-rooms-53215">expansion of those services in Australia</a> - and yet still, they are opposed.</p>
<p>The tabloid press would have us believe the drug “ice” is currently the biggest threat to Australian society. But doctors and drug professionals alike will tell you that potentially, the unfettered spread of carfentanil and the illicit synthetic fentanyls is much worthier of your fear.</p><img src="https://counter.theconversation.com/content/73270/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Caldicott is a recipient of an NH&NMRC Partnership Grant. He is affiliated with ATODA, and provides bipartisan medical advice on illicit drugs to state and federal agencies. He is the Clinical Lead of the Australian Drug Observatory (ANU)</span></em></p>Carfentanil is an ultra-potent synthetic opioid. Its only legitimate use is in veterinary practice for large animals such as elephants, but it sneaks into heroin shipments to increase its potency.David Caldicott, Emergency Medicine Consultant, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/732662017-02-26T19:04:40Z2017-02-26T19:04:40ZWeekly Dose: GHB, a party drug that’s easy to overdose on but was once used in childbirth<figure><img src="https://images.theconversation.com/files/157830/original/image-20170222-1340-1uyzyjt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People who take GHB at dance parties say it makes them feel euphoric and less inhibited. But the drug is easy to overdose on.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/573004459?src=HX483FdrXw1-JTtOy5jcIg-1-11&size=medium_jpg">from www.shutterstock.com</a></span></figcaption></figure><p><a href="http://www.drugwise.org.uk/ghb/">GHB</a> stands for gamma-hydroxybutyric acid (also known as 4-hydroxybutanoic acid) and is a naturally occurring neurotransmitter. It’s also a recreational drug.</p>
<p>People take it at dance parties and to enhance sex. Although it’s a depressant, like alcohol, in small doses people find it stimulates them.</p>
<p>It’s in the news in Australia because <a href="http://www.abc.net.au/news/2017-02-19/electric-parade-festival-more-than-20-overdose-hospital/8283828">at least 20 people</a> were taken to hospital recently with suspected GHB overdoses after attending a recent music festival in Melbourne.</p>
<p>Overdoses can happen easily because people do not know the strength of the drug they are taking. Also, the amount needed for the desired effect is not much less than the amount that <a href="http://europepmc.org/abstract/med/10869868">can cause an overdose</a>.</p>
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<a href="https://images.theconversation.com/files/158238/original/image-20170224-32729-126myhq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/158238/original/image-20170224-32729-126myhq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/158238/original/image-20170224-32729-126myhq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=717&fit=crop&dpr=1 600w, https://images.theconversation.com/files/158238/original/image-20170224-32729-126myhq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=717&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/158238/original/image-20170224-32729-126myhq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=717&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/158238/original/image-20170224-32729-126myhq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=901&fit=crop&dpr=1 754w, https://images.theconversation.com/files/158238/original/image-20170224-32729-126myhq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=901&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/158238/original/image-20170224-32729-126myhq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=901&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>How is it used?</h2>
<p>GHB has many street or slang names including G, fantasy, grievous bodily harm (GBH), juice, liquid ecstasy, liquid E, liquid X, Georgia Home Boy, soap, scoop, cherry meth and blue nitro. It is also called fishies because it is sometimes sold in the small fish-shaped soy sauce containers sold with sushi.</p>
<p>It’s generally made in small batches in people’s homes rather than <a href="http://europepmc.org/abstract/med/10869868">illicit drug labs</a> and <a href="http://www.australiandoctor.com.au/cmspages/getfile.aspx?guid=9be78a1b-dc64-4f9e-a191-15aeb295ba78">comes as a clear liquid</a> with no smell that often <a href="http://europepmc.org/abstract/med/10869868">tastes salty</a>. </p>
<p>It’s often sold in a small plastic container, or sometimes as a white powder, for about A$10 a dose. People usually swallow it, but can inject it or insert it anally.</p>
<h2>Who uses it</h2>
<p>A major 2013 drug survey found only <a href="http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129549848">0.1% or 24,000</a> Australians aged over 14 had used GHB in the past year.</p>
<p>People most likely to use GHB usually use other drugs as well. GHB use has recently increased among regular ecstasy and methamphetamine users but is still infrequent. Of those who reported using it in 2016, most said they had used it <a href="https://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/EDRS%20October%202016_FINAL.pdf">two or three times</a> that year.</p>
<h2>What are its effects?</h2>
<p>No-one is certain what naturally-occurring GHB does in the body. But we do know it increases levels of <a href="http://www.who.int/medicines/areas/quality_safety/4.1GHBcritical_review.pdf">dopamine in the brain</a>, a neurotransmitter that helps control the brain’s reward and pleasure centres.</p>
<p>Its effects on the body start within five to 20 minutes of taking the drug and last three to four hours. GHB causes a loss of inhibition, relaxes people, boosts their sex drive and promotes feelings of euphoria.</p>
<p>But side-effects include memory lapses, drowsiness, clumsiness, dizziness or headache, lowered temperature, tremors, nausea and diarrhoea.</p>
<p>The effects of the drug vary according to how much people take (usually 0.5-3g), their body weight, if they are used to taking it, and if they have taken other drugs, including alcohol.</p>
<p><a href="http://www.ajemjournal.com/article/S0735-6757(09)00553-1/abstract">Symptoms of a GHB overdose</a> include vomiting, sweating, shallow breathing, confusion, agitation, hallucinations, seizures, blackouts and unconsciousness for several hours.</p>
<p>Some people have died from GHB because they appear to have gone to sleep but are actually unconscious and have stopped breathing.</p>
<p>Children have also <a href="http://www.theage.com.au/news/national/recall-for-toy-that-turns-into-drug/2007/11/06/1194329225773.html">accidentally overdosed</a> on GHB after swallowing beads from a children’s toy called Bindeez. In 2007, three children were hospitalised after swallowing the beads, made using an incorrect chemical, which turned into GHB in the stomach.</p>
<h2>The date rape drug?</h2>
<p>GHB has been linked to drink spiking and sexual assault. This was the case for <a href="http://www.smh.com.au/national/three-face-charges-over-brimble-cruiseship-death-20080911-4ekv.html">Dianne Brimble</a>, who died on a cruise ship in 2002 after being given GHB and alcohol. So GHB is sometimes called the date rape drug.</p>
<p>Some campaigns about the dangers of drink spiking reported GHB makes people unable to <a href="https://web.archive.org/web/20120510151441/http://www.justice.gov/dea//ongoing/daterapep.html">resist sexual advances</a>.</p>
<p>GHB can only be detected in urine samples for <a href="https://pdfs.semanticscholar.org/a4a3/d2fce99c40bf3e3d3acb5632eac7c3bc7914.pdf">four hours</a> after the drug has been taken. This suggests GHB could have been used when people were drugged and sexually assaulted but it would have left their system by the time they sought help.</p>
<p>But more recent studies <a href="http://www.sciencedirect.com/science/article/pii/S1353113106000393">in Australia</a>, <a href="http://www.24housing.co.uk/news/no-evidence-to-suggest-widespread-date-rape-drug-use/">Netherlands</a> and elsewhere show alcohol is the drug most common in drink spiking, not GHB or other sedatives.</p>
<h2>Is GHB illegal?</h2>
<p>GHB is a chemical that occurs naturally in the body and helps messages travel to the brain. You can also find GHB in some <a href="http://europepmc.org/abstract/med/15939164">meats, fruit and wine</a>.</p>
<p>But as a synthesised chemical, its classification in Australia changed in 2014 from a prohibited drug to a controlled drug (a schedule 8 drug).</p>
<p>This is so doctors could prescribe it for the sleeping disorder <a href="https://theconversation.com/the-big-sleep-science-is-waking-up-to-the-curious-story-of-narcolepsy-45040">narcolepsy</a> under the brand name <a href="http://sleephub.com.au/xyrem-in-australia/">Xyrem</a>. Doctors can only access the drug by special request to the <a href="https://www.tga.gov.au/">Therapeutic Goods Administration</a>.</p>
<h2>An interesting history</h2>
<p>GHB has an <a href="http://www.who.int/medicines/areas/quality_safety/4.1GHBcritical_review.pdf">interesting history</a>.
Russian chemist Alexander Zaytsev synthesised it in 1874 but there are no reports about how it was used at the time. </p>
<p>It was not until 1964 when French doctor Dr Henri Laborit used GHB to drop people’s temperature during surgery, trying to reverse the symptoms of shock caused by their injuries and the operation.</p>
<p>GHB was widely used in Europe for several decades as an anaesthetic in childbirth because it helped the cervix dilate. It was also used to help people sleep. But the development of newer drugs has superseded it.</p>
<p>Reports of GHB use and overdose have been recorded internationally by the <a href="http://www.who.int/medicines/areas/quality_safety/4.1GHBcritical_review.pdf">World Health Organization</a> since 1990. Most reports are from the USA, western Europe and Australia, with spikes at different time periods indicating changes in availability.</p>
<p>Low price, easy administration and limited information about the risks of GHB can cause serious problems for people who try it.</p><img src="https://counter.theconversation.com/content/73266/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julaine Allan has received funding from the NHMRC, ARC, RIRDC, NSW Health and the Ian Potter Foundation to undertake research related to drug and alcohol use.</span></em></p>It’s easy to overdose on the recreational drug GHB, as recent cases in Melbourne show.Julaine Allan, Senior Research Fellow, Charles Sturt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/674442016-12-21T01:38:23Z2016-12-21T01:38:23ZWeekly Dose: doxycycline treats a host of human plagues, but it won’t work forever<figure><img src="https://images.theconversation.com/files/145951/original/image-20161115-13998-d0b8kk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pathogens like malaria get inside our cells - so an antibiotic to combat them needs to as well. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/pennstatelive/7694655428/in/photolist-cHX7YU-9M7z9X-njGj7X-bEw8gp-81RKbf-9y3cgk-bBzyvE-6KXii7-cVenpS-cVenw7-cVenub-7jxRvu-bu5fXr-cVenrQ-bmtm9b-a89QJq-cVenyA-8YRQTF-64Aerb-e9jtqQ-bBzywu-bQuffr-cVenny-bzodNi-koAcjr-9RM3wg-a86Us8-5KmsAb-cVengj-9RQrLJ-kh6DAs-bBzyDj-bBzyS5-cVenku-7XonZ4-5AZ8ha-dmmiS1-9RPWso-dBmmsz-oDtBij-dHmgZk-5MXsA2-dkd7Ty-njYAJr-8haqFS-cVeniA-boKniN-bxm5G3-nGYKh5-nvzhNr">Penn State/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Doxycycline is an antibiotic drug that kills a wide, weird and wonderful range of bugs that are often difficult to treat with other antibiotics. These include bacteria and parasites that take up residence inside our cells (called “intracellular organisms”), making them hard for most antibiotics to reach.</p>
<p>Unlike many other antibiotics, doxycycline penetrates deep into our tissues and ends up inside our cells, where it can kill these bugs. Examples of intracellular organisms susceptible to doxycycline include numerous “<a href="https://theconversation.com/first-hendra-now-bat-lyssavirus-so-what-are-zoonotic-diseases-12444">zoonotic infections</a>” (infections that are spread from animals to humans), <a href="https://theconversation.com/why-is-trachoma-blinding-aboriginal-children-when-mainstream-australia-eliminated-it-100-years-ago-63526">chlamydia</a>, <a href="https://theconversation.com/hospital-outbreak-of-legionella-should-we-be-worried-3031">legionella</a> (the cause of legionnaire’s disease) and <a href="https://theconversation.com/weekly-dose-mefloquine-an-antimalarial-drug-made-to-win-wars-55566">malaria</a>. </p>
<p>Other susceptible microorganisms include “spirochaetes” (that can cause syphilis and <a href="https://theconversation.com/explainer-what-is-lyme-disease-and-does-it-exist-in-australia-57717">Lyme disease</a>) and the <a href="https://theconversation.com/acne-treatment-antibiotics-dont-need-to-kill-bacteria-to-clear-up-your-skin-56188">bacteria that cause acne</a>, <a href="http://www.cdc.gov/anthrax/bioterrorism/threat.html">anthrax</a> and <a href="https://theconversation.com/has-haitis-cholera-epidemic-become-a-permanent-problem-55790">cholera</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/146183/original/image-20161116-13526-1z0ucg7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/146183/original/image-20161116-13526-1z0ucg7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=797&fit=crop&dpr=1 600w, https://images.theconversation.com/files/146183/original/image-20161116-13526-1z0ucg7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=797&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/146183/original/image-20161116-13526-1z0ucg7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=797&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/146183/original/image-20161116-13526-1z0ucg7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1002&fit=crop&dpr=1 754w, https://images.theconversation.com/files/146183/original/image-20161116-13526-1z0ucg7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1002&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/146183/original/image-20161116-13526-1z0ucg7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1002&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<h2>Mechanism</h2>
<p>Doxycycline interferes with a microorganism’s ability to manufacture proteins – the “building blocks” of life. Protein manufacture occurs in a part of the cell called the “ribosome” and is fundamental to any organism’s survival. </p>
<p>The reason doxycycline kills bacteria and parasites, but not our own cells, is that ours have a different type of ribosome to these simpler organisms. </p>
<h2>Uses</h2>
<p>Because doxycycline kills a wide range of bacteria that can infect the respiratory system, it is commonly prescribed for pneumonia and bronchitis. It is also widely used for treating acne and infections of the urinary and genital systems. </p>
<p>It is usually taken orally as tablets or capsules but can also very occasionally be given as an intravenous injection.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/145953/original/image-20161115-13995-zrxosm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/145953/original/image-20161115-13995-zrxosm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/145953/original/image-20161115-13995-zrxosm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/145953/original/image-20161115-13995-zrxosm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/145953/original/image-20161115-13995-zrxosm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/145953/original/image-20161115-13995-zrxosm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/145953/original/image-20161115-13995-zrxosm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/145953/original/image-20161115-13995-zrxosm.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">Doxycycline interferes with a microorganism’s ability to manufacture proteins - which is essential for survival.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/tep/373530231/">Tim Proctor/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Doxycycline continues to exert its effects for some time after being taken. This means it can be used not only as treatment, but also for prevention or “prophylaxis”. </p>
<p>Its most widespread use as prophylaxis is for tourists and other travellers (such as military personnel) going to tropical countries where it is used to <a href="https://theconversation.com/weekly-dose-mefloquine-an-antimalarial-drug-made-to-win-wars-55566">protect primarily against malaria</a>. It may also provide additional protection from <a href="https://theconversation.com/explainer-what-is-gastroenteritis-and-why-cant-i-get-rid-of-it-34351">common bacterial causes of diarrhoea</a>.</p>
<p>To be effective in preventing infection, it needs to be taken once a day during the time the person is at risk. Doxycycline is also active against a number of bacteria that could possibly be used as agents of “germ” warfare. This included, most notably, <a href="http://www.cdc.gov/anthrax/bioterrorism/threat.html">anthrax</a>. So it could be used as prophylaxis in military or other populations thought to be at risk of bio-warfare or following release of anthrax into the environment by terrorists.</p>
<h2>Development</h2>
<p>The development of doxycycline followed the <a href="https://theconversation.com/weekly-dose-penicillin-the-mould-that-saves-millions-of-lives-63770">momentous discovery of penicillin</a>, a natural compound produced by a certain type of mould. </p>
<p>This lead many pharmaceutical companies to investigate the microbe-killing properties of a large number of other natural products, such as those produced by other microorganisms and plants, a process termed “bio-discovery”. </p>
<p>This unearthed natural compounds with anti-microbial activity and further synthetic modification <a href="https://theconversation.com/natural-medicine-is-great-but-chemists-can-make-it-even-better-28362">improved these natural compounds</a>.</p>
<h2>Resistance</h2>
<p>Like all antibiotics, doxycycline is susceptible to bugs that <a href="https://theconversation.com/perspectives-on-antibiotic-resistance-how-we-got-here-where-were-headed-60140">develop resistance</a>. There is evidence this has already occurred in settings where the drug is widely used, <a href="http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00527-7/abstract">such as treatment of acne</a>. </p>
<p>This means its use may be curtailed or overtaken by alternative drugs for some conditions, now or in the future.</p>
<h2>Side effects and reactions</h2>
<p>The most commonly reported side effect is inflammation of the oesophagus (food pipe), causing heartburn. This can be quite unpleasant but is somewhat preventable by taking the medication with plenty of water, while standing and well before going to bed. </p>
<p>“Photosensitivity” (heightened sensitivity to sunlight resulting in being easily sunburnt) is also common ( in <a href="http://www.ajtmh.org/content/84/4/517.full">up to 20%</a> of people taking it). This is especially problematic for travellers using it as malaria prophylaxis in tropical countries. </p>
<p>Doxycycline should not be used in children or in pregnant women where it can result in permanent brown staining of teeth and have other effects on foetal bone development. </p>
<p>Doxycycline can <a href="https://theconversation.com/weekly-dose-methotrexate-the-anti-inflammatory-drug-that-can-kill-if-taken-daily-60322">increase the toxicity</a> of the anti-inflammatory drug <a href="https://theconversation.com/weekly-dose-methotrexate-the-anti-inflammatory-drug-that-can-kill-if-taken-daily-60322">methotrexate</a>.</p>
<h2>Controversies</h2>
<p><a href="https://theconversation.com/weekly-dose-mefloquine-an-antimalarial-drug-made-to-win-wars-55566">Recent high-profile controversies</a> regarding side-effects from antimalarial drug mefloquine in defence-force personnel and refugees have highlighted the role of doxycycline as one of two main alternatives to mefloquine.</p>
<p>It is now generally considered a preferable initial choice to mefloquine for malaria prophylaxis. Interestingly, previous studies suggest many people actually <a href="https://www.mja.com.au/journal/2005/182/4/mefloquine-and-doxycycline-malaria-prophylaxis-australian-soldiers-east-timor">prefer taking mefloquine</a> to doxycycline.</p>
<p>This may reflect the nature of doxycycline’s side effects, but also its less convenient daily dosing (mefloquine is taken weekly).</p>
<h2>Possible future uses</h2>
<p>It has <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064561">recently been found</a> doxycycline affects processes in human cells, especially a group of enzymes important for the body’s inflammatory response. This property may be beneficial and could lead to applications for treating various non-infectious conditions.</p>
<p>These include cancers (especially those involving bone), inflammatory and autoimmune conditions (including rheumatoid arthritis and multiple sclerosis) and atherosclerotic diseases (plaque build-up in your arteries that can cause heart disease). However, these applications are currently still mostly in the experimental stage.</p><img src="https://counter.theconversation.com/content/67444/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Harin Karunajeewa is supported by an Australian National Health and Medical Research Council fellowship. </span></em></p>Doxycycline is an antibiotic drug that kills a wide, weird and wonderful range of bugs that are often difficult to treat with other antibiotics.Harin Karunajeewa, Associate Professor, Walter and Eliza Hall InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/677042016-11-17T04:22:53Z2016-11-17T04:22:53ZWeekly Dose: Ritalin, helpful for many with ADHD but dangerous if abused by those without it<figure><img src="https://images.theconversation.com/files/144151/original/image-20161102-12150-17bcgq4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">For people with ADHD, Ritalin helps improve concentration and focus. </span> <span class="attribution"><span class="source">Kids in classroom from www.shutterstock.com</span></span></figcaption></figure><p>Ritalin is the most common brand name for methylphenidate, a stimulant used to treat attention deficit hyperactivity disorder (ADHD). </p>
<p>Pharmaceutical company Novartis owns the name Ritalin, but methylphenidate is marketed under other brand names by other manufacturers; such as Concerta which is produced by the company Janssen.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/146329/original/image-20161117-13383-1jk72bh.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/146329/original/image-20161117-13383-1jk72bh.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/146329/original/image-20161117-13383-1jk72bh.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=870&fit=crop&dpr=1 600w, https://images.theconversation.com/files/146329/original/image-20161117-13383-1jk72bh.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=870&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/146329/original/image-20161117-13383-1jk72bh.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=870&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/146329/original/image-20161117-13383-1jk72bh.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1093&fit=crop&dpr=1 754w, https://images.theconversation.com/files/146329/original/image-20161117-13383-1jk72bh.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1093&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/146329/original/image-20161117-13383-1jk72bh.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"></a>
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<h2>History</h2>
<p>Methylphenidate was <a href="http://www.cesar.umd.edu/cesar/drugs/ritalin.asp">developed in 1944</a> by pharmaceutical company CIBA, now Novartis, as a stimulant. Although methylphenidate is chemically different to amphetamines, its <a href="http://www.pbs.org/wgbh/pages/frontline/shows/medicating/backlash/un.html">pharmacological properties</a> are similar. </p>
<p>In the late 1950s, it was sold to treat chronic fatigue, depression, narcolepsy and also for <a href="https://www.ncbi.nlm.nih.gov/pubmed/13629025">sedation</a> caused by other medications.</p>
<p>It was later found to improve behaviour in children who were <a href="https://www.ncbi.nlm.nih.gov/pubmed/14410146">hyperactive and impulsive</a>. In the 1960s, research on Ritalin was focused around treatment of “hyperkinetic syndrome,” which would eventually be called attention deficit hyperactivity disorder.</p>
<p>In 1996, <a href="http://www.pbs.org/wgbh/pages/frontline/shows/medicating/backlash/un.html">it was reported</a> the United States accounted for around 90% of total world manufacture and consumption of Ritalin. </p>
<h2>What is attention deficit hyperactivity disorder?</h2>
<p>People with ADHD have deficits in their executive functioning, which means their thought processes are less efficient than those without the disorder. If a person with ADHD is going to <a href="http://www.intechopen.com/books/adhd-new-directions-in-diagnosis-and-treatment/therapy-for-adhd-directed-towards-addressing-the-dual-imbalances-in-mental-effort-and-reward-as-illu">complete a task</a>, the task either has to be easy, short, or sufficiently interesting or rewarding to fully engage their attention.</p>
<p>Tasks such as studying may require a prolonged and intense period of concentration which a person with ADHD would typically find difficult to maintain.</p>
<h2>How does Ritalin work?</h2>
<p>Methylphenidate is similar in structure and function to amphetamines, such as dexamphetamine, which is also used to treat ADHD. </p>
<p>These stimulants <a href="http://www.sciencedirect.com/science/article/pii/S0301008205000432">increase concentrations</a> of the neurotransmitters dopamine and noradrenaline in the brain, which <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Effects+of+methylphenidate+on+extracellular+dopamine%2C+serotonin%2C+and+norepinephrine%3A+comparison+with+amphetamine">enhances communication</a> between brain cells. Effectively, this makes the mind work more efficiently, requiring less effort to get a task done.</p>
<p>ADHD is not a categorical diagnosis but a continuum. This means although some people clearly have ADHD and some clearly do not, there are many shades of grey between the two extremes. </p>
<p>It is therefore not surprising stimulants also improve mental efficiency in people without ADHD. The main difference is people with ADHD have more concentration problems and therefore show more scope for improvement on stimulants.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/144134/original/image-20161102-6277-1mwy4dw.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/144134/original/image-20161102-6277-1mwy4dw.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=312&fit=crop&dpr=1 600w, https://images.theconversation.com/files/144134/original/image-20161102-6277-1mwy4dw.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=312&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/144134/original/image-20161102-6277-1mwy4dw.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=312&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/144134/original/image-20161102-6277-1mwy4dw.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=392&fit=crop&dpr=1 754w, https://images.theconversation.com/files/144134/original/image-20161102-6277-1mwy4dw.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=392&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/144134/original/image-20161102-6277-1mwy4dw.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=392&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Ritalin is the most common brand name for methylphenidate.</span>
<span class="attribution"><span class="source">Editor182/Wikimedia Commons</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>How is Ritalin taken?</h2>
<p>ADHD is most commonly diagnosed in primary school, and the child is usually started on treatment at this time.</p>
<p>Both methylphenidate and dexamphetamine come in immediate-release tablets which last for around three to six hours; dexamphetamine lasts slightly longer than methylphenidate. </p>
<p>After taking a dose, the drug concentration rises to a maximum and then falls. Everyone has their own therapeutic range, which is the concentration the drug has to be in order to be effective.</p>
<p>The doctor normally establishes the appropriate dose by starting at a low dose and gradually increasing it over several weeks to find the most effective dose. If the person’s optimal dose is exceeded, their functioning becomes less efficient and negative effects increase. </p>
<p>The executive function deficits associated with ADHD are consistent over time, but people change as they go through different stages of development. As children progress through school, the demands on their concentration increase, and untreated ADHD is often associated with declining grades.</p>
<h2>How many people use it?</h2>
<p>Around 11% of Australian children and adolescents <a href="https://www.ncbi.nlm.nih.gov/pubmed/11990891">had diagnosable ADHD</a> in 2007 although most were not treated. Between 2002 and 2009, <a href="http://www.smh.com.au/lifestyle/diet-and-fitness/males-fuel-rise-of-the-ritalin-generation-20110123-1a18d.html">prescriptions for stimulant drugs</a> to treat ADHD among Australians reportedly rose by nearly 90%.</p>
<p>This can be explained by the introduction of newer, sustained-release tablets, which meant doctors could better tailor treatment to the individual – by combining immediate-release and sustained-release formulations for instance. This led to more prescriptions per person per year.</p>
<p>In 2015, around 906,754 <a href="http://www.pbs.gov.au/info/statistics/asm/asm-2015#table-1">scripts were written</a> for methylphenidate and dexamphetamine.</p>
<h2>What does it cost?</h2>
<p>Methylphenidate is subsidised under the <a href="http://www.pbs.gov.au/medicine/item/3440C">Pharmaceutical Benefits Scheme</a> (PBS). One packet of 30 Ritalin 10 mg capsules costs A$38.30 for those with a prescription, or A$6.20 for health care card holders. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/145136/original/image-20161109-16707-1vwssy6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/145136/original/image-20161109-16707-1vwssy6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/145136/original/image-20161109-16707-1vwssy6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/145136/original/image-20161109-16707-1vwssy6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/145136/original/image-20161109-16707-1vwssy6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/145136/original/image-20161109-16707-1vwssy6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/145136/original/image-20161109-16707-1vwssy6.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">Ritalin and other stimulants are sometimes used by those who do not have ADHD to boost cognitive performance.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/stemonx/7209965342/in/photolist-bZ7Xvh-8KsHQi-4MVd7x-cNhBmf-9wpbUi-86pzDv-a1vR2q-8KvLgL-6YD2sU-6Xw3cw-GMgno-9WpdAh-cNhDBb-h6sMXB-ntp41t-a1cfTi-a1fcJQ-dnjKxW-4YiSdp-e3wk3A-iTGPv4-bZ3uRh-YFFY-akCDca-eDkcp3-eDea9z-ntroQy-335jX-a1cfsD-o3LcNr-5HDAMF-7GAHbc-5yb9sf-dAW32n-ahnorp-6myfGX-eDkhu3-a1sZ88-a1sYGc-a1cg4t-7U3Nqd-a1vQQy-a1vRdh-cEJusL-p9oPCQ-nrmFbU-qqLtzC-6y22DF-cNhAD5-mckoua">StefanoMontagner/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>What are the side effects?</h2>
<p>The <a href="https://www.ncbi.nlm.nih.gov/pubmed/9310521/">side effects</a> of stimulants are dose-related, the most common being appetite suppression and insomnia. </p>
<p>In overdose, methylphenidate is <a href="https://www.ncbi.nlm.nih.gov/pubmed/12595781/">associated</a> with rapid heart rate, high blood pressure, irritability and agitation. Ongoing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1925483/">stimulant abuse</a> can also be associated with malnutrition.</p>
<h2>Is it a performance-enhancing study drug?</h2>
<p>After leaving school a person with ADHD has more opportunity to choose a career that matches their strengths and interests and many stop treatment. But for those who go on to study at university, academic demands increase and students with ADHD are likely to remain on medication. </p>
<p>This means some people at university have legitimate access to Ritalin. But there is <a href="http://www.smh.com.au/national/education/hsc-students-use-drugs-to-get-through-exams-20161010-gryydk.html">ongoing concern</a> these stimulants are being diverted to, and abused by, those who do not have ADHD but are hoping for cognitive enhancement.</p>
<p>There is evidence of an increase in methylphenidate abuse by people who don’t have ADHD, with one <a href="https://www.ncbi.nlm.nih.gov/pubmed/26937669">study showing a threefold rise between 2004 and 2014 in NSW</a>.</p>
<p>It might be argued it’s not a problem for a person without ADHD, who understands how to use Ritalin, to take it for studying. But it is illegal, and it may give an unfair advantage in the same way as performance enhancing drugs in sport.</p><img src="https://counter.theconversation.com/content/67704/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alison Poulton works for the University of Sydney, has consulted for the Shire and owns shares in GSK. She has received research funding from the Australian Women and Children's Research Foundation and the Nepean Medical Research Foundation. She is a Fellow of the Royal Australasian College of Physicians and the Australasian ADHD Association.</span></em></p>Ritalin is the most common brand name for methylphenidate, a stimulant used to treat attention deficit hyperactivity disorder (ADHD).Alison Poulton, Senior Lecturer Paediatrics, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/641722016-10-19T05:56:41Z2016-10-19T05:56:41ZWeekly Dose: multiple sclerosis drug fingolimod comes from fungus Chinese medicine calls ‘eternal youth’<figure><img src="https://images.theconversation.com/files/140648/original/image-20161006-20152-10v1s0f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Multiple sclerosis involves the central nervous system, made up of the brain and spinal cord.</span> <span class="attribution"><span class="source">from shutterstock.com</span></span></figcaption></figure><p>Fingolimod is a drug used to treat multiple sclerosis (MS), an autoimmune disease. It is an immunosuppressant, which means it works by suppressing the immune system.</p>
<p>Fingolimod is an oral medication and is marketed in Australia under the brand name Gilenya®.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/142290/original/image-20161019-20333-14t0zq8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/142290/original/image-20161019-20333-14t0zq8.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=763&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142290/original/image-20161019-20333-14t0zq8.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=763&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142290/original/image-20161019-20333-14t0zq8.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=763&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142290/original/image-20161019-20333-14t0zq8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=959&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142290/original/image-20161019-20333-14t0zq8.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=959&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142290/original/image-20161019-20333-14t0zq8.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=959&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<h2>What is multiple sclerosis?</h2>
<p>Multiple sclerosis (MS) is a chronic disabling disease that involves the central nervous system, made up of the brain and spinal cord. </p>
<p>While the exact cause of MS is unknown, current evidence suggests an <a href="https://www.ncbi.nlm.nih.gov/pubmed/23709211">abnormal immune-system response</a> leads to the development of increased numbers of white blood cells, called lymphocytes. This causes damage to the nerve cells in the brain and spinal cord. </p>
<p>The damage is mainly characterised by unravelling of the outer layer, called a myelin sheath, of the affected nerve cells. Then, lesions form which interrupt the transmission of nerve signals. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/140644/original/image-20161006-20132-1a2davi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/140644/original/image-20161006-20132-1a2davi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/140644/original/image-20161006-20132-1a2davi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=260&fit=crop&dpr=1 600w, https://images.theconversation.com/files/140644/original/image-20161006-20132-1a2davi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=260&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/140644/original/image-20161006-20132-1a2davi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=260&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/140644/original/image-20161006-20132-1a2davi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=326&fit=crop&dpr=1 754w, https://images.theconversation.com/files/140644/original/image-20161006-20132-1a2davi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=326&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/140644/original/image-20161006-20132-1a2davi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=326&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In MS, an abnormal immune response causes unravelling of the outer layer of the affected nerve cells.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>Common <a href="http://www.msra.org.au/files/msra/docs/Key%20Facts%20and%20figures%20about%20MS%20September%202012.pdf">symptoms of MS include</a> muscle weakness and numbness, difficulty with thinking, fatigue, dizziness and visual disturbances. </p>
<p>The disease course of MS commonly involves a pattern of attacks where symptoms are severe, followed by relatively symptom-free periods.</p>
<h2>History of fingolimod</h2>
<p>Medications that suppress the immune system <a href="https://www.ncbi.nlm.nih.gov/pubmed/19812733">have a history</a> with fungus.</p>
<p>One of the earliest immunosuppresant medications, cyclosporin – used to prevent rejection of an organ transplant – was derived from fungus. Its success led to further investigations of fungi as a source of immunosuppresant compounds. </p>
<p>Fingolimod was first derived from the fungus <em>Isaria sinclairii</em> in 1992. In Chinese medicine, this fungus is known as “eternal youth”.</p>
<h2>How does fingolimod work?</h2>
<p>Fingolimod <a href="https://www.ncbi.nlm.nih.gov/pubmed/23709211">suppresses</a> the abnormal immune system response in people with MS, by acting on a specific receptor (S1P-type-1) on lymphocytes. This reduces the circulation of the abnormally activated cells and nerve damage potential. </p>
<hr>
<p><em><strong>Further reading:</strong> <a href="https://theconversation.com/explainer-how-do-drugs-work-48665">Explainer: how do drugs work?</a></em></p>
<hr>
<p>Fingolimod is also thought to have some protective effects by reducing inflammation in the central nervous system, as well as premature cell death. There is also some evidence it helps repair the damage to the myelin sheath damage. </p>
<p>Fingolimod was the first oral medication developed to treat MS. Its predecessors, such as interferon beta, were in injectable form. This has been a major breakthrough for patients who find injections unpleasant.</p>
<p>Studies have shown fingolimod <a href="http://www.mdedge.com/neurologyreviews/article/72585/multiple-sclerosis/oral-drug-reduces-relapse-rates-multiple-sclerosis">reduces the relapse rate</a> of MS attacks by more than 50% compared to placebo. This is a significant reduction when compared to its predecessors.</p>
<h2>What are the side effects?</h2>
<p>The most <a href="http://www.msra.org.au">common side effects</a> of fingolimod include viral infections, headaches, back pain, diarrhoea and cough.</p>
<p>Using fingolimod has been associated with more serious but less common side effects such as vision disturbances, irregular heart beat and infections such as herpes, which have the potential to become life-threatening due to a suppressed immune system.</p>
<p>Doctors will screen patients before starting therapy. This involves assessing a patient’s risk of side effects due to other chronic conditions and medications. Ongoing monitoring for side effects during treatment is also necessary. </p>
<p>The majority of side effects will disappear once treatment with fingolimod stops. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/142296/original/image-20161019-20308-xek0h9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/142296/original/image-20161019-20308-xek0h9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=364&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142296/original/image-20161019-20308-xek0h9.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=364&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142296/original/image-20161019-20308-xek0h9.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=364&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142296/original/image-20161019-20308-xek0h9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=457&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142296/original/image-20161019-20308-xek0h9.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=457&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142296/original/image-20161019-20308-xek0h9.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=457&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The fungus Isaria sinclairii.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/84829097@N04/8266909197/in/photolist-dAwdnR-dAw56c">Petra Gloyn/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Availability and cost</h2>
<p>Fingolimod became available on the <a href="http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2011-03/pbac-psd-fingolimod-march11">Australian Pharmaceutic Benefits Scheme</a> in 2011. It is available to patients whose diagnosis is confirmed with an x-ray or scan and who have had at least two attacks within a two-year period. </p>
<p>For those who qualify for treatment, one month’s treatment, which involves one 0.5mg capsule per day, will cost A$38.30 for general patients or A$6.20 for those with a concession card. </p>
<p>The cost of one month’s therapy to the Australian Government is A$2314.50.</p>
<p>Between July 2014 and June 2015, A$134,752,870 was spent on supplying fingolimod to eligible patients, making it the <a href="http://www.pbs.gov.au/info/statistics/asm/asm-2015">tenth top medication by cost</a> to the Australian government.</p>
<h2>Who shouldn’t use it?</h2>
<p>Fingolimod <a href="https://www.nps.org.au/__data/assets/pdf_file/0008/123758/nvcgilor.pdf">can’t be used</a> in women who are or intending to become pregnant as it is thought to cause harm to the developing foetus. </p>
<p>Fingolimod is not to be used in patients under 18 years of age due to a lack of research in the paediatric population. It should also not be used at the same time as other medications that treat MS.</p><img src="https://counter.theconversation.com/content/64172/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jodie Hillen 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>Fingolimod is a drug used to treat multiple sclerosis (MS), an autoimmune disease. It is an immunomodulator, which means it works by suppressing the immune system.Jodie Hillen, PhD Candidate, Quality Use of Medicines and Pharmacy Research Centre, University of South AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/644402016-10-12T05:10:10Z2016-10-12T05:10:10ZWeekly Dose: aspirin, the pain and fever reliever that prevents heart attacks, strokes and maybe cancer<figure><img src="https://images.theconversation.com/files/141186/original/image-20161011-3894-d6qg3p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Aspirin has an extraordinary history that involves many different discoveries around its many different effects.</span> <span class="attribution"><span class="source">from shutterstock.com</span></span></figcaption></figure><p>Aspirin is, <a href="https://theconversation.com/weekly-dose-ibuprofen-just-because-its-freely-available-doesnt-make-it-safe-56346">like ibuprofen</a> and Voltaren (diclofenac), a <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/medications-non-steroidal-anti-inflammatory-drugs">non-steroidal anti-inflammatory</a> drug (NSAID) used to treat pain and reduce fever. </p>
<p>What makes aspirin different from other NSAIDs is its ability to thin the blood, and it is used to prevent blood clotting in those at risk of heart disease and stroke. Recently, it has also shown potential to reduce the risk of some cancers.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/141337/original/image-20161012-8389-1feja4k.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/141337/original/image-20161012-8389-1feja4k.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/141337/original/image-20161012-8389-1feja4k.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/141337/original/image-20161012-8389-1feja4k.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/141337/original/image-20161012-8389-1feja4k.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1006&fit=crop&dpr=1 754w, https://images.theconversation.com/files/141337/original/image-20161012-8389-1feja4k.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1006&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/141337/original/image-20161012-8389-1feja4k.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1006&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<h2>How does it work?</h2>
<p>Aspirin works by <a href="https://www.ncbi.nlm.nih.gov/pubmed/14592543">inhibiting an enzyme called cyclooxygenase</a>, which generates prostaglandins. These are in turn associated with inflammation, pain and fever.</p>
<p>Through the same enzyme, aspirin also inhibits the production of substances called thromboxanes. These are responsible for the aggregation of platelets in the blood, a process needed to stop bleeding. This is what we mean when we say aspirin “thins the blood.” </p>
<p>The mechanism whereby aspirin might be protective against cancer is not fully understood but certain <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786609/">genetic and other characteristics</a> may identify those who might particularly benefit.</p>
<h2>History</h2>
<p>In the 16th century BC, <a href="https://books.google.com.au/books/about/Ancient_Egyptian_Medicine.html?id=WHfEnVU6z8IC&redir_esc=y">Egyptians documented on papyrus</a> that the bark and leaves of willow and related plants had pain-relieving and anti-inflammatory properties. The Greek physician Hippocrates later <a href="https://en.wikipedia.org/wiki/History_of_aspirin">noted these same properties </a> in the 5th century BC. </p>
<p>Aspirin’s more recent history came from purifying salicylate, the active component in ancient preparations. In 1897, this culminated in the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1119266/">development of acetylsalicylic acid</a> or aspirin.</p>
<p>Today’s interest in aspirin stems largely from the <a href="http://www.nature.com/nature-newbio/journal/v231/n25/abs/newbio231232a0.html">seminal 1971 publication</a> by English pharmacologists <a href="https://books.google.com.au/books?id=v9AZ76VD7ZYC&pg=PA227&lpg=PA227&dq=Vane+and+Piper+Aspirin&source=bl&ots=RYtUF9Uudc&sig=lQmcimixCjETOCOJDYsXM7GGgEY&hl=en&sa=X&ved=0ahUKEwjN8LnO-tHPAhVW5WMKHRZzBNoQ6AEIMjAD#v=onepage&q=Vane%20and%20Piper%20Aspirin&f=false">John Vane and Priscilla Piper</a>, who discovered its action in inhibiting prostaglandin production. In 1982, Vane shared the <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/1982/">Nobel Prize in Physiology or Medicine</a> for his work in this area. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/141179/original/image-20161011-3903-1edcryn.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/141179/original/image-20161011-3903-1edcryn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/141179/original/image-20161011-3903-1edcryn.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=643&fit=crop&dpr=1 600w, https://images.theconversation.com/files/141179/original/image-20161011-3903-1edcryn.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=643&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/141179/original/image-20161011-3903-1edcryn.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=643&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/141179/original/image-20161011-3903-1edcryn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=808&fit=crop&dpr=1 754w, https://images.theconversation.com/files/141179/original/image-20161011-3903-1edcryn.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=808&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/141179/original/image-20161011-3903-1edcryn.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=808&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">John Vane Vane shared the [Nobel Prize in Physiology or Medicine for his work on prostaglandins.</span>
<span class="attribution"><a class="source" href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/1982/">The Nobel Foundation website/Screenshot</a></span>
</figcaption>
</figure>
<p>In 1950, an American general practitioner Lawrence Craven noted that patients who had their tonsils removed and chewed Aspergum (<a href="http://www.drugstorenews.com/article/retrobrands-usa-looking-bring-aspergum-back-market">a gum containing Aspirin</a>) experienced severe bleeding. He later said daily aspirin <a href="https://www.ncbi.nlm.nih.gov/pubmed/17622365">appeared to prevent heart attacks</a> in his patients.</p>
<p>Craven’s claims were doubted by fellow doctors because they were not the subject of randomised trials. This was around the time that the importance of blood clots in events such as heart attack was recognised, and methodology that informed the robust design and interpretation of very large clinical trials was developed. </p>
<p>These trials included aspirin among the first therapies tested. A <a href="https://www.ncbi.nlm.nih.gov/pubmed/19482214">recent overview of such trials</a> showed that aspirin, when compared to inactive placebos, reduced serious vascular events such as heart attack and stroke by about 12% in those who had not previously had such conditions, and by about a fifth in those who had experienced them.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/141324/original/image-20161012-8411-drlvfy.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/141324/original/image-20161012-8411-drlvfy.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/141324/original/image-20161012-8411-drlvfy.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=793&fit=crop&dpr=1 600w, https://images.theconversation.com/files/141324/original/image-20161012-8411-drlvfy.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=793&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/141324/original/image-20161012-8411-drlvfy.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=793&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/141324/original/image-20161012-8411-drlvfy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=997&fit=crop&dpr=1 754w, https://images.theconversation.com/files/141324/original/image-20161012-8411-drlvfy.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=997&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/141324/original/image-20161012-8411-drlvfy.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=997&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Craven noted patients who chewed Aspergum experienced severe bleeding.</span>
<span class="attribution"><a class="source" href="http://www.drugstorenews.com/article/retrobrands-usa-looking-bring-aspergum-back-market">Drug Store News/screenshot</a></span>
</figcaption>
</figure>
<p>However, the overview also confirmed that benefits came at the cost of severe bleeding (due to aspirin’s ability to prevent clotting) from the stomach and bowel, or resulted in bleeding into the brain. </p>
<p>It is now apparent that factors such as advancing age, smoking and diabetes increase not only the risk of heart attack and stroke, but also major bleeding. This means aspirin can’t be prescribed indiscriminately for everyone.</p>
<h2>Aspirin and cancer</h2>
<p>In 1988, Melbourne surgeon Gabriel Kune reported that aspirin was associated with <a href="http://cancerres.aacrjournals.org/content/canres/48/15/4399.full.pdf">lower rates of bowel cancer</a>.</p>
<p>Subsequently, trials supported reduced cancer rate and death in those taking aspirin, not only of the bowel but also of some other organ types. However, cancer was not specified as a major outcome of interest at the beginning of these studies, and because of this, was not examined rigorously. </p>
<h2>How is it used?</h2>
<p><a href="https://heartfoundation.org.au/images/uploads/publications/Reducing-risk-in-heart-disease.pdf">Australian</a> guidelines for the use of low-dose aspirin to prevent heart events and stroke are clear cut. If aspirin does not cause problems, such as severe bleeding, it should be used life-long in everyone who has experienced heart-related events such as angina, heart attack, coronary bypass surgery and stroke.</p>
<p>In those who haven’t experienced these, decisions on aspirin use must be based on weighing up individual risk of bleeding and these events occurring in the future.</p>
<p>The latest, authoritative recommendations by the <a href="http://annals.org/article.aspx?articleID=2513179">U.S. Preventive Services Task Force</a> about prevention of cardiovascular disease and bowel cancer state that for those aged 50 to 69, taking aspirin depends on the estimated risk of events that might be prevented, and also of bleeding and life expectancy. </p>
<p>In those aged less than 50, or 70 years or over, there is insufficient evidence to assess the balance of benefits and harms of initiating aspirin use.</p>
<p>Present Australian <a href="http://www.cancer.org.au/content/pdf/HealthProfessionals/ClinicalGuidelines/ClinicalpracticeguidelinesJuly2008.pdf">guidelines for the prevention of bowel cancer</a> state there is insufficient evidence to recommend aspirin for all people at average risk, and emphasise that <a href="http://www.cancer.org.au/news/blog/prevention/does-an-aspirin-a-day-keep-cancer-away.html">diet and lifestyle improvements</a>, as well as screening, are effective in reducing risk. </p>
<p>However, those with a strong family history of bowel cancer should often be referred for specialist assessment and aspirin might be recommended after genetic testing.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/141340/original/image-20161012-8415-1r667mq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/141340/original/image-20161012-8415-1r667mq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/141340/original/image-20161012-8415-1r667mq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/141340/original/image-20161012-8415-1r667mq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/141340/original/image-20161012-8415-1r667mq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/141340/original/image-20161012-8415-1r667mq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/141340/original/image-20161012-8415-1r667mq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">For those aged 50 to 69, taking aspirin depends on the estimated risk of events that might be prevented, and also of bleeding and life expectancy.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>The low dose of aspirin typically used is 100mg daily. This is much less than that which might relieve a headache, other pain or fever, and for which paracetamol is generally recommended in the first instance.</p>
<h2>Who shouldn’t use it?</h2>
<p>Use of aspirin should be discussed with a doctor as it should not be used in those who have had a previous allergic reaction to aspirin or other NSAIDs, are pregnant or breastfeeding, have bleeding or clotting disorders, active stomach bleeding or a history of previous bleeding after treatment with aspirin, gastritis or an active or previous stomach ulcer, a history of gout, or severe kidney or liver failure. </p>
<p>Aspirin should be taken with water, with or without food. Taking an enteric-coated tablet, which is designed to prevent the aspirin from being released in the stomach, decreases the chance of an upset stomach.</p>
<h2>How much does it cost?</h2>
<p>Aspirin is relatively cheap and the cost can range from <a href="http://shop.coles.com.au/online/national/coles-tablets-aspirin-300mg">A$0.95 for a 24-pack</a> of 300mg tablets to <a href="http://www.chemistwarehouse.com.au/Shop-Online/723/Low-Dose-Aspirin">A$2.99</a> for 100 tablets of 100mg.</p>
<h2>Other points of interest</h2>
<p>The ongoing <a href="http://www.aspree.org/aus/">ASPirin in Reducing Events in the Elderly</a> (ASPREE) study, conceived and initiated in Australia, has completed recruitment and is following up more than 16,700 healthy Australians aged 70 years and over, and almost 2,500 people in the United States. It involves more than 2,000 Australian general practitioners as co-investigators. </p>
<p>The primary question investigated is whether aspirin improves healthy active life years (time lived free of dementia or physical disability), outcomes fundamentally important to the elderly. This encapsulates the net effect of benefits and risks of aspirin. </p>
<p>The trial will also provide unique data concerning whether aspirin prevents cancer in the elderly. It is anticipated that ASPREE’s findings will be reported in 2018.</p><img src="https://counter.theconversation.com/content/64440/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Professor Tonkin is a Chief Investigator on the ASPREE trial. </span></em></p>What makes aspirin different to other NSAIDs, used to relieve pain, is its ability to thin the blood. It is used to prevent blood clotting in those at risk of heart disease and stroke.Andrew Tonkin, Professor and Head, Cardiovascular Research Unit, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/644302016-10-05T01:59:54Z2016-10-05T01:59:54ZWeekly Dose: metformin, the diabetes drug developed from French lilac<figure><img src="https://images.theconversation.com/files/140206/original/image-20161003-20217-1bqbxvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Metformin was originally developed from natural compounds found in the plant known as French lilac.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/evergestis/14755129566/in/photolist-f53VB7-knNu4-f4NEY6-f53WnU-f53WLA-f53Vdu-ou2PVN-eo8vmw-ou2QgY-nXnEdz-fdVFFa-ocKcep-f9cDq4-cfyKeL-ouePbD-phNTVh-oTngVd-6qciLK-cRNFbh-cSifP9-otRTXC-wdReZL-J7MpWf-2EA72-53WPXo">Vlad Proklov/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Metformin is the most widely used drug to treat type 2 diabetes globally. In Australia, approximately <a href="http://www.ncbi.nlm.nih.gov/pubmed/17565410">two-thirds of patients</a> with type 2 diabetes are prescribed metformin, either alone or in combination with other pills, or with insulin injections. </p>
<p>Alongside diet and exercise, metformin is considered the <a href="http://www.racgp.org.au/your-practice/guidelines/diabetes/8-managing-glycaemia/83-glucose-lowering-agents/">first-choice drug</a> to improve glucose control in type 2 diabetes. </p>
<p>Metformin hydrochloride is the <a href="http://www.nhs.uk/chq/pages/1003.aspx?categoryid=73">scientific or generic name</a> for the active ingredient in tablets sold in Australia under 40 different <a href="https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=metformin">proprietary or brand names</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/140417/original/image-20161005-15886-zrlnzp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/140417/original/image-20161005-15886-zrlnzp.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=870&fit=crop&dpr=1 600w, https://images.theconversation.com/files/140417/original/image-20161005-15886-zrlnzp.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=870&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/140417/original/image-20161005-15886-zrlnzp.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=870&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/140417/original/image-20161005-15886-zrlnzp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1093&fit=crop&dpr=1 754w, https://images.theconversation.com/files/140417/original/image-20161005-15886-zrlnzp.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1093&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/140417/original/image-20161005-15886-zrlnzp.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>
</figcaption>
</figure>
<h2>History</h2>
<p>Metformin was originally developed from natural compounds found in the plant <em>Galega officinalis</em>, known as French lilac or goat’s rue. </p>
<p>Synthetic biguanides were developed in the 1920s in Germany, but their use was limited due to side effects. During the 1940s, however, French physician <a href="http://onlinelibrary.wiley.com/doi/10.1002/pdi.606/pdf">Jean Sterne</a> examined a new biguanide called dimethylbiguanide or metformin. At the time, it was being studied for the treatment of influenza, but Sterne recognised it had glucose-lowering properties. He proposed calling it glucophage, meaning glucose eater, a name with which it is still commercially associated today.</p>
<p>Metformin has been used to treat diabetes since the late 1950s. It is now on the World Health Organisation’s <a href="http://www.who.int/medicines/publications/essentialmedicines/en/">List of Essential Medicines</a> needed for a basic health care system. </p>
<h2>How does it work?</h2>
<p>Insulin suppresses the production of glucose by the liver. One reason glucose levels remain high in those with type 2 diabetes is due to insufficient insulin. The liver continues to inappropriately make large amounts of glucose, even when glucose levels are already high. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/138385/original/image-20160920-11131-12u3ppo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/138385/original/image-20160920-11131-12u3ppo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/138385/original/image-20160920-11131-12u3ppo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/138385/original/image-20160920-11131-12u3ppo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/138385/original/image-20160920-11131-12u3ppo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/138385/original/image-20160920-11131-12u3ppo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/138385/original/image-20160920-11131-12u3ppo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A French physician pioneered metformin for the treatment of diabetes and proposed calling it glucophage, meaning glucose eater.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>Metformin is able to reduce glucose production by the liver by approximately one-third, through <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676264/">mechanisms that remain to be fully understood</a>. When taken as directed, it will reduce the HbA1c, a marker of glucose control, by approximately <a href="http://www.ncbi.nlm.nih.gov/pubmed/27088241">0.5% to 1%</a>. </p>
<h2>Who uses it?</h2>
<p>Metformin is only indicated for lowering glucose levels in people with type 2 diabetes. However, it is also used off-label (<a href="https://theconversation.com/explainer-why-are-off-label-medicines-prescribed-44783">when medications are prescribed for conditions other than what they’ve been approved for</a>) to treat women with polycystic ovarian syndrome (PCOS) where it can be <a href="http://www.ncbi.nlm.nih.gov/pubmed/26060208">effective in some cases</a>.</p>
<p>Metformin is not used to treat people with gestational diabetes or type 1 diabetes, who must take insulin injections as required to control their glucose levels.</p>
<h2>How is it used?</h2>
<p>To work effectively, most people will take <a href="http://care.diabetesjournals.org/content/35/2/446">two to three grams of metformin</a> every day. To fit this much into a tablet, all medications containing metformin are the size of a small bullet and easily the biggest tablets people with type 2 diabetes will have to take. </p>
<p>Most people take their metformin twice a day (morning and night), although extended release formulations also allow for <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006121/">once-daily dosing</a>. </p>
<p>Because metformin is most commonly <a href="http://www.ncbi.nlm.nih.gov/pubmed/17565410">used in combination</a> with other glucose-lowering drugs to manage type 2 diabetes, <a href="https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=metformin">fixed-dose combinations</a> combining metformin with other oral glucose-lowering agents are also available. </p>
<h2>What are the side effects?</h2>
<p>The most commonly reported side effects from metformin are gastrointestinal disturbances, such as nausea, diarrhoea, cramping and flatulence. These effect around <a href="http://www.nps.org.au/conditions/hormones-metabolism-and-nutritional-problems/diabetes-type-2/for-individuals/medicines-and-treatments/metformin">one in five people to some degree</a>. </p>
<p>Usually the symptoms are mild and seen when people use high doses, when first starting metformin or increasing doses.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/140254/original/image-20161004-20213-158cq1f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/140254/original/image-20161004-20213-158cq1f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/140254/original/image-20161004-20213-158cq1f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=530&fit=crop&dpr=1 600w, https://images.theconversation.com/files/140254/original/image-20161004-20213-158cq1f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=530&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/140254/original/image-20161004-20213-158cq1f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=530&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/140254/original/image-20161004-20213-158cq1f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=666&fit=crop&dpr=1 754w, https://images.theconversation.com/files/140254/original/image-20161004-20213-158cq1f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=666&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/140254/original/image-20161004-20213-158cq1f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=666&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Around one in five people taking metformin will experience side effects to some degree.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/d/db/Metformin_500mg_Tablets.jpg">Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>The likelihood of developing side effects can be reduced by starting off with low doses and increasing them gradually. It is also recommended to take metformin with or after meals to reduce the initial risk of side effects. But even despite these precautions, side effects <a href="http://www.nps.org.au/conditions/hormones-metabolism-and-nutritional-problems/diabetes-type-2/for-individuals/medicines-and-treatments/metformin">prevent about 10% of people</a> with type 2 diabetes from taking meformin.</p>
<p>Metformin is associated with a rare but life-threatening condition known as <a href="http://www.ncbi.nlm.nih.gov/pubmed/26773926">lactic acidosis</a>, where the body builds up too much lactic acid. This can be caused by factors such as heart, liver or kidney failure. There is still controversy over whether metformin is the cause of lactic acidosis or whether it exacerbates the condition. </p>
<p>Unlike <a href="http://www.racgp.org.au/your-practice/guidelines/diabetes/11-glycaemic-emergencies/">some other anti-diabetic medications</a>, low blood-glucose levels are seldom observed when metformin is used on its own. Metformin also has the advantage over other agents in that it does not cause weight gain and in some people (especially women) with type 2 diabetes it may reduce their weight slightly.</p>
<p>Because metformin is largely removed from the body by the kidneys, people with type 2 diabetes who have impaired kidney function will <a href="http://www.nps.org.au/medical-tests/tests-by-conditions/for-individuals/kidney-problems-and-disorders-tests/for-health-professionals/medicines-to-be-aware-of/metformin-and-gfr">require lower doses</a> to maintain safe levels and prevent side effects. </p>
<h2>How much does it cost</h2>
<p>Metformin is fully funded through the <a href="http://www.pbs.gov.au/medicine/item/1801T">Pharmaceutical Benefits Scheme</a> for use in people with type 2 diabetes, with a maximum consumer price of A$19.08. </p>
<h2>Drug interactions</h2>
<p>Metformin competes for clearance by the kidneys with drugs including <a href="https://theconversation.com/weekly-dose-digoxin-the-heart-medicine-that-may-have-given-us-van-goghs-starry-night-57980">digoxin</a> (for heart rhythm problems) trimethoprim and vancomycin (antibiotics), ranitidine and cimetidine (for heartburn), nifedipine and furosemide (for blood pressure) which all have the potential to modestly increase metformin levels. </p>
<p>In practice, metformin can be safely given in people taking these other agents with cautious observation.</p>
<h2>Controversies</h2>
<p>Metformin was not approved by the United States Federal Drug Agency (FDA) until <a href="https://web.archive.org/web/20070929152824/http://www.fda.gov/bbs/topics/ANSWERS/ANS00627.html">late 1994</a>. This was because one arm of a large clinical trial was stopped prematurely in 1971 when participants receiving a potent biguanide (known as phenformin) <a href="http://jama.jamanetwork.com/article.aspx?articleid=338569">died more often</a> and had an increased risk of lactic acidosis. </p>
<p>It remains controversial as to whether metformin can be used to prevent diabetes as well as treat it. Some clinical trials have shown that metformin is at least as effective as diet and exercise for <a href="http://www.ncbi.nlm.nih.gov/pubmed/22442395">preventing diabetes</a> in those at high risk of developing it.</p>
<p>The requirement to always discontinue metformin in patients with renal impairment has also undergone a <a href="http://www.ncbi.nlm.nih.gov/pubmed/27330130">rethink</a> in the last few years, as the risks of its use appear to be less than those associated with alternative therapies that expose patients to risk of hypoglycaemia, fluid retention or other side effects.</p><img src="https://counter.theconversation.com/content/64430/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Merlin Thomas has received honoraria for educational symposia conducted on behalf of pharmaceutical companies that manufacture drugs for the management of diabetes, including metformin. He has received funding from NHMRC and JDRF for research into diabetes. </span></em></p>Metformin has been used to treat diabetes since the late 1950s. It is now on the World Health Organisation’s List of Essential Medicines needed for a basic health care system.Merlin Thomas, Adjunct Professor of Preventive Medicine, Baker Heart and Diabetes InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/646102016-09-28T05:59:42Z2016-09-28T05:59:42ZWeekly Dose: amyl started as a poison antidote, now a common party drug<figure><img src="https://images.theconversation.com/files/136550/original/image-20160905-25175-jglu1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Amyl nitrite is a liquid that evaporates at room temperature and is light-sensitive. It's used as an inhalant and kept in dark bottles so it doesn't evaporate. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>Amyl nitrite is the most well known of a group of chemicals called alkyl nitrites, usually referred to as poppers. Product names include rush, TNT, thrust, jungle juice, ram and kix.</p>
<p>Poppers are an inhalant. The most common method of use is to hold an open bottle to your nose and breathe in hard. </p>
<p>Inhaling nitrites relaxes muscles in the body. Blood vessels dilate, blood pressure drops and heart rate and blood flow increase. This physical effect causes body temperature to increase, dizziness, skin sensitivity and a feeling of excitement – a “rush” – that lasts for one or two minutes. Some people will get <a href="http://www.justaskus.org.au/drugs/inhalants-(amyl-nitrite,-poppers)/">headaches and nose bleeds</a> after use.</p>
<p>Poppers are a yellowish or clear liquid with a very low vapour point. This means it evaporates into the air almost immediately at room temperature if poured out of the bottle. The chemical is light-sensitive, so the bottles are usually dark brown or covered to <a href="https://drugs-forum.com/forum/showwiki.php?title=Amyl_Nitrite">protect the contents</a>.</p>
<p>Amyl nitrite should not be confused with <a href="https://cameochemicals.noaa.gov/chemical/2477">amyl nitrate</a>. Amyl nitrate is used as an additive in diesel fuel to accelerate the ignition of the fuel.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/136682/original/image-20160906-21893-ootc9d.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/136682/original/image-20160906-21893-ootc9d.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/136682/original/image-20160906-21893-ootc9d.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=769&fit=crop&dpr=1 600w, https://images.theconversation.com/files/136682/original/image-20160906-21893-ootc9d.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=769&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/136682/original/image-20160906-21893-ootc9d.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=769&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/136682/original/image-20160906-21893-ootc9d.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=966&fit=crop&dpr=1 754w, https://images.theconversation.com/files/136682/original/image-20160906-21893-ootc9d.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=966&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/136682/original/image-20160906-21893-ootc9d.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=966&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>Medicinal uses</h2>
<p>Amyl nitrite has been used for decades. Pharmaceutical-grade amyl was manufactured by Burroughs Wellcome and sold in small glass capsules, which were crushed to release the vapour. <a href="https://drugs-forum.com/forum/showwiki.php?title=Amyl__Nitrite">The name “poppers”</a> came from the popping sound made by crushing the capsule. </p>
<p>In the 1991 film The Doors, Jim Morrison, played by Val Kilmer, sniffs amyl nitrite from a glass capsule in an elevator immediately before receiving oral sex.</p>
<p>Amyl nitrite was used to combat the <a href="http://jama.jamanetwork.com/article.aspx?articleid=243540">effects of cyanide poisoning</a> in the 1930s. In the US, <a href="http://www.ncbi.nlm.nih.gov/pubmed/15628833">cyanide poisoning kits</a> still contain amyl nitrite, which changes some of the iron in the <a href="http://emedicine.medscape.com/article/814287-overview">blood to a molecule</a> that cyanide can bind to and then be excreted from the body. </p>
<p>It is less often used now because most cases of cyanide poisoning come from smoke inhalation in house fires rather than poisoning from direct contact with cyanide. Inhaling amyl nitrite after <a href="http://emedicine.medscape.com/article/814287-treatment#d11">smoke inhalation</a> is not recommended.</p>
<p>Amyl nitrite was used for the treatment of <a href="http://www.sciencedirect.com/science/article/pii/S001236921662250X">angina in the 1960s</a>. More effective treatments for angina are now available.</p>
<h2>Who takes poppers?</h2>
<p>Poppers are mostly used at clubs and parties to enhance the experience. The National Drug Strategy Household Survey found <a href="http://www.aihw.gov.au/alcohol-and-other-drugs/ndshs/">0.8% of the population, or 184,000 people</a>, in Australia had used an inhalant in 2013. However, this will include inhalants such as petrol, paint thinners and aerosols.</p>
<p>Use of poppers is more common among the <a href="https://ndarc.med.unsw.edu.au/blog/comparing-heterosexual-glbt-drug-use">LGBTIQ community</a> and people who use other party drugs. An <a href="https://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/AUSTRALIAN_EDRS_2015_0.pdf">annual study of illicit drug use</a> in Australia found 21% of regular ecstasy users also used amyl nitrite occasionally in 2015. This was an increase from 17% of study participants in 2014. </p>
<p>Poppers are often <a href="http://www.talktofrank.com/drug/poppers">taken during sex</a>. The drug’s effects can make it easier for people to have anal sex by helping to relax the anal sphincter muscles, although some men find they cannot get an erection after taking poppers. </p>
<h2>Side effects and interactions</h2>
<p>Even though poppers are taken to enhance experiences, they are a depressant drug like alcohol, because they <a href="http://www.druginfo.sl.nsw.gov.au/drugs/list/inhalants.html">slow down the central nervous system and reduce alertness</a>. Poppers are not addictive and not poisonous if inhaled, but can cause coma or death if swallowed.</p>
<p>Using poppers causes some <a href="http://www.talktofrank.com/drug/poppers">health problems</a>. The liquid can burn the skin on contact and they are extremely flammable. Frequent use can cause irritation of the nose and throat and chemical burns, including a rash around the nose and mouth.</p>
<p><a href="http://www.vice.com/read/hey-straight-people-youre-using-sex-drugs-wrong">People taking Viagra</a> should not use poppers because both drugs make blood pressure change unpredictably.</p>
<h2>Illegality</h2>
<p>Laws controlling the sale and use of poppers vary around the world. </p>
<p>Isobutyl nitrite was banned in the European Union in 2007 because it was strongly linked to cancer and reproductive problems. </p>
<p>Since it was banned, six frequent popper users in the UK have <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60887-4/abstract">lost their eyesight</a> as a <a href="https://www.ncbi.nlm.nih.gov/pubmed/21320953">result</a> of using a related product, isopropyl nitrite. Similar problems have been reported <a href="http://www.starobserver.com.au/news/national-news/sydney-cases-prompt-link-between-permanent-eye-damage-and-amyl-use/134805">in Australia</a>.</p>
<p>In Australia <a href="http://yourroom.com.au/wp-content/uploads/2013/05/AmylNitrate-facts.pdf">it is illegal</a> to sell, supply or inhale products containing amyl, iso- amyl, alkyl, butyl and octyl nitrites unless prescribed by a doctor. </p>
<p>However, poppers can be bought online or in sex shops in small bottles labelled as room deodoriser, polish remover <a href="http://www.druginfo.sl.nsw.gov.au/drugs/list/inhalants.html#nitrites">or video head cleaner</a>. </p>
<h2>Cost</h2>
<p>The cost of poppers varies. In September 2016 <a href="http://www.amylnitrate.com.au/index.php?route=common/home">one online store</a> was selling 10ml of rush for A$38 and 30ml of jungle juice for A$49.</p><img src="https://counter.theconversation.com/content/64610/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>Amyl nitrite is the most well known of a group of chemicals called alkyl nitrates, usually referred to as poppers.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">
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<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>
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<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>
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</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/560642016-09-14T06:22:41Z2016-09-14T06:22:41ZWeekly Dose: cannabis has been used medicinally for millennia, why is legalising it taking so long?<figure><img src="https://images.theconversation.com/files/134248/original/image-20160816-13011-7jq6u1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Legalisation of cannabis for therapeutic use is happening slowly in Australia. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>Cannabis has a long history, and its misuse hangs over it like a dark shadow. </p>
<p>Cannabis is used recreationally for its euphoriant effects. But it also has the potential for effective therapeutic use. With mounting evidence for its medicinal benefits, there have been increasing calls for its decriminalisation and legalisation.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/137899/original/image-20160915-30580-18oswne.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/137899/original/image-20160915-30580-18oswne.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=797&fit=crop&dpr=1 600w, https://images.theconversation.com/files/137899/original/image-20160915-30580-18oswne.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=797&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/137899/original/image-20160915-30580-18oswne.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=797&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/137899/original/image-20160915-30580-18oswne.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1001&fit=crop&dpr=1 754w, https://images.theconversation.com/files/137899/original/image-20160915-30580-18oswne.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1001&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/137899/original/image-20160915-30580-18oswne.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1001&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<h2>Some history</h2>
<p>Used for centuries across various ancient cultures both medicinally and recreationally, cannabis has its roots in Central and South East Asia from as early as the <a href="http://onlinelibrary.wiley.com/doi/10.1002/cbdv.200790144/abstract;jsessionid=1A799C682F2B119D305C54DA9864A3AD.f03t02">third millennium BCE</a>. </p>
<p>The use of cannabis for purposes of healing predates recorded history. The <a href="http://www.ncbi.nlm.nih.gov/pubmed/411037">earliest written reference</a> is found in the 15th century BC Chinese medicine list, the “Rh-Ya”. </p>
<p>Cannabis pollen was found on the mummy of Ramesses II, who died in 1213 BC. <a href="https://books.google.com.au/books/about/An_Ancient_Egyptian_Herbal.html?id=LPLEQgAACAAJ">Prescriptions for cannabis</a> in Ancient Egypt included treatment for the eyes (glaucoma), inflammation, as well as administering enemas. </p>
<p>In <a href="https://archive.org/details/marihuanasignalo00unit">ancient Greece</a>, cannabis was used as a remedy for earache, swelling, and inflammation. The history of mankind has a plethora of evidence for the use of medicinal cannabis dating back centuries.</p>
<p>It was used recreationally by the ancient Chinese and by Hindus of India in religious celebrations of the God Shiva. Around this era, the use of cannabis also expanded in ancient Egyptian ceremonies and swept throughout the Middle East as its psychoactive effects became popular.</p>
<p>Cannabis began to appear in conventional Western medicine in the 19th century, when its plant-derived formulations were believed to relieve pain, inflammation, spasms, and convulsions. </p>
<p>Today, evidence relating to medicinal benefits of cannabis in many patients is still more anecdotal than evidence-based, but there is <a href="http://jama.jamanetwork.com/article.aspx?articleid=2338251">mounting clinical evidence</a> to support the claim that cannabis has significant beneficial effects on various conditions.</p>
<h2>How it works</h2>
<p>Marijuana or cannabis are general terms used interchangeably to describe preparations of the cannabis plant. Cannabinoids are the active constituents of cannabis, with at least 60 of these constituents believed to have some pharmacological activity. The main psychoactive component is 9-tetrahydrocannabinol (THC). </p>
<p>Other more promising components include the non-psychoactive, anti-anxiety agent and antispasmodic cannabidiol (CBD), as well as cannabinol (CBN), which has non-psychoactive, anti-inflammatory effects.</p>
<p>THC acts on the CB1 cannabinoid receptors in the central nervous system, and is known to cause sedation, amnesia and appetite stimulation. It affects memory, motivation and pleasure. CBN is known to act on CB2 cannabinoid receptors, which influence our immune system and inflammatory activity, while CBD’s mechanism of action is still not fully understood.</p>
<p>Relatively few studies have investigated the evidence behind the medicinal use of cannabis. In a <a href="http://jama.jamanetwork.com/article.aspx?articleid=2338251">recent review of the literature</a> a total of 27 studies, all conducted after January 2000, were found. The reviewed articles explored cannabis use for the treatment of various symptoms, including pain, nausea and vomiting, anorexia, sleep, muscle spasm, urinary tract symptoms and inflammatory bowel disease symptoms. The majority of the studies found medicinal cannabis improved symptoms.</p>
<h2>What it’s used for</h2>
<p>Medicinal applications of cannabis include pain relief, treatment of multiple sclerosis, inflammatory bowel disease, cachexia (weakness from chronic illness), cancer-induced nausea and vomiting, Parkinson’s disease and potentially, sleep apnoea. Submissions for further investigation have been made and clinical trials are currently being undertaken to investigate the benefits of medicinal cannabis for epilepsy in both adults and children as well as terminal illnesses.</p>
<p>Recreationally, cannabis use or abuse is grounded on the psychoactive effects of the THC component, which cause euphoria, paranoia, sedation, cognitive impairment, and feelings of light-headedness, giddiness and relaxation. </p>
<p>Other more brief side effects include blurred vision, sedation, increased heart rate, and bloodshot eyes. Cannabis is also known to stimulate eating by activating sections of the brain that regulate food intake (the hypothalamus), and make food seem more palatable (the limbic system). It also instigates hunger from within the stomach and intestinal tissue.</p>
<p>Because of the relatively low number of cannabinoid receptors in the brain, overdosing on cannabis is virtually impossible and its potential to be addictive is based on the presence of THC. THC affects the reward centre of the brain, leading to a surge of dopamine – the pleasure chemical.</p>
<p>When using CBD or CBN extracts, these side effects on cognition and addiction are absent. Finding a standardised formulation that optimises the medicinal effect while minimising adverse effects is a difficult quest in the manufacturing and development of all medications.</p>
<h2>Costs</h2>
<p>The <a href="http://apo.org.au/files/Resource/iddr-201314-complete_0.pdf">Australian Crime Commission</a> estimates the street price of a gram of cannabis ranges between A$12 and A$50. </p>
<p>The projected costs in pharmacies are unclear, but based on pharmacoeconomics and calculations for currently registered products such as nabixamols (mouth sprays for treatment of spasticity in multiple sclerosis), it would cost A$15,000 to A$45,000 for a year of effective treatment.</p>
<p>If it was subsidised by the Pharmaceutical Benefits Scheme, the net cost per year is estimated to be <a href="http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2013-07/nabiximols">A$10 million to $30 million</a>, while the average cost to a patient is estimated to be around <a href="http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2013-07/nabiximols">A$500 to A$800 a month</a>.</p>
<p>These projections, however, are likely to be exaggerated, with current compassionate access schemes and clinical trials providing products with no charge. As awareness increases and legislative procedures made clearer, the pricing is also likely to drop.</p>
<h2>Legalising cannabis</h2>
<p>In Australia, the <a href="http://www.health.nsw.gov.au/cannabis/Documents/unregistered-cannabis-based-products.pdf">Therapeutic Goods Administration has approved</a> the man-made Dronabinol (for the treatment of anorexia in HIV/AIDS and chemotherapy-induced nausea and vomiting), Nabilone (also for chemo-induced vomiting) and Nabixamols.</p>
<p>Countries including the United Kingdom, Denmark, Czech Republic, Austria, Sweden, Germany, and Spain, as well as 23 US states, have all formally approved the use of cannabis-based products, thereby <a href="http://www.legislation.vic.gov.au/domino/Web_Notes/LDMS/PubPDocs.nsf/ee665e366dcb6cb0ca256da400837f6b/5973532394c874eeca257f150082d37d/$FILE/581168exi1.pdf">decriminalising its therapeutic use</a>. However, cannabinoids generally remain illegal everywhere else in the world.</p>
<p>Earlier this year, the Victorian government passed the <a href="http://www.legislation.vic.gov.au/domino/Web_Notes/LDMS/PubPDocs.nsf/ee665e366dcb6cb0ca256da400837f6b/5973532394c874eeca257f150082d37d/$FILE/581168exi1.pdf">Access to Medicinal Cannabis Bill 2015</a> as a plan to have medicinal cannabis available by 2017. Victoria, along with Queensland, joined NSW’s clinical trials into the cannabis-based drug Epidolex, with a focus on children with epilepsy, as well as a trial for the terminally ill taking place in Newcastle’s Calvary Master Hospital. </p>
<p>In February, the Australian Federal Parliament passed national legislation to allow the cultivation of cannabis in Australia for medical or scientific purposes, <a href="http://www.businessinsider.com.au/medical-marijuana-is-now-legal-in-australia-2016-2">described by the health minister</a> as:</p>
<blockquote>
<p>paving the way for the use of medicinal cannabis by people with painful and chronic illness. </p>
</blockquote>
<p>As of July 2016 the Therapeutic Goods Administration rescheduled cannabis from a prohibited substance (schedule nine) to a controlled drug (schedule eight), and cannabidiol became a prescribed substance (schedule four). </p>
<p>The greatest change occurred almost overnight in New South Wales, when The Poisons and Therapeutic Goods Amendment Regulation 2016 was implemented on August 1, 2016, allowing NSW doctors to apply for an authority to prescribe unregistered cannabis-based products for patients with unmanageable conditions who have exhausted all commercially available treatments.</p>
<p>Cautious progress has been made in making medicinal cannabis available and accessible in Australia; however, it is still a confusing tangle of state and federal legislation.</p>
<hr>
<p><em>Pharmacy honours graduate Sami Isaac also contributed to this article</em>. </p>
<p><em>* The graphic has been updated since publication to better relfect the classification of cannabidiol.</em></p><img src="https://counter.theconversation.com/content/56064/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Betty Chaar does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Cannabis has a long history, and its misuse hangs over it like a dark shadow.Betty Chaar, Senior Lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/637702016-09-07T05:00:29Z2016-09-07T05:00:29ZWeekly Dose: penicillin, the mould that saves millions of lives<figure><img src="https://images.theconversation.com/files/134720/original/image-20160819-12303-pka6ga.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A serendipitous discovery that saves millions of lives and garnered two Nobel prizes. </span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>In developed countries, infectious diseases accounted for most deaths until very recently. And in developing countries, infectious diseases remain the cause of death for a large percentage of the population. </p>
<p>It is in this setting that the discovery of penicillin in 1928 by Alexander Fleming was so instrumental in shaping modern health care. For the first time we had a reliable weapon against common infections; this was the start of the antibiotic era.</p>
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<a href="https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=618&fit=crop&dpr=1 600w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=618&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=618&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=777&fit=crop&dpr=1 754w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=777&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/136835/original/image-20160907-25260-2jsf3a.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=777&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>Discovery</h2>
<p>The serendipitous discovery of penicillin is testament to the importance of observation. Fleming noticed the mould Penicillium had antibacterial properties and deduced it must be secreting a substance that could kill bacteria – he named this substance penicillin. This led him to <a href="http://www.ncbi.nlm.nih.gov/pubmed/17187625">famously say</a>: “One sometimes finds what one is not looking for.”</p>
<p>As in many instances, there were clues in history that soil had healing properties for skin and wound infections. <a href="https://explorable.com/history-of-antibiotics">Healers in ancient Greece, India and Russia</a> used mouldy poultices (a moist package of herbs wrapped in cloth) to treat wounds. It was only in the early 1940s that laboratories such as Pfizer and USDA Northern Regional Research Laboratory developed methods to scale up to commercial production of penicillin.</p>
<p>The importance of penicillin is underscored by the fact its development yielded Nobel Prizes for physiology or medicine and chemistry in <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/">1945</a> and <a href="https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1964/">1964</a> respectively for the scientists involved in its discovery and development. One of them was Australian Howard Florey, who then prime minister Robert Menzies <a href="http://adb.anu.edu.au/biography/florey-howard-walter-10206">described</a> as the most important man ever born in Australia in terms of world well-being. </p>
<p>The impact of penicillin after its discovery was immediately relevant. Its use in the treatment of <a href="http://www.historylearningsite.co.uk/world-war-two/medicine-and-world-war-two/">wounded soldiers in the second world war</a> decreased the risk of gangrene of the wound. This allowed time for surgical intervention, thus saving many lives and avoiding limb amputations during the war.</p>
<h2>How it works</h2>
<p>There are several ways to cause the destruction of bacteria, through disruption of the external wall or membrane that encases them, or interfering with the internal workings that allow bacteria to survive and replicate. </p>
<p>Penicillin antibiotics bind to penicillin-binding proteins on the surface of bacterial cells and block the bacterium’s ability to remodel its wall. Thus the wall is weakened and the bacterial cell starts to leak and die.</p>
<h2>Chemical structure</h2>
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<a href="https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=942&fit=crop&dpr=1 600w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=942&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=942&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1184&fit=crop&dpr=1 754w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1184&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/134724/original/image-20160819-12274-g2p9t3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1184&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">Chemical structure of penicillin.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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<p>Penicillin has more recently become a class of drugs, which all have a common chemical structure. </p>
<p>Penicillin antibiotics belong to a group called β-lactam antibiotics, due to the β-lactam ring that is essential for their effect on bacteria as it binds the antibiotic to the penicillin receptor.</p>
<p>Through modification of this basic penicillin structure, chemists have been able to expand the class to include many of the drugs we use to treat common infections today. </p>
<p>If you are on an antibiotic at the moment, there is a good chance it is from the penicillin class. Think Amoxil®, Dicloxacillin® and Augmentin®. </p>
<p>Tazocin®, another brand of penicillin, has recently become a commonly used medication to treat severe infections in hospitals due to its ability to kill many different bacteria.</p>
<h2>Resistance</h2>
<p>Over the past 50 years, since penicillin-based antibiotics have been widely prescribed to treat all sorts of infections, bacteria have started to become resistant with varying success. </p>
<p>Bacteria have, over time, changed the target receptor for penicillin, decreasing its effectiveness. They have also started to produce β-lactamases, proteins that disrupt the β-lactam structure of penicillin and inhibit its function.</p>
<p>By 1942, strains of <em>Staphylococcus aureus</em> were <a href="http://cid.oxfordjournals.org/content/45/Supplement_3/S165.full">already resistant to penicillin</a>. Today, around the world, many of the bacteria originally sensitive to the effects of penicillin are resistant. </p>
<p>On the other hand, many common bacteria still retain sensitivity to penicillin. Penicillin remains the antibiotic of choice for pneumonia in the community, as common bacteria such as pneumococcus are still overwhelmingly sensitive to penicillin.</p>
<h2>Use and cost</h2>
<p>Penicillin and related antibiotics are still the most common group of antibiotics to treat a broad range of infections from chest or throat infections to skin and soft tissue infections. In 2014, Australian patients filed <a href="http://www.pbs.gov.au/info/statistics/asm/asm-2014#_Toc425339268">5.8 million prescriptions</a> of Amoxil alone. </p>
<p>The decision to use these antibiotics depends on the site of the infection and the likelihood the patient may be infected by a resistant bacterium. </p>
<p>The cost varies widely between the different penicillins from about A$15 for a course of penicillin VK (an oral penicillin) up to A$70 for a course of Tazocin®. However, most are on the PBS, so the price to consumers is A$38.30, or A$6.20 for concession card holders.</p>
<h2>How they make you feel</h2>
<p>Penicillin and related antibiotics have been associated with life-threatening allergy known as anaphylaxis. Fortunately this is very rare and occurs in <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255391/">less than 0.03% of patients</a>. Since penicillin antibiotics are commonly used, it is important people differentiate between serious allergy and mild side effects. </p>
<p>Penicillin is a very useful antibiotic group, so if the side effect is mild it is important to consider a re-challenge under the supervision of your doctor. There may even be cases where it is <a href="http://www.nejm.org/doi/pdf/10.1056/NEJM198505093121905">essential to desensitise patients</a> with severe reactions to penicillin.</p>
<p>The penicillins have a broad range of side effects. The most common are upset stomach, with nausea and/or diarrhoea and skin rashes. Rare side effects include liver and kidney inflammation. </p>
<p>And, like all antibiotics, penicillins can lead to infection with <em>Clostridium difficile</em>, an organism that causes severe diarrhoea, due to alteration of the normal gut bacteria.</p>
<p>Penicillins are generally safe to use with other medications. Occasionally, though, they can modify levels of certain medications such as methotrexate, which is used to treat cancer and autoimmune disorders.</p><img src="https://counter.theconversation.com/content/63770/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sergio Diez Alvarez is affiliated with the CEC Antimicrobial Stewardship Committee</span></em></p>The serendipitous discovery of penicillin is a testament to the importance of observation.Sergio Diez Alvarez, Director Of Medicine, The Maitland and Kurri Kurri Hospital, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/634592016-08-31T02:46:16Z2016-08-31T02:46:16ZWeekly Dose: Naloxone, how to save a life from opioid overdose<figure><img src="https://images.theconversation.com/files/133908/original/image-20160812-16327-x0jnkt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Naloxone has been made available over the counter from a pharmacist so loved-ones of drug users can have it on hand in the event of an overdose.</span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>Naloxone is an opioid antagonist, used as an “antidote” for opioid overdose which includes heroin, and opioid pain medicines such as morphine, fentanyl and codeine. It has been used since the 1970s by ambulance services and hospital emergency departments, and in these settings has been shown to be safe, reliable and effective.</p>
<p>Naloxone does not produce intoxication and has no effect on people who do not have opioids in their system. Over recent years, programs have been established in a number of countries to supply naloxone to people who use opioids, and their carers, family or friends to enable naloxone to be administered by a trained layperson in an emergency to prevent fatal opioid overdose. These programs <a href="http://www.ncbi.nlm.nih.gov/pubmed/27028542">have been found to</a> reduce overdose deaths, with few adverse events reported.</p>
<p>In Australia in February 2016, naloxone changed from being available only with a prescription to also being on sale over-the-counter in pharmacies. This aimed to make it easier for people who may witness an opioid overdose to access naloxone and keep it on hand.</p>
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<h2>How does it work?</h2>
<p>Naloxone is a competitive opioid antagonist, with high affinity for opioid receptors (the parts of the brain where opioids work) in the central nervous system. This means naloxone will compete with other opioids, such as heroin or morphine, to bind to the opioid receptors, knocking other opioids off the receptor. </p>
<p>Naloxone has no opioid effect at the receptor, and importantly in the case of an overdose, reverses the effects of opioids already in the body. As opioids depress respiration, when naloxone reverses this effect, it helps to restore respiration.</p>
<h2>How was it developed?</h2>
<p>Naloxone was developed by chemist <a href="http://www.nytimes.com/2013/12/15/business/jack-fishman-who-helped-develop-a-drug-to-treat-overdoses-dies-at-83.html?_r=1">Jack Fishman</a> more than 50 years ago in an attempt to treat constipation from opioids. </p>
<p>Since then it has been widely used to reverse the effects of opioids by paramedics and in hospitals. In the past 20 years, there has been a large expansion of programs where naloxone is supplied for people to take home for layperson administration (for a bystander who witnesses an overdose). </p>
<p>These programs have been recommended by the <a href="http://www.who.int/substance_abuse/publications/management_opioid_overdose/en/">World Health Organization</a> in response to rising opioid-related deaths.</p>
<h2>Australian experience</h2>
<p>In Australia, take-home naloxone programs have been operating in various states and territories, largely as small demonstration programs, <a href="https://theconversation.com/explainer-what-is-naloxone-and-how-can-it-help-save-drug-users-who-overdose-48812">since 2012</a>. </p>
<p>Many pilot programs involved peer advocacy groups and were operated through services for people who inject drugs. More recently, naloxone has become more embedded in routine health care in a small number of <a href="http://www.ncbi.nlm.nih.gov/pubmed/27071354">health services in NSW</a>.</p>
<h2>How is it used?</h2>
<p>Potential overdose bystanders (friends or family of people who use opioids) are trained to identify an overdose, call an ambulance, administer naloxone and start basic life support while they wait for the ambulance to come. </p>
<p>In Australia, it is usually given as an intramuscular injection (an injection into the muscle), and starts working within a few minutes. Usually a first dose of 400 micrograms is administered in the shoulder or thigh, followed by a second dose of 400mcg if there is no change after two to five minutes. </p>
<p>Naloxone has a short half-life so effects can wear off in 30 minutes to an hour. The person can then return to an overdose state, so it is important an ambulance is called and the person is monitored by others even if the initial dose has worked.</p>
<h2>Is naloxone just for heroin overdoses?</h2>
<p>Naloxone will reverse the effects of any opioid – heroin or pharmaceutical opioids. A common misconception is that naloxone is not effective for potent opioids such as <a href="https://ndarc.med.unsw.edu.au/blog/powerful-opioid-fentanyl-poses-serious-risk-fatal-overdose">fentanyl</a> or buprenorphine, but with <a href="http://www.ncbi.nlm.nih.gov/pubmed/16764215">higher doses</a>, naloxone does work. However, supporting breathing and calling an ambulance becomes even more important with stronger opioids. </p>
<p>In Australia, most (70%) fatal overdoses <a href="https://ndarc.med.unsw.edu.au/resource/changing-nature-opioid-overdose-deaths-australia">now involve pharmaceutical opioids</a>, with heroin involved in only three out of ten opioid overdoses.</p>
<h2>Side-effects</h2>
<p>The main concern is that after reversing the effects on opioids in an individual, they will experience opioid withdrawal. This is less common with the doses used in Australia though it was more common when larger doses were routinely used. </p>
<p>One concern with inducing opioid withdrawal symptoms is that a person may feel quite unwell, and then use more opioids to feel better, which may lead to a subsequent overdose.</p>
<h2>Current challenges</h2>
<p>The main challenges with naloxone are around the way it is delivered. Not all people feel comfortable giving an injection. The pre-filled syringe is relatively easy to use but there is currently very limited stock in Australia.</p>
<p>Ampoules are a little harder to draw up and administer the naloxone, but have been successfully used in Australia and internationally. Intranasal formulations (nasal sprays) have been developed in the United States but there are <a href="http://www.ncbi.nlm.nih.gov/pubmed/26840916">concerns</a> about how much of the naloxone is effective, and what dose needs to be given when administered in this way.</p><img src="https://counter.theconversation.com/content/63459/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>SN is supported by a NHMRC Research Fellowship (#1013803). The National Drug and Alcohol Research Centre at the University of New South Wales is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund.
SN has been an investigator on untied educational grants from Reckitt-Benckiser and Indivior.
</span></em></p><p class="fine-print"><em><span>Simon Lenton is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvement Grants Fund through its core funding of The National Drug Research Institute at Curtin University. For more than 10 years he has conducted research based advocacy calling for the wider availability of naloxone.</span></em></p>Naloxone is used as an “antidote” for opioid overdose which includes heroin, and opioid pain medicines such as morphine, fentanyl and codeine.Suzanne Nielsen, Senior Research Fellow, UNSW SydneySimon Lenton, Professor and Deputy Director, National Drug Research Institute, Curtin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/631182016-08-24T05:36:33Z2016-08-24T05:36:33ZWeekly Dose: flibanserin, the drug that gives women one extra sexually satisfying experience every two months<figure><img src="https://images.theconversation.com/files/135252/original/image-20160824-30259-or21wh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Addyi (flibanserin) is far from a pink viagra. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/span112/3555868788/">Jinx!/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The United States Food and Drug Administration (FDA) approved the drug flibanserin (sold under the brand name Addyi) for the treatment of women with hypo-active sexual desire disorder (HSDD) <a href="http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm458734.htm">in August 2015</a>. </p>
<p>Australia hasn’t followed suit, though flibanserin is available through internet pharmacies. However, its limited effectiveness and serious side-effects should cause potential users to rethink purchasing flibanserin online.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/135256/original/image-20160824-30216-76ssic.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/135256/original/image-20160824-30216-76ssic.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=639&fit=crop&dpr=1 600w, https://images.theconversation.com/files/135256/original/image-20160824-30216-76ssic.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=639&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/135256/original/image-20160824-30216-76ssic.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=639&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/135256/original/image-20160824-30216-76ssic.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=803&fit=crop&dpr=1 754w, https://images.theconversation.com/files/135256/original/image-20160824-30216-76ssic.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=803&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/135256/original/image-20160824-30216-76ssic.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=803&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<h2>What does it ‘treat’?</h2>
<p>Hypo-active sexual desire disorder HSDD <a href="http://www.ncbi.nlm.nih.gov/pubmed/19777334">was listed in the DSM-4</a>, the previous edition of the Diagnostic and Statistical Manual of Mental Disorders. The disorder relates to persistently deficient (or absent) sexual fantasies and desire for sexual activity, which causes marked distress and relationship problems. </p>
<p>For a diagnosis, HSDD could not be due to the physiological effects of a substance or a general medical condition. Estimates of the prevalence of sexual desire problems vary widely depending on the criteria used – from 3% to 31% in one <a href="http://www.ncbi.nlm.nih.gov/pubmed/23674067">study</a>. Others suggest <a href="http://www.ncbi.nlm.nih.gov/pubmed/24219879">up to 43%</a> of women may experience low sexual desire. </p>
<p>However, there is fierce debate about the definition of disorders of sexual desire, with HSDD described as a <a href="http://www.bmj.com/content/349/bmj.g6246.long">“highly controversial diagnostic construct”</a>. </p>
<p>The newer DSM-5, published in May 2013, combined features of HSDD and another condition known as female sexual arousal disorder, to form a new condition, <a href="http://dsm.psychiatryonline.org/doi/full/10.1176/appi.books.9780890425596.dsm13">female sexual interest/arousal disorder</a> (FSIAD). This has stricter diagnostic criteria and as yet unknown prevalence. </p>
<p>Originally <a href="http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0705341/abstract;jsessionid=B28607A50F7DD2EB8C13776392694326.f01t01">trialled</a> as an antidepressant, flibanserin found new life as a treatment for low sexual desire in women. </p>
<p>After being rejected for approval by the FDA in 2010, developers <a href="https://en.wikipedia.org/wiki/Boehringer_Ingelheim">Boehringer Ingelheim</a> transferred the rights to Sprout Pharmaceuticals, which finally and <a href="https://theconversation.com/the-drug-flibanserin-is-approved-for-the-treatment-of-low-sexual-desire-in-women-46335">controversially</a> secured FDA approval in August 2015.</p>
<h2>How it works</h2>
<p>Flibanserin <a href="http://www.ncbi.nlm.nih.gov/pubmed/20840530">modulates</a> neurotransmitters in the brain, increasing levels of dopamine and norepinephrine and decreasing serotonin. </p>
<p>As dopamine and norepinephrine promote sexual arousal, and serotonin reduces sexual arousal, flibanserin may <a href="http://www.ncbi.nlm.nih.gov/pubmed/26927498">increase</a> libido by improving the balance between these neurotransmitter systems.</p>
<h2>Problems and controversies</h2>
<p>The US FDA approval process was mired in controversy, particularly in relation to the active role of Sprout Pharmaceuticals in lobbying. It funded a high-profile public advocacy campaign called <a href="http://eventhescore.org/">Even the Score</a>, which <a href="http://www.bmj.com/content/349/bmj.g6246.long">misleadingly</a> claimed the drug was initially rejected because of FDA sexism. </p>
<p>Despite <a href="http://pharmedout.org/flibanserin.html">counter campaigns</a> by scientists and doctors, the FDA scientific advisory committee voted 18 to six in favour of approving the drug, with the condition that risk-management options were put in place. </p>
<p>The committee members were concerned the drug had significant risks from side-effects, particularly if used off label or taken in combination with alcohol, and few benefits. The committee’s recommendation that the drug be approved therefore attracted <a href="http://archinte.jamanetwork.com/article.aspx?articleid=2497778">widespread criticism</a> that it allowed politics to trump clinical science.</p>
<p>Within hours of the FDA approval, Sprout Pharmaceuticals was acquired by Valeant for $US1 billion. Valeant set the price of Addyi at $US800 per month, leading to <a href="http://fortune.com/2016/03/25/sprout-valeant-addyi/">accusations</a> of price gouging. </p>
<p>Sales flagged as insurers refused to cover the drug. With its stock value plummeting, Valeant <a href="https://www.thestar.com/business/2016/04/05/valeants-female-viagra-sales-team-axed-amid-low-demand.html">reportedly</a> dismissed the drug’s entire sales team and said it planned to reintroduce the drug at a later date. The company may be waiting until the 18-month restriction on direct-to-consumer marketing is over.</p>
<h2>Safety and efficacy</h2>
<p>A <a href="http://www.ncbi.nlm.nih.gov/pubmed/26927498">recent</a> review of studies – including five published and three unpublished randomised clinical trials involving 5,914 women – concluded the overall quality of the evidence for both efficacy and safety outcomes was very low. </p>
<p>The published studies reported more favourable outcomes than unpublished studies. The authors’ attempts to gain further information from study leaders and sponsors were not successful.</p>
<p><a href="http://www.ncbi.nlm.nih.gov/pubmed/27175717">Side-effects</a> include dizziness (11.4% of users), drowsiness (11.2%), nausea (10.4%), fatigue (9.2%), insomnia (4.9%) and dry mouth (2.4%). The most serious problems – low blood pressure and a resulting loss of consciousness – are <a href="http://www.ncbi.nlm.nih.gov/pubmed/26927498">amplified</a> by concurrent alcohol use. </p>
<p>Other serious adverse events were uncommon but flibanserin can’t be viewed as safe without further studies including a broader range of diverse women. </p>
<p>The FDA approved flibanserin on condition it carry a black-box warning not to drink alcohol while taking the medication. </p>
<p>The manufacturer is also <a href="http://archinte.jamanetwork.com/article.aspx?articleid=2497778">required</a> to undertake three additional studies to examine the side-effects among women using alcohol with the drug. Strangely, the evidence about alcohol interactions with flibanserin presented to the FDA included data on 25 healthy volunteers, of whom only two were women. </p>
<p>Side-effects are lessened if taken at night, but it has been <a href="http://www.ncbi.nlm.nih.gov/pubmed/27175717">reported</a> about one out of every eight women will discontinue flibanserin because of adverse effects.</p>
<p>A rigorous <a href="http://www.ncbi.nlm.nih.gov/pubmed/26927498">meta-analysis</a> showed that, on average, flibanserin led to <em>one-half</em> an additional sexually satisfying event per month. This is a less optimistic finding than the (still underwhelming) <em>one</em> extra sexually satisfying event per month frequently quoted by <a href="https://theconversation.com/a-sexually-satisfying-event-for-women-or-just-a-new-identity-for-an-old-antidepressant-42734">reports</a>.</p>
<h2>Availability and cost</h2>
<p>Flibanserin is approved for prescription only in the US; it is not available in Australia. US doctors must be <a href="http://www.ncbi.nlm.nih.gov/pubmed/27175717">certified</a> before prescribing it, and dispensing pharmacists must also complete training. </p>
<p>In the first month it was available, Addyi (the brand name of flibanserin) was <a href="Https://www.thestar.com/business/2016/04/05/valeants-female-viagra-sales-team-axed-amid-low-demand.html">prescribed</a> just 227 times, compared with more than half a million for Viagra in its first month. Doctors had prescribed the drug fewer than 4,000 times as of <a href="http://www.nytimes.com/2016/04/10/business/female-viagra-addyi-valeant-dysfunction.html?_r=2">February</a> this year.</p>
<p>In the US, a one-month supply of flibanserin (one 100mg tablet per day, taken at bed time) <a href="http://www.ncbi.nlm.nih.gov/pubmed/27175717">costs</a> between $US200 to $US830, depending on insurance coverage and means of acquisition. That’s a lot of money for an extra sexually satisfying experience every two months.</p><img src="https://counter.theconversation.com/content/63118/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jayne Lucke is the Director of the Australian Research Centre in Sex, Health and Society (ARCSHS) at La Trobe University. Jayne Lucke and ARCSHS receive funding from diverse sources listed in the annual report available from the website: <a href="http://www.latrobe.edu.au/arcshs">http://www.latrobe.edu.au/arcshs</a></span></em></p>The drug’s limited effectiveness and side-effects should cause potential users to rethink their purchase.Jayne Lucke, Professor & Director of the Australian Research Centre in Sex, Health & Society, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/637602016-08-17T07:00:55Z2016-08-17T07:00:55ZWeekly Dose: teriparatide, the osteoporisis drug that forms new bone<figure><img src="https://images.theconversation.com/files/134379/original/image-20160817-13720-28b10v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Teriparatide increases bone mineral density at the spine and hip.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-132307760/stock-photo-senior-couple-with-back-and-hip-pain.html?src=h16_M339bon6g08oCvpJcQ-1-10">aceshot1/Shutterstock</a></span></figcaption></figure><p>Teriparatide is an injectable drug to treat severe <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/osteoporosis">osteoporosis</a>, a condition where mineral loss causes the bones to become brittle and to fracture easily. </p>
<p>Teriparatide improves bone strength by stimulating the formation of new bone. It does this by increasing activity of bone-forming cells called osteoblasts. </p>
<p>Other, more common first-line treatments for osteoporosis aim to preserve bone strength and inhibit the activity of <a href="https://www.britannica.com/science/osteoclast">osteoclasts</a> – bone cells that resorb old bone tissue during the healing process. </p>
<p>By contrast, teriparatide stimulates bone formation by mimicking the action of parathyroid hormone (PTH) on bone cells.</p>
<p>We’ve long known that PTH could stimulate bone formation. But when PTH levels are chronically elevated, bone resorption is stimulated even more, resulting in bone loss. </p>
<p>A key discovery in 2001 was that daily injections of teriparatide below the skin caused a short-lived peak in PTH (1-34) levels. This peak stimulated bone formation due to the activation of pre-existing osteoblasts and the recruitment of new osteoblasts, instead of increasing the activity of osteoclasts. </p>
<p>Australia’s Therapuetic Goods Administration (TGA) <a href="http://www.health.gov.au/internet/publications/publishing.nsf/Content/teriparatide-independentreview-contents/$FILE/teriparatide_review.pdf">approved</a> teriparatide in 2003. </p>
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<h2>Benefits</h2>
<p>Teriparatide increases bone mineral density at the spine and hip. </p>
<p>In a <a href="http://www.ncbi.nlm.nih.gov/pubmed/11346808">randomised controlled trial of postmenopausal women</a> with osteoporosis who’d had one or more fractures, teriparatide reduced the risk of new spinal fractures by 65%. It also reduced back pain. </p>
<p>Other non-spinal fractures were reduced by 53% – but the study could not detect reductions in the rate of hip fractures. </p>
<p>The reduction of non-spinal fractures appears to be greater than with first-line anti-osteoporotic drugs, which typically reduce these fractures by about 20-25%. However, head-to-head studies are lacking. </p>
<h2>Side-effects</h2>
<p>Side-effects of teriparatide include headache (8%), nausea (8%), dizziness and reactions at the site of the injections. </p>
<p>Around 3-11% of users will have abnormally high levels of calcium just after dosing. Sustained high levels of calcium (hypercalcaemia) are rare but could result in weakened bones and problems with the heart and brain. </p>
<p>Teriparatide has a black-box warning about an increased incidence of <a href="http://www.cancer.org/cancer/osteosarcoma/detailedguide/osteosarcoma-what-is-osteosarcoma">osteosarcoma</a>, a type of cancer that starts in the bones. This was found in experiments on rats that were exposed to three times and 60 times the normal human exposure over a significant portion of their lives. </p>
<p>No signal for an increased risk of this type of cancer has been found in patients who have used teriparatide. Nevertheless, teriparatide is not recommended for patients who may be at increased risk of osteosarcoma, including those with a history of bone disorders. </p>
<p>Teriparatide should not be prescribed to adolescents or children.</p>
<h2>Length of treatment</h2>
<p>In Australia, because of the possible risk of osteosarcoma, the maximum lifetime duration of teriparatide therapy is <a href="http://www.nps.org.au/publications/health-professional/nps-radar/2009/may-2009/teriparatide">18 months</a>. In the rest of the world it is two years. </p>
<p><a href="http://www.ncbi.nlm.nih.gov/pubmed/23404615">Studies show</a> the anti-fracture benefits of teriparatide increase the longer the patient remains on treatment. Non-spinal fractures are reduced for up to two years of treatment, but less so in the first six months of treatment. </p>
<p>Non-spinal fractures are also reduced for up to two years after treatment stops, as <a href="http://www.ncbi.nlm.nih.gov/pubmed/26841258">bone formation continues</a>.</p>
<p>After teriparatide therapy finishes, <a href="http://www.ncbi.nlm.nih.gov/pubmed/21894214">antiresorptive therapy</a> should immediately begin to further improve bone strength and to increase spine and hip bone mineral density. Otherwise, the accrued benefits of bone mineral density and fracture prevention from teriparatide will be lost. </p>
<h2>Cost and barriers</h2>
<p>Teriparatide is subsidised on the Pharmaceutical Benefits Schedule (PBS), but only for patients with a history of at least two fractures with one occurring after taking a first-line anti-osteoporosis treatment, called antiresorptive therapy, for at least 12 months. </p>
<p>A bone mineral density test T score of below -3 is also required. </p>
<p>On the PBS, a month’s supply costs <a href="http://www.pbs.gov.au/medicine/item/9411H">A$38.30</a>. </p>
<p>Using a non-PBS prescription, the cost of teriparatide is about A$400 per month for 18 months, or about A$7,200 per treatment course. </p>
<p>Only medical specialists can start teriparatide therapy, but GPs can write subsequent teriparatide prescriptions.</p>
<p>Despite reimbursement for teriparatide in patients with severe osteoporosis, use in Australia is among the lowest in the world. The reasons are unclear, but may be due to lack of awareness among specialists, GPs and patients. It may also be because patients don’t like the idea of giving themselves daily injections.</p><img src="https://counter.theconversation.com/content/63760/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Robert Ebeling receives research funding from NHMRC and Eli-Lilly, and honoraria from Eli-Lilly. </span></em></p>Teriparatide is an injectable drug to treat severe osteoporosis, a condition where mineral loss causes the bones to become brittle and to fracture easily.Peter Robert Ebeling, Head, Department of Medicine, School of Clinical Sciences; Professor of Medicine, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.