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When Martin Williams' research plan was first rejected by an ethics committee in 2012, he understood why. The medicinal chemistry researcher could see some valid sticking points. For one, the psychiatrist attached to his detailed protocol didn't quite have the requisite clinical trials experience. Fair enough, Williams thought. Still, there were also less defensible reasons for the experiment being turned down. Troubling reasons. Williams was surprised, for instance, when the independent review board "overstepped their remit" by citing a lack of obvious funding for the proposal. And he was left shocked when they refused to enter into any dialogue around where the money would come from. Instead of judiciously questioning and assessing the merit of the trial – engaging in to and fro over the details – they seemed to just take his $5000 application fee, cut contact and move on. That's disappointing, Williams thought. "But we were able to learn a few things, make some changes," he said. "For next time." Messiah or naughty boy? Researcher Martin Williams will lobby for clinical trials of psychedelic drugs. Photo: Joe Armao Next time was only a few months ago, in December 2015. By then Williams, 51, had brought together a more bona fide team of potential researchers and also made particular note of the proposed funding model for the research, which would test a promising but bold new method of therapy for people suffering from acute post-traumatic stress disorder. He was confident and happy to submit what seemed like "water tight" plan to the ethics committee of a large university in Melbourne, yet the rejection letter this time was far more blunt. It wasn't a letter, either, so much as an unofficial pre-emptive email from the deputy vice chancellor of research. "It basically said 'forget it, this university is not interested'," Williams said. "I didn't bother remonstrating too loudly. I expect the same might happen with any Australian university." It is an expectation based solely on the drug Williams is proposing to use in his trial, namely MDMA – or methylendioxymethamphetamine – which is often a component in the party drug ecstasy but has also been used recently around the world – along with an array of other psychoactive substances or "psychedelic drugs" – to great therapeutic effect. Ecstasy or agony: what if MDMA had useful medical applications? Photo: Viki Yemettas You see Williams, a Yarra Glen winemaker, pilot and autodidact, is something of an outlier in Australian medical research. He is neither an established or esteemed name, but nor is he without experience. He has an honours degree in chemistry and biochemistry from the University of Sydney along with a PhD in medicinal chemistry and pharmaceutical science from Monash University at Parkville. He was until recently a post-doctoral research associate there, publishing papers with titles such as Backbone and side chain 1H, 15N and 13C assignments for the oxidised and reduced forms of the oxidoreductase protein DsbA from Staphylococcus aureus. Yet his most notable role is as president of PRISM or Psychedelic Research In Science & Medicine, a small not-for-profit lobbying group that would see global gold standard research replicated in Australia, using everything from "acid" (LSD) and "magic mushrooms" (psilocybin) to cure everything from end-of-life anxiety to nicotine addiction. The idea is far less far-fetched than it sounds. Over the past decade, such research has been ramping up all over the world at significant institutions from Switzerland to Canada and Tel Aviv to London. In the United States, schools including Johns Hopkins Medicine, NYU and UCLA have begun using psychedelics in randomised controlled trials to treat alcohol dependence, depression and anxiety. Others are exploring the potential benefits of mescaline (an alkaloid derived from the Peyote cactus and used in religious ceremonies by Native Americans for millennia) and dimethyltryptamine (found in the shamanic Peruvian brew known as Ayahuasca). Root cause: plants from which the pyschedelic brew Ayahuasca is brewed by Peruvians. Photo: Supplied But perhaps the most revelatory and well-chronicled therapeutic new frontier is the use of MDMA to treat PTSD. In 2000, it was used to treat female victims of sexual assault in Madrid. In 2001, the target group were South Carolina survivors of childhood abuse. Later studies have involved police and emergency responders – all of whom were well-served by the drug, which is not used as a prescription medication but rather administered in a clinical setting and followed by hours of intense psychotherapy. The pure synthetic compound reduces activity in the amygdala (where fear is processed) and increases activity in the frontal lobe (where people put ideas in context), meaning patients are able to look closely at traumatic events without being paralysed by fear. The subjects are screened and carefully prepared, and they are guided by a therapist – with whom they are better able to bond, again, thanks to the drug. The experience has virtually nothing in common with a warehouse dance party – except of course in the chemical sense. "The therapy itself achieves the positive outcomes – the MDMA is only an adjunct," Williams said. "There's no magic effect that cures the patient – it just enables them to get to the root cause of their condition and work through that." A group in the United States known as the Multidisciplinary Association for Psychedelic Studies (MAPS) has already guided its MDMA research through phase two trials. With good safety and efficacy data, they are preparing a submission to the Federal Drug Administration, and have begun fundraising for phase three trials – the final step before potential widespread US approval in 2021. Their process began 30 years ago, in 1986, when a man named Rick Doblin founded MAPS. Since then, he said, more than 1000 people have taken MDMA in clinical research, and more than 5000 papers on psychedelics and various therapies have been published on MedLine – the US National Library of Medicine. MAPS has also offered $25,000 in matching funds for any study launched locally. "It's a little bit hard for me to understand what the resistance is in Australia. It should be easier for PRISM – a simple regulatory challenge," Doblin said. "But how much of a follower does Australia want to be, and how much of a leader?" Williams in fact designed his protocol with the help of MAPS, to mirror their widely published research, which has already been subject to countless international review boards: "We're not ground breaking in any way other than we're trying to do it in Australia." Local researchers hope to trial MDMA to help treat war veterans with hard-to-treat PTSD. Photo: Melissa Adams He intends to trial the drug here on veterans of war, many of whom have tried cognitive behavioural therapy and anti-depressants and yet been "treatment resistant". The test group could just as easily be victims of rape, assault, or even family violence, but the target group is not the issue so much as the culturally-laden term "psychedelics" (which actually has a straight-forward and good faith meaning, namely "manifesting the mind"). One Melbourne psychiatrist with decades of experience counselling victims of trauma said he was stunned by the "establishment resistance" to such a promising treatment option. "There is an immediate reaction of fear," he said, on condition of anonymity. "The public perception needs to be altered, but it has to be done slowly and gradually. I think we have to tread warily." That psychiatrist, who is also a lecturer at a large university, has tried establishing his own small-scale study using MDMA, but the idea was quickly rebuffed by an academic ethics committee as "too dangerous". "The reaction is almost medieval in some ways," he said. "We're reasonable people with good reputations and a considerate, highly controlled proposal. It's not a slap-happy operation. We should be welcomed in, but we're not and it's unfortunate." Professor Suresh Sundram, head of the psychiatric neuroscience research program at Monash University – and a scientist with no grudge against or interest in such work – identified four major factors contributing to the dearth of local study in this area. First, he said, there is fear on the part of researchers, around the response they might expect from ethics committees who would likely ("and rightfully") view such studies with extreme caution. Second is the impact such research might have on a scientist's reputation. "They may not be received with the same respect," Dr Sundram said. "They might be seen as marginal and extreme." (Doblin is baffled by this: "Treating patients who are suffering with a life-threatening illness? You think that would be good for your reputation.") Third, funding bodies could perceive the work to be "too radical", meaning any trial would require the safety net of a large philanthropic contribution. (Perhaps $500,000 would be enough to launch a small study; a larger trial might cost $5 million.) And finally, the experts already studying depression or PTSD may not be as enamoured with psychedelics as they are current alternatives. (Researchers, Dr Sundram noted, often become "one-eyed about their drug".) Professor Patrick McGorry is watching the results of research being done on ketamine and cannabidiol Photo: Rob Gunstone Professor Patrick McGorry, executive director of Orygen, the National Centre of Excellence in Youth Mental Health, can attest to that notion, and said he had not even heard of the psychedelic research being done around the world. The "big thing" in research right now, he said, was ketamine (also often abused as a party drug), as well as work being done with cannabidiol to treat anxiety in young people. (Shrooms and Lucy in the Sky with Diamonds are just not on his radar.) "Don't get me wrong – my immediate reaction is curiosity," he said. "We do need to explore new treatments that examine the interaction of biology and psychology. But like most researchers, we need a benefactor to give us some blue sky funding." One final consideration is that the value of working with psychedelics may be far greater for developing our fundamental understanding of brain function than in treating psychological disorders. At Imperial College in London, healthy volunteers were recently given LSD after which researchers used fMRI and magnetoencephalography to see what activity took place in the brain, and came away amazed at what they saw. David Nutt, a former drugs adviser for the British government and a senior researcher on the study, told media that the work had profoundly deepened our understanding of consciousness: "This is to neuroscience what the Higgs boson was to particle physics." This image shows how, with eyes-closed, much more of the brain contributes to the visual experience under LSD than under placebo. The magnitude of this effect correlated with participants reports of complex, dreamlike visions. Photo: http://www3.imperial.ac.uk/ Dr Alex Wodak, president of the Australian Drug Law Reform Foundation, is one person you might expect to throw his full weight behind the therapeutic use of illicit drugs – but you would be wrong. His interest rests more in work like that above, from Imperial College, in finding out more about how the drugs work before coming up with how they might be used. "The more we know about the mechanisms," he said, "the more likely we are to get dividends." Dr Wodak just returned to Australia following a week at the United Nations in New York, attending a general assembly on the World Drug Problem. He noted that research will be hard to establish given the seemingly unending "War on Drugs". Little has changed since 1971 when Richard Nixon famously coined that term, and then branded Timothy Leary "the most dangerous man in America". (Leary, once a psychologist at Harvard University, was evangelical about the potential of LSD.) America, Dr Wodak said, frames the way drugs are regarded around the world, and no administration has shifted from the prohibitionist path set by Nixon 45 years ago. Not coincidentally, most research into illicit substances is related to the amount of damage they can do, rather than the benefits they might offer. The same is true locally, where there are actually no formal legal prohibitions against academic and clinical research using psychoactive substances. Research with "scheduled compounds" can take place with the permission of the local health ministers. Dr Stephen Bright, a clinical psychologist specialising in alcohol and other drugs and lecturer at Curtin University (and member of PRISM), points out that such research has already been done in Melbourne. The catch is that the research (so far) supports the "dominant pathogenic narrative of drugs", which limits discussion to the harm they can cause. The only recent local research using a psychedelic, he points out, was a 2010 study at Swinburne University entitled The effects of MDMA and methamphetamine on car driving simulator performance, cognitive skills and mood states, designed to measure how impaired people become when using such drugs. "But there's very little potential for psychedelic drugs to be abused in a clinical setting," he said. "They're low toxicity, and they're non dependence forming. They're not taking it and going to a rave." Fiona Patten, the Sex Party MP, has been lobbying for drug law reform for some time, mostly in the health and civil libertarian space, and believes an attitudinal shift is overdue. "The beauty of many of these substances – which is not great for anyone wanting to make money from them – is they don't need continued use. It's not like getting on Prozac for the rest of your life – the drugs are only used a few times for psychotherapy, and they can't be patented, which may be why 'Big Pharma' is not interested." Sex Party leader Fiona Patten has been a long-term campaigner for drug reform Photo: Joe Armao In some ways the problem is financial but the solution could be as well. The legal and ethical impediments to cannabis research, for instance, fell away rapidly after a BRW rich lister donated $33 million to the University of Sydney specifically to look at medical uses for pot. Williams can only sit back and hope a similar white knight emerges. He will keep nudging the change along, too. Within six months he will be ready to submit his protocol to yet another ethics committee. The ideal way things would play out? An eminent scientist says Yes, I would love to do this research with you. A wealthy private benefactor says, Here's $500,000. An ethics committee says, Looks good to us. The state health minister says, Sure, you can import that compound from Germany. Then PRISM would locate their subjects and get testing. For Williams, that would sate his twin appetites for knowledge and the desire to do something socially useful – more so than standing at a laboratory bench grinding away at the mysteries of biological science. He believes an injustice has been perpetrated and a lot of good denied to humanity in holding back this research for so long. "I just feel that it's time to pick up the ground swell and turn it into a wave of social change. At a time when society seems to be getting more and more restrictive and scared, we need to take a stance." In the meantime he will pursue his hobby, building a Glasair IIS-TD propeller plane in a little hangar at Lilydale Airfield. That's the thing about Williams – he loves projects, and challenges. In his former life as a winemaker and vineyard consultant, he used to fly planes to meetings among the vines at Coonawarra and Tocumwal, and has been making his own light aircraft for two years now. Can he make it fly? Reseacher Martin Williams, who lobbies for clinical trials of psychedelic drugs like magic mushrooms, is also building a Glasair IIS-TD. Photo: Joe Armao He imagines it will be ready to fly within 12 months, perhaps at the same time – hopefully, maybe – that his research dream takes off. He can picture it now. The twin-propeller beauty will wait its turn between parachute planes and cruising craft, between Piper Warriors and Cherokees, then barrel down a thin airstrip on the rural-urban fringe of the city. After reaching top speed it will soar up into the blue under his careful control. And he will look down from on high, floating above the clouds, seeing beyond the horizon. It will be quite the trip.

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