WA’s first trial of psilocybin from magic mushroom for depression is underway, with aim to recruit 60 patients

In a room inside the Harry Perkins Institute, with greenery on the walls, curtains to keep the light low and soothing music coming from the speakers, Robert (not his real name) takes a capsule containing psilocybin, or magic mushroom, in readiness for hours of intensive work with two psychotherapists. In his 60s, the Perth man has suffered episodes of major depression throughout his life, which have worsened in the past two decades. He’s been hospitalised, tried numerous antidepressants at high dosages and had cognitive behavioural therapy and other interventions to no avail. Earlier this year, Robert became the first patient in a groundbreaking WA trial using the psychedelic to enhance the effect of specialised therapy for those with treatment-resistant depression. Renewed interest in the use of psychedelics reached new highs in January last year when, to the surprise of many in the sector, the Therapeutic Goods Association reduced restrictions on MDMA and psilocybin for the treatment of PTSD and treatment-resistant depression respectively. The decision, which makes the substances available to authorised prescribers under strict conditions, sparked debate between those who believe the treatments can help patients in great need and others who fear they will be prohibitively costly, potentially risky and offer what could amount to false hope to desperate people. Back in that treatment room in Murdoch, Robert’s experience with the psilocybin itself is “very unpleasant” — “there were no beautiful colours or wonderful feelings of floating off. Distressing is probably the best word for it”. But with the guidance of the therapists, some four months later Robert says his mood is markedly better. “Overall for me, it’s been a very positive experience,” he tells STM. “The therapists have given me some really insightful ways of looking at how I think and why I think in certain ways, and how habitualised that becomes, and offered strategies to help, which I’ve followed … “It’s been quite a revelation. Everybody has difficulties, of course; it doesn’t suddenly all become sweetness and light, but it’s certainly a vast improvement.” The trial that Robert participated in is supervised by respected UWA professor of psychiatry, Sean Hood, WA’s only authorised prescriber of psilocybin (there are believed to be nine nationwide). He has another two patients underway and now, having cleared regulatory and ethics hurdles, bedded down the protocols and logistics, and trained the multidisciplinary team required, is ready to ramp up recruitment towards the study’s target of 60 people. The theory behind psychedelic-assisted therapy is that the mind-altering substance changes the patient’s perception of the world and increases brain activity, allowing them to benefit more deeply from a tailored form of psychotherapy. “The important thing to know about these psychedelic therapies is that they’re not medication therapies; they’re medications enhancing the psychological therapy,” Professor Hood explains. “It’s a package — you have to have the two things together. It’s not a matter of someone putting their hand up and saying, ‘I think I can give this person therapy’; we want to train people to do this, we want to share our data, we want others to be able to learn from our experience and be able to administer this in a way that we can be confident actually works.” Hood had been working on a clinical trial for more than two years before the TGA’s decision, determined to find out if psilocybin can help those with so-called treatment-resistant depression, where mainstream therapies have failed to provide any lasting relief. “It’s hard to get absolute numbers, but it may be a third to a quarter of people who have major depression that get into that treatment-resistant phase,” he tells STM. “Many of them are partly effective in their roles in life, some have impairments that they keep under cover and just live with, and many are very substantially impaired, such that they really can’t function at all. So there is a lot of unmet need … We’ve got a number of therapies (for depression) which is good. But if you fail those, there’s really nothing.” The WA trial is a collaboration between UWA, Edith Cowan University and Fiona Stanley Hospital, funded by Perth company Reset Mind Sciences, a subsidiary of medical cannabis business Little Green Pharma. As well as testing safety and effectiveness, it also looks at whether actively involving a loved one or carer can enhance the impact of the therapy — 50 per cent of patients will have a support person in their sessions. The trial is, by necessity, highly selective. It involves intensive screening, both physical and psychological. Candidates have to be referred by a GP or specialist and need to come off antidepressants for a month; a requirement Hood says is challenging, but necessary. If selected, patients undergo seven weeks of intensive sessions with specially-trained therapists — including two in which they are administered a 25mg dose of psilocybin, in the first and fourth weeks. Capsules of the substance, an organic product from Canada, are kept in a safe under lock and key. Once the patient has taken the drug, two therapists guide and supervise them for roughly six hours, until they are able to go safely home. They are closely monitored, both during and after, for everything from changes to their blood pressure to any increase in suicidal thoughts. The day after the experience, termed the integration phase, is an important time, where the therapists work with the patient to make sense of what happened and examine their life and illness. After the intensive phase, there are check-ups at three, six, nine and 12 months. Despite the TGA green light, which it said stemmed from a lack of options for patients with treatment-resistant mental illness, Hood accepts that the eyes of the sector are upon them. “There’s a great deal of scrutiny,” he says. “We’ve had three proper audits so far, which is highly unusual in my experience of having done 30 clinical trials. But it’s understandable that people want to keep a close eye on things.” From Hood’s perspective, it’s incumbent on researchers to properly test what could be a promising therapy. “It’s not about getting a high, is the first thing I’d say,” he explains. “This is an example of some novel therapies that can hopefully give people some hope, in an area where they are often running pretty low on it. It’s an opportunity and part of the reason I do clinical research is to try to push the envelope and find new ways to help … “From a personal point of view, I don’t mind giving my patients some hope.” But the prospect of offering too much hope is one of the concerns foremost in the mind of the Royal Australian and New Zealand College of Psychiatrists, which opposed the TGA’s decision to down-schedule. Professor Richard Harvey, chair of the college’s steering committee on the issue, says patient safety is paramount, and there must be clear communication to manage the expectations of potentially “desperate and vulnerable” patients. Psilocybin is not a miracle cure, he stresses, and carries risks, including fear, panic and re-traumatisation. “Our position remains very cautious,” Harvey says, pointing out that outside a clinical trial, such an intensive approach will also be extremely expensive. “It remains pretty unclear as to whether these are valid treatments or not … It certainly shouldn’t be something you consider until you have exhausted everything else and your current treating psychiatrist thinks this might be an option, and you are financially in a position to do it.” Harvey says in the past year, he has taken a lot of phone calls from interested patients and his advice is always to seek out a trial. “What we need is evidence to know whether this is valid or not,” he says. “It might work, we just don’t know. It’s up to some really high quality sound research to tell us whether it is effective and safe, and also that it’s financially worthwhile to do it.” Hood agrees that the clinical trial approach is important, not least because the cost is covered by the sponsor — “there’s no change from $20,000 per patient, if you work out all the costs”. And while there is a large amount of interest from psychiatrists about psychedelic-assisted therapy — a session on the subject at a major conference in Perth last year was full, with doctors spilling out the door — Hood says almost everyone agrees it is premature to use it outside a highly supervised setting, akin to a trial. As well as collecting data and protecting the patient, it allows for long-term monitoring. At this stage, Hood says it’s unknown whether people will require ongoing treatments. “I think there will be a variety of longer-term experiences and we will follow that for as long as we can,” he says. “If you treat depressive episodes comprehensively, the chances of having subsequent episodes is far less, which is important. We haven’t done this long enough to know but I would expect that the combination of the psychological skills they get, and the experiences from that, stay with the person. My expectation is that there’d be an increasing resilience in the long term.” As the trials are underway, the commercial potential of psilocybin-assisted therapy is also gaining momentum. Perth-based Reset Mind Sciences, the sponsor of Hood’s trial, has been granted licenses to grow psilocybin mushrooms; three batches have been produced so far in WA’s South West, cultivated in a purpose-built transportable room in an undisclosed location, tended by a dedicated staff member. Executive director Fleta Solomon says it can take years to go from growing the mushroom to manufacturing a drug that meets the strict requirements for medicines, but that is what Reset would ultimately like to do. The company has also signed a deal with not-for-profit health insurer HIF to set up a special clinic in Perth, which could be the first of a series. The partnership, announced last year to the ASX, involves HIF contributing $250,000 to development of the Reset owned-and-operated facility, where up to 100 of its eligible members will be given priority access to psychedelic assisted psychotherapy when it becomes available. A health economics study will also be run, so HIF can consider whether it is viable to offer coverage for the treatments. HIF CEO Justin James said at the time that given the sheer number of people affected by depression — one in seven Australians, or 3.5 million people, take antidepressants — “we simply can’t afford not to explore every legitimate avenue”. Solomon says the industry is in its early stages and given what is at stake, meticulous oversight is vital. “There’s also a lot that needs to happen in terms of integrating the psychiatric community, the health systems, comprehensive training programs, the regulatory framework — all of that has to happen first,” she says. “I guess what underpins this is the critical importance of conducting this clinical trial, because that’s really the proof of concept. That will then help give us a blueprint to train people and move forward in the space … We want to do it well, we want to do it safely and we want to be really credible, so we feel that relatively slow progress is important.” Hood’s hope is that the treatments can ultimately be given to those in need. But as a medical doctor, he has foremost in his mind his oath to first, do no harm. “Do I think this will be done outside of research? That is, of course, the hope,” he says. “The challenge of restricting it to research only is that there are people who could benefit, that can’t. But we also want to make sure that what we are doing is working for people first … “Most people who get into mental health care do so because they want to help … Seeing people getting better, back to their normal levels of functioning, getting back to work, to life, is one of the reasons that I think we persist with this work, particularly in the public sector.” Robert, meanwhile, is taking each day as it comes. His relationship has improved (he was selected to have his partner involved in his therapy) and he notices the difference in his mindset most when faced with something difficult. “I’d say the biggest symptom of my depression was very low resilience, so any kind of pressure or stress and I would just fold,” he says. “I’m handling that sort of thing much better; I’m not as reactive as I was. “I don’t know if it’s the psilocybin or the therapists, who were such high quality … But I think that given my age, and the number of people I’ve seen over the years, my feeling is that there is something else at play. “For me, there was also a little more at stake, because I felt like this is my last chance and so, I took the whole thing very seriously. I’ve gone into the trial with a very positive mindset that I really want change and I’m open to change. I think that helped as well.” *Not his real name Expressions of interest to participate in the trial can be sent to clinicaltrial@resetmind.com.au.