Five years ago, psychedelics helped break Ian Roullier free from depression. His mental health had been spiraling for years, despite various antidepressants, counseling, and personal efforts to meditate, walk, and journal his way back to health. In 2014, he heard researchers at Imperial College London were planning to test psilocybin, the psychedelic compound in magic mushrooms, as treatment for depression. Out of desperation, he volunteered to try it.
The treatment, involving two therapy sessions under the influence of psilocybin, was a challenging experience, says Roullier, involving confronting past traumas. But he felt profoundly different afterwards. For three months, Roullier says, he had no depression whatsoever. And for the three months after that, he only had mild symptoms. “Depression is such a brittle rigid state,” he says. “Psilocybin is the opposite end of that and allows you that flexibility and freedom to see things in a different way, maybe for the first time.”
Over time, though, the depression slowly creeped back. And because psilocybin is illegal in the UK, Roullier had no way of accessing the drug. “I didn’t want to just find some mushrooms in the woods somewhere and take them with no support or even with friends,” he says. “This is purely therapeutic, not a recreational experience.” He began emailing researchers, asking if there was any way he could access psilocybin.
The lead clinical psychologist for the study at Imperial’s Centre for Psychedelic Research, Rosalind Watts, heard similar stories from several participants. “Having worked in two psilocybin for depression studies, I could see what we were giving our participants was an experience that was really helpful,” says Watts. She repeatedly saw patients who got relief from the psilocybin study, but then had depression return when they couldn’t get more. “By the fiftieth time of seeing that same thing happen, I started to feel like rather than continuing research, I really wanted to build something for those people,” says Watts.
As we were getting desperate pleas for further access, it didn’t feel like something that could be left to programs that are years away in the UK.
Psilocybin is still illegal in the UK, and has not been approved as medical treatment. But Watts was approached by Synthesis, a psychedelic wellness retreat in Amsterdam, the Netherlands, with the idea for creating a therapy program there. Psilocybin-infused truffles—related to magic mushrooms—are legal in the Netherlands, and Synthesis has been offering them to clients since April 2018. Initially, Synthesis turned away potential visitors with depression, as staff were not qualified to offer mental health therapy. “We rejected around 40% of all folks that applied,” says co-founder Martijn Schirp. “It’s the thing I struggled the most with, because these were the individuals who needed us the most, and we had to tell them we’re not ready to accept you yet.”
Now that Synthesis has hired Watts, the retreat is prepared to accept participants with depression. Its first group has already had their first therapy session, part of a 13-month course that includes monthly group therapy and a five-day retreat with two psilocybin sessions. Those who enroll will typically pay $10,000 for the treatment, though, in order to make the program accessible, Synthesis plans to accept at least one person per eight-person group for free. The first to enroll are all former patients from previous Imperial psilocybin studies and received a significant discount, paying on average $775. Roullier is one of them.
The ethics of unproven treatment
The question of how to support patients who’ve been in a clinical trial and now can’t access further treatment is not unique to psychedelics. Many countries have “expanded access” programs, which allow patients who haven’t benefited from existing legal treatments to use an experimental drug. Such access for psilocybin is still very far off in the UK, says Watts: “As depression came back, and we were getting desperate pleas for further access, it didn’t feel like something that could be left to programs that are years away in the UK.”
Another way to extend access would be to create an observational follow-up clinical study, says Steve Hyman, director of the Stanley Center for psychiatric research at Broad Institute of MIT and Harvard. This would have the benefit of ethical regulatory approval, and would provide evidence about the long-term effects of psilocybin therapy. Watts sees this as a short-term solution: “What happens when they get depressed again? Another follow up study?,” she says.
Plus, the opportunity and funding for such a study wasn’t available at Imperial, says Watts. The psychedelic field has limited resources, and researchers face pressure to conduct new studies to advance the science rather than run follow-up studies to support previous participants.
The program at Synthesis is an unusual alternative borne of those limitations. It is legal and designed to benefit patients, but there are ethical concerns with offering a treatment to patients with depression before it’s been proven as safe and effective. According to contemporary medical standards, all treatments must go through three stages of trials involving hundreds if not thousands of patients before they can be approved for widespread use. Psilocybin studies for depression are currently in the most advanced stage of research, but haven’t yet met that bar.
There’s a reason why there’s this extensive infrastructure built around consent and risk evaluation and reporting and liability and accountability.
Some question why, if researchers are working in clinical trials to understand psilocybin’s safety and efficacy, they would offer the unproven treatment at Synthesis. “Have they already decided psilocybin is effective and minimal risk in multiple rounds of therapy?” asks Boris Heifets, a professor of anesthesiology at Stanford University. “There’s an inconsistency here. Why are you doing clinical trials if you already know the answer?” Heifets is running a psilocybin clinical trial on chronic pain and is not involved in Synthesis.
Rushing ahead while it’s still unproven could bring risks, says Heifets. Psychiatric treatments of the past, such as lobotomies or shock therapy, failed to adequately protect patients. “There’s a reason why there’s this extensive infrastructure built around consent and risk evaluation and reporting and liability and accountability when you try a new therapy, whatever it is,” he says.
For Watts, the existing research on psilocybin and her personal involvement in two studies is enough to convince her that the benefits outweigh risks. The research so far shows psilocybin therapy works well, and none of the 80 participants in the Imperial studies experienced worse suicidal thoughts following treatment. “The risk of suicide due to lack of available treatments for depression is probably greater than the risk of suicide from psilocybin therapy,” she writes.
Though unusual, Heifets says Synthesis can operate ethically as long as it commits to both transparency and oversight. Crucially, if a participant in the program suffers what’s known in clinical research as an “adverse event”, such as a suicide attempt, then Synthesis will report the incident to both the public and the Dutch medical regulatory agency, Inspectie Gezondheidszorg en Jeugd (IGJ.) The IGJ would investigate, and a consulting psychiatrist would also review the situation and share recommendations with the ICJ. “We are still at an early stage in forging a new path, there is no blueprint for everything yet, for instance where adverse events could be published,” says Watts.
When researchers are paid to provide a therapy they’re still evaluating, it adds an additional ethical tension. For any clinical research, Heifets says participants should be aware that Watts is paid for her work at Synthesis: “People need to understand that while I’m recommending a therapy, I also have a financial benefit,” he says. The therapy as Synthesis will not form part of a clinical trial, though Watts plans to write up patients’ experiences as part of a field study, and hopes to collaborate with a university to potentially do a follow-up study after participants have left the program.
Addressing the risks
Though the Synthesis program doesn’t fit neatly in the model of medical research on psychedelics, its creators hope they can apply these safety standards to a more communal version of psychedelic therapy.
Both Schirp and Watts say Synthesis will have a cautious approach to enrolling participants with depression. Four times a year, groups of eight people will attend Synthesis on the therapy program, though in-person visits are currently on hold amid the coronavirus pandemic. The program follows many of the same screening principles as Imperial’s research study, and won’t accept anyone with a personal history or first degree relative with schizophrenia, psychosis, or bipolar disorder. The Synthesis team will also be in touch with participants’ existing doctors, and won’t accept someone if their psychiatrist or GP (primary care doctor) advises against it. “We’re erring on the side of caution,” says Watts.
All over the world, people are engaging in psychedelic therapy with no support system.
In other ways, the Synthesis retreat intentionally deviates from clinical practices. Medical research into psychedelics is individualistic, and patients are alone with their therapists while taking the drugs. By contrast, the Synthesis program is inspired by indigenous Celtic group healing practices. At Synthesis, the group of eight will get to know each other through group therapy and will take psilocybin together—though each person will have their own guide and can choose to be alone while high. Participants will also have far more therapy both before and after the psychedelic experience than in a clinical trial, and the program draws on Celtic traditions that emphasize connections to nature and cyclical rhythms of healing.
Though there is more therapeutic support than in clinical trials, Watts acknowledges that any kind of therapy involves risks. Patients can be destabilized as they work to address mental health issues, and it’s impossible to rule out worsening depression. The solution, Watts believes, is to provide the best possible version of psychedelic therapy. Watts says she receives ever-growing requests for psilocybin treatment, and knows of many untrained, unregulated psychedelic retreats. Others are self-medicating by using magic mushrooms at home. “All over the world, people are engaging in psychedelic therapy with no support system,” she says.
Even when psychedelics do work in clinical studies, Watts emphasizes that it’s not an easy, quick fix. The “overhype effect,” whereby patients expect an instant cure, can cause dangerous levels of disappointment in patients with severe depression.
Roullier is aware that psychedelic therapy is part of a longer process. But even he had a disappointing experience. Last year, he managed to enroll in a second clinical trial on psilocybin therapy, this time run by psychedelic company Compass Pathways. “The effect wasn’t the same,” he says. Roullier was reminded of the work he needs to do to combat his depression, but didn’t have those months of relief without symptoms.
Still, he’s relieved to have the chance to try psilocybin therapy again through Synthesis, and hopes another couple of sessions will bring him permanent relief. “The aim for me is to get to a point where I no longer need it,” he says.