As voters in Oregon and DC opt to decriminalize psilocybin, there is growing evidence that the active compound in “magic,” or hallucinogenic, mushrooms might benefit individuals with moderate to severe depression—at least when used alongside psychotherapy under a doctor’s supervision.
“The findings that we have in our study, we believe, are related to the fact that it was in a controlled setting where we have trained professionals,” explained Alan Davis, a psychologist, social work researcher at Ohio State University, and adjunct assistant professor at Johns Hopkins University’s Center for Psychedelic and Consciousness Research.
“We certainly would not suggest that someone go out and take this on their own,” he added. “However, there are currently multi-site trials going on in the US and Europe, testing this in phase 2 and phase 3 trials in order to hopefully garner FDA approval in the next couple years.”
Davis and his colleagues published findings from a small phase 2 clinical trial on psilocybin-assisted therapy in the journal JAMA Psychiatry in early November. There, they reported a steep decline in symptoms in two-dozen individuals with major depressive disorder who received 11 hours of supportive psychotherapy, on average, along with two doses of synthetic psilocybin, downed with water in gel capsule form. To enroll in the trial, individuals could not be taking other antidepressant medication at the time.
Charles Reynolds III, a geriatric psychiatry expert and distinguished professor of psychiatry emeritus at the University of Pittsburgh School of Medicine, who was not involved in the study, but penned a related JAMA Psychiatry editorial, credited the team with doing “a nice rigorous job in the design of the study and in documenting both its positive effects but also its potentially negative effects.”
One week after treatment, the team saw a clinically meaningful dip in depression symptoms in 67 percent of the participants using a standard depression assessment method called the GRID-Hamilton Depression Rating Score, and 14 individuals appeared to be in remission. Four weeks out from treatment, more than half of participants were in remission and 71 percent had a significant response to the treatment.
When it came to potential side effects, some patients had headaches the evening of, or morning after, treatment, Davis noted, adding that temporary anxiety can turn up during psilocybin sessions but does not seem to last or require treatment.
The results are encouraging since a subset of individuals with major depressive disorder do not response to available treatment options such as selective serotonin reuptake inhibitor (SSRI) treatment, ketamine, or psychotherapy alone, or struggle to find a treatment that’s the right fit.
“Depression is one of the most prevalent and debilitating conditions globally, and the current medications approved for depression, and psychotherapy used for depression, are lacking in adherence and efficacy,” Davis said. “They don’t work for everyone.”
The study is not the first to find a potential psychiatric benefit for treatments that include psilocybin: results from studies done in the past few years suggest the hallucinogenic compound might benefit individuals with difficult-to-treat depression or depression symptoms that arise after cancer diagnoses.
“We first tested psilocybin to see whether it had an anti-depressant effect in 2016, in a published study of people with life-threatening illness like cancer,” Davis noted. “And what we found was that among the group of people with cancer who had subsequently become depressed because of the cancer diagnosis, that reduced their depression.”
But there’s much more to the proposed treatment than a mouthful, or a microdose, of magic mushrooms.
Investigators tested two sequential doses of psilocybin in major depressive disorder patients ranging in age from 21 to 75-years-old who were randomized to start the psilocybin-assisted therapy immediately or after a two month delay. The trial took place in an out-patient setting, which excluded very severe cases with psychotic disorder, suicide attempts, or hospitalization.
In both of those groups, psychotherapist guides talked them through their psychedelic trips, Davis explains, adding that this direction may have been key to the symptom relief reported by the study’s participants.
The benefit “seems to be related to the psychological experience that people have during the psilocybin session—so people typically report having what’s called a mystical or spiritual experience where they feel connected to the universe or outside of their normal sense of themselves,” Davis said. “But they also described having obtained or received insight into their life during the session.”
“It’s the combination of these experiences that seem to be related to the antidepressant effects of the experience,” he suggested, calling the therapeutic component “critical” in helping patients achieve and make sense of these events.
The team is continuing to explore psilocybin-assisted treatment in the context of depression, and expects to report long-term outcomes for the depression patients profiled in the current study using data collected over 12 months following the psilocybin-assisted therapy sessions.
It remains to be seen how long the effects last, and whether there may be a benefit to longer-term, maintenance treatments to avoid relapse. But such studies take time, and they’re not cheap.
The current research was partly supported by entrepreneur, author, and investor Tim Ferriss and a crowd-funding campaign he spearheaded. With the apparent success of the current study, some say more traditional funders may start to pay more attention to the field, too.
“In many ways, it’s still early days from a rigorous scientific perspective,” Reynolds suggested. “But I think Davis and colleagues at Hopkins really did a nice job in carrying out what I think of as a small, but important, proof-of-concept study.”
He called the work “a step forward,” but cautions that larger and more diverse randomized control trials are needed to understand if, and when, the psilocybin-supported psychotherapy is clinically warranted—and to look at how it fares compared to standard treatment options for depression and other conditions such a prolonged and debilitating grief disorders.
“What we need now, as I suggested in my editorial, is a randomized control trial that might use placebo or might use an active comparator of some kind, perhaps another antidepressant, that would allow us to see what is the specific impact of psilocybin” Reynolds said.