Could Psilocybin Treat Depression? New Head-To-Head Trial Shows It’s At Least As Effective…

A commonly expressed sentiment about how effective magic mushrooms might be at treating depression goes something like this: Self-reported studies are great, but they only go so far. How well would psilocybin actually perform against an existing treatment?

According to a small but rigorous study published in the New England Journal of Medicine, psilocybin could be as effective as a leading antidepressant—and while more research is still required, the study’s lead author says the results should give people hope for functional alternatives to SSRIs. 

Psilocybin Performs Better In All But One Outcome

Designed by Dr. Robin Carhart-Harris, head of the Centre for Psychedelic Research at Imperial College London, the study compared psilocybin therapy and a six-week course of escitalopram (an antidepressant sold under brand names like Cipralex and Lexapro) to see which would provide more favorable results. 

A total of 59 people with major depressive disorder participated in the phase 2 double-blind randomized controlled trial, funded almost entirely by the Alexander Mosley Charitable Trust. 

Participants in the psilocybin group received a dose of 25 milligrams on two different occasions three weeks apart, and also took placebo tablets for six weeks. (Psilocybin used in the trial, dubbed COMP360, was provided by Compass Pathways.) In the escitalopram group, participants received imperceptible doses of one milligram of psilocybin three weeks apart, and took two rounds of the SSRI, the first at 10 milligrams and a second at the maximum daily dose of 20 milligrams. 

All participants received psychedelic therapy on three different occasions: prior to, during, and after a psilocybin dosing session. “We standardized the amount of psychological support that people received in the two groups,” says Carhart-Harris. “The structure was consistent with the standard way of psychedelic therapy, involving preparation, supervision, and integration.” 

Results revealed that psilocybin performed better in all of the researchers’ predicted outcomes except for the primary one, which showed no significant statistical difference between the two treatments.

“The results of the primary outcome look anomalous in relation to the other measures reported in the trial,” says Carhart-Harris. “It was virtually the only measure in nearly 20 that didn’t significantly favor psilocybin.” (That measure, the QIDS-SR-16, is a series of questions participants answered to rate the severity of their depressive symptoms.)

Both groups saw reduced levels of depression, but a closer look at the research reveals that the psilocybin group saw greater results in a shorter period of time, including improvements in ability to feel pleasure, express emotions, and increased feelings of well-being. Feelings of anxiety and suicidal ideation were also reduced significantly.

According to Carhart-Harris, there was the same overall number of side effects, but significantly fewer cases of emotional blunting, sexual dysfunction, dry mouth, drowsiness and anxiety in the psilocybin group, the most common among them being headaches the day after a psilocybin dose. 

Lead Author Expects Readers To Be Confused By Results

Carhart-Harris is the first to admit that the results of this study need to be handled and discussed delicately.

“It’s hard to avoid looking at the values themselves and thinking, ‘hold on, psilocybin had twice as many people in remission than escitalopram’,” he says. 

“I think this will confuse readers, but in a sense, I think it’s healthy that this is happening with this paper, because it’s a bit of a further lesson to the public about scientific practice and the standards we abide by.”

Given the study’s small sample size, relatively short runway and lack of a straight placebo group, there were also some aspects of the trial that would be addressed more carefully if the Imperial team were to run it again. 

“We definitely regret not having a more diverse sample… because while suicide is more prevalent in males, depression is what we’re looking at, and that’s more prevalent in females,” he says. The sample was comprised of mostly of white men of an average age of about 40 years old.

“Ethnic diversity isn’t where we’d like it to be either, particularly because we’re running a trial in London, an ethnically diverse city. We’re learning as we go but certainly would prefer to have more diverse samples.”

While the results of the trial may be a little confusing, Carhart-Harris says people should still be encouraged when it comes to psychedelics for the treatment of mental illness, especially with plans for larger, longer trials in the future. For now, he dedicates his work on this trial to Sheri Eckert, one of the chief advocates behind Oregon’s successful ballot measure to legalize psilocybin, who passed away suddenly in December.

“For too long, mental illness generally and depression in particular hasn’t been treated well enough. To turn up to your GP and say that you’re depressed and know that it’s a coin flip whether you’ll respond to prescribed treatment? It’s not good enough,” he says.

“To hear that there is a new treatment that is being developed that on average achieves at least 70 percent response rates is reason to be optimistic about the future of depression treatment, and beyond.”