'Magic Mushroom' Compound May Work Just As Well As Antidepressants, Small Study Finds

The study compared psilocybin to the antidepressant escitalopram in people with moderate-to-severe depression.

Psilocybin, the hallucinogen found in "magic mushrooms," may work just as well as a common antidepressant drug at treating symptoms of depression, a small new study suggests.

The study found that people who took psilocybin twice under the supervision of psychiatrists showed similar reductions in depression symptoms — based on scores on a survey — compared with people who took a six-week course of the antidepressant escitalopram. And those in the psilocybin group were more likely to report remission from depression symptoms, compared with those in the escitalopram group, according to the study, published Wednesday (April 14) in The New England Journal of Medicine.

"One of the most important aspects of this work is that people can clearly see the promise of properly delivered psilocybin therapy by viewing it compared with a more familiar, established treatment in the same study," study lead author Robin Carhart-Harris, head of the Centre for Psychedelic Research at Imperial College London, said in a statement. "Psilocybin performed very favourably in this head-to-head [trial]."

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The findings agree with previous research suggesting that psilocybin may help some people with depression. However, the researchers caution that their study was small and more research is needed to confirm the findings. They stress that there was no statistically meaningful difference in depression scores between the psilocybin and escitalopram groups, meaning that psilocybin didn't perform better than escitalopram. In addition, the study didn't include a true placebo group — a group that received just dummy pills — so the researchers can't say based on their results whether either treatment works better than a placebo.

They also warn that people with depression should not self-medicate with psilocybin, because taking psilocybin in an unsupervised setting using an unregulated dose could have negative effects.(In addition, recreational use of psilocybin is illegal under U.S. federal law, although some cities and the state of Oregon have decriminalized the drug.)

"Context is crucial for these studies, and all volunteers received therapy during and after their psilocybin sessions," study co-author Rosalind Watts, a clinical psychologist formerly based at the Centre for Psychedelic Research, said in the statement. "Our team of therapists were on hand to offer full support through sometimes difficult emotional experiences."

Some of the study authors reported receiving consulting fees from COMPASS Pathways, a company that has developed a synthetic version of psilocybin.

Psilocybin for depression

Over the past decade, several small studies have suggested that psilocybin could provide benefits to patients with treatment-resistant depression or with cancer-related psychological distress. But few studies have directly compared psilocybin with standard treatments for depression.

For the new study, 59 people with long-term, moderate-to-severe depression were randomly assigned to one of two groups. One group received a 25 milligram dose of psilocybin at the start of the study and a second 25 mg dose of psilocybin three weeks later. They also took a placebo pill once a day for six weeks during the study.

The other group received a 1 mg dose of psilocybin at the start of the study and a second 1 mg dose three weeks later; and they took a daily pill with escitalopram for six weeks during the study. The 1 mg psilocybin dose is thought to be too low to have any effect, but it was given to "standardize expectations" so that both groups could be told they were taking psilocybin, even though they weren't aware of the dose.

At the start and end of the study, patients took a survey to assess the severity of their depression symptoms. Scores on the survey can range from 0 to 27, with high scores indicating greater levels of depression. At the start of the study, the average depression scores were around 14 to 16 points, but by the end of the study, patients in the psilocybin group and those in the escitalopram saw their scores drop by similar amounts, about 6 to 8 points.

However, remission from depression symptoms, which was defined as a depression score of 0 to 5 points, was more common in the psilocybin group, with 57% of people in this group experiencing remission, compared with 28% in the escitalopram group.

Questions remain

The new results "provide tantalizing evidence for the efficacy of psilocybin in the treatment of major depressive disorder," Dr. Jeffrey A. Lieberman, chairman of the Department of Psychiatry at Columbia University College of Physicians and Surgeons in New York, wrote in an editorial accompanying the study. But the study had limitations, including that most people volunteered for the trial in response to advertisements for a study on psilocybin, Lieberman wrote. In theory then, the participants may have been a select population of people with a preference for psilocybin over other treatments. In addition, the appropriate dose and frequency of psilocybin treatment for depression are still unclear, he said.

What's more, scientists still don't know if people need to have a "mystical experience" with psilocybin in order to have beneficial effects, or whether the same benefits could be achieved with a drug that's engineered to have similar pharmacologic action as psilocybin but without the mind-altering effects, Lieberman wrote.

"We are still awaiting definitive proof of the therapeutic efficacy of psychedelics and their capacity to improve the human condition," Lieberman said.

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