Psilocybin Effective for Treating Major Depressive Disorder, Research Suggests

An estimated 17.3 million adults in the United States had at least one major depressive episode in 2017, according to data from the National Survey on Drug Use and Health (NSDUH). Standard depression treatment options include a variety of anti-depressant medications, but in the future, there could be another way to treat the illness: the psychedelic substance psilocybin. 

A small study of adults with major depression, led by Johns Hopkins Medicine researchers and published in JAMA Psychiatry, found that two doses of psilocybin, in conjunction with supportive psychotherapy, led to “large, rapid, and sustained antidepressant effects.” Over a four-week period, most participants showed improvement in their depressive symptoms and half of them achieved remission. 

What Is Psilocybin?

Psilocybin is a naturally occurring psychedelic compound produced by more than 200 species of fungus (yes, we're talking about "magic mushrooms"). When ingested, psilocybin leads to visual and auditory hallucinations and major changes in consciousness, typically lasting for a few hours.

Back in 2016, Johns Hopkins Medicine researchers found that psilocybin treatment (with additional psychological support from a professional) significantly relieved existential anxiety and depression in people with a life-threatening cancer diagnosis.

What the New Study Involved

The researchers recruited 24 people (16 women and 8 men, with an average age of 39) with a long-term recorded history of depression. Most of the participants had experienced persistent symptoms for approximately two years before enrolling in the study.

Before the study started, all participants had to taper off any antidepressants they were taking, assisted by their own doctor. This ensured they were safe to be exposed to the new, experimental treatment.

Immediately after recruitment, 13 participants received the psilocybin treatment. The remaining 11 participants received the same preparation and treatment after an eight-week delay.

Study Findings

All participants were given the GRID-Hamilton Depression Rating Scale (a standard depression assessment tool) upon enrollment, then one week and four weeks after completing the treatment.

On this scale, a score of 24 or more indicates severe depression, 17-23 moderate depression, 8-16 mild depression, and 7 or less no depression. At the time of enrollment, the participants had an average depression scale rating of 23. However, at both one week and four weeks after treatment, the average depression scale score was 8.

Of the entire group, 67% showed a more than 50% reduction in depression symptoms at the one-week follow-up and 71% at the four-week follow-up. Overall, four weeks post-treatment, 54% of participants were considered in remission—meaning they no were no longer considered to be depressed.

“This is the first randomized controlled trial testing the efficacy of psilocybin therapy among people with depression,” says lead author Alan K. Davis, PhD, an adjunct assistant professor in the psychedelic research unit at Johns Hopkins University. “It advances the knowledge of this topic and helps set the foundation for phase III clinical trials testing the treatment against gold standard placebo.”

Crucially, no serious adverse effects were reported, which makes a strong case for adding psilocybin to the treatment options currently available for major depression. “Current medications and therapy are lacking in adherence and efficacy and many current medications have unwanted side effects," Davis says.

"Psilocybin therapy is safe, has minimal side effects, and data suggests it has a larger effect in decreasing depression symptoms compared to other medications and psychotherapies," says Davis. 

Limitations of the Study

It’s important to be aware that the study was very small and preliminary. “The results would have to be validated in a real sham-controlled study—i.e., one that’s not waitlist controlled, where everyone on the waitlist knows they did not get the treatment," says Aron Tendler, MD, chief medical officer at BrainsWay.

There were also safety concerns, Dr. Tendler notes. Many patients were excluded from the study because of potential issues like substance use and suicidality. 

Indeed, psilocybin won't be a suitable treatment for everyone who is diagnosed with depression, and there lies one of the biggest challenges. "You want to avoid causing harm, and that is certainly a possibility when you give an addictive hallucinogen to a psychiatric patient," Dr. Tendler says.

"You want to avoid giving it to addicts, schizophrenics, and prodromal schizophrenics. You don’t want it to turn it into medical marijuana, where everyone who does not need it gets it, with false advertising, and it heralds a pandemic of 'natural prescription addicts,'" Dr. Tendler says.

Other Challenges

Psilocybin will also be incredibly expensive, Davis adds. "It's still unknown whether insurance will cover this type of treatment," he says. "Plus, it's time-consuming and requires special infrastructure: two therapists, specialty session rooms, and advanced training beyond licensure for clinicians, for starters."