The Case for Psychedelics for Depression Is Getting Stronger

A day after Oregon legalizes psilocybin, a new study adds to a growing body of literature that psychedelics can be useful for psychiatry

This is the kind of news you might need the day after a nail-biting election night: A new study released today showed that psilocybin, the psychoactive ingredient in hallucinogenic mushrooms, is a powerful antidepressant. The research, unintentionally published with a remarkable sense of timing, comes a day after Oregon voted to become the first state in the country to legalize the drug in order to enable its use in therapeutic settings.

Researchers found that two separate doses of the psychedelic compound, combined with a total of 11 hours of therapy in the weeks before and after taking the drug, significantly reduced depression symptoms in 71% of people. More than half of the clinical trial participants (54%) were considered to be in remission for their depression four weeks after the treatment.

“These folks were people who… had lived with depression for decades. Their current depressive episode on average was two years or longer,” says Alan Davis, PhD, an adjunct assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, who led the study. “They had tried lots of medications, most of them had been in therapy of different types, and they had experienced some benefit from those, but it never really took the depression away. So the fact that this treatment was so effective in this type of population was pretty remarkable.”

The study, published in the journal JAMA Psychiatry, was small, conducted in only 24 people with an average age of 39 years, but the benefit was so large that experts say the results are promising for future research.

“What the earlier, smaller sample sizes do for you is show a proof of concept that there is value in exploring this topic further,” says Adam Stern, MD, an assistant professor of psychiatry at Harvard Medical School who was not involved in the research. “I think that psilocybin-assisted therapy is a potentially really exciting avenue for future treatment that definitely needs further investigation before it starts becoming available for the average patient.”

“The part of the results that is most potentially exciting is that these patients experience a really rapid improvement in their mood.”

As part of the clinical trial, run by the Johns Hopkins Center for Psychedelic and Consciousness Research, people first underwent eight hours of talk therapy with study staff to prepare themselves for the psychedelic experience. The first psilocybin session involved a moderate-to-high dose of the drug given in pill form — aka, not a magic mushroom. One to two weeks later, people came back for their second session with a higher dose, roughly 10 milligrams more than the first round. During the two daylong trips, participants were accompanied by staff members in case they needed anything, but they mostly hung out with a blindfold on listening to music and were encouraged to “focus their attention inward and stay with any experience that arose.” In the weeks following the psilocybin sessions, participants had another two to three hours of talk therapy.

Remarkably, most people’s symptoms improved just 24 hours after receiving the first dose of psilocybin, and the benefits lasted for at least four weeks.

“The part of the results that is most potentially exciting is that these patients experience a really rapid improvement in their mood,” Stern says. “In psychiatry, things take so much time that most antidepressants don’t start working for at least a few weeks to longer, up to a couple of months.”

However, this rapid effect can be a double-edged sword. “Oftentimes treatments that have very quick onset may not have the durability of response that other treatments have,” Stern adds.

Davis says they are currently following the people in the trial for a year to see how long the effect lasts.

Treating psychiatric conditions with psychedelic or recreational drugs has gained acceptance in recent years. In 2019, a variation of the drug ketamine, which has both anesthetic and dissociative effects, was authorized by the U.S. Food and Drug Administration to be used for treatment-resistant depression. Clinical trials testing MDMA, the primary ingredient in ecstasy or molly, to treat post-traumatic stress disorder have shown promising early results. And the new study is the latest in a series by the Johns Hopkins group to demonstrate the antidepressant effect of psilocybin. Clinical trials testing psilocybin for depression are also ongoing in the United Kingdom.

An interesting question that arises in regard to the psychiatric benefits of psychedelic drugs is whether the improvements are due to the hallucinogenic experience or the chemical changes the drugs exert on the brain. Psilocybin causes its psychedelic effects by increasing levels of the neurotransmitter serotonin. Serotonin has long been known to be involved in mood and depression, and it is also the key chemical involved in hallucinations. The most common antidepressant treatments, SSRIs (selective serotonin reuptake inhibitors), are thought to work at least in part by increasing serotonin levels in the brain; however, they obviously do not cause people to feel like their face is melting.

“From a biological standpoint, it’s no surprise that this is a psychoactive medication that could potentially help with people’s mood,” Stern says. “For the treatment effect to be that durable, it likely has a biological basis as opposed to just the memory of going through this psychedelic experience.”

Davis, however, says that there was a strong correlation in the study between people’s psychedelic experience on the drug and its antidepressant effects. “There was a significant relationship between the mystical experience and the insightful experience that people are getting… and the antidepressant effects of their treatment,” he says. “That suggests to us that the acute effects of the drug are important for people to be experiencing the benefit.”

It’s important to note that while psilocybin is very safe physically and has virtually no addictive potential, it can be quite psychologically stressful to take. Also, the psychiatric benefits of the study likely stemmed from taking the drug in a safe environment optimized for a therapeutic experience, not to mention pairing it with hours of therapy before and after. In other words, you might not get the same benefits from your next trip to Oregon.

Health and science writer • PhD in 🧠 • Words in Scientific American, STAT, The Atlantic, The Guardian • Award-winning Covid-19 coverage for Elemental

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