- Researchers studied if the psychedelic compound found in magic mushrooms can help depression.
- A single dose of the psilocybin reduced symptoms of major depression more than a placebo.
- The study improved on earlier research, but experts say longer-term trials are needed to know if the benefits are sustained beyond six months.
- Psilocybin is given with psychological support, including preparation before the dose and an integration session following.
A single dose of the psychedelic substance psilocybin, given with psychological support, reduced symptoms of major depression, with effects lasting up to six weeks, a new study shows.
The study was published in JAMA on August 31.
Researchers found that people who took psilocybin saw a greater improvement in depression scores, compared to those who took a placebo substance with no psychedelic properties.
Psilocybin is a psychedelic compound found in magic mushrooms.
People who took psilocybin also saw a decrease in the overall severity of their disease and improvements in anxiety symptoms and quality of life.
And unlike standard antidepressant medicines, psilocybin use did not lead to “emotional blunting,” or a numbness to positive and negative emotions.
The study adds to the evidence that psilocybin, alongside psychological support, may provide people with major depressive disorder an alternative treatment to antidepressants.
“Although the trial was relatively small, it demonstrated that a single dose of psilocybin in the context of a six-week period that included active psychotherapy resulted in a rapid, robust, and sustained reduction in depressive symptoms,” wrote Rachel Yehuda, PhD, and Amy Lehrner, PhD, of the Icahn School of Medicine at Mount Sinai, in an accompanying editorial.
Decrease in depression symptoms with psilocybin
Major depressive disorder, or clinical depression, is a significant medical condition that can impact mood and behavior, as well as physical functions such as appetite and sleep.
It is commonly treated with antidepressant medicines, which, within six to eight weeks, improve symptoms in 40% to 60% of people with moderate or severe depression.
However, these medications have a number of side effects — such as headaches, dizziness and sexual problems — that may cause people to stop their treatment.
In recent years, researchers have been studying the use of psychedelics such as psilocybin — the active compound in magic mushrooms — as a treatment for depression and other mental health conditions.
In a phase 2 clinical trial, published Aug. 31 in JAMA, researchers attempted to overcome some of the limitations of earlier psilocybin research, such as a small number of participants and the potential for researchers to know whether people were taking psilocybin or the placebo.
The new study included 104 participants between 21 and 65 years of age who met the criteria for major depressive disorder but were otherwise healthy.
Around half of the participants were women and the majority were white. Most were experiencing ongoing depression versus a first episode of depression.
The study was carried out at 11 sites in the United States between 2019 and 2022.
Potential participants were excluded from the study for certain reasons such as having moderate or severe alcohol use disorder, using a psychedelic within the past five years, having suicidal thoughts or behavior in the past year, or being treated for depression with deep brain stimulation.
Researchers randomly assigned people to receive either a single oral dose of 25 milligrams of psilocybin or 100 milligrams of niacin. This dose was given after participants slowly reduced and then stopped taking their regular antidepressants.
Niacin was used as an active placebo because it doesn’t have psychedelic effects, but produces a harmless flush of red on the skin. This reduces the chance that participants and researchers would be able to guess which compound people received.
Researchers assessed people’s depression symptoms at the start and then 2, 8, 15, 29, and 43 days after they received the psilocybin or niacin. They also asked participants about anxiety symptoms, side effects they experienced, and their quality of life.
These assessments were done over the telephone; again, to reduce the risk that researchers would know which group the participants were in.
Study sponsor Usona Institute Inc., a nonprofit medical research organization, provided the psilocybin for the trial, designed the study, and was involved in interpreting the study data and writing the scientific manuscript.
Psilocybin doesn’t work for everyone
After six weeks, people who took psilocybin saw a greater improvement in their depression symptoms, on average, compared to those who took niacin.
The average size of the improvement in the psilocybin group corresponded to “substantial clinical improvement” in people with treatment-resistant depression, researchers wrote.
These “improvements in depression [in the psilocybin group] were apparent within eight days of psilocybin dosing,” they added, “consistent with a rapid onset of action, and were maintained across the six-week follow-up period.”
However, not all participants benefitted at this level from psilocybin, which was also seen in earlier research.
“From this study, it looks like psilocybin is not going to work for everyone,” said Dr. Manish Sapra, psychiatrist and executive director for behavioral health services at Northwell Health.
However, “even the best antidepressant drugs that we have work in around two-thirds of the population, so anything more than that would be an improvement,” he told Healthline.
But it’s difficult to know how many people will benefit from psilocybin in the real world, given the small sample size of the study, he added.
Researchers also found that psilocybin was “generally well-tolerated,” with most of the negative side effects being “mild or moderate” in severity and short-lived.
The most common side effect was headache, followed by nausea and hallucinations. Visual effects occurred mainly on the day of dosing, with a small number experiencing them later on; these had gone away by the end of the study.
While the researchers were able to overcome some of the limitations of earlier research, the new study had its own shortcomings. One is the lack of ethnic and racial diversity, making it difficult to know if other groups would experience the same benefits.
In addition, the study doesn’t show whether the benefits of psilocybin last longer than six weeks. However, an earlier study suggests that the effects may extend to at least a year after dosing.
“The results are very encouraging,” said Sapra. “What we really need, though, are long-term trials to see how long this improvement is sustained in patients.”
Longer-term studies, such as a year, might also show whether patients will need repeated, or maintenance, treatments with psilocybin to keep those benefits, he told Healthline.
If psilocybin is approved by the Food and Drug Administration as a treatment for major depression, ongoing studies would provide additional data on the safety and effectiveness of this substance in real-world settings, he added.
Psychological support is key
As for other psychedelics, psilocybin treatment involves more than just giving people the dose and letting them go home.
“Psychedelics can … induce challenging and difficult experiences,” wrote Yehuda and Lehrner.
So these substances “need to be used carefully and in the presence of facilitators or therapists who are trained to work with people experiencing nonordinary states of consciousness,” they added.
In the new study, prior to receiving the dose of psilocybin (or niacin), participants spent six to eight hours with research staff to prepare for their experience.
The dosing session lasted seven to 10 hours and was conducted in a comfortable room under the supervision of staff. Participants were encouraged to wear eyeshades and listen to relaxing music on headphones.
This was followed by a four-hour integration session with staff, during which participants discussed their experience.
Yehuda and Lehrner wrote that additional research is needed to identify which patients will benefit the most from psychedelics, whether repeated treatments are beneficial and safe, and what the optimal dose and treatment approaches are.
If psychedelic treatments do prove to have lasting effects after a single or a few treatments, “they have the potential to offer not just a new approach to mental health care, but an entirely new paradigm of care,” they said.
In a 6-week clinical trial, researchers found that a single dose of psilocybin, given with psychological support, improved symptoms of depression more than a non-psychedelic placebo.
Psilocybin was generally well-tolerated, with headache, nausea and hallucination the most common side effects. Most visual effects occurred on the day of dosing, and all had gone away by the end of the study.
While psilocybin reduced symptoms of depression on average more than the placebo, not all participants benefitted from the psychedelic treatment.