A recent clinical trial in Sweden found that a single oral dose of psilocybin reduced depressive symptoms within 48 hours in participants suffering from moderate to severe depression. Participants also reported improvements that persisted for more than three months.
The study, carried out at the Northern Stockholm Psychiatric Clinic and published in JAMA Network, is the first randomized, double-blind trial of psilocybin for depression in Sweden. Researchers at Karolinska Institutet followed 35 participants for 12 months, making this one of the more rigorous long-term, placebo-controlled studies of psilocybin therapy for major depressive disorder.
Most antidepressants take anywhere from two to six weeks before patients begin to notice any change, and even then, about two out of three people don’t fully recover after their first round of treatment. If psilocybin’s fast-acting effect holds up in larger studies, it could provide doctors with a much-needed alternative method for treating depression.
Psilocybin vs. Placebo
All 35 participants suffered from recurrent moderate to severe major depressive disorder. Researchers randomly assigned 17 people to receive a 25 mg oral dose of psilocybin and 18 others to receive an active placebo. The placebo was niacin, a vitamin known to cause temporary flushing and tingling sensations to help mimic the experience of taking a drug.
Everyone in the study also participated in five psychotherapy sessions spread over 17 days. This included a session to prepare participants before taking the drug, the dosing session itself, and three follow-up sessions to help process their reported experiences. On the day of treatment, participants wore eyeshades and listened to music for several hours, with clinical staff nearby to monitor their safety.
Clinicians who did not know which treatment participants received used the Montgomery-Åsberg Depression Rating Scale (MADRS), a 0 to 60-point assessment, to measure depressive symptoms at days 8, 15, 42, and 365 after the initial dose.
Clinically Significant Results
By day 8, people who received the psilocybin dose had an average drop in MADRS score of 7.27 points compared with the placebo group. Researchers say that a difference of this size is statistically significant. This difference continued through day 15 and day 42. By the end of the first year, researchers no longer observed a clear difference between the groups.
Participants’ self-assessments began to show improvement even sooner. Using a self-report version of the MADRS, the group that received the psilocybin dose reported significant improvement starting on the second day; the difference in self-reported assessments between groups persisted until about day 102.
At six weeks, remission rates (defined as a MADRS score below 10) were at 53% in the psilocybin group and 6% in the niacin group. By the end of the year, both groups had similar outcomes, as the placebo group showed gradual improvement over time.
“Our results suggest that psilocybin can provide rapid, clinically meaningful improvement in depression and may serve as an alternative to standard treatment when fast symptom reduction is important,” said lead author Hampus Yngwe, a consultant psychiatrist and PhD student at Karolinska Institutet’s Department of Clinical Neuroscience.
The Psychedelic Caveat
The psychedelic effects of psilocybin made it difficult to keep participants unaware of which treatment they received. After the first year, 94% of those in the psilocybin group and all in the niacin group correctly identified which dose they received.
This is important to note because a person’s expectations can shape how they report their symptoms. The researchers pointed out this limitation and said the effect size might partly be due to participants believing they had received the real drug. Clinician ratings, which were also unaware of the administered doses, showed a similar, though smaller, benefit for the psilocybin group compared to self-reports, which supports this concern.
“We want to understand how factors such as treatment expectations and lack of blinding affect the results, as previous studies may have exaggerated the treatment effects,” Yngwe said.
What Comes Next
Most reported side effects were mild and brief. Headache, anxiety, and hallucinations were the most common adverse effects reported in the psilocybin group. However, two participants experienced severe anxiety that required medical attention in the weeks after dosing. The researchers say this finding highlights the need for careful patient selection and follow-up in future studies.
“It is important to emphasize that the treatment is not risk-free and that some patients may need extra support,” said senior author Johan Lundberg, professor at Karolinska Institutet’s Department of Clinical Neuroscience.
The research team plans to analyze PET scans and biological samples collected before and after dosing to see whether psilocybin changes synaptic density in the brain. This could help explain how the drug produces its rapid antidepressant effect and whether repeated dosing might extend this benefit.
While these results are encouraging, the study only included 35 people at one clinic, which makes it hard to draw broad conclusions about long-term effects. Larger and more diverse studies will be needed before psilocybin therapy could become a standard treatment.
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.