Depression affects an estimated 300 million people worldwide and remains the leading cause of disability. Conventional antidepressants are widely prescribed, yet they can take weeks to show effects, have limited efficacy, and often cause side effects that reduce patient adherence. Relapse rates are also high, with up to 60% of patients experiencing recurrent episodes.
Against this backdrop, psilocybin — a naturally occurring hallucinogen found in certain mushrooms — has gained attention as a potential alternative. Unlike selective serotonin reuptake inhibitors (SSRIs), psilocybin appears to act more rapidly, with some studies reporting improvements within hours or days after just one or two doses. Research also suggests the compound has low addictive potential and can be administered safely under clinical supervision.
A new systematic research and meta-analysis, led by Athina-Marina Metaxa based at the University of Oxford, and published in the British Medical Journal (BMJ), assessed nine randomized trials involving 436 participants with clinically significant depression. The results were encouraging:
- Symptom improvement: Psilocybin was associated with a moderate-to-large reduction in depression scores compared with placebo.
- Response rates: Patients were more than twice as likely to show a treatment response versus placebo.
- Remission rates: They were nearly three times as likely to achieve remission.
- Side effects: Reported adverse events were minor and short-lived, including headache, mild anxiety, and temporary increases in blood pressure.
Importantly, the research found no evidence of serious harm, withdrawal symptoms, or addictive potential.
“These results show that psilocybin has real potential to make a difference for people living with depression,” said Metaxa. “For patients who haven’t found relief with traditional antidepressants, psilocybin could be a game-changer.”
The data also suggested psilocybin may work especially well for certain groups. “The findings hint that psilocybin may be particularly effective for patients with secondary depression or those with prior positive experience using psychedelics. That opens the door to more personalized approaches in mental health care,” Metaxa explained.
Still, important caveats remain. Most of the included studies involved small sample sizes, lacked diversity, and often relied on self-reported measures, which may be influenced by patient expectations. “One of the biggest methodological challenges in psychedelic research is blinding, since patients can usually tell whether they’ve received psilocybin or placebo,” Metaxa noted. “That can inflate expectations and influence outcomes. Until we find better ways to control for this, interpreting the data will always require caution.”
Practical barriers also stand in the way of clinical rollout. In trials, psilocybin was delivered in highly controlled environments, often involving specially designed rooms, calming music, eye masks, and continuous therapist supervision. Replicating such complex and costly protocols in everyday healthcare settings may prove difficult. Without regulatory frameworks, training standards, and safeguards against misuse, large-scale adoption remains uncertain.
“Whether psychedelic medicines could become part of mainstream psychiatry remains to be seen,” said Metaxa. “But the fact that large pharmaceutical companies — including J&J and AbbVie — are investing in psychedelics shows that medical scientists see real commercial and clinical potential in treatments once considered taboo.”
Despite the hurdles, researchers stress that larger, more diverse trials are needed, particularly those involving patients already taking standard antidepressants. Future studies should also directly compare psilocybin with SSRIs and explore how expectancy effects shape outcomes.
Metaxa emphasized the importance of continuing this line of work: “I am very proud of this paper and the fact that it was featured in such a high-profile journal. Now the next step is to look into the effectiveness of more novel treatments for depression and investigate the factors that moderate this effectiveness. This work will hopefully help create a ‘map’ to guide researchers in identifying good candidate drugs for clinical trials.”
While psilocybin cannot yet be considered a mainstream treatment, the research concludes it holds real promise as a novel approach to tackling depression — provided its delivery can be made safe, accessible, and affordable.
