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Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis

Summary

This comprehensive analysis of clinical trials found that psilocybin, a compound found in certain mushrooms, shows promise as a treatment for depression compared to placebo. The treatment was particularly effective for patients with depression related to serious illness, those using self-reported symptom assessments, older adults, and those with prior experience with psychedelics. While side effects were minimal and temporary, researchers emphasize that more research is needed to fully understand how expectancy and individual factors influence treatment outcomes.

Background

Depression affects approximately 300 million people worldwide and is the leading cause of disability. Current antidepressant medications have limited efficacy, serious adverse effects, and are associated with low patient adherence. Psilocybin, a naturally occurring serotonergic hallucinogen, has been proposed as a potential treatment for depression with a different mechanism of action than conventional antidepressants.

Objective

To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs through a systematic review and meta-analysis of randomised controlled trials.

Results

Meta-analysis of seven studies showed significant benefit of psilocybin compared with comparator treatment (Hedges’ g=0.66, 95% CI 0.46 to 0.86). Greater improvements were associated with secondary depression, self-report depression scales, older age, and previous psychedelic use. Risk ratio for response was 2.17 and for remission was 2.96 compared with placebo. All studies had moderate risk of bias with moderate certainty of evidence.

Conclusion

Psilocybin demonstrated significantly larger treatment effects for secondary depression, when measured by self-report scales, and in participants with prior psychedelic experience. Further research is needed to clarify the influence of expectancy effects, moderating factors, and treatment delivery on psilocybin’s antidepressant efficacy.
  • Published in:BMJ (British Medical Journal),
  • Study Type:Meta-analysis,
  • Source: PMID: 38692686, DOI: 10.1136/bmj-2023-078084
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