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Trajectory of Antidepressant Effects after Single- or Two-Dose Administration of Psilocybin: A Systematic Review and Multivariate Meta-Analysis

Summary

This comprehensive analysis of 10 clinical trials shows that psilocybin, a compound from magic mushrooms, can rapidly reduce depression symptoms starting within one day of administration and maintain these benefits for up to 6 months. Higher doses and two treatment sessions produced better results than single lower doses. While psilocybin did raise blood pressure temporarily, it was generally well-tolerated with dropout rates similar to placebo.

Background

Psilocybin is a serotonergic hallucinogen that acts as a 5-HT2a receptor agonist with potential therapeutic applications for mental health disorders. Clinical and research interest in psychedelics has grown since the 1990s following increased understanding of their molecular and neurobiological mechanisms. This study examines the trajectory and safety profile of psilocybin’s antidepressant effects.

Objective

To systematically review and meta-analyze the trajectory of antidepressant effects following single or two-dose psilocybin administration, and to evaluate cardiovascular safety and acceptability. The study aimed to explore the promptness and duration of antidepressant effects using multivariate meta-analysis accounting for correlations between effect sizes at different timepoints.

Results

Psilocybin showed significant antidepressant effects from day 1 (SMD −0.75) through month 6 (SMD −1.12), with strongest effects at week 1 (SMD −1.74). Higher doses and two-dose regimens produced superior outcomes. Psilocybin increased systolic and diastolic blood pressure by 19.00 and 8.66 mmHg respectively, but showed comparable heart rate and discontinuation rates to placebo.

Conclusion

Single or two-dose psilocybin administration produces rapid onset and sustained antidepressant effects lasting up to 6 months with favorable cardiovascular safety and acceptability profiles. Higher doses and repeated dosing showed superior efficacy, though additional well-designed RCTs are needed to confirm findings and establish optimal dosing regimens.
  • Published in:Journal of Clinical Medicine,
  • Study Type:Meta-analysis, Systematic Review,
  • Source: PMID: 35207210, DOI: 10.3390/jcm11040938
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