Abstract
We examined the cardiovascular safety, acceptability, and trajectory of the antidepressant effects of psilocybin after single- or two-dose administration. Four major electronic databases were systematically searched. Data were pooled using a multivariate random-effects meta-analysis. Primary outcomes were changes in depressive symptoms. Secondary outcomes were cardiovascular safety and acceptability. Ten studies were included. The estimated effect sizes (standardized mean difference (SMD) with 95% confidence intervals) for psilocybin were −0.75 (−1.15 to −0.35) on day 1, −1.74 (−2.15 to −1.32) at 1 week, −1.35 (−1.77 to −0.93) at 1 month, −0.91 (−1.31 to −0.51) at 3 months, and −1.12 (−1.56 to −0.68) at 6 months. Higher doses and two sessions of psilocybin treatment were significantly associated with superior antidepressant effects. The all-cause discontinuation and heart rate after psilocybin administration were comparable to placebo; meanwhile, psilocybin increased systolic and diastolic blood pressure by 19.00 mmHg and 8.66 mmHg, respectively. There were no significant differences between SMD derived from placebo-controlled trials compared to those from pre–post changes and SMD in randomized controlled trials (RCTs) compared to those in non-RCTs. The present study demonstrates that single- or two-dose psilocybin administration has rapid and sustained antidepressant effects for up to 6 months, with favorable cardiovascular safety and acceptability.
Highlights
Psilocybin is a serotonergic hallucinogen that undergoes rapid dephosphorylation into psilocin
We performed a systematic review and meta-analysis of clinical trials examining the efficacy of psilocybin in reducing depressive symptoms
We focused on changes in depressive symptoms at different follow-up time points after either single- or two-dose administration of psilocybin, with the aim of exploring the trajectory of antidepressant effects
Summary
Psilocybin is a serotonergic hallucinogen that undergoes rapid dephosphorylation into psilocin. It is a 5-HT2a receptor agonist that causes distortions in perception, thoughts, and emotions, as well as self-boundary dissolution [1]. In the 1950s and the 1960s, psilocybin was used to treat psychological distress in clinical trials; in the 1970s, with the enactment of the Controlled Substances Act, its use was discontinued, and it was classified as a Schedule. With the increasing understanding of the molecular and neurobiological mechanisms of psychedelics, clinical and research interest in such agents as novel therapeutic targets for the management of mental disorders has steadily grown since the 1990s [3]. In. 2008, a guideline was developed to ensure the safety of studies using psychedelics as a treatment for mental disorders [4]. One of the most commonly reported side effects of psychedelics was an acute sympathetic response in dynamic blood pressure and heart rate
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