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

This review & meta-analysis (s=10, n=226) finds that two (vs one) sessions and a higher dose (up to 30mg) were associated with better antidepressant effects. The meta-analysis showed a robust antidepressant effect up to 6 months later (d = -1.12).

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.”

Authors: Chia-Ling Yu, Chih-Sung Liang, Fu-Chi Yang, Yu-Kang Tu, Chih-Wei Hsu, Andre F. Carvalho, Brendon Stubbs, Trevor Thompson, Chia-Kuang Tsai, Ta-Chuan Yeh, Szu-Nian Yang, Jae Il Shin, Che-Sheng Chu, Ping-Tao Tseng & Kuan-Pin Su

Summary of Trajectory of Antidepressant Effects after Single- or Two-Dose Administration of Psilocybin

Psilocybin is a serotonergic hallucinogen that causes distortions in perception, thoughts, and emotions. It is a 5-HT2a receptor agonist that causes self-boundary dissolution and an acute sympathetic response in dynamic blood pressure and heart rate.

Psilocybin may exert psychoactive effects through 5-HT2a receptor agonism, widely distributed in the frontal cortex and hippocampus and associated with antidepressant-like effects in animal models.

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