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

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.

A Phase I trial to inform clinical protocols for the safe administration of psilocybin-assisted psychotherapy

“…In a similar manner, DBP was only significantly elevated at 90 minutes post-administration. Yu et al (2022) conducted a meta-analysis that analyzed psilocybin's effect on the cardiovascular system as a secondary outcome. Compared with placebo, psilocybin treatment was associated with a significant increase in both systolic and diastolic blood pressure; an average increase of 19.00 mmHg and 8.66 mmHg was observed, respectively.…”

Acute but not long-lasting antidepressant-like effect of psilocybin in differential reinforcement of low-rate 72 schedule in rats

“…Treatment with three doses was used to maximize the chances of detecting the purported effect of drugs on DRL measures. This assumption was based on a recent Yu et al’s (2022) meta-analysis showing that two doses of psilocybin, separated by 1 week, were more effective than a single drug administration in reducing symptoms of depression in the patients.…”

Discovery and Structure–Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists

“…The mixture was left under stirring for 16 h. The reaction mixture was concentrated in vacuo and purified by flash column chromatography (25% EtOAc in heptane) to give the pure nitrile as a white solid (298 mg, 38%). TLC R f = 0.3 (25% EtOAc in heptane v/v) (development: ninhydrin); 1 H NMR (400 MHz, CDCl 3 ) δ 6.97 (s, 1H), 6.79 (s, 1H), 4.30−3.96 (m, 2H), 3.89 (s, 3H), 3.81 (s, 3H), 3.09 (ddt, J = 10.7, 7.3, 3.7 Hz, 1H), 2.80 (s, 2H), 1.98−1.88 (m, 1H), 1.74 (s, 1H), 1.69−1.54 (m, 3H), 1.46 (s, 10H); 13 2,5-Dimethoxy-4-(piperidin-3-yl)benzonitrile (10). A round-bottom flask, equipped with a stir bar, was charged with tert-butyl 3-(4-cyano-2,5-dimethoxyphenyl)piperidine-1-carboxylate (150 mg. 0.44 mmol) and MeOH (5 mL).…”

“…Serotonin is involved in a multitude of functions in the central nervous system (CNS) as well as in the periphery, where a total of 14 different receptor subtypes mediate the effects of the neurotransmitter. , Agonists of 5-HT 2A R such as psilocybin, LSD, and DMT are often referred to as psychedelics due to their perturbation of perception and state of mind. , Several of these compounds are presently receiving substantial attention as possible therapeutics for the treatment of a range of psychiatric disorders. − For example, psilocybin has shown promising effects in the treatment of depression, obsessive-compulsive disorder, and substance use disorder. − …”