Psilocybin may help ease depression symptoms

Treatment with psilocybin significantly improves the symptoms of depression, particularly when using self-report scales and when individuals have used psychedelics in the past, results of a systematic review and meta-analysis have shown.

“This review’s findings on psilocybin’s efficacy in reducing symptoms of depression are encouraging for its use in clinical practice as a drug intervention for patients with primary or secondary depression, particularly when combined with psychological support and administered in a supervised clinical environment,” according to investigators Athina-Marina Metaxa and Mike Clarke.

Metaxa is a master’s graduate researcher from Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK, while Clarke is a professor at Northern Ireland Methodology Hub, Centre for Public Health, ICS-A Royal Hospitals, Belfast, Ireland, UK.

Metaxa and Clarke searched the databases of Cochrane, Medline, Embase, ClinicalTrials.gov, and PsycInfo among other for randomized trials in which psilocybin was used as a standalone treatment for adults with clinically significant symptoms of depression and chance in symptoms was measured by a validated clinician-rated or self-report scale.

The two investigators extracted information on potential treatment effect, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure, and personal characteristics (eg, age, sex). They synthesized data using a random effects meta-analysis model and examined covariate effects through subgroup analyses and meta-regression.

Nine studies met the eligibility criteria, of which seven reported a significant benefit of using psilocybin (Hedges’ g, 1.64, 95 percent confidence interval [CI], 0.55‒2.73; p<0.001) on change in depression scores relative to comparator treatment in a total of 436 participants (age range, 36‒60 years, 228 female). [BMJ 2024;385:e078084]

In subgroup analyses, participants with secondary depression (Hedges’ g, 3.25, 95 percent CI, 0.97‒5.53), those assessed with self-report depression scales (Hedges’ g, 3.25, 95 percent CI, 0.97‒5.53), older individuals (meta-regression coefficient, 0.16, 95 percent CI, 0.08‒0.24), and those with previous use of psychedelics (coefficient, 4.2, 95 percent CI, 1.5‒6.9) had a greater reduction in depression symptoms.

The risk of bias in all studies included was low, but the change from baseline metric correlated with high heterogeneity and a statistically significant risk of small study bias. This suggested a low certainty of evidence rating.

Applicability

“In our meta-analysis, we found that psilocybin use showed a significant benefit on change in depression scores compared with placebo,” Metaxa and Clarke said.

These findings support those of recent meta-analyses and trials of psilocybin as a standalone treatment for depression or in combination with psychological support. [J Psychoactive Drugs 2023;55:40-50; Curr Psychiatry Rep 2022;24:573-581; Pharmaceuticals (Basel) 2021;14:793; Biomedicines 2020;8:331]

“Although this review’s findings are encouraging for psilocybin’s potential as an effective antidepressant, a few areas about its applicability in clinical practice remain unexplored,” Metaxa and Clarke said. For instance, “it is unclear whether the protocols for psilocybin interventions in clinical trials can be reliably and safely implemented in clinical practice.”

“Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant,” they said.