Work

Efficacy, safety, and tolerability of lysergic acid diethylamide for the treatment of depressive symptoms: A meta-analysis and systematic review

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Background: Since the Food and Drug Administration designated lysergic acid diethylamide (LSD) as a “breakthrough” treatment for generalized anxiety disorder, accumulating randomized clinical trials (RCTs) evaluating LSD’s anxiolytic effects have also reported improved depression symptoms. Evaluating the safety and efficacy of LSD in treating depression symptoms is warranted. Methods: MEDLINE/PubMED, Embase, and PsychINFO were searched from inception to December 9, 2025. RCTs evaluating efficacy of LSD on depression symptoms in adults with mental disorders were included. Cochrane Risk of Bias Tool 2.0 and χ 2 and I 2 tests measured quality and heterogeneity. This review was preregistered on PROSPERO (CRD420251063539). Results: Of 465 screened studies, 5 RCTs met selection criteria ( N = 227). Our synthesis and random-effects meta-analysis demonstrated that LSD treatment significantly reduced depression symptoms compared with the comparator (unadjusted standardized mean difference = −0.69; 95% CI: −0.96 to −0.42, p = 0.0000005; adjusted standardized mean difference = −0.65; 95% CI: −0.92 to −0.38, p = 0.000002). Studies varied in design and three of the included studies administered LSD with psychological support, although study-level heterogeneity was not significant. Three studies had low risk of bias. All-cause discontinuation demonstrated reasonable acceptability of LSD treatment. Severe adverse events possibly related to study parameters included hospitalizations ( N = 3) and acute anxiety/delusions ( N = 1). Conclusion: Our findings suggest that LSD, with and without psychological support, reduces depression scores in clinical populations. This review is limited by small sample size. Future well-designed RCTs are needed to establish the efficacy and safety of LSD in managing depression.

Source: Journal of Psychopharmacology

DOI: 10.1177/02698811261488460

Authors: Andreea Chiorean, Helena K. Kim, Andrew Lustig, Muhammad Ishrat Husain

Institutions: University of Toronto, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, University Health Network, Krembil Brain Institute

Language: English

Topic: Psychedelics and Drug Studies

Subfield: Clinical Psychology

Field: Psychology

Domain: Social Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,400