Efficacy and Safety of LSD in the treatment of mental and substance use disorders: A systematic review of randomized controlled trials.

Abstract

LSD (lysergic Acid Diethylamide), a psychedelic compound, has been investigated in recent studies for the treatment of mental disorders. We analyzed the efficacy and safety of LSD in the treatment of mental disorders and substance use disorders in adult patients. We searched Embase, PubMed, Scopus, PsycINFO, the Cochrane Library, CENTRAL, BVS, EBSCO, Epistemonikos, and the grey literature for double-blind randomized controlled trials (RCTs). The certainty of the evidence was assessed using the GRADE tool. Heterogeneity was assessed with I² statistics and Cochran's Q test, and random-effects models were used. A funnel plot was generated to assess publication bias, and R was used for statistical analysis. We initially identified 3133 publications and included 11 trials with 682 participants diagnosed with substance use disorders, anxiety, or depression. LSD was associated with a small but statistically significant effect for substance use disorders (SMD = 0.19 [0.06; 0.32], p < 0.01), with no observed heterogeneity (I² = 0 %). Notably, 45 % of the studies did not report adverse events, indicating the need for further studies to draw definitive conclusions. Serious adverse events were reported in only one study. The effectiveness of LSD appears to vary significantly depending on the type of mental disorder treated. Results suggest a positive effect on substance use disorders. High heterogeneity requires caution and highlights the need for more double-blind RCTs. Most included RCTs were conducted in the 1960s and 1970s, with only three studies conducted in more recent years. It underscores the need for high-quality contemporary research to strengthen evidence.