Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial.
Med (New York, N.Y.) – June 04, 2025
Source: PubMed
Summary
Higher doses of LSD combined with psychotherapy showed promising results in treating major depression, with patients experiencing significant mood improvements lasting up to 3 months. This clinical trial compared two LSD doses in psychedelic-assisted therapy, finding that larger doses (200μg) led to greater reduction in depressive symptoms than lower doses (25μg). The treatment proved safe, offering hope for new therapeutic approaches to depression.
Abstract
This trial aimed to assess the efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with moderate-to-severe major depressive disorder. This was a randomized, parallel, double-blind, low-dose controlled trial (Clinicaltrials.gov: NCT03866252). Patients were randomly assigned in a 1:1 ratio to receive supportive psychotherapy and either 100 μg + 200 μg LSD or 25 μg + 25 μg LSD in two dosing sessions. The primary endpoints were the changes in scores on the Inventory of Depressive Symptomatology, in the Clinician-Rated (IDS-C) version (assessed by the treating therapist) and the Self-Rated (IDS-SR) version, from baseline to 2 weeks after the second administration. The IDS scores were also assessed 6 and 12 weeks after the second administration. Thirty-one patients were randomized to the low-dose group, and 30 were randomized to the high-dose group. At the primary endpoint, least-squares mean change (LSM) in IDS-SR scores was -3.9 in the low-dose and -11.8 in the high-dose group (difference: -7.9; 95% CI, -16.0 to 0.3; effect size: -0.5; p = 0.059). LSM in IDS-C scores was -3.6 in the low-dose and -12.9 in the high-dose group (difference: -9.2; CI, -17.1 to -1.3; effect size: -0.6; p = 0.023; corrected <0.05). However, significance was not reached after adjusting for baseline depression scores (p = 0.086). Both outcomes remained numerically consistent up to the final follow-up at 12 weeks. Adverse events were comparable between groups. The findings of this exploratory study support further investigation of LSD-assisted therapy in depression in a larger phase 3 trial. Gertrud Thalmann Fund for depression research.