Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study.

Abstract

This study aimed to investigate the efficacy and safety of lysergic acid diethylamide (LSD)-assisted therapy in patients who experienced anxiety with or without association with a life-threatening illness. The study is an investigator-initiated 2-center trial that used a double-blind, placebo-controlled, 2-period, random-order, crossover design with 2 sessions with either oral LSD (200 μg) or placebo per period. The primary end point was anxiety symptoms 16 weeks after the last treatment session, assessed by the Spielberger State-Trait Anxiety Inventory-Global score in 42 patients. Further outcome measures included ratings for depression symptoms (Beck Depression Inventory and Hamilton Depression Rating Scale, 21-item version) and ratings for acute subjective drug effects. The outcomes for the first period (between-subjects analysis) are primarily shown due to carryover effects. LSD treatment resulted in significant reductions of State-Trait Anxiety Inventory-Global scores up to 16 weeks after treatment (least-square mean [standard error] change from baseline difference = -16.2 [5.8], 95% CI, -27.8 to -4.5, d = -1.18, p = .007). Similar effects were observed for ratings of comorbid depression on the Hamilton Depression Rating Scale, 21-item version (-7.0 [1.9], 95% CI, -10.8 to -3.2, d = -1.1, p = .0004) and the Beck Depression Inventory (-6.1 [2.6], 95% CI, -11.4 to -0.9, d = -0.72, p = .02). Positive acute subjective drug effects and mystical-type experiences correlated with the long-term reductions in anxiety symptoms. Transient, mild, acute untoward effects of LSD treatment were reported by 8 patients (19%). One treatment-related serious adverse event (acute transient anxiety) occurred (2%). LSD produced long-lasting and notable reductions in anxiety and comorbid depression symptoms up to 16 weeks.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

• State of the evidence: LSD for anxiety ↑Supports

  LSD-assisted therapy produced significant reductions in anxiety symptoms up to 16 weeks after treatment with a large effect size, and also reduced comorbid depression symptoms.

  Synthesized September 21, 2026

• State of the evidence: LSD for depression ↑Supports

  LSD-assisted therapy produced significant reductions in comorbid depression symptoms on the Hamilton Depression Rating Scale and Beck Depression Inventory up to 16 weeks after treatment.

  Synthesized September 21, 2026

Comparable studies

Other randomized controlled trials on LSD for depression, most cited first.