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

  Two 200 µg LSD sessions reduced anxiety scores up to 16 weeks after treatment with a large effect size, and also reduced comorbid depression symptoms.

  Synthesized October 22, 2026

• State of the evidence: LSD for depression ↑Supports

  A single 200 µg LSD-assisted therapy session significantly reduced comorbid depression scores on the Hamilton Depression Rating Scale (d = -1.1) and Beck Depression Inventory (d = -0.72) up to 16 weeks after treatment.

  Synthesized October 22, 2026

Comparable studies

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