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

Background: 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. Methods: 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. Results: 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%). Conclusions: LSD produced long-lasting and notable reductions in anxiety and comorbid depression symptoms up to 16 weeks.