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

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 mg) 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.

Automated summary

This study investigated the efficacy and safety of LSD-assisted therapy in patients with anxiety, with or without a life-threatening illness. The results showed that LSD treatment led to significant reductions in anxiety and comorbid depression symptoms, with effects lasting up to 16 weeks.