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.
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.