Background
This study aimed to investigate the efficacy and safety of lysergic acid diethylamide (LSD)-assisted therapy in patients who suffered from anxiety with or without association to a life threatening illness.

Methods
The study is an investigator-initiated two-center trial that used a double-blind, placebo-controlled, two-period, random-order, crossover design with two sessions with either oral LSD (200 μg) or placebo per period. The primary endpoint was anxiety symptoms 16 weeks after the last treatment session, assessed by Spielberger’s State-Trait Anxiety Inventory–Global (STAI-G) score in 42 patients. Further outcome measures included ratings for depression symptoms (BDI [Beck Depression Inventory] and HAM-D-21 [Hamilton Depression Rating Scale]) and ratings for acute subjective drug effects. The outcomes for the first period, (between-subjects analysis) are primarily shown due to carry-over effects.

Results
LSD treatment resulted in significant reductions of STAI-G scores up to 16 weeks after treatment (least square mean (± SE) change from baseline difference = -16.2 (5.8), 95% CI=-27.8 to -4.5, d=-1.18, p=0.007). Similar effects were observed for ratings of comorbid depression on the HAM-D-21 (-7.0 (1.9), 95% CI=-10.8 to -3.2, d=-1.1, p=0.0004) and the BDI (-6.1 (2.6), 95% CI=-11.4 to -0.9, d=-0.72, p=0.02). 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 eight patients (19%). One treatment-related serious adverse event (acute transient anxiety) occurred (2%).

Conclusion
LSD produced long-lasting and notable reductions of anxiety and comorbid depression symptoms up to 16 weeks.