722. Predictors of therapeutic response to LSD in anxiety: short- and long-term outcomes

Abstract Background Anxiety disorders are a major health burden and current treatment options yield unsatisfactory results. Psychedelics, such as lysergic acid diethylamide (LSD) that act via agonism on serotonin 2A receptors, have recently been shown to be effective in the treatment of anxiety symptoms. Aims & Objectives Here, we determine the relationship between the acute experience and short and long-term outcomes of in patients who suffered from anxiety with or without life-threatening illness.

Method: This study was 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 separated by 6 weeks. The study duration was 24 weeks per period (48 weeks total) and patients were followed up to 1 year after the end-of-study visit of the original trial. The primary endpoint was assessed 16 weeks after the last treatment session. We assessed symptoms of anxiety and long-term effects of psychedelics using Spielberger’s State-Trait Anxiety Inventory–Global (STAI-G) and the Persisting Effects Questionnaire (PEQ). Furthermore, acute drug effects were assessed using the 5 Dimension Altered State of Consciousness Questionnaire (5D-ASC) and the 30-item Mystical Effects Questionnaire (MEQ30).

Results: On the STAI-G, positive acute subjective drug effects measured with the 5D-ASC (Oceanic Boundlessness [OB]) and mystical-type experiences (MEQ30 total score) correlated with short-term reductions (16 weeks after last treatment) in anxiety symptoms (r = -0.40, p = 0.01 and r = - 0.34, p = 0.03, respectively) and also long-term reductions (1-yr follow-up; r = -0.33, p = 0.055 and r = - 0.34, p = 0.048, respectively). Negative subjective drug effects (Anxious Ego Dissolution [AED]) showed no correlations with therapeutic outcomes. On the PEQ, assessed at 1yr-follow-up, OB and the MEQ30 total score correlated significantly with “positive attitudes about life and/or self” (p = 0.035 and p = 0.015, respectively) and “positive mood changes” (p = 0.015 and p = 0.005, respectively). AED scores did not correlate significantly with long-term outcomes on the PEQ. Discussion & Conclusions Summarized, these findings indicate that acute positive drug effects and mystical-type experiences predict short and long-term therapeutic outcomes, while acute negative drug effects remain neutral.