LSD-assisted therapy in patients with anxiety: open-label prospective 12-month follow-up.

Abstract

Anxiety disorders are a major public health burden with limited treatment options. We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness. This study was an <i>a priori</i>-planned long-term follow-up of an investigator-initiated, two-centre 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. Participants (<i>n</i> = 39) were followed up 1 year after the end-of-study visit to assess symptoms of anxiety, depression and long-term effects of psychedelics using Spielberger's State-Trait Anxiety Inventory-Global (STAI-G), the Beck Depression Inventory (BDI), the Persisting Effects Questionnaire and measures of personality traits using the NEO<b>-</b>Five-Factor Inventory. Participants reported a sustained reduction of STAI-G scores compared with baseline (least square means (95% CI) = -21.6 (-32.7, -10.4), <i>d</i> = 1.04, <i>P</i> < 0.001, for those who received LSD in the first period (94 weeks after the last LSD treatment) and -16.5 (-26.2, -6.8), <i>d</i> = 1.02, <i>P</i> < 0.05, for those who received LSD in the second period (68 weeks after the last LSD treatment)). Similar effects were observed for comorbid depression with change from baseline BDI scores of -8.1 (-13.2, -3.1), <i>d</i> = 0.71, <i>P</i> < 0.01, and -8.9 (-12.9, -4.9), <i>d</i> = 1.21, <i>P</i> < 0.01, for the LSD-first and placebo-first groups, respectively. Personality trait neuroticism decreased (<i>P</i> < 0.0001) and trait extraversion increased (<i>P</i> < 0.01) compared with study inclusion. Individuals attributed positive long-term effects to the psychedelic experience. Patients reported sustained long-term effects of LSD-assisted therapy for anxiety.