LSD-assisted therapy in patients with anxiety: open-label prospective 12-month follow-up
In a planned 12‑month open‑label follow‑up of a double‑blind, placebo‑controlled crossover trial, LSD‑assisted therapy produced sustained, clinically significant reductions in anxiety and depression with large effect sizes lasting up to nearly two years after treatment. Participants also showed decreased neuroticism, increased extraversion and reported positive long‑term effects attributed to the psychedelic experience.
Authors
- Felix Müller
- Matthias Liechti
- Friederike Holze
Published
Abstract
Background
Anxiety disorders are a major public health burden with limited treatment options.
Aims
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.
Method
This study was an a priori-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 (n = 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-Five-Factor Inventory.
Results
Participants reported a sustained reduction of STAI-G scores compared with baseline (least square means (95% CI) = −21.6 (−32.7, −10.4), d = 1.04, P < 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), d = 1.02, P < 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), d = 0.71, P < 0.01, and −8.9 (−12.9, −4.9), d = 1.21, P < 0.01, for the LSD-first and placebo-first groups, respectively. Personality trait neuroticism decreased (P < 0.0001) and trait extraversion increased (P < 0.01) compared with study inclusion. Individuals attributed positive long-term effects to the psychedelic experience.
Conclusions
Patients reported sustained long-term effects of LSD-assisted therapy for anxiety.
Research Summary of 'LSD-assisted therapy in patients with anxiety: open-label prospective 12-month follow-up'
Introduction
Anxiety disorders are common, often chronic, and current treatments can be slow to produce benefit, leaving a need for new therapeutic approaches. Early clinical studies of classic psychedelics such as LSD and psilocybin have reported rapid and sometimes sustained reductions in anxiety and depressive symptoms after single-dose treatment, and there is emerging evidence that psychedelic experiences can induce changes in personality traits relevant to mood and anxiety disorders. However, the durability of these effects over longer follow-up intervals remains uncertain, and long-term safety data are limited. Holze and colleagues report a planned 12-month follow-up of participants from a previously published double-blind, placebo-controlled, crossover trial of LSD-assisted therapy in people with anxiety disorders, with or without life-threatening illness (LTI). The study aimed to assess whether reductions in anxiety and comorbid depression persisted one year after the end-of-study visit, and to explore enduring changes in general psychiatric symptoms, personality traits and self‑reported positive or negative long-term effects attributed to the psychedelic experience. The authors stated an initial hypothesis that therapeutic effects would not be sustained to the 12-month follow-up, and also examined correlations between acute subjective experiences during LSD sessions and long-term outcomes.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Holze, F., Gasser, P., Müller, F., Strebel, M., & Liechti, M. E. (2024). LSD-assisted therapy in patients with anxiety: open-label prospective 12-month follow-up. The British Journal of Psychiatry, 225(3), 362-370. https://doi.org/10.1192/bjp.2024.99
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