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

Friederike Holze; Peter Gasser; Felix Müller; Patrick C Dolder; Matthias E Liechti

doi:10.1016/j.biopsych.2022.08.025

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

Biol Psychiatry. 2023 Feb 1;93(3):215-223. doi: 10.1016/j.biopsych.2022.08.025. Epub 2022 Sep 5.

Authors

Friederike Holze¹, Peter Gasser², Felix Müller³, Patrick C Dolder¹, Matthias E Liechti⁴

Affiliations

¹ Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
² Clinic Dr. Peter Gasser, Solothurn, Switzerland.
³ Psychiatric University Hospital, University of Basel, Basel, Switzerland.
⁴ Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. Electronic address: matthias.liechti@usb.ch.

PMID: 36266118
DOI: 10.1016/j.biopsych.2022.08.025

Abstract

Background: 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.

Methods: 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.

Results: 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%).

Conclusions: LSD produced long-lasting and notable reductions in anxiety and comorbid depression symptoms up to 16 weeks.

Trial registration: ClinicalTrials.gov NCT03153579.

Keywords: Anxiety; Depression; LSD; Life-threatening-illness; Psychedelics; RCT.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Anxiety Disorders / therapy
Anxiety* / drug therapy
Cross-Over Studies
Double-Blind Method
Humans
Lysergic Acid Diethylamide* / therapeutic use
Treatment Outcome

Substances

Lysergic Acid Diethylamide

Associated data

ClinicalTrials.gov/NCT03153579