This comparative study (n=56) investigates the relationship between antidepressant effects and acute drug effects of LSD and psilocybin in 28 patients undergoing psychedelic-assisted therapy (PAT) in Switzerland and 28 healthy volunteers from a randomized, double-blind crossover trial. The study finds similar ratings of overall drug effect and mystical experience across groups, but lower ratings of ego dissolution in patients. It identifies relaxation during PAT sessions as the greatest predictor of antidepressant outcomes.
Abstract of Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response
“Background Psychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT.
Aims This study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers. For the patients, it also investigated the relationship between antidepressant effects and six measures of acute drug effects.
Methods We compared data on acute psychedelic drug effects between 28 PAT patients with data from 28 healthy participants who participated in a randomized, double-blind crossover trial. All participants received varying doses of psilocybin and LSD. Subjective effects were assessed on an hourly basis during the acute drug effects, and the Mystical Experience Questionnaire (MEQ) was completed retrospectively. For patients, depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).
Results Ratings of overall drug effect and mystical experience were similar across groups. Compared with healthy controls, patients reported lower ratings of ego dissolution. Patients showed a significant decrease in MADRS scores, and the greatest predictor of antidepressant outcome was relaxation during the PAT session. We did not observe a relationship between mystical-type experiences and antidepressant effects. Most patients experienced mild adverse effects which resolved within 48 h.
Conclusion PAT reduced depressive symptoms in this heterogeneous patient group. Patients may experience more challenging psychedelic effects and reduced ego dissolution. Hourly assessment of drug effects may predict clinical outcomes better than retrospectively assessed mystical experiences, and the impact of relaxation during PAT should be investigated further.“
Authors: Abigail E. Calder, Benjamin Rausch, Matthias E. Liechti, Friederike Holze & Gregor Hasler
Summary of Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response
Psychedelic-assisted therapy (PAT) has emerged as a promising treatment for various mental health conditions, including depression, anxiety, and substance use disorders. In Switzerland, PAT is permitted under a limited medical use program, providing a unique opportunity to study its real-world application. This research focuses on comparing the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers, as well as investigating the relationship between antidepressant effects and acute drug effects in patients.
The use of psychedelics in therapeutic settings has gained renewed interest in recent years, with several clinical trials demonstrating potential efficacy. However, most of these studies have been conducted in controlled research environments with carefully selected participants. The Swiss program offers a chance to examine PAT in a more diverse, real-world setting, potentially providing insights that are more representative of how these treatments might be applied in broader clinical practice.
Methods
Participants and Study Design
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https://doi.org/10.1177/02698811241278873
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Cite this paper (APA)
Calder, A. E., Rausch, B., Liechti, M. E., Holze, F., & Hasler, G. (2024). Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response. Journal of Psychopharmacology, 02698811241278873.
Study details
Compounds studied
LSD
Psilocybin
Topics studied
Healthy Subjects
PTSD
Anxiety
Obsessive-Compulsive Disorder
Alcohol Use Disorder
Autism
Treatment-Resistant Depression
Bipolar Disorder
Study characteristics
Original
Placebo-Controlled
Double-Blind
Randomized
Participants
56
Humans
Compound Details
The psychedelics given at which dose and how many times
LSD 100 μg | 1x Psilocybin 14 mg | 1x