Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response
In a naturalistic Swiss sample, psychedelic-assisted therapy with LSD or psilocybin produced significant reductions in depressive symptoms, and the strongest predictor of antidepressant response was participant-reported relaxation during the session rather than retrospectively assessed mystical-type experiences. Patients reported similar overall drug effects but lower ego dissolution and more challenging acute effects than healthy volunteers, suggesting hourly assessments of subjective effects may better predict clinical outcomes.
Authors
- Matthias Liechti
- Friederike Holze
- Gregor Hasler
Published
Abstract
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.
Research Summary of 'Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response'
Introduction
Psychedelic-assisted therapy (PAT) with psilocybin and LSD has shown promise for depression, anxiety and other neuropsychiatric disorders, and Switzerland permits PAT under a limited medical use programme. Calder and colleagues note that data from this programme provide a naturalistic, real-world complement to controlled trials because patients vary in diagnoses, concomitant medications, dosing schedules and number of sessions. The authors highlight ongoing debate about which acute subjective drug effects underpin therapeutic benefit: mystical-type experiences measured retrospectively (e.g. with the Mystical Experience Questionnaire, MEQ), overall intensity of the experience, ego dissolution, or the valence of acute effects (pleasant versus challenging). They also note that subjective effects are usually measured retrospectively but could be assessed in real time, which may be valuable clinically. This study set out to characterise acute subjective effects during PAT in Swiss clinical practice, to compare those effects with data from a randomized double-blind crossover trial in healthy volunteers receiving the same drug formulations, and to examine relationships between acute subjective effects and rapid antidepressant response in patients. Specific aims included analysing dose–response relations for LSD and psilocybin in patients, comparing patient and healthy-subject subjective profiles, assessing how hourly (real-time) ratings relate to retrospective MEQ scores, and testing whether particular acute effects predict changes in depressive symptoms as measured by the Montgomery–Åsberg Depression Rating Scale (MADRS).
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Study Details
- Study Typeindividual
- Journal
- Compounds
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- APA Citation
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, 38(10), 873-886. https://doi.org/10.1177/02698811241278873
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