Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials
This review (2020) presents the results of 11 randomised-controlled clinical trials (n=567) involving the therapeutic administration of LSD (20-800μg). Multiple variables regarding LSD treatment, therapeutic approach, and quality of experience were revealed and related to therapeutic outcomes. The authors find the most substantial evidence for the use of LSD in the treatment of alcoholism but highlight the lack of double-blind studies.
Authors
- Magí Farré
- Matilde Elices
- Marta Torrens
Published
Abstract
Lysergic acid diethylamide (LSD) was studied from the 1950s to the 1970s to evaluate behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders. LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction. However, most of the studies were not performed under contemporary standards, and it has taken several decades for a resurgence of interest in LSD research and its therapeutic potential for psychiatry. The aim of this review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry. PRISMA guidelines for systematic review were followed. A literature search of PubMed and Psychedelic bibliography from Multidisciplinary Association for Psychedelic Studies (MAPS) databases was performed as well as a manual search of references from evaluated studies. Only randomized-controlled clinical trials were included. Study quality was systematically calculated by using the Cochrane Collaboration Tool for assessing risk of bias. A final selection of 11 articles was made after considering inclusion and exclusion criteria. LSD was administered to 567 patients in a dose ranging from 20 to 800 mcg. Despite the design heterogeneity of clinical trials, positive results were observed, thus revealing the therapeutic potential of LSD to reduce psychiatric symptomatology, mainly in alcoholism. The vast majority of authors describe significant and positive short-term changes in patients, despite the fact that in some studies an important homogenization was observed between the LSD treatment group and control group at long-term follow-up. Multiple variables regarding LSD treatment therapeutic approach and quality of experience were revealed and related to therapeutic outcomes. LSD is revealed as a potential therapeutic agent in psychiatry; the evidence to date is strongest for the use of LSD in the treatment of alcoholism. Despite the difficulty of designing proper double blind clinical trials with this substance, new studies that conform to modern standards are necessary in order to strengthen our knowledge on its use and open new doors in the future.
Research Summary of 'Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials'
Introduction
Fuentes and colleagues situate lysergic acid diethylamide (LSD) within a long, interrupted history of psychiatric investigation: discovered in 1938, studied clinically from the late 1940s through the 1970s, then largely prohibited and neglected until a recent resurgence of interest. Earlier work used LSD for a range of psychiatric problems including anxiety, depression, psychosomatic disorders and addiction, but most of those studies predated contemporary methodological standards. The authors note LSD's pharmacology as a classical hallucinogen acting principally at serotonin 2A receptors, its typical subjective effects (altered time and self‑perception, visual phenomena, ego dissolution), and relevant safety considerations (challenging acute reactions, possible exacerbation of psychosis in vulnerable individuals, modest cardiovascular effects). They also introduce the key therapeutic variables historically emphasised in LSD research: dose, set (patients' mindset and expectations), and setting (physical and interpersonal environment), and three historical therapeutic approaches—psycholytic, psychedelic‑chemotherapy, and psychedelic‑peak therapy. This paper aims to identify and synthesise randomized controlled clinical trials (RCTs) that tested LSD as a therapeutic agent in psychiatric populations, extracting trial characteristics and variables that investigators controlled which might relate to outcomes. The stated objective is to inform discussion about integrating classical hallucinogen research into modern clinical trial designs and to provide guidance for future LSD research under contemporary standards.
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Fuentes, J. J., Fonseca, F., Elices, M., Farré, M., & Torrens, M. (2020). Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials. Frontiers in Psychiatry, 10. https://doi.org/10.3389/fpsyt.2019.00943
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