Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study
In a double‑blind, placebo‑controlled study, healthy adults received four repeated low doses of LSD (13 or 26 μg) at 3–4‑day intervals. The 26 μg dose produced modest subjective drug effects but neither dose improved mood or cognitive/emotional task performance, no residual effects were detected at follow‑up, and the regimen was well tolerated in this controlled, limited‑administration setting.
Authors
- Harriet de Wit
- Richard Lee
- Anya Bershad
Published
Abstract
The resurgence of interest in using psychedelic drugs, including lysergic acid diethylamide (LSD), in psychiatry has drawn attention to the medically unsupervised practice of ‘microdosing’. Thousands of users claim that very low doses of LSD, taken at 3–4‐day intervals, improve mood and cognitive function., However, few controlled studies have described the effects of the drug when taken in this way. Here, in a double‐blind controlled study, we studied the effects of four repeated doses of LSD tartrate (13 or 26 μg) or placebo, administered to healthy adults at 3–4 day intervals, on mood, cognitive performance and responses to emotional tasks. Participants were randomly assigned to one of three drug conditions: placebo (N = 18), 13 μg LSD (N = 19), or 26 μg LSD (N = 19). They attended four 5‐hour drug‐administration sessions separated by 3–4 days, followed by a drug‐free follow‐up session 3–4 days after the last session. LSD (26 μg) produced modest subjective effects including increased ratings of ‘feeling a drug effect’ and both stimulant‐like and LSD‐like effects, but the drug did not improve mood or affect performance on psychomotor or most emotional tasks. No residual effects were detected on mood or task performance on the drug‐free follow‐up session. We conclude that within the context of a controlled setting and a limited number of administrations, repeated low doses of LSD are safe, but produce negligible changes in mood or cognition in healthy volunteers.
Research Summary of 'Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study'
Introduction
Microdosing with lysergic acid diethylamide (LSD) — ingesting very low doses roughly every 3–4 days — has become popular amid widespread anecdotal claims of improved mood, cognition and overall functioning. Previous controlled work is limited: some single-dose studies document modest subjective and physiological effects at low doses, a small trial in older adults found altered time perception but no mood benefit, and a large naturalistic double-blind trial suggested expectancy/placebo effects may account for reported well‑being gains. Preclinical data indicate repeated small doses of psychedelics can produce antidepressant-like effects in animals, possibly via repeated 5‑HT2A receptor activation and subsequent receptor regulation, but whether repeated low doses yield measurable psychological benefits in humans remains uncertain. De Wit and colleagues set out to test whether repeated low doses of LSD produce measurable improvements in mood, cognitive performance or emotional processing in healthy volunteers. The investigators administered four sublingual administrations of either placebo, 13 μg or 26 μg LSD tartrate (roughly equivalent to 10 and 20 μg LSD base) at 3–4 day intervals and evaluated subjective, cognitive, emotional and physiological outcomes during dosing sessions and at a drug‑free follow‑up 3–4 days after the final dose. The primary hypothesis was that repeated low‑dose LSD, compared with placebo, would improve mood and cognitive performance and that any benefits would persist to the follow‑up session.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
de Wit, H., Molla, H. M., Bershad, A., Bremmer, M., & Lee, R. (2022). Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study. Addiction Biology, 27(2). https://doi.org/10.1111/adb.13143
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