A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers
In a randomised placebo‑controlled trial in healthy volunteers, repeated 15 µg LSD microdoses produced no overall analgesic effects on cold‑pressor pain tolerance or subjective pain ratings, despite increasing blood pressure and subjective drug effects. Post‑hoc analyses in participants without baseline ceiling effects suggested a transient increase in pain tolerance and reduced unpleasantness after the first dose, implying the dose may be below the threshold for consistent analgesia and that larger studies with higher doses are needed.
Authors
- Matthias Liechti
- Kim Kuypers
- Johannes Ramaekers
Published
Abstract
Background
Preliminary research indicates that psychedelics may hold promise as analgesic agents. This study investigated the potential analgesic effects of lysergic acid diethylamide (LSD) microdosing on pain tolerance and subjective pain perception in healthy participants.
Methods
Utilizing a randomised, placebo-controlled design, participants received 15 μg of LSD or placebo over four administrations. Pain tolerance was assessed using the Cold Pressor Task (CPT), along with subjective ratings of painfulness, unpleasantness, and stress.
Results
No analgesic effects of LSD were found on any of these measures in the whole sample. LSD increased blood pressure and subjective ratings of drug experience on administration days. Blood pressure was positively correlated to pain tolerance in the LSD group, whereas subjective drug experience was not. To explore whether the absence of analgesic effects of LSD could be explained by ceiling effects observed in CPT performance, post-hoc analyses were conducted in a smaller subsample of individuals that did not show ceiling effects at baseline. This post-hoc analysis suggested that LSD increased pain tolerance and reduced unpleasantness, but only after the first dose.
Conclusions
Overall, the present study provided no evidence for analgesic effects of 15 µg LSD. Post-hoc analyses only revealed a marginal analgesic effect of LSD in a subsample of participants. The dose used in this study may be below the threshold dose that is needed to produce a solid and consistent analgesic effect. Future research with larger, appropriately selected samples and higher doses is recommended to further elucidate LSD’s analgesic effects and its application in clinical settings.
Research Summary of 'A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers'
Introduction
Classic psychedelics act primarily at serotonergic receptors and have attracted renewed interest for potential therapeutic uses beyond psychiatry, including analgesia. Earlier observational and small experimental studies report pain relief after psychedelic use in conditions such as cluster headache, phantom limb pain and migraine, and one controlled healthy-volunteer study found increased tolerance to experimentally induced pain after a low (20 μg) dose of LSD. Microdosing—regular ingestion of sub-perceptual or mildly perceptual doses, often about one tenth of a full dose—has become popular and is reported anecdotally to reduce pain, but no controlled study had evaluated a repeated microdosing schedule for analgesia prior to this work. Cavarra and colleagues set out to test whether a microdosing regimen of 15 μg LSD, given twice weekly for 2 weeks (four administrations total), would increase pain tolerance and reduce subjective painfulness, unpleasantness and stress in healthy volunteers exposed to an experimental pain task. The study also examined physiological (blood pressure, heart rate) and subjective drug-effect measures, and whether these related to any analgesic effects; 15 μg was selected to minimise alterations in consciousness while aiming to retain potential analgesic action, given prior findings at 20 μg but not 10 μg.
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Study Details
- Study Typeindividual
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- APA Citation
Cavarra, M., Hutten, N. R. P. W., Schepers, J., Mason, N. L., Theunissen, E. L., Liechti, M. E., Kuypers, K. P. C., Bonnelle, V., Feilding, A., & Ramaekers, J. G. (2025). A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers. British Journal of Pain, 19(6), 434-445. https://doi.org/10.1177/20494637251371626
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