A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers

This randomised, placebo-controlled study (n=48) examining LSD microdosing (15 μg) for analgesia in healthy participants found no significant pain-relieving effects on pain tolerance or subjective pain perception using the Cold Pressor Task. LSD increased blood pressure, which correlated with pain tolerance, and post-hoc analysis in participants without ceiling effects suggested marginal improvements in pain tolerance and reduced unpleasantness only after the first dose, indicating that 15 μg may be below the threshold for consistent analgesic effects.

Abstract of A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers

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.

Authors: Mauro Cavarra, Nadia R. P. W. Hutten, Jan Schepers, Natasha L. Mason, Eef L. Theunissen, Matthias E. Liechti, Kim P. C. Kuypers, Valerie Bonnelle, Amanda Feilding & Johannes G. Ramaekers

Summary of A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers

Classic psychedelics are a group of substances known for altering perception and consciousness, largely through their effects on serotonin receptors in the brain. Over recent years, they have gained scientific attention for their potential therapeutic applications, particularly in treating psychiatric conditions such as treatment-resistant depression, addiction, and anxiety in people facing terminal illness.

Another emerging area of interest is the use of psychedelics in managing pain. Historical reports from the 1960s suggested that lysergic acid diethylamide (LSD) could provide pain relief in contexts such as phantom limb pain and end-of-life care. More recent work has supported these claims, with studies indicating that low doses of LSD may increase tolerance to experimental pain while causing only mild alterations in consciousness.

The practice of microdosing (taking very small, non-hallucinogenic amounts of psychedelics) has become increasingly popular. Anecdotal reports and survey studies suggest potential benefits for physical and psychological well-being, including pain relief. Microdosing typically involves taking around one-tenth of a standard psychedelic dose; for LSD, this is approximately 15 micrograms (µg). While some studies have explored single, low doses of LSD and their effect on pain, no controlled trials had yet examined repeated microdosing regimens.

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A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers

https://doi.org/10.1177/20494637251371626

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Cite this paper (APA)

Cavarra, M., Hutten, N. R., Schepers, J., Mason, N. L., Theunissen, E. L., Liechti, M. E., ... & 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, 20494637251371626.

Study details

Compounds studied
LSD Placebo

Topics studied
Microdosing Pain Healthy Subjects

Study characteristics
Original Placebo-Controlled Double-Blind Randomized

Participants
48 Humans

Compound Details

The psychedelics given at which dose and how many times

LSD 15 μg | 4x

Linked Clinical Trial

LSD microdosing - A repeated dosing study
This double-blind, randomized trial (n=60) conducted by Maastricht University Department of Psychology and Neurosciences, explores the effects of repeated doses of LSD (15µg) on mood, cognition, and neuroplasticity in healthy volunteers.

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