A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers.
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
British Journal of Pain September 4, 2025 DOI: 10.1177/20494637251371626 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, placebo-controlled trial Peer reviewed |
|---|---|
| Population | Healthy participants |
| Interventions | LSD placebo |
| Dose | 15 µg |
| Duration | Four administrations |
| Measures | Cold Pressor Task (CPT) |
| Topics | LSD Microdosing |
| Keywords | Pain Psychedelics |
| Key findings | No analgesic effects of 15 µg LSD were found on pain tolerance or subjective pain measures in the whole sample, though LSD increased blood pressure and drug-experience ratings. A post-hoc analysis in a subsample without baseline ceiling effects suggested increased pain tolerance and reduced unpleasantness after only the first dose. The authors propose the dose may be below the threshold for a solid analgesic effect. |
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.
Comparable studies
Other randomized controlled trials on LSD and microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity. Healthy young adults, 18 to 35 years old | 2019 | Randomized controlled trial | n = 20 |
| Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial. Healthy male volunteers | 2023 | Randomized controlled trial | n = 80 |
| Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity. Healthy adults | 2023 | Within-subject, double-blind, placebo-controlled experiment | n = 18 |
| Greater subjective effects of a low dose of LSD in participants with depressed mood. Adults with mild depressed mood (scoring high or low on the Beck Depression-II inventory) | 2024 | Randomized controlled trial | n = 39 |
| Inter-individual variability in neural response to low doses of LSD. Healthy participants | 2024 | Randomized controlled trial | n = 53 |