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.