Cavarra Mauro, Hutten Nadia R P W, Schepers Jan, Mason Natasha L, Theunissen Eef L, Liechti Matthias E, Kuypers Kim P C, Bonnelle Valerie, Feilding Amanda, Ramaekers Johannes G
Department of Neuropsychology & Psychopharmacology, Faculty of Psychology & Neuroscience, Maastricht University, Maastricht, The Netherlands.
Department of Methodology and Statistics, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Br J Pain. 2025 Sep 4:20494637251371626. doi: 10.1177/20494637251371626.
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.
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.
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.
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.
初步研究表明，迷幻剂可能有望成为镇痛剂。本研究调查了麦角酸二乙酰胺（LSD）微剂量给药对健康参与者疼痛耐受性和主观疼痛感知的潜在镇痛作用。
采用随机、安慰剂对照设计，参与者在四次给药过程中接受15微克LSD或安慰剂。使用冷加压试验（CPT）评估疼痛耐受性，同时对疼痛程度、不适感和压力进行主观评分。
在整个样本中，未发现LSD对这些指标有任何镇痛作用。在给药日，LSD会升高血压并增加药物体验的主观评分。在LSD组中，血压与疼痛耐受性呈正相关，而主观药物体验与疼痛耐受性无关。为了探讨LSD无镇痛作用是否可以用CPT表现中观察到的天花板效应来解释进行了事后分析，在一个较小的子样本中进行，这些个体在基线时未表现出天花板效应。事后分析表明，LSD增加了疼痛耐受性并降低了不适感，但仅在首次给药后。
总体而言，本研究没有提供15微克LSD具有镇痛作用的证据。事后分析仅在部分参与者子样本中发现LSD有微弱的镇痛作用。本研究中使用的剂量可能低于产生稳定和一致镇痛作用所需阈值剂量。建议未来进行更大规模、适当选择样本和更高剂量的研究，以进一步阐明LSD的镇痛作用及其在临床环境中的应用。
