While anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT_2A) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test sessions spaced 2 weeks apart. Subjects maintained headache diaries starting 2 weeks before the first session until 2 weeks after the second session. Physiological and psychological drug effects were monitored during sessions and several follow-up contacts with subjects were carried out to assure safety of study procedures. Ten subjects were included in the final analysis. Over the 2-week period measured after single administration, the reduction in weekly migraine days from baseline was significantly greater after psilocybin (mean, − 1.65 (95% CI: − 2.53 to − 0.77) days/week) than after placebo (− 0.15 (− 1.13 to 0.83) days/week; p = 0.003, t(9) = 4.11). Changes in migraine frequency in the 2 weeks after psilocybin were not correlated with the intensity of acute psychotropic effects during drug administration. Psilocybin was well-tolerated; there were no unexpected or serious adverse events or withdrawals due to adverse events. This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin. The separation of acute psychotropic effects and lasting therapeutic effects is an important finding, urging further investigation into the mechanism underlying the clinical effects of select 5-HT_2A receptor compounds in migraine, as well as other neuropsychiatric conditions. Clinicaltrials.gov: NCT03341689

虽然轶事证据表明，选择 5-羟色胺 2A (5-HT _2A ) 受体配体（包括裸盖菇素）在有限剂量治疗头痛后可能具有持久的治疗效果，但缺乏对照研究。在一项探索性双盲、安慰剂对照、交叉研究中，患有偏头痛的成年人在 2 次间隔 2 周的测试中接受口服安慰剂和裸盖菇素 (0.143 mg/kg)。受试者从第一次治疗前两周开始一直记录头痛日记，直到第二次治疗后两周。在会议期间监测生理和心理药物效应，并与受试者进行多次后续接触，以确保研究程序的安全。最终分析中纳入了十名受试者。在单次给药后的两周内，裸盖菇素治疗后每周偏头痛天数较基线的减少量显着大于安慰剂治疗后（平均 - 1.65（95% CI：- 2.53 至 - 0.77）天/周）（- 0.15 (− 1.13 至 0.83) 天/周； p = 0.003， t (9) = 4.11)。裸盖菇素给药后两周内偏头痛频率的变化与给药期间急性精神药物作用的强度不相关。裸盖菇素的耐受性良好；没有发生意外或严重的不良事件或因不良事件而退出。这项探索性研究表明，单次服用裸盖菇素后，对偏头痛有持久的治疗效果。 急性精神作用和持久治疗作用的分离是一项重要发现，促使进一步研究选择的 5-HT _2A受体化合物在偏头痛以及其他神经精神疾病中的临床作用的机制。临床试验。政府：NCT03341689