Department of Psychiatry, Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Psychopharmacol. 2024 Oct;38(10):911-923. doi: 10.1177/02698811241273772. Epub 2024 Sep 20.
Harmine is a component of the hallucinogenic brew, Ayahuasca, which also contains the psychoactive compound, , -dimethyltryptamine. Whether pharmaceutical-grade harmine hydrochloride (HCl) has psychoactive effects, the doses at which these might occur, and the dose-response relationship to side effects and safety in humans are unknown.
We conducted a Phase 1, open-label single ascending dose trial in healthy adults with normal body mass index and no prior psychiatric illness. The primary goal was to determine the maximum tolerated dose (MTD) of oral pharmaceutical-grade harmine HCl and to characterize safety and tolerability. A secondary goal was to ascertain whether any oral dose has psychoactive effects.
Thirty-four adult participants, aged 18-55 years, were screened for study eligibility. Twenty-five participants met eligibility criteria and were randomized to a single dose of 100, 200, 300, or 500 mg of harmine HCl, respectively, using a continuous reassessment method. The most common adverse events (AEs) observed were gastrointestinal and/or neurological, dose-related, and of mild to moderate severity. The MTD was determined to be between 100 and 200 mg and is weight-based, with 90% of those participants receiving >2.7 mg/kg experiencing a dose-limiting toxicity. No serious AEs of harmine HCl were identified.
Harmine HCl can be orally administered to healthy participants in doses <2.7 mg/kg with minimal or no AEs. Doses >2.7 mg/kg are associated with vomiting, drowsiness, and limited psychoactivity. This study is the first to systematically characterize the psychoactive effects of pharmaceutical quality harmine in healthy participants.
哈梅林是迷幻饮品 Ayahuasca 的成分之一，其中还含有精神活性化合物，β-二甲色胺。药用级盐酸哈梅林（HCl）是否具有精神活性作用、可能发生这些作用的剂量，以及在人类中出现副作用和安全性的剂量反应关系尚不清楚。
我们在身体质量指数正常且无既往精神疾病的健康成年人中进行了一项 1 期、开放标签、单递增剂量试验。主要目标是确定口服药用级盐酸哈梅林的最大耐受剂量（MTD），并描述安全性和耐受性。次要目标是确定任何口服剂量是否具有精神活性作用。
34 名年龄在 18-55 岁之间的成年参与者被筛选以确定是否符合研究入选标准。25 名参与者符合入选标准，并使用连续评估方法分别随机分配到 100、200、300 或 500mg 口服盐酸哈梅林的单剂量组。最常见的不良事件（AE）为胃肠道和/或神经系统，与剂量相关，且为轻度至中度。MTD 确定为 100-200mg，基于体重，90%接受>2.7mg/kg 剂量的参与者出现剂量限制毒性。未发现盐酸哈梅林的严重 AE。
在没有或很少有 AE 的情况下，健康参与者可口服给予<2.7mg/kg 的盐酸哈梅林。>2.7mg/kg 的剂量与呕吐、嗜睡和有限的精神活性有关。本研究首次系统地描述了健康参与者中药用级哈梅林的精神活性作用。
