Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, The Netherlands.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
J Neurochem. 2022 Jul;162(1):128-146. doi: 10.1111/jnc.15587. Epub 2022 Mar 8.
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring tryptamine that primarily acts as an agonist at the 5-HT1A and 5-HT2A receptors, whereby affinity for the 5-HT1A subtype is highest. Subjective effects following 5-MeO-DMT administration include distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution that usually are short-lasting, depending on the route of administration. Individual dose escalation of 5-MeO-DMT reliably induces a "peak" experience, a state thought to be a core predictor of the therapeutic efficacy of psychedelics. Observational studies and surveys have suggested that single exposure to 5-MeO-DMT can cause rapid and sustained reductions in symptoms of depression, anxiety, and stress. 5-MeO-DMT also stimulates neuroendocrine function, immunoregulation, and anti-inflammatory processes, which may contribute to changes in mental health outcomes. To date, only one clinical trial has been published on 5-MeO-DMT, demonstrating the safety of vaporized dosing up to 18 mg. Importantly, the rapid onset and short duration of the 5-MeO-DMT experience may render it more suitable for individual dose-finding strategies compared with longer-acting psychedelics. A range of biotech companies has shown an interest in the development of 5-MeO-DMT formulations for a range of medical indications, most notably depression. Commercial development will therefore be the most important resource for bringing 5-MeO-DMT to the clinic. However, fundamental research will also be needed to increase understanding of the neurophysiological and neural mechanisms that contribute to the potential clinical effects of 5-MeO-DMT and its sustainability and dissemination over time. Such studies are less likely to be conducted as part of drug development programs and are more likely to rely on independent, academic initiatives.
5-甲氧基-N,N-二甲基色胺（5-MeO-DMT）是一种天然存在的色胺，主要作为 5-HT1A 和 5-HT2A 受体的激动剂，其中对 5-HT1A 亚型的亲和力最高。5-MeO-DMT 给药后的主观效应包括听觉和时间感知扭曲、情绪状态放大以及自我解体感，这些感觉通常持续时间很短，具体取决于给药途径。5-MeO-DMT 的个体剂量递增可靠地诱导“峰值”体验，这种状态被认为是致幻剂治疗效果的核心预测因素。观察性研究和调查表明，单次暴露于 5-MeO-DMT 可迅速且持续减轻抑郁、焦虑和压力的症状。5-MeO-DMT 还刺激神经内分泌功能、免疫调节和抗炎过程，这可能有助于改变心理健康结果。迄今为止，仅有一项关于 5-MeO-DMT 的临床试验发表，证明了高达 18 毫克的蒸气给药的安全性。重要的是，5-MeO-DMT 体验的快速发作和短暂持续时间可能使其更适合于个体剂量发现策略，而不是作用时间更长的致幻剂。一系列生物技术公司对开发用于各种医学适应症（尤其是抑郁症）的 5-MeO-DMT 制剂表现出兴趣。因此，商业开发将成为将 5-MeO-DMT 引入临床的最重要资源。然而，也需要基础研究来增加对促成 5-MeO-DMT 潜在临床效果的神经生理和神经机制的理解，以及它的可持续性和随时间的传播。此类研究不太可能作为药物开发计划的一部分进行，更可能依赖于独立的学术举措。
