5-甲氧基-N,N-二甲基色胺（5-MeO-DMT）的临床药理学和潜在治疗应用,Journal of Neurochemistry

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5-甲氧基-N,N-二甲基色胺（5-MeO-DMT）的临床药理学和潜在治疗应用
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2022-02-11 , DOI: 10.1111/jnc.15587
Johannes T Reckweg ₁ , Malin V Uthaug ₁ , Attila Szabo _{2,

3} , Alan K Davis _{4,

5} , Rafael Lancelotta ₄ , Natasha L Mason ₁ , Johannes G Ramaekers ₁

Affiliation

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，因此对 5-HT1A 亚型的亲和力最高。5-MeO-DMT 给药后的主观影响包括听觉和时间感知的扭曲、情绪状态的放大和自我解体的感觉，这些感觉通常是短暂的，具体取决于给药途径。5-MeO-DMT 的个体剂量增加可靠地诱导“峰值”体验，这种状态被认为是迷幻药治疗效果的核心预测指标。观察性研究和调查表明，单次接触 5-MeO-DMT 可导致抑郁、焦虑和压力症状的快速和持续减轻。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，仅发表了一项关于 5-MeO-DMT 的临床试验，证明了高达 18 mg 的汽化剂量的安全性。重要的是，与长效迷幻药相比，5-MeO-DMT 体验的快速起效和短持续时间可能使其更适合个人剂量寻找策略。一系列生物技术公司对开发用于一系列医学适应症（尤其是抑郁症）的 5-MeO-DMT 制剂表现出兴趣。因此，商业开发将是将 5-MeO-DMT 引入临床的最重要资源。然而，还需要进行基础研究，以增加对有助于 5-MeO-DMT 的潜在临床效应及其随时间推移的可持续性和传播的神经生理学和神经机制的理解。此类研究不太可能作为药物开发计划的一部分进行，更有可能依赖独立的学术活动。

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The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)

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.

更新日期：2022-02-11

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