Ramaekers Johannes G, Reckweg Johannes T, Mason Natasha L
Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Am J Psychiatry. 2025 Jan 1;182(1):33-46. doi: 10.1176/appi.ajp.20230890.
Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an intense but brief psychedelic intervention. The current paper reviews the clinical pharmacology of 5-MeO-DMT and DMT and their potential benefits and challenges in the treatment of depression. Both compounds display affinities for a variety of monoamine receptors and transporters, but mostly so for serotonergic (5HT) receptors, including 5HT and 5HT. Early clinical trials in small samples have shown that short interventions (15-30 min) with 5-MeO-DMT and DMT are safe and well tolerated and can induce marked improvement in symptoms of depression within 24 hours that sustain for at least 1 week. Data on long-term efficacy are currently scarce but do suggest a prolongation of the treatment response. Potential benefits of these treatments include flexible, single day dosing regimens, achievement of treatment efficacy independent from integrative therapy, and ease of clinical implementation. Future challenges include establishing the duration of the antidepressant effect and strategies on how to sustain the antidepressant response, optimization of treatment delivery parameters, and a mechanistic understanding of the clinical response. Acceptance of ultra-fast, short-acting psychedelics will depend on future randomized, placebo-controlled trials with a focus on replication, duration and maintenance of antidepressant efficacy in large patient samples.
与传统抗抑郁药不同，诸如裸盖菇素之类的迷幻剂已被证明能引发快速的抗抑郁反应。随着这一进展，人们对超快速、短效的迷幻剂产生了兴趣，比如5-甲氧基-N,N-二甲基色胺（5-MeO-DMT）和N,N-二甲基色胺（DMT），期望它们在经过强烈但短暂的迷幻干预后能产生快速抗抑郁效果。本文综述了5-MeO-DMT和DMT的临床药理学及其在抑郁症治疗中的潜在益处与挑战。这两种化合物对多种单胺受体和转运体均有亲和力，但对血清素能（5HT）受体的亲和力尤其显著，包括5HT和5HT。小样本的早期临床试验表明，使用5-MeO-DMT和DMT进行的短期干预（15 - 30分钟）是安全且耐受性良好的，并且能在24小时内使抑郁症状显著改善，且这种改善至少持续1周。目前关于长期疗效的数据稀缺，但确实表明治疗反应有所延长。这些治疗方法的潜在益处包括灵活的单日给药方案、独立于综合治疗实现治疗效果以及易于临床实施。未来的挑战包括确定抗抑郁作用的持续时间以及如何维持抗抑郁反应的策略、优化治疗实施参数以及对临床反应的机制理解。对超快速、短效迷幻剂的接受程度将取决于未来聚焦于在大量患者样本中重复验证、确定抗抑郁疗效持续时间及维持情况的随机、安慰剂对照试验。
