Falchi-Carvalho Marcelo, Palhano-Fontes Fernanda, Wießner Isabel, Barros Handersson, Bolcont Raynara, Laborde Sophie, Ruschi B Silva Sérgio, Montanini Daniel, C Barbosa David, Teixeira Ewerton, Florence-Vilela Rodrigo, Almeida Raissa, K A de Macedo Rosana, Arichelle Flávia, J Pantrigo Érica, V Costa-Macedo José, da Cruz Nunes João Arthur, de Araújo Costa Neto Luiz Antonio, Nunes Ferreira Luis Fernando, Dantas Corrêa Luísa, da Costa Bezerra Romária Bárbara, Arcoverde Emerson, Galvão-Coelho Nicole, B Araujo Draulio
Center for Advanced Medical Psychedelics (CAMP), Natal, Rio Grande do Norte, Brazil.
Brain Institute, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Neuropsychopharmacology. 2025 May;50(6):895-903. doi: 10.1038/s41386-025-02091-6. Epub 2025 Apr 22.
Depression affects over 185 million people worldwide, with approximately one-third classified as treatment-resistant depression (TRD). Current treatments, such as oral antidepressants, often take around 3 weeks to become effective, with no immediate anti-suicidal benefits. The field urgently needs innovative therapies that provide rapid relief. Psychedelics like psilocybin and ayahuasca have shown promising antidepressant effects; however, their long duration (several hours) makes them costly and impractical for public health systems. N,N-Dimethyltryptamine (DMT), an endogenous psychedelic also found in ayahuasca, offers a viable alternative with a short duration of action (10-20 min) and non-invasive inhalation administration. Unlike ayahuasca, which contains monoamine oxidase inhibitors, vaporized DMT acts quickly and poses fewer pharmacological interaction risks. This open-label trial evaluated inhaled DMT for TRD for the first time, within the framework of interventional psychiatry. Fourteen patients (N = 6) participated in a fixed-order, dose-escalation study (15 mg and 60 mg). The treatment was safe, well-tolerated, and produced manageable psychedelic effects with no serious adverse events. A subpopulation using antidepressants showed similar safety outcomes. Results showed rapid and sustained antidepressant effects, with an average reduction of 21.14 points on the Montgomery-Asberg Depression Rating Scale by day 7 (p < 0.001). The response rate was 85.71%, and the remission rate was 57.14% 7 days post-administration, lasting up to 3 months. Suicidal ideation significantly decreased, with no severe ideation the day after dosing. Vaporized DMT offers a non-invasive, time-efficient, and cost-effective alternative to other psychedelics and traditional antidepressants, supporting its role in interventional psychiatry and public health. Clinicaltrials.gov NCT06094907.
抑郁症影响着全球超过1.85亿人，其中约三分之一被归类为难治性抑郁症（TRD）。目前的治疗方法，如口服抗抑郁药，通常需要大约3周才能起效，且没有立即的抗自杀益处。该领域迫切需要能提供快速缓解的创新疗法。像裸盖菇素和死藤水这样的迷幻药已显示出有前景的抗抑郁效果；然而，它们作用时间长（数小时），这使其成本高昂且对公共卫生系统而言不切实际。N,N-二甲基色胺（DMT），一种也存在于死藤水中的内源性迷幻药，提供了一种可行的替代方案，其作用时间短（10 - 20分钟）且可通过非侵入性吸入给药。与含有单胺氧化酶抑制剂的死藤水不同，汽化的DMT起效迅速且产生的药理相互作用风险更小。这项开放标签试验首次在介入精神病学框架内评估了吸入式DMT治疗TRD的效果。14名患者（N = 6）参与了一项固定顺序、剂量递增研究（15毫克和60毫克）。该治疗安全、耐受性良好，并产生了可控制的迷幻效果，没有严重不良事件。使用抗抑郁药的亚组显示出类似的安全结果。结果显示出快速且持续的抗抑郁效果，到第7天，蒙哥马利-阿斯伯格抑郁评定量表平均降低21.14分（p < 0.001）。给药7天后的缓解率为85.71%，缓解率为57.14%，持续长达3个月。自杀意念显著降低，给药后第二天没有严重的自杀意念。汽化的DMT为其他迷幻药和传统抗抑郁药提供了一种非侵入性、高效且经济有效的替代方案，支持了其在介入精神病学和公共卫生中的作用。Clinicaltrials.gov NCT06094907。
