Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression
Almeida, R., Araújo, D. B., Arcoverde, E., Arichelle, F., Barbosa, D. C., Barros, H., Bolcont, R., Costa-Macedo, J. V., da Costa Bezerra, R. B., da Cruz Nunes, J. A., Dantas Correa, L., de Araujo Costa Neto, L. A., Falchi-Carvalho, M., Florence-Vilela, R., Galvão-Coelho, N. L., Laborde, S., Macedo, R. K. A., Montanini, D., Nunes Ferreira, L. F., Palhano-Fontes, F., Pantrigo, E. J., Silva, S. R. B., Teixeira, E., Wießner, I.
This open-label fixed-order dose-escalation trial (n=14) evaluated inhaled DMT (15mg & 60mg) for treatment-resistant depression (TRD) for the first time. Results showed rapid and sustained antidepressant effects with a 21-point reduction on the Montgomery-Asberg Depression Rating Scale by day 7 (p<0.001), an 86% response rate, and a 57% remission rate lasting up to 3 months, with significant decreases in suicidal ideation (SI).
Abstract
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 (Nfemale = 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.