Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder.
Deepak Cyril D'Souza, Shariful A. Syed, L Taylor Flynn, Hamideh Safi-Aghdam, Nicholas V. Cozzi, Mohini Ranganathan
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology September 1, 2022 DOI: 10.1038/s41386-022-01344-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label, fixed-order, dose-escalation exploratory phase 1 study Pilot study Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Treatment-resistant individuals with major depressive disorder (MDD) and healthy controls |
| Intervention | Intravenous DMT |
| Dose | 0.1 mg/kg followed by 0.3 mg/kg |
| Topics | Depression Psychedelic-assisted therapy 5-MeO-DMT DMT |
| Keywords | Rapid-onset psychedelic Potent compound Hallucinogens Psychotropic drugs Entheogens Depression treatment Antidepressant effects Mood improvements Mood disorders Clinical research Researchers explored Well-tolerated Positive results Drug development Medical research Safety studies Efficacy studies Clinical trials Mental health Therapeutic potential Well-being Psychological health Behavioral health |
| Citations | 156 |
| Key points | Intravenous DMT at 0.3 mg/kg was associated with a significant next-day reduction in depression scores in treatment-resistant MDD patients. |
Abstract
There is considerable interest in the therapeutic potential of psychedelic drugs. Dimethyltryptamine (DMT) is a potent, rapid-onset, and short-acting psychedelic drug that has not yet been independently tested for the treatment of depression. The safety, tolerability, and efficacy of intravenous DMT were investigated in treatment-resistant individuals with major depressive disorder (MDD) and healthy controls (HC) in an open-label, fixed-order, dose-escalation (0.1 mg/kg followed by 0.3 mg/kg) exploratory phase 1 study that was conducted in a typical hospital setting with strategic psychoeducation/support, but minimal psychotherapy. Tolerability, safety, cardiovascular function, abuse liability, psychedelic, and psychotomimetic effects, mood, and anxiety were assessed at each dosing session. In addition, depression was measured using the HAMD-17 in MDD participants 1 day after each dosing session. DMT was tolerated by both HC (n = 3) and MDD participants (n = 7) studied; there were no dropouts. HAMD-17 scores decreased significantly (p = 0.017) compared to baseline in MDD participants the day after receiving 0.3 mg/kg DMT (mean difference -4.5 points, 95% CI: -7.80 to -1.20, Hedge's g = 0.75). Adverse events were mostly mild with one self-limited serious event. DMT increased blood pressure, heart rate, anxiety, psychedelic effects, and psychotomimetic effects, which resolved within 20-30 min of injection. There were no dose-related differences in measures of drug reinforcement and abuse liability. In this small exploratory pilot study, intravenous DMT at doses of 0.1 and 0.3 mg/kg was mostly safe and tolerated and may have next-day (rapid) antidepressant effects in patients with treatment-resistant MDD. Further rigorous trials are warranted to replicate these findings and to determine the durability of antidepressant effects.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Intravenous DMT at 0.3 mg/kg was associated with a significant next-day reduction in HAMD-17 depression scores in treatment-resistant MDD patients.
Synthesized
Comparable studies
Other non-randomized and open-label trials on DMT for depression, most cited first.