Researchers in the UK conducted a small, randomized, placebo-controlled trial in people with major depression. Compared to controls, people on DMT experienced a faster decline in their depressive symptoms, which continued for at least 12 weeks afterward. Although larger studies are needed, the findings suggest that DMT may become the next psychedelic drug designated as a psychoactive drug.
“A single dose of DMT with psychotherapy support led to a rapid, significant reduction in depressive symptoms, which persisted for up to 3 months,” the researchers write in their paper published Monday in Nature Medicine.
psychedelic drug
Psychedelic drugs have recently attracted much scientific attention due to their ability to treat various mental health conditions, usually in combination with other forms of therapy. Drugs such as LSD, MDMA and psilocybin, the active ingredients in magic mushrooms, have shown promise in small trials for anxiety, depression and post-traumatic stress disorder. Other studies have shown that these drugs can rewire the brains of people with these conditions in positive ways.
DMT has received less attention than these drugs. Yet the researchers behind the study argue that it may have its own unique advantages, namely time. Typically, the drug’s most profound effects wear off much more quickly than other psychedelics, with a half-life of about five minutes. (That said, DMT is also one of the ingredients in the psychedelic brew ayahuasca, which has a much longer shelf life). This limited period may then allow shorter, more convenient and possibly less expensive sessions of therapy to be added – provided the drug works as expected.
The researchers’ new Phase IIa trial involved 34 volunteers who suffered from moderate to severe depression. Half of the volunteers were randomized to receive a single injection of DMT plus therapy at the beginning of the study, followed by a second dose two weeks later; The other half were given a placebo infusion, followed by the actual dose of DMT two weeks later. This design ensured that all participants could receive the potentially beneficial treatment, while also enabling the researchers to have a placebo control group for comparison – at least for the immediate, short-term effects of the drug.
On average, people who took DMT at the beginning of the study had significantly fewer symptoms of depression than those in the delayed treatment group. And once the second group took DMT, they also reported a reduction in their depression. Although two doses of DMT do not appear to be more effective than one dose, both groups had similar levels of improvement that persisted for at least three months, and for some participants even up to six months. By three months, 47% of participants (in both groups) had improved enough to be considered.
DMT also appeared to be safe and well tolerated. No serious adverse events were reported, and the most common drug-associated events were pain at the infusion site, nausea, and transient anxiety.
The future of DMT therapy
These results are still based on a very small sample size, so it is far from definitive proof that DMT should be widely used to treat depression. However, at the very least, the results justify more research.
“Longer and larger trials, including comparisons with existing treatments, are needed to further evaluate the efficacy, safety, and cost-effectiveness of DMT in the treatment of depression,” the study authors wrote.
Some research teams and companies are already moving forward with larger trials of DMT for depression and other mental health conditions, including versions of DMT that stay in the body relatively long. But psychedelics like DMT still have a long way to go before they become routine psychiatric treatments.
In 2024, the FDA rejected Lycos Therapeutics’ MDMA-assisted therapy for PTSD, saying more positive Phase III data were needed to secure approval (the company rebranded as Resilient Therapeutics last year, though the current status of its application is unclear). And although the Trump administration has at times encouraged psychedelic research, senior officials last week rejected the FDA’s plan to accelerate the regulatory review process of Compass Pathway’s psilocybin-based treatment for severe depression.
The era of psychedelic medicine may yet arrive, but not without some obstacles along the way.
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