Over the last few years, evidence has piled up that psychedelic drugs can provide relatively rapid relief from the symptoms of clinical depression. The drugs seemingly work by boosting the brain’s ability to remodel connections among neurons and incorporate new experiences. While we have a good picture of which proteins are responsible for the drug’s hallucinogenic effects, we’re still figuring out how those pathways plug into the brain’s ability to change itself.
Those lingering uncertainties aren’t standing in the way of people trying to develop potentially life-altering treatments. One of the big challenges is probably the hallucinations themselves, which can potentially incapacitate someone for hours after a treatment. But researchers have now described a study showing that the shortest-acting psychedelic, DMT, appears to be just as effective as the rest.
Fast-acting
DMT, or dimethyltryptamine, is probably best known as a key component of ayahuasca, a liquid made from a combination of two or more plants. The mixture is important because the body produces an enzyme that rapidly digests DMT, blocking its effects. The additional plants contain a chemical that inhibits this enzyme, providing a longer-lasting experience.
In the absence of this inhibitor, however, the body clears DMT pretty quickly (it has a half-life of only about five minutes). Which means it’s potentially a great treatment, given that patients could be released from care shortly after receiving the drug. But it’s also possible that this brief stimulation wouldn’t be as effective at generating the sort of long-term changes in the brain triggered by other psychedelics. While there’s some evidence for an antidepressant effect, it has been limited so far.
A large collaboration set up a small clinical trial based at some London hospitals to gather more evidence of the effects. The study involved a blinded trial of a single DMT dose with a placebo control group (there were 47 people each in the experimental and control arms), coupled with counseling for depression. Two weeks later, everybody involved in the study got an open-label dose. Whether you can actually have a blinded trial of a psychedelic depends strongly on the degree to which you can have placebo-driven hallucinations, which seems pretty debatable. Depression symptoms were tracked weekly for 14 weeks after the initial dose.
One week after the initial dose, only 6 percent of the control group (meaning two individuals) reported improvements in their depression symptoms. In contrast, nearly half (44 percent) of those who received DMT reported feeling better. While the effect began to fade by the 14-week time point, this population was still far better off than when things started.
The control group participants, who only got one dose and got it two weeks into the study, showed an interesting trajectory. Their symptoms improved slightly over the first two weeks through some combination of a placebo effect and the counseling that everyone received. But then they got substantially better after the DMT dose, ending up somewhat better by the end of the study.
There were no serious side effects following treatment, and the less-than-serious ones tended to be short-lived, like a bit of pain at the injection site. There was also a very brief spike in heart rate and blood pressure.
Promising start
One of the big questions about psychedelics has been whether their hallucinogenic effects and their antidepressant effects are separable. There are definitely indications that the two act through different mechanisms. But this study suggests that may not be the case with DMT. “Antidepressant effects two weeks after participants’ first active DMT dose were observed to be moderated by their ‘Mystical Experience’ Questionnaire (MEQ) scores, as well as Ego Dissolution Inventory,” the authors note.
None of this is to say that DMT will be the right solution for everyone—we’ll have to wait for a larger trial and longer follow-up to get a sense of its effectiveness. And it’s important to note that this study administered it as part of a general care plan. Still, it’s promising as a drug, since even its apparently brief period of mind alteration seems to have a significant impact on clinical depression, while also greatly simplifying care for those receiving the drug.
Given that many people don’t respond to traditional antidepressants, anything that provides an additional option would be welcome.
Nature Medicine, 2026. DOI: 10.1038/s41591-025-04154-z (About DOIs).
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