The psychedelic DMT reduces depression symptoms after just one dose

A single dose of dimethyltryptamine (DMT), a psychedelic drug, had a rapid and sustained effect on depressive symptoms in a small trial.

DMT – a fast-acting and extremely potent psychedelic found in many plants around the world – is subject to the strictest international controls, with the United Nations considering it a substance with a high potential for abuse and no recognized medical use.

But a wave of observational research suggests that DMT and other psychedelics could help people with serious mental health problems, particularly those who don’t respond to conventional treatments.

In the latest study, David Erritzoe of Imperial College London and colleagues studied 34 people who had suffered from moderate to severe depression for an average of 10 years and who had unsuccessfully tried at least two treatments based on conventional medicine or psychotherapy.

Along with psychotherapeutic support, half of the participants received a large dose of 21.5 micrograms of DMT intravenously over 10 minutes, while the rest received a placebo infusion.

All participants completed a depression assessment questionnaire at the start of the study. Two weeks after the infusions, the DMT group saw their depression scores decrease by 7.4 points more, on average, than the placebo group. This was consistently maintained for three months, and up to six months for some participants.

In another part of the study, all participants were free to receive a dose of DMT, either as a second dose or, for the placebo group, as a first, with the support of a therapist. This did not significantly improve results beyond the first dose, suggesting that a single treatment is enough to achieve a lasting effect.

In terms of safety, side effects were mild, with some participants reporting anxiety, nausea, and temporary pain at the infusion site.

“We have shown that a single DMT experience, lasting only about 25 minutes, can be safe, well tolerated, and associated with significant improvements in depression that appear to persist beyond the acute psychedelic state,” says Erritzoe. “What is promising is how comparable these early signals appear to results seen in trials of longer-acting psychedelics, such as psilocybin.” A shorter psychedelic experience should reduce treatment costs, he says.

But the nature of consuming a psychedelic means that people can usually judge whether or not they are in the placebo group, so the results may reflect both the effects of DMT and participants’ expectations.

The researchers noted that the intensity of mystical-like experiences reported by the DMT group about 25 minutes after receiving the drug was related to their degree of therapeutic improvement. “The more a person felt a sense of unity, a profoundly positive emotional change, a change in the way they perceived time and space, and something so profound that it was difficult to express in words, the more they were likely to report it afterwards,” says team member Tommaso Barba, also at Imperial.

While it’s unclear how psychedelics like DMT may be beneficial for treating depression, research suggests that taking them provides a temporary window of neuroplasticity, where the brain can form new connections, or that they may alleviate inflammation associated with poor mental health.

Rick Strassman – a pioneer in psychedelic research – says these findings build on previous studies in which participants knew what drug they were taking. He nevertheless insists on the importance of moving forward with caution. “Although the DMT experience is briefer than that of psilocybin and LSD, it can be much more disorienting than that of longer-acting psychedelics and requires careful preparation, monitoring, and follow-up.”

Erritzoe and his team say the findings should help guide testing of a modified form of DMT called HLP004 for anxiety by Helus Pharma. Meanwhile, a similar molecule, called 5-MeO-DMT, is in more advanced stages of testing for depression. For example, promising results from New York-based AtaiBeckley mean development of its treatment-resistant depression candidate can be accelerated, making approval in the United States likely.