The psychedelic DMT reduces depression symptoms after just one dose

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

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

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

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

Alongside psychotherapeutic support, half of the participants were given a large, 21.5-microgram dose of DMT intravenously over 10 minutes, while the rest received a placebo infusion.

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

In another part of the study, all of the participants were free to have a dose of DMT, either as a second dose or, for the placebo group, the first, alongside therapist support. This didn’t significantly improve outcomes beyond the first dose, suggesting that one treatment is sufficient for a lasting effect.

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

“We’ve shown that a single DMT experience, lasting only around 25 minutes, can be safe, well-tolerated and associated with meaningful improvements in depression that appear to persist beyond the acute psychedelic state,” says Erritzoe. “What’s promising is how comparable these early signals look 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 taking a psychedelic means people can typically gauge whether or not they are in the placebo group, so the results may reflect both DMT’s effects and the participants’ expectations.

The researchers noted that the intensity of mystical-type experiences that the DMT group reported about 25 minutes after receiving the drug was linked to their degree of therapeutic improvement. “The more someone felt a sense of unity; a deeply positive emotional shift; a change in how they experienced time and space; and something so profound it was hard to put into words, the more benefit they tended to report afterwards,” says team member Tommaso Barba, also at Imperial.

Although it is unclear exactly 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 dampen inflammation associated with poor mental health.

Rick Strassman – a pioneer in psychedelics research – says these results build upon previous studies in which the participants were told which drug they were taking. Yet he still stresses the importance of progressing cautiously. “While the DMT experience is briefer than psilocybin and LSD, it can be significantly more disorienting than longer-acting psychedelics and requires careful preparation, monitoring and follow-up.”

Erritzoe and his team say the results should help guide the testing of a modified form of DMT called HLP004 for anxiety by Helus Pharma. In the meantime, a similar molecule, called 5-MeO-DMT, is at a more advanced testing stage for depression. For instance, promising results from the firm AtaiBeckley in New York mean that the development of its candidate for treatment-resistant depression can be expedited, making US approval likely.