People with major depressive disorder can see a rapid and lasting improvement after a single dose of the psychedelic drug dimethyltryptamine (DMT) when it is combined with psychotherapy, doctors have said.
A small clinical trial involving 34 people found that psychedelic-assisted therapy prompted a swift reduction in depressive symptoms that endured long after the drug had worn off, with some still feeling the benefits six months later.
“There is an immediate antidepressant effect that is significantly sustained over a three-month period and that’s exciting because this is one session with a drug, embedded in psychological support,” said Dr David Erritzoe, a psychiatrist at Imperial College London and lead investigator on the trial.
Although preliminary, the results add to a growing body of evidence that psychedelic drugs, when coupled with psychotherapy, could help to alleviate depression in the millions of people worldwide who do not respond to existing antidepressants or therapies.
An estimated 100 million people worldwide have treatment-resistant depression, defined as a major depressive disorder that has not responded to at least two antidepressants. About half are unable to perform routine daily tasks.
The trial, reported in Nature Medicine, focused on people with moderate to severe treatment-resistant depression. One half received a single 21.5mg dose of DMT infused into a vein over 10 minutes. The other half received a placebo infused the same way. All of the participants had psychotherapy and follow-up assessments.
Patients given DMT improved significantly compared with the placebo group, as measured by scores on a standard depression questionnaire, with the antidepressant effects lasting from three to six months.
DMT is an active ingredient of the ayahuasca brew used in shamanistic rituals in South America. The drug induces powerful and often mystical hallucinogenic trips that can alter people’s sense of time and space, dissolve their sense of self, and conjure up meetings with otherworldly beings.
In the second stage of the trial, all participants received a dose of DMT with therapy, but the researchers found no additional benefit in those who had two doses in total, suggesting a single dose may suffice. The trial was designed, funded and sponsored by Cybin UK, a neuropsychiatric firm.
The study follows a positive trial with psilocybin, the active ingredient in magic mushrooms, which has raised hopes for the drug being approved for treatment of depression later this year.
Psychedelics are thought to enhance the effects of psychotherapy by helping people break entrenched and unhelpful patterns of thinking. Erritzoe likens the effect to shaking up the snow on a mountain and flattening the hills and valleys so people can easily find new routes. “You redistribute the snow so it’s easier to take new tracks, and at the same time it becomes easier to take new routes because the landscape has been flattened,” he said.
At doses used in the trials, DMT induces a shorter but more intense trip than psilocybin, with the experience lasting about 25 minutes compared with a couple of hours for psilocybin. That could make DMT-assisted therapy easier for clinics to deliver, although patients may need more support to recover from particularly intense DMT trips.
If regulators were to approve psychedelics for treating depression in the UK, researchers expect them to become available only through private clinics, said Dr James Rucker, a consultant psychiatrist at King’s College London who worked on the psilocybin trial.
Last year the Feilding commission was set up to guide the safe, ethical and equitable rollout of psychedelic-assisted therapies amid concerns that commercial pressures at private clinics could undermine safety, leading to patient harm.
Rucker said: “Quite how these drugs will fit in this world of financial austerity, stigma and opprobrium towards anything that has the word psychoactive in it, I don’t know. It’s interesting to be a part of, but I can’t call it.”

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