Single Dose of DMT Produces Rapid, Lasting Depression Relief in Landmark Clinical Trial

The waiting room at Imperial College London’s Centre for Psychedelic Research looks nothing like its reputation might suggest. No blacklights, no incense — just the bland, institutional calm of any National Health Service outpatient suite. It was here, over the course of two years, that 34 men and women with treatment-resistant depression sat in reclining chairs, received a 10-minute intravenous infusion, and — in roughly half the cases — experienced something that conventional medicine had failed to deliver: meaningful relief .

The results, published Monday in Nature Medicine, describe the first randomised, placebo-controlled trial of dimethyltryptamine (DMT) for major depressive disorder. A single 21.5-milligram dose, administered intravenously alongside psychotherapeutic support, produced a statistically significant reduction in depression scores within one week. The effect persisted for at least three months, and in some participants for six .

A Drug With Ancient Roots and a Controlled-Substance Classification

DMT is the principal psychoactive compound in ayahuasca, a brew used for centuries in shamanic rituals across South America. It is also one of the most tightly regulated substances on earth: the United Nations classifies it under Schedule I, designating it as having high abuse potential and no recognised medical use . That classification has made clinical research extraordinarily difficult. The Imperial trial, led by psychiatrist Dr David Erritzoe and neuroscientist Tommaso Barba, is among the first to clear those regulatory hurdles and produce peer-reviewed data from a controlled setting .

The trial enrolled adults who had lived with moderate to severe depression for an average of 10 years and had tried at least two conventional treatments — antidepressants, psychotherapy, or both — without adequate improvement. An estimated 100 million people worldwide meet this definition of treatment-resistant depression. Roughly half are unable to perform routine daily tasks .

How the Trial Worked

Participants were divided into two groups of 17. In a double-blind first phase, one group received intravenous DMT while the other received an active placebo. A therapist sat with each participant throughout the infusion and the roughly 25-minute psychedelic experience that followed, remaining silent but present to ensure safety .

Two weeks later, all participants were offered an open-label DMT dose. The researchers found no significant additional benefit from a second dose, suggesting that a single treatment may be sufficient .

Depression severity was measured using the Montgomery–Åsberg Depression Rating Scale (MADRS), a standard clinical instrument. At the two-week mark, the DMT group’s scores had dropped by an average of 7.4 points more than the placebo group’s — a clinically meaningful difference. A remission rate of 57 percent was recorded at three months .

The Mystical-Experience Connection

One of the study’s more intriguing findings concerned the quality of the psychedelic experience itself. Participants who reported more intense mystical-type experiences — a sense of unity, profound emotional shifts, altered perceptions of time and space, and feelings that defied verbal description — tended to show greater 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,” said Barba .

This correlation is consistent with findings from psilocybin research, where the depth of subjective experience has similarly tracked with clinical outcomes. It raises a question that regulators and clinicians will eventually have to address: if the therapeutic mechanism depends partly on a profoundly altered state of consciousness, how do you standardise that?

Shorter Trips, Lower Costs — But Harder Landings

DMT’s chief practical advantage over other psychedelics is speed. A psilocybin session lasts four to six hours and requires multiple clinicians to be present throughout. DMT’s effects peak within minutes and resolve in roughly half an hour . That difference has significant implications for cost and scalability — two factors that have dogged psychedelic-assisted therapy as it moves from academic labs toward potential clinical deployment.

“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,” said Erritzoe. “What’s promising is how comparable these early signals look to results seen in trials of longer-acting psychedelics such as psilocybin” .

But brevity comes with intensity. Rick Strassman, a pioneer in DMT research and author of the influential 2001 book DMT: The Spirit Molecule, urged caution. “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,” he said .

The Placebo Problem

Skeptics and supporters alike acknowledge a methodological challenge that hangs over virtually all psychedelic research: blinding. Participants who receive a powerful hallucinogen typically know they are not in the placebo group. This means the reported improvements could reflect a combination of DMT’s pharmacological effects and the participants’ expectations .

The researchers attempted to mitigate this with an active placebo designed to produce some physiological sensations, but acknowledged the limitation. It is a problem the field has struggled with since the earliest psilocybin trials, and one that has not been definitively solved.

Competing Molecules and Commercial Stakes

The Imperial trial was designed, funded, and sponsored by Cybin UK (formerly Small Pharma), a neuropsychiatric firm now positioning DMT as a commercially viable treatment . The study is not happening in isolation. A related molecule, 5-MeO-DMT, is at a more advanced testing stage through the New York-based firm AtaiBeckley, whose candidate for treatment-resistant depression may be eligible for expedited US approval following promising results .

Meanwhile, the compound psilocybin — the active ingredient in magic mushrooms — has generated positive trial data that has raised hopes for regulatory approval for depression treatment later this year .

The commercial landscape is crowded, and the stakes are high. Treatment-resistant depression represents an enormous unmet medical need, and whoever brings the first approved psychedelic therapy to market stands to capture a significant share of a multi-billion-dollar opportunity.

Regulatory Uncertainty and Access Questions

Even if regulators approve psychedelic-assisted therapies, access remains an open question. In the UK, researchers expect such treatments to be available initially only through private clinics — placing them out of reach for many of the patients who need them most .

Last year, the Feilding Commission was established to guide the safe, ethical, and equitable rollout of psychedelic-assisted therapies, partly in response to concerns that commercial pressures at private clinics could compromise safety .

“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,” said Dr James Rucker, a consultant psychiatrist at King’s College London who worked on a separate psilocybin trial. “It’s interesting to be a part of, but I can’t call it” .

The question of how psychedelics transition from controlled research settings to broader clinical practice — without sacrificing the therapeutic framework that appears essential to their effectiveness — remains one of the field’s defining challenges.

What the Brain Data Suggests

Although the exact mechanism by which psychedelics alleviate depression is not fully understood, two leading hypotheses have emerged from neuroimaging research. The first suggests that psychedelics create a temporary window of neuroplasticity — a period during which the brain can more easily form new neural connections. The second proposes that these compounds may dampen neuroinflammation associated with chronic depression .

Erritzoe has described the effect using a mountain metaphor: psychedelics redistribute the snow on the brain’s landscape, flattening the deep grooves of entrenched thinking patterns so that new cognitive pathways become accessible. “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 .

Neither hypothesis has been conclusively proven, and both may operate simultaneously. What the clinical data increasingly supports, however, is that something measurable happens — and that the effect outlasts the drug by weeks or months.