People with major depressive disorder saw significant and lasting reductions in their symptoms from a single dose of the psychedelic compound DMT in a small study.
People with major depressive disorder saw significant and lasting reductions in their symptoms from a single dose of the psychedelic compound DMT in a small study.
In the Phase IIa randomised clinical trial, led by researchers at Imperial College London and Cybin UK (now trading as Helus), the team found that participants with depression had greater reductions in depression severity when treated with dimethyltryptamine (DMT), compared to a placebo.
In a group of 34 people they found that those treated with DMT had a greater average reduction in scores of a clinical questionnaire for depression, compared to placebo, with effects lasting up to six months for some.
Although such early trial results should always be interpreted with some caution, they hold great promise for DMT therapy as a potential treatment for clinical depression Dr David Erritzoe Clin Associate Professor in Psychopharmacology & Psychiatry
The results are published in Nature Medicine.
The researchers say that while these are early-stage findings, they suggest that DMT could potentially provide similar therapeutic benefits seen with other psychedelics (such as psilocybin or ketamine). They explain that as the DMT psychedelic experience is far shorter – lasting minutes rather than hours – it could offer similar benefits at reduced cost and with a similar safety profile, but that further work is now needed to assess the treatment in larger groups of patients.
Dr David Erritzoe, from Imperial's Department of Brain Sciences, and lead investigator of the trial, said: "We have shown that a single DMT experience of just around 25 minutes duration is safe, effective and durable, with effects comparable to other promising psychedelic treatments often requiring much longer treatment sessions."
"Although such early trial results should always be interpreted with some caution, they hold great promise for DMT therapy as a potential treatment for clinical depression. It is also likely to be more cost-effective than longer-acting psychedelics due to the shorter dosing sessions."
DMT is a naturally occurring psychedelic, similar in structure to both psilocybin (found in 'magic' mushrooms) and the neurotransmitter serotonin. It is the major psychoactive compound in ayahuasca. But unlike many other psychedelics, DMT breaks down quickly in the body, allowing for shorter therapeutic sessions.
In the last decade, several studies have shown initial evidence for the potential of DMT as a therapy for depression. But to date there have been very few placebo controlled clinical trials.
The latest trial looked at 34 participants, all with moderate-to-severe depression, and a history of at least two previously unsuccessful treatments, either conventional medicine or psychotherapy.
Initially, half of the patients received a single 21.5mg dose of DMT infused into a vein over 10 minutes, whilst the other half received a placebo (same dose, same delivery method, but without the psychoactive compound). All participants received the same psychotherapeutic support, including pre-dose consultations, visualisation practices, and in-person support during the dosing period.
Before and after DMT/placebo treatment, the severity of the symptoms were measured with a standardised questionnaire – the Montgomery–Åsberg Depression Rating Scale (MADRS). Differences in scores was used as the primary measure of change in depressive symptoms.
Two weeks after dosing, the DMT group showed a greater reduction in average scores compared to the placebo group (mean change of 7.4 points from baseline).
The DMT group also showed significantly larger reductions just one week after the dosing, with an average of 10.8 points larger drop in MADRS scores. The antidepressant effects were still present 3 months later, and up to 6 months in some participants. The treatment regimen was generally well tolerated and safe. No serious adverse events occurred related to the treatment and there were no concerning changes in suicidal thoughts.
The researchers noted that DMT's efficacy appears to be dependent on the intensity of the acute psychedelic experience it generates, with it seeming most effective for people who reported the most intense experiences.
In a subsequent trial phase, the DMT and placebo groups received a dose of DMT. Secondary analyses found no significant differences in clinical outcomes between participants who received one dose of DMT versus those who received two, suggesting that a single dose may suffice for long-lasting benefits.
The researchers highlight that the study had several limitations, including a lack of ethnic diversity in the participant group and that participants with a history of serious suicide attempts were excluded.
They say that longer and larger trials are now needed to further evaluate the efficacy, safety, and cost-effectiveness of DMT-assisted therapy compared with existing standard treatments.
The trial was designed, funded and sponsored by Cybin UK Ltd (now trading as Helus and previously known as Small Pharma), which also provided the DMT fumarate [SPL026] used in the trial.
The trial was conducted at Hammersmith Medicines Research Ltd (HMR; London, UK), MAC Clinical Research (MAC; Liverpool, UK) and with follow-up undertaken by Imperial College London Hammersmith Campus (London, UK).
'A short-acting psychedelic intervention for major depressive disorder: randomized placebo-controlled IIa trial of intravenous dimethyltryptamine (DMT) with therapeutic support' by David Erritzoe, Tommaso Barba, Ellen James et al, is published in Nature Medicine. DOI 10.1038/s41591-025-04154-z.
