Summary: While psychedelic research often focuses on hours-long “trips” with psilocybin or LSD, a landmark Phase IIa trial has proven that a much shorter experience can be just as potent. Using DMT, the primary psychoactive compound in ayahuasca, researchers found that a single intravenous dose lasting only about 25 minutes produced significant and rapid antidepressant effects in patients with moderate-to-severe treatment-resistant depression.
Most importantly, these benefits weren’t fleeting; participants experienced substantial reductions in symptoms for up to six months. This “fast-acting” profile could revolutionize psychedelic therapy by making sessions more resource-efficient and accessible within traditional healthcare systems.
Key Facts
- The “Fast” Advantage: The acute psychedelic experience from DMT lasts only 20–30 minutes, compared to the 6–8 hours required for psilocybin or LSD.
- Significant Symptom Drop: One week after dosing, the DMT group showed a 10.8-point larger drop in depression scores (MADRS) compared to the placebo group.
- Long-Term Durability: Antidepressant effects remained significant at three months, with some participants maintaining improvements for the full six-month follow-up.
- Intensity Matters: The study noted that the efficacy of the treatment was closely tied to the intensity of the “peak” psychedelic experience.
- Scalability: Because sessions are significantly shorter, DMT therapy could be more cost-effective and easier to implement in clinics than longer-acting psychedelics.
Source: Imperial College London
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.
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.
Funding: 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).
Key Questions Answered:
A: Chemically, they are similar, but the experience is very different. DMT provides a much more rapid, intense “blast-off” that is over in minutes rather than hours. This study proves that the brain doesn’t need a long session to achieve the “reset” effect seen in other psychedelic therapies.
A: No. This study used medical-grade DMT (SPL026) delivered intravenously in a highly controlled clinical setting with professional psychological support. The “integration” sessions with therapists are considered a vital part of why the results lasted for six months.
A: The trial reported that the treatment was generally well-tolerated and safe. No serious adverse events were related to the drug, and there were no concerning changes in suicidal thoughts or cardiovascular health during the sessions.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this depression and psychopharmacology research news
Author: Samantha Rey
Source: Imperial College London
Contact: Samantha Rey – Imperial College London
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial” by David Erritzoe, Tommaso Barba, Tiffanie Benway, Zelah Joel, Meghan Good, Marie Layzell, Michelle Baker Jones, Graham Campbell, Ashleigh Murphy-Beiner, Peter Rands, Malcolm Boyce, Helen Topping, Brandon Weiss, Christopher Timmermann, David Nutt, Robin Carhart-Harris, Carol Routledge & Ellen James . Nature Medicine
DOI:10.1038/s41591-025-04154-z
Abstract
A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial
Major depressive disorder (MDD) is a leading cause of disability worldwide, yet many patients have inadequate responses to current treatments. Dimethyltryptamine (DMT), a serotonergic psychedelic with rapid onset and short duration, shows promise as a potential antidepressant (AD), although clinical evidence in MDD remains limited.
We conducted a phase IIa, double-blind, placebo-controlled, randomized clinical trial to evaluate the efficacy and safety of intravenous DMT (SPL026; DMT fumarate) in adults with moderate-to-severe MDD.
Participants received a single 21.5-mg dose of DMT or placebo infused over 10 min, along with supportive psychotherapeutic support, followed by a 2-week assessment. A subsequent open-label phase offered all participants a second DMT dose.
The primary outcome was the change in Montgomery–Åsberg Depression Rating Scale (MADRS) at 2 weeks. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS ≤ 10). A total of 34 participants were randomized, 17 to placebo–active and 17 to active–active.
At 2 weeks, the DMT group showed a significantly greater reduction in MADRS score than placebo (mean difference = −7.35; 95% CI = −13.62 to −1.08; P = 0.023). In the open-label phase, AD effects persisted up to 3 months, with no significant differences between those who received one versus two doses.
Adverse events were mostly mild to moderate, commonly infusion site pain, nausea and transient anxiety. No serious adverse events occurred.
A single dose of DMT with psychotherapeutic support produced a rapid, significant reduction in depressive symptoms, sustained up to 3 months. The treatment was well-tolerated and safe.
ClinicalTrials.gov registration: NCT04673383.
