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Results from a phase II randomised controlled trial published in Nature Medicine looks at the psychedelic DMT (dimethyltryptamine) for the treatment of major depressive disorder.
Prof Ian Maidment, Professor in Clinical Pharmacy, Aston University, said:
“This phase 2a clinical trial involved 34 patients, who received two infusions: 17 were allocated to receive one dose of placebo and one dose of the active drug dimethyltryptamine (DMT) and 17 allocated to two doses of DMT. Patients also received psychological support. Patients received the second dose of DMT two weeks after the initial dose of DMT or placebo. Patients and staff were blinded to the first dose; the second dose of DMT was open label (patients and staff were aware that it was DMT).
“In total, 28 patients completed the trial (received both doses). At two weeks, after the first dose, people who had received DMT had fewer depressive symptoms than those who had received placebo. However, at 14 weeks people who had received one dose of placebo and one dose of DMT had fewer symptoms than those who had received two doses of DMT.
“A phase 2a clinical trial is a pilot study. It is primarily designed to determine the most effective dose for future trials. Phase 2 studies should identify key adverse events and give some indication of initial efficacy. However, the number of participants is generally small and phase 2 trials are not designed to definitively determine whether the drug works. Phase 3 studies, which follow on from phase 2 studies, should be conducted prior to any conclusion about efficacy of any drug.
“In terms of safety, side-effects were more common in the group who received DMT: 64.7% of participants after the first dose had at least one side-effect and 62.5% after the second dose compared with 23.5% of people who received placebo. The most frequent side-effects with DMT were anxiety and nausea; both these side-effects were experienced by six people on DMT compared to no-one on placebo. Overall, we need more data from a larger more diverse population to confirm whether or not DMT is safe.
“The vast majority of study participants (88.2%) were white ethnicity limiting generalisability to other races. The researchers also did not assess blinding integrity (whether participants knew if they received DMT or placebo). Thus, a placebo effect cannot be excluded.
“Based on the number of people treated, the risk of a placebo effect and because phase 2 studies aren’t designed to definitively test whether the drug works it is premature to conclude that DMT is an effective treatment for depression. Therefore, overall DMT should not be taken outside of a controlled clinical trial for depression.”
Prof James Stone, Professor of Psychiatry, Brighton and Sussex Medical School and Honorary Consultant Psychiatrist, Sussex Partnership NHS Trust, said:
“This is an exciting and well-designed proof of concept study from a respected research group that gives the first suggestion that DMT might be useful as an antidepressant agent. In terms of safety concerns, there may be a risk of negative experiences during the psychedelic experience that could be frightening or traumatising. Certain groups of people may be more susceptible to these types of effects and further studies are required to identify how often these types of negative experience occur.
“It is likely that participants in these studies will have a particular belief in the likely benefit of the psychedelic experience and so there will be a large expectation effect which will translate into a large improvement in symptoms not directly related to the drug effects. It is almost impossible to adequately blind participants in these studies because of the particular distinctive effects of psychedelic drugs.
“This study fits closely with previous research on psychedelic drugs including psilocybin – suggesting that a combination of a psychedelic experience combined with psychological reintegration might be helpful in people with depression.
“There remain risks associated with DMT and other psychedelic drugs when taken recreationally. It is also important to note that although this and other psychedelic psychotherapy studies are promising, the numbers of people included are very small compared to definitive trials of antidepressants and so it is too early to say with certainty that this approach is effective and safe. Further research is needed before psychedelic therapies can be recommended as treatments for depression and other mental health conditions.”
Dr James Rucker, Consultant Psychiatrist and Senior Clinical Lecturer at the South London & Maudsley NHS Foundation Trust and King’s College London, said:
“This trial adds to a growing body of evidence that psychedelic drugs may have rapid and enduring antidepressant effects when given in a medically-controlled, psychologically supportive setting. The nature of a psychedelic drug means that blinding participants to whether they received the drug is impossible, so the improvements seen here are likely a reflection both of a drug effect and an expectancy effect. This is a common issue of interpretation seen in other drug trials, as well as in trials examining non-drug interventions like psychotherapy and surgery. This trial is small in scale, and therefore not a definite test of whether DMT is effective. However, it supports the development of further, larger trials that would better address this question.”
‘A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial’ by David Erritzoe et al. was published in Nature Medicine at 16:00 UK time on Monday 16th February.
DOI: https://doi.org/10.1038/s41591-025-04154-z
Declared interests
Prof Ian Maidment: No conflicts of interest
Prof James Stone: “No declarations of interest.”
Dr James Rucker: James Rucker leads commercially and publicly funded clinical trials using psychedelics, alongside other trials in mood disorders, within these institutions.