image: ©agrobacter| iStock

Building on these findings, researchers at Imperial College London have found that a single dose of dimethyltryptamine (DMT), the primary psychedelic compound in ayahuasca, can significantly reduce symptoms of major depression, with effects lasting for months after treatment.

To explore this potential treatment further, in a Phase IIa clinical trial involving adults with treatment-resistant depression, participants who received DMT alongside psychotherapeutic support showed greater and more sustained improvements in mood than those given a placebo, highlighting the potential of this fast-acting psychedelic therapy.

The results are published in Nature Medicine.

DMT is a natural psychedelic, structurally analogous to psilocybin and serotonin. It is the chief psychoactive ingredient in ayahuasca. DMT’s rapid metabolism enables briefer therapeutic sessions.

Over the past decade, research has indicated that DMT may treat depression, yet few placebo-controlled clinical trials exist.

Addressing this gap, the Imperial College 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.

Participants were randomly assigned to two groups: 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, symptom severity was measured using the standardised Montgomery–Åsberg Depression Rating Scale (MADRS). The difference in scores was used as a 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 after one week of dosing, with an average drop of 10.8 points in MADRS scores. These antidepressant effects were still present three months later, and up to six months in some participants.

No serious adverse events were identified, nor were there changes in suicidal thoughts. The researchers noted that DMT’s effectiveness is linked to the intensity of the acute psychedelic experience, with maximal benefit for those reporting more intense effects.

In a subsequent trial phase, both the DMT and placebo groups received a DMT dose. The researchers found no significant differences in clinical outcomes between participants who received a single dose of DMT and those who received two doses, suggesting that a single dose may suffice for long-lasting benefits.

The study has several limitations. Firstly, the participant group was not ethnically diverse, which may restrict the generalizability of the findings. Secondly, individuals with a history of serious suicide attempts were excluded from participation, so the safety and effectiveness of DMT in this population remain unknown. The relatively small sample size and short follow-up period, compared with those of larger clinical trials, also limit the conclusions that can be drawn from these results.

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.”