Can DMT help treat depression?

What is DMT?

N,N-dimethyltryptamine, often called DMT, is a psychedelic compound that can alter perception, thoughts and mood. It acts on serotonin signalling, but a receptor mechanism does not prove a treatment effect. The duration and effects depend on the formulation and route. A regulated investigational infusion with trained support is a different intervention from a plant preparation or an unverified product.12

Is 5-MeO-DMT the same as DMT?

No. 5-MeO-DMT, also called mebufotenin, is a different molecule from N,N-DMT. Similar names do not mean identical effects, risks or trial results.

A 2026 phase 2b trial studied a defined intranasal mebufotenin preparation with psychological support in 193 adults with treatment-resistant depression. The main comparison was a higher amount against a very low amount of the same investigational drug, not an inactive placebo.

After 29 days, the higher group improved by an adjusted average of 5.3 points more on the MADRS depression scale; the 95% confidence interval was 1.8 to 8.9 points.

Adverse events were reported by 85% in the higher-amount group and 73% in the low-amount comparison group. Most reported events across the study were mild or moderate. Follow-up in the blinded phase lasted eight weeks. The preparation was developed by Beckley Psytech, and several authors reported company employment or other financial relationships. This is encouraging evidence for that specific formulation and selected population, not proof about N,N-DMT, an unverified product, longer-term safety or an individual outcome. The full paper remains to be assessed; this summary uses its published abstract.

A separate 2026 trial studied GH001, an inhaled mebufotenin formulation, in 81 adults with treatment-resistant depression. At day eight, the drug group improved by an average 15.5 points more than placebo on the MADRS depression scale.

On a secondary measure, 23 of 40 in the drug group and none of 41 in the placebo group met the study’s symptom-score definition of remission; that is not proof of a lasting cure.

During the controlled week, adverse events were reported by 29 of 40 and 3 of 41, respectively; none were classified as severe or serious in that period.

The later six-month extension was open-label, so it cannot establish sustained benefit against placebo.

Independent raters were kept unaware of assignment, but the study did not formally assess whether participants or clinical staff guessed it; the noticeable effects could influence expectations.

GH Research funded the trial, and company employees contributed to its design and data collection and analysis. The two 5-MeO-DMT studies used different products, routes and comparisons and cannot rank them against each other.34

Is ayahuasca the same as DMT?

No. Ayahuasca is a traditional Amazonian plant preparation, and its composition varies. A commonly described preparation combines a DMT-containing plant with a vine containing substances that inhibit monoamine oxidase, an enzyme involved in breaking down DMT and other compounds. The mixture, route and additional active substances make it different from the defined intravenous DMT preparation described below. A result for one cannot automatically be transferred to the other.

In a 2019 Brazilian placebo-controlled trial, 29 adults with treatment-resistant depression received a single studied ayahuasca preparation or placebo under clinical supervision. After seven days, 64% in the ayahuasca group and 27% in the placebo group met the researchers’ response criterion on a depression scale. This was a small, selected sample and one-week comparison, not evidence of lasting benefit or safety for every preparation. Nausea and vomiting were reported; the placebo was designed to resemble the preparation, but the follow-up psychiatrists’ masking was not formally assessed.

Monoamine oxidase inhibition can create dangerous interactions with some medicines and other substances. A person taking medication should discuss possible interactions with a qualified clinician rather than stopping prescribed treatment or assuming a plant preparation is safe. Severe agitation, high temperature, confusion, seizures or collapse warrant emergency assessment; tell responders what may have been taken.567

What did the controlled trial find?

A 2026 phase 2a trial randomly assigned 34 adults with moderate-to-severe major depression to a defined intravenous DMT preparation or placebo, with psychological support. After two weeks, the average improvement on the clinician-rated MADRS depression scale was 7.35 points greater with DMT than placebo; the reported confidence interval ranged from 1.08 to 13.62 points. This is an average difference, not a prediction for an individual.

The sponsor, Small Pharma, now Cybin UK, designed and supported the trial and supplied the investigational preparation. Independent site raters assessed symptoms, but the researchers did not measure whether participants could guess their assignment. Noticeable psychedelic effects could weaken masking and influence expectations. The small, selected sample limits confidence in the size of the benefit.12

Did the effect last?

After the two-week blinded comparison, participants were offered DMT in an open-label phase: both groups could receive it and knew what was being given. Researchers observed improvements during later follow-up, but without a continuing placebo-only group those observations cannot establish how much was caused by DMT, how long a benefit lasts, or whether a second administration adds benefit. Larger, longer controlled studies are needed.12

What about harms and access?

Reported effects included infusion-site pain, nausea and anxiety; the researchers reported no serious adverse events in this small study. That does not rule out uncommon or delayed harms, or establish safety in people excluded from the trial. The studied intervention included screening, monitoring and psychological preparation and follow-up. Research access, authorisation and legal rules depend on the product and jurisdiction. Do not stop prescribed treatment or substitute an unverified product for mental-health care; discuss symptoms and treatment options with a qualified professional. For a different compound, see psilocybin and depression research.

For example, the intravenous DMT trial excluded people with a personal or immediate-family history of psychosis, a history of serious suicide attempts, or a positive pregnancy test. These are selected exclusions from this particular study, not a list of criteria for every DMT or 5-MeO-DMT trial. Its findings do not establish safety in those excluded groups.12