DMT and 5-MeO-DMT: 51-Study Review Points to Depression

Psiconáutica Editorial Team · October 19, 2026

Short-acting psychedelics have been on the radar of psychiatric research for some time. A team from the University of Toronto has just published a systematic review that synthesizes what is known about three related compounds: N,N-DMT, 5-MeO-DMT, and zalsupindole. The work is a literature review, not a new trial, and serves primarily to map out where each piece of the puzzle currently stands.

Two similar molecules, two distinct profiles

DMT and 5-MeO-DMT share the same family but do not behave identically. The authors note differences in pharmacokinetics, the receptors they act upon, and the subjective experience described by those who take them. That brevity is precisely what makes them clinically interesting: with intravenous DMT, acute effects resolved in 20 to 30 minutes, and sublingual 5-MeO-DMT showed an elimination half-life of about 28 minutes.

For those familiar with psilocybin or LSD, which involve sessions lasting several hours, the contrast is significant. An intervention that lasts less time could require less commitment from a therapeutic team, although this is a starting hypothesis rather than a proven result.

What the review found

The team searched databases from their inception through December 22, 2025, and updated the search on July 7, 2026. Two reviewers screened the papers, extracted data, and independently assessed the risk of bias. 51 publications met the criteria.

Depression is the area with the most progress. Both compounds were associated with rapid reductions in depressive symptoms. Notable data includes GH001, an inhalable formulation of 5-MeO-DMT, which met its primary endpoint in a phase 2b trial for treatment-resistant depression, consistent with results we previously covered regarding postpartum depression. In contrast, evidence for substance use disorders, post-traumatic stress, and eating disorders is described as preliminary.

Regarding safety, the most common adverse effects were nausea, headache, and transient increases in cardiovascular parameters.

Zalsupindole, the big question mark

The third subject is an analog expected to retain some of the effects on neuronal plasticity without inducing a trip. The review found only one preclinical study: it showed antidepressant-like behaviors and effects related to plasticity, without the “head-twitch” response used in rodents as an indicator of hallucinogenic activity. Everything else, from its efficacy to its actual hallucinogenic potential in humans, remains unknown.

What this implies

An honest reading is that there are promising signals and a foundation that is still thin. A systematic review is only as solid as the studies it gathers, and here, small trials and early phases abound. The authors themselves call for studies that link dosage and blood exposure, receptor pharmacology, neurobiological markers, subjective experience, and clinical outcomes, and that clarify whether plasticity effects can be separated from the hallucinogenic experience.

For those seeking information from a harm reduction perspective, the useful takeaway is that the brevity of these compounds does not equate to an absence of physiological effects: transient cardiovascular spikes appear in the literature. If you are interested in the broader context, you can read our overview of ayahuasca and DMT and the general map of the psychedelic renaissance on our site.

Source

• Collyer C, Le GH, Hassan M, Wong S, McIntyre RS. Pharmacological, clinical, and translational evidence for N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and zalsupindole: a systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry, October 6, 2026.

Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.