Therapeutic Effects of N,N-Dimethyltryptamine (DMT) and Related Short-Acting Psychedelic Tryptamines in Mental Disorders: A Scoping Review Protocol

Abstract

This preregistration outlines the protocol for a scoping review examining the therapeutic effects of N,N-Dimethyltryptamine (DMT)—both as a standalone compound and in preparations like ayahuasca—and related short-acting psychedelic tryptamines for the treatment of mental disorders and clinically significant psychological symptoms. Although interest in psychedelic-assisted therapies has grown substantially, most clinical research to date has focused on long-acting psychedelics like LSD and psilocybin. Short-acting tryptamine psychedelics like N,N-Dimethyltryptamine (DMT) may offer similar therapeutic benefits with reduced treatment duration, thus increasing the accessibility of psychedelic therapy and reducing its clinical resource burden. However, the evidence on clinical use of such compounds is fragmented, and no comprehensive synthesis has been conducted to date. Accordingly, the purpose of the planned scoping review is to systematically map the extent, nature, and characteristics of the existing evidence. Specifically, it aims to identify the clinical populations and compounds that have been studied, describe the characteristics of psychedelic interventions, and summarise relevant clinical outcomes. The proposed review will include a broad range of study types (e.g., clinical trials, observational studies, case series, qualitative studies) that assess therapeutic effects in clinical or well-characterised naturalistic settings. Populations of interest are individuals with a DSM- or ICD-defined mental disorder, and those experiencing clinically significant psychological symptoms in the absence of a formal diagnosis (e.g., terminally ill with psychological distress). The review will focus on studies where DMT and other short-acting tryptamines like 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) and N,N-Dipropyltryptamine (DPT) are administered with therapeutic intent. While the DMT-containing oral concoction ayahuasca produces longer-lasting effects than the isolated compound, it will be included in this review to contextualise clinical findings on DMT and allow for comparisons between short- and long-acting DMT-based interventions. Outcomes assessed will include direct therapeutic effects (i.e., change in symptoms associated with the primary psychological issue), psychotherapy-related outcomes (e.g., changes in emotional processing, therapeutic alliance, insight generation), and any reported adverse effects. By synthesizing the available evidence on short-acting psychedelic tryptamines, this project aims to clarify how these compounds are being used, studied, and experienced as therapeutic agents in mental health contexts. In doing so, it will identify evidence gaps in the literature and potentially inform future clinical research.

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