¹Maastricht University, FPN, Maastricht, Netherlands

Background: Short-acting psychedelics such as 5-MeO-DMT and DMT may induce rapid relief of depressive symptoms after brief but intense psychedelic experiences.

Aims & Objectives: This presentation examines their clinical pharmacology and therapeutic potential in depression.

Method: Review of clinical data.

Results: Both compounds primarily target serotonergic receptors, notably 5-HT1A and 5-HT2A. Early small-scale trials indicate that short interventions (15–30 minutes) are safe, well tolerated, and can yield significant antidepressant effects within 24 hours. Although long-term data are limited, findings suggest sustained benefits.

Discussion & Conclusions: Advantages include single-day dosing, reduced reliance on integrative therapy, and straightforward clinical implementation. Key challenges remain, including determining effect duration, maintaining treatment response, optimizing delivery, and clarifying mechanisms of action. Broader acceptance will require large, randomized, placebo-controlled trials demonstrating replicable and durable antidepressant efficacy.