Research library / Systematic review

Short-term safety and tolerability profile of 5-methoxy-N,N-dimethyltryptamine in human subjects: a systematic review of clinical trials

Kwaśny A, Wilkowska A, Cubała WJ. Frontiers in Psychiatry 2024;15:1477996

This systematic review set out to collect every clinical trial reporting on the short-term safety of 5-MeO-DMT, a fast-acting psychedelic found in the secretion of the Sonoran Desert toad and also made synthetically. After searching five databases, the authors found only three trials that qualified, involving 78 people in total: two studies in healthy volunteers and one in patients with treatment-resistant depression. None of these trials reported a serious adverse event, and no one withdrew because of side effects. The authors read this as a favourable early safety picture. The evidence base is very thin, though: three small, early-phase studies cannot reveal rare or delayed harms, and the review says nothing about uncontrolled or ceremonial use. The authors call for larger placebo-controlled trials with longer follow-up.