Ayahuasca and Its Main Component N,N-Dimethyltryptamine (DMT) for the Treatment of Mental Disorders: Mechanisms of Action, Clinical Studies, and Tools to Explore the Human Mind
Biomedicines February 25, 2026 Alice Melani, Giorgia Papini, Marco Bonaso et al.
Psychedelics are gaining renewed scientific interest as breakthrough therapies for mental disorders, with ayahuasca and its active component DMT showing particular promise. DMT acts primarily as a serotonin 5-HT2A receptor partial agonist, while 5-MeO-DMT has higher affinity for 5-HT1A receptors; both foster neuroplasticity and reorganize brain networks involved in perception, cognition, and mood. Current evidence offers an optimistic outlook for treatment-resistant depression and major depressive disorder, with four phase II studies of 5-MeO-DMT and one of DMT for TRD, plus two phase II studies of DMT fumarate for MDD. Evidence for other mental disorders remains preliminary.