Psychedelic Therapy: A Primer for Primary Care Clinicians – Part III. N,N-dimethyltryptamine (DMT) and Ayahuasca

Background: N,N-dimethyltryptamine (DMT) is a naturally-occurring serotonergic psychedelic found in natural plants around the globe. As the main psychoactive component in ayahuasca, which also contains monoamine oxidase (MAO) inhibitors, DMT has been consumed as plant-based brew by indigenous peoples for centuries. Further research is required to delineate the therapeutic utility of DMT.Areas of Uncertainty: Although previous research has shown that DMT is synthesized endogenously, it may not be produced at physiologically relevant concentrations. Additionally, the phenomenological similarities between the DMT-induced state and near-death experiences led to the popular hypothesis that endogenous DMT is released during the dying process; however, this hypothesis continues to be debated. Generally, DMT and ayahuasca appear to be physiologically and psychiatrically safe, though ayahuasca is known to cause transient vomiting.Therapeutic Advances: A double-blind, randomized, placebo-controlled trial showed that, within one week, ayahuasca causes remission in 36% of patients with treatment-resistant depression. According to top-line results from a recent Phase IIa trial, 57% of patients with major depressive disorder experienced remission 12 weeks after receiving a single dose of DMT. Conclusions: DMT requires further research to understand its therapeutic and clinical potential as a psychedelic. Given its possible endogenous role in human physiology, further research is also needed to understand DMT’s role in human biology, behaviour, and consciousness.