Ayahuasca Therapy: Possible Reduction of Suicidal Ideation in Treatment-Resistant Depression - A Systematic Review.

In people with treatment-resistant depression, ayahuasca—a traditional Amazonian psychedelic—rapidly reduces suicidal thoughts and depressive symptoms. A systematic review of five studies found consistent evidence of these effects, attributed to the synergistic action of β-carbolines and DMT. Neurobiologically, ayahuasca promotes neuroplasticity by upregulating Brain-Derived Neurotrophic Factor and decreasing Default Mode Network activity, enabling profound introspection and emotional processing. Despite promising results, large-scale, rigorous longitudinal studies are needed to establish safe clinical guidelines.

Study at a glance

Abstract

Suicide, particularly in treatment-resistant depression (TRD), remains a pressing global health issue, with over 700,000 annual deaths. Existing treatments often have limited efficacy and delayed onset, creating a need for rapid-acting interventions. Ayahuasca, a traditional Amazonian psychedelic, has shown potential for rapidly reducing suicidal ideation. Our systematic review evaluated the clinical evidence regarding ayahuasca's effects on suicidality. From 6,633 initial records, five studies met the inclusion criteria. These studies, despite methodological heterogeneity, consistently demonstrate that ayahuasca administration is associated with rapid and significant reductions in suicidal ideation and depressive symptoms in patients with depressive disorders. The therapeutic effects were attributed to the synergistic action of β-carbolines and DMT present in ayahuasca. Neurobiologically, ayahuasca promotes neuroplasticity, partly through the upregulation of Brain-Derived Neurotrophic Factor, and modulates key brain networks, most notably by decreasing the activity of the Default Mode Network. Psychologically, this neural reconfiguration facilitates profound introspection, emotional processing, and transformative insights, which are central to its therapeutic effects. This review highlights the potential of ayahuasca as a novel therapeutic tool for suicidality but underscores the critical need for large-scale, methodologically rigorous longitudinal studies to establish definitive clinical guidelines for its safe and effective integration into psychiatric practice.