Recent Evidence on the Antidepressant Effects of Ayahuasca

Depression is a mood disorder with profound negative effects on the individual’s quality of life and augmented suicidal risks. Despite substantial progress in the development of new antidepressants that have been made in the last decades, remission rates are modest, around 50% after the first treatment. Besides, antidepressants usually take about 2 weeks for the effects to take place. In the search for alternative treatments for depression, serotonergic psychedelics, such as ayahuasca, are emerging with promising results. Recent clinical trials have suggested a potential antidepressant effect of ayahuasca. In a first open-label trial, 17 patients with depression took part in a single ayahuasca session conducted in a hospital, and depressive symptoms were monitored by clinical scales to assess depression severity at 1, 2, 7, 14, and 21 days after the session. Depressive symptoms improved significantly already 1 day after the session, an improvement that persisted for 21 days. In a follow-up randomized placebo-controlled trial, 29 patients with treatment-resistant depression participated in a single session in a hospital, half took one dose of ayahuasca, and the other half with a placebo substance that, similar to ayahuasca, produced some gastrointestinal distress. We observed significant antidepressant effects of ayahuasca already 1 day after the session with ayahuasca, which was even more pronounced 7 days later. In addition to the antidepressant effects, we explored potential biological processes that might be related to the antidepressant effects observed. These included biochemical markers, functional magnetic resonance imaging (fMRI), and sleep electroencephalography (EEG). This chapter aims to review some general aspects of depression, discuss the motivations to use ayahuasca as a novel antidepressant, and present the latest scientific findings that should help clarify the mechanisms behind the observed antidepressant effect of ayahuasca.