Surprisingly on the opposite to the common belief, DMT is not the main compound that produces antidepressant activity although it affects Sigma-1 receptors and 5-HT receptors in our brain that can help to combat depression. Also, we should not underestimate the effect of the spiritual experience on the healing process as well as a work of a shaman during the ceremony.
The main antidepressant effect comes from the presence of B-Carbolins (MAOIs) in the brew.
Harmine appears to exert pharmacological properties that might be translated into new clinical drugs [1
]. In fact, harmine and other harmala alkaloids that inhibit MAO have been long used as antidepressants in humans outside clinical practice, proving to modulate mood and anxiety.
Moreover, chronic administration of MAOIs (harmine) reduces immobility time, reverses anhedonia, increases adrenal gland weight, and increases BDNF levels in the hippocampus (Fortunato et al.
). All of these are compatible with antidepressant effects.
Aside from this Ayahuasca stimulate neurogenesis of human neural progenitor cells, derived from pluripotent stem cells (Dakic et al.
), and progenitor cells from adult mice brains (Morales-García et al.
), a mechanism also observed in rodents following antidepressant treatment.
Also recent researches found that a single ayahuasca session in patients with depression increases blood flow in brain regions consistently implicated in the regulation of mood and emotions, such as the left nucleus accumbens, right insula and left subgenual area (Otte et al.
; Sanches et al.
). Moreover, research has shown that ayahuasca reduces the activity of the Default Mode Network (Palhano-Fontes et al.
), a brain network found to be hyperactive in depression (Sheline et al.
Over the last two decades, mental health evaluations of regular ayahuasca consumers have shown preserved cognitive function, increased well-being, reduction of anxiety, and depressive symptoms when compared to non-ayahuasca consumers (Grob et al.
; Bouso et al.
; Barbosa et al.
). Moreover, a recent study observed that a single dose of ayahuasca enhanced mindfulness-related capacities (Soler et al.
), and meditation practices have been associated with antidepressant effects (Segal et al.