The antidepressant effects of the psychedelic brew known as ayahuasca appear to be related to anti-inflammatory activity, according to new research from scientists in Brazil. Their findings, published in the Journal of Psychopharmacology, provide new insights into the biological mechanisms behind the observed antidepressant effects of the substance.
Ayahuasca, a concoction used for centuries by indigenous Amazon tribes, contains the powerful psychedelic drug dimethyltryptamine (DMT) and monoamine oxidase inhibitors. The brew is typically prepared using leaves from the Psychotria viridis shrub and the bark of the Banisteriopsis caapi vine.
The authors of the new study were interested in examining the effects of alternative treatments such as ayahuasca because of the widespread prevalence of depressive disorders.
“Major Depression Disorder (MDD) is one of the most prevalent mood disorders, reaching about 350 million people worldwide. One third of patients with depression do not show a satisfactory response to antidepressants leading to a large proportion of patients developing recurrent MDD with multiple depressive episodes,” said study author Nicole Leite Galvão-Coelho, a professor at the Federal University of Rio Grande do Norte.
In the study, the researchers briefed 28 patients with treatment-resistant depression and 45 healthy controls about the physiological and psychological effects associated with ayahuasca. The participants were then randomly assigned to received either a single oral dose of ayahuasca or a placebo substance.
The placebo substance was a brownish liquid that mimicked the look and taste of ayahuasca. In addition, the placebo contained zinc sulphate, which induces nausea — a common side effect of ayahuasca.
After consuming their dose, the participants stayed in a comfortable room at a hospital for about six hours, where they listened to curated music playlists.
The researchers collected and analyzed blood samples from the participants immediately before dosing and again two days later. They were particularly interested in two blood inflammatory biomarkers: C-reactive protein and interleukin 6.
Galvão-Coelho and her colleagues observed significant antidepressant effects among patients who received ayahuasca. These improvements in depressive symptoms were associated with reductions in inflammation.
Patients with treatment-resistant depression tended to have higher C-reactive protein levels compared to the control group at baseline. The researchers found that C-reactive protein levels were reduced in both patients and healthy controls 48 hours after consuming ayahuasca, but not after consuming the placebo.
“Besides changes in emotions, MDD also induces biological changes. A better comprehension of these biological changes can help in the development of more efficient treatments. For instance, treatment-resistant depression has been associated with mild chronic systemic inflammation. In this study, a single dose of ayahuasca, and not the placebo, reduced both depressive symptoms and systemic inflammation of treatment-resistant depressive patients two days after the treatment,” Galvão-Coelho told PsyPost.
“The commercial antidepressants when work spend about 15 days to start the first effects on reduction of depressive symptoms. Regarding their anti-inflammatory action there is not a consensus of how they are acting.”
Patients and controls showed similar levels of interleukin 6 at baseline and there was no change after treatment.
“Although ayahuasca does not lead to compulsive drug-seeking behaviors or induce physiological toxicity, it does induce acute and mild sympathetic activity. Therefore, patients with cardiovascular disease and who have mania or psychosis must not use it,” Galvão-Coelho cautioned.
“The next step in this field is to test multiple sessions of ayahuasca associated with psychotherapy as treatment for depression. The studies with psychedelics for mental disorders have shown promising results, but we need a bit more understanding to turn them into an accessible treatment.”
The study, “Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca“, was authored by Nicole Leite Galvão-Coelho, Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida, Fernanda Palhano-Fontes, Isaac Campos Braga, Bruno Lobão Soares, João Paulo Maia-de-Oliveira, Daniel Perkins, Jerome Sarris, and Draulio Barros de Araujo.