Moderators of ayahuasca’s biological antidepressant action

In a double-blind, placebo-controlled trial with 72 participants, ayahuasca's effects on depression-related biomarkers were examined two days after dosing. Larger reductions in depressive symptoms during the session were linked to higher serum cortisol levels in patients with treatment-resistant depression. Smaller changes in salivary cortisol during ayahuasca use were associated with higher brain-derived neurotrophic factor (BDNF) levels in patients who showed greater clinical improvement in depressive symptoms. No moderating effects were found for the cortisol awakening response, interleukin-6, or C-reactive protein in patients, nor for any biomarker in healthy controls or the placebo group. The findings suggest that acute emotional and physiological responses during ayahuasca sessions may influence key biomarkers of depression.

Study at a glance

Abstract

Introduction The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR). Methods Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial ( n = 72). Results Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient’s CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group. Discussion In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy.