This randomised, placebo-controlled parallel trial (n=35) tested a single oral dose of ayahuasca versus placebo in patients with treatment-resistant depression.
This randomized, parallel-group trial evaluated the antidepressant effects of a single oral dose of ayahuasca compared with a passive placebo in patients with treatment-resistant major depression (n=35), with acute and longer-term follow-up.
Outcomes included depressive symptom scales (HAM-D, MADRS), psychiatric and neuropsychological assessments, MRI (structural and functional), polysomnography, and serum biomarkers (BDNF, TNF-α, cortisol, IL-6, IL-10).
Single-dose ayahuasca treatment arm.
1 ml/kg of ayahuasca brew; single dosing session. Brew composition: mean ± SD: 0.36 ± 0.01 mg/ml of N,N-DMT, 1.86 ± 0.11 mg/ml of harmine, 0.24 ± 0.03 mg/ml of harmaline, and 1.20 ± 0.05 mg/ml of tetrahydroharmine.
Passive inert placebo comparator.
1 ml/kg of active placebo. Per 1 ml of water: 0.1 g of yeast, 0.02 g of zinc sulfate, and 0.02 g of citric acid. Designed to imitate bitter/sour taste, brownish color, and gastrointestinal distress of ayahuasca.
A single dose of ayahuasca acutely raised salivary cortisol and, 48 hours later, normalised the blunted awakening salivary cortisol response in treatment‑resistant depression patients to levels seen in healthy controls, without changing plasma cortisol.