Ayahuasca vs. Placebo for Social Anxiety Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot

Randomized, double-blind, placebo-controlled, parallel-group pilot (University of São Paulo, Brazil; conducted September 2015 – July 2019) of a single oral dose of ayahuasca (2 mL/kg; prepared by a Santo Daime church and stored refrigerated; alkaloid concentrations verified by UPLC-MS) versus placebo (2 mL/kg; mineral water, glycerin, propylene glycol, methylparaben; organoleptic match) in 17 undergraduate volunteers (15 women) meeting DSM-5 Social Anxiety Disorder criteria confirmed by SCID-5-CV (SPIN ≥19 or excessive social fear on screening). From 894 screened, 17 met criteria and were randomised: 9 to ayahuasca, 8 to placebo. Key exclusions: current SAD treatment, major medical or other psychiatric disorders (except comorbid anxiety), psychoactive medications, recurrent illicit drug use, prior ayahuasca use (>2 lifetime hallucinogen uses), pregnancy/lactation. Primary outcome: Self-Statements During Public Speaking Scale (SSPS) state version during a Simulated Public Speaking Test (SPST; anticipatory, preparation and speech phases) administered 300–355 minutes post-dose. Secondary outcomes: Visual Analogue Mood Scale (VAMS; anxiety, sedation, cognitive impairment, discomfort factors) at 11 time points from baseline to 355 minutes; Bodily Symptoms Scale (BSS); Beck Anxiety Inventory (BAI; baseline, 240 min, follow-ups); Recognition of Emotions in Facial Expressions (REFE) task; cardiovascular measures. Follow-up at days 7, 14, and 21. Analysis: two-way repeated-measures ANOVA (time × group), Bonferroni correction, α=0.05, η² effect sizes. No formal sample size calculation (pilot feasibility study). All 17 completed the experimental session and three follow-ups; equipment failure reduced some outcome analyses to 14 participants (7 per group). No trial registry number reported.