Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial

Feasibility and adherence were high: all 17 randomised volunteers completed the session and the three follow-ups, and no serious adverse events or dropouts occurred. Due to equipment issues, primary and most secondary analyses were conducted on 14 participants (7 per group). Primary outcome (SSPS): Analyses showed a significant between-group effect favouring ayahuasca: F1,12 = 7.740, P = 0.017, η2 = 0.392. The ayahuasca group exhibited progressive increases in positive self-statements across the SPST phases, with significant differences at anticipatory speech (P = 0.049), speech performance (P = 0.013), end of speech (P = 0.016) and postspeech (P = 0.008). Subjective mood and anxiety (VAMS and BAI): The VAMS anxiety factor showed a significant effect of time (F5.243, 62.916 = 3.848, P = 0.004, η2 = 0.243), with anxiety increasing during the early SPST phases, but no significant time×group interaction or between-group differences. A significant time×group interaction was observed for the cognitive deterioration VAMS factor (F3.152, 37.823 = 4.422, P = 0.008, η2 = 0.269), although pairwise group differences were not significant. Sedation showed a time effect (F3.650, 43.806 = 6.776, P < 0.001, η2 = 0.361); discomfort did not change. The BAI (the only measure with data for all 17 participants) showed no significant effects of time, group or interaction. Bodily Symptoms Scale (BSS): Significant effects of time (F3.551, 42.611 = 3.293, P = 0.023, η2 = 0.215), group (F1.12, 42.611 = 7.507, P = 0.018, η2 = 0.385) and time×group interaction (F3.551, 42.611 = 2.938, P = 0.036, η2 = 0.197) were reported. Compared with placebo, ayahuasca increased somatic symptoms at 90 minutes (P = 0.036) and 120 minutes (P = 0.041), with near-significant increases at 40 minutes (P = 0.05) and 180 minutes (P = 0.052). Recognition of emotions in facial expressions (REFE): There were significant effects of time for overall accuracy (F5, 60 = 4.650, P = 0.001, η2 = 0.279) and reaction time (F2.858, 34.293 = 7.843, P = 0.003, η2 = 0.327), and emotion-specific time effects (for sadness accuracy and reaction-time changes for fear, disgust and anger). However, no significant time×group interactions or between-group differences were found; the authors note that all significant time effects were observed within the ayahuasca group. BDNF and other measures: Plasma BDNF showed no significant changes, but only a few valid samples were available and results were presented descriptively. Observer impressions and spontaneous reports indicated mainly mild-to-moderate psychedelic effects in the ayahuasca group; some volunteers reported calmness or reduced anxiety in the week after the session. Tolerability and cardiovascular effects: Ayahuasca-associated adverse effects included gastrointestinal discomfort and nausea (n = 4), vomiting (n = 3), drowsiness (n = 2), transient confusion (n = 2), headache (n = 2), diarrhea, fear/distress and one transient dissociative/depersonalisation episode that resolved with researcher support. Heart rate showed a significant effect of time during the session (F10, 12 = 15.49, P < 0.01, η2 = 0.563) but no group differences; systolic and diastolic blood pressures showed significant time×group interactions but no between-group differences. Transient moderate hypertension and episodes of tachycardia occurred in both groups. No serious cardiovascular events were reported. Blinding efficacy: Blinding failed in this trial—participants and the session researchers correctly guessed the administered substance in 100% of sessions.

Dos Santos and colleagues report that a single ayahuasca dose was feasibly administered in this pilot randomised trial and that the primary hypothesis was supported: compared with placebo, ayahuasca significantly improved self-perception of speech performance on the SSPS across most SPST phases. The authors emphasise that this procognitive effect on self-perception occurred independently of measurable reductions in task-related anxiety on standard scales, although some participants reported subjective calmness and reduced anxiety in follow-up. The authors note that baseline anxiety in the sample was generally mild (mean BAI ~9.8), which may have limited detection of anxiolytic effects on the scales. Regarding social cognition, ayahuasca did not produce significant between-group changes in the REFE task despite time-related improvements in accuracy and reaction time that were observed only in the ayahuasca group; the authors suggest these could reflect learning effects or increased sensitivity to emotional faces, but the small sample size, task ceiling/learning effects and the predominantly female, highly educated sample may have influenced results. No significant BDNF effects were observed, but data were sparse. Safety findings replicated earlier work: the most common adverse effects were transient gastrointestinal and mild cognitive/perceptual symptoms, and one brief challenging episode was managed without pharmacological intervention. The authors regard the tolerability as acceptable for a single dose in this controlled setting. The discussion highlights several limitations acknowledged by the investigators: significant degradation of ayahuasca alkaloids over the prolonged storage period (with DMT declining from 1.53 mg/mL to 0.23 mg/mL over 46 months), use of comparatively low DMT concentrations, failure of blinding (participants and staff guessed drug assignment perfectly), small sample size, reliance on self-report measures for speech performance and an unrepresentative sample (mostly female undergraduate students). These constraints reduce generalisability and may have attenuated some effects. The authors recommend systematic dose–response studies, better storage and periodic chemical verification of ayahuasca, improved blinding strategies (including consideration of active psychoactive placebos), more objective and ecological outcome measures, and trials in clinical SAD populations with varied severity and with repeated dosing and neuroimaging to clarify mechanisms. Overall, they interpret the findings as preliminary evidence that ayahuasca can specifically improve cognitive self-perception of performance in people with SAD and propose further research to explore therapeutic applications and mechanisms.

Compared with placebo, a single ayahuasca dose significantly improved self-perception of speech performance in volunteers with SAD, indicating a potential procognitive effect relevant to a core feature of the disorder—a negative self-perception. The authors conclude that ayahuasca merits further exploration as an adjunct or novel intervention to enhance self-confidence in performance contexts (for example, art therapy or as an exposure-like technique within CBT), while emphasising the need for larger, better-controlled trials to confirm efficacy, clarify mechanisms and address methodological limitations.