2026 ECNP Congress

PS01-1203

Single-dose ayahuasca for depressive and anxiety symptoms associated with cancer diagnosis: a single-blind feasibility proof-of-concept trial

Renan Maekawa — L. Guerra, B. Villanova, C. de Paula, A. Zacharias, L. Rodrigues, J. Reis, G. Rossi, J. Bouso, J. Hallak, R. dos Santos · USP, Mental Health and Behavioral Sciences, Ribeirão Preto, Brazil

2026 ECNP Congress

Ayahuasca is a psychoactive brew traditionally used by Indigenous Amazonian groups for healing and spiritual rituals. Prepared from Psychotria viridis, which contains N,N-dimethyltryptamine (DMT), and Banisteriopsis caapi, which contains reversible monoamine oxidase inhibitors, ayahuasca has attracted scientific interest because of its possible relevance to mood and anxiety disorders [1,2, 3]. This study examined the safety, tolerability, and possible clinical effects of a single oral dose of ayahuasca in oncology patients with clinically relevant anxiety and depressive symptoms.

This single-blind clinical trial included six women aged 18 to 60 years with a current or previous diagnosis of solid tumour cancer and clinically relevant mood and/or anxiety symptoms. Each participant received a single oral dose of ayahuasca (1 mL/kg). Primary outcomes were assessed using the Beck Depression Inventory-II (BDI-II), Patient Health Questionnaire-9 (PHQ-9), and Beck Anxiety Inventory (BAI) at baseline and 7, 14, and 21 days after dosing; some measures also included assessments at 5 hours and 3 months. Secondary outcomes included the Hospital Anxiety and Depression Scale (HADS), Beck Hopelessness Scale (BHS), Dysfunctional Attitudes Scale (DAS), sleep quality, pain intensity, dissociative symptoms, suicidality, cardiovascular parameters, and adverse events. Repeated-measures ANOVA assessed change over time, followed by paired t-tests against baseline where appropriate. Pearson correlations explored associations between symptom change and acute psychoactive effects. Statistical significance was set at p ≤ 0.05.

The sample included patients with breast (50.0%), cervical (33.3%), and ovarian cancer (16.7%); most met criteria for generalised anxiety disorder (n = 5) and major depressive disorder (n = 4). Significant time effects were observed for BDI-II (F₅,₂₅ = 4.54; p ≤ 0.01), PHQ-9 (F₄,₂₀ = 4.88; p ≤ 0.01), and BAI (F₅,₂₅ = 3.96; p ≤ 0.01). BDI-II scores decreased from 31 ± 4.71 at baseline, with significant reductions at 1 and 2 weeks. PHQ-9 scores were significantly reduced at 1, 2, and 3 weeks, whereas BAI scores were lower at 5 hours and 2 weeks. HADS-D (F₄,₂₀ = 10.51; p ≤ 0.01), HADS-A (F₄,₂₀ = 3.21; p = 0.03), DAS (F₄,₂₀ = 2.99; p = 0.04), and sleep quality (F₃,₁₅ = 7.96; p = 0.03) also showed significant time effects, whereas BHS and pain intensity did not. Forty-three adverse events were recorded, mainly drowsiness, difficulty concentrating, nausea, and gastrointestinal discomfort; all were mild to moderate and transient, and no serious adverse events were observed.

In conclusion, a single oral dose of ayahuasca was feasible and generally well tolerated in this small sample. Reductions in depressive and anxiety symptoms were observed across several outcome measures during follow-up. However, given the small sample size, single-blind design, and absence of a control group, these findings should be interpreted cautiously. Larger randomised controlled studies are needed to clarify safety, tolerability, and potential clinical effects in this population.

References

  1. Osório F de L, Sanches RF, Macedo LR, Santos RG, Maia-de-Oliveira JP, Wichert-Ana L, Araujo DB, Riba J, Crippa JA, Hallak JE. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Braz J Psychiatry. 2015 Jan-Mar;37(1):13-20. doi: 10.1590/1516-4446-2014-1496. PMID: 25806551.
  2. Palhano-Fontes F, Barreto D, Onias H, Andrade KC, Novaes MM, Pessoa JA, Mota-Rolim SA, Osório FL, Sanches R, Dos Santos RG, Tófoli LF, de Oliveira Silveira G, Yonamine M, Riba J, Santos FR, Silva-Junior AA, Alchieri JC, Galvão-Coelho NL, Lobão-Soares B, Hallak JEC, Arcoverde E, Maia-de-Oliveira JP, Araújo DB. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med. 2019 Mar;49(4):655-663. doi: 10.1017/S0033291718001356. Epub 2018 Jun 15. PMID: 29903051; PMCID: PMC6378413.
  3. Dos Santos RG, Osório FL, Rocha JM, Rossi GN, Bouso JC, Rodrigues LS, de Oliveira Silveira G, Yonamine M, Hallak JEC. Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial. J Clin Psychopharmacol. 2021 Sep-Oct 01;41(5):540-550. doi: 10.1097/JCP.0000000000001428. PMID: 34166299.