Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members

Ayahuasca is a traditional psychoactive brew prepared from Banisteriopsis vines combined with leaves containing N,N-dimethyltryptamine (DMT); indigenous and syncretic religious groups in South America, notably Santo Daime, Barquinha and União do Vegetal, use it as a sacrament and healing tool. The brew contains beta-carbolines such as harmine, harmaline and tetrahydroharmine (THH) that inhibit monoamine oxidase A (MAO-A) and can also affect serotonin reuptake, thereby allowing orally administered DMT to reach the central nervous system. Previous biomedical observations in long-term users have reported apparent improvements in mood, social functioning and peripheral serotonergic markers, but there remain few studies that apply rigorous experimental methods to test acute psychological effects. This study set out to examine whether acute ayahuasca ingestion modifies psychometric measures related to anxiety, panic-like symptoms and hopelessness in long-term members of a Santo Daime community. Using a double-blind, placebo-controlled, crossover protocol, the investigators assessed state- and trait-anxiety (STAI), panic-like sensitivity (ASI-R) and hopelessness (Beck Hopelessness Scale) in volunteers with at least ten years’ use of ayahuasca within the church context, testing the hypothesis that the brew’s pharmacology might attenuate these affective measures.

Nine healthy volunteers (six males, three females), aged 35–56 and all long-term Santo Daime members (minimum ten years of use at about once every two weeks), were enrolled after informed consent. Exclusion criteria included history of hypertension, diabetes or cardiac disease, current treatment with antipsychotics/anxiolytics/antidepressants/mood stabilisers or amphetamine-related appetite suppressants, and pregnancy or breastfeeding. Participants were requested to avoid alcohol and other drugs for 24 h before testing; five individuals had, however, consumed ayahuasca 6–22 h before data collection and these instances were not treated differently in analyses. The protocol received university ethics approval and followed the Declarations of Helsinki and Tokyo. A 2-litre standard sample of Santo Daime ayahuasca (Banisteriopsis caapi plus Psychotria viridis leaves) was used for all active doses. To blind participants, the active brew and a vehicle-control solution shared the same grape juice, cherry essence and artificial sweetener admixtures. The vehicle-control contained mineral water rather than ayahuasca, but to impart ayahuasca flavour during experimental sessions a small amount of the brew (60 ml per litre) was added to the vehicle used in those sessions so that each 50 ml placebo dose contained roughly 3 ml ayahuasca; solutions were served in opaque cups in a double-blind fashion. Chemical profiling of a 500 ml sample was performed by gas chromatography–mass spectrometry (GC–MS) to identify principal alkaloids. Psychological assessment employed the State–Trait Anxiety Inventory (STAI) for state and trait anxiety, the Anxiety Sensitivity Index–Revised (ASI-R, Brazilian version) for panic-like sensitivity, and the Beck Hopelessness Scale (BHS) for hopelessness. A preparatory, non-blinded pre-treatment ritual was conducted in which all participants received the inert vehicle solution while seated and chanting; questionnaires were handed out 1 h after ingestion to match the typical 60–120 min window of ayahuasca’s peak effects. The experimental phase used a within-subject, crossover design with two weekly sessions. In the first experimental session five participants received full ayahuasca and four received the ayahuasca-flavoured vehicle; in the second session the treatments were swapped. Questionnaires were randomised across participants to reduce timing bias. Statistical analyses used t-tests to assess order effects and treatment effects on change scores (each experimental score minus baseline), with significance set at P < 0.05.

GC–MS analysis identified the expected constituents of ayahuasca in the sample: the beta-carbolines harmine, tetrahydroharmine (THH), harmaline and harmol, together with N,N-dimethyltryptamine (DMT). Initial t-tests found no significant order-of-ingestion effects on any outcome, so data from the two experimental sessions were pooled. Change scores were computed by subtracting baseline (pre-treatment) values from experimental-session values; the authors defined a positive change score as a reduction in the measured symptom. Comparing change scores between vehicle and ayahuasca conditions, t-tests indicated significant reductions for panic-like related signs (ASI-R) with t(8) = 7.84, P < 0.001, and for hopelessness (BHS) with t(8) = 6.20, P < 0.001. By contrast, there were no statistically significant changes in trait-anxiety (STAI-trait), t(8) = 1.01, P = 0.2, or state-anxiety (STAI-state), t(8) = 0.64, P = 0.5. The authors present mean change values graphically, but the extracted text reports only the statistical tests and associated t and P values. The sample size for all analyses was nine participants.

Santos and colleagues interpret their findings to mean that an acute dose of Santo Daime ayahuasca produced measurable reductions in psychometric indices of hopelessness and panic-like sensitivity in long-term church members, while leaving state and trait anxiety scores unchanged. They link these acute effects to the brew’s pharmacology: beta-carbolines in ayahuasca (harmine, harmaline, THH) inhibit MAO-A and, in the case of THH, may inhibit serotonin reuptake, thereby increasing central monoaminergic activity; DMT is a 5-HT2A/2C agonist and may contribute to anxiolytic effects via serotonergic mechanisms. The investigators caution that the sample consisted of experienced users and long-term members of a religious community who may have begun the study with relatively low anxiety, limiting the scope for anxiolytic effects to be detected. They also acknowledge that participants’ expectations and the ritual context—set and setting—could have contributed to the observed psychological changes, and that the acute psychological effects of ayahuasca (euphoria, visions, insights, mystical-type experiences) might themselves produce beneficial mood effects independently of pharmacology. The authors note the complexity of ayahuasca’s action across multiple receptor subtypes, which could produce mixed anxiogenic and anxiolytic influences that cancel out for some measures. Finally, the paper emphasises caution in generalising the findings to clinical populations: none of the volunteers met criteria for panic disorder or pathological depression, so clinical implications remain speculative. The researchers recommend further work with ayahuasca-naïve participants, attention to dose and product consistency, and careful management of extrapharmacological variables if the therapeutic potential of ayahuasca-like substances is to be explored rigorously.