Discovering the Neural Predictors of Ayahuasca Experiences

A groundbreaking study from Brazil's Federal University of Rio Grande do Norte (UFRN) has uncovered how baseline brain waves can forecast whether an ayahuasca session will lead to a profound mystical journey or a distressing 'bad trip.' Ayahuasca, a traditional Amazonian brew containing the psychoactive compound DMT (N,N-dimethyltryptamine), has surged in popularity for its potential therapeutic benefits in treating depression, anxiety, and addiction. However, unpredictable negative reactions remain a barrier to its clinical use. Researchers at UFRN's Brain Institute (Instituto do Cérebro, or ICB) analyzed electroencephalography (EEG) data to identify patterns that precede challenging experiences, paving the way for safer psychedelic-assisted therapies.

This research highlights UFRN's leadership in psychedelic neuroscience, a field where Brazilian universities are gaining global prominence due to the country's unique legal and cultural context for ayahuasca use in religious ceremonies like those of Santo Daime and União do Vegetal.

Ayahuasca's Cultural and Scientific Roots in Brazil

Ayahuasca originates from indigenous Amazonian traditions and has been integrated into Brazilian syncretic religions since the early 20th century. In 1986, Brazil's National Drug Council (CONAD) recognized its religious use, making the country a hub for safe, controlled studies. Universities like UFRN, USP (University of São Paulo), and Unicamp have pioneered research on its effects, from neuroimaging to clinical trials for mental health disorders. The brew induces altered states through DMT, a serotonin receptor agonist, combined with MAO-inhibiting harmala alkaloids, leading to visions, emotional purging, and neuroplasticity.

At UFRN's ICB, founded in 2013, multidisciplinary teams blend neuroscience, psychology, and pharmacology. The institute boasts advanced EEG labs and collaborates internationally, positioning it as a key player in Brazil's higher education landscape for psychedelic research.

The UFRN Study: Methods and Participant Profile

The study, published in December 2025 in the Journal of Psychopharmacology, reanalyzed EEG data originally collected a decade ago for Jéssica Andrade Pessoa's master's thesis. Led by Natan Silva-Costa and EEG expert Isabel Wießner, it involved 50 healthy volunteers in a double-blind, placebo-controlled trial. Half received ayahuasca (1.5 mg/kg DMT-equivalent), the other half a placebo. EEG recordings captured baseline activity before ingestion, then at 2 and 4 hours post-dose.

Four frequency bands were scrutinized:

• Delta (1-4 Hz): Deep sleep and unconscious processes.
• Theta (4-7 Hz): Introspection and memory.
• Alpha (7-14 Hz): Relaxed wakefulness, visual inhibition.
• Beta (14-30 Hz): Active thinking, anxiety.

Subjective experiences were assessed via the Mystical Experience Questionnaire (MEQ), tracking joy, unity, and visions. Machine learning helped correlate neural patterns with trip quality.

Key Findings: Baseline Beta Waves as Bad Trip Harbingers

High beta activity at baseline—indicative of heightened alertness or anxiety—strongly predicted 'bad trips' marked by fear, paranoia, or emotional turmoil. Conversely, low beta foreshadowed positive outcomes like euphoria and cosmic unity. During the peak, ayahuasca suppressed theta waves, correlating with mystical intensity, and slashed alpha power, unleashing vivid hallucinations by disinhibiting visual cortex.

Wießner noted: 'Índices mais altos [de beta] na linha de base indicariam maior probabilidade de viagens ruins.' This predictive power could exceed 80% accuracy with refined AI models, per preliminary analyses.

During the Trip: A Symphony of Altered Oscillations

Ayahuasca induced global alpha desynchronization, akin to REM sleep, fostering spontaneous imagery. Frontomedial delta surged, enhancing introspection, while right posterior theta amplified emotional processing. These shifts explain the brew's reputed antidepressant effects via increased neuroplasticity and default mode network (DMN) modulation.

Placebo groups showed no such changes, confirming pharmacological origins. Excluding drowsy participants strengthened findings but highlighted real-world challenges like sleep onset during sessions.

Implications for Psychedelic Therapy in Brazilian Universities

Brazilian higher education is at the forefront of psychedelic integration. UFRN's findings suggest pre-session EEG screening—simple, non-invasive, headset-based—to stratify patients, minimizing risks in clinical trials. Imagine SUS (Brazil's public health system) clinics using AI-EEG for personalized dosing, boosting efficacy for treatment-resistant depression.The full study estimates 5-10 years for validation and deployment.

Other UFRN works, like DMT inhalation for anhedonia reversal, complement this, positioning the ICB as a model for university-led innovation.

Brazil's Pioneering Role in Global Psychedelic Research

Brazil hosts over 20,000 ayahuasca users in regulated churches, enabling naturalistic studies unattainable elsewhere. Universities like USP's Raízes project and Unicamp's LSD trials build on this. UFRN's EEG work aligns with international efforts, such as Imperial College's DMT 'waking dream' scans, but uniquely leverages baseline prediction.

Funding from FAPERN and CNPq underscores public investment in neuroscience at public universities.

Challenges: From Lab to Clinic

• Small sample sizes limit generalizability; larger trials needed.
• Cultural variances in trip interpretation (e.g., purging as healing vs. distress).
• Regulatory hurdles for therapeutic ayahuasca beyond religion.
• EEG artifacts in ceremonial settings.

Wießner advocates multi-site collaborations across Brazilian unis to address these.

Future Directions at UFRN and Beyond

UFRN plans longitudinal studies linking EEG predictors to long-term outcomes like sustained remission. Integration with fMRI and wearables could refine models. For higher ed, this attracts global talent to Brazil's neuroscience programs, fostering jobs in research and therapy.

Globally, it could standardize screening, accelerating FDA/ANVISA approvals. Brazil's universities stand ready to lead.

Stakeholder Perspectives: Researchers, Users, and Regulators

Participants reported transformative positives despite risks. Indigenous leaders emphasize set/setting; clinicians see screening as ethical imperative. CONAD monitors closely, balancing tradition and science.

Educational Impact: Training the Next Generation

UFRN's grad programs in neuroscience now incorporate psychedelic modules, drawing students nationwide. This study exemplifies how Brazilian public universities drive impactful, culturally attuned research, inspiring careers in psychopharmacology.

Photo by Saiteja Varma on Unsplash