Predicting and exploring ayahuasca effects: Perception, mind-wandering, and EEG oscillations

Ayahuasca is a DMT-containing traditional Amazonian psychedelic that is increasingly used in religious, shamanic and therapeutic settings. Earlier research had shown that psychedelics can strongly alter perception, emotion, cognition and mystical-type experience, and EEG studies had repeatedly found broad frequency changes, especially reduced alpha power. However, ayahuasca’s effects on mind-wandering had not been explored, and the predictive value of baseline EEG for acute ayahuasca experiences remained unclear. The paper also notes that relationships between mind-wandering and EEG under psychedelics were largely unknown. Silva-Costa and colleagues therefore set out to examine how ayahuasca affects subjective psychedelic experience, mind-wandering and EEG oscillations, and whether baseline EEG activity can predict acute subjective responses. They also aimed to relate EEG changes to the reported experiences, with a particular focus on perception, mystical effects and internally directed thinking. The study is presented as the first to investigate ayahuasca-related mind-wandering together with neural correlates and EEG-based prediction of experience in a controlled laboratory design.

Silva-Costa and colleagues used a randomised, double-blind, placebo-controlled, parallel-arm design with two groups: ayahuasca and placebo. The study was approved by the relevant ethics committee and registered prospectively. Fifty healthy adults aged 18 to 60 years were recruited, with no previous ayahuasca experience. Exclusion criteria included schizophrenia-spectrum or bipolar disorder symptoms and substance misuse. After exclusions, 46 participants remained in the main sample. Participants received 1 mL/kg of ayahuasca or placebo orally. The ayahuasca was supplied by a Brazilian ayahuasca church and contained DMT together with beta-carbolines such as harmine, harmaline and tetrahydroharmine. The placebo was designed to mimic ayahuasca’s colour, taste and mild gastrointestinal effects using substances including caramel colourant, yeast, citric acid and zinc sulphate. The researchers assessed subjective psychedelic experience using the Hallucinogen Rating Scale (HRS) and the Mystical Experience Questionnaire (MEQ), and mind-wandering using the Amsterdam Resting-State Questionnaire (ARSQ). EEG was recorded with a 32-channel cap at baseline, 2 hours and 4 hours after administration, during 5-minute eyes-closed resting periods. The session lasted about 8 hours in a quiet hospital-based room, with participants resting on a bed or recliner and listening to a predefined music playlist. EEG preprocessing included band-pass and notch filtering, artefact removal using independent component analysis, interpolation of removed channels, visual epoch rejection, and exclusion of sleep epochs identified by sleep staging. Power spectra were calculated in delta, theta, alpha and beta bands across predefined brain regions as well as globally. Drug effects on subjective scales were tested with t-tests and Bonferroni correction. EEG effects were analysed with general linear mixed models using drug, time and their interaction, followed by Sidak-corrected pairwise comparisons. The authors also examined correlations between EEG and subjective measures, and whether baseline EEG predicted acute ayahuasca experience, using Spearman correlations with Bonferroni correction.

After exclusions, the final sample for the main analyses was 46 participants, although the sample was smaller for some questionnaire measures and EEG correlations. Ayahuasca produced broad subjective effects relative to placebo on the HRS. It significantly increased cognitive distortion, agitation, visual distortion, quality of experience and sensitive distortion, while security/control was not significantly changed. Several individual items also increased, including bodily, emotional, visual and unusual experiential items such as Body, Sad, Crying, Visual Synesthesia, Dream, Unconscious, Emotional Sounds, Breathe and Wavelike Experience. Ratings of having received placebo were reduced. On the MEQ, ayahuasca increased the total score and several domains, including Positive Mood, Transcendence of Time and Space, Ineffability, Mystical, Internal Unity and Sacredness, but not External Unity or Noetic Quality. The MEQ was completed by 37 participants. Ayahuasca also altered mind-wandering. On the ARSQ, completed by 36 participants, it increased Discontinuity of Mind, Visual Thought and Verbal Thought, while decreasing Planning. Specific items such as Feeling the Same, Thoughts under Control, Feeling Nothing and Feeling Bored were also reduced. The authors interpret this as a shift towards more fragmented but also more vivid and content-rich spontaneous thinking. EEG analyses showed that ayahuasca was associated with widespread oscillatory changes. The clearest finding was a global reduction in alpha power, particularly at +2 hours and still evident at +4 hours in several regions. There were also increases in fronto-medial delta, and in theta and beta over temporo-parieto-occipital regions depending on time and scalp location. More specifically, theta showed drug-by-time interactions in parietal and occipital regions, alpha decreased in frontal, temporal, parietal and occipital sites, and beta increased in occipital, right parietal and right temporal areas. Some comparisons were significant versus placebo, and the authors report effect sizes for the significant pairwise tests. Correlational analyses suggested that, under ayahuasca, mystical and content-related experiences were linked to EEG activity. MEQ factors were negatively associated with certain ARSQ items such as Feeling the Same and Feeling Nothing, and positively associated with Deep Thoughts and HRS Quality of Experience. For EEG-specific correlations, lower theta was associated with higher HRS Visual Synesthesia and Sad, and with higher MEQ Total, Positive Mood and External Unity. Lower posterior alpha was linked with Thoughts about Nothing, whereas Feeling Bored was positively correlated with right parietal theta. In the placebo condition, several correlations were also observed, including associations between alpha and Ease or Current Life, and between ARSQ items such as Planning or Sleepiness and EEG power. For prediction from baseline EEG, lower baseline theta was associated with higher acute somatic or interoceptive-type experiences, including Heartbeat, Rush and Somatic Awareness. Lower baseline beta was associated with higher HRS Happy. The authors note that these predictive correlations were exploratory and did not replicate all prior findings.

The authors argue that this is the first study to examine ayahuasca’s effects on mind-wandering, underlying EEG mechanisms and prediction of experience from baseline EEG. They interpret the findings as showing that ayahuasca alters not only perception and emotion but also the structure of spontaneous thought, increasing discontinuous, visual, verbal and content-laden mind-wandering while reducing planning. They also view the EEG findings as consistent with a state resembling visionary, dream-like or trance-like consciousness, particularly because alpha power was broadly reduced and frontal delta and temporo-parieto-occipital theta and beta were altered. In relation to earlier research, they state that the HRS and MEQ results broadly match previous reports with oral ayahuasca, inhaled or intravenous DMT and other classic psychedelics. They emphasise that the exploratory item-level findings add nuance, especially around bodily, emotional and consciousness-related changes. For mind-wandering, they compare the results with earlier LSD work and suggest that psychedelics may produce both chaotic and meaningful internal mentation. They also link the alpha suppression findings to earlier ayahuasca, DMT, LSD and psilocybin studies, and discuss potential parallels with wake-to-sleep transitions, meditation and hypnosis. For the EEG-experience correlations, the authors interpret the negative association between theta and mystical or visual experiences as supporting a role for theta in meaningful psychedelic states. They suggest that lower theta and higher alpha may relate to richer, more content-laden internal thought, and that placebo correlations reflect more typical brain-experience relationships that were altered under ayahuasca. They also interpret the baseline findings as suggesting that lower theta and beta may predispose to stronger interoceptive and positive emotional responses, although they say previous findings on baseline theta and mystical experience were not fully replicated. The authors acknowledge several limitations. Blinding was difficult despite participant naivety, and participants’ inexperience with ayahuasca may have affected how they interpreted scale items. Many EEG recordings were excluded because participants became sleepy, particularly in the placebo condition, which may have been influenced by the hospital setting and early morning procedures. They also note that the laboratory environment, with participants largely alone, differed from traditional group or ritual contexts, and that the ARSQ was administered 2 days later rather than immediately after rest, which may have affected reliability. Finally, the correlation analyses used smaller subsamples than the main drug analyses, so they emphasise that these correlations are exploratory rather than confirmatory. They suggest that EEG measures may eventually offer a practical and economical way to help predict ayahuasca responses and potentially support safer or more effective therapeutic use, but they frame this as a future possibility rather than a demonstrated clinical application.

The authors conclude that ayahuasca significantly altered perception, especially visual, bodily, emotional and mystical experience, and also changed mind-wandering towards more discontinuous, uncontrolled and content-rich thinking. They summarise the EEG findings as showing reduced alpha and increased frontal delta plus temporo-parieto-occipital theta and beta. In their final interpretation, lower theta and higher alpha were linked to more meaningful subjective experiences, while lower baseline theta and beta may predict stronger interoceptive and positive emotional responses, with possible implications for using EEG as a predictor of psychedelic effects.