Altered State of Consciousness and Mental Imagery as a Function of N, N-dimethyltryptamine Concentration in Ritualistic Ayahuasca Users

Ayahuasca is a traditional Amazonian plant brew combining Psychotria viridis (containing the psychedelic N, N-dimethyltryptamine, DMT) and Banisteriopsis caapi (containing β-carboline monoamine‑oxidase inhibitors such as harmine, harmaline and tetrahydroharmine). Earlier research has shown that DMT and related serotonergic 5HT2A agonists produce pronounced alterations in perception, visual phenomena and ‘‘entheogenic’’ or spiritual experiences. Neuroimaging and pharmacological studies have linked mental imagery and perceptual alterations to brain networks that are rich in 5HT2A receptors, and prior work suggests that psychedelics acutely alter default mode network connectivity, increase bottom‑up sensory influence, and change cognitive control processes relevant to imagery, creativity and flexible cognition. Ramaekers and colleagues designed an observational, baseline‑controlled, within‑subject study in experienced Santo Daime ritual participants to test whether acute ayahuasca intake enhances mental imagery and whether such effects scale with peak serum DMT concentration. The investigators measured altered states of consciousness and several objective and subjective indices of mental imagery and related cognitive processes on two consecutive days: a sober baseline day and a day on which participants self‑administered their usual ayahuasca dose. The primary hypothesis was that ayahuasca would increase mental imagery, particularly in individuals with higher peak DMT concentrations.

This was a within‑subject, fixed‑order observational study enrolling 24 experienced Santo Daime members (14 males, 10 females). Exclusion criteria reported in the extracted text included MRI contraindications (ferromagnetic implants), pregnancy, and use of medicinal or other substances within the previous 24 hours. Participants had a mean (SD) age of 55.2 (10.2) years, mean membership duration of 14.2 (8.3) years and a mean (SD) reported attendance of 563 (650) ceremonies; mean weight was 75.5 (12.6) kg. Ethical procedures were followed although the extraction cuts off mid‑sentence where the ethics statement appears. Participants attended two consecutive test days. On Day 1 they were sober (baseline); on Day 2 they drank a self‑selected volume of ayahuasca equivalent to their usual dose (mean 24 ml, SD 8.16, range 11–40 ml) prepared by the Church from a single batch. Ceremonies were communal and supervised by the church; the research team did not organise dosing or production. The brew was analysed by LC‑MS and contained 0.14 mg/ml DMT, 4.50 mg/ml harmine, 0.51 mg/ml harmaline and 2.10 mg/ml tetrahydroharmine. Venous blood was sampled approximately 60 and 160 minutes after intake to assess serum alkaloid concentrations; MRI scans were obtained but imaging results are reported elsewhere. Cognitive tests and questionnaires were administered between 150 and 210 minutes after drinking. Outcome measures included the 5‑Dimensional Altered States of Consciousness Questionnaire (5D‑ASC) and the Ego Dissolution Inventory (EDI) for subjective altered states. Mental imagery and cognition were assessed with the Vividness of Visual Imagery Questionnaire (VVIQ, eyes open/closed), an Ambiguous Image Perspective Switching Task (three classic bistable images), the Cognitive Flexibility Scale (CFS), and a Chain Free Association Task (CFAT) with forward‑flow semantic distance and fluency measures derived from large corpora. Parallel versions of CFAT were used across test days; other tasks used the same versions. Statistical analysis used linear mixed models (restricted maximum likelihood) with a first‑order autoregressive residual covariance structure; condition was a fixed effect and a random intercept was included. Pearson correlations examined relationships between self‑selected dose, peak serum concentrations (Cmax) of DMT and β‑carbolines, and behavioural/subjective measures. The study was powered pragmatically for up to 24 participants, based on prior within‑subject studies showing effects with 6–18 participants.

Self‑selected doses of ayahuasca ranged from 11 to 40 ml (mean 24 ml). Measured peak serum concentrations of DMT and β‑carbolines varied substantially across individuals, and importantly individual dose was not significantly correlated with peak DMT or β‑carboline concentrations, suggesting interindividual pharmacokinetic variability. Subjective measures of altered consciousness showed robust increases under ayahuasca. All five key 5D‑ASC dimensions increased (t = 3.79–8.23; df = 23; p < .001) and the EDI increased (t = 7.89; df = 23; p < .001). The EDI correlated strongly with total 5D‑ASC score (r = .75; p < .001). Mean ratings for oceanic boundlessness, visual restructuralization and ego dissolution were the most affected (approximately 30–40% of the maximal score), with some individuals reporting maximal ratings of 70–100%. Individual peak DMT concentration correlated positively with oceanic boundlessness (r = .47; p = .023), visual restructuralization (r = .58; p = .004), and ego dissolution (r = .52; p = .012). Peak harmaline showed a modest correlation with EDI (r = .41; p = .048). No significant correlations were observed between self‑selected dose and subjective measures. Measures related to mental imagery showed limited group‑level change. The number of perspective shifts on ambiguous images, vividness on the VVIQ, and associative measures from the CFAT did not differ significantly between baseline and the ayahuasca condition. Mean word fluency in the CFAT under ayahuasca was higher than baseline but narrowly missed significance (F(1, 22.3) = 4.02; p = .057). Cognitive flexibility ratings decreased under ayahuasca versus baseline (F(1, 22.5) = 4.91; p = .037; partial η2 = .17). At the individual level, perspective shifts correlated positively with peak DMT concentration (r = .56; p = .007). Conversely, cognitive flexibility ratings correlated negatively with peak DMT (r = -.42; p = .042) and peak harmine (r = -.45; p = .032). No other significant correlations between alkaloid Cmax and mental imagery measures were reported.

Ramaekers and colleagues interpret the results as confirming that DMT is the principal constituent in ayahuasca driving core phenomenological features of the acute experience: oceanic boundlessness, visual restructuralization and ego dissolution all increased under ayahuasca and scaled with peak DMT concentrations in serum. The lack of correlation between self‑selected dose and serum alkaloid concentrations led the investigators to emphasise interindividual differences in absorption and metabolism, and they note the need for standardised pharmacokinetic studies to characterise dose–concentration relationships for ayahuasca. Despite clear subjective psychedelic effects, the study found only limited and mixed effects on mental imagery and imagery‑related cognition at the group level. Cognitive flexibility decreased under ayahuasca and individual differences in perspective shifting and cognitive flexibility related to peak DMT (positive for perspective shifting, negative for flexibility). The authors suggest two non‑exclusive explanations for the generally modest effects on imagery in this sample. First, the cohort consisted of highly experienced Santo Daime users (mean reported attendance 563 ceremonies), and long‑term familiarity with the ayahuasca state could result in psychological coping or reduced distraction during tasks. Second, neuroadaptive changes such as reduced 5HT2A receptor density or signalling after repeated psychedelic exposure might blunt acute cognitive effects; the authors cite preclinical evidence for receptor downregulation and draw a parallel to selective tolerance seen with other drugs. The discussion acknowledges further complexities: some cognitive enhancements related to psychedelics have been reported subacutely rather than acutely, and prior imaging work suggests acute decreases but postacute increases in default mode network connectivity and other neurochemical changes that could underpin delayed cognitive or psychological effects. Key limitations are noted: the fixed test order (baseline always preceding ayahuasca) introduces potential learning or order effects, though parallel task versions and the detection of some impairments argue against a simple practice effect explanation. The study used structured, closed assessments and did not collect open‑ended descriptions of imagery or subacute wellbeing measures, limiting insight into qualitative or longer‑term outcomes. Finally, the authors reiterate that evaluating blood concentration rather than nominal dose may be more informative for predicting 5HT2A receptor occupancy and subjective intensity across individuals.