Autonomic nervous system activity correlates with peak experiences induced by DMT and predicts increases in well-being

Psychedelics produce marked alterations in perception, cognition and emotion, and intensely positive self‑transcendent or 'peak' experiences that occur during psychedelic therapy have been shown in earlier research to predict beneficial mental health outcomes such as reductions in depression, anxiety and substance craving. Despite the clinical relevance of these peak states, the biological mechanisms that produce them remain unclear; work to date has concentrated on central nervous system effects while largely overlooking peripheral bodily systems. The autonomic nervous system (ANS), which comprises sympathetic (SNS) and parasympathetic (PNS) branches and exerts strong influence over cardiac function, is increasingly recognised as important in emotional processing and may be implicated in the affective qualities of psychedelic experiences. Bonnelle and colleagues set out to test whether cardiac indices of SNS and PNS activity relate to subjective peak experiences evoked by the short‑acting psychedelic N,N‑dimethyltryptamine (DMT). Specifically, they hypothesised that (1) individuals who begin the session from a state of greater sympatho‑vagal balance would be more likely to report peak experiences, and (2) peak experiences during DMT would be associated with concurrent sympatho‑vagal coactivation (joint SNS and PNS influence). The study used the brief timecourse of DMT to link minute‑by‑minute autonomic measures with self‑reported phenomenology and subsequent changes in wellbeing.

The study was a single‑blinded, placebo‑controlled experimental trial in healthy volunteers. Participants underwent continuous simultaneous fMRI‑EEG resting‑state scanning for 28 minutes, with DMT or placebo administered at the end of the eighth minute; they lay with eyes closed and ECG was recorded throughout. After scanning, participants completed retrospective questionnaires indexing altered states (the 11‑Dimension Altered States of Consciousness questionnaire, ASC‑11D, and the Mystical Experience Questionnaire, MEQ‑30) and a wellbeing measure (WHO‑5) at baseline and two weeks post‑session. A second session with in‑scanner verbal intensity ratings is noted in the protocol, but the present report concerns ECG data from the uninterrupted resting‑state scans. Twenty participants with prior psychedelic experience completed visits, but only 17 (11 males; mean age 33.8 y, SD 8.3) provided ECG recordings with <10% noisy segments and were included. ECG was recorded with two electrodes and an MR‑compatible amplifier at 5 kHz with a 250 Hz hardware low‑pass filter. Recordings lasted 28 minutes (8 minutes baseline, 20 minutes post‑injection). Preprocessing involved demean and 1–30 Hz bandpass filtering, automatic R‑peak detection in Kubios followed by manual inspection and correction; datasets with >10% noisy segments were discarded. Autonomic indices were computed in Kubios from overlapping 180 s RR‑interval windows updated every 20 s. A composite SNS index used mean heart rate, Baevsky's stress index and the Poincaré plot SD2; a PNS index used mean RR interval, RMSSD and Poincaré SD1. Sympatho‑vagal balance was indexed by SD1/SD2 from the Poincaré plot, and sympatho‑vagal coactivation was operationalised as the product of the SNS and PNS indexes (SNSxPNS), transformed into strictly positive values. The authors focused analyses on a post‑onset 'core' window (minutes 11–25, i.e. ~3 minutes after injection onward) and a baseline window (minutes 3–7 of the recording), reflecting the timing of autonomic and subjective effects. Statistical analyses visualised timecourses averaged across participants and used paired t‑tests to compare DMT and placebo at each timepoint. After checking normality, Spearman correlations assessed relations between ANS measures and ASC‑11D subscales; significance was set at p < .05 two‑sided, with Bonferroni correction applied for correlations that were not predicted. Minute‑by‑minute correlations between ANS indexes and subjective ratings were also computed to localise effects in time. For longer‑term wellbeing analyses, participants were split by median change in WHO‑5 from baseline to two‑week follow‑up and SNSxPNS during the core experience was compared between groups via independent t‑test. Where procedural details (for example DMT dose) were relevant but not provided in the extracted text, the extraction does not clearly report them.

Timecourse of autonomic activity: SNS and PNS indexes were plotted across the 8 minute baseline and 20 minute post‑injection periods and compared between DMT and placebo. SNS increased and PNS decreased significantly in the DMT condition relative to placebo from the time of injection. SNS remained significantly higher than placebo for 11 minutes post‑injection, while PNS remained significantly lower for 8 minutes. Primary associations with subjective peak experiences: The sympatho‑vagal coactivation index (SNSxPNS) computed during the core DMT experience correlated strongly with two ASC‑11D subscales linked to peak experiences. Specifically, SNSxPNS correlated with Spiritual Experience (n=17, Spearman r = .625, p = 0.007, uncorrected) and with Insightfulness (n=17, r = .692, p = 0.002, uncorrected). These relations were highlighted as central findings. SNS and PNS separately: During the core experience, SNS activity showed positive correlations with Experience of Unity (n=17, r = .517, p = 0.034) and Elementary Imagery (n=17, r = .528, p = 0.035), and negative correlations with Impaired Control and Cognition (r = −.590, p = 0.013) and Anxiety (r = −.514, p = 0.034). The authors note that these latter relations were not explicitly predicted and did not survive correction for multiple comparisons. PNS showed generally weaker and often inverse relationships compared with SNS. Temporal specificity (minute‑by‑minute): Minute‑by‑minute correlations revealed that SNS was positively associated with Experience of Unity from approximately minutes 2–17 post‑injection and with Elementary Imagery from minutes 1–17. SNS was negatively associated with Impaired Cognition from minutes 2–15 and with Anxiety from minutes 4–10. PNS exhibited weaker, often opposite trends, with negative correlations with Experience of Unity appearing around minutes 15–17 and positive correlations with Anxiety around minutes 5–8. The SNSxPNS index correlated significantly with Spiritual Experience between minutes 4–13 post‑injection, and with Insightfulness both at a pre‑injection baseline window (minutes −5 to −3, peaking at −3) and later around minutes 12–13 (peaking at minute 13). Baseline sympatho‑vagal balance predicts peak quality: Baseline SD1/SD2 (Poincaré‑derived sympatho‑vagal balance) related to Spiritual Experience (n=17, r = .555, p = 0.021) and showed a marginal relationship with Insightfulness (r = .413, p = 0.099). Individuals with baseline SD1/SD2 closer to 1 (interpreted as a more balanced ANS) scored higher on Spiritual Experience. Baseline SNS and PNS indexes alone did not predict subjective ratings. Relation to wellbeing two weeks later: Wellbeing (WHO‑5) change scores were available for 16 participants and a median split produced two groups (Group 1: no change or reduction in wellbeing, n=8, mean change −1.50 ± 1.6; Group 2: improved wellbeing, n=8, mean change 1.62 ± 0.91). Group 2 reported higher Blissful Experience than Group 1 (t = 2.7, df = 14, p = 0.017). Importantly, during the core experience Group 2 showed higher SNSxPNS coactivation than Group 1 (t = 2.32, df = 14, p = 0.036), whereas SNS and PNS alone did not differ between groups.

Bonnelle and colleagues interpret their results as evidence that both sympathetic and parasympathetic branches of the ANS are involved in key elements of psychedelic‑induced peak experiences, particularly Spiritual Experience and Insightfulness. The sympatho‑vagal coactivation index (SNSxPNS) during the DMT session was a stronger predictor of subsequent improvements in wellbeing than retrospective subjective reports alone. Contrary to the authors' expectation that negatively valenced experiences would be linked to parasympathetic withdrawal, negative elements were instead associated with reduced SNS engagement during the core experience. The discussion situates these findings relative to limited prior work on psychedelics and cardiac autonomic activity, noting methodological gaps in earlier studies (for example sparse HRV sampling and lack of baseline measures). The authors propose that sympatho‑vagal coactivation may index a physiological state conducive to peak experiences and suggest potential translational applications, including biofeedback or behavioural techniques (for instance breathing practices) to steer the ANS toward favourable states prior to or during psychedelic‑assisted therapy. They also link the baseline balance finding to contemplative practices, suggesting that training which increases sympatho‑vagal balance might prepare individuals for deeper experiences. Caveats and future directions acknowledged by the investigators include ambiguity about causality between ANS and central nervous system changes — it remains unclear whether ANS changes drive phenomenology or follow central processes — and the need to compare ANS timecourses with EEG or fMRI to address this. They further recommend complementing cardiac measures with other autonomic indices such as electrodermal activity, pupillometry or piloerection. The authors caution that sympatho‑vagal coactivation is not specific to positive peak experiences and can occur in other states (for example freezing or certain panic presentations); they note theories that subdivide parasympathetic function (ventral versus dorsal branches) as a possible explanatory nuance. Overall, the researchers conclude that DMT produced a pronounced sympathetic activation that paralleled subjective intensity and that both the initial physiological stress response and the subsequent balance between stress and recovery are important components of peak experiences and improved wellbeing; they propose further work to validate physiological markers of 'readiness' and to test whether these findings generalise to other psychedelics and non‑drug altered states of consciousness.