- DMT/harmine reduced EEG microstate duration while increasing microstate occurrence and complexity compared with harmine and placebo.
- First-order Markov analysis showed transition sequences became less random and more predictable under DMT/harmine.
- Results support models of increased metastability and signal diversity, revealing a more diverse repertoire of neural state sequences in the psychedelic peak.
J Psychopharmacol. 2026 Sep 22:2698811261481062. doi: 10.1177/02698811261481062. Online ahead of print.
ABSTRACT
BACKGROUND: Psychoactive serotonin 5-HT2A receptor agonists are potent modulators of awareness. Influential theories propose that psychedelics alter whole-brain dynamics by increasing neural signal diversity and dynamic flexibility. Beyond temporal variability, it is an open question whether psychedelics impact the characteristics of transient neural state sequences themselves.
AIMS: Our goal was to assess how an ayahuasca-inspired formulation (intranasal N,N-Dimethyltryptamine (DMT) and buccal harmine) modulates parameters of neural state sequences close to the peak of the psychedelic state.
METHODS: In a double-blind, randomised, placebo-controlled Electroencephalography (EEG) study, participants (n = 25) were administered the following interventions on separate testing days: (1) a DMT/harmine formulation; (2) harmine alone and (3) a placebo. We used EEG microstate analysis to compare the neural dynamics between the three conditions.
RESULTS/OUTCOMES: Compared to harmine and placebo, DMT/harmine was linked to reduced microstate duration but increased microstate occurrence and complexity. Higher first-order Markov statistics revealed that transition sequences became less random when DMT/harmine was administered.
CONCLUSIONS/INTERPRETATION: Our finding that DMT/harmine is associated with more complex and predictable neural state sequences as well as accelerated state transitions is consistent with models of increased metastability and signal diversity. By revealing a more diverse repertoire of neural state sequences under DMT/harmine, our findings improve our understanding of neural dynamics in psychedelic states.
CLINICAL TRIAL REGISTRATION: Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-DMT and harmine in healthy subjects. https://clinicaltrials.gov/ct2/show/NCT04716335.
PMID:42768932 | DOI:10.1177/02698811261481062
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