Ayahuasca Shifts Brain Dynamics Toward Higher Entropy: Persistent Elevation of Ising Temperature Correlates with Acute Subjective Effects

Abstract

Serotonergic psychedelics profoundly alter high-order cognition, emotion, and sensory perception, creating dynamic, unpredictable brain states consistent with the entropic brain hypothesis. Although these acute effects are short-lived, users often experience lasting improvements in emotional and social functioning. Yet, few studies have quantitatively linked subjective experiences to neural dynamics. To bridge this gap, we investigate the acute and subacute effects of ayahuasca using fMRI data and the 2D Ising model, estimating the Ising brain temperature to quantify the shift from ordered to disordered resting state configurations and expose the critical transitions that characterize ayahuasca-induced brain dynamics. To complement our analysis, we investigated cortical functional connectivity changes through graph-theoretical metrics, quantifying how psychedelic ingestion alters functional network architecture in acute and subacute phases. Only the Ising temperature reliably differentiated the subacute phase. Applying a recently developed method that combines cortical connectivity analyses with Graph Neural Networks trained on Ising networks, our results robustly revealed significant Ising temperature increases during the acute (p < 0.001) and subacute (p < 0.05) phases compared with placebo, reflecting heightened brain entropy and a persistent shift toward a more disordered, paramagnetic state. To evaluate longer-term effects, the subacute temperature change correlated linearly with affective scores on the Hallucinogenic Rating Scale (HRS) captured during the acute session (p < 0.01), with HRS scores explaining substantially greater variance in the subacute group (adjusted R2 = 0.58) than in the placebo group (adjusted R2 = -0.05). These observations suggest that ayahuasca elevates system entropy and that the magnitude of lasting functional alterations scales with the intensity of the acute subjective experience.