A critical review of brain entropy as a biomarker of the psychedelic state

Serotonergic psychedelics induce profound changes in consciousness, producing an altered state often referred to as the psychedelic state. The entropic brain hypothesis proposes that this state is marked by increased brain entropy (i.e., greater randomness in neural activity) which is assumed to reflect expanded phenomenal richness, or a broader range of accessible conscious contents. Given the numerous neuroimaging studies reporting heightened entropy under psychedelics, a substantial portion of the field has embraced entropy as a reliable biomarker of the psychedelic state. We argue that this view is inherently oversimplified and offer a more nuanced and comprehensive perspective. We first review evidence supporting the use of entropy metrics and discuss their potential utility. We then identify key empirical, methodological, and conceptual limitations associated with using brain entropy as a psychedelic biomarker, organized into four themes: (1) entropy alterations are not specific to psychedelics; (2) current entropy-based approaches do not accommodate multidimensional operationalizations of conscious states; (3) multiple entropy metrics exist, each with distinct interpretations and varying levels of mutual consistency; and (4) insufficient evidence supports the neurophenomenological equivalence between brain entropy and phenomenal richness. Although substantial questions remain about the validity of entropy-based biomarkers of the psychedelic state, we conclude that the concept warrants further investigation and offer practical suggestions for future research to address these limitations.