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

The entropic brain hypothesis suggests that brain entropy—the uncertainty in brain state distributions—increases during psychedelic states and other states of expanded consciousness, while decreasing in states of diminished consciousness. Many neuroimaging studies have reported heightened entropy under psychedelics, leading some to consider entropy a reliable biomarker of the psychedelic state. This paper argues that view is oversimplified. It reviews evidence for entropy metrics, then identifies four challenges: entropy changes are not specific to psychedelics; current methods do not capture multidimensional conscious states; multiple entropy metrics exist with different interpretations and limited consistency; and there is little evidence linking brain entropy directly to phenomenal richness. The authors conclude the concept warrants further investigation and offer suggestions for future research.

Study at a glance

Abstract

Serotonergic psychedelics induce profound alterations in consciousness, giving rise to an altered state commonly referred to as the psychedelic state. The entropic brain hypothesis proposes that brain entropy (i.e., the degree of uncertainty in the distribution of brain states) is elevated during the psychedelic state, as well as in other states characterized by an expanded breadth of phenomenal consciousness, whereas the opposite pattern is observed in states of diminished or absent consciousness. 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 may be 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 challenges associated with using brain entropy as a psychedelic biomarker, organized into four themes: (1) entropy alterations are not specific to psychedelics or other states of heightened phenomenal richness; (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) limited 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.