Ayahuasca and Salvia divinorum as contrasting modes of consciousness reorganization: Implications for psychedelic-assisted psychotherapy
Year: 2026
Type: article
Abstract: Background and aims Contemporary psychedelic science has focused predominantly on serotonergic compounds such as psilocybin and ayahuasca which act primarily via 5-HT 2A receptors. They are associated with characteristic patterns of large-scale brain network organization and elicit similar subjective experiences. By contrast, Salvia divinorum , whose active compound salvinorin A is a potent and selective kappa-opioid receptor (KOR) agonist, remains marginal to prevailing models of psychedelic action. This review compares these entheogens as distinct neurophenomenological pathways into altered states of consciousness. Methods This is a comparative, non-empirical review integrating evidence from Indigenous ritual frameworks, pharmacology, human and preclinical studies, phenomenology, and systems neuroscience. Results Ayahuasca exemplifies serotonergic psychedelic action, characterized by reduced default mode network coherence, increased cross-network connectivity, and emotionally and symbolically rich experiences, alongside emerging evidence for antidepressant effects within psychedelic-assisted psychotherapy. In contrast, S. divinorum produces a rapid and short-lived state marked by KOR-mediated modulation of dopaminergic and glutamatergic systems, with prominent effects on interoception, body ownership, and sensory integration. Recent findings suggest that salvinorin A alters large-scale functional connectivity, but in a manner distinct from serotonergic psychedelics, and is associated with a qualitatively distinct pattern of large-scale network coordination together with a phenomenology of disembodiment and discontinuity. Conclusions These profiles represent distinct modes of consciousness reorganization through suspension of the brain's self-model: serotonergic psychedelics through integrative expansion, and KOR agonism through destabilization and rupture. Within psychedelic-assisted psychotherapy, therapeutic change may arise through both integrative and disruptive mechanisms. While serotonergic approaches are advancing toward clinical translation, carefully controlled research on S. divinorum may be warranted.
Source: Journal of Psychedelic Studies
Author: Brian M. Ross
Institution: NOSM University
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: diamond
OpenAlex ID: W7202362192