Ayahuasca-Inspired DMT/HAR Formulation Reduces Brain Differentiation Between Self and Other Faces

Background

Psychedelics are known to profoundly alter perception and self-referential processing, yet their specific effects on face recognition -particularly regarding recognition of face familiarity-remain underexplored.

Objective

This study investigates the effects of an ayahuasca-inspired novel DMT/HAR (N,N-dimethyltryptamine/Harmine) formulation and Harmine alone on face recognition and self-referential processing, as measured by event-related potentials (ERPs) and subjective behavioral measures.

Methods

In a within-subject, double-blind, placebo-controlled design, 30 healthy male participants underwent EEG recording during a visual oddball task involving Self, Familiar, and Unknown Faces. The study compared the effects of a DMT/HAR formulation, harmine alone, and placebo on key visual ERP components: P1, N170, and P300.

Results

DMT/HAR enhanced early visual processing (P1) but attenuated structural encoding (N170) across all face categories, suggesting altered perceptual integration. Crucially, DMT/HAR selectively reduced P300 amplitudes for self-faces, blurring the neural differentiation between self-other faces at posterior sites. Concurrently, frontal electrodes showed increased self-face responses and decreased unknown-face responses, indicating a dynamic reorganization of self-referential salience rather than a general dissolution of self-boundaries. Familiar face processing remained stable across conditions, suggesting that socially meaningful representations were preserved despite psychedelic-induced perceptions shifts.

Conclusion

These findings reveal that psychedelics reshape self-referential processing by balancing perceptual instability with compensatory cognitive mechanisms, leading to a restructuring rather than an erasure of self-boundaries. This reorganization of self-salience may underlie the therapeutic effects of psychedelics in disorders characterized by rigid self-processing, such as depression and social anxiety. By reducing neural differentiation between self and others, psychedelics may facilitate flexibility in social and emotional processing, offering new insights into their potential clinical applications.