Ayahuasca-inspired DMT/HAR formulation reduces brain differentiation between self and other faces

Abstract Background Psychedelics are known to profoundly alter perception and self-referential processing, yet their specific effects on face recognition —particularly with regard to the 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 increased the P1 and decreased the N170 amplitudes across all face categories, indicating enhanced early visual responsiveness and disrupted face structural encoding. Crucially, DMT/HAR reduced the neural differentiation between self and other faces occurring within the P300 wave compared to Harmine alone, and Placebo. Familiar face processing remained stable across conditions, suggesting that socially meaningful representations were preserved despite psychedelic-induced perceptions shifts. Conclusion While broadly disrupting early visual processing across face categories, the DMT/HAR formulation selectively attenuated the neural distinction between self and other faces, revealing a potential neural correlate of diminished self-referential processing. This effect underscores the serotonergic modulation of face recognition and suggests a reorganization of self-related neural dynamics under psychedelics. By reducing self-other differentiation, psychedelics may promote cognitive and emotional flexibility. These mechanisms could support therapeutic effects in conditions marked by rigid self-focus, such as depression and social anxiety, offering new perspectives on their clinical application.