Harmaline

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.

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.

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.

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.

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.

The human telomeric repeat CCCTAA has been reported to form a higher-order structure called an intercalated motif (i-motif) that plays important roles in telomere function and telomerase activity regulation, and small molecule ligands targeting human telomeric i-motif (hTelo-iM) is a promising therapeutic strategy for cancer treatment, yet the i-motif folding pattern of long CCCTAA repeats and the hTelo-iM ligand screening have not been studied extensively. In this study, we systematically investigated the i-motif structures formed by four and eight telomeric C-rich repeats d(CCCTAA)₄ (hTeloC-24mer) and d(CCCTAA)₈ (hTeloC-48mer) under varied conditions and found that the long hTeloC-48mer probably forms unstacked tandem i-motif consisting of two hTeloC-24mer i-motif monomers under near physiological conditions. Moreover, natural bisbenzylisoquinoline (BBI) alkaloids, isofangchinoline, fangchinoline, cepharanthine, and tetrandrine, were screened from 33 natural small molecules to effectively disrupt and destabilize the hTelo-iM structures mainly through major groove hydrogen bonding and van der Waals interactions. Further, telomerase repeated amplification protocol (TRAP) assay suggested that the selected BBI alkaloids can inhibit the telomere extension by telomerase. These findings provide a theoretical basis for further telomere structure research as well as a novel class of natural small molecule compounds regulating the hTelo-iM structure and telomerase activity, which may contribute to the anticancer drug design and strategy development taking the hTelo-iM as a target.