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Therapeutic Divergence in 5-HT2A Agonism: Psilocybin and Phenalkylamines for Demoralization Syndrome

Robert B. Kargbo

ACS Medicinal Chemistry Letters August 15, 2025 DOI: 10.1021/acsmedchemlett.5c00475 (opens in new tab)

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AI-extracted from the abstract
Characteristics Review Peer reviewed
Topics Psilocybin
Keywords Agonism Hallucinogen Divergence linguistics 5-HT Receptor Psychotherapist Pharmacology
Key findings Structural modifications of phenalkylamines and tryptamines can yield functional selectivity at 5-HT receptors, reducing hallucinogenic risk while preserving therapeutic efficacy for demoralization syndrome and depression-related conditions.

Abstract

Novel phenalkylamines and tryptamines such as psilocybin demonstrate promising nontraditional pharmacological profiles for treating psychiatric syndromes. Structural modifications yield functional selectivity at 5-HT receptors, mitigating hallucinogenic risk while preserving therapeutic efficacy. This study integrates receptor and behavioral data to support phenalkylamines and psilocybin as rational therapeutics for demoralization syndrome and depression-related conditions.

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