Modification of natural tryptamines for the treatment of neuropsychiatric diseases
Journal of Psychopharmacology October 4, 2025 Michael G. Palfreyman, Geoffrey B. Varty, Erik M. Stang et al. 3 citations
Classic psychedelic tryptamines show promise for neuropsychiatric disorders, but their broad utility is limited by properties requiring complex delivery and the enigmatic role of the 'psychedelic experience' in therapeutic efficacy. Reducing their mechanism to mere 5-HT2A receptor activation raises the question of whether efficacy is achievable without psychedelic effects. These molecules also interact with other serotonin receptors (e.g., 5-HT1A, 5-HT2C) and non-serotonergic receptors, necessitating further scrutiny of their polypharmacology. This perspective reviews limitations of current non-conjugated tryptamines, explores approaches to improve them, and discusses developing next-generation psychedelic and non-psychedelic compounds, along with the pharmacology underlying these potential therapies.