Novel Indoline Derivatives Serotonergic Psychedelic Agents as 5‑HT2A Agonists for Treating Psychosis, Mental Illness and CNS Disorders.
ACS Med Chem Lett April 27, 2026
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5 results for "Meta-analysis: what did research on serotonin find in april 2026?"
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Serotonergic Polypharmacology of 2-Halogenated Tryptamines.
bioRxiv : the preprint server for biology April 21, 2026 Jeanine Yacoub, Elena Bray, Jude Bayyat et al.
Halogenating the 2-position of DMT and psilacetin reduces their activity at 5-HT2A and 5-HT2B receptors, which are linked to psychedelic effects and heart valve toxicity, while preserving activity at other therapeutic targets like 5-HT6. The 2-Br-psilacetin analogue did not cause head-twitch behavior in mice and reduced head-twitch caused by another psychedelic, indicating lower potential for psychedelic effects. Intermediate doses improved stress-related mood measures and cued learning. These findings suggest that 2-halogenated tryptamines could be developed as safer, non-psychedelic therapeutics for psychiatric and neurodegenerative disorders.
Psilocybin elicits a conserved glucocorticoid-responsive gene signature across five 5-HT2A receptor-rich brain regions in rat.
Acta neuropsychiatrica April 10, 2026 Ashkan Veysi, Daniela Atanasovski, Maryam Ardalan et al.
Psilocybin, a psychedelic known for hallucinogenic and potential therapeutic effects, alters gene expression in rat brains in a region-specific manner. Ninety minutes after injection, several genes were upregulated across multiple brain regions, including Nfkbia and Sgk1 in all studied areas and Ddit4 in four regions. Other genes like Gpd1, Apold1, Sox9, Tsc22d3, and Slc2a1 changed in two regions. Psilocybin did not affect genes related to serotonin signaling or other neurotransmitter systems. Many affected genes are known to be activated by glucocorticoids, suggesting a link to stress hormone pathways.
Dorsal Raphe Revisited: A Systems Neuroscience Lens on Psychedelic Drug Action
Psychedelic Medicine April 9, 2026 Alex C. Kwan
Classical psychedelics like LSD were studied soon after the midbrain raphe was identified as the brain's main source of serotonin. Early work in 1968 showed that LSD suppresses the firing of serotonergic neurons in the rat midbrain raphe. For over 15 years, researchers intensively examined the pharmacology and receptor mechanisms involved. Initial hypotheses incorrectly proposed that these serotonergic neurons directly caused hallucinogenic effects, but the framework shifted as neural activity was linked to behavior. This review traces that arc of discovery and revisits the early findings in light of current knowledge about serotonergic circuits, showing how pioneering studies laid the foundation for understanding psychedelics' neural actions.
Hallucinogenic Therapy in Alzheimer's Disease targeting Mitochondria-Associated Membranes.
Neuroscience April 6, 2026 Fernando Minauro-Sanmiguel, Hector Vargas-Perez
Mitochondrial dysfunction is a key driver of Alzheimer's disease, fueling neuroinflammation, synaptic failure, and energy collapse. Emerging preclinical evidence suggests that classic hallucinogens like psilocybin, LSD, DMT, and mescaline may restore mitochondrial integrity by activating serotonin 2A and sigma-1 receptors. In experimental models, these pathways enhance mitochondrial biogenesis, reduce oxidative stress, and preserve ER-mitochondrial coupling. DMT and 5-MeO-DMT specifically engage sigma-1 receptors at mitochondria-associated membranes, improving calcium homeostasis and cellular resilience. However, evidence for clinical efficacy in Alzheimer's remains limited and largely preclinical. This framework is presented as a hypothesis-generating model, emphasizing that neuropsychiatric safety, patient selection, and translational feasibility must be carefully addressed.