Current Topics in Behavioral Neurosciences
January 1, 2017
Juan F López-Giménez, Javier González-Maeso
302 citations
Hallucinogens such as mescaline, psilocybin, and LSD profoundly alter consciousness, emotion, and cognition. Their discovery, particularly LSD's similarity to serotonin, suggested that biogenic amines like serotonin are involved in mental disorders such as schizophrenia. Although hallucinogens bind to multiple G protein-coupled receptor subtypes, their key effects involve agonist activity at the serotonin 5-HT2A receptor. This chapter reviews recent advances in understanding hallucinogen action by characterizing the structure, neuroanatomical location, and function of the 5-HT2A receptor.
bioRxiv (Cold Spring Harbor Laboratory)
March 23, 2026
Marco Taddei-Tardón, Lidia Medina-Rodríguez, Jessica L Maltman et al.
Serotonergic psychedelics, including tryptamines, phenethylamines, and ergolines, promote structural and transcriptional changes in neurons through an integrated signaling network involving the 5-HT2A receptor and TrkB. Using a neural stem cell-derived model, the study shows that TrkB silencing blocks dendritogenesis induced by psychedelics, ketamine, and TrkB agonists, while 5-HT2A silencing selectively impairs psychedelic-induced plasticity. Most compounds increase synaptogenesis and immediate-early gene expression, though psilocin and the phenethylamines DOI and Ariadne show ligand-specific differences. Lactate production, dependent on 5-HT2A and both Gq/11 and Gi/o protein signaling, also occurs. These results establish a platform for dissecting psychedelic action.
Molecular Psychiatry
July 16, 2026
Marco Taddei-Tardón, Lidia Medina-Rodríguez, Jessica L Maltman et al.
Serotonergic psychedelics recruit an integrated 5-HT2A-TrkB signaling network that drives neuroplastic changes. Using a neural stem cell-derived in vitro model, a panel of tryptamines, phenethylamines, and ergolines was tested alongside ketamine and TrkB agonists. TrkB silencing abolished dendritogenic responses to all tested compounds, while 5-HT2A receptor silencing selectively impaired psychedelic-induced plasticity. Most compounds increased synaptogenesis and induced c-Fos and Egr-2 expression, with ligand-specific differences for psilocin, DOI, and Ariadne. Gq/11 or Gi/o protein coupling differentially modified neuroplastic and transcriptional responses. Psychedelics also induced a 5-HT2A receptor-dependent lactate response sensitive to disruption of either Gq/11 or Gi/o coupling.
bioRxiv : the preprint server for biology
November 26, 2025
Sandra M. Martin-Guerrero, Marco Taddei-Tardón, Jessica L Maltman et al.
preprint
Chemically diverse psychedelics trigger a coordinated reorganization of phosphorylation patterns across many proteins in neural cells. This global signaling response contains a distinct signature that separates hallucinogenic compounds from non-hallucinogenic counterparts of similar structure. Using a glycolysis-regulating transcription factor as an example, hallucinogenic psychedelics, but not their non-hallucinogenic analogues, enhance markers of glycolytic metabolism. These findings reveal that hallucinogenic and non-hallucinogenic psychedelics engage separable intracellular architectures, establishing a framework for understanding how different psychoactive compounds couple receptor activation to specific cellular states.