A newly designed compound, (+)-JRT, structurally similar to LSD but with reduced hallucinogenic effects, promotes the growth of dendritic spines in the cortex—a process that is diminished in neuropsychiatric diseases such as depression, addiction, and schizophrenia. In behavioral tests, (+)-JRT showed antidepressant-like and cognition-enhancing effects without worsening signs related to psychosis. This suggests that nonhallucinogenic compounds that promote neuroplasticity could be safer alternatives to psychedelics for treating conditions where psychedelics pose risks.
A general chemical synthesis method for tropane alkaloids—compounds with a characteristic 8-azabicyclo[3.2.1]octane core—enables late-stage structural diversification at positions N8, C3, C6, and C7, which are important for biological activity. The approach constructs the core via aziridination of a cycloheptadiene intermediate followed by vinyl aziridine rearrangement, yielding six tropane alkaloids and several analogues in 5-7 steps. Testing five tropane-containing compounds in cultured cortical neurons for dendritic spine growth—a marker of structural neuroplasticity—suggests that the orientation of the C3 substituent may influence psychoplastogenic effects. This platform supports future structure-activity relationship studies.