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 new technique called CaST (calcium-activated split-TurboID) uses an enzyme to rapidly tag cells that have elevated calcium levels in living animals, marking activated cells within 10 minutes. The tagging signal increases with both calcium concentration and labeling time, acting as a time-gated integrator of total calcium activity. Unlike transcriptional reporters that take hours to produce a signal, CaST provides readout immediately after activity labeling. The method was used to tag prefrontal cortex neurons activated by psilocybin in untethered mice, and the CaST signal correlated with psilocybin-induced head-twitch responses.
A new enzyme-based method called CaST (Ca2+-activated Split-TurboID) biochemically tags cells with elevated calcium levels in living animals within 10 minutes, without requiring implants or light delivery. The signal increases with calcium concentration and labeling time, acting as a time-gated integrator of calcium activity. Unlike transcriptional reporters that take hours, CaST allows immediate read-out after activity labeling. The approach was used to tag prefrontal cortex neurons activated by psilocybin in untethered mice, and the CaST signal correlated with psilocybin-induced head-twitch responses.
Nonhallucinogenic psychoplastogens like tabernanthalog (TBG) promote cortical neuroplasticity through the same biochemical pathway as classic psychedelics—involving 5-HT2A, TrkB, mTOR, and AMPA receptor activation—but without inducing an immediate glutamate burst or immediate early gene activation. TBG-induced cortical spinogenesis is required for its sustained antidepressant-like behavioral effect in rodents. These findings clarify how certain psychoplastogens can produce neuroplasticity without hallucinogenic effects, challenging assumptions that glutamate burst and IEG activation are necessary for psychedelic-induced neuroplasticity.