Psychedelics, part of a broader class called psychoplastogens, promote structural and functional neural plasticity in brain circuits relevant to mental health. They produce lasting therapeutic effects after a single dose and show promise for depression, PTSD, anxiety, and substance use disorders. A theoretical framework explains their broad efficacy. Challenges like scalability and hallucinogenic effects may be addressed by non-hallucinogenic psychoplastogens. This shift in neuropsychiatry aims to cure mental illness by repairing underlying pathophysiology, not just treating symptoms.
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.