Pharmacological regulation of adult brain neuroplasticity: Synergistic roles of neuropeptide signaling, psychedelics, and synaptic modulators.

The brain's ability to reorganize itself, known as neuroplasticity, is now understood to be more flexible and treatable in adults than previously believed. This review examines drugs that target key synaptic receptors (NMDA, AMPA, GABA), neuropeptide systems (BDNF, oxytocin, vasopressin), and psychedelic compounds (psilocybin, LSD, ketamine). Evidence shows that NMDA antagonists produce rapid antidepressant effects, classic psychedelics reorganize brain structure and function through 5-HT2A receptor activation, and neuropeptides support synaptic repair. The authors emphasize safety concerns, risks of harmful plasticity, and the need for controlled dosing and patient selection. Emerging non-hallucinogenic neuroplastogens and combination therapies may offer safer ways to enhance plasticity for treating neuropsychiatric and neurodegenerative disorders.

Study at a glance

Abstract

Neuroplasticity refers to the ability of the brain to modify synaptic connections and reorganize neural circuits, underpinning cognitive function, emotional regulation, and recovery from injury. Recent advances have redefined adult neuroplasticity as more dynamic and therapeutically accessible than previously thought, spurring investigation into pharmacological interventions that can augment these adaptive processes. This review dissects current evidence for drug strategies targeting synaptic modulators (NMDA, AMPA, and GABA receptors), neuropeptide systems (including BDNF, oxytocin, vasopressin), and psychedelic compounds (psilocybin, LSD, ketamine), integrating insights from cellular, preclinical, and clinical studies. We detail how these agents modulate molecular pathways governing synaptic transmission, dendritic remodeling, and gene expression linked to neuronal growth and resilience. Highlighted findings include the rapid-acting antidepressant effects of NMDA antagonists, the structural and functional reorganization induced by classic psychedelics via 5-HT2A receptor activation, and the neurorestorative roles of neuropeptides in synaptic and network adaptation. Alongside these advances, we critically address safety, ethical considerations, and the risk of maladaptive plasticity, underscoring the importance of dosing, patient selection, and controlled therapeutic environments. Non-hallucinogenic neuroplastogens and combinatorial approaches that are still emerging offer new avenues to fine-tune plasticity with an improved safety profile. The collective evidence positions neuroplasticity-targeting pharmacology as a promising and complex frontier for the treatment of neuropsychiatric and neurodegenerative disorders in adulthood.