Nicotine in Neurodegenerative and Neuropsychiatric Disorders: Mechanisms and Clinical Evidence

Nicotine, a psychoactive compound primarily known for its role in tobacco addiction, has attracted increasing interest for its neuromodulatory and neuroprotective properties. Acting predominantly through nicotinic acetylcholine receptors, nicotine influences multiple neurotransmitter systems, modulates neuroinflammation, and supports synaptic plasticity. These mechanisms may be therapeutically relevant in disorders characterized by neurodegeneration or disrupted neurocircuitry, including Parkinson's disease, Alzheimer's disease, schizophrenia, attention-deficit/hyperactivity disorder, depression, and post-traumatic stress disorder. This review critically examines the current state of preclinical and clinical evidence, with particular attention to receptor subtype activity, cognitive and emotional modulation, and human trial data. Although nicotine's addictive potential and receptor desensitization remain concerns, advances in selective ligands offer new therapeutic avenues. By consolidating mechanistic insights and disease-specific data, this review highlights both the promise and challenges of developing nicotinic-based therapeutics for brain disorders.