The Nicotine Hypothesis

We hypothesize that dysfunction of the nicotinic acetylcholinergic neurotransmitter system plays a role in the pathogenesis and the pathophysiology of a multitude of nervous and mental disorders and that novel analogues of nicotine will ameliorate both the positive and the negative symptoms of schizophrenia and associated conditions. Multiple research findings suggest that nicotine may at least temporarily protect the human nervous system from the development of several neurological and psychiatric conditions. Additionally nicotine appears to reduce the symptoms of some people with certain nervous and mental disorders. Thus, nicotine and nicotine congeners may exert neuroprotective effects in healthy humans and in patients with schizophrenia and other neuropsychiatric disorders. The nicotine hypothesis posits that (1) dysfunction of nicotinic acetylcholinergic neurotransmission plays a key role in the pathogenesis and the pathophysiology of schizophrenia and other neuropsychiatric disorders and (2) novel therapies utilizing yet undiscovered congeners of nicotine will alleviate the positive and the negative symptoms of schizophrenia and other neuropsychiatric disorders. Estimation of the density and the distribution of neuronal nicotinic acetylcholine receptors in the living human brain may provide (1) a basis to identify individuals at risk for the development of neuropsychiatric disorders, (2) a means to quantify the efficacy of therapeutic interventions, and (3) a tool to monitor novel targeted treatments. These items support the nicotine hypothesis that dysfunction of the nicotinic system in the brain plays a role in schizophrenia and other neurological and psychiatric conditions.