Nicotine Withdrawal

Abstract

An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs) have been shown to predispose individuals to consume larger amounts of nicotine more frequently—as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction.

α2-Null mutant mice have altered levels of neuronal activity in restricted midbrain and limbic brain regions during nicotine withdrawal as demonstrated by cfos expression

“…An important mediator of continued tobacco use relates to the aversive withdrawal symptoms induced by smoking cessation [2–5]. Thus, by understanding the mechanisms mediating tobacco withdrawal symptoms, more effective therapeutic interventions could be provided.…”

“…Depending on their subunit composition, neuronal nAChRs display varying sensitivities to a wide range of agonists and antagonists [14]. To better understand how these unique receptors contribute to nicotine-modulated behaviors, including withdrawal, genetic animal models have been developed [2, 5, 15, 16]. Findings illustrate that certain nicotinic receptor subunit null mutant mice, but not others, differentially regulate nicotine withdrawal (for review see [2]).…”

“…While less is known about the mechanisms mediating withdrawal symptoms in humans, genome-wide association and candidate gene studies have found consistent trends for polymorphisms in a number of nicotinic receptor subunit genes predicting tobacco addiction [17–19]. Thus, both clinical and preclinical evidence suggest that nicotinic receptors are important contributors to addiction, with possible relationships to the mechanisms mediating nicotine withdrawal [5, 20]. Such studies are assisting in the development of novel therapeutic ligands specific for selective nicotinic receptors for the purpose of combatting the tobacco addiction pandemic [21–24].…”

“…Indeed, recent evidence has shown that multiple nAChR subunits within the habenulo-IPN axis influence nicotine reward and withdrawal [4, 5, 30–33]. The IPN is a midline structure located within the midbrain that receives a vast majority of its input bilaterally from the medial habenula via a pathway known as the fasciculus retroflexus [34].…”

Correlates of nicotine withdrawal severity in smokers during a smoke-free psychiatric hospitalization

“…In the event of symptom overlap (e.g., severity of depression), it would be a mistake to make a default attribution of the symptom to other mental illness. A substantial literature has well-established the symptom profile of NW in persons both with and without comorbid mental illness (Hughes et al, 1994; Hughes, 2007; McLaughlin et al, 2015). Further, to seek a conception of NW that is completely separate from other psychopathology, while appealing from a diagnostic standpoint, would perpetuate a false dualism that ignores the reality of NW presentation.…”