NicW has both an affective/cognitive component (e.g., irritability, frustration, anxiety, depressed mood, restlessness, and difficulty concentrating) and a somatic component (e.g., insomnia, decreased heart rate, increased appetite, constipation, cough, and dizziness).8 NicW symptoms are thought to be mediated by neuroadaptations that affect the function of nicotinic acetylcholine receptors (nAChR), notably α2, β2, α5, α6, and β4.9–11 For example, single-photon emission computed tomography (SPECT) studies indicate that β2*-nAChR availability increases during early abstinence and remains at elevated levels for ~1 month before returning to baseline.12, 13 Changes in the firing of dopaminergic neurons in the ventral tegmental area (VTA) that reduce the amount of dopamine released into the nucleus accumbens (NA) may also contribute to the development of symptoms of NicW,14, 15 as well as symptoms of withdrawal from opioids, cocaine and alcohol.16 Human fMRI neuroimaging studies have provided additional insight into the neuroadaptations that may be responsible for NicW, and several studies have shown that NicW disrupts resting state functional connectivity in the brain.17 These cessation-induced disruptions in functional connectivity are associated with cognitive impairments and craving to smoke.18
