Effects of acute abstinence, reinstatement, and mecamylamine on biochemical and behavioral measures of cigarette smoking in schizophrenia

Abstract

Background: Schizophrenics have higher rates of smoking than the general population, and more difficulty with smoking cessation. However, there has been little study of differences between schizophrenics and controls with respect to biochemical and behavioral indices of smoking. We compared smokers with schizophrenia (SS; n=27) and control smokers (CS; n=26) on smoking and psychiatric outcomes at baseline, during acute smoking abstinence and reinstatement, and with pre-treatment using the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (MEC) in a human laboratory setting.

Methods: Biochemical (e.g., plasma nicotine) and behavioral (e.g., craving, withdrawal) outcomes were assessed at baseline, after overnight abstinence, and after smoking reinstatement during three consecutive test weeks. Each week, participants received one of three doses of MEC (0.0, 5.0, or 10.0 mg/dayx3 days) in a randomized, counterbalanced manner.

Results: Compared to CS, SS displayed similar levels of craving and withdrawal, but higher plasma nicotine and cotinine levels, and cotinine/CPD ratio. During reinstatement, SS consumed significantly more cigarettes than CS, but MEC did not significantly alter indices of smoking, psychiatric symptoms, or cigarette consumption during reinstatement.

Conclusions: 1) The reinforcing effects of smoking may be increased in SS versus CS after overnight abstinence; 2) the lack of effects of nAChR antagonism may suggest that non-nicotinic components of cigarettes may contribute to the behavioral effects of smoking in both SS and CS; and 3) consistent with previous studies, SS may exhibit higher baseline levels of nicotine and cotinine, and greater extraction of nicotine per cigarette than CS.

Figure 1

Single Subject Study Timeline for Smokers with Schizophrenia and Control Smokers

Figure 2

Comparison of Smokers with Schizophrenia (SS; n=27) and Control Smokers (CS; n=26) and the effects of MEC Dose on total number of cigarettes smoked during the 1-hour smoking reinstatement session.