High-dose transdermal nicotine and naltrexone: Effects on nicotine withdrawal, urges, smoking, and effects of smoking.

Abstract

Although treatment with transdermal nicotine replacement (TNR) has improved smoking abstinence rates, higher doses of TNR could improve effects on urge to smoke, nicotine withdrawal, and reinforcement from smoking, and naltrexone might further reduce reinforcement and urges. A laboratory investigation with 134 smokers using a 3 x 2 parallel-group design evaluated the effects of TNR (42-mg, 21-mg, or 0-mg patch) as crossed with a single dose of naltrexone (50 mg) versus placebo on urge to smoke, withdrawal, and responses to an opportunity to smoke (intake, subjective effects) after 10 hr of deprivation. Urge and withdrawal were assessed both prior to and after cigarette cue exposure. Only 42 mg TNR, not 21 mg, prevented urge to smoke, heart rate change, and cue-elicited increase in withdrawal. Both 21 and 42 mg TNR blocked cue-elicited drop in heart rate and arterial pressure. Naltrexone reduced cue-elicited withdrawal symptoms but not urges to smoke or deprivation-induced withdrawal prior to cue exposure. Neither medication significantly affected carbon monoxide intake or subjective effects of smoking except that 42 mg TNR resulted in lower subjective physiological activation. No interaction effects were found, and no results differed by gender. Results suggest that starting smokers with 42 mg TNR may increase comfort during initial abstinence, but limited support is seen for naltrexone during smoking abstinence.

Effects of repeated days of smoking cue exposure on urge to smoke and physiological reactivity

“…This finding is consistent with some other studies (e.g., Rohsenow et al, 2007;Tidey et al, 2005). A methodological concern that has been raised about smoking cuereactivity paradigms is that smoking deprivation alone may raise craving to levels where the cue-reactivity effects are no longer noticeable due to ceiling effects, possibly explaining why weaker reactivity effects have been observed when participants are nicotine deprived as compared to non-deprived (e.g., Sayette et al, 2001;Tidey et al, 2005).…”

“…Second, this study compared participants' reactivity to smoking cues with their responses following a relaxation period rather than with their responses to a neutral cue condition; although our previous work indicated that this approach should make no difference (Rohsenow et al, 2007), this methodology should be taken into consideration when generalizing these findings to other cue reactivity studies. In addition, while caffeine has known effects on physiological reactivity (but not on urge to smoke or withdrawal measures), participants were not asked to abstain from caffeine prior to the laboratory session and recent caffeine consumption was not assessed.…”

“…Participants were monitored through a one-way mirror throughout the exposure session to ensure that the procedures were followed properly. A neutral cue exposure was not included given previous work indicating no differences in measures between relaxation and a neutral cue condition (Rohsenow et al, 2007).…”

Goal-directed and transfer-cue-elicited drug-seeking are dissociated by pharmacotherapy: Evidence for independent additive controllers.

“…The dual-controller account elaborated above provides a framework for explaining why tonic cigarette craving but not cue-elicited craving is modulated by abstinence/satiety (Drobes & Tiffany, 1997;Hogarth, et al, 2010;Maude-Griffin & Tiffany, 1996) nicotine replacement therapy (Havermans, et al, 2003;Morissette, et al, 2005;Niaura, et al, 2005;Rohsenow, et al, 2007;Shiffman, et al, 2003;Tiffany, et al, 2000;Waters, et al, 2004), bupropion (Hussain, et al, 2010) and varenicline (Brandon, et al, 2011;Franklin, et al, 2011;Hitsman, et al, under review;Hitsman, et al, 2006). The current analysis suggests that these treatments induce or mimic internal states which have undergone incentive learning and so modulate expectations regarding the current incentive value of tobacco, which determines overall propensity to engage in goal-directed tobacco-seeking (tonic craving).…”

Menstrual Cycle Phase Effects in the Gender Dimorphic Stress Cue Reactivity of Smokers

“…21,22 Future research examining gender differences in responses to smoking and stress cues should account for menstrual phase of female participants to maximize the chance of detecting effects that may be present. Another gainful line of future research could employ imaging methodologies to determine if stress cue-elicited neural activation differs between female and male smokers and if those differences vary by cycle phases (cf., Dagher et al 23 ).…”