Efficacy of naltrexone in smoking cessation: A preliminary study and an examination of sex differences

Department of Health Studies, University of Chicago, Chicago, Illinois, United States
Nicotine & Tobacco Research (Impact Factor: 3.3). 10/2006; 8(5):671-82. DOI: 10.1080/14622200600789767
Source: PubMed


This double-blinded, placebo-controlled trial evaluated the efficacy of naltrexone as an adjunct to standard smoking cessation treatment. Participants (N = 110) were adult male and female nicotine-dependent smokers who expressed interest in quitting smoking. All subjects received six sessions of behavioral counseling (1 hr/session for 6 weeks), and 1 month of the nicotine patch (21 mg for the first 2 weeks, 14 mg the third week, 7 mg the fourth week). Subjects were randomly assigned to the naltrexone or placebo group. The naltrexone group started at 25 mg daily for 3 days prior to the quit date, and increased to 50 mg/day on the quit date and following 8 weeks. At the end of medication treatment, the naltrexone group had better quit rates versus the placebo group (48% quit on naltrexone vs. 41% on placebo), but this difference was not statistically significant. However, men and women differed on several measures: in the placebo group, women had significantly lower quit rates than men (39% vs. 67%, p<.05), but in the naltrexone group, women had quit rates comparable with those of men (58% vs. 62%, p = ns). Further examination revealed that naltrexone significantly reduced men's and women's cessation-related weight gain and selectively reduced women's urge to smoke to relieve negative affect and withdrawal. The results suggest continued examination of naltrexone as an adjunct in smoking cessation, particularly in female smokers, who have historically shown worse outcomes with traditional treatment methods.

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    • "Varenicline is a front-line treatment for smoking cessation and in heavy drinking smokers has been shown to reduce the number of cigarettes smoked and alcoholic beverages consumed per day, while also attenuating alcohol craving (Fucito et al., 2011; McKee et al., 2009; Mitchell et al., 2012). Naltrexone (50 mg) is FDAapproved for the treatment of alcohol dependence but has also shown some promise as an adjunct treatment for smoking cessation (King et al., 2006, 2012). Of note, NTX may be primarily effective among heavy drinking smokers by preferentially reducing alcohol consumption and smoking urge while also improving smoking quit rates in comparison with non-heavy drinking smokers (Fridberg et al., 2014; Pharmacology, Biochemistry and Behavior 134 (2015) 92–98 ⁎ Corresponding author at: University of California, Los Angeles, Psychology Department, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, United States. "
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    ABSTRACT: Heavy drinking smokers constitute a distinct sub-population of smokers for whom traditional smoking cessation therapies may not be effective. Recent evidence suggested that combined varenicline (VAR) and naltrexone (NTX) therapy may be more efficacious than either monotherapy alone in reducing smoking and drinking-related behavior in this population. The manner in which individuals smoke a cigarette (i.e., smoking topography) may be predictive of smoking cessation outcomes, yet the effects of smoking pharmacotherapies on puffing behavior have not been thoroughly examined. Therefore, the current double-blind medication study examined the effects of VAR alone (1mg BID), low dose NTX alone (25mg QD), the combination of VAR+NTX, and placebo on smoking topography measures in heavy drinking, non-treatment seeking daily smokers (n=120). After a 9-day titration period, participants completed a laboratory session in which they smoked their first cigarette of the day using a smoking topography device following 12-hrs of nicotine abstinence and consumption of an alcoholic beverage (BrAC = 0.06 g/dl). The primary measures were puff count, volume, duration, and velocity and inter-puff interval (IPI). Independent of medication group, puff velocity and IPI increased, while puff volume and duration decreased, over the course of the cigarette. The active medication groups, vs. the placebo group, had significantly blunted puff duration and velocity slopes over the course of the cigarette, and this effect was particularly evident in the VAR+NTX group. Additionally, the VAR+NTX group demonstrated lower average IPI than the monotherapy groups and lower average puff volume than all other groups. These results suggest that smoking pharmacotherapies, particularly the combination of VAR+NTX, alter smoking topography in heavy drinking smokers, producing a pattern of less intense puffing behavior. As smoking topography has been predictive of the ability to quit smoking, future studies should examine how smoking pharmacotherapies' effects on puffing behavior relate to smoking cessation outcomes. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Apr 2015 · Pharmacology Biochemistry and Behavior
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    • "An estimated 44 million Americans smoke cigarettes, with a prevalence of 17% for women (Centers for Disease Control, Prevention [CDC], 2011). Research has shown that women may be less successful in quitting smoking compared to men (King et al., 2006; Perkins, 2001; Scharf & Shiffman, 2004) and also experience significantly greater smoking-related morbidity and mortality (U.S. Department of Health and Human Services [USDHHS], 2001). "
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    ABSTRACT: Menstrual phase and depressive symptoms are known to minimize quit attempts in women. Therefore, the influence of these factors on smoking- and menstrual-related symptomatology during acute smoking cessation was investigated in a controlled cross-over lab-study. Participants (n = 147) completed two six-day testing weeks during their menstrual cycle with testing order randomly assigned (follicular vs. luteal). The testing week consisted of two days of ad libitum smoking followed by four days of biochemically verified smoking abstinence. Daily symptomatology measures were collected. Out of the 11 total symptoms investigated, six were significantly associated with menstrual phase and nine were significantly associated with level of depressive symptoms. Two significant interactions were noted indicating that there may be a stronger association between depressive symptoms with negative affect and premenstrual pain during the follicular phase compared to the luteal phase. Overall, these observations suggest that during acute smoking abstinence in premenopausal smokers, there is an association between depressive symptoms and symptomatology whereas menstrual phase appears to have less of an effect. Further study is needed to determine the effect of these observations on smoking cessation outcomes, as well as to define the mechanism of menstrual phase and depressive symptoms on smoking-related symptomatology.
    Full-text · Article · May 2014 · Addictive behaviors
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    • "In contrast, opioid peptides derived from prodynorphin, which are the main endogenous ligands for k-opioid receptors (KOR), seem to participate in nicotine aversive responses since the deletion of the prodynorphin gene improved nicotine self-administration (Galeote et al, 2009). In agreement with these preclinical results, the non-selective opioid antagonist naltrexone has shown efficacy for smoking cessation mainly in female smokers (King et al, 2006), and smokers reporting high rates of depressive symptoms (Walsh et al, 2008). DOR is highly expressed in the olfactory bulb, cortex, amygdala, caudate-putamen, and nucleus accumbens, while moderate levels of this receptor are reported in the interpeduncular and pontine nuclei, hippocampus, spinal cord, and dorsal root ganglia (Mansour et al, 1987; Goody et al, 2002; Pradhan and Clarke, 2005). "
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    ABSTRACT: Multiple studies in animal models and humans suggest that the endogenous opioid system is an important neurobiological substrate for nicotine addictive properties. In this study, we evaluated the participation of δ-opioid receptors in different behavioral responses of nicotine by using δ-opioid receptor knockout mice. Acute nicotine administration induced hypolocomotion and antinociception in wild-type mice, which were similar in knockout animals. The development of tolerance to nicotine-induced antinociception was also similar in both genotypes. In agreement, the expression and functional activity of δ-opioid receptors were not modified in the different layers of the spinal cord and brain areas evaluated after chronic nicotine treatment. The somatic manifestation of the nicotine withdrawal syndrome precipitated by mecamylamine was also similar in wild-type and δ-opioid receptor knockout mice. In contrast, nicotine induced a conditioned place preference in wild-type animals that was abolished in knockout mice. Moreover, a lower percentage of acquisition of intravenous nicotine self-administration was observed in mice lacking δ-opioid receptors as well as in wild-type mice treated with the selective δ-opioid receptor antagonist naltrindole. Accordingly, in-vivo microdialysis studies revealed that the enhancement in dopamine extracellular levels induced by nicotine in the nucleus accumbens was reduced in mutant mice. In summary, the present results show that δ-opioid receptors are involved in the modulation of nicotine rewarding effects. However, this opioid receptor does not participate either in several acute effects of nicotine or in the development of tolerance and physical dependence induced by chronic nicotine administration.
    Full-text · Article · Jun 2012 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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