Naloxone challenge in smokers. Preliminary evidence of an opioid component in nicotine dependence.
ABSTRACT This study used an opioid antagonist challenge procedure to evaluate the responsivity of the endogenous opioid system in nicotine-dependent individuals, as evidenced by naloxone-induced alterations in both behavioral (withdrawal, craving) and neuroendocrine (cortisol levels) parameters.
Twenty subjects (9 smokers and 11 nonsmokers) participated in 4 laboratory sessions during which they were challenged with 0, 0.8, 1.6, or 3.2 mg/70 kg of naloxone and then monitored for 1 hour for subjective signs and symptoms of opiate-like withdrawal, nicotine craving, and alterations in cortisol levels.
Nicotine-dependent subjects evidenced naloxone dose-dependent increases in withdrawal signs and symptoms. Lower doses of naloxone also produced increases in urges to smoke (craving) and tiredness in smokers. Smokers, when compared with nonsmokers, had lower prenaloxone baseline levels of cortisol and attenuated cortisol release in response to challenge with naloxone.
These results provide preliminary evidence to suggest that long-term exposure to cigarette smoke is associated with alterations in the responsivity of the endogenous opioid system and the hypothalamic-pituitary-adrenal axis that may contribute to the development of nicotine dependence.
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ABSTRACT: This meta-analysis sought to evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. Post-treatment abstinence was examined as a secondary outcome and effects on withdrawal symptoms, craving and reduced consumption were also explored. The search strategy for this meta-analysis included clinical trials (published and unpublished data) in the Cochrane Tobacco Addiction Group Specialized Register and MEDLINE. Adult smokers. We included randomised trials comparing opioid antagonists to placebo or an alternative therapy for smoking cessation and reported data on abstinence for a minimum of 6 months. Outcomes included smoking abstinence at long-term follow-up (primary); abstinence at end of treatment (secondary); and effects on withdrawal, craving and smoking consumption (exploratory). 8 trials with a total of 1213 participants were included. Half the trials examined the benefit of adding naltrexone versus placebo to nicotine replacement therapy (NRT). There was no significant difference between naltrexone and placebo alone (relative risk (RR) 1.00; 95% CI 0.66 to 1.51) or as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30), with an overall pooled estimate of RR 0.97; 95% CI 0.76 to 1.24. Findings for naltrexone effects on withdrawal, craving and reduced smoking were equivocal. The findings indicate no beneficial effect of naltrexone alone or as an adjunct to NRT on short-term or long-term smoking abstinence. While further trials may narrow the confidence limits, they are unlikely to appreciably alter the conclusion.BMJ Open 03/2014; 4(3):e004393. · 2.06 Impact Factor
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ABSTRACT: Background Heavy drinking smokers (HDS) have more difficulty quitting smoking than lighter drinkers or abstainers. The opioid antagonist naltrexone may improve smoking quit rates and reduce alcohol use in drinker–smokers, but its relative efficacy in smokers with a range of drinking patterns is unknown. The current study tested the hypothesis that HDS would show differential benefit of naltrexone versus placebo relative to moderate-to-light or nondrinking smokers in terms of improving smoking outcomes and reducing alcohol consumption.Methods Adult smokers (N = 315) enrolled in a 12-week, double-blinded, placebo-controlled trial of 50 mg naltrexone for smoking cessation were categorized into subgroups based upon past 6-month drinking patterns: HDS (n = 69; i.e., averaged ≥2 heavy drinking episodes per month), moderate-to-light drinking smokers (n = 204, i.e., consumed 1 drink up to a maximum of <2 heavy drinking episodes per month on average), or nondrinking smokers (n = 42, no alcohol consumed in the past 6 months). The groups were compared on the main study outcomes of biochemically verified prolonged abstinence quit rates (i.e., no smoking weeks 2 to 12), and smoking urge and alcohol use (drinks/wk) during treatment.ResultsNaltrexone significantly increased 12-week smoking abstinence rates and decreased smoking urge and alcohol use among HDS, but not moderate-to-light or nondrinking smokers. Mediation analyses in HDS revealed that naltrexone's effect on smoking urge during the first 4 weeks of treatment mediated its effect on quit rates.ConclusionsHDS appear to be particularly sensitive to naltrexone effects on smoking and drinking outcomes. This group may represent an important target for adjunctive treatment with naltrexone to optimize smoking cessation outcomes.Alcoholism Clinical and Experimental Research 10/2014; · 3.31 Impact Factor
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ABSTRACT: The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward.PLoS ONE 12/2014; 9(12):e113694. · 3.53 Impact Factor