Naloxone challenge in smokers - Preliminary evidence of an opioid component in nicotine dependence
Department of Psychiatry, Yale University, New Haven, Connecticut, United States Archives of General Psychiatry
(Impact Factor: 14.48).
08/1999; 56(7):663-8. DOI: 10.1001/archpsyc.56.7.663
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.
Available from: Elise M Weerts
- "Nicotine activates nicotinic acetylcholine receptors, which in turn increases the release of DA and endogenous opioids. Similar to preclinical findings (Malin et al., 1993), acute intravenous administration of the opioid antagonist naloxone increased withdrawal symptoms in nicotine dependent smokers (Krishnan-Sarin et al., 1999), Studies in human subjects have shown that cigarette smoking increased plasma levels of endogenous opioid peptides (Pomerleau et al., 1983), and increased DA release in the ventral striatum (Brody et al., 2004). In controlled laboratory studies, administration of naltrexone reduced the relative reinforcing value of nicotinized cigarettes in a cigarette smoking choice paradigm (Rukstalis et al., 2005), and blocked the pleasurable subjective effects of cigarette smoking in heavy smokers (King and Meyer, 2000). "
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ABSTRACT: Persons with a history of alcohol dependence are more likely to use tobacco and to meet criteria for nicotine dependence compared with social drinkers or non-drinkers. The high levels of comorbidity of nicotine and alcohol use and dependence are thought to be related to interactions between nicotinic, opioid and dopamine receptors in mesolimbic regions. The current study examined whether individual differences in regional μ-opioid receptor (MOR) availability were associated with tobacco use, nicotine dependence and level of nicotine craving in 25 alcohol-dependent (AD) subjects. AD subjects completed an inpatient protocol, which included medically supervised alcohol withdrawal, monitored alcohol abstinence, transdermal nicotine maintenance (21 mg/day) and Positron Emission Tomography (PET) imaging using the MOR agonist [(11) C]-carfentanil (CFN) before (basal scan) and during treatment with 50 mg/day naltrexone (naltrexone scan). Subjects who had higher scores on the Fagerström Nicotine Dependence Test had significantly lower basal scan binding potential (BP(ND) ) across mesolimbic regions, including the amygdala, cingulate, globus pallidus, thalamus and insula. Likewise, the number of cigarettes per day was negatively associated with basal scan BP(ND) in mesolimbic regions. Higher nicotine craving was significantly associated with lower BP(ND) in amygdala, globus pallidus, putamen, thalamus and ventral striatum. Although blunted during naltrexone treatment, the negative association was maintained for nicotine dependence and cigarettes per day, but not for nicotine craving. These findings suggest that intensity of cigarette smoking and severity of nicotine dependence symptoms are systematically related to reduced BP(ND) across multiple brain regions in AD subjects.
Addiction Biology 12/2012; 19(4). DOI:10.1111/adb.12022 · 5.36 Impact Factor
Available from: Daniel James Olan Roche
- "Morphine produces a leftward shift of the nicotine dose-response curve (Huston-Lyons et al., 1993) and there is cross-tolerance between morphine and nicotine (Zarrindast et al., 2003). In both pre-clinical and clinical studies, opioids and nicotine produce similar withdrawal patterns (Hynes et al., 1976; Malin et al., 1993, 1996a,b; Krishnan-Sarin et al., 1999; Berrendero et al., 2002, 2005). "
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ABSTRACT: Both opioid antagonist administration and cigarette smoking acutely increase hypothalamic-pituitary-adrenal (HPA) axis activity as measured by adrenocorticotropic hormone (ACTH) and cortisol levels. However, male and female smokers may differ in their response to the opioid antagonist naltrexone, which may be partially mediated by sex differences in HPA axis function. Smokers, as a group, have frequently been shown to have HPA axis dysfunction, which may have relevance to the course and maintenance of nicotine dependence. The purpose of this study was to examine possible sex differences in HPA axis function by comparing stress-hormone response to naltrexone within healthy male and female smokers. Additionally, exploratory analyses compared the combined effects of naltrexone and cigarette smoking on hormonal responsivity between the sexes.
Thirty-eight healthy smokers (22 men) were tested in two separate morning sessions after 12h of smoking abstinence. For women, self-reports of menstrual cycle information were obtained prior to each session (date of last menstruation, cycle length, reproductive phase, etc.). Each participant received 50mg naltrexone or placebo capsule (in random order) and plasma levels of ACTH and cortisol were assessed at regular intervals for several hours. A subgroup of 12 participants underwent a similar, additional session in which they smoked a single cigarette three hours after naltrexone administration.
Naltrexone significantly increased ACTH and cortisol levels in women, but not men (DrugxSexxTime, p<0.05). A post hoc analysis suggested that women at an estimated 'high estrogen' phase had a greater cortisol response (DrugxEstrogen level, p<0.05) than those at an estimated 'low estrogen' phase. Exploratory analyses showed that smoking a single cigarette potentiated naltrexone-induced increases in ACTH (p<0.05) and cortisol (p<0.01) in all participants.
The findings support the hypothesis that women are more sensitive to opioid antagonism at the level of the HPA axis. Although further studies are needed to examine mechanisms underlying these responses, both results may have clinical implications for the use of naltrexone as a treatment for nicotine dependence.
Psychoneuroendocrinology 10/2009; 35(4):596-606. DOI:10.1016/j.psyneuen.2009.09.016 · 4.94 Impact Factor
Available from: Mustafa al'Absi
- "Cellular studies show that hypothalamic neurons release beta endorphin in response to acute nicotine treatment, have desensitized beta endorphin response with chronic nicotine exposure, and demonstrate withdrawal response after cessation of nicotine intake (Boyadjieva and Sarkar, 1997). Opioid blockade with naloxone also led to withdrawal symptoms and attenuated cortisol response in smokers compared to nonsmokers (Krishnan-Sarin et al., 1999). The dose-dependent rise in plasma beta endorphin response to nicotine suggests that the rate of nicotine infusion is critical to nicotine reinforcement value (Pomerleau, 1992), however animal studies show that chronic nicotine intake produces an opioid deficient state which may contribute to maintenance of nicotine dependence (Rasmussen, 1998). "
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ABSTRACT: Stress has been cited as an important precipitator of smoking relapse. Dysregulation of neurobiological pathways related to stress might mediate effects of stress on smoking relapse. This study assessed the extent to which beta endorphin response to stress is associated with early smoking relapse. Forty-five smokers interested in smoking cessation were recruited and attended a laboratory session 24 h following the beginning of their abstinence period. During this session beta endorphin samples were collected before and after performing two acute stressors (public speaking and cognitive tasks). Participants also attended four weekly follow-up sessions to assess their smoking status. Results were compared between smokers who relapsed within the 4-week follow-up period and those who maintained abstinence over the same period. The acute stressors were associated with significant increases in measures of craving and withdrawal symptoms (ps<0.01). While baseline measures of beta endorphin did not differ between relapsers and successful abstainers (F<1), results demonstrated that smokers who relapsed exhibited attenuated beta endorphin response to the two stressors relative to those who maintained abstinence over the same period (ps<05). These results support recent evidence indicating that a dysregulated stress response is a key component in predicting smoking relapse.
Pharmacology Biochemistry and Behavior 09/2008; 90(3):357-62. DOI:10.1016/j.pbb.2008.03.020 · 2.78 Impact Factor
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