Varenicline decreases alcohol consumption in heavy-drinking smokers.
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ABSTRACT: Rationale
Emerging evidence suggests that the ?4?2 form of the nicotinic acetylcholine receptor (nAChR) modulates the rewarding effects of alcohol. The nAChR ?4?2 subunit partial agonist varenicline (Chantix™), which is approved by the Food and Drug Administration for smoking cessation, also decreases ethanol consumption in rodents (Steensland et al., Proc Natl Acad Sci U S A 104:12518-12523, 2007) and in human laboratory and open-label studies (Fucito et al., Psychopharmacology (Berl) 215:655-663, 2011; McKee et al., Biol Psychiatry 66:185-190 2009).Objectives
We present a randomized, double-blind, 16-week study in heavy-drinking smokers (n?=?64 randomized to treatment) who were seeking treatment for their smoking. The study was designed to determine the effects of varenicline on alcohol craving and consumption. Outcome measures included number of alcoholic drinks per week, cigarettes per week, amount of alcohol craving per week, cumulative cigarettes and alcoholic drinks consumed during the treatment period, number of abstinent days, and weekly percentage of positive ethyl glucuronide and cotinine screens.Results
Varenicline significantly decreases alcohol consumption (? (2)?=?35.32, p?ConclusionsVarenicline can produce a sustained decrease in alcohol consumption in individuals who also smoke. Further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking.
SUBMITTER: Mitchell JM
PROVIDER: S-EPMC3438402 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThere is a strong bidirectional relationship between the use of alcohol and cigarettes which results in various challenges for treating those who co-use both substances. While varenicline and naltrexone each have FDA-approval for nicotine and alcohol use disorder, respectively, there is evidence that their clinical benefit may extend across the two disorders. Critically, the effect of combined varenicline and naltrexone on neural reactivity to alcohol cues among heavy drinking smokers has not yet been studied. Probing the effect of the combination therapy on alcohol cue-reactivity may give insight to the mechanisms underlying its efficacy.MethodsForty-seven heavy drinking smokers enrolled in two medication studies were randomized to receive varenicline alone (n = 11), varenicline plus naltrexone (n = 11), or placebo (n = 25). Participants completed an fMRI alcohol cue-reactivity task and rated their in-scanner alcohol craving. Whole-brain analyses examined the effect of medication on alcohol cue-elicited neural response.ResultsVarenicline plus naltrexone attenuated alcohol cue-elicited activation in mesolimbic regions relative to varenicline alone and to placebo (Z > 2.3, p < 0.05). The combination varenicline and naltrexone group also endorsed lower in-scanner alcohol craving relative to varenicline alone group (p = 0.04).ConclusionsThese findings provide evidence for the benefit of combined therapy of varenicline and naltrexone over varenicline alone for the attenuation of alcohol cue-elicited neural activation. This study provides a preliminary proof-of-mechanism for this combination pharmacotherapy and suggests that naltrexone may be driving the reductions in cue-elicited alcohol craving in the brain. Further clinical studies using the combined therapy to treat heavy drinking smokers are warranted.
| S-EPMC9059649 | biostudies-literature
Project description:Heavy-drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available.The present study used a double-blind, randomized, 2?×?2 medication design, testing varenicline alone (VAR; 1 mg twice daily), low dose naltrexone alone (L-NTX; 25 mg once daily), varenicline plus naltrexone, and placebo for effects on cigarette craving and subjective response to alcohol and cigarettes in a sample (n?=?130) of heavy-drinking daily smokers (?10 cigarettes/day).All participants were tested after a 9-day titration period designed to reach a steady state on the target medication. Testing was completed at 12 h of nicotine abstinence, after consuming a standard dose of alcohol (target breath alcohol concentration?=?0.06 g/dl) and after smoking the first cigarette of the day.The combination of VAR?+?L-NTX was superior to placebo, and at times superior to monotherapy, in attenuating cigarette craving, cigarette and alcohol "high," and in reducing ad-lib consumption of both cigarettes and alcohol during the 9-day medication titration period.These preliminary findings indicate that clinical studies of the combination of VAR?+?L-NTX for heavy drinkers trying to quit smoking are warranted and may ultimately improve clinical care for this sizeable and treatment-resistant subgroup of smokers.
| S-EPMC4161630 | biostudies-literature
Project description:ObjectivesCombined smoking and heavy drinking is a significant health burden. Varenicline, an efficacious tobacco pharmacotherapy that also shows promise for drinking, has yielded mixed results among heavy-drinking smokers. This pilot study investigated integrated tobacco and alcohol counselling plus varenicline for this vulnerable group.DesignTwelve-week parallel, randomized controlled pilot trial of two behavioural interventions in combination with open-label varenicline. Participants were randomized using computer-generated tables, stratified by sex.SettingOutpatient academic medical centre research clinic.ParticipantsVolunteers who reported smoking and heavy drinking and sought tobacco or alcohol treatment (N = 26). Intervention. (1) Integrated tobacco + alcohol counselling (INT; n = 13) or (2) counselling focused on their presenting concern (i.e., tobacco or alcohol) (SINGLE; n = 13), plus varenicline (2 mg) for 12 weeks.Main outcomesFeasibility/acceptability, smoking quit rates and heavy drinking.ResultsINT feasibility/acceptability was high among men but not women. More participants quit smoking in INT than SINGLE. This outcome was only in men, not significant, but had a medium effect size. Both conditions yielded significant drinking reductions.ConclusionIntegrated tobacco and alcohol behavioural counselling plus varenicline may be feasible and promote smoking cessation among men who smoke and drink heavily, but a larger sample is needed to replicate this finding.
| S-EPMC7731353 | biostudies-literature
Project description:AimsWomen often experience poorer smoking cessation outcomes in comparison to men. Menstrual cycle phase and sex hormones may influence smoking behavior and alter response to opioid antagonist medications. Less is known about the effects of sex hormones in response to pharmacotherapy for female heavy drinking smokers.MethodsThis study is a secondary analysis of premenopausal female heavy drinking smokers who completed a 12-week randomized clinical trial comparing varenicline plus placebo versus varenicline plus naltrexone for smoking cessation and drinking reduction. Participants (n = 26; total observations = 66) provided saliva samples for assays of progesterone (P4) and estradiol (E2) post-randomization at Weeks 4, 8 and 12. We examined the effects of P4/E2 ratio and medication on smoking and drinking outcomes.ResultsFor drinking outcomes, there was a significant interaction for percent days abstinent (b = 0.017, P = 0.05), suggesting that greater P4/E2 ratio is associated with greater percent days abstinent for women assigned to the varenicline plus naltrexone condition. There were no interaction effects for the remaining drinking outcomes (P's ≥ 0.12). Results found no significant interaction effect of P4/E2 ratio and medication on smoking abstinence (P = 0.19).ConclusionOur results imply that when women show a greater P4/E2 ratio, typically observed during the luteal phase of the menstrual cycle, they experience an added benefit of naltrexone, versus placebo, for drinking outcomes as shown by greater percent days abstinent. Additional studies in larger samples are warranted as sex hormones offer important information above and beyond comparing women versus men.
| S-EPMC9465527 | biostudies-literature
Project description:A strong link exists between cigarette smoking and alcohol use, which may be explained by the experimental observation that alcohol ingestion promotes cigarette craving and precipitates smoking. At the neuroanatomic level, it is unclear where and how alcohol exerts these effects, although the process likely involves the ventral striatum given its function in motivational salience and appetitive reinforcement. In a double-blinded, placebo-controlled, crossover study, heavy drinking nondaily social smokers (ie, light smokers or 'chippers') were examined using functional magnetic resonance imaging after they ingested an acute dose of alcohol or placebo. We probed reactivity in the ventral striatum and other brain regions during exposure to visual smoking vs nonsmoking control cues. We found that alcohol enhanced self-reported ratings of desire to smoke, and in this context, significantly increased ventral striatum responses to smoking compared with control cues. In exploratory analyses, we observed that alcohol dampened orbitofrontal activity across both cue types, whereas dorsolateral prefrontal and anterior cingulate cortex activation to smoking cues was not affected by alcohol. This study bridges a pharmacological challenge approach to the study of brain reactivity to smoking cues, extends prior cigarette cue imaging studies to nondependent smokers, and elucidates a potential neurobiological mechanism to explain the co-consumption of alcohol and cigarettes in nondependent users.
| S-EPMC2868310 | biostudies-other
Project description:High average daily consumption of alcohol has been associated with elevated mortality risk, but more moderate consumption, relative to abstinence, has been associated with reduced mortality risk. However, average daily consumption can be complicated to assess, limiting its usefulness in both research and clinical practice. There are also concerns that average consumption fails to capture the risk associated with certain drinking patterns, such as heavy episodic drinking. This study assessed mortality associated with drinking pattern, operationalized as the frequency of both heavy and nonheavy drinking occasions.Data from the 1997 to 2001 administrations of the National Health Interview Survey (NHIS; n = 111,511) were paired with the current release of the NHIS Linked Mortality Files, which provided mortality follow-up data through the end of 2006. We estimated the impact of drinking pattern on all-cause mortality, operationalized as the frequency of heavy (5+ drinks) and nonheavy (<5 drinks) drinking occasions. Other covariates in the model included survey wave, sex, age, race/ethnicity, ratio of family income to poverty threshold, educational attainment, body mass index, and smoking status.Over a third of past-year drinkers reported heavy drinking. Mortality risk increased steadily as heavy drinking frequency increased; daily heavy drinkers exhibited an almost 2-fold risk of death compared with abstainers (p < 0.001). Regular nonheavy drinking was associated with decreased mortality, similar to the "J-shaped curve" highlighted in past research on alcohol mortality; this potential protective effect peaked around 2 nonheavy occasions per week.Any heavy drinking likely elevates mortality risk, and substantial health benefits could be realized by reducing heavy drinking occasions or limiting overall drinking. Heavy and nonheavy drinking frequencies are valid targets for clinical screening and could be helpful in assessing risk and promoting less harmful drinking behavior.
| S-EPMC3872245 | biostudies-literature
Project description:BACKGROUND:Rate of nicotine metabolism is an important factor influencing cigarette smoking behavior, dependence, and efficacy of nicotine replacement therapy. The current study examined the hypothesis that chronic alcohol abuse can accelerate the rate of nicotine metabolism. Nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism) and patterns of nicotine metabolites were assessed at three time points after alcohol cessation. METHODS:Participants were 22 Caucasian men randomly selected from a sample of 165 smokers entering a 7-week alcohol dependence treatment program in Poland. Data were collected at three time points: baseline (week 1, after acute alcohol detoxification), week 4, and week 7. Urine was analyzed for nicotine and metabolites and used to determine the nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism), and total nicotine equivalents (TNE, a biomarker for total daily nicotine exposure). RESULTS AND CONCLUSIONS:There was a significant decrease in urine NMR over the 7 weeks after alcohol abstinence (F(2,42)=18.83, p<0.001), indicating a decrease in rate of nicotine metabolism. On average NMR decreased 50.0% from baseline to week 7 (9.6±1.3 vs 4.1±0.6). There was no change in urine TNE across the three sessions, indicating no change daily nicotine intake. The results support the idea that chronic alcohol abuse may increase the rate of nicotine metabolism, which then decreases over time after alcohol cessation. This information may help to inform future smoking cessation interventions in this population.
| S-EPMC4880506 | biostudies-literature
Project description:BACKGROUND:Low socioeconomic status (SES) has been associated with lower alcohol consumption, but also with heavier drinking. To explain this contradictory relationship, we examined SES differences in drinking patterns from an age-period-cohort (APC) perspective. METHODS:Data are from seven waves of the U.S. National Alcohol Surveys from 1979 to 2010. As a proxy for SES, educational attainment was used. Past-year alcohol volume was calculated from frequency (never-to-every day) and usual quantity (1-2, 3-4, or 5-6 drinks). Past-year frequency of heavy episodic drinking was labelled as total days of 5+ drinks. Gender-stratified APC fixed-effects models were conducted controlling for demographics and adjusting for survey design and weights. RESULTS:Significant APC effects by education were found, but the direction varied by alcohol measure. Education and total volume were positively associated across APC. Cross-over effects for age occurred with a positive education-heavy drinking relationship in young adulthood and negative relationship in mid-adulthood. Cohort-by-education effects showed greater heavy drinking among less educated women in 1956-60 cohort and more educated men and women in younger cohorts (post-1976). CONCLUSIONS:Higher SES is consistently associated with total volume across age, period, and cohort, but less consistently with heavy drinking. While there are currently significant intervention efforts to reduce heavy drinking in young adulthood, our study suggests the need for age-specific strategies targeting lower-SES groups in mid-adulthood and cohort-specific strategies for lower-SES women in the baby boomer cohort and higher-SES men and women in younger birth cohorts.
| S-EPMC6003414 | biostudies-literature
Project description:Clinical trials and human laboratory studies have established that varenicline can reduce rates of alcohol use among heavy drinkers. Less is known about the mechanisms by which varenicline has this effect on drinking behavior. Reactivity to alcohol cues is often cited as the primary cause of relapse among those being treated for alcohol use disorder, and several front-line treatments for alcohol use disorder work, at least in part, by minimizing cue-induced alcohol craving.The current double-blind, placebo-controlled human laboratory study tested the effects of varenicline on alcohol cue reactivity in a group of heavy-drinking adult smokers and nonsmokers.As part of a larger series of sequential human laboratory experiments testing the effects of varenicline on drinking outcomes, participants were assigned (between-participant) to receive either active varenicline (2 mg/day) or placebo. Following a titration period, participants (n = 77) attended a laboratory session during which they were exposed to alcohol and neutral cues using a standard cue reactivity paradigm.Alcohol cue exposure increased craving for alcohol in both medication groups. However, participants receiving varenicline showed a smaller increase in alcohol craving compared to participants receiving placebo. The medication effect did not differ between smokers and nonsmokers. Among smokers, alcohol cue exposure also increased tobacco craving. Varenicline did not attenuate this effect.Results support the use of varenicline for reducing alcohol use in heavy drinkers and identify a potential mechanism by which varenicline reduces drinking. Varenicline continues to show promise as a pharmacological treatment for alcohol use disorder.
| S-EPMC5709183 | biostudies-literature
Project description:IntroductionPrevious studies have highlighted a strong bidirectional relationship between cigarette and alcohol consumption. To advance our understanding of this relationship the present study uses a behavioral economic approach in a community sample (N = 383) of nontreatment seeking heavy drinking smokers.Aims and methodsThe aims were to examine same-substance and cross-substance relationships between alcohol and cigarette use, and latent factors of demand. A community sample of nontreatment seeking heavy drinking smokers completed an in-person assessment battery including measures of alcohol and tobacco use as well as the Cigarette Purchase Task and the Alcohol Purchase Task. Latent factors of demand were derived from these hypothetical purchase tasks.ResultsResults revealed a positive correlation between paired alcohol and cigarette demand indices (eg, correlation between alcohol intensity and cigarette intensity) (rs = 0.18-0.46, p ≤ .003). Over and above alcohol factors, cigarette use variables (eg, Fagerström Test for Nicotine Dependence and cigarettes per smoking day) significantly predicted an additional 4.5% (p < .01) of the variance in Persistence values but not Amplitude values for alcohol. Over and above cigarette factors, alcohol use variables predicted cigarette Persistence values (ΔR2 = .013, p = .05), however, did not predict Amplitude values.ConclusionsThese results advance our understanding of the overlap between cigarette and alcohol by demonstrating that involvement with one substance was associated with demand for the other substance. This asymmetric profile-from smoking to alcohol demand, but not vice versa-suggests that it is not simply tapping into a generally higher reward sensitivity and warrants further investigation.ImplicationsTo our knowledge, no study to date has examined alcohol and cigarette demand, via hypothetical purchase tasks, in a clinical sample of heavy drinking smokers. This study demonstrates that behavioral economic indices may be sensitive to cross-substance relationships and specifically that such relationships are asymmetrically stronger for smoking variables affecting alcohol demand, not the other way around.
| S-EPMC7976931 | biostudies-literature