Longitudinal Findings from a Randomized Clinical Trial of Varenicline for Alcohol Use Disorder with Comorbid Cigarette Smoking

Bold, Krysten W.; Zweben, Allen; Fucito, Lisa M.; Piepmeier, Mary; Muvvala, Srinivas; Wu, Rongqian; Gueorguieva, Ralitza; O’Malley, Stephanie S.

doi:10.1111/acer.13994

Cited by 17 publications

(9 citation statements)

References 52 publications

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“…This conclusion is somewhat inconsistent with previous evidence in rodents showing reductions in alcohol use following the administration nicotinic treatments (e.g. varenicline 75,76 ), although evidence from RCTs in humans is mixed 77,78 and efficacy may not translate into the long-term 79 .…”

Section: Discussioncontrasting

confidence: 65%

Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study

Schoeler

Baldwin

Allegrini

et al. 2021

Preprint

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Addiction to nicotine, alcohol and cannabis commonly co-occurs, which is thought to partly stem from a common heritable liability. To elucidate its genetic architecture, we modelled the common liability to addiction, inferred from genetic correlations among six measures of dependence and frequency of use of nicotine, alcohol and cannabis. Forty-two genetic variants were identified in the multivariate genome-wide association study on the common liability to addiction, of which 67% were novel and not associated with the six phenotypes. Mapped genes highlighted the role of dopamine (e.g., dopamine D2 gene), and showed enrichment for several components of the central nervous systems (e.g., mesocorticolimbic brain regions) and molecular pathways (dopaminergic, glutamatergic, GABAergic) that are thought to modulate drug reinforcement. Genetic correlations with other traits were most prominent for reward-related behaviours (e.g., risk-taking, cocaine and heroin use) and mood (e.g., depression, insomnia). These genome-wide results triangulate and expand previous preclinical and human studies focusing on the neurobiological substrates of addiction, and help to elucidate the common genetic architecture underlying addiction.

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Section: Discussioncontrasting

confidence: 65%

Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study

Schoeler

Baldwin

Allegrini

et al. 2021

Preprint

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“…In a sample of participants with alcohol use disorders who were co-morbid smokers, larger decreases in drinking were observed in men, vs. the smaller decreases observed in women [ 115 ]. In addition, men had higher rates of ‘no heavy drinking’ with varenicline vs. placebo than women [ 116 ].…”

Section: Alcoholmentioning

confidence: 99%

Consideration of sex and gender differences in addiction medication response

McKee

McRae‐Clark

2022

Biol Sex Differ

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Substance use continues to contribute to significant morbidity and mortality in the United States, for both women and men, more so than any other preventable health condition. To reduce the public health burden attributable to substances, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism have identified that medication development for substance use disorder is a high priority research area. Furthermore, both Institutes have stated that research on sex and gender differences in substance use medication development is a critical area. The purpose of the current narrative review is to highlight how sex and gender have been considered (or not) in medication trials for substance use disorders to clarify and summarize what is known regarding sex and gender differences in efficacy and to provide direction to the field to advance medication development that is consistent with current NIH ‘sex as a biological variable’ (SABV) policy. To that end, we reviewed major classes of abused substances (nicotine, alcohol, cocaine, cannabis, opioids) demonstrating that, sex and gender have not been well-considered in addiction medication development research. However, when adequate data on sex and gender differences have been evaluated (i.e., in tobacco cessation), clinically significant differences in response have been identified between women and men. Across the other drugs of abuse reviewed, data also suggest sex and gender may be predictive of outcome for some agents, although the relatively low representation of women in clinical research samples limits making definitive conclusions. We recommend the incorporation of sex and gender into clinical care guidelines and improved access to publicly available sex-stratified data from medication development investigations.

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“…In substantia nigra and VTA, the nAChRs can regulate the release of dopamine which is critical for the mesolimbic pathway signaling . Varenicline is a partial agonist of the α 4/β 2 subtypes of nAChR, and it has been shown to successfully treat smoking as well as alcohol addiction in clinical trials . Thus, they are considered as novel therapeutic targets for the management of smoking and comorbid alcohol addiction.…”

Section: Transmuted Neurotransmitter Signaling Across the Brain Rewar...mentioning

confidence: 99%

“…37 Varenicline is a partial agonist of the α 4/β 2 subtypes of nAChR, and it has been shown to successfully treat smoking as well as alcohol addiction in clinical trials. 38 Thus, they are considered as novel therapeutic targets for the management of smoking and comorbid alcohol addiction.…”

Section: Serotonergic System During Alcohol Addictionmentioning

confidence: 99%

Probing the Manipulated Neurochemical Drive in Alcohol Addiction and Novel Therapeutic Advancements

Chouhan

Uniyal

Gadepalli

et al. 2020

ACS Chem. Neurosci.

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Alcohol addiction is one of the highly prevalent neurological disorders and a major threat to public health in the 21st century. Alcohol addiction affects people from all age groups and often leads to other serious comorbidities. The pathophysiology of alcohol addiction involves imbalance between the excitatory and inhibitory neurotransmitters in the brain. These changes occur in various regions of the brain including reward circuit such as the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex. In this review, we have discussed several neurochemical circuitries which get manipulated and maladapted during alcohol addiction. To date there is no effective therapeutic intervention in clinics devoid of side effects that can successfully treat the patients suffering from alcohol addiction. Understanding the neurobiological intricacies of alcohol addiction is critical for the development of novel anti-addiction therapeutics. Apart from this, we have also discussed the recent therapeutic milestones for the management of alcohol addiction including vasopressin receptors, corticotrophin-releasing factor, GABA receptors, glucocorticoid receptors, brain stimulation and mindfulness-oriented recovery enhancement.

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Longitudinal Findings from a Randomized Clinical Trial of Varenicline for Alcohol Use Disorder with Comorbid Cigarette Smoking

Cited by 17 publications

References 52 publications

Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study

Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study

Consideration of sex and gender differences in addiction medication response

Probing the Manipulated Neurochemical Drive in Alcohol Addiction and Novel Therapeutic Advancements

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