Naltrexone for the Treatment of Alcoholism: Clinical Findings, Mechanisms of Action, and Pharmacogenetics

Abstract

Naltrexone is an opioid receptor antagonist with established efficacy, albeit moderate, for the treatment of alcohol dependence. This manuscript provides a critical review of the literature on naltrexone as a pharmacotherapy for alcoholism by covering the following areas: (a) clinical findings from treatment studies; (b) pharmacokinetics and safety data; (c) medication compliance and persistence; and (d) neurobiological and biobehavioral mechanisms of action of naltrexone for the indication of alcohol dependence. This review will then focus on the emerging literature on naltrexone pharmacogenetics, which has the potential to identify responders on the basis of genetic variation and to use genetic tools to individualize the use of this medication. Limitations and future directions in the research and practice of naltrexone for alcoholism are also outlined.

The Neuroimmune Transcriptome and Alcohol Dependence: Potential for Targeted Therapies

“…There are a limited number of repositioned drugs that have been identified as potential AUD therapeutics. These include topiramate, which was originally used as an anticonvulsant drug used to treat epilepsy [131,132], naltrexone, an opiate receptor antagonist [133] and aripiprazole, an atypical antipsychotic, with potential for treating alcohol dependence [134]. And, rele vant to the current review and the role of the neuroimmune system in AUD, there is evidence that ibudilast, a nonselective phosphodiesterase inhibitor, decreases alcohol consumption in animal models [135].…”

Alteraciones neurobiológicas en el alcoholismo: revisión

“…The efficacy of naltrexone to suppress alcohol consumption, craving, and rates of relapse, albeit moderate, has attributed an important role to endogenous opioid peptides with affinity for the mu opioid receptor (endorphins and enkephalins) in mediating various alcohol-related effects and behaviours (Ray, Chin & Miotto, 2010).…”

“…At last, it is important to note that there is considerable heterogeneity among people with alcohol addiction, and that this heterogeneity suggests a need for personalized treatment approaches based on, among other factors, genetic variation. There is emerging literature on naltrexone pharmacogenetics, which has the potential to identify responders on the basis of particular genetic polymorphisms (Ray et al 2010). Genetic variations on the corticotropin-releasing factor systems is also likely to moderate alcoholism treatment effects ((Markus Heilig, Goldman, Berrettini & O'Brien, 2011;Zorrilla et al, 2013).…”

Pharmacogenomics of alcohol addiction: Personalizing pharmacologic treatment of alcohol dependence

“…Furthermore, given the signifi cance of clinical trials assessing implementation of pharmacogenomics in routine clinical practice, completed and ongoing clinical trials on alcohol addiction pharmacogenomics are listed in Table 3. pleasure and, ultimately, less craving and relapse. μ-opioid receptors primarily bind β-endorphin and diff use this binding via Gprotein signaling that alters neuronal fi ring and leads to neuroadaptive changes [27]. Other opioid receptor antagonists with similar to naltrexone properties are naloxone and nalefene, however, naltrexone is more commonly prescribed in alcohol addiction therapy.…”

“…Th is substitution has been reported to increase binding of β-endorphin and increase functional activity in vitro. Carriers of 118G (40Asp) allele have 3-fold higher affi nity for β-endorphin binding compared to 118AA (40AsnAsn) individuals ( Since naltrexone targets the μ-opioid receptor, OPRM1 118A>G gene polymorphism is an attractive candidate to assess the interindividual diff erential response to naltrexone [27]. Indeed, results of several studies suggest that 118G carriers respond better to naltrexone treatment.…”