« Treatment for Alcoholism

The Nociceptin/Orphanin FQ System as a Target for Treating Alcoholism.
Primary Author:
Primary Author: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California at Los Angeles, 760 Westwood Plaza, Los Angeles, California 90024-1759, USA. nmurphy@ucla.edu.
Date Published: 2010 03 05
Abstract: Nociceptin (known also as orphanin FQ) is the most recently discovered member of the endogenous opioid peptide family, albeit nearly 15 years ago. Nociceptin renders or influences many behavioral, psychological and neurobiological processes, including memory, anxiety, stress and reward. Since its discovery, results of a steady stream of studies have suggested that endogenous nociceptin might be involved in responses to addictive drugs, and that targeting the nociceptin system may be beneficial in treating addictions. The current review summarizes and critically appraises those studies, particularly those that point to an application in treating alcoholism. Overall, most, studies suggest that the endogenous nociceptin system has a physiological role in mediating or regulating behavioral responses to alcohol, and that activating nociceptin receptors suppresses ongoing alcohol consumption or reinstatement of responding for alcohol. These findings encourage the development of therapies targeted at the nociceptin system for the treatment of alcoholism in humans, though a minor number of studies showing continuous activation of the nociceptin receptor can produce increased, rather than reduced, alcohol consumption emphasize the necessity of further investigation.

Pre-Clinical Evidence that Corticotropin-Releasing Factor (CRF) Receptor Antagonists are Promising Targets for Pharmacological Treatment of Alcoholism.
Primary Author: Emily G Lowery
Primary Author: Department of Psychology, University of North Carolina, Chapel Hill, NC 27599-3270, USA. thiele@unc.edu.
Date Published: 2010 03 05
Abstract: Alcoholism is a chronic disorder characterized by cycling periods of excessive ethanol consumption, withdrawal, abstinence and relapse, which is associated with progressive changes in central corticotropin-releasing factor (CRF) receptor signaling. CRF and urocortin peptides act by binding to the CRF type 1 (CRF1R) or the CRF type 2 (CRF2R) receptors, both of which have been implicated in the regulation of neurobiological responses to ethanol. The current review provides a comprehensive overview of preclinical evidence from studies involving rodents that when viewed together, suggest a promising role for CRFR antagonists in the treatment of alcohol abuse disorders. CRFR antagonists protect against excessive ethanol intake resulting from ethanol dependence without influencing ethanol intake in non-dependent animals. Similarly, CRFR antagonists block excessive binge-like ethanol drinking in non-dependent mice but do not alter ethanol intake in mice drinking moderate amounts of ethanol. CRFR antagonists also protect against increased ethanol intake and relapse-like behaviors precipitated by exposure to a stressful event. Additionally, CRFR antagonists attenuate the negative emotional responses associated with ethanol withdrawal. The protective effects of CRFR antagonists are modulated by CRF1R. Finally, recent evidence has emerged suggesting that CRF2R agonists may also be useful for treating alcohol abuse disorders.

Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics.
Primary Author: Lara A Ray
Primary Author: Department of Psychology, University of California Los Angeles, USA. lararay@psych.ucla.edu.
Date Published: 2010 03 05
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 effects of alcoholism comorbidity on neurocognitive function following traumatic brain injury.
Primary Author: Daniel N Allen
Primary Author: Department of Psychology, University of Nevada Las Vegas, Las Vegas, Nevada 89154-5030, USA. daniel.allen@unlv.edu
Date Published: 2010 02 25
Abstract: Alcoholism and traumatic brain injury (TBI) often produce neuropsychological deficits. However, the extent and manner by which these factors interact is unclear. In this study, it was hypothesized that alcoholism would have compounding cognitive effects in individuals with TBI and alcoholism. Participants were divided into three groups, including a patient comparison (PC) group and groups with TBI with or without alcoholism histories. Participants were administered the Wechsler Adult Intelligence Scale-Revised and major components of the Halstead-Reitan Neuropsychological Test Battery. Comparing the groups on test performance, the TBI groups performed significantly worse than the PC group but did not significantly differ from each other. Thus, the effects of TBI on cognitive function overshadow preexisting deficits from the alcoholism.