Abstract

Craving for alcohol has been related to loss of control drinking and is a major target of biological and behavioral interventions for alcohol dependence. Our previous research has demonstrated that olanzapine (a dopamine antagonist) attenuates craving for alcohol, that a variant in the gene that expresses D4 receptors influences craving for alcohol, and that olanzapine is particularly effective at reducing craving among individuals with this variant. Pilot data from a recent 12week trial of olanzapine indicates that olanzapine is well tolerated and that olanzapine reduces drinking, particularly among individuals with the aforementioned genetic variant. The objective of the present application is to examine the effectiveness of olanzapine (5 mg/day), as compared to olanzapine (2.5 mg/day) and a placebo control, in terms of reducing craving and alcohol use behavior among treatment seeking alcoholics. Furthermore, the present application will examine whether the effects of olanzapine on drinking outcomes are mediated by its effects on a specific putative mechanism (i.e., cue-elicited craving for alcohol) and determine whether the DRD4 VNTR polymorphism is a marker for the effectiveness of olanzapine. To that end, 202 alcohol dependent subjects will be randomly ; assigned to medication group and receive 12 weeks of medication. Subjects will complete follow-up assessments at 3 and 6 months after the end of the treatment. It is expected that olanzapine will significantly reduce cue-elicited craving and alcohol use behavior in a dose dependent fashion over the course of the 12 week trial and follow-up period, as compared to the placebo condition. Furthermore, it is expected that the effects of olanzapine on alcohol use behavior will be mediated by the effect of olanzapine on cue-elicited craving and that the effects of olanzapine on cue-elicted craving and alcohol use behavior will be moderated by the DRD4 VNTR, such that olanzapine will be more effective among individuals with the 7 repeat allele. The successful completion of the proposed research is expected to advance a new medication for alcohol dependence and advance genetic markers that predict the effectiveness of this medication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA014886-04
Application #
7324111
Study Section
Special Emphasis Panel (ZAA1-CC (47))
Program Officer
Fertig, Joanne
Project Start
2005-12-01
Project End
2010-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
4
Fiscal Year
2008
Total Cost
$538,897
Indirect Cost

  Institution

Name
The Mind Research Network
Department
Type
DUNS #
098640696
City
Albuquerque
State
NM
Country
United States
Zip Code
87106

  Publications

Bidwell, L Cinnamon; Karoly, Hollis C; Thayer, Rachel E et al. (2018) DRD2 promoter methylation and measures of alcohol reward: functional activation of reward circuits and clinical severity. Addict Biol :
Mayer, Andrew R; Hanlon, Faith M; Claus, Eric D et al. (2018) An Examination of Behavioral and Neuronal Effects of Comorbid Traumatic Brain Injury and Alcohol Use. Biol Psychiatry Cogn Neurosci Neuroimaging 3:294-302
Karoly, Hollis C; Thayer, Rachel E; Hagerty, Sarah L et al. (2017) TLR4 Methylation Moderates the Relationship Between Alcohol Use Severity and Gray Matter Loss. J Stud Alcohol Drugs 78:696-705
Gardiner, Casey K; YorkWilliams, Sophie L; Bryan, Angela D et al. (2017) Body mass is positively associated with neural response to sweet taste, but not alcohol, among drinkers. Behav Brain Res 331:131-134
Littlewood, Rae A; Claus, Eric D; Arenella, Pamela et al. (2015) Dose specific effects of olanzapine in the treatment of alcohol dependence. Psychopharmacology (Berl) 232:1261-8
Monnig, Mollie A; Yeo, Ronald A; Tonigan, J Scott et al. (2015) Associations of White Matter Microstructure with Clinical and Demographic Characteristics in Heavy Drinkers. PLoS One 10:e0142042
Harlaar, Nicole; Bryan, Angela D; Thayer, Rachel E et al. (2014) Methylation of a CpG site near the ALDH1A2 gene is associated with loss of control over drinking and related phenotypes. Alcohol Clin Exp Res 38:713-21
Yeo, Ronald A; Thoma, Robert J; Gasparovic, Charles et al. (2013) Neurometabolite concentration and clinical features of chronic alcohol use: a proton magnetic resonance spectroscopy study. Psychiatry Res 211:141-7
Liu, Jingyu; Calhoun, Vince D; Chen, Jiayu et al. (2013) Effect of homozygous deletions at 22q13.1 on alcohol dependence severity and cue-elicited BOLD response in the precuneus. Addict Biol 18:548-58
Wilcox, Claire E; Claus, Eric D; Blaine, Sara K et al. (2013) Genetic variation in the alpha synuclein gene (SNCA) is associated with BOLD response to alcohol cues. J Stud Alcohol Drugs 74:233-44

Showing the most recent 10 out of 21 publications