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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA014886-06
Application #
7741750
Study Section
Special Emphasis Panel (ZAA1-CC (47))
Program Officer
Fertig, Joanne
Project Start
2005-12-01
Project End
2011-08-30
Budget Start
2009-12-01
Budget End
2011-08-30
Support Year
6
Fiscal Year
2010
Total Cost
$547,578
Indirect Cost
Name
The Mind Research Network
Department
Type
DUNS #
098640696
City
Albuquerque
State
NM
Country
United States
Zip Code
87106
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Blaine, Sara; Claus, Eric; Harlaar, Nicole et al. (2013) TACR1 genotypes predict fMRI response to alcohol cues and level of alcohol dependence. Alcohol Clin Exp Res 37 Suppl 1:E125-30
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
Claus, Eric D; Feldstein Ewing, Sarah W; Filbey, Francesca M et al. (2013) Behavioral control in alcohol use disorders: relationships with severity. J Stud Alcohol Drugs 74:141-51
Claus, Eric D; Hutchison, Kent E (2012) Neural mechanisms of risk taking and relationships with hazardous drinking. Alcohol Clin Exp Res 36:932-40

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