Methamphetamine (MA) misuse has increased dramatically in the United States during the past decade. Nevertheless, efficacious pharmacotherapies for MA dependence remain elusive despite extensive research on the neurobiology of the effects of amphetamines. Naltrexone (NTX) is an opioid receptor antagonist with empirically supported efficacy and FDA-approval for the treatment of alcoholism. A recent placebo-controlled study has suggested that NTX may be promising for the treatment of amphetamine dependence as it significantly increased abstinence, measured by amphetamine-negative urine samples, compared to placebo. This New Investigator R21 seeks to (a) examine the biobehavioral mechanisms of action of NTX for MA use disorders;and (b) test the pharmacogenetics of NTX for these disorders. We propose to recruit 50 non- treatment seeking individuals who meet criteria for MA dependence. Participant will complete two double- blinded, within-subjects MA administration laboratory sessions, one after taking NTX (50 mg/day) and one after taking placebo for four days. It is hypothesized that NTX will blunt MA-induced reward and craving and will improve response inhibition. In addition, we hypothesize that genetic polymorphisms of the mu, kappa, and delta opioid receptors will be useful in identifying responders to NTX and individual differences in MA-induced reward. The successful completion of this application will provide an initial characterization of the mechanisms of action of NTX among MA abusers and its pharmacogenetics. The long-term objective of this research is to develop and optimize pharmacotherapies for MA dependence by combining behavioral pharmacology and pharmacogenetics to elucidate the mechanisms of action of NTX for MA use disorders and their genetic bases.

Public Health Relevance

Efficacious pharmacotherapies for methamphetamine (MA) dependence remain elusive despite extensive research on the neurobiology of MA. The successful completion of this application will provide an initial characterization of the mechanisms of action of naltrexone, a promising pharmacotherapy for MA use disorders, and will identify genes that may help us identify responders to this medication.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21DA029831-02S1
Application #
8656896
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (03))
Program Officer
Walton, Kevin
Project Start
2011-09-15
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$25,196
Indirect Cost
$1,866
Name
University of California Los Angeles
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Bujarski, Spencer; Roche, Daniel J O; Lunny, Katy et al. (2014) The relationship between methamphetamine and alcohol use in a community sample of methamphetamine users. Drug Alcohol Depend 142:127-32