Marijuana is the most commonly used illicit drug in the United States. Although its use and potential health consequences are widespread and basic science research on cannabinoids is well developed, little research has focused on the clinical treatment of marijuana use disorders. Buspirone, a partial serotonin 1-A (5-HT1A [5-hydroxytryptamine1A]) receptor agonist, has shown promise for reducing marijuana use in preliminary trials. Accordingly, we propose a double-blind randomized trial of buspirone in marijuana-dependent individuals. A contingency management (CM) intervention coupled with motivational enhancement therapy (MET) will be incorporated to encourage study engagement and retention. We hypothesize that individuals who receive buspirone treatment combined with MET and CM will have improved marijuana use outcomes compared to individuals receiving a placebo treatment combined with MET and CM. Further, as genetic variations in 5-HT1A receptors have been identified, and may alter the response to buspirone, we propose to extract genomic DNA to characterize subjects according to polymorphisms of genes relevant to 5-HT1A receptor activity. We hypothesize that individuals with functionally deficient 5-HT1A receptors will have poorer treatment outcomes than individuals without functional deficiency at the 5-HT1A receptor. Finally, as a reliable assessment of compliance is critical to interpretation of outcome measures, we propose as a secondary aim to develop and validate an assay of a major metabolite of buspirone (6-hydroxy-buspirone) to measure compliance with treatment. Results from this study could lead to the development of a new pharmacotherapy for marijuana dependence, increase our knowledge of a potential genetic biomarker for prediction of outcomes, and improve clinical trial methodology in the investigation of marijuana dependence. .

Public Health Relevance

Marijuana is the most commonly used illicit drug, yet few clinical trials have evaluated pharmacotherapy treatments for marijuana dependence. This study will evaluate the efficacy of buspirone for reducing marijuana use in marijuana-dependent adults. A contingency management intervention and motivational enhancement therapy will be incorporated to encourage study engagement and retention. An assay determining serum levels of a major metabolite of buspirone will be employed to measure compliance, and genomic DNA will be extracted to characterize subjects according to polymorphisms of genes potentially relevant to the activity of buspirone.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA026782-05
Application #
8460582
Study Section
Special Emphasis Panel (ZDA1-MXH-H (01))
Program Officer
Hampson, Aidan
Project Start
2009-08-15
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$302,725
Indirect Cost
$72,253
Name
Medical University of South Carolina
Department
Psychiatry
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425