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 vilazodone for reducing marijuana use in marijuana-dependent adults. A contingency management intervention (CM)and motivational enhancement therapy (MET)will be incorporated to encourage study engagement and retention, and genomic DNA will be extracted to characterize subjects according to polymorphisms of genes potentially relevant to the activity of vilazodone. It is hypothesized that vilazodone combined with MET and CM will reduce the percent of marijuana-positive urine drug screen results in marijuana-dependent individuals as compared to a placebo treatment combined with MET and CM.

The purpose of this study is to determine if the medication vilazodone is effective in helping frequent marijuana smokers cut down or stop using marijuana. Vilazodone is FDA approved for the treatment of depression- in this study, vilazodone's effect on marijuana dependence is being investigated.

Participation in the study takes 10 visits over a period of approximately two to three months. The first visit is a screening visit to determine if participants are eligible to participate. After the initial assessment visit, the weekly visits take about 30 minutes, with the exception of three therapy sessions which take approximately 60-90 minutes. The three therapy sessions will focus on participant's marijuana use and reasons they may have for stopping or cutting down on use. After completing an initial therapy session, participants will be randomly selected to receive the study medication, either vilazodone or placebo (a capsule that does not contain any active medication). Participants will have weekly study visits with a clinician. At each study visit, they will be asked to fill out forms and answer specific questions concerning their substance use, anxiety symptoms, and feelings in general. They will be providing urine samples to check for illegal drugs of abuse including marijuana and other drugs. They will also have blood samples drawn during to determine if you are taking the medication as directed.

Inclusion Criteria:

• Must meet DSM-IV criteria for marijuana dependence
• Must be between the ages of 18 and 65 years old
• If female and of childbearing potential, must agree to use acceptable method of birth control for duration of the trial.
• Cannabis-positive urine drug screen at screening
• Must consent to random assignment
• Must be able to read and provide informed consent

Exclusion Criteria:

• Women who are pregnant, nursing, or plan to become pregnant during course of study
• Must not have a history of or current psychotic disorder, bipolar disorder, or eating disorder
• Must not pose a current suicidal or homicidal risk
• Must not have evidence or history of serious medical disease
• Must not require concomitant therapy with psychotropic medication or CYP3A4 inhibitors
• Must not be currently dependent on other substances, with the exception of nicotine;
• Patients who, in the investigator's opinion, would be unable to comply with study procedures or assessments

Limitations included small sample size, significant attrition, and difficulty with UCT (urine cannabinoid test) interpretation due to long excretion half-life of cannabis in urine.