Demand for treatment for marijuana-related problems in the U.S. increased nearly 2-fold during the past 15 years. Despite the efficacy of behavioral treatments, many individuals do not initiate abstinence during treatment and many who do relapse to use either during or after treatment, pointing to the difficulty treating cannabis dependence and the need for efficacious pharmacological treatments. Selegiline, a monoamine oxidase-B inhibitor, increases dopamine activity in mesolimbic and other brain regions involved in dependence on addictive drugs, including nicotine, cocaine and cannabis. Selegiline has recently shown efficacy in treating nicotine-dependence and reducing the rewarding effects of nicotine and cocaine, but it has not yet been studied in cannabis-dependence. Consequently, we are proposing a placebo-controlled, double blind, pilot clinical trial of selegiline for treating cannabis dependence.
Specific aims of the proposed study are: 1) to conduct a pilot study to obtain efficacy data regarding the effect size between selegiline compared to placebo for reducing cannabis use in cannabis-dependent patients; and 2) to explore the impact of selegiline and placebo on acute and protracted withdrawal symptoms. Cannabis-dependent participants (N=40) will be randomly assigned to 8 weeks of treatment with selegiline (10 mg/day) or placebo. All participants will receive weekly individual standard medical management provided by a specially :rained physician. Primary outcome measures include reduction in frequency of cannabis use and weeks of consecutive cannabis abstinence (as assessed by self-report and verified by twice weekly quantitative urine tests). Secondary outcomes include reduction in cannabis withdrawal symptoms, mood change, and safety and tolerability of the medication. Data analyses will focus on an intention-to-treat sample and will utilize mixed-model analysis of variance. Findings will provide a reliable estimate of the effect size of the difference between selegiline and placebo that will be used to determine the sample size needed to provide sufficient power to detect significant differences in a subsequent full-scale clinical trial. Study findings will also be important in exploring potential mechanism of action of selegiline and establishing a program of research to evaluate medications for cannabis-dependence.
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