The objective of this research proposal is to use functional magnetic resonance imaging (fMRI) and a laboratory model of cannabis self-administration to evaluate an innovative type of repetitive transcranial magnetic stimulation (rTMS) in human volunteers as a potential treatment approach to cannabis dependence. There is preliminary evidence that rTMS with standard coils applied to the dorsolateral prefrontal cortex in cocaine and tobacco users reduce drug craving and drug self-administration. This study proposes to use rTMS with the H1 coil, which allows for the stimulation of deeper brain structures than previously available. The H1 coil will be directed at the dorsomedial prefrontal cortex (PFC) and anterior cingulate (ACC), areas shown to be affected in addiction, including cannabis dependence. Using fMRI and the Stroop color-naming task, we will compare baseline BOLD activation in the PFC and ACC of abstinent (but not treatment-seeking) chronic cannabis users and control subjects. The Stroop task assesses response to conflicting stimuli and response inhibition, functions subserved by the ACC and DLPFC. Cannabis using subjects will be randomized to receive active vs. sham rTMS for 11 days. We will repeat fMRI to measure any changes in BOLD activation in the PFC and ACC resulting from active rTMS administration, compared to sham. In addition, a laboratory model of cannabis seeking behavior will be used to investigate the potential of rTMS to reduce cannabis self-administration in human subjects. Laboratory based self-administration sessions can provide a model of withdrawal and relapse, and can be used to evaluate potential treatments for drug dependence. The overall hypothesis is that active rTMS administration will increase activity in the PFC and ACC and reduce the choice the self-administer cannabis. The results from this study will provide important pilot- data for a future larger study using this novel method as an imaging probe and as a potential treatment for cannabis abuse and dependence.
Cannabis (marijuana) is the most frequently used illicit drug in the United States, and while heavy cannabis use can lead to a variety of functional impairments, users attempting abstinence on their own can experience significant withdrawal symptoms and ultimately relapse into use. Preventing relapse and reducing the severity of cannabis use are clinically relevant problems, yet there are no effective pharmacotherapeutic treatments for cannabis dependence available as of now. The objective of this research proposal is to explore electromagnetic stimulation (repetitive transcranial magnetic stimulation, rTMS) as a novel treatment approach for cannabis dependence and to evaluate associated changes in the brain with functional imaging, providing pilot data for a future larger study.