Poster Session III

Abstract

Background: Chronic cannabis dependence presents a public health challenge, as about 10% of regular users develop dependence, and there are currently no biological treatments available. There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) with standard figure-8 coils applied to the dorsolateral prefrontal cortex (DLPFC) in cocaine and tobacco users reduces drug craving and drug self-administration. In this study we used functional magnetic resonance imaging (fMRI) and a laboratory model of cannabis self-administration to evaluate an innovative type of rTMS in human volunteers as a potential treatment approach to cannabis dependence. We used the H7 coil, allowing for the stimulation of deeper brain structures, directed at the dorsomedial prefrontal cortex (dmPFC) and anterior cingulate cortex (ACC), areas shown to be affected in addiction, including in cannabis dependence. Our hypothesis was that active rTMS administration would normalize activity in the PFC and ACC and reduce the choice the self-administer cannabis. Methods: To this date, 10 medically healthy non-treatmentseeking participants with chronic daily cannabis use (CD, age 35.9 ± 8. 5,2 females, 8 males) were admitted to our research unit for a 21 day study. Following 4 days of inpatient monitored abstinence, the participants underwent baseline cannabis self-administration sessions. Laboratory based self-administration sessions were conducted at baseline and after the complete period of rTMS to provide a model of withdrawal and relapse. Participants were given 6 opportunities to choose 0, 1, 2, or 3 puffs of standardized marijuana cigarettes containing 5.5% D9-tetrahydrocannabinol (THC) at 1.5 hour intervals, at $0.5 per puff, deducted from their study earnings. Subjective effects of cannabis and craving were rated. Participants were then randomly assigned to two groups: high frequency (n=5) and sham (n=5). Participants underwent a total of 11 treatments (over 2 weeks) with rTMS using the H7 coil at 110% of motor threshold at a frequency of 10 Hz; sham controls underwent the same scenario, but with a coil set to produce noise artefacts only. The cannabis self-administration sessions were repeated after 5 and after 11 rTMS sessions, and the outcome measure was the number of puffs chosen. Using fMRI and the Rapid Simon interference task, we also compared baseline BOLD activation in the PFC and ACC post-treatment activation. The Rapid Simon task assesses response to conflicting stimuli and response inhibition, functions subserved by the ACC and DLPFC. An SPM8 analysis was performed of the congruent and incongruent stimuli and hypotheses were tested with Random Field Theory correction for multiple comparisons set to a significance level ofp