Topiramate for Co-occurring Cannabis Use and Bipolar Disorders in Adolescents

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DESCRIPTION (provided by applicant): There is a bidirectional overlap between bipolar and cannabis use disorders, with a particularly severe illness course for individuals with both conditions. Specifically, patients with co-occurring bipolar and cannabis use disorders exhibit higher relapse rates of both illnesses compared with individuals with either illness alone. Adolescents with co-occurring cannabis use and bipolar disorders have a poorer outcome of both disorders than even occurs in similar adults and have an elevated risk of developing other substance use disorders. However, adolescents with bipolar and cannabis use disorders are routinely excluded from controlled pharmacological treatment studies of either condition. Thus, clinicians are left with no evidence- based guidance on how to treat these adolescents. Research on the treatment of adolescents with co- occurring bipolar and cannabis use disorders is critical because adolescence may be the best time to interrupt the progression of these illnesses into lifelong substance use dependence and treatment refractory bipolar disorder, both of which are associated with significant morbidity and mortality. Topiramate is an antiepileptic agent with a dual mechanism of action that leads to reduction of midbrain dopamine neurotransmission, and therefore, may be useful to reduce the reward and craving associated with cannabis use. Recently, topiramate has been found to be safe and efficacious for reducing alcohol and cocaine consumption and craving in adults. Our preliminary work suggests that topiramate also may be effective for the treatment of mania in adolescents with bipolar disorder. However, the efficacy of topiramate as a treatment for cannabis use disorders in bipolar adolescents has not been explored. Therefore, the goal of this proposal is to conduct a double-blind placebo-controlled 16-week pilot study examining the efficacy and tolerability of topiramate as a treatment for reducing cannabis consumption in adolescents with co-occurring bipolar and cannabis use disorders. The aims of this proposal are consistent with the goals of RFA-DA-06-002, which include conducting "pilot clinical trials of pharmacotherapies for substance related disorders." We will randomize 90 bipolar adolescents with a current cannabis use disorder to treatment with topiramate or placebo. All adolescents will also receive quetiapine and a single Motivational Interview followed by Compliance Enhancement Therapy that is manual-driven, as standardized treatments for mania and cannabis use disorders, respectively. Change in cannabis consumption is the primary outcome measure. We will also examine the efficacy of topiramate in combination with quetiapine for the treatment of manic symptoms and explore the relationships among changes in cannabis use, mood symptoms, and other substance use. The proposed study would be the first to examine a pharmacological intervention for the treatment of cannabis use disorders in bipolar adolescents. The preliminary data from this project will inform and guide the design of future larger, more definitive, controlled studies of topiramate as a treatment for adolescent substance use disorders.