Project Summary

Vladmir Coric, M.D. (Young Investigator 2005) of Connecticut Mental Health Center and Yale University, plans to study the use of a cannabinoid drug to treat patients with obsessive compulsive disorder (OCD) as a new approach to treating the condition. Dr. Coric wants to test the cannabinoid drug, which acts on the glutamatergic system, because evidence suggests this pathway may be involved in OCD. First, patients who take dopamine antagonists or SSRIs only obtain partial relief. Second, recent preclinical and neuroimaging studies implicate increased glutamatergic activity in the pathogenesis of OCD. The glutamatergic pathway is thought to modulate the initiation of behaviors while the GABAergic pathway is thought to modulate behavior cessation. Hyperactivity in the glutamatergic pathway relative to the GABAergic pathway is thought to create an imbalance that results in a circuit that may be a major cause of symptoms in OCD. Only a few published trials have described the effect of drugs that specifically target glutamatergic function in individuals with OCD. Cannabinoid receptors are thought to modulate glutamatergic neurotransmission and are located throughout the central nervous system with particularly high density found in the striatum. Cannabinoid receptor activation within the striatum is thought to reduce striatal glutamatergic outflow, inhibit GABA reuptake, and enhance GABA neurotransmission. The effect of cannabinoid receptors on striatal neurotransmission has clinical relevance to disorders known to involve excessive striatal activity, such as OCD. To test cannabinoid’s role in OCD, Dr. Coric proposes a double-blind, placebo-controlled study to evaluate the efficacy of dronabinol, a synthetic version of the active ingredient in marijuana (tetrahydrocannabinol), in patients with OCD who are no longer responding to SSRIs.

Program Area: ANXIETY DISORDERS\Obsessive Compulsive Disorder (OCD)

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