Prenatal Cannabis Effect on the Endocannabinoid System

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DESCRIPTION (provided by applicant): Cannabis sativa (Marijuana) is one of the most widely abused drugs in many countries and has long been recognized as a centrally acting drug with extensive effects on motor and cognitive functions. In spite of being the most widely abused drug among women of reproductive age, there is a relative paucity of literature dealing with the neurochemical and neurobehavioral consequences in offspring particularly the longer-term effects. The endocannabinoids in the central nervous system bind to G-protein coupled CB1 receptors that modulate adenylyl cyclase, ion channels and extracellular signal-regulated kinases. The endocannabinoid system is known to play an important role in many aspects of health and disease including drug addiction. Since delta-9 tetrahydrocannabinol (?9-THC) is a major psychoactive component of the marijuana and partial agonist of CB1 receptor, it is hypothesized that the in utero ?9-THC exposure alters the function of endocannabinoid system and CB1 receptor-mediated signaling pathway. In the proposed study, we will investigate the effect of prenatal ?9-THC exposure on the status of endocannabinoids system in the brain of offspring during postnatal development using C57BL/6J mice as an animal model. The proposed study is timely and the findings of this study would be of great potential for developing drug therapies in the intervention of prenatal cannabis related birth defects. Among drugs of abuse, prenatal cannabis abuse has become a major public health concern. The long- term goal of this study is to understand the cellular and molecular mechanisms of in utero THC exposure on the developing CNS and to examine possible utility of the endocannabinoid system as potential therapeutic target for the treatment of behavioral deficits associated with prenatal cannabis abuse.