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Long-term impact of cannabis exposure on the adolescent brain

Institution: University of California, Irvine
Investigator(s): Daniele Piomelli,
Award Cycle: 2019 (Cycle 29) Grant #: T29IR0618 Award: $937,500
Subject Area: Neuroscience of Nicotine Addiction and Treatment
Award Type: High Impact Research Project Award

Initial Award Abstract
Cannabis use often starts in early teenage years and progressively increases during adolescence. Teenage boys and girls experiment with cannabis more than any other recreational drug, a trend that is likely to increase in States, like California, where cannabis has been legalized for both medical and non-medical use. Research has shown that the adolescent brain is especially vulnerable to the long-term effects of cannabis. Neural networks that control learning, memory and emotions are still actively developing during teenage years and are, therefore, more likely to be altered by exposure to brain-active substances such as cannabis. In fact, there is evidence from human population studies that use of the drug in adolescence is associated with deficits in memory and emotion that continue into adulthood, even after use has stopped. These findings are supported by other studies showing how administration of THC, cannabis intoxicating constituent, in adolescence causes a variety of long-lasting cognitive and emotional problems. How do these problems arise? To address this question, we asked whether THC modifies the ability of the brain to produce its own cannabis-like substances. These molecules, called endocannabinoids, recognize the same receptors that combine with THC (the cannabinoid receptors) and play important roles in the normal function of the adolescent and adult brain. Our preliminary results in mice show that excessive activation of cannabinoid receptors during adolescence causes enduring changes in the way the endocannabinoids are produced and destroyed. In the present application, we propose a series of studies to determine, first, how exactly endocannabinoid production changes in response to THC exposure in adolescence; second, what patterns of exposure are necessary and sufficient to alter endocannabinoid signaling; and, third, what molecular mechanisms underpin the long-lasting effects caused by THC on endocannabinoid signaling. Understanding the persistent consequences of cannabis use during adolescence will help, among other things, to provide a solid evidence-based ground for policy decisions concerning levels and timing of medical and recreational cannabis exposure in vulnerable sectors of the population such as teenagers.