Cannabis is the most prevalent illicit substance used by adolescents in the U.S. Although available treatments can help adolescent cannabis users achieve abstinence, longer term outcome studies have demonstrated high rates of relapse to cannabis use in this population. Preclinical and clinical studies have shown that cannabis use exerts sustained disruptive effects on learning and memory, which appear to be more pronounced with earlier age at onset of cannabis use. Preclinical work has also provided evidence of neuroadaptive changes in reward circuitry, including reduced dopaminergic neurotransmission, following chronic exposure to ?9-tetrahydrocannabinol (THC), the active component of cannabis. Many treatments for adolescent cannabis abuse and dependence, such as cognitive behavioral therapy, motivational enhancement therapy, and contingency management therapy, involve processing of rewards, learning new information, and retaining this new information over time. Understanding how exposure to cannabis during adolescent development alters the function of neurocircuitry that supports reward processing, learning and memory, and the integration of neurocircuits that support these cognitive functions is thus an important problem in addiction neuroscience. The goal of this proposal is to develop and refine a paradigm for the assessment of reward-motivated learning, and the function of neurocircuitry that supports reward-motivated learning, in adolescent cannabis users. Thirty-five adolescent cannabis users and 35 matched non-cannabis using comparison subjects will undergo behavioral assessment using four versions of a reward- motivated learning task that will test two levels of reward (high and low) and two stimuli types (verbal and nonverbal stimuli). Data collected from these assessments will be used to test the hypothesis that response to positive and negative rewards in the context of learning are blunted in adolescent cannabis users. The reward level and stimuli type found to be most sensitive to the effects of cannabis on reward-motivated learning in adolescents will be used to develop a functional magnetic resonance imaging (fMRI) activation paradigm. Fifteen adolescent cannabis users and 15 matched comparison subjects will undergo fMRI imaging with this paradigm to explore the effect of cannabis exposure on neurocircuitry that supports reward motivated learning and to estimate the size of this effect. All subjects will undergo four weeks of monitored abstinence from substances of abuse, other than nicotine, prior to behavioral and fMRI assessments. Cannabis use among adolescents is common. Although treatment can often help adolescents stop using cannabis in the short term, longer term follow-up studies have shown high rates of relapse to cannabis use among these teenagers. Studies of animals and of humans have shown that cannabis use disrupts learning and memory. Studies of animals have also shown that reward circuitry undergoes neuroadaptive changes in response to chronic exposure to the active component of cannabis,tetrahydrocannabinol (THC). Many treatments for adolescent cannabis abuse and dependence involve processing of rewards, learning new information, and retaining this new information over time. The goal of this proposal is to develop and refine a paradigm for the assessment of reward-motivated learning, and the function of neurocircuitry that supports reward- motivated learning, in adolescent cannabis users. This work will form the foundation for future planned projects that will examine the relationship between the function of neurocircuitry supporting reward motivated learning and treatment outcome in adolescent cannabis users. Findings from these studies will provide a rational basis for tailoring treatment interventions to the ability of adolescents to respond to interventions that involve rewards (eg: contingency management) and/or learning (eg: cognitive-behavioral therapy), and to provide methods for monitoring changes in the function of neurocircuitry supporting reward-motivated learning associated with treatment and with sustained abstinence from cannabis use. ? ? ?
| Jacobsen, Leslie K; Picciotto, Marina R; Heath, Christopher J et al. (2009) Allelic variation of calsyntenin 2 (CLSTN2) modulates the impact of developmental tobacco smoke exposure on mnemonic processing in adolescents. Biol Psychiatry 65:671-9 |
