Chronic cocaine abuse in the United States continues to be a major public health concern, with a variety of medical, neuropsychological, and societal sequelae. Cocaine dependence in adolescents and young adults can be particularly devastating and has been associated with increased rates of involvement with the criminal justice system, impaired educational and career progress, family breakdown, medical difficulties (neurologic and psychiatric), and mortality (due to suicide and violence). Intense research efforts over the past decade have resulted in several successful treatment interventions for cocaine dependence. However, even these methods are effective in only approximately half of patients and relapse is common. Studies such as these indicate an important and highly clinically relevant direction for future research: specifically, the need to identify dysfunctional neurobiological changes associated with cocaine dependence and determination of their reversibility in individuals who are successful through treatment in stopping their cocaine use. In this exploratory study, we hypothesize that regions of the brain which have been shown to be subject to large changes in cerebral blood flow following acute cocaine use, will also undergo longer term dysfunctional neuronal changes that can be detected with proton spectroscopic imaging and quantitative single voxel proton MRS. This will be investigated in phase one in which cocaine dependent individuals and matched controls are compared. Following the establishment of the brain regions showing neuronal dysfunction, a second study phase will be conducted to determine whether these changes remit in individuals who are able to stop using cocaine through treatment with cognitive-behavioral therapy. Since it is more likely that longer term exposure to cocaine will produce permanent brain changes, young research volunteers between the ages of 15 and 21 will be recruited to maximize the chances of reversibility. Specifically, proton spectroscopic imaging will be used to measure the N-Acetyl-Aspartate/Creatine (NA/Cr) ratio, an index of neuronal viability, in multiple brain regions, and quantitative single voxel proton MRS will be utilized to measure glutamine/glutamate (Glx) and myo-inositol (mI) concentration in the frontal lobe and striatum. These functional neurochemical indices may have important implications for the evaluation of novel treatments for cocaine dependence. Delineating a neurochemical index for the assessment of the effectiveness of proposed therapeutic interventions for cocaine dependence is clearly a worthwhile endeavor.
