ubiquinone and Cocaine-Related-Disorders

To conduct a medication screening trial on the efficacy of olanzapine, valproate or coenzyme Q10/L-carnitine combination versus placebo for the treatment of cocaine dependence.. A four-arm, modified blinded, parallel group study in an out-patient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design.. The study was performed at the New York Medications Development Research Unit (MDRU).. All participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2-week screening period. Sixty-eight participants were enrolled with 39 completing the study.. After a 2-week screening period, 68 subjects were assigned randomly to receive either olanzapine (10 mg/day), valproate (1500 mg/day), coenzyme Q10 (200 mg/day) and L-carnitine (500 mg/day) combination or placebo for an 8-week treatment period. All subjects also received individual cognitive behavioral counseling during treatment.. Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self-report of drug use, and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs, and extrapyramidal side-effects tests.. Study retention was similar across all treatment groups, and all groups showed improvement across most measures of treatment efficacy over the duration of the study. None of the study medications, however, were superior to placebo on any of the primary or secondary outcome measures. Cocaine use, as measured by urine BE levels and self-report, was not significantly lower than placebo in any of the drug treatment groups. All study medications were equally well tolerated, and few medication side effects were observed.. This pilot study does not support the effectiveness of olanzapine, valproate or coenzyme Q10/L-carnitine combination for the treatment of cocaine dependence.

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Carnitine; Cocaine-Related Disorders; Coenzymes; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Selective Serotonin Reuptake Inhibitors; Ubiquinone; Valproic Acid

The goal of this study was to assess mitochondrial function and ROS production in an experimental model of cocaine-induced cardiac dysfunction. We hypothesized that cocaine abuse may lead to altered mitochondrial function that in turn may cause left ventricular dysfunction. Seven days of cocaine administration to rats led to an increased oxygen consumption detected in cardiac fibers, specifically through complex I and complex III. ROS levels were increased, specifically in interfibrillar mitochondria. In parallel there was a decrease in ATP synthesis, whereas no difference was observed in subsarcolemmal mitochondria. This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine. MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-volume data. Taken together, these results extend previous studies and demonstrate that cocaine-induced cardiac dysfunction may be due to a mitochondrial defect.

Topics: Animals; Antioxidants; Cocaine; Cocaine-Related Disorders; Disease Susceptibility; Drug Evaluation, Preclinical; Heart Diseases; Male; Mitochondria, Heart; Mitochondrial Diseases; Molecular Targeted Therapy; Organophosphorus Compounds; Oxygen Consumption; Rats; Rats, Wistar; Reactive Oxygen Species; Ubiquinone