New Research on Crack-Cocaine Addiction
Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence.
Montoya ID, Gorelick DA, Preston KL, Schroeder JR, Umbricht A, Cheskin LJ, Lange WR, Contoreggi C, Johnson RE, Fudala PJ.Clin Pharmacol Ther. 2004 Jan;75(1):34-48.
Division of Treatment Research and Development and Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA.
BACKGROUND: Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. METHODS: Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. RESULTS: The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P =.0135 for 8 mg and P <.001 for 16 mg) or benzoylecgonine concentrations (P =.0277 for 8 mg and P =.006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events. CONCLUSIONS: A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use.
Severity of neuropsychological impairment in cocaine and alcohol addiction: association with metabolism in the prefrontal cortex.
Goldstein RZ, Leskovjan AC, Hoff AL, Hitzemann R, Bashan F, Khalsa SS, Wang GJ, Fowler JS, Volkow ND.Neuropsychologia. 2004;42(11):1447-58.
Brookhaven National Laboratory, P.O. Box 5000, Upton, NY 11973-5000, USA.
We used exploratory and confirmatory statistical approaches to study the severity of neuropsychological (NP) impairment in 42 crack/cocaine addicted subjects and in 112 comparison subjects (40 alcoholics and 72 controls). Twenty neuropsychological test indices most reliably defining predetermined cognitive domains were submitted to exploratory factor analysis. A four-dimensional model of neurocognitive function was derived: Verbal Knowledge, Visual Memory, Verbal Memory, and Attention/Executive functioning accounted for 63% of the variance. We then examined this model's association with resting glucose metabolism in the brain reward circuit measured with 2-deoxy-2[ [Formula: see text] ]fluoro-d-glucose positron emission tomography. Results revealed that (1) cocaine addicted individuals had a generalized mild level of neurocognitive impairment (<1 S.D. below control mean); and (2) controlling for age and education, relative metabolism in the dorsolateral prefrontal cortex significantly predicted the Visual Memory and Verbal Memory factors and relative metabolism in the anterior cingulate gyrus significantly predicted the Attention/Executive factor. Nevertheless, it remains to be determined whether metabolic changes in these regions are associated with addiction. Our results also suggest that compared to cocaine, alcohol has a more detrimental effect on Attention/Executive functioning, as assessed with traditional NP measures. We conclude that relative to other psychopathological disorders (such as schizophrenia), the severity of neuropsychological impairment in cocaine addiction is modest, albeit not indicative of the absence of neurocognitive dysfunction. The impact of such small differences in performance on quality of life, and possibly on craving and relapse, may be substantial. Tasks that simulate real-life decision-making or that target specific putative cognitive-behavioral or motivational-emotional mechanisms might offer greater sensitivity in characterizing the changes that accompany addiction to drugs. Obtaining valid estimates of alcohol use in cocaine addicted subjects is essential in characterizing neurocognitive functioning in individuals addicted to drugs.
Cocaine effects on the developing brain: current status.
Harvey JA.Neurosci Biobehav Rev. 2004 Jan;27(8):751-64.
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia PA 19102-1192, USA. john.harvey@drexel.edu
The present paper reports on the results obtained in a rabbit model of prenatal cocaine exposure that mimics the pharmacokinetics of crack cocaine in humans, and relates these findings to studies in other species including humans. A general finding is that prenatal exposure to cocaine during neurogenesis produces dysfunctions in signal transduction via the dopamine D(1) receptor and alterations in cortical neuronal development leading to permanent morphological abnormalities in frontocingulate cortex and other brain structures. Differences in the precise effects obtained appear to be due to the dose, route and time of cocaine administration. Related to these effects of in utero cocaine exposure, animals demonstrate permanent deficits in cognitive processes related to attentional focus that have been correlated with impairment of stimulus processing in the anterior cingulate cortex. The long-term cognitive deficits observed in various species are in agreement with recent reports indicating that persistent attentional and other cognitive deficits are evident in cocaine-exposed children as they grow older and are challenged to master more complex cognitive tasks.
Montoya ID, Gorelick DA, Preston KL, Schroeder JR, Umbricht A, Cheskin LJ, Lange WR, Contoreggi C, Johnson RE, Fudala PJ.Clin Pharmacol Ther. 2004 Jan;75(1):34-48.
Division of Treatment Research and Development and Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA.
BACKGROUND: Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. METHODS: Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. RESULTS: The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P =.0135 for 8 mg and P <.001 for 16 mg) or benzoylecgonine concentrations (P =.0277 for 8 mg and P =.006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events. CONCLUSIONS: A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use.
Severity of neuropsychological impairment in cocaine and alcohol addiction: association with metabolism in the prefrontal cortex.
Goldstein RZ, Leskovjan AC, Hoff AL, Hitzemann R, Bashan F, Khalsa SS, Wang GJ, Fowler JS, Volkow ND.Neuropsychologia. 2004;42(11):1447-58.
Brookhaven National Laboratory, P.O. Box 5000, Upton, NY 11973-5000, USA.
We used exploratory and confirmatory statistical approaches to study the severity of neuropsychological (NP) impairment in 42 crack/cocaine addicted subjects and in 112 comparison subjects (40 alcoholics and 72 controls). Twenty neuropsychological test indices most reliably defining predetermined cognitive domains were submitted to exploratory factor analysis. A four-dimensional model of neurocognitive function was derived: Verbal Knowledge, Visual Memory, Verbal Memory, and Attention/Executive functioning accounted for 63% of the variance. We then examined this model's association with resting glucose metabolism in the brain reward circuit measured with 2-deoxy-2[ [Formula: see text] ]fluoro-d-glucose positron emission tomography. Results revealed that (1) cocaine addicted individuals had a generalized mild level of neurocognitive impairment (<1 S.D. below control mean); and (2) controlling for age and education, relative metabolism in the dorsolateral prefrontal cortex significantly predicted the Visual Memory and Verbal Memory factors and relative metabolism in the anterior cingulate gyrus significantly predicted the Attention/Executive factor. Nevertheless, it remains to be determined whether metabolic changes in these regions are associated with addiction. Our results also suggest that compared to cocaine, alcohol has a more detrimental effect on Attention/Executive functioning, as assessed with traditional NP measures. We conclude that relative to other psychopathological disorders (such as schizophrenia), the severity of neuropsychological impairment in cocaine addiction is modest, albeit not indicative of the absence of neurocognitive dysfunction. The impact of such small differences in performance on quality of life, and possibly on craving and relapse, may be substantial. Tasks that simulate real-life decision-making or that target specific putative cognitive-behavioral or motivational-emotional mechanisms might offer greater sensitivity in characterizing the changes that accompany addiction to drugs. Obtaining valid estimates of alcohol use in cocaine addicted subjects is essential in characterizing neurocognitive functioning in individuals addicted to drugs.
Cocaine effects on the developing brain: current status.
Harvey JA.Neurosci Biobehav Rev. 2004 Jan;27(8):751-64.
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia PA 19102-1192, USA. john.harvey@drexel.edu
The present paper reports on the results obtained in a rabbit model of prenatal cocaine exposure that mimics the pharmacokinetics of crack cocaine in humans, and relates these findings to studies in other species including humans. A general finding is that prenatal exposure to cocaine during neurogenesis produces dysfunctions in signal transduction via the dopamine D(1) receptor and alterations in cortical neuronal development leading to permanent morphological abnormalities in frontocingulate cortex and other brain structures. Differences in the precise effects obtained appear to be due to the dose, route and time of cocaine administration. Related to these effects of in utero cocaine exposure, animals demonstrate permanent deficits in cognitive processes related to attentional focus that have been correlated with impairment of stimulus processing in the anterior cingulate cortex. The long-term cognitive deficits observed in various species are in agreement with recent reports indicating that persistent attentional and other cognitive deficits are evident in cocaine-exposed children as they grow older and are challenged to master more complex cognitive tasks.