Drug abusers vary widely in their acute and chronic responses to drugs and in their response to drug abuse treatment. A better understanding of the factors associated with individual differences in response should result in the development of more effective and efficient treatment. This project assesses biological and psychosocial characteristics of drug abusers and correlates them with abusers' response to their abused drug, their biomedical consequences from drug use (such as HIV infection), or to the abusers' treatment outcome. One component is evaluating the psychological, physiological, and neuropharmacological manifestations and time course of cocaine withdrawal, with the goal of identifying predictors of relapse to cocaine use. This study, in collaboration with the Department of Radiology, Johns Hopkins University, uses positron emission tomography (PET) scanning with 11C-carfentanil (a synthetic, potent mu-opiate receptor agonist) to evaluate the effect of chronic cocaine abuse on mu-opiate receptor function in the brain. Results from the first phase indicated that chronic heavy cocaine users have increased mu-opiate receptor binding in some brain regions (compared to non-drug using healthy controls), which correlates with their self-reported cocaine craving. The increased binding persists over 28 days of cocaine abstinence, while psychological (e.g., cocaine craving, mood) and physiological parameters (sleep, heart rate) normalize over 7-10 days. The current phase of this study evaluates cocaine abstinence over 90 days, including neurophysiological measures such as EEG and cerebral blood flow by Doppler (in collaboration with Molecular Neuropsychiatry Section). Initial results suggest that mu-opiate receptor binding remains increased even after 90 days of monitored abstinence. The more receptor binding normalized over the 90 days, the longer until subjects relapsed to cocaine use after discharge from the research ward. Furthermore, in subjects receiving a cocaine challenge during PET scanning, the acute change in binding caused by cocaine correlated significantly with the subjective effects produced by the cocaine challenge. These findings suggest an important role for the brain mu- opiate system in cocaine addiction, with interesting treatment implications. A second component assesses psychiatric and medical co-morbidity (including HIV infection), personality traits, mood, neuropsychological function, and sociodemographic characteristics in drug abusers using structured and semi-structured diagnostic interviews and computer- administered psychological tests. Preliminary findings suggest that lifetime, but currently inactive, psychiatric comorbidity has little influence on drug abuse treatment outcome. For example, cocaine addicts with histories of pathological gambling had the same outpatient treatment response as those without such a history (even though the gambling preceded the onset of cocaine addiction). A third component evaluates the subclinical effects of acute and chronic cocaine use on cardiovascular function, using 24-hour ambulatory monitoring, high-resolution EKG, echocardiography, and analysis of heart rate variability. Preliminary findings suggest that heavy cocaine users may have subtle changes in autonomic regulation of heart rate in response to posture changes, but no significant changes in circadian variation of heart rate and blood pressure. A fourth component is evaluating individual differences in activity of the main cocaine-metabolizing enzyme in humans, butyrylcholinesterase (in collaboration with the Gerontology Research Center, National Institute on Aging), and of various neurotransmitter-associated genotypes (in collaboration with the Molecular Neurobiology Branch) as factors influencing the acute response to cocaine.
| Kanneganti, Praveen; Huestis, Marilyn A; Kolbrich, Erin A et al. (2008) Signal-averaged electrocardiogram in physically healthy, chronic 3,4-methylenedioxymethamphetamine (MDMA) users. Am J Drug Alcohol Abuse 34:712-20 |
| Kolbrich, Erin A; Goodwin, Robert S; Gorelick, David A et al. (2008) Physiological and subjective responses to controlled oral 3,4-methylenedioxymethamphetamine administration. J Clin Psychopharmacol 28:432-40 |
| Kolbrich, Erin A; Goodwin, Robert S; Gorelick, David A et al. (2008) Plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine after controlled oral administration to young adults. Ther Drug Monit 30:320-32 |
| Kanneganti, Praveen; Nelson, Richard A; Boyd, Susan J et al. (2008) Exercise stress testing in recently abstinent chronic cocaine abusers. Am J Drug Alcohol Abuse 34:489-98 |
| Levin, Kenneth H; Copersino, Marc L; Epstein, David et al. (2008) Longitudinal ECG changes in cocaine users during extended abstinence. Drug Alcohol Depend 95:160-3 |
| Martins, Silvia S; Copersino, Marc L; Soderstrom, Carl A et al. (2007) Sociodemographic characteristics associated with substance use status in a trauma inpatient population. J Addict Dis 26:53-62 |
| Ghitza, Udi E; Rothman, Richard B; Gorelick, David A et al. (2007) Serotonergic responsiveness in human cocaine users. Drug Alcohol Depend 86:207-13 |
| Martins, Silvia S; Copersino, Marc L; Soderstrom, Carl A et al. (2007) Risk of psychoactive substance dependence among substance users in a trauma inpatient population. J Addict Dis 26:71-7 |
| Kurlander, Jacob E; Simon-Dack, Stephanie L; Gorelick, David A (2006) Spending of remuneration by subjects in non-treatment drug abuse research studies. Am J Drug Alcohol Abuse 32:527-40 |
| Gorelick, David A (2006) Health Insurance Portability and Accountability Act Privacy Rule and research consent documents. Ann Intern Med 145:790; 790-1 |
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