Clinical Pharmacology and Therapeutics Research Branch
Clinical Pharmacology Section
Mission Statement
The mission of the Clinical Pharmacology Section is to develop more effective treatments for drug abuse through better understanding of the clinical pharmacology of drugs of abuse.
Program Areas
• Pharmacokinetic approach to cocaine addiction treatment
• Role of cocaine withdrawal in relapse to cocaine use
• Role of cannabinoid (CB1) receptors in effects of smoked marijuana
• Microecology of drug abuse and crime
Name: David A. Gorelick, M.D., Ph.D.
Title: Chief, Clinical Pharmacology Section
Telephone Number: (410) 550-1478 (voice)
Fax Number: (410) 550-1528 (fax)
Synopsis of Research
Pharmacokinetic approach to cocaine addiction treatment
Enhancing cocaine's rate of metabolism or clearance from the body could be a useful treatment approach because of blunting or delaying the onset of cocaine effects and/or decreasing their duration of action. The success of this approach does not depend on understanding where and how cocaine is acting in the brain. The Clinical Pharmacology Section is studying this approach using the naturally occurring cocaine-metabolizing enzyme butyrylcholinesterase (BChE). BChE (EC 3.1.1.8) is a major cocaine-metabolizing enzyme in humans, catalyzing its hydrolysis to ecgonine methyl ester (EME). We have conducted a series of in vitro and in vivo animal studies in collaboration with Dr. Charles Schindler and colleagues at the NIDA IRP Behavioral Pharmacology Section to attempt to validate the concept of enhanced metabolism by exogenous administration of BChE as a safe way of decreasing behavioral effects of cocaine in rats. Planned future work, continuing in collaboration with the Behavioral Pharmacology Section, will evaluate the safety, efficacy, and duration of action of human BChE in monkeys. The ultimate goal is a human trial to evaluate the efficacy and safety of BChE and, hopefully, demonstrate proof of the concept.
Role of cocaine withdrawal in relapse to cocaine use
A better understanding of the phenomena of cocaine abstinence (“withdrawal”) after heavy use, both those that normalize and those that persist, may improve treatment outcome by shedding light on processes relevant to relapse. We are comprehensively evaluating the neuropharmacological, physiological, and psychological aspects of early (first 3-4 weeks) and more prolonged (up to 3 months) cocaine abstinence, using the valuable resource of the NIDA IRP closed residential research unit, which allows long-term study of individuals undergoing monitored abstinence in a controlled environment. Current studies are evaluating risk-reward decision-making processes during cocaine abstinence and the relationship been brain mu-opiate receptor binding, measured by positron emission tomography (PET) scanning in collaboration with Dr. James Frost at the Johns Hopkins University PET Center, and relapse to cocaine use.
Role of cannabinoid (CB1) receptors in effects of smoked marijuana
The recent discovery of specific neuronal receptors (cannabinoid CB1 receptor) for delta-9-tetrahydrocannabinol (THC) and of a selective antagonist at these receptors (SR 141716) offers a unique scientific opportunity to understand the mechanisms of action of marijuana and to develop improved treatment for marijuana abuse. The Clinical Pharmacology Section, in collaboration with other investigators in the Clinical Pharmacology & Therapeutics Branch, is conducting the first human studies evaluating the role of CB1 receptors in mediating acute physiological and psychological effects of smoked marijuana. These studies will also provide clues as to the role of the endogenous cannabinoid system in human psychological and behavioral function.
Microecology of drug abuse and crime
The ability of substance abuse treatment to reduce criminal behavior among those treated has been well documented by clinical studies. However, the effect of substance abuse treatment programs (i.e. the location of a treatment program within a neighborhood) on the ecology of neighborhoods has not been studied. The goal of this project is to evaluate the effect of substance abuse treatment programs on crime in the surrounding community, using computerized mapping methods (Geographic Information Systems (GIS)) to conduct geographic analyses of anonymous, publicly available databases. In this method, concentric circular “buffers” are defined around sites of interest, the occurrence of different events (e.g. arrests) counted within each buffer area, and counts compared among areas. This technique allows the comparison of very small geographic areas (the smallest buffer has a radius of 25 meters, an area of approximately one tenth of a city block).
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Clinical Pharmacology and Therapeutics Research Branch
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