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Biomedical subjects

D A Gorelick

Publications and source records attributed to D A Gorelick.

At least 37 records · Page 2Linked to original sources
PubMed1997

Alcoholism at the time of injury among trauma center patients: vehicular crash victims compared with other patients.

A structured in-depth interview employing standardized criteria was used to determine the prevalence of lifetime and current alcohol dependence (alcoholism) in unselected consecutive patients admitted to a regional Level I trauma center. Of 629 patients, 157 (25.0%) were current alcoholics at the time of injury. An additional 87 (13.8%) were diagnosed as lifetime non-current alcoholics. There was no significant difference in the rates of current alcohol dependence among patients injured in vehicular crashes (23.5%), other unintentional trauma victims (29.3%), and those injured as a result of violence (24.6%). Of BAC+ (blood alcohol concentration positive) patients, 54.5% were current alcoholics. However, 14.4% of alcohol-negative patients were also diagnosed as alcohol dependent.

Accidents, Traffic↗
PubMed1997

Changes in cigarette smoking not observed following repeated cocaine self-administration.

Acute administration of some psychoactive drugs (e.g., cocaine, heroin, methadone d-amphetamine) has been found to increase spontaneous cigarette smoking for 1-3 hr, but the effects of chronic drug administration have not been systematically studied. Computerized cigarette dispensers were used to study the effects of multiple daily cocaine administrations on cigarette smoking. Participants were 8 (5 male) cocaine-dependent cigarette smokers who resided on a closed clinical research ward and smoked an average of 16.7 cigarettes per day during the week prior to starting the study. During test sessions on Monday, Wednesday, and Friday of each week, participants could obtain either cocaine (25 mg i.v.) on 2 days or saline (1 ml i.v.) on the other day, 3 times per day at 2-hr intervals under double-blind conditions. The number of cigarettes dispensed during study days was analyzed in 2-hr increments. No significant cocaine effect was found. These findings fail to show a change in the number of cigarettes smoked after chronic cocaine self-administration over time intervals longer than 1-3 hr.

Adult↗
PubMed1997

The accuracy of the CAGE, the Brief Michigan Alcoholism Screening Test, and the Alcohol Use Disorders Identification Test in screening trauma center patients for alcoholism.

OBJECTIVE: To evaluate the accuracy of questionnaire screening instruments to identify lifetime alcohol dependence among trauma center patients. METHODS: The study was conducted at a Level I trauma center between September 1994 and November 1996. Patients meeting eligibility requirements (> or = 18 years old, admission from injury scene, > or = 2 days of hospitalization, intact cognition) were evaluated for alcohol abuse and dependence. Screening instruments consisted of the CAGE, the Brief Michigan Alcoholism Screening Test, and the Alcohol Use Disorders Identification Test. Screening results were compared with lifetime alcohol dependence diagnoses made using the in-depth Psychoactive Substance Use Disorders section of the Structured Clinical Interview. Accuracy was quantified as sensitivity, specificity, positive/negative predictive values, and receiver operating characteristic curves (used to calculate area under the curve). RESULTS: Of the 1,118 patients studied, lifetime alcohol dependence was diagnosed by Structured Clinical Interview in 397 (35.5%), and abuse was diagnosed in 90 (8.1%) others. The CAGE was the best predictor of lifetime alcohol dependence, i.e., had the largest area under the curve (93%) and the highest sensitivity (84%), specificity (90%), positive predictive value (82%), and negative predictive value (91%). Among patients testing positive for alcohol, 63% had a lifetime alcohol dependence diagnosis. CONCLUSION: The CAGE is an efficient screening test to detect alcohol dependence in trauma center populations. It should be used in combination with alcohol testing to identify patients at risk of alcohol use problems.

Adolescent↗
PubMed1997

Characteristics of smoked drug use among cocaine smokers.

The authors collected data by structured interview from a convenience sample of 228 physically healthy, largely (82%) treatment-seeking, cocaine smokers with minimal histories of other smoked (other than tobacco and marijuana) or injection drug use. The vast majority of subjects also smoked either marijuana only (17.5%), tobacco only (17%), or both (61%), with onset of such smoking almost always (97%) preceding the initiation of regular cocaine smoking. There were few significant differences in sociodemographic or cocaine use characteristics among the subgroups of subjects smoking either cocaine only or cocaine and marijuana and/or tobacco. More than one-third of marijuana smokers quit (45%) or decreased (38%) their use after starting regular cocaine smoking, whereas only 5% of tobacco smokers did so. These findings suggest that marijuana smoking is more influenced by regular cocaine smoking than is tobacco smoking.

Adult↗
PubMed1996

Plasma butyrylcholinesterase activity and cocaine half-life differ significantly in rhesus and squirrel monkeys.

In vitro studies have implicated butyrylcholinesterase (BChE, E.C.3.1.1.8) as the major enzyme for metabolizing cocaine in humans, but little is known about endogenous BChE activity in monkeys and other animals often used in preclinical studies of cocaine. We compared BChE activity in 18 rhesus and 11 squirrel monkeys, using the colorimetric method of Ellman with butyrylthiocholine as substrate, and in vitro cocaine half-life in pooled plasma samples measuring cocaine concentrations over 60 minutes by GC-MS. Rhesus monkeys had a significantly higher plasma BChE activity than squirrel monkeys (8.2 +/- 0.5 U/L vs. 2.8 +/- 0.5 U/L), and a three-fold shorter in vitro cocaine half-life (20.1 min vs. 60.2 min). BChE activity in rhesus monkeys was comparable to the activity reported in humans. There was no significant influence of age, weight, or prior cocaine exposure. These results indicate that BChE level can vary between species of non-human primates, a factor that should be taken into account when studying drugs such as cocaine which are metabolized by BChE.

Animals↗
PubMed1996

Acute sensitivity vs. context-specific sensitization to cocaine as a function of genotype.

Individual variability in the acute and chronic effects of psychomotor stimulants is due, in part, to genetic factors. The purpose of this series of studies was to utilize a behavioral model of sensitization, namely increased locomotor activity, to assess individual variability in sensitization to the chronic effects of cocaine and its relationship to the acute stimulant effects of cocaine. Because the degree of sensitization is proportional to the training dose, genetic differences in acute sensitivity to cocaine were assessed and incorporated into the sensitization paradigm. Acute sensitivity and context-dependent sensitization were determined in six inbred mouse strains. Large quantitative and qualitative differences were found in the acute potency and efficacy of cocaine to stimulate locomotor activity. The ED50 was higher in the strains in which cocaine was most efficacious. Context-specific sensitization was determined via chronic administration of equiactive doses of cocaine (ED50) specifically paired with the test apparatus or with the home colony. Sensitization was time, environment, and genotype dependent. The differences in the number of trials required to show sensitization were unrelated to the acute locomotor stimulant effects of cocaine. These findings suggest that acute cocaine-induced locomotor activity and context-specific sensitization reflect different pharmacological properties of cocaine.

Animals↗
PubMed1996

Cocaine cross-sensitization to dopamine uptake inhibitors: unique effects of GBR12909.

Repeated administration of cocaine will cross-sensitize the locomotor response to a variety of psychomotor stimulants. The ability of cocaine to cross-sensitize the locomotor effects of other psychomotor stimulants provides information relevant to the pharmacological mechanisms underlying the sensitization process. The purpose of the current experiment was to investigate the ability of cocaine to cross-sensitize the locomotor effects of several dopamine uptake blockers with unique pharmacological profiles. Cocaine (40 mg/kg, IP) or saline was administered prior to a locomotor session on day one. On day 2, a full dose-effect curve was established for the locomotor effects of cocaine, RTI-55, mazindol, and GBR12909. Previous exposure to cocaine significantly affected locomotor activity and stereotopy-like behavior produced by cocaine, mazindol, RTI-55, and GBR12909. However, GBR12909 was unique in that the maximal stimulant effect and slope of the dose-effect curve was significantly depressed and the stereotopy-like behavior was unchanged. Thus, despite the similarity of these compounds in their ability to inhibit dopamine uptake, cocaine-induced sensitization did not generalize to GBR12909. This study further demonstrates the unique pharmacology of GBR12909 and supports the further study of this compound as a potential treatment medication for cocaine abuse.

Animals↗
PubMed1996

Increased mu opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving.

The endogenous opioid system has been recently implicated in the reinforcing actions of cocaine and other addictive drugs. In this study we examined mu opioid receptor binding in ten cocaine-dependent men and seven nonaddicted controls using positron emission tomography and [11C] carfentanil. Mu opioid binding was increased in several brain regions of the cocaine addicts studied 1-4 days after their last use of cocaine. Binding was positively correlated with the severity of cocaine craving experienced at the time. The upregulation of mu opioid receptor binding persisted after 4 weeks of monitored cocaine abstinence. These findings demonstrate for the first time the involvement of the endogenous opioid system in cocaine dependence and cocaine craving in living human subjects.

Adult↗
PubMed1995

Effects of intravenous cocaine on plasma cortisol and prolactin in human cocaine abusers.

The aim of the present work was to examine the cortisol and prolactin responses to acute cocaine administration in human cocaine users. Each subject served as his own control during intravenous saline placebo and cocaine (40 mg) infusion sessions. Cocaine significantly elevated plasma cortisol but did not affect prolactin. The rise in cortisol coincided with an increase in heart rate and blood pressure after cocaine. In agreement with studies in animals, our data suggest that cocaine activates the hypothalamic-pituitary-adrenal axis in humans. However, based on the well-known importance of dopamine as a prolactin-inhibiting factor, the failure of cocaine to suppress prolactin in the present study raises questions concerning the role of dopamine in the mechanism of acute cocaine action in humans.

Adult↗
PubMed1995

Double-blind comparison of carbamazepine and placebo for treatment of cocaine dependence.

This study was conducted to determine the effectiveness of carbamazepine (CBZ) for treatment of cocaine dependence. Sixty-two (CBZ = 28, placebo = 34) cocaine-dependent (DSM-III-R criteria) volunteers consented to be treated for eight weeks with standardized outpatient individual counseling twice a week plus double-blind CBZ or inactive placebo. During the 8-week trial, both groups showed increased number of urine samples negative for cocaine, significantly (P < 0.01) decreased self-reported cocaine use (money spent and grams used), and decreased Beck Depression Inventory and Symptom Check List-90-Revised (SCL-90-R) total scores. However, there were no significant differences between CBZ and placebo. This study does not support the effectiveness of CBZ for outpatient treatment of cocaine dependence.

Adult↗
PubMed1994

Lack of evidence for context-dependent cocaine-induced sensitization in humans: preliminary studies.

Cocaine-induced behavioral sensitization is the well-documented phenomenon where repeated doses of cocaine elicit increasingly greater effects on motoric activity in rats. Some observations suggest that behavioral sensitization may provide a model for understanding the mechanisms of drug-craving elicited by environmental triggers or cues. The process of fully validating such an animal model for its ability to detect effective anticraving medicines is a difficult and long-term undertaking. As a first step in that direction, we decided to determine if cocaine can produce conditioned behavioral sensitization in humans using a paradigm fairly similar to that used for rodents. Because humans do not react to cocaine with the pronounced motor activation observed in rodents, we measured a variety of end points, including blood pressure (BP), heart rate (HR), respiratory rate, pupil diameter, hormones (prolactin and cortisol), and subjective responses using the questionnaire for drug-related feelings (QDRF) and the EEG. To mimic the home and test cages used in rodent studies, two rooms were used: a small test chamber and a regular room with a window and furnishings. On day 1 each subject received a drug infusion (either saline or 40 mg cocaine IV) in both locations. On day 2, all subjects received an infusion (saline or 25 mg cocaine IV) in the test chamber. All drug infusions were conducted double blind. The paired group received cocaine on both days in the test chamber. The unpaired group received cocaine in regular room on day 1, and cocaine in the test chamber on day 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Cocaine and metabolite excretion in saliva under stimulated and nonstimulated conditions.

The accessibility of saliva for rapid, noninvasive sampling makes it an attractive biological fluid for detecting drug use. However, little is known about salivary excretion patterns of the major cocaine metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME). Additionally, there is a general lack of information on the effects of salivary collection conditions on cocaine excretion in saliva. This study documents the profile of cocaine and metabolites in human saliva under stimulated and nonstimulated saliva flow conditions. Saliva samples were obtained periodically from six healthy volunteers who were administered three, equally spaced, single intravenous doses of 25 mg of cocaine during a 6-h test session. On different days, whole saliva was obtained either under nonstimulated or stimulated (sour candy) conditions. The samples were analyzed for cocaine and metabolites by GC/MS. Cocaine, BE, and EME were detected and quantitated in the saliva of all subjects. Cocaine was the predominant analyte identified in all samples. Nonstimulated saliva contained substantially more drug than stimulated samples. The ratio of the area under the curve (AUC) of cocaine in nonstimulated saliva to that of stimulated saliva was variable and ranged from 3.0 to 9.5. The AUC ratios of BE and EME were similar to those observed for cocaine. The lowering of cocaine concentration in saliva in the stimulated flow condition was likely due to an increase in saliva pH associated with increased saliva flow rate; it is known that an increase in saliva pH retards cocaine partitioning into this biological fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Recent developments in alcoholism:pharmacological treatment.

Neurobiological research over the past decade has greatly expanded our knowledge of alcohol's interaction with the nervous system and promises significant improvement in pharmacological treatment for all phases of alcoholism. Although no new treatment has yet become standard clinical practice, over the next decade benzodiazepine receptor antagonists and inverse agonists should improve treatment of acute alcohol intoxication, adrenergic agents and anticonvulsants should improve treatment of acute alcohol withdrawal, and serotonin uptake blockers and mu opiate receptor antagonists should improve long-term treatment of alcohol dependence. Future clinical research should reduce the current lack of knowledge on pharmacological treatment of alcoholism in special populations such as women, the elderly, and those with concurrent psychiatric diagnoses.

Adult↗
PubMed1993

Overview of pharmacologic treatment approaches for alcohol and other drug addiction. Intoxication, withdrawal, and relapse prevention.

Medication plays an increasingly important role in the treatment of alcohol and other drug addictions, in part because many patients do not respond to existing psychosocial treatment alone. This article provides a conceptual overview of current pharmacologic treatment approaches, and covers all three aspects of drug abuse--intoxication, withdrawal, and relapse prevention.

Alcoholic Intoxication↗
PubMed1992

Psychoactive substance dependence among trauma center patients.

INTRODUCTION: The practice of assessing only trauma patients with elevated blood alcohol concentrations (BACs) or positive drug screens for psychoactive substance use disorders (PSUDs) was evaluated. METHODS: Twenty-four BAC-negative (BAC-) (BAC, 0) and 21 BAC-positive (BAC+) (BAC, greater than or equal to 22 mmol/L or 100 mg/dL; mean, 41 mmol/L; range, 24.3 to 79 mmol/L) adult trauma patients were evaluated for alcoholism and other PSUDs using the Structured Clinical Interview (SCI) from the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R). Approximately half were vehicular crash victims and 78% were men. RESULTS: A total of 64 PSUDs were diagnosed in 31 (68.9%) of the 45 patients; all but one was for dependence (vs abuse). Of the BAC+ patients, 14 (66.7%) met DSM-III-R criteria for alcohol dependence, 11 (78.6%) of whom also had other PSUDs not related to alcohol. Two other BAC+ patients had nonalcohol PSUDs. Of the BAC- patients, 11 (45.8%) had alcohol dependence, six (54.5%) of whom also had nonalcohol PSUDs. Another four BAC- patients had nonalcohol PSUDs. Overall, 76.2% of the BAC+ patients and 62.5% of the BAC- patients had a diagnosis of psychoactive substance dependence. CONCLUSION: All patients admitted to trauma centers should be assessed for alcoholism and other PSUDs.

Alcoholism↗
PubMed1992

Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers.

Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D2 dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2 dopamine receptor Taq I A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects; Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D2 dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.

Alcoholism↗