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Biomedical subjects

D A Gorelick

Publications and source records attributed to D A Gorelick.

At least 19 recordsLinked to original sources
PubMed2001

Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716.

BACKGROUND: SR141716, a recently developed CB1 cannabinoid receptor antagonist, blocks acute effects of Delta-9-tetrahydrocannabinol (THC) and other CB1 cannabinoid agonists in vitro and in animals. These findings suggest that CB1 receptors mediate many of the effects of marijuana, but this has not been evaluated in humans. METHODS: Sixty-three healthy men with a history of marijuana use were randomly assigned to receive oral SR141716 or a placebo in an escalating dose (1, 3, 10, 30, and 90 mg) design. Each subject smoked an active (2.64% THC) or placebo marijuana cigarette 2 hours later. Psychological effects associated with marijuana intoxication and heart rate were measured before and after antagonist and marijuana administration. RESULTS: Single oral doses of SR141716 produced a significant dose-dependent blockade of marijuana-induced subjective intoxication and tachycardia. The 90-mg dose produced 38% to 43% reductions in visual analog scale ratings of "How high do you feel now?" "How stoned on marijuana are you now?" and "How strong is the drug effect you feel now?" and produced a 59% reduction in heart rate. SR141716 alone produced no significant physiological or psychological effects and did not affect peak THC plasma concentration or the area under the time x concentration curve. SR141716 was well tolerated by all subjects. CONCLUSIONS: SR141716 blocked acute psychological and physiological effects of smoked marijuana without altering THC pharmacokinetics. These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana.

Administration, Oral↗
PubMed2000

An open-label study of a functional opioid kappa antagonist in the treatment of opioid dependence.

Several lines of evidence, including the well-established observation that kappa opiate agonists produce dysphoria and psychotomimetic effects in humans, suggest that dysfunction of the endogenous kappa opioid system may contribute to opioid and cocaine addiction. The objective of this open-label study was to determine the effectiveness of a functional kappa antagonist as a treatment for opioid dependence. This was accomplished by combining a partial mu agonist/kappa antagonist (buprenorphine, 4 mg, sublingual) with a mu antagonist (naltrexone, 50 mg by mouth), theoretically leaving kappa antagonism as the major medication effect. Subjects were treatment-seeking heroin-dependent (as per Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) men (41 +/- 7 years old; 19 +/- 8 years heroin use) eligible for methadone maintenance. After inpatient detoxification and a naloxone-challenge test to verify that they were not physically dependent on opioids, subjects received naltrexone. Starting on the fourth day, patients also received liquid buprenorphine. All patients received medication at the clinic 6 days per week and a full program of psychosocial treatment. The major endpoints of the study were: pupil diameter to determine if the mu agonist effects of buprenorphine were blocked by naltrexone, urine toxicology, and retention in treatment. Five patients (33%) completed the 3-month study. Four were abstinent from opioids and cocaine for the entire study, and one was abstinent from opioids and cocaine for the last 9 weeks. Six subjects dropped out due to either minor side effects or disliking the sensation of sublingual buprenorphine. There were no significant changes in pupillary diameter. The positive response to treatment exceeds that expected from naltrexone alone (90% dropout). These promising results suggest that controlled studies of this medication combination should be conducted.

Administration, Sublingual↗
PubMed2000

Gender differences in the EEG of abstinent cocaine abusers.

Gender differences in the EEG were explored in cocaine-abusing individuals not seeking treatment. Twenty currently abstinent cocaine-abusing females aged 21-41 were studied. Their cocaine use history was matched to 20 currently abstinent cocaine-abusing males. Twelve female and 20 male non-drug-abusing individuals served as a control group. Resting eyes closed EEG was recorded from 8 leads. The males who used cocaine had elevated EEG beta (p<0.0125) and reduced alpha (p<0.0125) when compared to the cocaine-abusing females and control subjects. These findings suggest that the EEG of cocaine-abusing women may be more normal than that of cocaine-abusing men. Such gender-specific differences for cocaine-abusing populations may require gender-specific treatment to improve outcome.

Adult↗
PubMed2000

Pathological gambling among cocaine-dependent outpatients.

OBJECTIVE: The authors investigated the occurrence of pathological gambling among cocaine-dependent outpatients, its influence on short-term outcome of treatment, and comparative characteristics of patients with and without pathological gambling. METHOD: The subjects were 313 cocaine-dependent (200 also opiate-dependent) outpatients in clinical trials of medication for cocaine dependence. Pathological gambling (DSM-III-R criteria) was assessed with the Diagnostic Interview Schedule, and sociodemographic and socioeconomic characteristics were determined with the Addiction Severity Index. Outcome was defined as time in treatment (proportion of maximum scheduled time) and proportion of cocaine-positive urine samples during treatment. RESULTS: Pathological gambling had a lifetime occurrence rate of 8.0% and a current (past month) occurrence of 3.8%. Onset preceded the onset of cocaine dependence in 72.0% of the patients (and preceded onset of opiate dependence in 44.4%). Patients with pathological gambling (lifetime or current) did not differ significantly from other patients in length of treatment or proportion of cocaine-positive urine samples. Those with lifetime pathological gambling were significantly more likely to have tobacco dependence (84.0% versus 61.1%) and antisocial personality disorder (56.0% versus 19.8%), to be unemployed (84.0% versus 49.3%), to have recently engaged in illegal activity for profit (64.0% versus 38.5%), and to have been incarcerated (62.5% versus 33.9%). CONCLUSIONS: Pathological gambling is substantially more prevalent among cocaine-dependent outpatients than in the general population. Patients with pathological gambling differ from other cocaine-dependent outpatients in some sociodemographic characteristics but not in short-term outcome of treatment for cocaine dependence.

Adolescent↗
PubMed2000

Butyrylcholinesterase accelerates cocaine metabolism: in vitro and in vivo effects in nonhuman primates and humans.

Butyrylcholinesterase (BChE) is known to metabolize cocaine in humans. In the present study, three different experiments were performed to determine whether the addition of horse serum-derived BChE would accelerate the metabolism of cocaine. In the first experiment, the addition of BChE to squirrel monkey plasma in vitro reduced the half-life of cocaine by over 80%, decreased the production of the metabolic product benzoylecgonine, and increased ecgonine methyl ester formation. The effect of BChE on cocaine metabolism was reversed by a specific BChE inhibitor. In the second, in vivo, experiment, exogenously administered BChE reduced peak cocaine concentrations when given to anesthetized squirrel monkeys. Finally, incubation of cocaine with added BChE in human plasma in vitro resulted in a decrease in cocaine half-life similar to that observed with squirrel monkey plasma. The magnitude of the decrease in cocaine half-life was proportional to the amount of added BChE. Together, these results indicate that exogenously administered BChE can accelerate cocaine metabolism in such a way as to potentially lessen the behavioral and toxic effects of cocaine. Therefore, BChE may be useful as a treatment for cocaine addiction and toxicity.

Animals↗
PubMed1998

Sociodemographic representation in published studies of cocaine abuse pharmacotherapy.

This study evaluated: (1) the reporting of sociodemographic characteristics of research subjects in published outpatient studies of cocaine abuse pharmacotherapy; (2) the association of study characteristics with such reporting and with the distribution of characteristics; and (3) the comparison of sociodemographic characteristics in the research subjects with those of a community-based sample of cocaine abusers who had sought treatment. Medline search identified 68 articles on cocaine abuse outpatient pharmacotherapy published from 1983 to 1993 in an English language, peer-reviewed journal. Sociodemographic characteristics of research subjects (n = 1802) were compared with those of respondents (weighted n = 135) to the National Comorbidity Survey (1990-1992), who reported at least one cocaine-related problem and had sought substance abuse treatment. Only three (4.4%) articles reported all six of the following sociodemographic characteristics of their subjects: 82.4%, reported mean age; 58.8%, race/ethnicity; 85.3%, sex; 22.1%, employment status; 13.2%, educational status; and 5.9%, socioeconomic status/income. Compared to survey respondents, research subjects were significantly more likely to be African-American and live in the Northeast region of the US and marginally more likely to be male and currently unemployed. These findings indicate that many published articles do not follow currently recommended guidelines for describing sociodemographic characteristics of research subjects and that, aside from race/ethnicity and geographic location, research subjects are fairly comparable in basic sociodemographic characteristics to the larger population of treatment-seeking individuals with cocaine-related problems.

Adult↗
PubMed1998

Mechanisms of alcohol craving and their clinical implications.

Craving for alcohol is frequently given as a reason for drinking and is often used as a surrogate measure in studies of alcoholism and its treatment. Despite this wide use, there is little consensus on what craving for alcohol means, the best way to measure it, what mechanism accounts for the urge to drink, or what is its true relationship to alcohol use. This chapter reviews theoretical and measurement issues about the possible mechanisms involved in craving for alcohol and the clinical implications of evidence supporting them. Until recently, most instruments for assessing craving assumed it was a univariate construct and usually contained only one or a few items. Several multi-item and multidimensional rating instruments have now been developed that offer the promise of more useful assessment of clinically relevant behavior. Most models of craving have assumed that a consistent and positive relationship exists between craving and drinking. The incentive sensitization model and the cognitive theory of drug use and drug urges may account better than the older models for the frequent clinical observation of a dissociation between craving and drinking. However, no single model or theory of craving accounts for the wide variation in findings reviewed here, suggesting that multiple mechanisms may be involved. A comprehensive, multidisciplinary approach is necessary to elucidate the nature of craving for alcohol and its implications for pharmacological and psychosocial treatment of alcoholism.

Alcohol Drinking↗
PubMed1998

Attenuation of cocaine-induced locomotor activity by butyrylcholinesterase.

A primary enzyme for the metabolism of cocaine is butyrylcholinesterase (BChE). To determine whether the systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect, rats were tested in a locomotor activity chamber after receiving 17 mg of cocaine per kg intraperitoneally. In rats pretreated intravenously with 5,000 IU of horse serum-derived BChE, the locomotor activity effect was significantly attenuated. BChE pretreatment increased plasma BChE levels approximately 400-fold. When added to rat plasma, this amount of BChE reduced the cocaine half-life from over 5 hr to less than 5 min. BChE altered the cocaine metabolic pattern such that the relatively nontoxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. These results suggest that systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect of cocaine and thus should be investigated as a potential treatment for cocaine abuse.

Animals↗
PubMed1998

Screening trauma patients for alcoholism according to NIAAA guidelines with alcohol use disorders identification test questions.

Drinking pattern criteria (drinking frequency and number of drinks per occasion) issued by the National Institute on Alcohol and Abuse and Alcoholism (NIAAA) to screen primary practice patients for alcohol problems were evaluated in 1216 injured patients treated in a regional trauma center. Vehicular crash victims predominated (50.2%, of whom 64.5% were drivers), followed by victims of violence (31.2%) and nonviolent-injury victims (18.5%). Alcohol Use Disorders Identification Test (AUDIT) questions #1 (drinking frequency) and #2 (drinks/day) were used to assess the patients for current alcohol dependence (CAD). AUDIT responses roughly approximating NIAAA guidelines (high threshold: drinks > or = 4 times/week, > or = 5 drinks/day) and those indicating less drinking (low threshold: drinks > or = 2-3 times/ week, > or = 3 drinks/day) were chosen. Comparisons were made relative to sensitivity and specificity of responses in detecting CAD. When low threshold responses were used for either question, sensitivity to detect CAD increased overall (#1 from 0.53 to 0.80, #2 from 0.62 to 0.88) as well as among the subgroups of patients, whereas specificity remained high or at acceptable levels overall (#1 from 0.95 to 0.82, #2 from 0.92 to 0.71) and among the subgroups of patients. Study findings suggest that, among injured drivers and other groups of trauma center patients, lesser amounts of drinking should be used as screening criteria for CAD than are used for the general population.

Accidents, Traffic↗
PubMed1998

Cigarette smoking during early cocaine abstinence.

Use of cocaine has been reported to increase cigarette smoking, but there are no published studies of cigarette smoking during early cocaine abstinence. The authors assessed ad libitum cigarette smoking of 12 cocaine-dependent smokers housed on a closed research ward. Last cocaine use averaged 0.6 grams 1.8 days before admission. Smoking was measured indirectly with computerized cigarette dispensers. There was no significant difference between self-reported daily number of cigarettes smoked before admission and the number of cigarettes dispensed daily for the first 7 full days after admission. These findings suggest that early cocaine abstinence does not significantly alter cigarette smoking.

Adult↗
PubMed1997

Enhancing cocaine metabolism with butyrylcholinesterase as a treatment strategy.

Existing pharmacodynamic approaches to cocaine abuse treatment have not been widely successful. An alternative, pharmacokinetic, approach is to enhance cocaine metabolism by administration of butyrylcholinesterase (BChE), a major cocaine-metabolizing enzyme in primates. Initial studies in rodents suggest that BChE pretreatment can substantially reduce the acute physiological and behavioral effects of cocaine, at enzyme doses that themselves have no behavioral or toxic effects. A single enzyme injection may increase plasma BChE activity for several days, suggesting that exogenous administration may be practical. BChE treatment may also produce a favorable pattern of cocaine metabolites. Further research is needed to evaluate the long-term effects of BChE administration.

Animals↗
PubMed1997

Psychoactive substance use disorders among seriously injured trauma center patients.

OBJECTIVE: To assess the prevalence of psychoactive substance use disorders (PSUDs) among a large, unselected group of seriously injured trauma center patients, using a standardized diagnostic interview and criteria. DESIGN: Prevalence study. SETTING: A level I regional trauma center. PATIENTS: Trauma center patients fulfilling the following criteria were eligible subjects: aged 18 years or older, admission from injury scene, length of stay of 2 days or longer, and intact cognition. OUTCOME MEASURES: The PSUDs were diagnosed using the Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) and were categorized as abuse or dependence and past or current (within past 6 months). The SCID results were analyzed with respect to demographic factors, injury type, and blood alcohol concentration and urine toxicology results, using chi2 and logistic regression techniques. RESULTS: Of the 1220 patients approached for study, 1118 (91.6%) consented. More than half (54.2%) had a diagnosis of a PSUD in their lifetime. Approximately 90% of alcohol and other drug use diagnoses were for dependence and more than 62% were current. Overall, 24.1% of patients were currently alcohol dependent (men, 27.7%; women, 14.7%; P<.001), and 17.7% were currently dependent on other drugs (men, 20.2%; women, 11.2%; P<.001). Current alcohol dependence rates were not associated with race; rates of dependence on other drugs were higher among nonwhites and victims classified with intentional injuries. While 54.3% of blood alcohol-positive patients were currently alcohol dependent and 38.7% of patients with positive urine screening test results for drugs other than alcohol and nicotine were currently drug dependent, 11.7% of blood alcohol-negative and 3.9% of drug-negative patients, respectively, had current diagnoses of dependence on psychoactive substances. CONCLUSIONS: A high percentage of seriously injured trauma center patients are at risk of having current PSUDs. Patients with positive toxicology screening test results and/or positive screening questionnaire responses should be referred for formal evaluation and treatment.

Adult↗
PubMed1997

Neurophysiological signs of cocaine dependence: increased electroencephalogram beta during withdrawal.

To determine whether a central nervous system marker of cocaine dependence might exist, the resting electroencephalogram (EEG) of 33 drug-free, cocaine-dependent men (DSM-III-R criteria) was compared with two control groups [nondrug group (n = 10) and drug group who abused drugs, but were not cocaine dependent (n = 20)]. The EEG was recorded from eight sites after about 10 days of monitored abstinence (range 4-15 days) on a closed research ward for the drug-using individuals. The EEG was recorded for the nondrug control group as outpatients. The drug history was determined by the drug history questionnaire and a medical screening interview. The percent of EEG beta activity for the cocaine-dependent subjects was greater than that of both control groups (p < .05) as well as a normative database (HZI: Tarrytown, NY). The percent of EEG beta in frontal and central areas of the cocaine-dependent individuals was correlated with the frequency of cocaine use during the last 30 days. High levels of EEG beta may be a neurophysiological withdrawal sign in cocaine-dependent men.

Adult↗