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Biomedical subjects

D A Gorelick

Publications and source records attributed to D A Gorelick.

At least 55 records · Page 3Linked to original sources
PubMed1992

Hypothalamic-pituitary function during alcohol exposure and withdrawal and cocaine exposure.

This chapter examines the neuroendocrine effects of acute exposure to and withdrawal from alcohol and cocaine, with special emphasis on the hypothalamic-pituitary-adrenal (HPA) axis. We present the results from two preliminary controlled inpatient studies that document HPA dysfunction during acute exposure to alcohol and cocaine and during withdrawal from alcohol. We discuss the methodological approach of these studies in comparison to related attempts in the literature to use measures of thyroid and prolactin regulation to predict risk of relapse to alcohol and cocaine use, respectively. Our data and the results of related studies are presented in the context of a proposed index of HPA axis dysfunction that may provide a useful clinical measure of susceptibility to relapse during protracted abstinence from alcohol or cocaine.

Adrenocorticotropic Hormone↗
PubMed1992

Effect of fluoxetine on alcohol consumption in male alcoholics.

To test the effect of inhibiting serotonin uptake on voluntary alcohol intake, 20 alcohol-dependent males were housed on a locked hospital ward with 60-ml drinks of 97.5 proof alcohol available in a fixed interval drinking decision paradigm 13 times each day. After a 3-day, single-blind placebo baseline period, 10 subjects each received the serotonin uptake blocker fluoxetine (up to 80 mg po daily) or placebo double-blind for 28 days. The fluoxetine group had a 14% lower alcohol intake during the 1st week only, associated with a lower proportion of requests for alcohol and less craving for alcohol (as rated by research staff). There were no significant effects in later weeks, nor any differences in scores on the Hamilton Depression and Anxiety Scales or the Hopkins Symptom Checklist.

Adult↗
PubMed1992

Pathophysiological effects of cocaine in humans: review of scientific issues.

Almost all data on pathophysiological abnormalities associated with human cocaine use comes from clinical observation and testing of cocaine abusers seeking treatment. Such data are subject to several confounding factors which preclude drawing definitive conclusions about the pathophysiological mechanism for the observed abnormality, its prevalence and prognosis, and individual differences in susceptibility. Confounding factors include the unknown purity of cocaine used, uncertainty as to quantity and duration of cocaine exposure, effects of other substances frequently used by cocaine users, abnormalities associated with drug route of administration and the drug abuse lifestyle, and selection bias. Future studies can address these issues by employing more sophisticated research designs, such as prospective, longitudinal follow-up of large, representative samples of cocaine users, case-control comparisons of well characterized cocaine users with appropriately matched groups, and experimental administration of cocaine under safe, controlled conditions.

Catecholamines↗
PubMed1992

Progression of dependence in male cocaine addicts.

We studied the self-reported temporal sequence of cocaine-related problems in 45 male predominantly Black (85%), lower SES cocaine addicts undergoing inpatient treatment at a large urban VA psychiatric hospital. Subjects reported recent average use of 2.5 g of cocaine per day for 14 days each month and experiencing a mean of 14 cocaine-related problems. The temporal sequence of cocaine-related problems was roughly consistent with the sequence of alcohol-related problems reported for alcoholics, with the earliest problems being interpersonal (e.g., arguments with others) and the most recent problems the severest (e.g., job loss, marital separation). The cocaine addicts showed a faster progression from first cocaine use to first cocaine-related problems (mean of 3.75 years) than that reported for alcoholics from first drink to first heavy drinking (8-10 years). Cocaine smokers had a faster course (3.4 years) than intranasal users (5.3 years).

Adult↗
PubMed1992

Alcohol and cocaine. Clinical and pharmacological interactions.

Both clinical experience and epidemiological studies in community and specialized (e.g., treatment) populations indicate that the prevalence of co-use of alcohol and cocaine, and the comorbidity of alcoholism and cocaine addiction, are greater than would be expected from the chance occurrence of two independent conditions. Alcohol and cocaine have pharmacokinetic and pharmacodynamic interactions that may account for some of this co-use. While their reinforcing properties have neuropharmacological and behavioral differences, a unified theory of reinforcement by alcohol and cocaine has been proposed, involving dopamine activity in the ventral tegmental area-nucleus accumbens circuit. Regardless of their pharmacology, the prevalent co-use of alcohol and cocaine has important implications for drug abuse treatment and indicates the need for future research on this topic.

Alcoholism↗
PubMed1992

Age, alcoholism and depression are associated with low levels of urinary melatonin.

Two normal control populations, separated by 8,000 miles and 24 degrees of latitude, had similar six-month mean values for overnight urinary melatonin concentrations. These values were significantly higher than six-month values for depressed subjects and abstinent alcoholic subjects, while the means for the two clinical populations were similar. Age and urinary melatonin concentration in the control and clinical populations were inversely related, but the slopes of the linear regression equations were ten times steeper for the control populations than for the clinical populations. Differences in age and sex distributions accounted for some of the differences in values between controls and the clinical populations, although controls still differed from the clinical populations, even after sex and age were factored out. The disparate slopes for age and melatonin concentrations may contribute to some of the conflicting findings of studies comparing populations of different ages. The total melatonin content in the samples from alcoholic subjects, but not the depressed subjects, was lower than that for controls. The difference in the urinary melatonin concentration between the controls and the two patient groups was not accounted for by difference in duration of urine collection period, hours of sleep or body weight.

Adult↗
PubMed1989

Myocardial ischemia during cocaine withdrawal.

STUDY OBJECTIVE: To determine the prevalence of myocardial ischemia in patients with cocaine addiction. DESIGN: Myocardial ischemia in chronic cocaine users was detected by serial 24-hour electrocardiographic ambulatory (Holter) monitoring and exercise treadmill testing in chronic cocaine users. The Holter tapes were coded, scanned in a blinded manner, and mixed with the tapes of 42 normal volunteers and 119 patients with either stable or unstable angina. SETTING: A 28-day inpatient, substance abuse treatment program followed by an outpatient treatment program. PATIENTS: Twenty-one consecutive male chronic cocaine users. MAIN RESULTS: Eight of the 21 patients with cocaine addiction had frequent episodes of ST elevation during Holter monitoring; these episodes occurred almost exclusively during the first 2 weeks of withdrawal. None of the volunteers and patients with stable angina and only 4% of the patients with unstable angina had episodes of ST elevation during Holter monitoring (cocaine users compared with volunteers, P = 0.0004). Of the 20 cocaine patients who had exercise treadmill testing, only 1 had a positive test for ischemia. CONCLUSIONS: Cocaine users frequently develop silent myocardial ischemia manifesting as episodes of ST elevation during the first weeks of withdrawal. The underlying mechanisms for these changes remain unknown, but our observations support the hypothesis that coronary vasospasm plays an important role in cocaine-related ischemic syndromes.

Adult↗
PubMed1989

Serotonin uptake blockers and the treatment of alcoholism.

There is growing research and clinical interest in the role of brain serotonin in regulating alcohol consumption, based on two lines of evidence: negative correlations between brain serotonin levels and spontaneous alcohol consumption in rodents, and decreased alcohol intake produced by drug-induced increases in brain serotonin activity in rodents and humans. Specific blockers of neuronal serotonin uptake, such as citalopram, fluoxetine, and zimelidine, are the major drugs used in such studies. More than a dozen studies have consistently found that such specific serotonin uptake blockers reduce alcohol preference and intake in rodents, whereas nonspecific monoamine uptake blockers (e.g., amitriptyline, doxepin) do not. The effect begins within 1 hr of administration, wears off within several days of stopping drug, and often shows tolerance after 4-10 days of daily administration (the opposite time course from antidepressant action in humans). In four human, double-blind, placebo-controlled studies, citalopram (40 mg but not 20 mg daily), fluoxetine (80 mg daily), and zimelidine (200 mg more than 300 mg daily) significantly reduced alcohol intake 10-26% in social drinkers, early problem drinkers, and chronic alcoholics. The effect occurred within a few days, wore off within several days of stopping drug, and lasted throughout the 2-4 weeks of drug administration, except that in the fluoxetine study with chronic alcoholics the effect was significant only during the first week. The reduced alcohol intake was not due to sedation, antidepression, or antianxiety effects, or an aversive drug-alcohol interaction, but could be explained in part by decreased appetitive behavior (two studies found that subjects lost weight) or a conditioned (taste) aversion to alcohol promoted by serotonin (as occurs in animals). Further research is also needed to clarify the neuropharmacological mechanism of action, since the alcohol intake-reducing effects in rodents are not blocked by serotonin receptor antagonists or brain serotonin depletion. Regardless of mechanism, serotonin uptake blockers offer a potentially promising new treatment for alcoholism.

Alcohol Drinking↗
PubMed1989

Outpatient treatment of PCP abusers.

Despite the persistence of phencyclidine (PCP) abuse as a public health problem in many urban areas of the United States, there are no published data on outpatient treatment outcome. We studied 37 unselected male PCP abusers (mean age 32 years, 73% Black, 19% married, 68% unemployed) who attended at least one outpatient treatment session at the Brentwood Division, West Los Angeles VA Medical Center. Subjects had smoked PCP for an average of 7 years, with 84% using it at least weekly (38% daily) and 76% using other drugs (alcohol, marijuana, or cocaine). All subjects reported psychological dependence on PCP (i.e., liking PCP use and difficulty stopping despite adverse consequences), while none reported a physiological withdrawal syndrome when stopping PCP use. Subjects stayed in treatment an average of 21 weeks (range 1-155 weeks), attending an average of 68% of the group meetings. PCP was detected in weekly urine samples 78% of the time, with verbal self-report of recent PCP use occurring before 29% of the group meetings. Four subjects (11%) achieved at least 1 year of abstinence, 10 (30%) transferred to residential treatment or a community recovery home, 16 (48%) dropped out of treatment, and two (6%) were jailed. Treatment outcome was not significantly associated with subject characteristics. Age was the only subject characteristic that significantly predicted length of stay (r = .40).

Adult↗
PubMed1989

Inpatient treatment of PCP abusers and users.

Screening of 155 consecutive admissions to a voluntary, 4-6 week substance abuse inpatient rehabilitation program revealed a 13% prevalence of PCP abuse (defined by DSM-III criteria) and a 23% prevalence of nonabusive PCP use. The 20 PCP abusers were significantly younger (31.6 vs 40.2 years) and had more prior arrests (2.0 vs 0.8) than the 36 nonabusive users, but did not differ in other sociodemographic characteristics. The age range of patients was older than previously reported in the literature, with three PCP abusers (15%) and 15 users (42%) 40 years of age or older. A majority of both abusers (80%) and users (97%) also abused other drugs, including alcohol (57%), opiates (29%), marijuana (29%), and stimulants (18%). The mean length of stay for PCP abusers was 27 days, with 11 completing inpatient treatment. Urine samples were collected upon admission from all patients and assayed for PCP by gas chromatography with N-P detection (sensitivity = 0.1 ng/mL). Patients with initial positive PCP results had follow-up urines collected at least weekly until the PCP assay was negative or they left the treatment program. Twenty-seven percent of patients had PCP detected in admission urine samples, one-third of whom initially denied PCP use. Six patients still had PCP detected after 4 weeks of hospitalization, without evidence of PCP reuse. These findings suggest that PCP abuse and use are common among unselected patients seeking substance abuse inpatient treatment and that they are not confined to the adolescent/young adult age group.

Adult↗
PubMed1988

Dental management of the cocaine addict.

Addiction to cocaine is a growing problem in the United States. The detrimental physiologic aspects of addiction require that certain precautions be observed during dental care to avoid a morbid reaction or a possible fatality. The adverse psychological and social aspects of addiction must also be understood by the dentist in order to properly manage this troubled group of patients.

Cocaine↗
PubMed1987

Alcoholism and dental management.

Alcohol is widely used and abused in the United States. Because alcohol affects all parts of the body, it is important for dentists as well as all other medical practitioners to be aware of the signs of alcoholism. Some dental problems occur more frequently in alcoholic patients, and often general dental care for these patients must be modified.

Alcoholism↗
PubMed1986

Clinical neuroendocrinology and neuropharmacology of alcohol withdrawal.

A number of alcohol research groups have measured anterior and posterior pituitary hormones, the endogenous opiates, CNS peptides, and putative neurotransmitters during alcohol withdrawal. The data are often complex and contradictory, though a number of themes have emerged. Activity of the hypothalamic-pituitary-adrenal axis (HPA) is increased during chronic alcohol exposure and appears to remain altered for at least 2 to 4 weeks after cessation of drinking. There is increased turnover of norepinephrine and enhanced binding of CNS adrenergic receptors. By contrast, there are decreases in CNS activity of select endogenous opiates and GABA. Other CNS compounds that may play a role in alcohol withdrawal are prolactin, thyrotropin-releasing hormone (TRH), vasopressin, cyclic 3'5'-adenosine monophophate (cAMP), Delta-sleep-inducing peptide (DSIP), and iron. Despite many studies in humans and animals, the roles of CNS dopamine and serotonin in withdrawal remain unclear. A number of peptides, including cholecystokinin (CCK), neurotensin, and bombesin, have been shown to interact with the CNS actions of alcohol and may play a role in alcohol withdrawal. Inadequate work has been performed on acetylcholine (ACh), human growth hormone (HGH) and luteinizing hormone (LH). Studies of the recently identified GABA-benzodiazepine-barbituate receptor complex indicate that this system is likely to be involved in the pathophysiology of alcohol withdrawal. Perturbation studies with corticotropin-releasing factor (CRF) and TRH (with measures of ACTH and cortisol and TSH and prolactin, respectively), may identify patients with withdrawal-related autonomic dysfunction.

Animals↗
PubMed1986

Special aspects of human alcohol withdrawal.

There are still surprising gaps in our knowledge of alcohol withdrawal. While quantitative alcohol consumption accounts for about one third of the variability in severity of acute withdrawal, there is little systematic knowledge about the other factors involved. Thus, we cannot precisely predict the severity of withdrawal in individual patients. Controversy exists as to the role of medical vs. social detoxification approaches to acute withdrawal, the influence of acute withdrawal and its treatment on the long-term outcome of alcoholism, and the importance (or even existence) of chronic withdrawal. There is little systematic data to guide withdrawal treatment in special clinical settings, e.g., with concurrent medical or psychiatric illness or with mixed substance dependence. This chapter reviews the published literature, tries to point out methodological and conceptual problems, and suggests areas for future research.

Alcoholism↗