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Biomedical subjects

J R Volpicelli

Publications and source records attributed to J R Volpicelli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Psychometric properties of the Penn Alcohol Craving Scale.

BACKGROUND: This study introduces the Penn Alcohol Craving Scale (PACS), which has been used in several clinical trials at the University of Pennsylvania's Treatment Research Center. The PACS is a five-item, self-report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week. Each question is scaled from 0 to 6. METHODS: To examine the questionnaire's psychometric properties, we sampled responses from 147 individuals participating in a 9-month combined natrexone (100 mg/day)/psychotherapy trial. The psychotherapy consisted of weekly sessions of nurse-administered medication compliance and supportive treatment. RESULTS: The PACS proved to have excellent internal consistency. Predictive validity was demonstrated via a logistic regression analysis of craving during the 2nd week of the study on alcohol relapse during weeks 3-12 of the trial. Construct validity of the PACS was demonstrated via its convergence with two commonly used measures for assessing craving, the Obsessive Compulsive Drinking Scale and the Alcohol Urge Questionnaire. Lack of correlation between PACS scores and several other noncraving, self-report measures indicates that the PACS also had good discriminant validity. Additional analyses revealed that there were significant differences in craving scores during the initial 3 weeks of the trial among those who did and those who did not relapse during weeks 3-12. CONCLUSION: The PACS is a reliable and valid measure of alcohol craving and can predict which individuals are at risk for subsequent relapse.

Adult↗
PubMed1998

A comparison of the effects of the opioid antagonists naltrexone, naltrindole, and beta-funaltrexamine on ethanol consumption in the rat.

The effects of the universal opioid antagonist naltrexone were compared to the delta-selective opioid antagonist naltrindole and the mu-selective opioid antagonist beta-funaltrexamine on ethanol consumption in the absence of food or fluid deprivation using a limited access procedure in Wistar rats. Both naltrexone, at doses of 0.1, 0.25, 0.5, 1.0, 3.0, and 10 mg/kg, and beta-funaltrexamine, at doses of 5.0 and 20.0 mg/kg, significantly decreased consumption of a 6% ethanol solution compared to saline control groups. Naltrindole, at doses of 5.0 and 15.0 mg/kg, failed to significantly reduce ethanol consumption. In addition, the highest doses of naltrexone, which antagonize delta as well as mu-opioid receptors, did not differ significantly from the lowest doses in their ability to reduce ethanol consumption. These data suggest that ethanol consumption using the limited access paradigm in the outbred rat is modulated by mu rather than delta-opioid receptors. Although this is not consistent with other data showing that delta antagonists decrease ethanol consumption, it is suggested that these difference may be related to the alcohol-preferring rats used in those experiments.

Alcohol Drinking↗
PubMed1998

Effects of naltrexone administered repeatedly across 30 or 60 days on ethanol consumption using a limited access procedure in the rat.

The present study examined the effects of naltrexone, 1.0 mg/kg, administered repeatedly across both 30 and 60 days on the consumption of an unsweetened ethanol solution by outbred Wistar rats in a limited access procedure. Naltrexone significantly suppressed consumption of ethanol across both 30 and 60 days. These results provide no evidence for the development of tolerance based on such factors as receptor upregulation or supersensitivity due to the repeated administration of naltrexone across extended periods. Ethanol consumption during the final one-third of the naltrexone sessions, for both the 30- and 60-day groups, was significantly lower than during the initial sessions. These results suggest an associative component. That is, the rats apparently learned that ethanol consumption was no longer reinforcing across repeated exposures. After termination of naltrexone treatment, consumption of ethanol immediately increased. However, consumption in those rats who were administered naltrexone for 60 days remained significantly suppressed, compared with consumption in those rats who were administered naltrexone for 30 days. These results suggest that naltrexone reduces ethanol consumption by blocking endogenous opioid receptors that mediate, at least in part, ethanol's reinforcing properties. In addition, these data suggest that longer clinical use of naltrexone, as a pharmacological adjunct to psychosocial treatment for alcohol-dependent patients, may be beneficial in reducing the number of relapses experienced.

Alcoholism↗
PubMed1997

Naltrexone and alcohol dependence. Role of subject compliance.

BACKGROUND: Two previous double-blind, placebo-controlled studies demonstrated that naltrexone (50 mg/d) reduces alcohol drinking in alcohol-dependent subjects. In both studies, treatment compliance was excellent. However, a robust treatment effect size for naltrexone relative to placebo has been shown for compliant subjects but not for subjects who missed research visits. The goal of this study was to determine the effectiveness of naltrexone in subjects who received psychosocial treatment in a more naturalistic setting with respect to the role of treatment attendance and medication compliance. METHODS: Ninety-seven alcohol-dependent subjects were randomly assigned to receive either naltrexone (n = 48) or matching placebo (n = 49) for 12 weeks. All subjects received individual counseling (twice per week for the first month followed by once per week). RESULTS: Overall, naltrexone showed only modest effects in reducing alcohol drinking for the 12 weeks of treatment. However, naltrexone treatment efficacy improved across a variety of outcome measures for subjects who completed treatment and were highly compliant with taking medication. CONCLUSIONS: Naltrexone is clinically effective relative to placebo in individuals who comply with the treatment protocol and take medication. The modest treatment effects in the entire sample suggest that the clinical efficacy of naltrexone could be improved by enhancing treatment compliance.

Adult↗
PubMed1997

Effect of naltrexone on subjective alcohol response in subjects at high and low risk for future alcohol dependence.

We investigated specific subjective effects of naltrexone pretreatment or placebo during various intervals on the breath alcohol level (BAL) curve in nonalcoholic volunteers. Fifteen high-risk (social drinkers with an alcoholic father) and 14 low-risk (no alcoholic relatives in at least two generations) subjects were tested in a double-blind placebo-controlled study of the effects of 50 mg oral naltrexone on response to a moderate dose of alcohol. Dependent measures included subjective stimulation and sedation subscales from the Biphasic Alcohol Effects Scale (BAES) and mood subscales from the Profile of Mood States (POMS). At rising BALs, high-risk subjects showed a naltrexone-related attenuation of BAES stimulation. This effect was not evident in low-risk subjects, who directionally showed the opposite effect, although nonsignificant. For both groups, there were no significant naltrexone-related effects for BAES sedation; however, naltrexone did affect several POMS scales on alcohol response, such as decreased vigor, and increased fatigue, tension, and confusion. Confusion was significantly elevated for the high-risk group during rising BALs of the naltrexone session. The results suggest a differential response to naltrexone, based on paternal history of alcoholism and level of stimulation experienced during alcohol drinking.

Adult↗
PubMed1997

Naltrexone biotransformation and incidence of subjective side effects: a preliminary study.

When administered orally, naltrexone undergoes extensive biotransformation and is metabolized to 6 beta-naltrexol and other minor metabolites. Naltrexone has been recently approved by the Food and Drug Administration for the treatment of alcohol dependence. An important clinical issue with naltrexone treatment is predicting patient compliance, which may be influenced by adverse side effects experienced during the medication. We investigated whether subjective side effects were related to urinary concentrations of naltrexone and its metabolite 6 beta-naltrexol 3 hr after administration of 50 mg po naltrexone in 24 male moderate-to-heavy social drinkers. The results showed significantly higher levels of urinary 6 beta-naltrexol (p < 0.05) in those subjects who experienced one or more side effect (i.e., headache, nausea, anxiety, or erection). Urinary naltrexone levels did not differ between the groups. Results also showed an approximate 10:1 ratio of 6 beta-naltrexol to naltrexone levels and a significant positive correlation between the parent compound and metabolite, suggesting parallel renal clearance. The results of this study suggest a possible mechanism for the side effects observed after acute administration of naltrexone.

Administration, Oral↗
PubMed1996

Amantadine in the early treatment of cocaine dependence: a double-blind, placebo-controlled trial.

A 4-week, double-blind, placebo-controlled trial of amantadine was conducted in 61 cocaine dependent outpatients. Subjects received 100 mg of amantadine 3 times daily. A follow-up visit was conducted at week 8. There were no significant differences between groups in treatment retention, or in the number of benzoylecgonine positive urine samples. Self-reported drug and alcohol use declined in both groups. At week 8 follow-up, self-reported drug use was significantly lower in the placebo group. Amantadine was not effective, and discontinuation of it may have been associated with an increase in cocaine use.

Adult↗
PubMed1996

A risk-benefit assessment of naltrexone in the treatment of alcohol dependence.

There is a great deal of interest in the use of naltrexone as a treatment for alcohol (ethanol) dependence since there is a rapidly expanding body of evidence to support its efficacy and tolerability in this indication. Naltrexone, a long-acting, nonselective opioid receptor antagonist has been shown to reduce alcohol intake when combined with behavioural treatment. Naltrexone may prevent the return to clinically significant drinking by blocking the pleasurable effects or "high' associated with alcohol drinking. Results from controlled studies showed that in alcohol dependent patients taking naltrexone 50 mg/day in combination with behavioural treatment, relapse rates were reduced by 50% compared with placebo treated patients. Historically, several factors have limited the use of effective pharmacological adjuncts in the treatment of alcohol dependence. These include safety considerations in this vulnerable population, and the fact that some treatment programmes discourage alcohol-dependent patients from taking medications. The most common adverse effects reported with the use of naltrexone at a dosage of 50 mg/day include nausea and vomiting. Naltrexone does not appear to be hepatotoxic in dosages recommended in the treatment of alcohol dependence, i.e. 50 mg/day. Thus, naltrexone appears to offer significant therapeutic benefits at a relatively low risk, when used judiciously and with behavioural treatment for alcohol dependent patients.

Alcoholism↗
PubMed1995

Decrease in alcohol tolerance: clinical significance in alcohol dependence.

In 237 male inpatients with alcohol dependence, clinical, demographic and biochemical data were analyzed in relation to alcohol tolerance. All subjects had a history of marked tolerance. At the time of assessment, 46% of subjects continued to meet the criteria for marked tolerance and 54% of the subjects reported a loss or decreased tolerance. Subjects with decreased tolerance were older than those with high tolerance and had a longer duration of illness. The age of onset was similar in both groups. Patients with decreased tolerance had more mental confusion and psychotic symptoms, and were less likely to be currently married.

Adult↗
PubMed1995

Effect of naltrexone on alcohol "high" in alcoholics.

OBJECTIVE: Subjective effects of alcohol in alcoholics treated with naltrexone or placebo were compared. METHOD: In a previously reported double-blind clinical trial of 50 mg/day of naltrexone or placebo for treatment of alcoholism, 36 of 70 detoxified male veterans deviated from abstinence. Of these 36, 29 subsequently reported on the subjective effects of drinking during the trial. RESULTS: A larger proportion of naltrexone-treated subjects (seven of 12) than placebo-treated subjects (two of 17) reported that the "high" produced by alcohol during the study was significantly less than usual. The naltrexone-treated subjects also drank less alcohol than the placebo-treated subjects during the first drinking episode. There was no difference between groups in reported intoxication, craving, memory, or loss of temper. CONCLUSIONS: The lower alcohol consumption by the naltrexone-treated subjects may have resulted from naltrexone's blockage of the pleasure produced by alcohol.

Alcohol Drinking↗
PubMed1995

Naltrexone in the treatment of alcoholism: predicting response to naltrexone.

The pooled results of 99 subjects from our Veterans Affairs population show that naltrexone-treated subjects had a greater reduction in alcohol craving, number of drinking days, and alcoholic relapse rates when compared with placebo-treated subjects. Based on our findings and results from other double-blind trials of naltrexone, we conclude that naltrexone is a safe and useful adjunct in the rehabilitation of alcohol-dependent patients. Increased baseline levels of psychological distress and craving as well as higher levels of somatic distress, anxiety, phobic anxiety, and obsessive-compulsive symptoms predicted an increased number of drinking days during the study. Significant interactions between naltrexone treatment, initial craving, and somatic distress suggest that naltrexone may be useful for subjects who present with high levels of craving and somatic symptoms.

Adult↗
PubMed1995

Opiates and alcohol self-administration in animals.

During the past 25 years, numerous animal studies have demonstrated a relationship between alcohol consumption and opiates. Converging lines of evidence suggest that (1) alcohol consumption enhances opioid receptor activity and (2) conditions associated with relative deficiencies in opioid receptor activity stimulate increases in alcohol preference. This evidence leads to the hypothesis that alcohol drinking is reinforced, in part, by enhanced opioid receptor activity; thus, these effects should be blocked by opiate antagonists. In fact, the animal data are consistent with this prediction. Opiate antagonists reduce excessive alcohol intake without reducing the ingestion of other biologically important reinforcers.

Alcohol Drinking↗
PubMed1995

Medical management of alcohol dependence: clinical use and limitations of naltrexone treatment.

Historically, pharmacological and psychosocial treatments for alcohol dependence have demonstrated only modest effectiveness in reducing alcohol drinking. However, the recent US Food and Drug Administration approval of naltrexone for the treatment of alcohol dependence offers a new, safe and effective medication to reduce relapse following alcohol detoxification. This paper reviews the various psychosocial and pharmacological treatments currently available and the effectiveness of these treatments. This paper also reviews preclinical research which demonstrates the involvement of the opioid system in the reinforcing effects of alcohol. This research led to clinical trials on the use of the opioid antagonist, naltrexone, to reduce alcohol's pleasurable effects and enhance the effectiveness of psychosocial therapy. In two randomized clinical trials, naltrexone treatment reduced rates of alcohol relapse, number of drinking days and alcohol craving. The clinical efficacy of all pharmacological treatments for substance abuse are limited by compliance with taking the medication. Also, pharmacological treatment does not address the psychosocial complications which often result from chronic alcohol dependence. Therefore, the integration of medications such as naltrexone and psychosocial therapies may offer the best treatment. The further development and investigation of new pharmacological agents will enable matching of patient populations with specific treatments, offering more successful treatment outcomes.

Alcoholism↗
PubMed1992

Naltrexone in the treatment of alcohol dependence.

Seventy male alcohol-dependent patients participated in a 12-week, double-blind, placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to treatment following alcohol detoxification. Subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. During the 12-week study, only 23% of the naltrexone-treated subjects met the criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed. The primary effect of naltrexone was seen in patients who drank any alcohol while attending outpatient treatment. Nineteen (95%) of the 20 placebo-treated patients relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone-treated patients exposed to alcohol met relapse criteria. Naltrexone was not associated with mood changes or other psychiatric symptoms. Significant side effects (nausea) occurred in two naltrexone-treated subjects, and one naltrexone-treated subject complained of increased pain from arthritis. These results suggest that naltrexone may be a safe and effective adjunct to treatment in alcohol-dependent subjects, particularly in preventing alcohol relapse.

Adult↗
PubMed1990

Circadian rhythmicity and behavioral depression: I. Effects of stress.

Rats were exposed to repeated sessions of inescapable footshock, and behavioral depression was subsequently assessed by measuring escape performance during exposure to escapable shock in a different testing environment. Free-running circadian activity rhythms were assessed using running wheels for approximately three weeks before and after administration of inescapable shock. Several animals showed lengthening of free-running period and decreases in activity level following shock. Similar effects were also seen in rats that were removed from their running wheels, placed within the shock apparatus, and not given shock, but not in nonhandled control animals. Furthermore, period lengthening in shocked and handled rats was positively correlated with escape performance, suggesting that circadian rhythm alterations occurred in those animals that were best able to cope with shock or handling-related stressors. In contrast, individual differences in circadian period and activity level during baseline conditions were not predictive of either escape performance or circadian rhythm alterations. These results suggest that successful behavioral adaptation to stress may be associated with alterations of circadian rhythmicity.

Affect↗
PubMed1990

Circadian rhythmicity and behavioral depression: II. Effects of lighting schedules.

Two studies explore the relationship between rhythmicity and behavioral depression. Behavioral depression was induced using inescapable footshock, and assessed by measuring subsequent responses to escapable shock, in rats housed under different light-dark conditions. Experiment 1 compared escape performance in free-running and entrained animals following inescapable shock. Free-running and entrained animals did not exhibit differential vulnerability to the effects of inescapable shock. In addition, there were no systematic effects on phase following shock. However, several free-running animals showed increased circadian period following shock, and lengthening of period was significantly correlated with escape performance. Individual differences in baseline period or phase were not predictive of escape performance. In Experiment 2, "aftereffects" of entrainment to long or short light-dark cycles were utilized to create groups of animals with long or short free-running periods. After the administration of inescapable shock, escape performance was tested. There were no significant differences among experimental groups in escape performance. These results suggest that plasticity of circadian period, but not baseline period per se, may be associated with the ability to adapt to environmental challenges.

Affect↗