Alcoholism, clinical and experimental research
-
Alcohol. Clin. Exp. Res. · Apr 2007
Randomized Controlled TrialOpioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study.
Pharmacotherapy of alcohol dependence (AD) is at an early stage of development; currently available medications have limited efficacy. It would be clinically valuable to identify, before initiation of a course of treatment, those patients who, based on genetic markers, are most likely to respond to a specific pharmacotherapy. A previous report suggested that a functional variant at the genetic locus encoding the mu opioid receptor (Asn40Asp) is such a marker, in short-term (3-month) treatment with the opioid-blocking drug naltrexone (NTX). ⋯ These results do not support association of the OPRM1 Asn40Asp polymorphism with NTX treatment response for AD.
-
Alcohol. Clin. Exp. Res. · Feb 2007
Randomized Controlled TrialA double-blind evaluation of gabapentin on alcohol effects and drinking in a clinical laboratory paradigm.
There has been increasing interest in the use of anticonvulsant agents in the treatment of alcoholism. Anticonvulsant agents have mostly been evaluated as an alternative to benzodiazepines in the treatment of alcohol withdrawal. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol (i.e., interactions that could increase psychomotor deficits, cognitive impairment, and increase intoxication). This is particularly important in the treatment of alcohol withdrawal and relapse prevention in outpatients. Unfortunately, these untoward clinical interactions between anticonvulsants and alcohol in alcoholic patients have not been thoroughly assessed. The current clinical laboratory study was conducted to evaluate the safety and tolerability of the anticonvulsant gabapentin in alcoholic subjects. In addition, the ability of gabapentin to reduce alcohol craving and consumption was evaluated. ⋯ This study provides initial evidence that the anticonvulsant gabapentin is safe if used in conjunction with alcohol consumption in alcoholic individuals. Further study is needed with this and other lab models to determine the utility and safety of gabapentin in the treatment of alcoholism.
-
Alcohol. Clin. Exp. Res. · Mar 2006
Randomized Controlled Trial Comparative StudySingle- and multiple-dose pharmacokinetics of long-acting injectable naltrexone.
Oral naltrexone is effective in the treatment of alcohol dependence; however, a major limitation of its clinical utility is poor patient adherence to the daily dosing schedule. A biodegradable, long-acting naltrexone microsphere formulation was developed to achieve continuous naltrexone exposure for 1 month in the treatment of alcohol dependence. ⋯ This study demonstrated that the long-acting naltrexone formulation was well tolerated, displayed predictable pharmacokinetics, and resulted in no meaningful drug accumulation upon multiple dosing. Intramuscular administration avoids first-pass metabolism and changes the exposure ratio of 6beta-naltrexol to naltrexone compared with oral administration. By providing continuous exposure to naltrexone for several weeks following IM injection, this long-acting naltrexone formulation may offer therapeutic benefit to those patients who experience difficulty adhering to the daily administration schedule necessitated by oral naltrexone therapy.
-
Alcohol. Clin. Exp. Res. · Dec 2005
Randomized Controlled TrialAICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats.
Previous work with metformin has shown that this antidiabetic agent improves nonalcoholic fatty liver in ob/ob mice. AMP-activated protein kinase (AMPK) is one of the major cellular regulators of lipid and glucose metabolism, and reportedly mediates the beneficial metabolic effects of metformin. In this study, we examined the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an AMPK activator, on an experimental model of ethanol-induced hepatic steatosis. ⋯ In this preclinical rat model, AICAR, an AMPK activator, appears to protect the liver from fatty changes associated with chronic alcohol use. As such, AICAR may have a role in the treatment and prevention of alcohol-induced fatty liver.
-
Alcohol. Clin. Exp. Res. · Aug 2003
Randomized Controlled Trial Comparative Study Clinical TrialMeasurement and prediction of medication compliance in problem drinkers.
A variety of methods have been used to measure medication compliance. Although electronic monitoring has been considered to be the best method, it has some potential for error and its high cost may limit its feasibility. This study examined the concordance of data on medication compliance that was obtained by using an electronic monitoring system (Medication Event Monitoring System, or MEMS), daily diary reports, and tablet counts. ⋯ Compliance measurement using a daily diary method yielded results that are comparable to those obtained with electronic monitoring, which served as a criterion measure. In contrast, tablet counts provided data that were less concordant with the criterion measure. The unique nature of the study sample (i.e., the majority of subjects were not committed to a goal of abstinence), combined with the targeted approach to treatment, may explain the lack of association between compliance and alcohol-related outcomes. Further research should aim to ascertain the factors affecting the relationship between compliance and outcomes.