Effects of Naltrexone on Alcohol Self-Administration in Heavy Drinkers

Abstract

The mechanisms underlying the suppressant effects of naltrexone (NTX) on ad libitum alcohol drinking in a bar/restaurant setting were investigated in heavy beer drinkers. Fifty-one male and female heavy drinkers (mean age = 22) received 50 mg of NTX or placebo (PBO), p.o., on two separate occasions in a randomized, double-blind crossover protocol. After 7 days of taking medication, subjects were provided with the opportunity to consume beer ad libitum during two, 90-min test sessions that were held 1 to 2 weeks apart. Blood samples were collected on test days to ensure medication compliance and to measure blood levels of NTX and the active beta-naltrexol. Less beer was consumed during NTX treatment. NTX decreased urges to consume alcohol. NTX-treated subjects also took significantly longer to finish each glass of beer and were more likely to terminate beer drinking early. Self-report stimulation and ratings of positive mood states were lower during NTX treatment. Negative side effects of NTX, such as nausea and headache, were reported more frequently with NTX. Not all of the subjects decreased their beer intake on NTX, and some subjects drank more beer. Nonresponders to NTX were not related to blood levels of the active metabolite beta-naltrexol or to a family history of alcoholism. Overall, the results of this study suggest that NTX affects a number of the components of alcohol drinking sequence, including lowering cravings, decreasing the positive reinforcing effects of alcohol, and increasing headache and nausea, each of which may contribute to reducing alcohol intake.

Naltrexone vs. Nefazodone for Treatment of Alcohol Dependence A Placebo-Controlled Trial

“…In that study, NTX treatment was discontinued in 15.0% of patients because of adverse events, most frequently nausea. However, studies of former opioid addicts (Crowley et al 1985), normal control subjects (Swift et al 1994, Mendelson et al 1979, and heavy drinkers (Davidson et al 1999) have shown the drug to produce substantial rates of both neuropsychiatric and gastrointestinal adverse effects. Overall, it seems that, irrespective of diagnosis, there are substantial numbers of individuals who experience dysphoria, nausea, and other poorly tolerated adverse effects of opioid blockade.…”

“…Additional research on individual responses to the effects of NTX may help to determine the relative importance of decreased craving for alcohol, decreased positive reinforcement induced by drinking, and aversive effects of the medication in reducing the risk of alcoholic relapse (Davidson et al 1999). Clinically, such information may also help in the development of methods to enhance patients' capacity to tolerate the medication.…”

Effects of Acute Tryptophan Depletion on Negative Symptoms and Smoking Topography in Nicotine-Dependent Schizophrenics and Nonpsychiatric Controls

“…The influence of ATD on smoking behavior was measured via the following topography variables: time to first puff, number of puffs per cigarette, puff duration, interpuff interval, cigarette duration, and percentage of cigarette smoked. Acute changes in smoking topography and other drug consummatory behaviors have been found to reflect changes in drug motivation (Davidson et al, 1999;Renkin et al, 1979). Topography data were obtained by hand-timing the smoking behavior of participants who had been videotaped Effects of ATD on schizophrenic smokers B Hitsman et al while smoking.…”

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

“…NTX reduces alcohol consumption, craving, and relapse in subjects with a history of alcohol abuse (O'Brien et al, 1996;Anton et al, 1999;Davidson et al, 1999;Hernandez-Avila et al, 2006;see Heidbreder, 2005 for a recent review). Moreover, NTX significantly reduces ethanol consumption in rats (Stromberg et al, 1998) and monkeys (Boyle et al, 1998).…”

“…One possibility is that NTX decreases the rewarding effect of alcohol intake (Swift et al, 1994;Volpicelli et al, 1995;Sinclair, 2001). Another possibility is that NTX reduces drinking by generating aversive side effects, such as nausea, when ethanol is consumed (Davidson et al, 1999;de Wit et al, 1999;McCaul et al, 2000;Mitchell et al, 2005a). However, there is also evidence that NTX significantly reduces alcohol craving in alcoholics during abstinence (Monti et al, 1999;Rohsenow et al, 2000;O'Malley et al, 2002), and improves resistance to thoughts, urges, and behaviors associated with drinking (Anton et al, 1999).…”