Opioid antagonists in the treatment of alcohol dependence

Towell JF III, Cho JK, Roh BL, et al.: Disulfiram and erythrocyte aldehyde dehydrogenase inhibition. Clin Pharmacol Ther 1983, 33:517–521.

Petersen EN: The pharmacology and toxicology of disulfiram and its metabolites. Acta Psychiatr Scand 1992, 86:7–13.

Fishman J, Hahn EF, Norton BI: Comparative in vivo distribution of opiate agonists and antago means of double isotope techniques. Life Sci 1975, 17:1119–1125.

Verebey K, Mule SJ: Naltrexone pharmacology, pharmacokinetics, and metabolism: current status. Am J Drug Alcohol Abuse 1975, 2:357–363.

Martin WR, Jasinski DR, Mansky PA: Naltrexone, an antagonist for the treatment of heroin dependence: effects in men. Arch Gen Psychiatry 1973, 28:784–791.

Michel ME, Bolger G, Weissman BA: Binding of a new opiate antagonist, nalmefene, to rat brain membranes. Exp Clin Pharmacol 1985, 7:175–177.

Heilman RD, Hahn EF, Fishman J: Narcotic antagonists, IV. Carbon-6 derivatives of N-substituted noroxymorphones as narcotic antagonists. J Med Chem 1975, 18:259–262.

Gal TJ, DiFazio CA, Dixon R: Prolonged blockade of opioid effect with oral nalmefene. Clin Pharmacol Ther 1986, 40:537–542.

Cohen G, Collins M: Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism. Science 1970, 167:1749–1751.

Davis VE, Walsh MJ: Alcohol, amines, and alkaloids: a possible biochemical basis for alcohol addiction. Science 1970, 167:1005–1007.

Reid LD, Delconte JD, Nichols ML, et al.: Tests of opioid deficiency hypotheses of alcoholism. Alcohol 1991, 8:247–257.

Sinclair JD, Adkins J, Walker S: Morphine-induced suppression of voluntary alcohol drinking in rats. Nature 1973, 246:425–427.

Tabakoff B, Hoffman PL: Alcohol interactions with brain opiate receptors. Life Sci 1983, 32:197–204.

Froehlich JC, Zink RW, Li T-K, et al.: Analysis of heritability of hormonal responses to alcohol in twins: beta-endorphin as a potential biomarker of genetic risk for alcoholism. Alcohol Clin Exp Res 2000, 24:265–277.

Gianoulakis C, Beliveau D, Angelogianni P, et al.: Different pituitary β-endorphin and adrenal cortisol response to ethanol in individuals with high and low risk for future development of alcoholism. Life Sci 1989, 45:1097–1109.

Gianoulakis C, Krishnan B, Thavundayil J: Enhanced sensitivity of pituitary β-endorphin to ethanol in subjects at high risk of alcoholism. Arch Gen Psychiatry 1996, 53:250–257.

Verebey K, Volavka J, Mule SJ, et al.: Naltrexone: disposition, metabolism, and effects after acute and chronic dosing. Clin Pharmacol Ther 1976, 20:315–328.

McCaul ME, Wand GS, Rohde C, et al.: Serum 6-beta-naltrexol levels are related to alcohol responses in heavy drinkers. Alcohol Clin Exp Res 2000, 24:1385–1391.

Anton RF, Moak DH, Waid LR, et al.: Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial. Am J Psychiatry 1999, 156:1758–1764. This study included 131 recent abstinent individuals who received CBT and either naltrexone or placebo. In addition to having significantly longer periods of time to relapse, greater percentage of days abstinent, fewer drinking days, and fewer drinks per drinking day, naltrexone and CBT subjects reported a greater control over certain characteristics of craving including alcohol-related thoughts and urges. Naltrexone and CBT may be of particular benefit to those alcohol-dependent individuals who have these markers of craving.

Croop RS, Faulkner EB, Labriola DF, et al.: The safety profile of naltrexone in the treatment of alcoholism. Results from a multicenter usage study. Arch Gen Psychiatry 1997, 54:1130–1135.

O’Malley SS, Jaffe AJ, Chang G, et al.: Naltrexone and coping skills therapy for alcohol dependence: a controlled study. Arch Gen Psychiatry 1992, 49:881–887.

Volpicelli JR, Alterman AI, Hayashida M, et al.: Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 1992, 49:876–880.

King AC, Volpicelli JR, Frazer A, et al.: Effect of naltrexone on subjective alcohol response in subjects at high and low risk for future alcohol dependence. Psychopharmacol 1997, 129:15–22.

Rohsenow DJ, Colby SM, Monti PM, et al.: Predictors of compliance with naltrexone among alcoholics. Alcohol Clin Exp Res 2000, 24:1542–1549. In this study, 128 alcohol-dependent subjects were randomized in a placebo-controlled study to receive naltrexone or placebo for 12 weeks. Naltrexone-treated subjects were more likely to be compliant with treatment if they believed that medication would help with abstinence. The subjects who had a greater urge to drink during an alcohol cue-related assessment were also more likely to be compliance with naltrexone. The severity of comorbid substance abuse, as well as nausea and fatigue, during the first week of treatment was negatively associated with compliance.

Atkinson RL, Berke LK, Drake CR, et al.: Effects of long-term therapy with naltrexone on body weight in obesity. Clin Pharmacol Ther 1985, 38:419–422.

Mitchell JE, Morley JE, Levine AS, et al.: High-dose naltrexone therapy and dietary counseling for obesity. Biol Psychiatry 1987, 22:35–42.

Dixon R, Howes J, Gentile J, et al.: Nalmefene: intravenous safety and kinetics of a new opioid antagonist. Clin Pharmacol Ther 1986, 39:49–53.

Fudala PJ, Heishman SJ, Henningfield JE, et al.: Human pharmacology and abuse potential of nalmefene. Clin Pharmacol Ther 1991, 49:300–306.

Mason BJ, Salvato FR, Williams LD, et al.: A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. Arch Gen Psychiatry 1999, 56:719–724. One-hundred and five alcohol-dependent individuals were randomized in a double blind, placebo-controlled manner to receive a 12-week treatment with CBT and 1) nalmefene 10 mg twice per day, 2) nalmefene 40 mg twice per day, or 3) placebo. When compared with the placebo-treated subjects, nalmefene-treated subjects, regardless of the dose, were less likely to relapse to heavy drinking during the study period.

Mason BJ, Ritvo EC, Morgan RO, et al.: A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCI for alcohol dependence. Alcohol Clin Exp Res 1994, 18:1162–1167.

Chick J, Anton R, Checinski K, et al.: A multicenter, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Alcohol Alcohol 2000, 35:587–593. This 12-week, multicenter, randomized, placebo-controlled study of 169 subjects receiving usual psychosocial treatment plus naltrexone or placebo showed that naltrexone-treated subjects had significant reductions in serum GGT and alcohol craving when compared to control subjects.

O’Malley SS, Jaffe AJ, Chang G, et al.: Six-month follow-up of naltrexone and psychotherapy for alcohol dependence. Arch Gen Psychiatry 1996, 53:217–224.

Anton RF, Moak DH, Latham PK, et al.: Post-treatment results of combining naltrexone with cognitive-behavior therapy for the treatment of alcoholism. J Clin Psychopharmacol 2001, 21:72–77. This 14-week post-treatment follow-up study examined 124 of the original 131 alcohol-dependent subjects who received naltrexone and CBT in an earlier study. Gradual increases in relapse rates, heavy drinking days, number of abstinent days, as well as fewer abstinent days occurred during the duration of the 14-week follow-up period after the subjects discontinued treatment with naltrexone and CBT treatment.

Swift RM, Whelihan W, Kuznetsov O, et al.: Naltrexoneinduced alterations in human ethanol intoxication. Am J Psychiatry 1994, 151:1463–1467.

Davidson D, Palfai T, Bird C, et al.: Effects of naltrexone on alcohol self-administration in heavy drinkers. Alcohol Clin Exp Res 1999, 23:195–203. Fifty-four individuals who consumed beer heavily were randomly assigned to receive either naltrexone 100 mg or placebo. At two 90-minute drinking sessions held 1 to 2 weeks apart, naltrexone-treated subjects had a diminished urge to drink, drank less beer, took longer to finish a beer, and stopped drinking sooner than placebo control individuals.

O’Malley SS, Jaffe AJ, Rode S, et al.: Experience of a "slip" among alcoholics treated with naltrexone or placebo. Am J Psychiatry 1996, 153:281–283.

Monterosso JR, Flannery BA, Pettinati HM, et al.: Predicting treatment response to naltrexone: the influence of craving and family history. Am J Addict 2001, 10:258–268.

Kranzler HR, Tennen H, Penta C, et al.: Targeted naltrexone treatment of early problem drinkers. Addict Behav 1997, 22:431–436.

Rohsenow DJ, Monti PM, Hutchinson KE, et al.: Naltrexone’s effects on reactivity to alcohol cues among alcoholic men. J Abnorm Psychol 2000b, 109:738–742. ty-three alcohol-dependent men were randomized to receive either naltrexone or placebo. Naltrexone-treated subjects demonstrated a significantly decreased urge to drink in response to alcohol-related cues 4 hours after they initially ingested 50 mg of naltrexone. This effect was not seen in the placebo-treated subjects

June HL, McCane SR, Zink RW, et al.: The d2-opioid receptor antagonist naltriben reduces motivated responding for ethanol. Psychopharmacol 1999, 147:81–89. opioid antagonist naltriben caused inhibition of alcohol selfadministration in rats bred for high alcohol intake. The authors suggest that naltriben may be a potential pharmacologic agent