Naltrexone and Cognitive Behavioral Therapy for the Treatment of Outpatient Alcoholics: Results of a Placebo-Controlled Trial

Anton, Raymond F.; Moak, Darlene H.; Waid, L. Randolph; Latham, Patricia K.; Malcolm, Robert; Dias, James W.

doi:10.1176/foc.1.2.183

Cited by 160 publications

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“…The results pertaining to the reduction in craving for amphetamine are in concordance with the reduction in the VAS 'want more', adding strength to the concept of using NTX as an anticraving medication. Similar results have also been noted in studies with alcohol dependence (Anton et al, 1999;Chick et al, 2000). NTX is Effects of naltrexone in amphetamine dependent patients N Jayaram-Lindström et al currently used worldwide as an anticraving medication for alcoholism (O'Brien, 2005) and the results of the present study could be indicative of its efficacy also in the amphetamine-dependent population.…”

Section: Resultssupporting

confidence: 90%

Naltrexone Attenuates the Subjective Effects of Amphetamine in Patients with Amphetamine Dependence

Jayaram‐Lindström

Konstenius

Eksborg

et al. 2007

Neuropsychopharmacol

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Amphetamine abuse and dependence is a global health concern with a collateral increase in medical and social problems. Although some of the neurobiological mechanisms underlying amphetamine dependence and its devastating effects in humans are known, the development of rational and evidence-based treatment is lagging. There is evidence from preclinical studies suggesting that the endogenous opioid system plays a role in mediating some of the behavioral and neurochemical effects of amphetamine in a variety of controlled settings. In the present study we assessed the effects of naltrexone, an opioid antagonist (50 mg) on the subjective physiological and biochemical response to dexamphetamine (30 mg) in 20 amphetamine-dependent patients. Patients received naltrexone/amphetamine followed by placebo/amphetamine, 1 week apart in a randomized double-blind placebo-controlled design. The primary objective of the study was to evaluate the effect of pretreatment with naltrexone on the subjective response to amphetamine, using a Visual Analog Scale. The secondary objective was to investigate the effects of naltrexone on physiological and biochemical responses to amphetamine, as measured by changes in blood pressure, heart rate, skin conductance, and cortisol. Naltrexone significantly attenuated the subjective effects produced by dexamphetamine in dependent patients (po0.001). Pretreatment with naltrexone also significantly blocked the craving for dexamphetamine (po0.001). There was no difference between the groups on the physiological measures. The results suggest that the subjective effects of amphetamine could be modulated via the endogenous opioid system. The potential of naltrexone as an adjunct pharmaceutical for amphetamine dependence is promising.

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Section: Resultssupporting

confidence: 90%

Naltrexone Attenuates the Subjective Effects of Amphetamine in Patients with Amphetamine Dependence

Jayaram‐Lindström

Konstenius

Eksborg

et al. 2007

Neuropsychopharmacol

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“…therapeutic efficacy of NTX in treating alcoholism (O'Malley et al, 1992(O'Malley et al, , 1996Volpicelli et al, 1992Volpicelli et al, , 1997Anton et al, 1999;Chick et al, 2000;Johnson and Ait-Daoud, 2000;Heinala et al, 2001;Krystal et al, 2001;Morris et al, 2001;Guardia et al, 2002), identifying factors that predict therapeutic response to NTX is a critical goal of alcoholism research. Although the cognitive effects of acute and chronic NTX may differ, recent data supports equivalent or greater efficacy of acute NTX dosing, relative to daily maintenance, in reducing excessive alcohol intake (Hernandez-Avila et al, 2006).…”

Section: Discussion Ntx Effects On Impulsive Choicementioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

“…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). Thus, it is plausible that NTX acts, in part, via alteration of certain cognitive processes.…”

Section: Introductionmentioning

confidence: 99%

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Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

Mitchell

Fields

et al. 2006

Neuropsychopharmacol

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The opioid receptor antagonist naltrexone (NTX) is one of few approved treatments for alcoholism, yet the mechanism by which it reduces drinking remains unclear. In rats, NTX reduces morphine-induced impulsive choice bias; however, nothing is known about the drug's effect on discrete aspects of impulsive behavior in humans, such as decision-making and inhibitory control. Here, we used a modified delay discounting procedure to investigate whether NTX improves decision-making or inhibitory control in humans. We measured the effect of acute NTX (50 mg) on choice between smaller sooner (SS) and larger later monetary rewards and on response errors (motor mismatch) in a high conflict condition in a group of abstinent alcoholics (AA) and healthy control subjects (CS). We previously reported that AA selected the SS option significantly more often than did CS in this paradigm. If the choice bias of AA is due to enhanced endogenous opioid signaling in response to potential reward, NTX should reduce such bias in the AA group. We found that NTX did not reliably reduce impulsive choice in the AA group; however, NTX's effect on choice bias across individuals was robustly predictable. NTX's effect on choice bias was significantly correlated with scores on Rotter's Locus of Control (LOC) scale; increasingly internal LOC scores predicted increasing likelihood of impulsive choices on NTX. In addition, we found that NTX significantly enhanced control of motor responses, particularly within the CS group. These results suggest that endogenous opioids may impair response selection during decision-making under conflict, and that NTX's effects on explicit decision-making are personality-dependent. Determining the biological basis of this dependence could have important implications for effective alcoholism treatment.

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“…It has been hypothesized that alterations in HPA axis function may play a role in various stages of addiction, including initiation, maintenance, and relapse (Kreek 1992). Naltrexone (50 mg oral) has shown efficacy in the treatment of alcohol dependence (Volpicelli et al 1992(Volpicelli et al , 1997O'Malley et al 1992;Anton et al 1999), which led to its FDA-approval for adjunctive treatment of alcoholism. Studies examining HPA axis response after oral naltrexone administration might be of potential clinical relevance as neuroendocrine changes and sensitivity to naltrexone could relate to individual differences and treatment response.…”

mentioning

confidence: 99%

Hypothalamic-Pituitary-Adrenocortical (HPA) Axis Response and Biotransformation of Oral Naltrexone Preliminary Examination of Relationship to Family History of Alcoholism

King

Schluger

Gunduz

et al. 2002

Neuropsychopharmacology

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We examined HPA axis response to 50 mg oral naltrexone compared with placebo in 17 healthy male and female nonalcoholic subjects, approximately half of whom had a positive family history of alcoholism (FH ϩ ) and half of whom who did not (FH Ϫ)The endogenous opioid system plays a role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis (Cushman and Kreek 1974;Johnson et al. 1992;Kreek 1972Kreek , 1973Kreek , 1978. Opioid antagonist administration blocks the tonic opioid inhibition of HPA axis activity, thereby resulting in release of POMC-derived hormones in the pituitary and cortisol from the adrenal gland. Indeed, numerous studies have demonstrated acute increases in adrenocorticotropin (ACTH) and cortisol levels in man after intravenous infusion of the opioid antagonists naloxone (Cohen et al. 1983;Conaglen et al. 1985;Delitala et al. 1994;Naber et al. 1981;Martin del Campo et al. 1994;Morley et al. 1980;Schluger et al. 1998;Volavka et al. 1979a) and nalmefene . However, few studies have examined acute neuroendocrine response to the opioid antagonist naltrexone, which, in contrast to naloxone and nalmefene, is not available for intravenous administration.The two published studies on the acute HPA axis effects of orally administered naltrexone have both been conducted with relatively small sample sizes (n р 10). NO . 6 Naltrexone, HPA Axis, and Biotransformation 779The first study (Volavka et al. 1979b), conducted in ten normal male subjects, showed that oral naltrexone significantly increased cortisol levels two hours after administration and directionally (but nonsignificantly) increased ACTH levels one hour after administration. However, due to the small sample studied, the power may not have been sufficient to detect differences. The results may also have been confounded by the co-occurrence of pain sensitivity testing (i.e., 2-min cold pressor task) during the protocol, which may have produced independent HPA axis responses. A more recent study in six abstinent alcoholic patients (Farren et al. 1999) showed significant increases in cortisol and ACTH to three doses of oral naltrexone (25, 50, and 100mg) with no dose-dependent effects (Farren et al. 1999). It has been hypothesized that alterations in HPA axis function may play a role in various stages of addiction, including initiation, maintenance, and relapse (Kreek 1992). Naltrexone (50 mg oral) has shown efficacy in the treatment of alcohol dependence (Volpicelli et al. 1992(Volpicelli et al. , 1997O'Malley et al. 1992;Anton et al. 1999), which led to its FDA-approval for adjunctive treatment of alcoholism. Studies examining HPA axis response after oral naltrexone administration might be of potential clinical relevance as neuroendocrine changes and sensitivity to naltrexone could relate to individual differences and treatment response. Hypothetically, the effects of an opioid antagonist, such as naltrexone, in modulating tonic inhibition of the opioid system at various receptors, including primarily , but also ␦ and , may relate to tr...

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Naltrexone and Cognitive Behavioral Therapy for the Treatment of Outpatient Alcoholics: Results of a Placebo-Controlled Trial

Cited by 160 publications

References 0 publications

Naltrexone Attenuates the Subjective Effects of Amphetamine in Patients with Amphetamine Dependence

Naltrexone Attenuates the Subjective Effects of Amphetamine in Patients with Amphetamine Dependence

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

Hypothalamic-Pituitary-Adrenocortical (HPA) Axis Response and Biotransformation of Oral Naltrexone Preliminary Examination of Relationship to Family History of Alcoholism

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