Anticraving Medications for Relapse Prevention: A Possible New Class of Psychoactive Medications

University of Pennsylvania/Philadelphia VA Medical Center, Philadelphia, PA 19104-6178, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 09/2005; 162(8):1423-31. DOI: 10.1176/appi.ajp.162.8.1423
Source: PubMed


Psychiatrists have gradually developed a list of medications that are effective in the treatment of addictive disorders. Although alcoholism has received the most attention, nicotine, heroin, and cocaine have all been shown to be influenced by heredity. Of course, the immediate goal is the reduction of drug craving and the prevention of relapse to compulsive drug taking. A medication that can aid in the maintenance of the opiate-free state is naltrexone, a specific opiate antagonist. Naltrexone is also a good example of an anticraving medication used in the treatment of alcoholism. Clinicians currently have two types of medication to aid in the treatment of tobacco use disorder, arguably the most important addiction. Bupropion and nicotine replacement can be given in a coordinated fashion to provide the best available results. At present, no medication is approved by the Food and Drug Administration for the indication of cocaine addiction. Recently, however, five different medications, already approved for other purposes, have been found to be effective among cocaine addicts. Despite clinical trials that show benefit, anticraving medications are not well known and are underused by clinicians. Addiction is a heterogeneous condition, with variability in reactivity to the drug of abuse and to the medications available to treat it. Recent developments in pharmacogenetics may result in improved selection of medications based on genotype.

Download full-text


Available from: Charles P O'Brien, May 17, 2015
1 Follower
18 Reads
  • Source
    • "Preventing relapse is perhaps the most difficult aspect of treating drug addiction (O’Brien, 2005), and accumulating evidence suggests that the Pa is involved in sensitization to drug-associated environmental cues. The Pa is activated to contextual cues to a methamphetamine or cocaine-paired environment (Rhodes et al., 2005; James et al., 2011), and lesions of the Pa block the conditioned locomotor response to a cocaine-paired environment (Young and Deutch, 1998). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this review is to describe how the function and connections of the paraventricular thalamic nucleus (Pa) may play a role in the regulation of stress and negative emotional behavior. Located in the dorsal midline thalamus, the Pa is heavily innervated by serotonin, norepinephrine, dopamine (DA), corticotropin-releasing hormone, and orexins (ORX), and is the only thalamic nucleus connected to the group of structures comprising the amygdala, bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAcc), and infralimbic/subgenual anterior cingulate cortex (sgACC). These neurotransmitter systems and structures are involved in regulating motivation and mood, and display abnormal functioning in several psychiatric disorders including anxiety, substance use, and major depressive disorders (MDD). Furthermore, rodent studies show that the Pa is consistently and potently activated following a variety of stressors and has a unique role in regulating responses to chronic stressors. These observations provide a compelling rationale for investigating the Pa in the link between stress and negative emotional behavior, and for including the Pa in the neural pathways of stress-related psychiatric disorders.
    Frontiers in Behavioral Neuroscience 03/2014; 8:73. DOI:10.3389/fnbeh.2014.00073 · 3.27 Impact Factor
  • Source
    • "). These medications are well established in the clinical management of opiate and alcohol dependence (O'Brien, 2005). Preclinical evidence indicates that opioid receptors are distributed widely in the mesolimbic system, and can modulate dopamine transmission (Spanagel et al., 1992). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gambling is characterized by cognitive distortions in the processing of chance and skill that are exacerbated in pathological gambling. Opioid and dopamine dysregulation is implicated in pathological gambling, but it is unclear whether these neurotransmitters modulate gambling distortions. The objective of the current study was to assess the effects of the opioid receptor antagonist naltrexone and the dopamine D2 receptor antagonist haloperidol on gambling behavior. Male recreational gamblers (n = 62) were assigned to receive single oral doses of naltrexone 50 mg, haloperidol 2 mg or placebo, in a parallel-groups design. At 2.5 h post-dosing, participants completed a slot machine task to elicit monetary wins, "near-misses," and a manipulation of personal choice, and a roulette game to elicit two biases in sequential processing, the gambler's fallacy and the hot hand belief. Psychophysiological responses (electrodermal activity and heart rate) were taken during the slot machine task, and plasma prolactin increase was assessed. The tasks successfully induced the gambling effects of interest. Some of these effects differed across treatment groups, although the direction of effect was not in line with our predictions. Differences were driven by the naltrexone group, which displayed a greater physiological response to wins, and marginally higher confidence ratings on winning streaks. Prolactin levels increased in the naltrexone group, but did not differ between haloperidol and placebo, implying that naltrexone but not haloperidol may have been functionally active at these doses. Our results support opioid modulation of cognition during gambling-like tasks, but did not support the more specific hypothesis that naltrexone may act to ameliorate cognitive distortions.
    Frontiers in Behavioral Neuroscience 10/2013; 7:138. DOI:10.3389/fnbeh.2013.00138 · 3.27 Impact Factor
  • Source
    • "Moreover, the fact that vulnerability to relapse in addicts can persist after many years of abstinence implies that addiction is caused by long-lasting changes in brain function as a result of pharmacological insult (repeated remission and relapse episodes), genetic predisposition, and environmental associations made with drug use (learning). Thus, a primary problem for the treatment of drug abuse remains to be the understanding of the brain neuroadaptations following repeated drug use that might be responsible for the persistent vulnerability to drug craving and seeking after abstinence [5,6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats' sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse.
    12/2012; 2(3):421-33. DOI:10.3390/brainsci2030421
Show more