The Neurobiology of Craving: Potential Mechanisms for Acamprosate

  • J. Littleton
  • M. al Qatari
  • H. Little


There now seems no doubt that acamprosate is effective at reducing relapse into drinking in detoxified alcoholic patients (Lhuintre et al. 1985; HiRemand et al. 1984, 1989; Tran et al. 1990). However, the mechanism by which the drug achieves this effect is far from understood. Most conventional mechanisms of drugs that prevent relapse (see Liljequist and Borg 1993), such as making alcohol aversive or reducing the rewarding effects of the drug (Fig. 1), are not supported by the known pharmacology of acamprosate (see Littleton 1995). Self-reports from patients and clinical experience suggest that a major effect of acamprosate on relapse is to reduce the tendency for drinking episodes to escalate “out of control”, and this is supported by increased indices of social stability in clinical trials of acamprosate (see Pelc et al. 1994; Lesch et al. 1994). This pattern suggests that acamprosate has a unique mechanism, and that its efficacy against relapse is a consequence of an ability to interrupt the process leading to loss of control in drinking behaviour. This might be described as an “anti-craving” action (see below, and Littleton 1995), but this leaves several important questions unanswered. First, how exactly are craving and loss of control related? Second, how could any drug interfere with such a mechanism (i.e. what is its chemical basis)? Third, how can we investigate such a mechanism? And fourth, does any of the known pharmacology of acamprosate support such a mechanism? This review attempts to answer some of these questions and suggests the approaches that we believe to be necessary to unravel the mystery of the mechanism of action of acamprosate.


Conditioned Stimulus Excitatory Amino Acid Negative Aspect Drinking Behaviour Alcohol Exposure 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • J. Littleton
    • 1
  • M. al Qatari
    • 1
  • H. Little
    • 2
  1. 1.Pharmacology GroupKings CollegeLondonUK
  2. 2.Psychology DepartmentUniversity of DurhamDurhamUK

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