The effects of acamprosate on alcohol-cue reactivity and alcohol priming in dependent patients: a randomized controlled trial
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Acamprosate is a widely utilized, efficacious treatment for relapse prevention in alcohol-dependent patients; yet, little is known regarding its therapeutic mechanism of action.
The aim of the present study was to examine the effect of acamprosate on cue reactivity and alcohol priming in alcohol-dependent patients.
In a double-blind design, 56 treatment seeking patients were randomized to 21 days of either acamprosate or placebo treatment and then participated in a series of cue- and alcohol-priming sessions. Alcohol cues consisted of a mixture of alcohol related visual, tactile, olfactory, and auditory stimuli. Non-alcohol-related cues were contextually similar but had no connection to alcohol. In the alcohol-priming procedure, patients were provided with an alcohol drink of their own choice at a dose corresponding to 0.20 gr. EtOH/kg bodyweight. Subjective, physiological, and biological measurements were recorded before and after each test session. Following study completion, all patients were referred to formal treatment.
The results showed that acamprosate attenuated the subjective craving induced by alcohol priming in comparison to placebo-treated patients. Furthermore, acamprosate reduced alcohol-induced elevation in blood-cortisol levels. Lastly, there was a negative correlation between acamprosate plasma levels and alcohol craving following a priming drink. No effects of acamprosate on cue reactivity, or on the acute rewarding and sedating effects of the priming drink, were observed.
These results suggest a potential mechanism by which acamprosate mediates its therapeutic effect in the treatment of alcoholism, by attenuating the urge to drink following an alcohol slip.
KeywordsAlcohol dependence Treatment Acamprosate Priming Craving
We are grateful to Margareta Gard-Hedander, RN and Else-Britt Hillner, RN for handling the study medication and Ms. Ingrid Dahlin for handling and management of blood samples. This study was supported by AFA Insurance, the Swedish Science Council (14645-04-3), the Research Council of the Swedish Alcohol Retail Monopoly (grants no 06-24:1 and 07-19:1), Milan Valverius stiftelse, and Psykiatrifonden. Study medication was generously donated by Merck-Lipha s.a.
None of the authors reported any biomedical financial interests or potential conflicts of interest.
- Chick J, Howlett H, Morgan MY, Ritson B (2000) United Kingdom Multicentre Acamprosate Study (UKMAS): a 6-month prospective study of acamprosate versus placebo in preventing relapse after withdrawal from alcohol. Alc & Alc 35(2):176–187Google Scholar
- Dahchour A, De Witte P, Bolo N, Nédélec JF, Muzet M, Durbin P, Macher JP (1998) Central effects of acamprosate: part 1. Acamprosate blocks the glutamate increase in the nucleus accumbens microdialysate in ethanol withdrawn rats. Psychiatry Res 82(2):107–14Google Scholar
- Flannery BA, Volpicelli JR, Pettinati HM (1999) Psychometric properties of the penn alcohol craving scale. Alcohol Clin Exp Res 23(8):1289–1295Google Scholar
- Paille FM, Guelfi JD, Perkins AC, Royer RJ, Stern L, Parot P (1995) Double-blind randomised multicentre trial of acamprosate in maintaining abstinence from alcohol. Alc & Alc 30:239–247Google Scholar
- Rammes G, Mahal B, Putzke J, Parsons C, Spielmanns P, Pestel E, Spanagel R, Zieglgänsberger W, Schadrack J (2001) The anti-craving compound acamprosate acts as a weak NMDA-receptor antagonist, but modulates NMDA-receptor subunit expression similar to memantine and MK-801. Neuropharmacology 40(6):749–746PubMedCrossRefGoogle Scholar
- Sass H, Soyka M, Mann K, Zieglegansberger W (1996) Relapse prevention by acamprosate: Results from a placebo-controlled study on alcohol dependence. Arch Gen Psych 53:673–680Google Scholar
- Sobell LC, Sobell MB (1992) Timeline Follow Back. A technique for assessing self-reported alcohol consumption. In: Litten R, Allen J (eds) Measuring Alcohol Consumption. Humana Press, Totowa, pp 41–72Google Scholar
- Spanagel R, Hölter SM, Allingham K, Landgraf R, Zieglgänsberger W (1996) Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat. Eur J Pharmacol 305(1–3):39–44Google Scholar
- Tempesta E, Janiri L, Bignamini A, Chabac S, Potgieter A (2000) Acamprosate and relapse prevention in the treatment of alcohol dependence: a placebo controlled study. Alc & Alc 35:202–209Google Scholar
- Watson D, Clark LA, Tellegren A (1998) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54(6):1063–1070Google Scholar
- World Health Organization (2004) WHO global status report on alcohol. WHO, Geneva, pp 30–48Google Scholar