CASE REPORT Suppression of Craving for g-Hydroxybutyric Acid by Naltrexone Administration Three Case Reports Fabio Caputo, MD, PhD,* Teo Vignoli, MD,* Francesca Lorenzini, MD,* Elena Ciuffoli, MD,* Arfedele Del Re, MD,*† Giuseppe Francesco Stefanini, MD,‡ Giovanni Addolorato, MD,§ Franco Trevisani, MD,* Mauro Bernardi, MD,* and the Alcoholism Treatment Study Group k Abstract: g-Hydroxybutyric acid (GHB) is currently used to induce and maintain abstinence from alcohol. Cases of craving and desire to increase doses of GHB have been reported in both clinical trials and nonclinical self-administration. The enhancement of dopamine activ- ity induced by GHB receptor activation might play a role in the euphoric effect and potential craving and the consequent abuse of this drug. Naltrexone (NTX), a m-opioid antagonist, is effective in inducing and maintaining abstinence from alcohol, reducing relapses in heavy drinking and craving for alcohol in alcohol-dependent outpatients. Taking into account the alcohol antireward property of NTX, we tested its activity in reducing craving for GHB in 3 con- secutive cases of alcoholics who manifested craving for this drug. In all patients the combination with NTX suppressed the craving for GHB. The antireward effect of NTX likely results from its inter- ference with the GHB-induced dopamine release, leading to a partial blockade of the GHB reinforcing effect responsible of the craving for the drug. A combined therapy with GHB and NTX seems to be able to suppress craving for the former, thus improving the manageability and safety of treatment. Key Words: suppression of craving for g-hydroxybutyric acid, naltrexone, combined treatment (Clin Neuropharmacol 2005;28:87–89) g-H ydroxybutyric acid (GHB) is a short-chain fatty acid, structurally similar to the inhibitory neuro- transmitter g-amino-butyric acid, that exerts an ethanol- mimicking effect on the central nervous system. 1–3 Because of this biologic property, GBH is currently used to induce and maintain abstinence from alcohol. 4–6 However, cases of crav- ing and desire to increase doses of GHB have been reported. This has occurred with nonclinical self-administration, in a single dose ranging from 2.5 to 30 g per day, 5,7,8 and in 10%–15% of patients with alcohol or psychoactive substance dependence treated with 50 mg/kg of body weight divided into 3 daily doses. 5,8 Among them a case of GHB dependence has been also reported. 9 The lack of manageability and safety of the drug have correctly induced physicians to use GHB for short periods of treatment, and under continuous strict medical surveillance and supervision of a referred family member. 6,7 Naltrexone (NTX), a m-opioid antagonist, is effective in inducing and maintaining abstinence from alcohol, reducing relapses in heavy drinking and craving for alcohol in alcohol- dependent outpatients. 10–14 Its favorable effects are likely related to the blockade of alcohol-induced release of dopamine in the nucleus accumbens. This would lead to a reduction in the positive reinforcing and pleasurable effects of alcohol and, hence, craving for alcohol. 15–17 Our preliminary results have documented that the efficacy of the association GHB plus NTX induces abstinence from alcohol and reduces craving for alcohol in about 30% of outpatient nonresponders to GHB. 18 Taking into account the ethanol-mimicking effect of GHB on the central nervous system 1–3 and the antialcohol reward property of NTX, we hypothesized that NTX is able to suppress craving for GHB. Therefore, we tested this assumption in 3 consecutive alcoholics who manifested craving for GHB during a multi- disciplinary treatment of maintaining abstinence from alcohol consisting of psychosocial support and pharmacological therapy with GHB. The drug and its administration were entrusted to a referred family member. Patients were checked weekly as outpatients. Craving level for alcohol was evaluated by administration of the Alcohol Craving Scale (ACS) 4,5 at the time of admission and after 15, 30, and 90 days of treatment. The abstinence from alcohol, the amount of alcohol intake, recorded as daily drinks, and craving for GHB were reported on the basis of the participant’s self-evaluation, the inter- view of a family member, and the determination of alcohol From the *‘‘G. Fontana’’ Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Internal Medicine, Cardioangiology and Hepatology, Alma Mater Studiorum, University of Bologna, Bologna, Italy; †Unit for Addiction Treatment, Department of Primary Care, University of Bologna, Bologna, Italy; ‡Department of Internal Medicine, Ospedale degli Infermi, Faenza, Italy; and §Institute of Internal Medicine, Catholic University of the Sacred Heart, Roma, Italy. k Institute of Internal Medicine, Catholic University of the Sacred Heart, Roma: Ludovico Abenavoli, Lorenzo Leggio, Giovanni Gasbarrini. Unit for Addiction Treatment, Department of Primary Care, Bologna: Carla Bandini, Carmine D’Angelo, Sara Gubellini, Mariella Lofrumento, Roberta Piazzi, Rosa Alba Russo, Catia Leoni, Claudio Comaschi, Luisa Prata. Reprints: Fabio Caputo, ‘‘G. Fontana’’ Centre for the Study and Multi- disciplinary Treatment of Alcohol Addiction, Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Via Massarenti n°9, 40138 Bologna, Italy (e-mail: fabio-caputo@libero.it). Copyright Ó 2005 by Lippincott Williams & Wilkins Clin Neuropharmacol  Volume 28, Number 2, March-April 2005 87