The End of My Addiction

agonist(s).
    References
    1. Nava F, Premi S, Manzato E, Campagnola W, Lucchini A, Gessa GL. Gammahydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam. Am J Drug Alcohol Abuse 2007; 33 (3):379–392.
    2. Andriamampandry C, Taleb O, Kemmel V, Humbert JP, Aunis D, Maitre M. Cloning and functional characterization of a gamma-hydroxybutyrate receptor identified in the human brain. FASEB J 2007 Mar; 21 (3):885–895. Epub 2006 Dec 28.
    3. Ameisen O. Gamma-hydroxybutyrate (GHB)-deficiency in alcohol-dependence? Alcohol Alcohol 2007; 42 (5):506. Epub 2007 Aug 1.

 
    Reply to the Letter “Are the Effects of Gamma-Hydroxybutyrate (GHB) Treatment Partly Physiological in Alcohol Dependence?” by Olivier Ameisen
     
    Felice Nava, M.D., Ph.D., Department of Addiction Medicine, Hospital of Castelfranco Veneto, Treviso, Italy
     
    We find Dr. Ameisen’s comment appealing. The gamma-hydroxybutyrate (GHB) antialcohol molecular effects are yet largely obscure. Clinically speaking, the GHB seems to act as a true “substitute” of alcohol 1 and this aspect may explain two of the major effects of GHB for the treatment of alcoholism: the suppression of both withdrawal syndrome and craving. 2,3
    We know that several of the pharmacological effects induced by GHB are due to a potentiation of GABAergic transmission. 4 This effect may be due to a simple brain conversion of exogenous GHB in gamma-aminobutyric acid (GABA) and/or to a direct GHB activation of own receptors that have been recently identified in the human brain. 5 Moreover, since some of the most important central effects of GHB, that is also a naturally occurring GABA B receptor agonist, are shared with the GABA B agonist baclofen, we may suppose that several of the GHB actions may also be mediated through the activation of GABA B receptors. 4
    In light of the above evidence and considering our recent work, 3 Dr. Ameisen is correct in pointing out that alcoholism may be a disease characterized by a GHB deficiency in the brain. In accord with this hypothesis, in alcoholics the ethanol would act as a “substitute” for the insufficient effects of GHB. In other words, it is the alcohol that may act as a “substitute” for GHB and not the contrary. Furthermore, since baclofen has been demonstrated to suppress both in animals and humans the intake of several drugs including alcohol,6–9 we may suppose a key role of the endogenous GHB not only in the alcoholism but also in several other forms of drug dependence. If the previous hypothesis will be demonstrated, the role of endogenous GHB will be elucidated and the potential properties of GHB as medication will be better developed.
    References
    1. Gessa GL, Agabio R, Carai MA, Lobina C, Pani M, Reali R, Colombo G. Mechanism of the antialcohol effect of gamma-hydroxybutyric acid. Alcohol 2002; 20 :71–76.
    2. Nava F, Premi S, Manzato E, Lucchini A. Comparing treatments of alcoholism on craving and biochemical measures of alcohol consumptionists. J Psychoactive Drugs 2006; 38 :211–217.
    3. Nava F, Premi S, Manzato E, Campagnola W, Lucchini A, Gessa GL. Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam. Am J Drug Alcohol Abuse 2007; 33 :379–392.
    4. Wong CG, Gibson KM, Snead OC. 3rd. From the street to the brain: neurobiology of the recreational drug gamma-hydroxybutyric acid. Trends Pharmacol Sci 2004; 25 :29–34.
    5. Andriamampandry C, Taleb O, Kemmel V, Humbert JP, Aunis D, Maitre M. Cloning and functional characterization of a gamma-hydroxybutyrate receptor identified in the human brain. FASEB J 2007; 21 :885–895.
    6. Addolorato G, Caputo F, Capristo E, Domenicali M, Bernardi M, Janiri L, Agabio R, Colombo G, Gessa GL, Gasbarrini G. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol 2002; 37 :504–508.
    7. Haney M, Hart CL, Foltin RW. Effects of baclofen on cocaine self-administration: opioid and nonopioid-dependent volunteers. Neuropsychopharmacology 2006; 31 :1814–1821.
    8. Spano MS, Fattore L, Fratta W, Fadda P. The GABA B receptor agonist baclofen prevents heroin-induced reinstatement of heroin-seeking behavior in rats. Neuropsychopharmacology 2007; 52 :1555–1562.
    9. Walker BM, Koob GF. The gamma-aminobutyric acid-B receptor agonist baclofen attenuates responding for ethanol