The End of My Addiction

its ability to interfere with the neuronal substrates mediating the reinforcing properties of ethanol. GABA B receptors located in the ventral tegmental area (VTA) have been reported to control the activity of mesolimbic dopamine neurons, a major neural pathway in the regulation of the reinforcing properties of addictive drugs, including alcohol (see Di Chiara, 1995; Koob et al ., 1998; Spanagel and Weiss, 1999). Accordingly, pharmacological stimulation of VTA GABA B receptors has been found to inhibit the firing activity of these neurons (Kalivas, 1993) as well as basal (Yoshida et al ., 1994) and alcohol-stimulated (Carta et al ., 2001) dopamine release from their terminals in the nucleus accumbens.
    Moreover, it is conceivable that the suppressing effect of baclofen on alcohol withdrawal symptomatology (Addolorato et al ., 2002) may have helped the patients to achieve and maintain alcohol abstinence.
    In contrast to the observation by Krupitsky et al . (1993) that baclofen ameliorates affective disorders in alcoholics, in the present study baclofen was found to be effective in reducing state anxiety, but not current depression. It may be hypothesized that the decrease in state anxiety found in the present study and the decrease in depression observed by Krupitsky et al . (1993) in alcoholics after a 3-week treatment with baclofen were secondary to the ability of baclofen to achieve both a rapid detoxification (Addolorato et al ., 2002) and a decrease in craving, resulting in a rapid reduction of physical and psychological symptoms. Finally, it should be emphasized that the absence of a significant decrease in Zung depression scale score in the present study could be influenced by the relatively low score recorded in some patients at the start of the study.
    In agreement with both previous observations (Krupitsky et al ., 1993; Ling et al ., 1998; Addolorato et al ., 2000 a ), baclofen proved to be devoid of serious side-effects in alcoholics. Moreover, side-effects were present only during the first week of the treatment.
    Preclinical data suggest that baclofen might be liable to misuse since the drug shares several pharmacological effects with the alcohol-mimicking agent, [.gamma]-hydroxybutyrate (GHB), and craving for and abuse of GHB have been observed in different alcoholic patients (see Addolorato et al ., 2000 a ). However, baclofen failed to show euphorigenic effects and no patient consumed the drug above the prescribed dose. The lack of misuse liability of baclofen is an important factor in pharmacological treatments of alcohol and other substance addictions.
    In conclusion, with the limits of the low number of patients recruited and the short time of observation, the results of the present preliminary double-blind study confirm that baclofen, because of its anti-craving and anti-reward action on the one hand, and safety on the other, may have an important role in the treatment of patients with alcohol problems. Future studies with larger patient samples and longer periods of observation are surely warranted to confirm the results of the present study.
    Acknowledgements
    This study was supported by grants from Associazione Ricerca in Medicina, Bologna-Rome, Italy. The authors are grateful to C. Ancona, MD and R. Mascianà, MD (Università Cattolica, Rome, Italy), F. Lorenzini MD (University of Bologna, Bologna, Italy), S. Serra and G. Vacca (Neuroscienze S.c.a.r.l., Cagliari, Italy) for technical support, and to A. Farmer for language editing of the manuscript.
    References
    Addolorato, G., Viaggi, M., Gentilini, L., Castelli, E., Nicastro, P., Stefanini, G. F. and Gasbarrini, G. (1993) Alcohol addiction: evaluation of the therapeutic effectiveness of self-managed self-help group in the maintenance of abstinence from alcohol. Alcologia, European Journal of Alcohol Studies 5 , 261–263.
    Addolorato, G., Caputo, F., Capristo, E., Stefanini, G. F. and Gasbarrini, G. (2000 a ) Gamma-hydroxybutyric acid: efficacy, potential abuse and dependence in the treatment of alcohol addiction. Alcohol 20 , 217–222.
    Addolorato, G., Caputo, F., Capristo, E., Colombo, G., Gessa, G. L. and Gasbarrini, G. (2000 b ) Ability of baclofen in reducing alcohol craving and intake: II—preliminary clinical evidence. Alcoholism: Clinical and Experimental Research 24 , 67–71.
    Addolorato, G., Caputo, F., Capristo, E., Janiri, L., Bernardi, M., Agabio, R., Colombo, G., Gessa, G. L. and Gasbarrini, G. (2002) Rapid suppression of