1. ¹Department of Medical Genetics, Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
2. ²Department of Biology, William Paterson University, Wayne, NJ, USA
3. ³National Hospital Organization, Kurihama Alcoholism Center, Nobi, Yokosuka, Kanagawa, Japan
4. ⁴Department of Psychiatry, Sapporo Medical University, School of Medicine, Chuuouku, Sapporo, Hokkaido, Japan

Correspondence: Dr H Ishiguro, Department of Medical Genetics, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan. E-mail: hishigur@md.tsukuba.ac.jp

Received 25 July 2006; Revised 30 August 2006; Accepted 24 September 2006; Published online 26 December 2006.

Abstract

We tested if cannabinoid type 2 receptor (CB2) in the central nervous system plays a role in alcohol abuse/dependence in animal model and then examined an association between the CB2 gene polymorphism and alcoholism in human. Mice experiencing more alcohol preference by drinking showed reduced Cb2 gene expression, whereas mice with little preference showed no changes of it in ventral midbrain. Alcohol preference in conjunction with chronic mild stress were enhanced in mice treated with CB2 agonist JWH015 when subjected to chronic stress, whereas antagonist AM630 prevented development of alcohol preference. There is an association between the Q63R polymorphism of the CB2 gene and alcoholism in a Japanese population (P=0.007; odds ratio 1.25, 95% CI, (1.06–1.47)). CB2 under such environment is associated with the physiologic effects of alcohol and CB2 antagonists may have potential as therapies for alcoholism.