Reduced CYP2D6 activity is a negative risk factor for methamphetamine dependence

Kyohei Otani, Hiroshi Ujike, Ayumu Sakai, Yuko Okahisa, Tatsuya Kotaka, Toshiya Inada, Mutsuo Harano, Tokutaro Komiyama, Toru Hori, Mitsuhiko Yamada, Yoshimoto Sekine, Nakao Iwata, Masaomi Iyo, Ichiro Sora, Norio Ozaki, Shigetoshi Kuroda

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Because methamphetamine (METH) is metabolized by CYP2D6 at the first step of hydroxylation and demethylation, it is possible that functional variants of CYP2D6 alter susceptibility to methamphetamine-induced dependence. We genotyped CYP2D6*1, *4, *5, *10, and *14 for 202 patients with METH dependence and 337 controls in a Japanese population and found a significant association of the CYP2D6 gene with METH dependence (p = 0.0299). The patients had fewer *10 and *14 alleles, which are hypofunction alleles, than the controls. CYP2D6 genotypes were divided into three phenotypes: extensive metabolizers, intermediate metabolizers, and poor metabolizers. There was no poor metabolizer among our Japanese subjects, and intermediate metabolizers of CYP2D6 were significantly fewer in methamphetamine-dependent subjects than in controls (p = 0.0212), with an odds ratio of 0.62 (95% confidence interval: 0.51-0.76). The present study demonstrated that reduced CYP2D6 activity was a negative risk factor for methamphetamine dependence.

Original languageEnglish
Pages (from-to)88-92
Number of pages5
JournalNeuroscience Letters
Issue number1
Publication statusPublished - 21-03-2008

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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