Department of Psychiatry, University of California San Diego, La Jolla, California 92093-0847, USA.
J Int Neuropsychol Soc. 2010 Sep;16(5):890-901. doi: 10.1017/S1355617710000779. Epub 2010 Aug 23.
While neuropsychological deficits are evident among methamphetamine (meth) addicts, they are often unrelated to meth exposure parameters such as lifetime consumption and length of abstinence. The notion that some meth users develop neuropsychological impairments while others with similar drug exposure do not, suggests that there may be individual differences in vulnerability to the neurotoxic effects of meth. One source of differential vulnerability could come from genotypic variability in metabolic clearance of meth, dependent on the activity of cytochrome P450-2D6 (CYP2D6). We compared neuropsychological performance in 52 individuals with a history of meth dependence according with their CYP2D6 phenotype. All were free of HIV or hepatitis C infection and did not meet dependence criteria for other substances. Extensive metabolizers showed worse overall neuropsychological performance and were three times as likely to be cognitively impaired as intermediate/poor metabolizers. Groups did not differ in their demographic or meth use characteristics, nor did they evidence differences in mood disorder or other substance use. This preliminary study is the first to suggest that efficient meth metabolism is associated with worse neurocognitive outcomes in humans, and implicates the products of oxidative metabolism of meth as a possible source of brain injury.
虽然在 methamphetamine（冰毒）成瘾者中明显存在神经心理学缺陷，但它们通常与 lifetime consumption 和 abstinence length 等 methamphetamine 暴露参数无关。一些 methamphetamine 使用者出现神经心理学损伤，而其他具有相似药物暴露的使用者没有，这表明他们对 methamphetamine 的神经毒性作用可能存在个体易感性差异。易感性差异的一个来源可能来自 methamphetamine 代谢清除的基因型变异性，这取决于细胞色素 P450-2D6（CYP2D6）的活性。我们根据 CYP2D6 表型比较了 52 名有 methamphetamine 依赖史的个体的神经心理学表现。所有人均无 HIV 或丙型肝炎感染，且不符合其他物质依赖的标准。完全代谢者的整体神经心理学表现更差，认知障碍的可能性是中间/差代谢者的三倍。两组在人口统计学或 methamphetamine 使用特征上没有差异，也没有在情绪障碍或其他物质使用方面存在差异。这项初步研究首次表明，methamphetamine 的有效代谢与人类更差的神经认知结果相关，并暗示 methamphetamine 氧化代谢的产物可能是脑损伤的一个潜在来源。
