Intermediate cannabis dependence phenotypes and the FAAH C385A variant: an exploratory analysis.
Intermediate cannabis dependence phenotypes and the FAAH C385A variant: an exploratory analysis.
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DOI：
10.1007/s00213-008-1397-z
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发表时间：
2009-04
影响因子：
3.4
通讯作者：
Hutchison, Kent E.
中科院分区：
文献类型：
--
作者：
Schacht, Joseph P.;Selling, Rebecca E.;Hutchison, Kent E.
对于经常吸食大麻的人来说，大麻依赖是一个日益严重的问题，而基因差异使一些使用者更容易发展成依赖。大麻依赖中间表型的鉴定可能有助于候选基因分析。有希望的中间表型包括对大麻的渴望、戒断后的戒断症状以及对其急性效应的敏感性。脂肪酸酰胺水解酶 (FAAH) 编码基因中的单核苷酸多态性 (SNP) 已被证明与物质使用障碍诊断相关，但尚未针对这些较窄的表型进行研究。 FAAH 是一种使 anandamide 失活的酶，anandamide 是 CB1 受体（与 Δ9-四氢大麻酚结合）的内源性激动剂。 CB1 结合调节中皮质边缘多巴胺的释放，这是成瘾的许多方面的基础。对 SNP FAAH C385A (rs324420) 进行了检查，以确定其方差是否与大麻戒断后的渴望和戒断、线索暴露后的渴望或对大麻急性效应的敏感性的变化相关。 40 名每天吸食大麻的人戒酒 24 小时，在实验室中接受提示引发的渴望范式并吸食大麻香烟。 C385A 方差与戒断后戒断的变化显着相关，并且以预测方向吸食大麻后的幸福感与以与预测方向相反的方向吸食后心率的变化相关，并且与渴望或其他急性效应的变化无关。这些数据为之前的一些 C385A 关联研究提供了支持，但表明有必要进一步完善这些中间表型。
Cannabis dependence is a growing problem among individuals who use marijuana frequently, and genetic differences make some users more liable to progress to dependence. The identification of intermediate phenotypes of cannabis dependence may aid candidate genetic analysis. Promising intermediate phenotypes include craving for marijuana, withdrawal symptoms after abstinence, and sensitivity to its acute effects. A single nucleotide polymorphism (SNP) in the gene encoding for fatty acid amide hydrolase (FAAH) has demonstrated association with substance use disorder diagnoses, but has not been studied with respect to these narrower phenotypes. FAAH is an enzyme that inactivates anandamide, an endogenous agonist for CB1 receptors (to which Δ9-tetrahydrocannabinol binds). CB1 binding modulates mesocorticolimbic dopamine release, which underlies many facets of addiction. The SNP, FAAH C385A (rs324420), was examined to determine whether its variance was associated with changes in craving and withdrawal after marijuana abstinence, craving after cue exposure, or sensitivity to the acute effects of marijuana. Forty daily marijuana users abstained for 24 h, were presented with a cue-elicited craving paradigm and smoked a marijuana cigarette in the laboratory. C385A variance was significantly associated with changes in withdrawal after abstinence, and happiness after smoking marijuana in the predicted directions, was associated with changes in heart rate after smoking in the opposite of the predicted direction, and was not associated with changes in craving or other acute effects. These data lend support to some previous association studies of C385A, but suggest that further refinement of these intermediate phenotypes is necessary.
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DOI：
10.1073/pnas.95.17.10269
发表时间：
1998-08-18
影响因子：
11.1
作者：
Diana, M;Melis, M;Gessa, GL
通讯作者：
Gessa, GL
影响因子：
11.3
作者：
GYNTHER, LM;CAREY, G;VOGLER, GP
通讯作者：
VOGLER, GP
影响因子：
17.7
作者：
Kalivas, PW;Volkow, ND
通讯作者：
Volkow, ND
影响因子：
6
作者：
Budney, AJ;Novy, PL;Hughes, JR
通讯作者：
Hughes, JR
影响因子：
22.4
作者：
Hutchison, KE;Stallings, M;Bryan, A
通讯作者：
Bryan, A