Fatty acid amide hydrolase is lower in young cannabis users.

Fatty acid amide hydrolase is lower in young cannabis users.
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DOI:
10.1111/adb.12872
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发表时间:
2021-01
期刊:
影响因子:
3.4
通讯作者:
Mizrahi R
Mizrahi R
中科院分区:
医学2区
文献类型:
--
作者:
Jacobson MR;Watts JJ;Da Silva T;Tyndale RF;Rusjan PM;Houle S;Wilson AA;Ross RA;Boileau I;Mizrahi R

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我们最近发现,脂肪酸酰胺水解酶(FAAH)的水平,代谢内源性大麻素anandamide的酶,在成年大麻使用者(34±11岁)的大脑中较低,在早期戒断期间进行测试。在这里,我们研究了较低FAAH水平在一个单独的年轻队列(23±5岁)中的复制。18名健康志愿者(HV)和14名大麻使用者(CU)使用FAAH放射性配体[11 C]CURB进行正电子发射断层扫描。采用不可逆双组织房室模型和代谢物校正的动脉血浆输入函数计算局部[11 C]CURB结合。FAAH C385 A遗传多态性(rs324420)作为协变量纳入。所有CU都进行了尿液筛查,以确认最近使用大麻,并测量了血清大麻素。一个CU通过血清对大麻素筛选为阴性,并从分析中移除。所有HV在研究开始前一个多月报告了少于5次终生大麻暴露。当从分析中去除两个A/A(rs324420)HV以匹配CU组(n=16 HV,n=13 CU)的基因型时,组的效果显著(F(1,26)=4.31; p=0.048)。总体而言,CU中的[11 C]CURB λk3比HV低12%。探索性相关性表明,较低的大脑[11 C]CURB结合与过去一年中更多地使用大麻有关。我们证实了我们之前的报告,并通过在累积大麻暴露较少的年轻队列中检测较低的[11 C]CURB结合来扩展这些发现。
We have recently shown that levels of fatty acid amide hydrolase (FAAH), the enzyme that metabolises the endocannabinoid anandamide, are lower in the brains of adult cannabis users (34±11 years of age), tested during early abstinence. Here, we examine replication of the lower FAAH levels in a separate, younger cohort (23±5 years of age). Eighteen healthy volunteers (HV) and fourteen cannabis users (CU) underwent a positron emission tomography scan using the FAAH radioligand [11C]CURB. Regional [11C]CURB binding was calculated using an irreversible two-tissue compartment model with a metabolite-corrected arterial plasma input-function. The FAAH C385A genetic polymorphism (rs324420) was included as a covariate. All CU underwent a urine screen to confirm recent cannabis use and had serum cannabinoids measured. One CU screened negative for cannabinoids via serum and was removed from analysis. All HV reported less than five lifetime cannabis exposures more than a month prior to study initiation. There was a significant effect of group (F(1, 26)=4.31; p=0.048) when two A/A (rs324420) HV were removed from analysis to match the genotype of the CU group (n=16 HV, n=13 CU). Overall, [11C]CURB λk3 was 12% lower in CU compared to HV. Exploratory correlations showed that lower brain [11C]CURB binding was related to greater use of cannabis throughout the past year. We confirmed our previous report and extended these findings by detecting lower [11C]CURB binding in a younger cohort with less cumulative cannabis exposure.
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