Circulating Endocannabinoids and N-Acylethanolamines in Individuals with Cannabis Use Disorder-Preliminary Findings.

Circulating Endocannabinoids and N-Acylethanolamines in Individuals with Cannabis Use Disorder-Preliminary Findings.
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DOI:
10.3390/brainsci13101375
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发表时间:
2023-09-27
期刊:
影响因子:
3.3
通讯作者:
--
中科院分区:
医学4区
文献类型:
--
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背景资料:内源性大麻素及其相关的N-酰基乙醇胺(NAE)是一类具有重要生理功能的生物活性脂质,在精神健康和成瘾方面具有重要作用。虽然慢性大麻使用与内源性大麻素系统的变化有关,但大麻使用障碍(CUD)患者中循环内源性大麻素和相关NAE的状态尚不确定。研究方法:使用对照参与者(HC)的11名CUD患者和54名健康非大麻患者提供血浆,通过高效液相色谱-质谱法测量内源性大麻素(2-花生四烯酸甘油(2-AG)和N-花生四烯酸乙醇胺(AEA))和相关NAE脂肪酸(N-二十二碳六烯乙醇胺(DHEA)和N-油酰乙醇胺(OEA))。对参与者进行了FAAH功能基因变体(rs324420、C385 A)的基因分型,该变体可能影响AEA以及其他NAE(OEA、DHEA)的浓度。结果如下:在过夜戒断的CUD中,相对于HC,AEA、OEA和DHEA浓度显著更高(31-40%; p < 0.05),并且内源性大麻素2-AG的浓度略微升高(55%,p = 0.13)。内源性大麻素/NAE浓度与大麻分析物、自我报告的大麻使用频率或戒断症状之间没有显著相关性。DHEA浓度与大麻渴望呈负相关(r =-0.86; p = 0.001)。基因型对血浆内源性大麻素/NAE浓度无显著影响。结论:我们的初步研究结果,需要复制,可能表明,内源性大麻素系统的活性在慢性大麻使用者中升高。目前尚不清楚这种升高是一种补偿反应还是一种捕食状态。研究检查内源性大麻素和NAE在长期禁欲以及潜在的作用DHEA渴望是必要的。
Background: Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain. Methods: Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography–mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which may affect concentrations of AEA as well as other NAEs (OEA, DHEA). Results: In overnight abstinent CUD, AEA, OEA and DHEA concentrations were significantly higher (31–40%; p < 0.05) and concentrations of the endocannabinoid 2-AG were marginally elevated (55%, p = 0.13) relative to HC. There were no significant correlations between endocannabinoids/NAE concentrations and cannabis analytes, self-reported cannabis use frequency or withdrawal symptoms. DHEA concentration was inversely related with marijuana craving (r = −0.86; p = 0.001). Genotype had no significant effect on plasma endocannabinoids/NAE concentrations. Conclusions: Our preliminary findings, requiring replication, might suggest that activity of the endocannabinoid system is elevated in chronic cannabis users. It is unclear whether this elevation is a compensatory response or a predating state. Studies examining endocannabinoids and NAEs during prolonged abstinence as well as the potential role of DHEA in craving are warranted.
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