Evaluation of plasma-free endocannabinoids and their congeners in abstinent cocaine addicts seeking outpatient treatment: impact of psychiatric co-morbidity
Evaluation of plasma-free endocannabinoids and their congeners in abstinent cocaine addicts seeking outpatient treatment: impact of psychiatric co-morbidity
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DOI：
10.1111/adb.12107
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发表时间：
2013-11-01
影响因子：
3.4
通讯作者：
Rodriguez de Fonseca, Fernando
中科院分区：
文献类型：
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作者：
Javier Pavon, Francisco;Araos, Pedro;Rodriguez de Fonseca, Fernando
便秘与严重的健康问题有关，包括精神病合并症。需要鉴定用于可卡因成瘾受试者分层的生物标志物。一些研究已经评估了循环内源性大麻素相关脂质作为炎症，代谢和精神障碍的生物标志物。然而，对物质使用障碍知之甚少。本研究的特点都是免费的N-酰基-乙醇胺（NAEs）和2-酰基-甘油戒毒可卡因成瘾者从门诊治疗计划谁被诊断为可卡因使用障碍（CUD; n=88），年龄/性别/体重匹配的健康对照志愿者（n=46）。根据精神疾病诊断和统计手册，第4版，文本修订版（DSM-IV-TR），通过半结构化访谈“物质和精神疾病的精神病学研究访谈”评估物质滥用中常见的物质和精神障碍，并通过液相色谱-串联质谱系统定量血浆游离酰基衍生物。结果表明，血浆酰基衍生物的改变，在戒断可卡因成瘾的科目与CUD（CUD科目）。与对照组相比，CUD受试者的NAE增加，2-酰基甘油减少。开发了基于这些脂质作为解释变量的多变量预测模型，以区分CUD受试者和对照组，提供高区分力。然而，这些变化并没有受到影响的DSM-IV-TR标准可卡因滥用和依赖可卡因特质严重程度的措施。与此相反，我们观察到，一些游离酰基衍生物在CUD主题被发现受到一些共病精神疾病的诊断。因此，我们发现，与非共病CUD受试者相比，诊断为情绪[N-油酰-乙醇胺和N-棕榈油酰-乙醇胺（POEA）]和焦虑（POEA）障碍的CUD受试者的单不饱和NAE显著升高。有趣的是，酒精使用障碍的共存并没有影响这些游离酰基衍生物的循环水平。总之，我们已经确定了无血浆酰基衍生物，它们可能作为CUD的可靠生物标志物。此外，我们发现，单不饱和NAE水平也提高了共病情绪和焦虑障碍的可卡因成瘾者。这些发现为开发可卡因成瘾诊断和治疗的新策略开辟了道路。
Cocaine is associated with serious health problems including psychiatric co-morbidity. There is a need for the identification of biomarkers for the stratification of cocaine-addicted subjects. Several studies have evaluated circulating endocannabinoid-related lipids as biomarkers of inflammatory, metabolic and mental disorders. However, little is known in substance use disorders. This study characterizes both free N-acyl-ethanolamines (NAEs) and 2-acyl-glycerols in abstinent cocaine addicts from outpatient treatment programs who were diagnosed with cocaine use disorder (CUD; n=88), and age-/gender-/body mass-matched healthy control volunteers (n=46). Substance and mental disorders that commonly occur with substance abuse were assessed by the semi-structured interview Psychiatric Research Interview for Substance and Mental Diseases' according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision' (DSM-IV-TR) and plasma-free acyl derivatives were quantified by a liquid chromatography-tandem mass spectrometry system. The results indicate that plasma acyl derivatives are altered in abstinent cocaine-addicted subjects with CUD (CUD subjects). While NAEs were found to be increased, 2-acyl-glycerols were decreased in CUD subjects compared with controls. Multivariate predictive models based on these lipids as explanatory variables were developed to distinguish CUD subjects from controls providing high discriminatory power. However, these alterations were not influenced by the DSM-IV-TR criteria for cocaine abuse and dependence as cocaine trait severity measure. In contrast, we observed that some free acyl derivatives in CUD subjects were found to be affected by the diagnosis of some co-morbid psychiatric disorders. Thus, we found that the monounsaturated NAEs were significantly elevated in CUD subjects diagnosed with mood [N-oleoyl-ethanolamine and N-palmitoleoyl-ethanolamine (POEA)] and anxiety (POEA) disorders compared with non-co-morbid CUD subjects. Interestingly, the coexistence of alcohol use disorders did not influence the circulating levels of these free acyl derivatives. In summary, we have identified plasma-free acyl derivatives that might serve as reliable biomarkers for CUD. Furthermore, we found that monounsaturated NAE levels are also enhanced by co-morbid mood and anxiety disorders in cocaine addicts. These findings open the way for the development of new strategies for cocaine addiction diagnosis and treatment.