Department of Psychiatry, Faculty of Medicine, Fernand-Seguin Research Centre, Université de Montréal Montréal, QC, Canada.
Front Psychiatry. 2012 Sep 25;3:85. doi: 10.3389/fpsyt.2012.00085. eCollection 2012.
Schizophrenia is a complex psychiatric disorder strongly associated with substance use disorders. Theoretically, schizophrenia and SUD may share endocannabinoid alterations in the brain reward system. The main endocannabinoids, anandamide, and 2-arachidonoylglycerol, are lipids which bind cannabinoid receptors. Oleoylethanolamide (OEA), a fatty-acid ethanolamide, binds peroxisome proliferator-activated receptors. The endocannabinoid system has been shown to be impaired in schizophrenia, and recently, our group has shown that schizophrenia patients with SUD have elevated peripheral levels of anandamide and OEA that do not normalize after 3-month treatment with quetiapine. Objective For comparative purposes, we aimed to measure endocannabinoids in non-psychosis substance abusers and non-abusing schizophrenia patients. Methods Using liquid chromatography and mass spectrometry, we measured plasma levels of anandamide and OEA in non-psychosis SUD patients, non-abusing schizophrenia patients, and healthy controls. In an open-label manner, all patients received 12-week treatment with quetiapine. Results Anandamide and OEA were reduced in substance abusers without schizophrenia, relative to healthy controls (p < 0.05). Both endocannabinoids were unchanged in non-abusing schizophrenia patients. After quetiapine, anandamide, and OEA levels remained significantly reduced the SUD group (p < 0.05). Discussion Taken together with results of our previous study performed in dual-diagnosis patients, our results suggest that peripheral anandamide and OEA levels are impaired in patients with SUD in opposite ways according to the presence or absence of schizophrenia. Endocannabinoid alterations did not change with treatment, suggesting that they are trait markers. Further studies are necessary to understand the role of endocannabinoids in substance abusers with and without schizophrenia and to examine therapeutic implications.
精神分裂症是一种与物质使用障碍密切相关的复杂精神疾病。从理论上讲，精神分裂症和 SUD 可能在大脑奖励系统中共享内源性大麻素的改变。主要的内源性大麻素，即花生四烯酸乙醇酰胺和 2-花生四烯酰甘油，是与大麻素受体结合的脂质。油酰乙醇酰胺（OEA）是一种脂肪酸乙醇酰胺，与过氧化物酶体增殖物激活受体结合。内源性大麻素系统已被证明在精神分裂症中受损，最近，我们的研究小组发现，伴有 SUD 的精神分裂症患者外周血中花生四烯酸乙醇酰胺和 OEA 水平升高，而在接受喹硫平治疗 3 个月后并未恢复正常。目的 为了进行比较，我们旨在测量非精神病物质滥用者和非滥用精神分裂症患者的内源性大麻素。方法 使用液相色谱和质谱法，我们测量了非精神病物质滥用者、非滥用精神分裂症患者和健康对照者的血浆中花生四烯酸乙醇酰胺和 OEA 的水平。所有患者均以开放标签的方式接受 12 周的喹硫平治疗。结果 与健康对照组相比，无精神分裂症的物质滥用者中花生四烯酸乙醇酰胺和 OEA 水平降低（p<0.05）。非滥用精神分裂症患者的两种内源性大麻素均未改变。在喹硫平治疗后，SUD 组的花生四烯酸乙醇酰胺和 OEA 水平仍显著降低（p<0.05）。讨论 结合我们之前在双重诊断患者中进行的研究结果，我们的结果表明，根据是否存在精神分裂症，SUD 患者的外周花生四烯酸乙醇酰胺和 OEA 水平以相反的方式受损。内源性大麻素的改变并未随着治疗而改变，这表明它们是特质标记。需要进一步的研究来了解内源性大麻素在伴有和不伴有精神分裂症的物质滥用者中的作用，并探讨其治疗意义。
