Potvin Stéphane, Kouassi Edouard, Lipp Olivier, Bouchard Roch-Hugo, Roy Marc-André, Demers Marie-France, Gendron Alain, Astarita Giuseppe, Piomelli Daniele, Stip Emmanuel
Fernand-Seguin Research Center, Louis-H Lafontaine Hospital and Biomedical Sciences Program, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
J Psychopharmacol. 2008 May;22(3):262-9. doi: 10.1177/0269881107083816.
Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulatory effects on ECB. To verify these two assumptions, 29 patients (24 completers) with schizophrenia and substance use disorders (SUD) were treated with quetiapine for 12 weeks, and peripheral ECB levels were measured, using high-performance liquid chromatography/mass spectrometry, in patients (weeks 0, 6 and 12) and 17 healthy volunteers. Baseline anandamide levels were significantly higher in patients, relative to controls. This result is consistent with studies describing ECB dysfunctions in schizophrenia. SUD parameters improved during treatment, but no changes in ECB occurred over time. Improvements in substance abuse were probably not mediated by modulatory effects of quetiapine on ECB. Lastly, baseline anandamide predicted endpoint SUD scores (alcohol/ cannabis). Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.
精神分裂症患者内源性大麻素（ECB）系统紊乱可能导致其对精神活性物质的敏感性增强，第二代抗精神病药物对精神分裂症患者药物滥用的有益作用可能涉及对ECB的调节作用。为验证这两个假设，对29例患有精神分裂症和物质使用障碍（SUD）的患者（24例完成治疗）使用喹硫平治疗12周，并在患者（第0、6和12周）和17名健康志愿者中，采用高效液相色谱/质谱法测量外周ECB水平。与对照组相比，患者的基线花生四烯乙醇胺水平显著更高。该结果与描述精神分裂症中ECB功能障碍的研究一致。治疗期间SUD参数有所改善，但ECB水平未随时间发生变化。药物滥用的改善可能并非由喹硫平对ECB的调节作用介导。最后，基线花生四烯乙醇胺可预测终点SUD评分（酒精/大麻）。花生四烯乙醇胺是旨在缓解精神分裂症患者SUD的药物的潜在靶点。
