Leweke F M, Giuffrida A, Wurster U, Emrich H M, Piomelli D
Department of Clinical Psychiatry and Psychotherapy, Medizinische Hochschule Hannover, Germany.
Neuroreport. 1999 Jun 3;10(8):1665-9. doi: 10.1097/00001756-199906030-00008.
Evidence suggests that cannabinoid receptors, the pharmacologcial target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia. To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal fluid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were purified from cerebrospinal fluid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quantified by isotope dilution gas-chromatography/mass-spectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than non-schizophrenic controls (p < 0.05). By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups. The findings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.
有证据表明，大麻衍生药物的药理学靶点大麻素受体及其内源性激活剂伴随系统在精神分裂症中可能功能失调。为验证这一假设，我们研究了与非精神分裂症对照相比，精神分裂症患者脑脊液中的内源性大麻素浓度是否发生改变。通过高效液相色谱法从10例精神分裂症患者和11例非精神分裂症对照的脑脊液中纯化内源性大麻素，并通过同位素稀释气相色谱/质谱法定量。精神分裂症患者脑脊液中两种内源性大麻素（花生四烯乙醇胺和棕榈酰乙醇胺）的浓度显著高于非精神分裂症对照（p < 0.05）。相比之下，两组中另一种内源性大麻素脂质2-花生四烯酸甘油酯的水平均低于检测限。这些发现似乎与性别、年龄或药物治疗无关。精神分裂症患者脑脊液中花生四烯乙醇胺和棕榈酰乙醇胺水平升高可能反映了内源性大麻素信号失衡，这可能导致精神分裂症的发病机制。
