Leweke F Markus, Giuffrida Andrea, Koethe Dagmar, Schreiber Daniela, Nolden Brit M, Kranaster Laura, Neatby Miriam A, Schneider Miriam, Gerth Christoph W, Hellmich Martin, Klosterkötter Joachim, Piomelli Daniele
Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
Schizophr Res. 2007 Aug;94(1-3):29-36. doi: 10.1016/j.schres.2007.04.025. Epub 2007 Jun 13.
Previous studies have shown that cerebrospinal fluid (CSF) from schizophrenic patients contains significantly higher levels of the endogenous cannabinoid anandamide than does CSF from healthy volunteers. Moreover, CSF anandamide levels correlated inversely with psychotic symptoms, suggesting that anandamide release in the central nervous system (CNS) may serve as an adaptive mechanism countering neurotransmitter abnormalities in acute psychoses. In the present study we examined whether cannabis use may alter such a mechanism.
We used liquid chromatography/mass spectrometry (LC/MS) to measure anandamide levels in serum and CSF from first-episode, antipsychotic-naïve schizophrenics (n=47) and healthy volunteers (n=81). Based on reported patterns of cannabis use and urine delta9-tetrahydrocannabinol (delta9-THC) tests, each subject group was further divided into two subgroups: 'low-frequency' and 'high-frequency' cannabis users (lifetime use < or = 5 times and > 20 times, respectively). Serum delta9-THC was investigated to determine acute use and three patients were excluded from the analysis due to detectable delta9-THC levels in serum.
Schizophrenic low-frequency cannabis users (n=25) exhibited > 10-fold higher CSF anandamide levels than did schizophrenic high-frequency users (n=19, p=0.008), healthy low-frequency (n=55, p<0.001) or high-frequency users (n=26, p<0.001). In contrast, no significant differences in serum anandamide levels were found among the four subgroups. CSF anandamide levels and disease symptoms were negatively correlated in both user groups.
The results indicate that frequent cannabis exposure may down-regulate anandamide signaling in the CNS of schizophrenic patients, but not of healthy individuals. Thus, our findings suggest that alterations in endocannabinoid signaling might be an important component of the mechanism through which cannabis impacts mental health.
先前的研究表明，精神分裂症患者的脑脊液（CSF）中内源性大麻素花生四烯乙醇胺的含量显著高于健康志愿者的脑脊液。此外，脑脊液中花生四烯乙醇胺水平与精神病症状呈负相关，这表明中枢神经系统（CNS）中花生四烯乙醇胺的释放可能是一种对抗急性精神病中神经递质异常的适应性机制。在本研究中，我们检测了使用大麻是否会改变这种机制。
我们使用液相色谱/质谱联用（LC/MS）技术测量首发、未使用过抗精神病药物的精神分裂症患者（n = 47）和健康志愿者（n = 81）血清和脑脊液中花生四烯乙醇胺的水平。根据报告的大麻使用模式和尿液中Δ9-四氢大麻酚（Δ9-THC）检测结果，每个受试者组进一步分为两个亚组：“低频”和“高频”大麻使用者（终生使用次数分别≤5次和>20次）。检测血清中Δ9-THC以确定近期使用情况，由于血清中可检测到Δ9-THC水平，三名患者被排除在分析之外。
精神分裂症低频大麻使用者（n = 25）脑脊液中花生四烯乙醇胺水平比精神分裂症高频使用者（n = 19，p = 0.008）、健康低频使用者（n = 55，p < 0.001）或高频使用者（n = 26，p < 0.001）高出10倍以上。相比之下，四个亚组之间血清中花生四烯乙醇胺水平没有显著差异。在两个使用者组中，脑脊液中花生四烯乙醇胺水平与疾病症状均呈负相关。
结果表明，频繁接触大麻可能会下调精神分裂症患者中枢神经系统中花生四烯乙醇胺信号，但对健康个体无此影响。因此，我们的研究结果表明，内源性大麻素信号的改变可能是大麻影响心理健康机制的重要组成部分。
