Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.
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DOI：
10.1038/tp.2012.15
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发表时间：
2012-03-20
影响因子：
6.8
通讯作者：
Koethe D
中科院分区：
文献类型：
--
作者：
Leweke FM;Piomelli D;Pahlisch F;Muhl D;Gerth CW;Hoyer C;Klosterkötter J;Hellmich M;Koethe D
大麻二酚是大麻的一种成分，它不激活大麻素受体，但适度抑制内源性大麻素anandamide的降解。我们以前报道过脑脊液中大麻素水平的升高与精神病症状呈负相关。此外，增强的大麻素信号传导使从初始前驱状态到坦率的精神病的转变率较低，以及延迟转变。在我们的翻译方法中，我们进行了一项双盲，随机临床试验，大麻二酚与氨磺必利，一种有效的抗精神病药，在急性精神分裂症，以评估我们的初步研究结果的临床相关性。两种治疗都是安全的，并导致了显着的临床改善，但大麻二酚显示出显着优越的上级副作用。此外，大麻二酚治疗伴随着血清大麻素水平的显著增加，这与临床改善显著相关。结果表明，抑制大麻素失活可能有助于大麻二酚的抗精神病作用，这可能是治疗精神分裂症的一种全新机制。
Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
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