Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Transl Psychiatry. 2012 Mar 20;2(3):e94. doi: 10.1038/tp.2012.15.
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.
大麻二酚是大麻的一种成分，它不会激活大麻素受体，但能适度抑制内源性大麻素的降解。我们之前的研究报告表明，脑脊液中花生四烯酸酰胺水平的升高与精神病症状呈负相关。此外，增强的花生四烯酸酰胺信号导致从最初的前驱状态到明显的精神病的转变率降低，并且延迟了转变。在我们的转化研究中，我们对大麻二酚与安非他酮（一种有效的抗精神病药物）进行了一项双盲、随机临床试验，以评估我们最初发现的临床相关性。两种治疗方法均安全且显著改善了临床症状，但大麻二酚显示出明显更好的副作用特征。此外，大麻二酚治疗伴随着血清花生四烯酸酰胺水平的显著升高，这与临床改善显著相关。这些结果表明，抑制花生四烯酸酰胺失活可能有助于大麻二酚的抗精神病作用，这可能代表了治疗精神分裂症的一种全新机制。
