Seeman P
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
Transl Psychiatry. 2016 Oct 18;6(10):e920. doi: 10.1038/tp.2016.195.
Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects.
尽管目前所有的抗精神病药物都是通过干扰多巴胺在多巴胺D2受体上的作用来发挥功效，但最近有两份报告显示，每天服用800至1000毫克的大麻二酚可缓解精神分裂症的体征和症状，尽管目前尚不清楚大麻二酚是否作用于多巴胺受体。由于这些最新的临床研究结果可能表明，所有抗精神病药物都通过干扰多巴胺在多巴胺D2受体上的作用这一普遍规律存在重要例外情况，因此本研究使用氚标记的多潘立酮来标记大鼠脑纹状体D2受体，以检测大麻二酚是否直接作用于D2受体。研究发现，大麻二酚抑制放射性多潘立酮的结合，在多巴胺D2高亲和力受体上的解离常数为11纳米，在多巴胺D2低亲和力受体上的解离常数为2800纳米，其方式与阿立哌唑等多巴胺部分激动剂抗精神病药物相同，呈双相性。大麻二酚的临床剂量足以占据功能性D2高亲和力位点。由此得出结论，大麻二酚的多巴胺部分激动剂作用可能是其临床抗精神病作用的原因。
