Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Drug Alcohol Depend. 2010 Nov 1;112(1-2):126-33. doi: 10.1016/j.drugalcdep.2010.05.019.
In contrast to the numerous reports on the pharmacological effects of Δ(9)-tetrahydrocannabinol (THC), the pharmacological activity of another substituent of Cannabis sativa, cannabichromene (CBC) remains comparatively unknown. In the present study, we investigated whether CBC elicits cannabinoid activity in the tetrad assay, which consists of the following four endpoints: hypomotility, antinociception, catalepsy, and hypothermia. Because cannabinoids are well documented to possess anti-inflammatory properties, we examined CBC, THC, and combination of both phytocannabinoids in the lipopolysaccharide (LPS) paw edema assay. CBC elicited activity in the tetrad that was not blocked by the CB(1) receptor antagonist, rimonabant. Moreover, a behaviorally inactive dose of THC augmented the effects of CBC in the tetrad that was associated with an increase in THC brain concentrations. Both CBC and THC elicited dose-dependent anti-inflammatory effects in the LPS-induced paw edema model. The CB(2) receptor, SR144528 blocked the anti-edematous actions of THC, but not those produced by CBC. Isobolographic analysis revealed that the anti-edematous effects of these cannabinoids in combination were additive. Although CBC produced pharmacological effects, unlike THC, its underlying mechanism of action did not involve CB(1) or CB(2) receptors. In addition, there was evidence of a possible pharmacokinetic component in which CBC dose-dependently increased THC brain levels following an i.v. injection of 0.3mg/kg THC. In conclusion, CBC produced a subset of behavioral activity in the tetrad assay and reduced LPS-induced paw edema through a noncannabinoid receptor mechanism of action. These effects were augmented when CBC and THC were co-administered.
与大量关于Δ(9)-四氢大麻酚（THC）的药理学作用的报告相反，大麻的另一种取代物大麻色烯（CBC）的药理学活性仍然相对未知。在本研究中，我们研究了 CBC 是否在四联体测定中引起大麻素活性，该测定由以下四个终点组成：运动减弱、镇痛、僵住和体温降低。由于大麻素有很好的抗炎特性，我们在脂多糖（LPS）爪肿胀测定中检查了 CBC、THC 和两种植物大麻素的组合。CBC 在四联体中引起的活性不能被 CB(1)受体拮抗剂利莫那班阻断。此外，行为上无活性的 THC 剂量增强了 CBC 在四联体中的作用，这与 THC 脑浓度的增加有关。CBC 和 THC 均在 LPS 诱导的爪肿胀模型中表现出剂量依赖性的抗炎作用。CB(2)受体、SR144528 阻断了 THC 的抗水肿作用，但不阻断 CBC 产生的作用。等比分析显示这些大麻素在组合中的抗水肿作用是相加的。尽管 CBC 产生了药理作用，但与 THC 不同，其作用机制不涉及 CB(1)或 CB(2)受体。此外，有证据表明存在一种可能的药代动力学成分，即静脉注射 0.3mg/kg THC 后，CBC 剂量依赖性地增加 THC 脑水平。总之，CBC 在四联体测定中产生了行为活动的一个子集，并通过非大麻素受体作用机制减少 LPS 诱导的爪肿胀。当 CBC 和 THC 同时给药时，这些作用会增强。
