Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol.
Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol.
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DOI：
10.1016/j.drugalcdep.2010.05.019
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发表时间：
2010-11-01
影响因子：
4.2
通讯作者：
Lichtman, Aron H.
中科院分区：
文献类型：
--
作者：
DeLong, Gerald T.;Wolf, Carl E.;Poklis, Alphonse;Lichtman, Aron H.
关键词：
与许多关于Δ-9-四氢大麻酚药理作用的报道相比，大麻的另一种取代基--大麻红烯的药理活性仍然相对未知。在本研究中，我们在四分体实验中研究了CBC是否能引起大麻素活性，四分体实验包括以下四个终点：动力减退、抗伤害性、嗜睡和体温过低。由于大麻类化合物有良好的抗炎作用，我们在脂多糖(LPS)足肿胀试验中检测了CBC、THC以及两种植物大麻素的组合。CBC在四分体中激发活性，CB1受体拮抗剂利莫那班不能阻断这一活性。此外，行为不活跃剂量的THC增强了CBC在四分体中的作用，这与THC脑浓度的增加有关。CBC和THC在脂多糖诱导的小鼠足肿胀模型中均有剂量依赖性的抗炎作用。CB2受体SR144528可阻断THC的抗肿作用，但不能阻断CBC产生的抗肿作用。等位相图分析表明，这些大麻素的抗水肿性作用是相加的。尽管CBC具有药理作用，但与THC不同，其潜在的作用机制不涉及CB1或CB2受体。此外，有证据表明，在静脉注射后，CBC剂量依赖地增加了脑内的THC水平，这可能是一种药代动力学成分。注射0.3 mg/kg THC。总之，CBC在四分体实验中产生了行为活动的一个亚群，并通过非大麻素受体的作用机制减轻了内毒素诱导的足爪肿胀。当CBC和THC联合给药时，这些效应被放大。
In contrast to the numerous reports on the pharmacological effects of Δ9-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 CB1 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 CB2 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 CB1 or CB2 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 0.3 mg/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.
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影响因子：
4.2
作者：
Booker, Lamont;Naidu, Pattipati S.;Lichtman, Aron H.
通讯作者：
Lichtman, Aron H.
影响因子：
1.6
作者：
Ilan, AB;Gevins, A;de Wit, H
通讯作者：
de Wit, H
影响因子：
64.8
作者：
GILL, EW;PATON, WDM;PERTWEE, RG
通讯作者：
PERTWEE, RG
DOI：
10.1300/j175v01n03_08
发表时间：
2001-01-01
期刊：
Journal of Cannabis Therapeutics
影响因子：
--
作者：
McPartland, J. M.;Russo, E. B.
通讯作者：
Russo, E. B.
影响因子：
5.8
作者：
BURSTEIN, S;HUNTER, SA;RENZULLI, L
通讯作者：
RENZULLI, L