Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception
Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception
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DOI：
10.1016/j.drugalcdep.2009.06.009
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发表时间：
2009-11-01
影响因子：
4.2
通讯作者：
Lichtman, Aron H.
中科院分区：
文献类型：
--
作者：
Booker, Lamont;Naidu, Pattipati S.;Lichtman, Aron H.
相当多的临床前研究已经证明了Delta（9）-四氢大麻酚（Delta（9）-THC）（大麻的主要精神活性成分）在各种各样的疼痛动物模型中的功效，但很少有研究考察其他植物大麻素。事实上，其他植物来源的大麻素，包括大麻二酚（CBD）、大麻酚（CBN）和大麻环萜（CBC）在一些测定中引起抗伤害感受作用。相比之下，大麻的另一种成分四氢大麻酚（THCV）拮抗Delta（9）-THC的药理作用。这些结果表明，这种植物的各种成分可能以复杂的方式相互作用，以调节疼痛。本研究的主要目的是评估这些其他流行的植物大麻素在醋酸拉伸试验（啮齿动物内脏痛模型）中的抗伤害作用。在测试的大麻素化合物中，Delta（9）-THC和CBN与CB 1受体结合并产生抗伤害感受作用。CB 1受体拮抗剂利莫那班，但不是CB 2受体拮抗剂，SR 144528，阻断了这两种化合物的抗伤害作用。虽然THCV与CB 1受体的结合亲和力与Delta（9）-THC相似，但单独给药时没有作用，但当两种药物联合给药时，可拮抗Delta（9）-THC的抗伤害作用。重要的是，Delta（9）-THC和CBN的抗伤害感受作用发生在比产生运动抑制所需的剂量更低的剂量下，这表明运动功能障碍不能解释乙酸诱导的腹部拉伸的减少。这些数据提出了一种有趣的可能性，即大麻的其他成分可用于通过引发抗伤害效应（即，CBN）或拮抗（即，THCV）Δ（9）-THC的作用。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids. Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC. These results suggest that various constituents of this plant may interact in a complex manner to modulate pain. The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model. Of the cannabinoid compounds tested, Delta(9)-THC and CBN bound to the CB1 receptor and produced antinociceptive effects. The CB1 receptor antagonist, rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the antinociceptive effects of both compounds. Although THCV bound to the CB1 receptor with similar affinity as Delta(9)-THC, it had no effects when administered alone, but antagonized the antinociceptive effects of Delta(9)-THC when both drugs were given in combination. Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching. These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC. (C) 2009 Elsevier Ireland Ltd. All rights reserved.