Effect of cannabidiolic acid and Δ9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain
Effect of cannabidiolic acid and Δ9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain
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DOI：
10.1007/s00213-018-5034-1
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发表时间：
2018-11-01
影响因子：
3.4
通讯作者：
Parker, Linda A.
中科院分区：
文献类型：
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作者：
Rock, Erin M.;Limebeer, Cheryl L.;Parker, Linda A.
大麻二酚（CBD）是大麻的一种非致醉成分，或具有精神活性的（9）-四氢大麻酚（THC），具有抗痛觉过敏和抗炎的特性。当全身给药（腹膜内，i. p.）或在角叉菜胶之前和/或之后口服。此外，我们还评估了口服THC或CBDA的效果，它们的作用机制，以及THC和CBDA联合无效剂量在该模型中的疗效。最后，我们比较了CBD和CBDA.ResultsCBDA的疗效。在角叉菜胶前60分钟（但角叉菜胶后60分钟）给予腹腔注射CBDA产生剂量依赖性的抗痛觉过敏和抗炎作用。此外，在角叉菜胶之前60分钟通过口服管饲给予THC或CBDA产生抗痛觉过敏作用，并且THC减少炎症。THC的抗痛觉过敏作用被SR 141716（大麻素1受体拮抗剂）阻断，而CBDA的作用被AMG 9810（瞬时受体电位阳离子通道亚家族V成员1拮抗剂）阻断。与CBDA相比，同等低剂量的CBD没有减少痛觉过敏，表明CBDA比CBD更有效。有趣的是，当无效剂量的CBDA或THC单独组合，这种组合产生了抗痛觉过敏的效果和减少inflammation.ConclusionCBDA或THC单独，以及非常低剂量的联合CBDA和THC，具有抗炎和抗痛觉过敏的影响，在这种动物模型的急性炎症。
RationaleCannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive (9)-tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti-inflammatory properties.ObjectivesThe present study evaluates the anti-inflammatory and anti-hyperalgesia effects of CBD's potent acidic precursor, cannabidiolic acid (CBDA), in a rodent model of carrageenan-induced acute inflammation in the rat hind paw, when administered systemically (intraperitoneal, i.p.) or orally before and/or after carrageenan. In addition, we assess the effects of oral administration of THC or CBDA, their mechanism of action, and the efficacy of combined ineffective doses of THC and CBDA in this model. Finally, we compare the efficacy of CBD and CBDA.ResultsCBDA given i.p. 60min prior to carrageenan (but not 60min after carrageenan) produced dose-dependent anti-hyperalgesia and anti-inflammatory effects. In addition, THC or CBDA given by oral gavage 60min prior to carrageenan produced anti-hyperalgesia effects, and THC reduced inflammation. The anti-hyperalgesia effects of THC were blocked by SR141716 (a cannabinoid 1 receptor antagonist), while CBDA's effects were blocked by AMG9810 (a transient receptor potential cation channel subfamily V member 1 antagonist). In comparison to CBDA, an equivalent low dose of CBD did not reduce hyperalgesia, suggesting that CBDA is more potent than CBD for this indication. Interestingly, when ineffective doses of CBDA or THC alone were combined, this combination produced an anti-hyperalgesia effect and reduced inflammation.ConclusionCBDA or THC alone, as well as very low doses of combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in this animal model of acute inflammation.