Jenkins Bryan W, Moore Catherine F, Weerts Elise M
Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Pharmacol Exp Ther. 2025 Jul;392(7):103625. doi: 10.1016/j.jpet.2025.103625. Epub 2025 Jun 11.
Cannabis products used for pain typically contain Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) in varied amounts, but data on the effects of specific cannabinoid formulations on different pain types are lacking. This study used the carrageenan-induced inflammatory pain model to test oral Δ9-THC, CBD, or their combination on acute edema and pain hypersensitivity. Male and female Sprague-Dawley rats (n = 10-14 per sex/group) were pretreated (1 hour) with vehicle (sesame oil), Δ9-THC (1, 3, and 10 mg/kg, p.o.), CBD (10, 30, 100 mg/kg, p.o.), or select doses of Δ9-THC + CBD combinations prior to an intraplantar λ-carrageenan injection into the hind paw. The nonsteroidal anti-inflammatory drug ketoprofen (10 and 20 mg/kg i.p.) or its vehicle (1:1:18 ethanol:Cremophor EL:saline [Millipor Sigma]) was administered to a separate group as a positive control. Measurements were conducted at baseline and 1, 3, and 5 hours after carrageenan injection. Carrageenan produced edema and hypersensitivity to radiant heat (hyperalgesia) and mechanical pressure (allodynia). Δ9-THC alone sex- and dose-dependently decreased hyperalgesia and allodynia but not inflammation, with effects of Δ9-THC being greater in females than males, and the lowest Δ9-THC dose was proinflammatory in males. CBD alone did not affect pain sensitivity but had modest anti-inflammatory effects in males. Isobolographic and dose addition analyses indicated Δ9-THC + CBD was subadditive relative to Δ9-THC alone. These data demonstrate that prophylactic oral Δ9-THC alleviates acute inflammatory pain with sex-dependent effects, and CBD diminishes Δ9-THC antinociception when combined. The findings suggest oral Δ9-THC is superior to CBD or combined Δ9-THC + CBD for acute inflammatory pain. SIGNIFICANCE STATEMENT: Despite the popularity of cannabis for pain management, empirical data on how specific cannabinoid formulations affect acute inflammatory pain are limited. This study in rats found that pure Δ-9-tetrahydrocannabinol (Δ9-THC) formulations were most effective at improving inflammatory pain compared to pure cannabidiol or Δ9-THC + cannabidiol combinations, and females were more sensitive than males to the antinociceptive effects of Δ9-THC.
用于止痛的大麻产品通常含有不同含量的Δ-9-四氢大麻酚（Δ9-THC）和大麻二酚（CBD），但缺乏关于特定大麻素配方对不同疼痛类型影响的数据。本研究使用角叉菜胶诱导的炎性疼痛模型来测试口服Δ9-THC、CBD或它们的组合对急性水肿和疼痛超敏反应的影响。将雄性和雌性斯普拉格-道利大鼠（每组每种性别n = 10 - 14只）用赋形剂（芝麻油）、Δ9-THC（1、3和10 mg/kg，口服）、CBD（10、30、100 mg/kg，口服）或选定剂量的Δ9-THC + CBD组合预处理（1小时），然后在后爪足底注射λ-角叉菜胶。将非甾体抗炎药酮洛芬（10和20 mg/kg，腹腔注射）或其赋形剂（1:1:18乙醇:聚氧乙烯蓖麻油EL:盐水[默克密理博]）给予另一组作为阳性对照。在角叉菜胶注射后的基线以及1、3和5小时进行测量。角叉菜胶引起水肿以及对辐射热（痛觉过敏）和机械压力（异常性疼痛）的超敏反应。单独使用Δ9-THC可性别和剂量依赖性地减轻痛觉过敏和异常性疼痛，但对炎症无影响，Δ9-THC对雌性的作用大于雄性，且最低剂量的Δ9-THC对雄性具有促炎作用。单独使用CBD不影响疼痛敏感性，但对雄性有适度的抗炎作用。等效线图和剂量相加分析表明，与单独使用Δ9-THC相比，Δ9-THC + CBD具有次相加性。这些数据表明，预防性口服Δ9-THC可减轻急性炎性疼痛，且具有性别依赖性效应，而CBD与Δ9-THC联合使用时会减弱其镇痛作用。研究结果表明，对于急性炎性疼痛，口服Δ9-THC优于CBD或Δ9-THC + CBD组合。重要声明：尽管大麻在疼痛管理中很受欢迎，但关于特定大麻素配方如何影响急性炎性疼痛的实证数据有限。这项在大鼠中的研究发现，与纯大麻二酚或Δ9-THC +大麻二酚组合相比，纯Δ-9-四氢大麻酚（Δ9-THC）配方在改善炎性疼痛方面最有效，并且雌性对Δ9-THC的镇痛作用比雄性更敏感。
