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大鼠口服大麻二酚(CBG):拟大麻作用、焦虑样行为及炎症性疼痛

Orally administered Cannabigerol (CBG) in rats: Cannabimimetic actions, anxiety-like behavior, and inflammation-induced pain.

作者信息

Weerts Elise M, Jenkins Bryan W, Kuang Robbie Y, Hausker Alma, Moore Catherine F

机构信息

Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA.

Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA.

出版信息

Pharmacol Biochem Behav. 2024 Dec;245:173883. doi: 10.1016/j.pbb.2024.173883. Epub 2024 Sep 23.

DOI:10.1016/j.pbb.2024.173883
PMID:39322049
Abstract

Cannabigerol (CBG) is a phytocannabinoid found in cannabis that is promoted for medical use and other health benefits, but current empirical data on the behavioral effects of CBG are lacking. The purpose of this study was to evaluate the effects of a wide dose range of orally administered CBG on outcomes related to its potential cannabimimetic effects (cannabinoid tetrad), as well as effects on anxiety-like behavior, inflammation and related pain hypersensitivity. In a series of experiments, male and female Sprague Dawley rats received oral CBG (per os [p.o.]) or vehicle prior to testing of effects on 1) the cannabinoid tetrad (30-600 mg/kg, p.o.): assessments of locomotor activity, body temperature, antinociception (tail flick test), and catalepsy (bar test); 2) acoustic startle response (ASR) test of anxiety-like behavior (30-300 mg/kg, p.o.); 3) carrageenan-induced inflammation (paw edema), hyperalgesia (Hargreaves test), and allodynia (von Frey test) tests (10-60 mg/kg, p.o.). Positive control groups were administered THC (0-30 mg/kg, p.o.) for the cannabinoid tetrad assay, the benzodiazepine lorazepam (0-3 mg/kg, intraperitoneal [i.p.]) for the ASR test, or the opioid analgesic morphine (0-10 mg/kg, i.p.) for the carrageenan-induced inflammation and pain hypersensitivity tests. CBG did not produce cannabimimetic actions in the tetrad, but increased locomotor activity at the highest doses (300-600 mg/kg). THC produced typical dose-related cannabimimetic effects. CBG did not produce anxiolytic effects in the ASR test, while groups pretreated with lorazepam showed reductions in ASR. Finally, pretreatment with CBG prior to an intraplantar injection of carrageenan did not prevent the induction of an acute inflammatory state (i.e., increased paw edema and associated hyperalgesia and allodynia). In contrast, morphine alleviated hyperalgesia and allodynia induced by intraplantar carrageenan but did not affect the development of paw edema. In sum, these data do not support the use of oral CBG for anxiety or inflammatory pain.

摘要

大麻二酚(CBG)是一种存在于大麻中的植物大麻素,因其具有医疗用途和其他健康益处而受到推崇,但目前缺乏关于CBG行为效应的实证数据。本研究的目的是评估口服不同剂量范围的CBG对与其潜在大麻模拟效应(大麻素四联症)相关的结果的影响,以及对焦虑样行为、炎症和相关疼痛超敏反应的影响。在一系列实验中,雄性和雌性斯普拉格-道利大鼠在测试以下效应之前接受口服CBG(经口给药)或赋形剂:1)大麻素四联症(30 - 600毫克/千克,经口给药):评估运动活动、体温、抗伤害感受(甩尾试验)和僵住症(杆试验);2)焦虑样行为的听觉惊吓反应(ASR)试验(30 - 300毫克/千克,经口给药);3)角叉菜胶诱导的炎症(爪肿胀)、痛觉过敏(热辐射甩尾试验)和异常性疼痛(von Frey试验)试验(10 - 60毫克/千克,经口给药)。阳性对照组在大麻素四联症试验中给予四氢大麻酚(0 - 30毫克/千克,经口给药),在ASR试验中给予苯二氮䓬类药物劳拉西泮(0 - 3毫克/千克,腹腔注射),或在角叉菜胶诱导的炎症和疼痛超敏反应试验中给予阿片类镇痛药吗啡(0 - 10毫克/千克,腹腔注射)。CBG在四联症试验中未产生大麻模拟作用,但在最高剂量(300 - 600毫克/千克)时增加了运动活动。四氢大麻酚产生了典型的剂量相关大麻模拟效应。CBG在ASR试验中未产生抗焦虑作用,而用劳拉西泮预处理的组ASR降低。最后,在足底注射角叉菜胶之前用CBG预处理并不能阻止急性炎症状态的诱导(即爪肿胀增加以及相关的痛觉过敏和异常性疼痛)。相比之下,吗啡减轻了足底注射角叉菜胶诱导的痛觉过敏和异常性疼痛,但不影响爪肿胀的发展。总之,这些数据不支持将口服CBG用于治疗焦虑或炎性疼痛。

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