Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
Pharmacol Biochem Behav. 2019 Sep;184:172741. doi: 10.1016/j.pbb.2019.172741. Epub 2019 Jul 20.
Cannabidiol (CBD), a compound found in many strains of the Cannabis genus, is increasingly available in e-cigarette liquids as well as other products. CBD use has been promoted for numerous purported benefits which have not been rigorously assessed in preclinical studies.
To further validate an inhalation model to assess CBD effects in the rat. The primary goal was to determine plasma CBD levels after vapor inhalation and compare that with the levels observed after injection. Secondary goals were to determine if hypothermia is produced in male Sprague-Dawley rats and if CBD affects nociception measured by the warm water tail-withdrawal assay.
Blood samples were collected from rats exposed for 30 min to vapor generated by an e-cigarette device using CBD (100, 400 mg/mL in the propylene glycol vehicle). Separate experiments assessed the body temperature response to CBD in combination with nicotine (30 mg/mL) and the anti-nociceptive response to CBD.
Vapor inhalation of CBD produced concentration-related plasma CBD levels in male and female Wistar rats that were within the range of levels produced by 10 or 30 mg/kg, CBD, i.p. Dose-related hypothermia was produced by CBD in male Sprague-Dawley rats, and nicotine (30 mg/mL) inhalation enhanced this effect. CBD inhalation had no effect on anti-nociception alone or in combination with Δ-tetrahydrocannabinol inhalation.
The vapor-inhalation approach is a suitable pre-clinical model for the investigation of the effects of inhaled CBD. This route of administration produces hypothermia in rats, while i.p. injection does not, at comparable plasma CBD levels.
大麻属植物的许多品种中都含有大麻二酚(CBD),这种化合物在电子烟液和其他产品中的应用越来越广泛。CBD 的使用被宣传为具有多种所谓的益处,但这些益处尚未在临床前研究中得到严格评估。
进一步验证一种吸入模型,以评估 CBD 在大鼠体内的作用。主要目标是确定吸入 CBD 后大鼠的血浆 CBD 水平,并将其与注射后观察到的水平进行比较。次要目标是确定雄性 Sprague-Dawley 大鼠是否会出现体温过低,以及 CBD 是否会影响通过温水尾巴退缩试验测量的痛觉。
使用含有 CBD(丙二醇溶液中的 100、400mg/ml)的电子烟设备,让大鼠暴露于 30 分钟的蒸汽中,收集血液样本。单独的实验评估了 CBD 与尼古丁(30mg/ml)联合使用对体温的影响,以及 CBD 对痛觉的影响。
雄性和雌性 Wistar 大鼠吸入 CBD 产生了浓度相关的血浆 CBD 水平,这些水平与腹腔注射 10 或 30mg/kg CBD 产生的水平相当。雄性 Sprague-Dawley 大鼠吸入 CBD 产生了剂量相关的体温过低,而尼古丁(30mg/ml)吸入则增强了这种效应。CBD 吸入单独或与 Δ-四氢大麻酚吸入联合使用对痛觉无影响。
吸入 CBD 的方法是研究吸入 CBD 效应的合适临床前模型。这种给药途径在大鼠中产生体温过低,而腹腔注射则不会在可比的血浆 CBD 水平下产生这种效应。