School of Life Sciences, University of Hertfordshire, CP Snow Building, Hatfield, UK.
Pulm Pharmacol Ther. 2013 Jun;26(3):373-9. doi: 10.1016/j.pupt.2013.02.002. Epub 2013 Feb 18.
(-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders.
(-)-Δ(9)-四氢大麻酚已被证明在气道中具有有益作用，但由于其精神活性作用，排除了其用于治疗气道疾病的治疗用途。在本研究中，我们研究了大麻的非精神活性成分(-)-大麻二酚对气道平滑肌的作用及其在体外和体内的作用。通过等长方式测量豚鼠气道平滑肌对外源性痉挛剂引起的收缩。此外，还研究了(-)-大麻二酚在卵白蛋白致敏豚鼠存在或不存在(-)-大麻二酚的情况下对支气管平滑肌收缩的影响。此外，在卵白蛋白致敏的豚鼠中研究了(-)-大麻二酚对卵白蛋白诱导的气道阻塞的体内作用。(-)-大麻二酚不影响乙酰胆碱、组胺或神经激肽 A 引起的气道平滑肌收缩。相比之下，(-)-大麻二酚抑制了大麻素和维罗达明引起的分离支气管的反应。脂肪酸酰胺水解酶抑制剂苯甲磺酰氟逆转了(-)-大麻二酚对大麻素诱导收缩的抑制作用。此外，(-)-大麻二酚抑制了来自过敏豚鼠的卵白蛋白诱导的支气管的收缩反应。在体内，(-)-大麻二酚减轻了卵白蛋白诱导的气道阻塞。总之，我们的结果表明，大麻二酚可以影响抗原诱导的气道平滑肌张力，表明该分子可能对治疗阻塞性气道疾病有益。
