Karuppagounder Vengadeshprabhu, Chung Juliet, Abdeen Ahmed, Thompson Amy, Bouboukas Andreas, Pinamont William J, Yoshioka Natalie K, Sepulveda Diana E, Raup-Konsavage Wesley M, Graziane Nicholas M, Vrana Kent E, Elbarbary Reyad A, Kamal Fadia
Center for Orthopedic Research and Translational Science (CORTS), Penn State College of Medicine, Hershey, Pennsylvania, USA.
Department of Orthopedics and Rehabilitation, Departments of Penn State College of Medicine, Hershey, Pennsylvania, USA.
Cannabis Cannabinoid Res. 2023 Dec;8(6):1030-1044. doi: 10.1089/can.2021.0244. Epub 2022 Aug 22.
Osteoarthritis (OA) is disabling and degenerative disease of the joints that is clinically characterized by pain and loss of function. With no disease-modifying treatment available, current therapies aim at pain management but are of limited efficacy. Cannabis products, specifically cannabinoids, are widely used to control pain and inflammation in many diseases with no scientific evidence demonstrating their efficacy in OA. We investigated the effects of non-euphorigenic cannabis extracts, CBD oil and cannabigerol oil (CBG oil), on pain and disease progression in OA mice. Twelve-week-old male C57BL/6J mice received either sham or destabilization of the medial meniscus (DMM) surgery. DMM mice were treated with vehicle, CBD oil, or CBG oil. The gait of DMM mice was impaired as early as 2 weeks following surgery and continued deteriorating until week 8, which was restored by CBD oil and CBG oil treatments throughout the disease course. Mechanical allodynia developed in DMM mice, however, was not ameliorated by any of the treatments. On the other hand, both CBD oil and CBG oil ameliorated cold allodynia. In open field test, both oil treatments normalized changes in the locomotor activity of DMM mice. CBD oil and CBG oil treatments significantly reduced synovitis in DMM mice. Only CBG oil reduced cartilage degeneration, chondrocyte loss, and matrix metalloproteinase 13 expression, with a significant increase in the number of anabolic chondrocytes. Subchondral bone remodeling found in vehicle-treated DMM mice was not ameliorated by either CBD or CBG oil. Our results show evidence for the therapeutic efficacy of CBD oil and CBG oil, where both oils ameliorate pain and inflammation, and improve gait and locomotor activity in OA mice, representing clinical pain and function. Importantly, only CBG oil is chondroprotective, which may provide superior efficacy in future studies in OA patients.
骨关节炎(OA)是一种导致关节功能丧失的退行性疾病,其临床特征为疼痛和功能丧失。由于尚无改善病情的治疗方法,目前的治疗旨在控制疼痛,但疗效有限。大麻产品,特别是大麻素,被广泛用于控制多种疾病的疼痛和炎症,但尚无科学证据证明其对骨关节炎有效。我们研究了无致欣快作用的大麻提取物、CBD油和大麻二醇油(CBG油)对骨关节炎小鼠疼痛和疾病进展的影响。12周龄雄性C57BL/6J小鼠接受假手术或内侧半月板不稳定(DMM)手术。DMM小鼠分别接受赋形剂、CBD油或CBG油治疗。DMM小鼠的步态在手术后2周就开始受损,并持续恶化至第8周,而在整个病程中,CBD油和CBG油治疗可使其恢复。然而,DMM小鼠出现的机械性异常性疼痛并未因任何一种治疗而改善。另一方面,CBD油和CBG油均能改善冷异常性疼痛。在旷场试验中,两种油治疗均使DMM小鼠的运动活动变化恢复正常。CBD油和CBG油治疗显著减轻了DMM小鼠的滑膜炎。只有CBG油减少了软骨退变、软骨细胞丢失和基质金属蛋白酶13的表达,同时合成代谢软骨细胞数量显著增加。赋形剂治疗的DMM小鼠出现的软骨下骨重塑并未因CBD或CBG油而改善。我们的结果证明了CBD油和CBG油的治疗效果,两种油均可减轻疼痛和炎症,改善骨关节炎小鼠的步态和运动活动,反映了临床疼痛和功能。重要的是,只有CBG油具有软骨保护作用,这可能在未来对骨关节炎患者的研究中提供更好的疗效。