School of Nursing (S.O.V., S.G.K.) and Department of Psychological Sciences (S.O.V.), University of Connecticut, Storrs, Connecticut; Department of Orthodontics (A.Z., C.N.D.) and Department of Biomedical Engineering (C.N.D.), School of Dental Medicine, University of Connecticut, Farmington, Connecticut; and Department of Orthopedic Surgery and Department of Cell Biology, School of Medicine, University of Connecticut, Farmington, Connecticut (C.N.D.).
School of Nursing (S.O.V., S.G.K.) and Department of Psychological Sciences (S.O.V.), University of Connecticut, Storrs, Connecticut; Department of Orthodontics (A.Z., C.N.D.) and Department of Biomedical Engineering (C.N.D.), School of Dental Medicine, University of Connecticut, Farmington, Connecticut; and Department of Orthopedic Surgery and Department of Cell Biology, School of Medicine, University of Connecticut, Farmington, Connecticut (C.N.D.)
J Pharmacol Exp Ther. 2024 Oct 18;391(2):222-230. doi: 10.1124/jpet.124.002189.
Patients with arthritis report using cannabis for pain management, and the major cannabinoid delta-9-tetrahydrocannabinol (Δ-THC) has anti-inflammatory properties, yet the effects of minor cannabinoids on arthritis are largely unknown. The goal of the present study was to determine the antiarthritic potential of the minor cannabinoid delta-8-tetrahydrocannabinol (Δ-THC) using the collagen-induced arthritis (CIA) mouse model. Adult male DBA/1J mice were immunized and boosted 21 days later with an emulsion of collagen and complete Freund's adjuvant. Beginning on the day of the booster, mice were administered twice-daily injections of Δ-THC (3 or 30 mg/kg), the steroid dexamethasone (2 mg/kg), or vehicle for two weeks. Dorsal-ventral paw thickness and qualitative measures of arthritis were recorded daily, and latency to fall from an inverted grid was measured on alternating days, to determine arthritis severity and functional impairment. On the final day of testing, spontaneous wire-climbing behavior and temperature preference in a thermal gradient ring were measured to assess CIA-depressed behavior. The Δ-THC treatment (30 mg/kg) reduced paw swelling and qualitative signs of arthritis. Δ-THC also blocked CIA-depressed climbing and CIA-induced preference for a heated floor without producing locomotor effects but did not affect latency to fall from a wire grid. In alignment with the morphologic and behavioral assessments in vivo, histology revealed that Δ-THC reduced synovial inflammation, proteoglycan loss and cartilage and bone erosion in the foot joints in a dose-dependent manner. Together, these findings suggest that Δ-THC not only blocked morphologic changes but also prevented functional loss caused by collagen-induced arthritis. SIGNIFICANCE STATEMENT: Despite increasing use of cannabis products, the potential effects of minor cannabinoids are largely unknown. Here, the minor cannabinoid delta-8-tetrahydrocannabinol blocked the development of experimentally induced arthritis by preventing both pathophysiological as well as functional effects of the disease model. These data support the development of novel cannabinoid treatments for inflammatory arthritis.
关节炎患者报告使用大麻来进行疼痛管理，而主要大麻素Δ-9-四氢大麻酚（Δ-THC）具有抗炎特性，但关于次要大麻素对关节炎的影响在很大程度上尚不清楚。本研究的目的是使用胶原诱导性关节炎（CIA）小鼠模型来确定次要大麻素Δ-8-四氢大麻酚（Δ-THC）的抗关节炎潜力。成年雄性 DBA/1J 小鼠用胶原和完全弗氏佐剂的乳液免疫并加强 21 天后。从加强之日起，每天给小鼠两次注射Δ-THC（3 或 30mg/kg）、类固醇地塞米松（2mg/kg）或载体，持续两周。每天记录背-腹爪厚度和关节炎的定性测量值，每隔一天测量从倒置网格上跌落的潜伏期，以确定关节炎的严重程度和功能障碍。在测试的最后一天，通过测量在热梯度环中的自发攀爬行为和对温度的偏好来评估 CIA 引起的行为抑制。Δ-THC 处理（30mg/kg）可减轻爪肿胀和关节炎的定性体征。Δ-THC 还阻止了 CIA 引起的攀爬抑制和 CIA 引起的对加热地板的偏好，而没有产生运动效应，但不影响从金属丝网格上跌落的潜伏期。与体内形态学和行为评估一致，组织学显示Δ-THC 以剂量依赖的方式减少了滑膜炎症、蛋白聚糖丢失以及足部关节的软骨和骨侵蚀。总之，这些发现表明，Δ-THC 不仅阻断了形态学变化，而且防止了胶原诱导性关节炎引起的功能丧失。意义声明：尽管大麻素产品的使用不断增加，但次要大麻素的潜在影响在很大程度上尚不清楚。在这里，次要大麻素Δ-8-四氢大麻酚通过预防疾病模型的生理病理和功能影响，阻止了实验性诱导关节炎的发展。这些数据支持开发新型大麻素治疗炎症性关节炎。
