Shilo-Benjamini Yael, Lavy Eran, Yair Nadav, Milgram Joshua, Zilbersheid Daniel, Hod Atara, Barasch Dinorah, Abu Ahmad Wiessam, Cern Ahuva, Barenholz Yechezkel
Department of Biochemistry, Hadassah Medical School, Laboratory of Membrane and Liposome Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Front Vet Sci. 2023 Aug 23;10:1224452. doi: 10.3389/fvets.2023.1224452. eCollection 2023.
Osteoarthritis is a common disease in dogs resulting in chronic pain and decreased wellbeing. Common analgesics such as non-steroidal anti-inflammatories may fail to control pain and can produce major adverse effects. Study objectives were to evaluate pharmacokinetics, therapeutic efficacy, and safety of subcutaneous liposomal-cannabidiol (CBD) as an additional analgesic therapy in dogs suffering from naturally-occurring osteoarthritis.
Six such dogs were recruited following ethics approval and owner consent. Dogs were administered a single subcutaneous injection of 5 mg/kg liposomal-CBD. Plasma concentrations of CBD, blood work, activity monitoring collar data, wellbeing questionnaire (owners) and pain scoring (veterinarian) were performed at baseline and monitored up to six weeks following intervention. Data overtime were compared with baseline using linear-regression mixed-effects. -value was set at 0.05.
CBD plasma concentrations were observed for 6 weeks; median (range) peak plasma concentration (C) was 45.2 (17.8-72.5) ng/mL, time to C was 4 (2-14) days and half-life was 12.4 (7.7-42.6) days. Median (range) collar activity score was significantly increased on weeks 5-6; from 29 (17-34) to 34 (21-38). Scores of wellbeing and pain evaluations were significantly improved at 2-3 weeks; from 69 (52-78) to 53.5 (41-68), and from 7.5 (6-8) to 5.5 (5-7), respectively. The main adverse effect was minor local swelling for several days in 5/6 dogs.
Liposomal-CBD administered subcutaneously produced detectable CBD plasma concentrations for 6 weeks with minimal side effects and demonstrated reduced pain and increased wellbeing as part of multimodal pain management in dogs suffering from osteoarthritis. Further placebo-controlled studies are of interest.
骨关节炎是犬类的一种常见疾病，会导致慢性疼痛和健康状况下降。常见的镇痛药如非甾体抗炎药可能无法控制疼痛，还会产生严重的不良反应。本研究的目的是评估皮下注射脂质体大麻二酚（CBD）作为患有自然发生的骨关节炎犬类的辅助镇痛疗法的药代动力学、治疗效果和安全性。
在获得伦理批准并征得主人同意后，招募了6只此类犬。给犬单次皮下注射5mg/kg脂质体CBD。在基线时检测CBD的血浆浓度、血液指标、活动监测项圈数据、健康问卷（主人填写）和疼痛评分（兽医评定），并在干预后的六周内进行监测。使用线性回归混合效应模型将随时间变化的数据与基线数据进行比较。P值设定为0.05。
观察到CBD血浆浓度持续6周；血浆峰值浓度（Cmax）的中位数（范围）为45.2（17.8 - 72.5）ng/mL，达峰时间为4（2 - 14）天，半衰期为12.4（7.7 - 42.6）天。第5 - 6周时，项圈活动评分中位数（范围）显著增加；从29（17 - 34）增至34（21 - 38）。健康和疼痛评估评分在第2 - 3周时显著改善；分别从69（52 - 78）降至53.5（41 - 68），以及从7.5（6 - 8）降至5.5（5 - 7）。主要不良反应是6只犬中有5只出现了持续数天的轻微局部肿胀。
皮下注射脂质体CBD可在6周内检测到CBD血浆浓度，副作用最小，并在患有骨关节炎的犬类多模式疼痛管理中显示出疼痛减轻和健康状况改善。进一步开展安慰剂对照研究很有意义。
