Glare Paul, Chye Richard, Bloch Mark, Arya Mark, Moore Andrew, Montgomery John
Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
School of Clinical Medicine, UNSW, Sydney, NSW, Australia.
Med Cannabis Cannabinoids. 2023 Jul 7;6(1):66-76. doi: 10.1159/000531232. eCollection 2023 Jan-Dec.
The aim was to demonstrate the safety and tolerability of cannabidiol (CBD) with Δ9-THC in patients with moderate to severe chronic back or neck pain unresponsive to over-the-counter non-opioid analgesics.
This was a non-randomized, single-arm, open-label study. Participants received escalating doses of an oromucosal-administered combination containing 10 mg/mL of Δ9-THC, 25 mg/mL of CBD. On day 1, patients received once-daily 0.5 mL Cybis 10:25 (5 mg Δ9-THC plus 12.5 mg CBD daily), escalated at days 8, 15, and 22 to 0.5 mL twice-daily (bd) (10 mg Δ9-THC plus 25 mg CBD daily), 1.0 mL bd (20 mg Δ9-THC plus 50 mg CBD daily), and 1.5 mL bd (30 mg Δ9-THC plus 75 mg CBD daily), respectively. The primary outcome was safety and tolerability, with secondary objectives including pharmacokinetic and efficacy outcomes.
28 patients were enrolled in the study. Their median age was 63.3 years, and half were female. The median history of neck/back pain was 10 years. The pharmacokinetics following single doses of 0.5 mL were variable; however, there were dose-dependent increases in trough levels of CBD and Δ9-THC. Cybis 10:25 was well tolerated, with the majority of adverse events of mild severity. The most common adverse events were nausea, vomiting, fatigue, dizziness, headache, paresthesia, and anxiety. There were dose-dependent improvements in numerical pain rating scores ( < 0.001), with clinically significant reductions in pain at 1.0 mL bd and 1.5 mL bd doses (28.8% and 34.1% reductions, respectively, < 0.001). Depressive symptoms and stress had dose-dependent reductions ( = 0.0182, < 0.01, respectively).
In patients with chronic neck/back pain, CBD and Δ9-THC are well tolerated and doses of 1.0 mL bd and 1.5 mL bd showed clinically significant reductions in pain compared to baseline pain scores.
目的是证明大麻二酚（CBD）与Δ9-四氢大麻酚（Δ9-THC）联合使用对中度至重度慢性背痛或颈痛且对非处方非阿片类镇痛药无反应的患者的安全性和耐受性。
这是一项非随机、单臂、开放标签研究。参与者接受递增剂量的经口腔黏膜给药的组合药物，其中含有10mg/mL的Δ9-THC和25mg/mL的CBD。在第1天，患者每日一次接受0.5mL Cybis 10:25（每日5mg Δ9-THC加12.5mg CBD），在第8、15和22天分别递增至每日两次（bid）0.5mL（每日10mg Δ9-THC加25mg CBD）、每日两次1.0mL（每日20mg Δ9-THC加50mg CBD）和每日两次1.5mL（每日30mg Δ9-THC加75mg CBD）。主要结局是安全性和耐受性，次要目标包括药代动力学和疗效结局。
28名患者参与了该研究。他们的中位年龄为63.3岁，半数为女性。颈/背痛的中位病史为10年。单次服用0.5mL后的药代动力学存在差异；然而，CBD和Δ9-THC的谷浓度呈剂量依赖性增加。Cybis 10:25耐受性良好，大多数不良事件为轻度。最常见的不良事件是恶心、呕吐、疲劳、头晕、头痛、感觉异常和焦虑。数字疼痛评分（Numeric Pain Rating）得分有剂量依赖性改善（<0.001），在每日两次1.0mL和每日两次1.5mL剂量时疼痛有临床显著降低（分别降低28.8%和34.1%，<0.001）。抑郁症状和压力有剂量依赖性降低（分别为=0.0182，<0.01）。
在慢性颈/背痛患者中，CBD和Δ9-THC耐受性良好，与基线疼痛评分相比，每日两次1.0mL和每日两次1.5mL剂量显示出疼痛有临床显著降低。
