一项随机、对照试验研究了大麻二酚在特发性和糖尿病性胃轻瘫中的疗效和安全性。
A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis.
机构信息
Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
出版信息
Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22.
BACKGROUND & AIMS: Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis.
METHODS
We performed a randomized, double-blinded, placebo-controlled study of CBD twice daily (Epidiolex escalated to 20 mg/kg/d; Jazz Pharmaceuticals, Dublin, Ireland) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by the Gastroparesis Cardinal Symptom Index Daily Diary. After 4 weeks of treatment, we measured GES, gastric volumes, and Ensure (Abbott Laboratories, Abbott Park, IL) satiation test (1 kcal/mL, 30 mL/min) to assess volume to comfortable fullness and maximum tolerance. Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using analysis of variance including baseline measurements and body mass index as covariates.
RESULTS
Among 44 patients (32 idiopathic, 6 diabetes mellitus type 1, and 6 diabetes mellitus type 2), 5 patients did not tolerate full-dose escalation; 3 withdrew before completing 4 weeks of treatment (2 placebo, 1 CBD); 95% completed 4 weeks of treatment and diaries. Compared with placebo, CBD reduced the total Gastroparesis Cardinal Symptom Index score (P = .008), inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall symptom severity (P = .034). Patients treated with CBD had a higher volume to comfortable fullness and maximum tolerance and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14 patients), fatigue (8 patients), headache (8 patients), and nausea (7 patients).
CONCLUSIONS
CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES.
CLINICALTRIALS
gov NCT #03941288.
背景与目的
大麻（Δ-9-四氢大麻酚），一种非选择性大麻素受体激动剂，可缓解恶心和疼痛。大麻素受体 2 反向激动剂 CBD（具有中枢作用）也可减少肠道感觉和炎症。我们比较了 4 周治疗期内使用药用 CBD 与安慰剂治疗特发性或糖尿病（糖尿病）胃轻瘫患者的效果。
方法
我们对胃排空延迟的非手术性胃轻瘫患者（固体 GES）进行了 CBD 每日两次（Epidiolex 逐渐增至 20 mg/kg/d；都柏林 Jazz 制药公司，爱尔兰）的随机、双盲、安慰剂对照研究。通过胃轻瘫卡特尔症状指数日常日记评估症状。治疗 4 周后，我们测量了 GES、胃容量和确保（雅培实验室，雅培公园，IL）饱腹感测试（1 kcal/mL，30 mL/min），以评估达到舒适饱腹感和最大耐量所需的容量。患者接受了特定的 FAAH 和 CNR1 基因分型。使用包括基线测量和体重指数作为协变量的方差分析比较 2 种治疗方法。
结果
在 44 名患者（32 名特发性、6 名 1 型糖尿病和 6 名 2 型糖尿病）中，有 5 名患者不能耐受全剂量递增；3 名患者在完成 4 周治疗前退出（2 名安慰剂，1 名 CBD）；95%的患者完成了 4 周的治疗和日记记录。与安慰剂相比，CBD 降低了总胃轻瘫卡特尔症状指数评分（P =.008）、无法完成正常大小的餐食（P =.029）、24 小时内呕吐次数/天（P =.006）和整体症状严重程度（P =.034）。接受 CBD 治疗的患者有更高的舒适饱腹感和最大耐量，并且 GES 更慢。FAAH rs34420 基因型显著影响营养饮料摄入。报告的最常见不良事件是腹泻（14 例）、疲劳（8 例）、头痛（8 例）和恶心（7 例）。
结论
CBD 可缓解胃轻瘫患者的症状，并改善液体营养摄入的耐受性，尽管 GES 减慢。
临床试验
gov NCT #03941288。
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