A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis

Abstract

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.

Trial registration: ClinicalTrials.gov NCT03941288.

Keywords: Accommodation; Cannabinoid; FAAH; Receptor; Satiation; Stomach.

Figure 1.. Experimental design:

After screening and baseline measurement of symptoms based on daily diary, patients with gastroparesis were randomized to 4 weeks’ treatment with oral CBD or placebo. Patients underwent gastric emptying of solids at baseline, and tests of GES, volumes, and satiation at end of treatment. At baseline and (GES) throughout the study, suicidal risk was assessed using the Columbia-suicide severity risk scale (C-SSRS). AE=adverse events; BDQ=Bowel Disease Questionnaire; HAD=Hospital Anxiety Depression scale.

Figure 2.. Effects of 4 weeks’ treatment with cannabidiol (n=21) or placebo (n=23) on GCSI components measured daily.

Analysis is based on ANCOVA with BMI and baseline symptoms as covariates. Left panel shows summary of the six elements in the GCSI as total GCSI, and the perceived severity of the gastroparesis (both statistically significant between the two treatments); right panel shows individual symptoms with significant improvements.

CONSORT FLOW DIAGRAM