“Background: Cannabis (^Δ9THC), a non-selective cannabinoid receptor (CBR) agonist relieves nausea and pain. Cannabidiol (CBD), a CBR2 inverse agonist with central effects, also reduces gut sensation and inflammation.

Aims: To compare effects of 4 weeks’ treatment with pharmaceutical CBD vs. placebo in patients with idiopathic (IG) or diabetic (DM) gastroparesis.

Methods: We performed a randomized, double-blinded, placebo-controlled study of CBD b.i.d. (Epidiolex® escalated to 20mg/kg/day) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD). After 4 weeks’ treatment, we measured GES, gastric volumes, and Ensure® satiation test (1kcal/mL, 30mL/min) to assess volume to comfortable fullness (VTF) and maximum tolerance (MTV). Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using ANOVA including baseline measurements and BMI as covariates.

Results: Among 44 patients (32 IG, 6 DM1, and 6 DM2), 5 patients did not tolerate full dose escalation; 3 withdrew before completing 4 weeks’ treatment (2 placebo, 1 CBD); 95% completed 4 weeks’ treatment and diaries. Compared to placebo, CBD reduced total GCSI score (P=0.008), inability to finish a normal-sized meal (P=0.029), number of vomiting episodes/24 hours (P=0.006), and overall symptom severity (P=0.034). Patients treated with CBD had higher VTF and MTV and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14), fatigue (8), headache (8), and nausea (7).

Conclusions: CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES.”

https://pubmed.ncbi.nlm.nih.gov/37482172/

https://www.cghjournal.org/article/S1542-3565(23)00543-8/pdf