Am J Gastroenterol. 2022 May 9. doi: 10.14309/ajg.0000000000001805. Online ahead of print.


Background: Cannabidiol (CBD), a CBR2 agonist with limited psychic effects, antagonizes CB1/CB2 receptors. Allelic variation CNR1 (gene for CBR1) rs806378 and FAAH rs324420 were associated with altered gut motility and sensation. This study aimed to compare pharmacodynamics and clinical effects of 4-week treatment with pharmaceutical grade CBD vs. placebo and also to assess interactions of FAAH and CNR1 gene variants on effects of CBD in patients with functional dyspepsia (FD).

Methods: We performed a randomized, double-blinded, placebo-controlled (1:1 ratio) study of CBD b.i.d. (20mg/kg/day according to FDA escalation guidance) in FD patients with non-delayed gastric emptying (GE) at baseline. Symptoms were assessed by validated daily symptom diary (0-4 scale for upper abdominal pain, nausea, bloating), weekly assessment of adequate relief, Leuven Postprandial Distress Scale (LPDS, 8 symptoms, adjectival scores rated 0-4 for severity), and quality of life [Short Form Nepean Dyspepsia Index (average of 10 dimensions each on 5-point scale)]. After 4-week treatment, all patients underwent measurements of GE of solids, gastric volumes, and Ensure® nutrient satiation test. Statistical analysis compared 2 treatments for all endpoints and effects of CBD in association with FAAH rs324420 and CNR1 rs806378.

Results: CBD and placebo effects on physiological and patient response outcomes were not significantly different. There were borderline CBD treatment-by-genotype interactions: rs806378 CNR1 with LPDS (p=0.06), and GE solids (p=0.12).

Discussion: Approved doses of CBD used off-label do not relieve FD with normal baseline GE solids or alter gastric motor functions and satiation. CBD treatment-by-gene interactions suggest potential benefit for postprandial distress with CNR1 rs806378 T allele.