Oct. 20, 2022
About 20% of the population experiences symptoms consistent with functional dyspepsia (FD), a disorder of gut-brain interaction (DGBI) affecting the upper gut. Although nonprescribed cannabis and cannabinoid agents are used in the management of patients with DGBI, evidence derived from clinical trials evaluating the efficacy of these products is scarce. To address this knowledge gap, Michael Camilleri, M.D., and colleagues conducted the first randomized, double-blind, placebo-controlled trial of pharmaceutical-grade cannabidiol (CBD) in patients with functional dyspepsia. Dr. Camilleri, a gastroenterologist at Mayo Clinic in Rochester, Minnesota, and co-authors published the results of the study in The American Journal of Gastroenterology in 2022.
Background and study goals
The Mayo Clinic researchers sought to compare the pharmacodynamics and clinical effects of a four-week treatment with CBD versus placebo in patients with functional dyspepsia and normal baseline gastric emptying. They assessed the impact of treatment on gastric motor functions and symptom response endpoints. Because variations in the cannabinoid receptor 1 (CNR1) gene and the fatty acid amide hydrolase (FAAH) gene are associated with altered gut motility and sensation, Dr. Camilleri and colleagues also examined whether these genetic variations influenced the participants' responses to treatment with CBD.
Study methods
The researchers enrolled 48 study participants ages 18 to 70 years with functional dyspepsia and nondelayed gastric emptying at baseline. The participants were randomized to two groups, with 23 receiving placebo and 25 receiving a formulation of CBD approved by the Food and Drug Administration, administered orally, twice daily for four weeks.
Participants reported symptom severity using a variety of validated instruments, including daily symptom diaries, weekly global symptom assessments, the Leuven Postprandial Distress Scale and the Short-Form Nepean Dyspepsia Index assessment of quality of life. After treatment, the patients underwent measurements of gastric emptying of solids, fasting and postprandial gastric volumes and an Ensure nutrient satiation test. The researchers compared the two treatments for all endpoints and examined whether FAAH and CNR1 gene variants (previously reported to functionally modify the genes' functions) influenced the participants' outcomes to treatment.
Results
Overall, Dr. Camilleri and colleagues noted that the effects of CBD and placebo on physiological functions and participant response outcomes were not significantly different.
"Our results demonstrated that both CBD and placebo improved symptoms when compared to baseline," explains Dr. Camilleri. "Because there was no benefit of CBD over placebo on symptoms or on diverse gastric motor functions, including gastric emptying, gastric accommodation or satiation, CBD does not appear to be indicated for treating symptoms of functional dyspepsia in patients with normal gastric emptying."
Additionally, although there were no significant CBD treatment-by-genotype interactions, Dr. Camilleri notes that "a subset of patients with a variation in the function of the gene controlling the CB1 receptor showed a borderline benefit of CBD in reducing postprandial distress."
Study limitations and next steps
Dr. Camilleri acknowledges that the size of the study does not completely exclude the potential benefit of CBD in treating patients with FD and normal gastric emptying. However, the study provides estimates of the coefficient of variation in outcomes, which can be used to project the size required for future trials.
"Demonstrating clinical benefits would thus require randomizations of at least 100 patients per treatment arm in any future placebo-controlled trial," says Dr. Camilleri. "We also need to consider that patients with functional dyspepsia often are exposed to polypharmacy, particularly with modulators of serotonergic and dopaminergic pathways. This may be an additional confounder in assessing the efficacy of CBD."
Mayo Clinic investigators are currently engaged in a single-center, placebo-controlled trial of CBD in patients with similar symptoms and delayed gastric emptying, also known as gastroparesis. Completion of that trial is expected to occur during 2023.
For more information
Atieh J, et al. Cannabidiol for functional dyspepsia with normal gastric emptying: A randomized controlled trial. The American Journal of Gastroenterology. 2022;117:1296.
Refer a patient to Mayo Clinic.