Oct. 31, 2023
Individuals with gastroparesis experience a variety of upper gastrointestinal symptoms, including nausea, bloating, abdominal pain, vomiting, early satiety and postprandial fullness. The condition is characterized by delays in gastric emptying of solids that are not due to a mechanical obstruction. Often idiopathic or secondary to diabetes mellitus, gastroparesis can develop after surgery or a viral or bacterial infection. Other risk factors include use of medications that impair gastric emptying, as well as neurological or autoimmune disorders.
According to Michael Camilleri, M.D., D.Sc., a gastroenterologist and researcher at Mayo Clinic in Rochester, Minnesota, there is a significant unmet need in the treatment of gastroparesis.
"The only medication approved by the Food and Drug Administration (FDA) is metoclopramide, which has a black box warning and cannot be prescribed for more than 12 weeks, due to adverse effects," explains Dr. Camilleri.
Because metoclopramide has known adverse effects, many patients with gastroparesis use cannabis to relieve their symptoms. Concerns about the psychological effects associated with cannabis, however, have led researchers to study the use of cannabidiol, also known as CBD, to treat gastroparesis.
"CBD acts through peripheral cannabinoid type 2 receptors to reduce sensation and inflammation," explains Dr. Camilleri. "It also has central effects that reduce anxiety and pain by actions on other receptors, without causing the psychic effects associated with cannabis."
Published evidence derived from clinical trials evaluating the efficacy and safety of CBD in patients with gastrointestinal disorders is still scarce. That fact led Dr. Camilleri and Mayo Clinic colleagues to conduct a randomized controlled trial investigating the use of CBD in patients with gastroparesis. Their goal was to compare the effects of four weeks of treatment with a pharmaceutical-grade, FDA-approved formulation of CBD versus placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis. The results of this study were published in Clinical Gastroenterology and Hepatology in 2023.
Methods
The researchers identified 44 patients with nonsurgical gastroparesis (32 with idiopathic, six with diabetes mellitus type 1 and six with diabetes mellitus type 2). Study participants were divided into two groups, and each participant received twice-daily, escalating doses of either CBD (administered as a formulation approved by the FDA for seizure disorders) or placebo for four weeks. Participants' symptoms were assessed using the Gastroparesis Cardinal Symptom Index Daily Diary.
After four weeks of treatment, the researchers measured participants' gastric emptying of solids (GES) and gastric volumes. They also conducted a nutrient drink satiation test (1 kcal/mL, 30 mL/min) to assess participants' volume to comfortable fullness and maximum tolerance. Participants underwent genotyping of specific fatty acid amide hydrolase (FAAH) and cannabinoid receptor 1 (CNR1) genes. The researchers then compared the effects of treatment with CBD versus placebo using analysis of variance, including baseline measurements and body mass index as covariates.
Results
Overall, Dr. Camilleri and co-investigators observed that participants in the CBD group had favorable outcomes.
"CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing GES ," says Dr. Camilleri. "In patients with idiopathic or diabetic gastroparesis, we observed that CBD reduced the total Gastroparesis Cardinal Symptom Index scores, the inability to finish a normal-sized meal, the number of vomiting episodes in 24 hours and overall severity of gastroparesis symptoms. Patients treated with CBD also tolerated a greater volume of a nutrient drink volume when invited to drink as much as was tolerated."
Dr. Camilleri notes that the results from this single center, placebo-controlled study should be replicated in a multicenter, placebo-controlled trial.
For more information
Zheng T, et al. A randomized, controlled trial of efficacy and safety of cannabidiol in idiopathic and diabetic gastroparesis. Clinical Gastroenterology and Hepatology. In press.
Refer a patient to Mayo Clinic.