in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.
There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.
The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.
They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.
Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.
The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).
CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.
There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.
Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.
Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.
CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.
Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.
The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.