CBD and PEA Reduced Gut-Barrier Disruption in a Small Human Study
A 2019 study found that cannabidiol (CBD) and palmitoylethanolamide (PEA) reduced a temporary increase in intestinal permeability in healthy volunteers. The findings suggest that both compounds may influence the gut barrier, but they do not show that CBD can treat inflammatory bowel disease (IBD).
Published in Inflammatory Bowel Diseases, the University of Nottingham study combined laboratory experiments with a small randomized, double-blind, placebo-controlled human trial. The researchers examined whether CBD and PEA could counteract inflammation-related changes in the intestinal barrier.
The gut lining acts as a selective barrier. It allows water and nutrients to pass into the body while limiting the movement of potentially harmful substances, including bacteria and bacterial components. Inflammation can disrupt this barrier, a feature associated with conditions such as Crohn’s disease and ulcerative colitis. Symptoms of IBD can include abdominal pain, diarrhea, rectal bleeding, fatigue and weight loss; more background is available from the National Institute of Diabetes and Digestive and Kidney Diseases.
For the human portion of the study, 30 healthy male participants received 600 milligrams of CBD, 600 milligrams of PEA or a placebo alongside 600 milligrams of aspirin. Aspirin was used to produce a short-lived increase in gut permeability. Participants then consumed lactulose and mannitol, two sugar probes that can be measured in urine to estimate how readily substances cross the intestinal lining.
Mannitol is relatively small and is normally absorbed through the intestine, while the larger molecule lactulose passes through more readily when the barrier is disrupted. Researchers therefore assessed both sugars and calculated the lactulose-to-mannitol ratio, or LMR. In the placebo group, aspirin increased urinary concentrations of both sugars and raised the LMR, consistent with increased permeability. Participants who received CBD or PEA showed smaller increases in these measures, and their LMRs were significantly lower than those of the aspirin-and-placebo group.
The study also reported supportive findings from experiments using cultured intestinal cells and human colonic tissue obtained during surgery. In those models, CBD and PEA reduced the movement of dextran molecules across inflamed cell layers. CBD also prevented an inflammation-associated reduction in claudin-5 messenger RNA in human colonic tissue, while both compounds affected signaling pathways and other markers involved in intestinal-barrier function.
However, the results have important limitations. The participants were healthy people without IBD, and the researchers did not test whether CBD or PEA reduced bowel symptoms, intestinal inflammation, disease activity or complications in patients with Crohn’s disease or ulcerative colitis. In addition, aspirin-induced permeability is only a temporary experimental model and may not reproduce the complex immune processes involved in IBD. Six participants in the PEA group had undetectable mannitol levels, preventing calculation of their LMRs and leading to their exclusion from that analysis. The trial was also not registered on a clinical-trials registry.
The findings provide an early indication that CBD and PEA may affect intestinal-barrier function in humans. They do not establish CBD as an IBD therapy, identify an appropriate dose for patients, or demonstrate long-term safety or effectiveness. The U.S. Food and Drug Administration warns that nonprescription CBD products have not been evaluated for their safety, effectiveness, dosage or potential drug interactions; its CBD guidance notes that the agency has approved a prescription CBD product for certain seizure disorders, not for IBD. Patients should not replace prescribed IBD treatment with CBD without discussing it with a qualified health professional.
