Researchers at the University of Arkansas for Medical Sciences (UAMS) and the University of Mississippi are warning in the first study of its kind that CBD supplements in high doses can be harmful to the gut microbiome.

The study, “Potential Probiotic or Trigger of Gut Inflammation – the Janus-Faced Nature of Cannabidiol-Rich Cannabis Extract,” is published in the Journal of Dietary Supplements. While sales of cannabidiol (CBD) have skyrocketed, little is known about its potential side effects, said UAMS’ Igor Koturbash, M.D., Ph.D., the study’s senior author and principal investigator.

CBD is extracted from hemp (Cannabis sativa), which was removed from the federal list of controlled substances in 2018. The research team found that when taken orally, CBD disrupts the gut microbiome of mice and can damage the inner lining of the digestive tract, known as the gut mucosa.

“Cannabidiol significantly affects the gut microbiome, which in turn may affect the mucosa,” said Koturbash, associate professor in the College of Public Health, Department of Environmental and Occupational Health, and co-director of the Center for Dietary Supplements Research. “In low doses, it may potentially improve gut health as a probiotic, but in high doses it can cause leaky gut syndrome.”

Leaky gut syndrome is characterized by gaps in the intestinal walls that allow bacteria and other toxins into the bloodstream. It has serious health consequences and can be fatal.

Koturbash said the study’s findings point to the need for clinical trials to determine the safest, most effective CBD dosages for people. 

The study involved a dozen researchers – nine from UAMS and three from the University of Mississippi. It drew expertise from several disciplines in the UAMS College of Public Health and the College of Medicine departments of Internal Medicine, Biomedical Informatics, Pharmacology and Toxicology, Pathology, and Pediatrics.

Among the changes in the gut, researchers observed multiple pro-inflammatory responses to CBD in the colon tissue. In addition, there were significant decreases in a gene that is closely associated with gut integrity.

“Taken together, these findings raise concerns about the safety of long-term CBD usage and underline the need for additional well-designed studies into its tolerability and efficacy,” the study concludes.

Other UAMS authors on the study are:

• Charles M. Skinner, B.S., senior research associate at the Center for Dietary Supplements Research, College of Public Health, Department of Environmental and Occupational Health.
• Intawat Nookaew, Ph.D., associate professor in the College of Medicine Department of Biomedical Informatics
• Laura E. Ewing, M.Sc., a Ph.D. student at the College of Medicine Department of Pharmacology and Toxicology
• Thidathip Wongsurawat, Ph.D., instructor in the College of Medicine Department of Biomedical Informatics
• Piroon Jenjaroenpun, Ph.D., instructor in the College of Medicine Department of Biomedical Informatics
• Charles M. Quick, M.D., associate professor in the College of Medicine Department of Pathology
• Eric U. Yee, M.D., assistant professor in the College of Medicine Department of Pathology
• Brian D. Piccolo, Ph.D., assistant professor in the College of Medicine Department of Pediatrics at the USDA-ARS-Arkansas Children’s Nutrition Center (ACNC), at Arkansas Children’s Hospital

University of Mississippi authors on the study are:

• Mahmoud A. ElSohly, Ph.D., research professor at The National Center for Natural Products Research, and Professor of Pharmaceutics and Drug Delivery, School of Pharmacy, and director of the National Institute on Drug Abuse (NIDA) Marijuana Project at the University of Mississippi
• Larry A. Walker, Ph.D., director emeritus of the National Center for Natural Products Research at the University of Mississippi.
• Bill J. Gurley, Ph.D., a principal scientist at the National Center for Natural Products Research at the University of Mississippi, Oxford.

The study was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant numbers 1P20GM109005 and P20GM125503; the National Institute of General Medical Sciences grant number T32GM106999; Clinical and Translational Science Awards UL1TR000039 and KL2TR000063; and the Arkansas Biosciences Institute.