Forthcoming NIDA-Funded Study to Investigate Cannabis, the Oral Microbiome, and Neurological Impacts

Cannabis researchers are on the cusp of a new discovery that could have a major impact on the way people consume their stash. Wei Jiang, M.D., a professor of Microbiology and Immunology at the Medical University of South Carolina (MUSC), and her team are keen to find out more about the cannabis-caused changes to the oral microbiome and their impacts on neurological disease.

They’re already halfway there, with a December 2021 EBioMedicine cannabis oral microbiome study displaying oral microbiome (the bacteria that live inside the mouth) alterations after frequent cannabis use. Now, thanks to a fresh source of funding from the National Institute on Drug Abuse (NIDA), Jiang and her clang are in a prime position to accurately identify the specific effects of common cannabinoids on oral microbiome dysbiosis and mental health.

Specifically, the new grant funding ($3.7 million) will be used to investigate the underlying mechanisms that connect high levels of A. meyeri in the oral microbiome of regular cannabis consumers to the risks of neurological disease. “We think that long-term exposure to THC, but not CBD, will increase levels of A. meyeri in saliva and lead to harmful neurological effects in mice,” said Jiang. 

Amsterdam Boat Tour Inspired Research Into Cannabis and the Oral Microbiome

Plumes of cannabis smoke, a picturesque canal, and Amsterdam’s historically charming buildings served as the setting for Jiang’s inspiration ahead of her first scientific foray into cannabis and the oral microbiome.

“Everyone was smoking cannabis except me,” said Jiang, as she described a life-changing moment aboard an Amsterdam boat tour during an international conference in 2018. “I was studying the microbiome at the time, so after talking to them, I figured out their oral health was affected by smoking and wanted to understand this further.”

Despite being one of the most commonly used drugs in the U.S. with numerous purported mental benefits, including mood improvement and anxiety relief, Jiang noted that consumers might be at higher risk of memory, learning, and motor skill impairment if they use cannabis regularly. Moreover, she noted that smokable cannabis contains harmful compounds that can negatively impact oral health. When changes occur in the oral microbiome unnaturally, it is referred to as “dysbiosis.”

Dysbiosis can lead to organ (and even brain) damage caused by an influx of harmful bacteria entering the mouth and spreading throughout the blood. People who experience abnormalities and changes in oral bacteria may be more likely to have a preterm birth, Alzheimer’s disease, and cardiovascular disease.

“Psychological dependency on a drug can have harmful neurological effects, but we don’t know what is driving these effects in heavy cannabis users. We know that oral health affects your mental health. However, we don’t know exactly what role the microbiome plays,” explained Jiang, adding that “this will be the first study to investigate the cannabis-altered oral microbiome and its effects on the brain.”

Specific Effects of Cannabinoids to Be Outlined in Forthcoming Study

Jiang hopes that her new research effort will build off of the solid foundation that she and her collaborators laid during a December 2021 EBioMedicine study of cannabis use and the oral microbiome. 

The South Carolina Clinical and Translational Research Institute funded her previous research effort, which highlighted abnormally high levels of the bacterium Actinomyces meyeri (A. meyeri) in regular marijuana consumers but not in cocaine or tobacco users. “In general, the amount of A. meyeri should be very low in a healthy oral microbiome,” said Jiang, whose team analyzed rodents that were exposed to A. meyeri orally over a six-month period.

Based on the results, the mice had more inflammation and amyloid-beta proteins in their brains. Studies like this one published in the Journal Nature have drawn a connection between these proteins and Alzheimer’s disease. “After we saw these changes in mice given this bacterium, we became very intrigued by what was happening in their brains,” said Jiang.

The new research initiative will involve exposing mice to varying levels of cannabidiol (CBD) and tetrahydrocannabinol (THC) to understand their effects on A. meyeri. In her previous work, Jiang did not identify which cannabinoid was causing the changes.

The research will also take place outside of mouse models and look into human cases of cannabis use disorder to ascertain how changes in the oral microbiome influence memory. 

“We expect memory-related deficits to be associated with greater levels of A. meyeri in frequent cannabis users compared with nonusers,” said Jiang. “If our hypothesis is correct, a therapeutic strategy targeting A. meyeri could reduce irregularities in brain function in frequent cannabis users,” said Jiang. “In the future, it may also be useful to screen for certain bacteria as biomarkers of different diseases that affect the brain, such as Alzheimer’s disease.”