Researchers from universities in South Carolina and North Carolina were awarded $3.7 million to explore further alterations that cannabis smoking makes to the community of microorganisms in the mouth and how those changes affect the brain.
It is the first study to investigate the cannabis-altered oral microbiome and its effects on the brain, Dr. Wei Jiang, a professor of microbiology and immunology at the Medical University of South Carolina, said in a university press release dated January 12.
"Psychological dependency on a drug can have harmful neurological effects, but we don't know what is driving these effects in heavy cannabis users," Jiang said. "We know that oral health affects your mental health. However, we don't know exactly what role the microbiome plays."
Currently, 21 states and the District of Columbia have approved adult possession and consumption of recreational marijuana, and 31 have approved medical marijuana use. As more states legalize recreational and medical marijuana, cannabis use increases. In November 2022, the ADA reported that about half of U.S. dentists say that patients have arrived at appointments high on marijuana or other drugs, and more patients are telling clinicians that they regularly use cannabis now that it has been legalized in many states.
Additionally, heart diseases, preterm birth, and Alzheimer's disease have been associated with changes in oral bacteria. Dysbiosis in the oral microbiome allows harmful bacteria to thrive in the mouth and even enter the bloodstream, damaging other organs, such as the brain.
In research published in December 2021, Jiang and her collaborators at the University of North Carolina at Chapel Hill showed that frequent cannabis use alters the oral microbiome. In addition, they found unusually high levels of the bacterium Actinomyces meyeri (A. meyeri) in frequent cannabis users but not in those who used tobacco or cocaine. Generally, a person with a healthy oral microbiome has a very low amount of A. meyeri.
For six months, mice that were orally exposed to A. meyeri showed elevated inflammation and more amyloid-beta proteins, which are the proteins thought to be associated with long-term memory loss and Alzheimer's disease, according to the release.
"After we saw these changes in mice given this bacterium, we became very intrigued by what was happening in their brains," Jiang said in the release.
The new funding, which was provided by the National Institute on Drug Abuse, will enable the team to explore the mechanisms underlying the link between high levels of A. meyeri in the mouths of frequent cannabis users and neurological disease. Specifically, the authors will focus on what component of cannabis -- the psychoactive element tetrahydrocannabinol (THC) or the nonpsychoactive cannabidiol (CBD) -- causes changes to the oral microbiome. THC and CBD interact with the brain and nervous system in different ways.
To identify the specific effects of THC and CBD on oral microbiome dysbiosis and mental health, the researchers will expose mice to different levels of each cannabis component to determine how they affect A. meyeri levels, Jiang said in the release.
Jiang hypothesizes 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. After the animal study concludes, they will focus on people with cannabis use disorder and how their changed oral microbiomes affect memory, according to the release.
Finally, the research allows Jiang and her colleagues to lay a foundation for developing therapies that target the oral microbiome in frequent cannabis users with neurological disorders.
"If our hypothesis is correct, a therapeutic strategy targeting A. meyeri could reduce irregularities in brain function in frequent cannabis users," Jiang said. "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."
