Combating Periodontal Diseases With Cannabidiol

Periodontal diseases are highly prevalent around the globe, affecting approximately 538 million individuals worldwide. In the United States, 64.7 million adults (46%) age 30 and older are impacted.^1–4

Periodontal diseases are chronic disorders of the periodontium, and many modalities exist to combat, reduce, and prevent these oral health problems.^5,6 In some instances, adjunctive local and systemic antibiotic therapies and even surgery may be necessary. A new and emerging modality, however, cannabidiol (CBD) may help reduce the inflammatory response associated with this chronic destructive disease. 

Background 

Used for centuries, the Cannabis plant has both medicinal and recreational purposes.⁷ Its two principal compounds—tetrahydrocannabinol (THC) and CBD—are referred to as cannabinoids.^7-9 More than 100 types of cannabinoids exist. They are classified as: 

• Either endogenous (a substance created within the body) or endocannabinoids (produced in humans and animals and used as lipid messengers)
• Synthetic (produced in a laboratory)
• Phytocannabinoid (from stalks, seeds, leaves, and flowers of the cannabis plant)

In addition to THC and CBD, other cannabinoids include cannabinol (CBN), cannabigerol (CBG), and cannabichromene (CBC).^7–9 

Cannabinoids are a group of secondary metabolites that act on the cellular cannabinoid receptors (CB1 and CB2) throughout the body’s endocannabinoid system. These receptors possess lipophilic ligands derived from arachidonic acid, an essential fatty acid that is necessary for chemical messaging.¹⁰ The CB1 receptor is most abundant in the cerebellum, hippocampus, and basal ganglia of the brain, and is also located in peripheral sites, such as the heart, lungs, adrenal glands, and peripheral neurons. CB1 receptors are also found in retinal; fat; intestinal; and reproductive tissues (testes, sperm cells, uterus, and ovary).¹⁰ The CB2 receptor is chiefly expressed in immune cells (spleen, tonsils, thymus) and has been shown to exert anti-inflammatory effects on leukocytes.¹¹ Recent evidence indicates that the CB2 receptor is also present in central nervous tissue, and both receptors are known to bind endocannabinoids and phytocannabinoids.^10,11 Unlike the cannabinoid CBD, THC acts mainly on the CB1 receptor of the central nervous system contributing to psychotropic effects such as alterations in mood, behavior, thoughts, and perception. 

CBD has anti-inflammatory, antimicrobial, immunomodulatory, and antioxidant properties, which help in preventing inflammation, regulating the immune system, and protecting cells from tissue damage.^8,12 Various forms of CBD have been used to effectively reduce and prevent seizures in patients with severe pediatric epilepsy, help quell anxiety and improve insomnia, and alleviate chronic pain associated with cancer, nausea, neuropathic pain, and multiple sclerosis.^8,12–14 Studies have shown CBD provides protective effects in those who have experienced stroke and in patients with Alzheimer disease who have amyloid plaques; CBD may even help patients with Huntington disease and Parkinson disease.¹² 

Cannabidiol and other cannabinoids have demonstrated antimicrobial effects against deadly bacteria including methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile.^15,16 

Dental Research 

The inflammatory response of periodontal diseases directly impacts systemic health. Inflammation, whether chronic or acute, results in a host response. Activation of either the inflammatory (innate) and/​or immune (adaptive) system triggers the body to initiate a series of protective responses, including the secretion of sulcular fluid composed primarily of leukocytes, enzymes, and other cellular elements. The stimulation of the inflammatory response system is largely responsible for tissue destruction in periodontal diseases. 

Cytokines, prostaglandins, and matrix metalloproteinases are among several biochemical mediators that initiate tissue destruction and bone loss in chronic inflammatory disease.¹⁷ The anti-inflammatory, antibacterial, and immunomodulatory properties of CBD have prompted researchers to investigate its ability to combat periodontal diseases. 

Napimoga et al¹⁸ induced periodontitis in rats and compared the treatment with CBD vs a saline control. In this in vivo study, the control group did not receive a suture but did receive the injection. In the two other groups, a suture was placed around the mandibular first molar and the rats were divided into groups: 

• Control group: no suture placement but still injected with saline
• Suture injected with saline
• Suture injected with CBD (5 mg/​kg)

After 30 days, the animals were euthanized and the right and left mandibular areas were reviewed to determine bone loss. The gingival tissues were also removed, and interleukin-1β levels, tumor necrosis factor levels, and neutrophil infiltration were evaluated. Results showed that the rats who received daily intraperitoneal injections with CBD for 30 days had less alveolar bone loss, and the gingival tissue had decreased neutrophil migration compared to the control group. Reduced neutrophil migration signifies a depression in pro-inflammatory markers, suggesting that the modulation of the host response by CBD may be an alternative method to traditional periodontal treatment approaches. 

Vasudevan and Stahl^19–21 conducted three studies on human subjects using dental plaque from patients with varying levels of periodontal diseases. The studies investigated CBD’s antibacterial properties in toothpaste, mouthrinse, and tooth polishing powder. In the first study, the researchers compared cannabinoids and toothpaste products to identify the efficiency of cannabinoids in reducing dental bacteria.¹⁹ This was the first known study testing samples of human dental plaque with CBD. The study compared the antibacterial activity of 12.5% cannabinoids (CBD, CBC, CBN, CBG, and cannabigerolic acid), against two well-known brands of toothpaste. Broth agar-prepared petri dishes were subdivided into four sections, and each section was smeared with an individual cannabinoid or toothpaste. Plaque samples were collected from human interdental spaces and spread on each section. The samples were incubated (37° C) for 24 hours. After incubation, total bacteria counts were taken for each section and compared. Cannabidiol and all other cannabinoid-treated samples demonstrated less colony growth than the toothpaste-treated samples, with CBN and CBC proving to be most effective in reducing total bacterial growth. This study suggests that cannabinoids, including CBD, may be an effective antimicrobial agent against dental plaque-associated bacteria.  

In the second study, Vasudevan and Stahl²⁰ conducted a randomized controlled trial comparing the bactericidal activity of cannabinoid-infused mouthrinses against total-culturable bacterial content from human dental plaque samples. The infused mouthrinses contained less than 1% of either CBD or CBG and were compared against a mouthrinse containing 0.2% chlorhexidine (higher than traditionally prescribed) and two commercially available mouthrinses: one containing essential oils with alcohol and one containing fluoride/​potassium nitrate without alcohol. Human dental plaque samples were collected from interdental spaces and processed for in vitro assay. Using both the agar well diffusion method (30μl undiluted mouthrinse) and disc diffusion method (15μl undiluted mouthrinse), plaque samples were spread on the petri dishes and incubated (37° C) for 36 hours. After incubation, the zone of inhibition was measured. The in vitro assay was performed three times for each mouthrinse. The CBD-infused mouthrinse exhibited superior bactericidal efficacy over chlorhexidine in the inhibition of bacterial content from the human dental plaque samples. Cannabigerol also demonstrated higher inhibition of bacterial content when compared to chlorhexidine; however, it was not statistically significant. The two commercially available types of mouthrinse did not show any significant antimicrobial activity. This study supports cannabinoids’ antibacterial activity against bacterial content in dental plaque. 

In Vasudevan and Stahl’s²¹ most recent study, regular tooth polishing powder was supplemented with CBD to determine if supragingival- and subgingival bacteria-forming colonies would be suppressed. Synthetic CBD powder was added to sodium bicarbonate tooth polishing powder at an equal 1% weight/​weight ratio. The teeth of the 12 participants were polished with either the CBD-infused polishing powder or the control noninfused polishing powder. Two separate tooth polishing machines were used to prevent cross-contamination with CBD. Oral plaque samples were collected from the identical interdental spaces both pre- and post-treatment. The samples were prepared for in vitro assay. Broth agar plates were prepared and smeared with samples. The samples were incubated (37° C) and colony-forming units of bacteria were analyzed after 36 hours. Results suggested that the noninfused powder was only effective in removing dental plaque from gingival spaces and had no effect on the inhibition of colony-forming units. Conversely, teeth polished with the CBD-infused powder showed a significant reduction in colony-forming bacteria. 

Safety and Concerns 

The market is flooded with commercially available CBD and THC products designed for therapeutic, medicinal, and recreational purposes.^7,8,12–16 These products are distributed in various forms, including but not limited to oils, candies, gummies, balms, lotions, capsules, incense/​herbal blends, and sprays. Such products can be purchased online and at many retail stores and dispensaries.^7,22–24 

Although THC and CBD are both cannabinoids, they should not be used interchangeably. Products containing doses greater than 0.3% dry weight of THC (the legal dose in the United States) elicit the “high” commonly associated with marijuana, whereas CBD products containing less than the legal dose of THC do not cause psychotropic reactions.^7,24 

Additionally, CBD has a safer profile than THC, which can alter cardiovascular functions, body temperature, or psychomotor or psychological function.¹² CBD oil (sometimes referred to as hemp oil) and hemp seed oil can easily be confused; however, hemp seed oil does not actually contain any cannabinoids (CBD or THC).²⁴ 

The standard level of CBD, THC, and other cannabinoids allowed in products has not been established. The majority of CBD products are not regulated by the US Food and Drug Administration (FDA) and the only FDA-approved CBD product is a prescription medication used to treat severe seizures in children.²⁵ Products manufactured without undergoing FDA review are subject to the following: inconsistent quality controls, no guarantee on the accuracy or level of the active ingredients present, and inability to verify the safety and efficacy of the product.²⁵ Some products have been found to contain mold, pesticides, and heavy metals.²⁶ Inaccurate labeling and marketing of CBD and other cannabis-derived products place consumers’ health and safety at risk.^23–25 

Conclusion 

Emerging research—although controlled and limited with small sample sizes—is promising and it supports the adjunctive use of CBD, as well as other cannabinoids for the treatment of periodontal diseases. Continued ­trials are necessary to support CBD’s validity in combating periodontal diseases and should be further expanded to include other types of cannabinoids and modalities. The studies provided did not include THC or actual marijuana smoking; smoking cannabis/​marijuana has deleterious effects on gingival tissue and increases the risk of head and neck cancer.²⁷ 

Practitioners should be mindful that each individual’s host response will be different and is contingent on the patient’s health. Because the majority of CBD products are not FDA regulated, it is imperative to understand the ingredients, risks, and benefits prior to speaking with patients. Considerations for pre-existing conditions and the interaction of prescribed pharmaceutical drugs are critical in determining the effect of CBD on periodontal diseases. Moreover, patients should be advised to consult with their physician before use to discuss potential adverse reactions. Oral health professionals can stay up to date on the most current FDA regulations and state laws related to cannabis and cannabis-derived products by visiting: https:/​/​bit.ly/​3jPCnJz and https:/​/​bit.ly/​3yJP0vV. 

References

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From Dimensions of Dental Hygiene. September 2021;19(9):14-17.