You must be signed in to read the rest of this article.
Registration on CDEWorld is free. You may also login to CDEWorld with your DentalAegis.com account.
In the past decade cannabis has shown therapeutic potential in medicine for the treatment of pain, migraine, anxiety, insomnia, seizures, glaucoma, and more.1,2 Cannabis is being used to replace dangerous pharmaceuticals1,3 amidst the height of an opioid epidemic in the United States. In addition, there is evidence to support the use of cannabis in dentistry for the treatment of oral cancer, periodontal disease, dental caries, mucositis, burning mouth syndrome, salivary gland infections, TMJ disorders, and more.4-6
Cannabis indica and Cannabis sativa are flowering plants of the Cannabaceae species, which also includes hemp, hops, and hackberries (celtis). The term "hemp" is used to describe cannabis strains containing 0.3% THC (a psychoactive cannabinoid) or less. This article discusses cannabis and hemp, which differ in their cannabinoid content (THC) but also in legality. The Agriculture Improvement Act in 2018 (commonly referred to as the Farm Bill) legalized hemp in 50 states, however cannabis remains a Schedule I drug, thus illegal federally but legal for medical programs that exist throughout the country.
Over 545 compounds can be derived from cannabis, including cannabinoids (THC, CBD, etc.), terpenes (aromatic oils influencing cannabis aroma and therapeutic effects), flavonoids (antioxidant-rich plant metabolites), non-cannabinoid phenols, steroids, fatty acids, and more.2 The primary psychoactive compound is ∆9-tetrahydrocannabinol (THC), which was first isolated in 1964.7 Other therapeutic cannabinoids are cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG). and cannabinoid acids (THC-A, CBD-A). These compounds are noted for their anti-cancer, anti-inflammatory, antioxidant, analgesic, anxiolytic, and anti-microbial properties.1,2,4,8,9 Cannabinoids, terpenes, and flavonoids work in concert to produce an "entourage effect,"4 in which cannabis compounds other than cannabinoids act synergistically to modulate the overall psychoactive effects of the plant.4,10
Targeting the Endocannabinoid System
As of 2021, 34 US states have legalized various degrees of cannabis access, including adult-use (recreational) and medicinal (states determine conditions that are then qualified by a healthcare professional). The state of Maryland provides an example of cannabis use in dentistry, where a licensed dentist can prescribe cannabis to qualifying patients after completion of a two-hour online course. Table 1 summarizes the applications of cannabis in dentistry.
The endocannabinoid system (ECS) is a complex cell signaling system found in vertebrates and invertebrates. There are two major cannabinoid receptors (CB1 and CB2). The CB1 receptors are widely distributed in the brain, heart, lungs, adrenal glands, gastrointestinal tract, spinal cord, reproductive organs, and immune cells. CB2 receptors are principally expressed in immune cells (spleen, tonsils, thymus).4,7 The ECS maintains internal homeostasis and directly influences the physiological process regulating anxiety, behavior, appetite, emotions, depression, nervous functions, endocrine regulation, energy balance, and more.4 The discovery of cannabinoid receptors in the oral cavity and teeth suggests that the endocannabinoid system may be a target for the treatment of oral diseases and dental pain.11
Forms & Methods of Administration
Cannabinoids are metabolized by the liver and gut enzymes but demonstrate low bioavailability when taken orally. Therefore, rectal, transdermal, nasal, inhaled, and oral transmucosal delivery formulations enable uptake directly into the blood by eliminating first-pass metabolism, increasing uptake and effectiveness. The combustion and inhalation (smoking) of cannabis cigarettes is generally considered an inappropriate method for the therapeutic administration of cannabis.7 A vaporizer, on the other hand, can heat the cannabis plant material at a moderate temperature, causing the active cannabinoids to evaporate into an aerosol that contains far fewer harmful components when compared to combustion carcinogens produced by smoking cannabis.12 Dental professionals should counsel their patients on the dangers of smoking, but also discuss the benefits of vaporizing the flower (not cartridges, liquids, etc) or recommend alternative deliveries (transdermal, rectal, oral).
Dental Anxiety & Fear
Dental anxiety significantly impairs patients' quality of life and may prevent them from seeking treatment. The use of benzodiazepines and nitrous oxide are the traditional methods of anxiety management, but these pose significant risks to the patient and operator. CBD has well documented anti-depressant, anxiolytic, panic, and fear-reducing effects.1-4 It should be noted that the psychoactive cannabinoid THC may exacerbate anxiety3 and should be used with caution.
Dental Pain & Healing
Studies have shown that cannabinoid receptor agonists block pain in various pain models with both CB1 and CB2 receptors demonstrating anti-nociceptive activity.7 Cannabinoids also have anxiolytic, anti-depressant, and euphoric-inducing ability, helping patients to cope with pain. In addition, there is supporting evidence that cannabis may assist in opioid detoxification and weaning, thus making it a potential weapon in battling the opioid epidemic.1,4,7,8
Periodontal Diseases & Bone Maintenance
The endocannabinoid system may be a promising target in the treatment of periodontal disease as it has been shown to play a role in the modulation/suppression of inflammatory responses by periodontal ligament cells.4,5 In an animal study of periodontitis, rats who were treated with CBD showed decreased alveolar bone loss, decreased neutrophil migration, and lower pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α production.13 Traditionally, much of the focus of periodontal disease treatment has been on reducing bacterial load. However, an opportunity exists to modulate the host inflammatory response and apply the anti-inflammatory and anti-bacterial properties of cannabinoids.
It is important to note that the method of cannabis consumption strongly relates to the action, benefit, and potential side effects. Several studies have linked cannabis smoking to periodontal disease, gingival enlargement, gingival recession, and even necrotizing ulcerative gingivitis.14
Inhibition of Bacteria
Studies demonstrate that cannabinoids have excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol's primary mechanism.15 Cannabinoid-infused mouthwashes have demonstrated inhibition of bacteria with the same efficacy as chlorhexidine.9 CBD-supplemented tooth polishing powder and cannabinoid infused toothpaste have also inhibited dental plaque and bacterial growth in research.4 Due to the antibacterial properties, cannabidiol may have a therapeutic applicability in the treatment of dental caries.4,9
Treatment & Prevention of Cancers
Cannabis has demonstrated antioxidant, anti-metastatic, anti-tumorigenic, apoptotic, and anti-angiogenic properties in various cancer cell lines and thus may have therapeutic benefit in the treatment of oral cancers. It is also suggested that squamous cell carcinoma of the tongue may be the result of a dysregulation of endocannabinoid system signaling.16 Cannabis also has a therapeutic effect useful in cancer for its anti-emetic effect, appetite stimulation, analgesic, anxiolytic, anti-depressant, and sleep-inducing properties.1,2,3,7,8
Oral Mucositis & Burning Mouth Syndrome
Oral mucositis (OM) is characterized by a marked inflammatory reaction that results in erythematous lesions, ulcers, dysphagia, and inability to afford and ensure a physiological caloric intake that ultimately leads to interrupting life-saving treatments in cancer patients.17
β-caryophyllene (BCP) is a cannabis terpene also found in cinnamon, cloves, and black pepper. It has analgesic, anti-inflammatory, neuropathic pain reduction, antioxidant, anticancer, and protective effects. BCP has a curative effect on mucositis and may enhance the appropriateness of cannabis therapy in cancer.8,17
Burning mouth syndrome (BMS) is an intraoral burning sensation for which presently no medical or dental causes have been found, and in which the oral mucosa appears normal. Studies indicated an increase in the expression of transient receptor potential vanilloid channel type 1 (TRPV1) and CB2 receptors in BMS patients. Multiple studies have investigated and confirmed the safety and efficacy of cannabinoids against the symptoms of BMS.4,6
The Future of Cannabis in Dentistry
The cannabis user may face stigma in many forms, ranging from judgment from medical and dental professionals to criminal charges depending on legalities in their state. Rates of legalization and use statistics do not capture the often subtle struggles those in the cannabis community face in their everyday lives.18 Dental and medical professionals can contribute to the normalization of cannabis as a therapeutic agent by discussing the harms of smoking while also feeling confident to recommend cannabis in clinical applications based on the therapeutic potential demonstrated.
Despite the vast anecdotal, experimental, and animal studies evidence for the use of cannabinoids to treat oral and dental disorders, there is limited rigorous scientific evidence for the use of cannabinoids in dentistry to date.4 However, it should be noted that there is strong evidence to support the wide therapeutic window and properties of cannabinoids, including-but not limited to-their analgesic, antioxidant, anti-inflammatory, anti-microbial, anti-pruritic, and anti-cancer properties. Patients should seek professional medical advice before beginning a cannabinoid-based therapy program.
About the Author
Nicole Greco, RDH, BS, MA
Canal & Calem Periodontics
Moorestown, New Jersey
1. Lucas P, Baron EP, Jikomes N. Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients. Harm Reduct J. 2019;16(1):9.
2. Gonçalves J, Rosado T, Soares S, et al. Cannabis and its secondary metabolites: their use as therapeutic drugs, toxicological aspects, and analytical determination. Medicines (Basel). 2019;6(1):31.
3. Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in anxiety and sleep: a large case series. Perm J. 2019;23(1):18-041.
4. Lowe H, Toyang N, Steele B, et al. The current and potential application of medicinal cannabis products in dentistry. Dent J (Basel). 2021;9(9):106.
5. Jäger A, Setiawan M, Beins E, et al. Analogous modulation of inflammatory responses by the endocannabinoid system in periodontal ligament cells and microglia. Head Face Med. 2020;16(1):26.
6. Borsani E, Majorana A, Cocchi MA, et al. Epithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis. Histol Histopathol. 2014;29(4):523-533.
7. Bruni N, Della Pepa C, Oliaro-Bosso S. Cannabinoid delivery systems for pain and inflammation treatment. Molecules. 2018;23(10):2478.
8. Baron EP. Medicine properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in migraine, headache, and pain: an update on current evidence and cannabis science. Headache. 2018;58(7):1139-1186.
9. Vasudevan K, Stahl V. Cannabinoids infused mouthwash products are as effective as chlorhexidine on inhibition of total-culturable bacterial content in dental plaque samples. J Cannabis Res. 2020;2(1):20.
10. Ferber SG, Namdar D, Hen-Shoval D, et al. The "entourage effect": terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Curr Neuropharmacol. 2020;18(2):87-96.
11. Beneng K, Renton T, Yilmaz Z, et al. Cannabinoid receptor CB1-immunoreactive nerve fibres in painful and non-painful human tooth pulp. J Clin Neurosci. 2010;17(11):1476-1479.
12. Varlet V, Concha-Lozano N, Berthet A, et al. Drug vaping applied to cannabis: is "cannavaping" a therapeutic alternative to marijuana? Sci Rep. 2016;6:25599.
13. Napimoga MH, Benatti BB, Lima FO, et al. Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats. Intl Immunopharmacol. 2009;9(2):216-222.
14. Mederos M, Francia A, Chisini LA, et al. Influence of cannabis use on periodontal disease: a scoping review. Odontoestomatología. 2018;20(31):4 -15.
15. Blaskovich M, Kavanagh A, Elliot A, et al. The antimicrobial potential of cannabidiol. Commun Biol. 2021;4(1):7.
16. Alhouayek M, Boldrup L, Fowler CJ. Altered mRNA expression of genes involved in endocannabinoid signalling in squamous cell carcinoma of the oral tongue. Cancer Invest. 2019.37(8): 327-338.
17. Picciolo G, Pa