LC-MS/MS Tests Saliva Endocannabinoids, Cavities

The goal of researchers from Trakya University (Edirne, Turkey) was to determine whether levels of certain natural compounds (endocannabinoids) in saliva (collected without any stimulation, like chewing) are linked to how much tooth decay a person has had, in adults who are otherwise healthy. The researchers also checked other saliva-related factors known to affect cavity risk. Salivary concentrations of anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A paper based on this research was published in the Journal of the American Dental Association.¹

Why Might the Endocannabinoid System Be Relevant to Tooth Decay?

Saliva plays a key role in keeping the mouth healthy; it helps rinse away food and debris, fights off harmful microbes, keeps acidity in check, and helps repair the hard tissue of teeth. Because the salivary glands are so well-supplied with blood vessels, whatever is happening in the body, locally in the mouth or elsewhere, tends to show up in saliva. This is a major reason why saliva has become a go-to option for testing that is reliable and does not require anything invasive, such as a blood draw.²

Laboratory studies suggest that when the body's endocannabinoid system gets activated, it can reduce saliva production. This happens through two types of receptors (CB1 and CB2) that interfere with a key process cells use to keep sodium and potassium in balance. Less saliva means the mouth loses some of its natural protection, which could make teeth more prone to decay. On top of that, inflammation in the body has also been shown to affect how well the salivary glands work, again through pathways involving the endocannabinoid system.^3-6

“Despite growing interest in the role of the endocannabinoid system in oral biology,” write the authors of the paper,¹ “evidence regarding its relationship with caries (tooth decay) remains limited. Accordingly, our study aimed to evaluate unstimulated salivary concentrations of endocannabinoids (AEA, 2-AG) and related N-acylethanolamines (PEA, OEA) in adults with low and high caries experience and to investigate their associations with salivary flow rate and pH.”

Is There a Link Between Salivary Endocannabinoid Levels and Tooth Decay?

For this study, the researchers looked at 74 adults between the ages of 19 and 35, splitting them into two groups based on how much tooth decay they had experienced. a low-cavity group and a high-cavity group. They then measured how much saliva each person naturally produced, how acidic or alkaline it was, and how much plaque tended to build up. They also measured levels of four natural compounds in saliva (anandamide, 2-AG, PEA, and OEA) using LC-MS/MS, then compared the two groups statistically.¹

The people with more cavities produced noticeably less saliva, had more acidic saliva, and built up plaque faster than those with fewer cavities. However, when it came to the four compounds being measured, there was not any meaningful difference between the two groups. In other words, how much decay someone had was clearly tied to saliva flow, acidity, and plaque, but not to the levels of these compounds in saliva.¹

“Unstimulated salivary endocannabinoid concentrations,” write the authors of the paper,¹ “were not directly associated with caries experience in adults. Accordingly, salivary endocannabinoids do not appear to constitute reliable biomarkers for caries susceptibility.”

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References

1. Tekbaş-Atay, M.; Güler, M.; Büyükgöze-Dindar, M. et al. Association Between Salivary Endocannabinoid Levels and Caries Experience in Adults. J Am Dent Assoc. 2026, S0002-8177 (26), 00351-X. DOI: 10.1016/j.adaj.2026.05.019
2. Pellegrini, G.; Carmagnola, D.; Toma, M. et al. Involvement of the Endocannabinoid System in Current and Recurrent Periodontitis: A Human Study. J Periodontal Res. 2023, 58 (2), 422-432. DOI: 10.1111/jre.13103
3. Zhang, C. Z.; Cheng, X. Q.; Li, J. Y. et al. Saliva in the Diagnosis of Diseases. Int J Oral Sci. 2016, 8 (3), 133-137. DOI: 10.1038/ijos.2016.3
4. Kopach, O.; Vats, J.; Netsyk, O. et al. Cannabinoid Receptors in Submandibular Acinar Cells: Functional Cupling Between Saliva Fluid and Electrolytes Secretion and Ca2+ Signalling. J Cell Sci. 2012, 125 (Pt 8), 1884-1895. DOI: 10.1242/jcs.088930
5. Fernandez-Solari, J.; Prestifilippo, J. P.; Ossola, C. A. et al. Participation of the Endocannabinoid System in Lipopolysaccharide-Induced Inhibition of Salivary Secretion. Arch Oral Biol. 2010, 55 (8), 583-590. DOI: 10.1016/j.archoralbio.2010.05.006
6. Prestifilippo, J. P.; Fernández-Solari, J.; de la Cal, C. et al. Inhibition of Salivary Secretion by Activation of Cannabinoid Receptors. Exp Biol Med (Maywood) 2006, 231 (8), 1421-1429. DOI: 10.1177/153537020623100816