Saliva: The New Frontier in Understanding Body's Cannabinoid Signals

The endocannabinoid system regulates a broad range of psychological and physiological processes throughout the body, and its dysregulation has been implicated in numerous pathological conditions. As a result, components of this system are common targets in diagnostic and therapeutic research. Given the challenges associated with obtaining tissue samples from human participants, current research commonly relies on the quantification of circulating endocannabinoids in blood as a surrogate for tissue-level endocannabinoid activity. However, this approach presents limitations due to the invasive nature of blood collection and its potential to induce pain or stress-related activation of the endocannabinoid system. New methods to study the activity of the endocannabinoid system in humans are therefore needed. This narrative review examines the current literature investigating the measurement, origin, and significance of the endocannabinoid ligands N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) in human saliva, a non-invasive and easily accessible biological matrix. Mass spectromic analysis have demonstrated that AEA and 2-AG levels are dynamic and can be influenced by physiological challenges, including fear, stress, and exercise. Salivary endocannabinoid profiles have also been shown to reflect longer-term traits, such as metabolic status, and can distinguish between patients and healthy individuals in conditions like orofacial pain. Collectively, salivary endocannabinoids reflect both acute and chronic aspects of endocannabinoid system activity and may represent a promising non-invasive matrix for assessing endocannabinoid function. However, further understanding of the mechanisms underlying endocannabinoid production in the oral cavity is required for accurate interpretation of salivary measurements in future studies.