Endocannabinoid Reactivity to Acute Stress: Investigation of the Relationship between Salivary and Plasma Levels

The endogenous cannabinoid (eCB) system has been shown in animal models to regulate the initiation and termination of central nervous responses to stress. In human studies, the role of peripherally measured eCBs is much less clear and the effect in salivary eCBs has not been studied. In this study, we use a novel method to quantify cortisol and eCBs arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) in human saliva, as well as in plasma samples. Forty-five females and 32 males completed a mixed physiological/psychosocial stress-induction study where saliva, and blood samples in males, were collected at baseline, immediately following, 30-minutes following, and 45-minutes following stress induction. Cortisol significantly increased after stress, but there were sex differences in the cortisol response to stress, with females having higher cortisol after stress compared to males. There was a significant increase in salivary levels of 2-AG immediately following stress induction, but no effect of AEA. Salivary AEA was higher in males compared to females. Surprisingly, there was no effect of stress on plasma AEA or 2-AG levels in the male cohort, though small effect sizes for 2-AG were observed, which is consistent with most other human literature. This study is the first to show that the eCB system is active in human saliva and is responsive to acute stress, possibly as part of the sympathetic nervous system response.