Hair endocannabinoids predict physiological fear conditioning and salivary endocannabinoids predict subjective stress reactivity in humans

On the basis of substantial preclinical evidence, the endogenous cannabinoid system has been proposed to be closely involved in stress reactivity and extinction of fear. Existing human research supports this proposal to some extent, but existing studies have used only a narrow range of tools and biomatrices to measure endocannabinoids during stress and fear experiments. In the present study we collected hair and saliva samples from 99 healthy participants who completed a fear conditioning and intrusive memory task. Subjective, physiological and biological stress reactivity to a trauma film, which later served as unconditional stimulus during fear conditioning, was also measured. We found that salivary endocannabinoid concentrations predicted subjective responses to stress, but not cortisol stress reactivity, and replicated previous findings demonstrating a sex dimorphism in hair and salivary endocannabinoid levels. Hair 2-arachidonoyl glycerol levels were significantly associated with better retention of safety learning during extinction and renewal phases of fear conditioning, while hair concentrations of oleoylethanolamide and palmitoylethanolamide were associated with overall physiological arousal, but not conditional learning, during fear conditioning. This study is the first to test the relationship between hair and salivary endocannabinoids and these important psychological processes. Our results suggest that these measures may serve as biomarkers of dysregulation in human fear memory and stress.