Endocannabinoid contributions to the perception of socially relevant, affective touch in humans.

Social relationships are central to well-being. A subgroup of afferent nerve fibers, C-tactile (CT) afferents, are primed to respond to affective, socially relevant touch and may mitigate the effects of stress. The endocannabinoid ligand anandamide (AEA) modulates both social reward and stress. We thus hypothesized that AEA levels would be associated with the perceived pleasantness of affective touch in humans. Across two studies, we explored perceptions of affective, socially relevant touch and general affective stimuli. In study 1, adult participants (N = 101) were recruited based on presence (CM+) or absence (CM-) of documented childhood maltreatment (N = 52 CM+; N = 49 CM-). In study 2, healthy individuals were randomized to receive an inhibitor of fatty acid amide hydrolase (FAAH; PF-04457845) to increase AEA levels (n = 16) or placebo (n = 29). Outcomes included self-report ratings of touch pleasantness and intensity, valence and arousal ratings of affective images, and plasma levels of endocannabinoids AEA and 2-AG, cortisol, and oxytocin. In study 1, higher AEA levels were associated with a reduced preference for affective, CT-optimal touch. In study 2, pharmacological elevation of AEA resulted in reduced preference for affective touch. These effects were specific to social processing, as AEA levels were not related to ratings of affective images. In contrast to our hypothesis, elevated AEA was associated with reduced pleasantness ratings of CT-optimal, affective touch. This provides novel, in-human data linking AEA to social processing, adding nuance to the rationale for its use as a potential novel therapeutic target in disordered in social processing.