Jones Madeleine R, Haggarty Connor J, Petrie Gavin N, Lunge Abigail R, Morrison India, Hill Matthew N, Heilig Markus, Mayo Leah M
Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience, Linköping University, Linköping, Sweden.
Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Neuropsychopharmacology. 2025 Apr;50(5):849-855. doi: 10.1038/s41386-025-02053-y. Epub 2025 Jan 22.
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.
社会关系对幸福感至关重要。传入神经纤维的一个亚组，即C触觉（CT）传入神经，准备好对情感上、与社会相关的触摸做出反应，并可能减轻压力的影响。内源性大麻素配体花生四烯乙醇胺（AEA）调节社会奖励和压力。因此，我们假设AEA水平与人类对情感触摸的感知愉悦度相关。在两项研究中，我们探讨了对情感上、与社会相关的触摸以及一般情感刺激的感知。在研究1中，根据是否有童年虐待记录（N = 52名有童年虐待记录者；N = 49名无童年虐待记录者）招募成年参与者（N = 101）。在研究2中，健康个体被随机分为接受脂肪酸酰胺水解酶（FAAH；PF - 04457845）抑制剂以提高AEA水平（n = 16）或安慰剂（n = 29）。结果包括触摸愉悦度和强度的自我报告评分、情感图像的效价和唤醒评分，以及内源性大麻素AEA和2 - AG、皮质醇和催产素的血浆水平。在研究1中，较高的AEA水平与对情感上、CT最佳触摸的偏好降低相关。在研究2中，AEA的药理学升高导致对情感触摸的偏好降低。这些效应特定于社会加工，因为AEA水平与情感图像的评分无关。与我们的假设相反，AEA升高与CT最佳情感触摸的愉悦度评分降低相关。这提供了将AEA与社会加工联系起来的新的人体数据，为其作为社会加工障碍潜在新治疗靶点的理论依据增添了细微差别。
