Reductions in circulating endocannabinoid 2-arachidonoylglycerol levels in healthy human subjects exposed to chronic stressors

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 67; pp. 92 - 97
• Main Authors: Yi, Buqing, Nichiporuk, Igor, Nicolas, Michel, Schneider, Stefan, Feuerecker, Matthias, Vassilieva, Galina, Thieme, Detlef, Schelling, Gustav, Choukèr, Alexander
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 03.06.2016
• Subjects: 2-Arachidonoylglycerol; Adult; Arachidonic Acids - blood; Brain - physiopathology; Catecholamines - urine; Chromatography, High Pressure Liquid; Chronic stress; Electroencephalography; Endocannabinoid; Endocannabinoids - blood; Female; Glycerides - blood; Healthy Volunteers; HPA axis; Humans; Linear Models; Male; N-arachidonylethanolamine; Psychiatric Status Rating Scales; Stress, Psychological - blood; Stress, Psychological - etiology; Stress, Psychological - physiopathology; Stress, Psychological - urine; Tandem Mass Spectrometry; 2-Arachidonoylglycerol; Chronic stress; HPA axis; Endocannabinoid; N-arachidonylethanolamine
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2016.01.004

Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal–medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p<0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors. •We examined the effects of prolonged isolation as a means of chronic stress.•The subjects showed reduced positive emotions and decreased brain cortical activity.•Urinary epinephrine and norepinephrine were increased.•The eCB 2-AG was found to decrease in response to chronic isolation stress.•The results suggest that chronic stress may impact eCB signaling in healthy humans.