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

Yi, Buqing; Ничипорук, И. А.; Marilleau, Nicolas; Schneider, Stefan; Feuerecker, Matthias; Vassilieva, Galina; Thieme, Detlef; Schelling, Gustav; Choukèr, Alexander

doi:10.1016/j.pnpbp.2016.01.004

Cited by 40 publications

(21 citation statements)

References 44 publications

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“…Furthermore, it is believed that the ECS-in particular a dysregulation of 2-AG signaling-plays an important role in the regulation of chronic stress [45]. Stress, in turn, is the most relevant environmental factor that increases tics [46].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome

Müller‐Vahl

Bîndilă

Lutz

et al. 2020

Neuropsychopharmacol.

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Gilles de la Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of motor and vocal tics as well as psychiatric comorbidities such as attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), depression, and anxiety. The underlying cause of the disease is still unknown, but several lines of evidence suggest a paramount role of the dopaminergic system. Based on the clinical observation that cannabis-based medicine including cannabis and delta-9-tetrahydrocannabinol (THC, dronabinol) may improve TS, alternatively, an involvement of the endocannabinoid system (ECS) has been suggested. In this study we measured cerebrospinal fluid (CSF) levels of the two most important endocannabinoids "N"-arachidonoylethanolamine (AEA, anandamide) and 2-arachidonoylglycerol (2-AG), the endocannabinoid-like molecule palmitoyl ethanolamide (PEA), and the lipid arachidonic acid (AA) in a sample of adult patients with TS (n = 20) compared with controls (n = 19) using liquid-liquid lipid extraction and simultaneous quantification by liquid chromatography multiple reaction monitoring (LC/MRM). CSF levels of AEA (p = 0.0018), 2-AG (p = 0.0003), PEA (p = 0.02), and AA (p < 0.0001) were significantly increased in TS compared with controls. Levels of 2-AG correlated with the severity of comorbid ADHD (p < 0.01). This is the first study, demonstrating alterations in the ECS suggesting an involvement of this system in the pathophysiology of TS. It can be speculated that elevated endocannabinoid levels either represent secondary changes in order to compensate for alterations in other neurotransmitter systems such as the dopaminergic system, are simply an epiphenomenon or, alternatively, represent the primary cause of TS.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome

Müller‐Vahl

Bîndilă

Lutz

et al. 2020

Neuropsychopharmacol.

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“…Regarding the 2-AG, reduced [112] and increased [110] levels among individuals meeting diagnostic criteria for PTSD were described. Healthy humans that were subjected to prolonged stress (520day isolation period and simulating a flight to Mars) showed reduced blood levels of 2-AG, but not AEA [113].…”

Section: Endocannabinoid Levels In Anxietymentioning

confidence: 96%

The endocannabinoid system in mental disorders: Evidence from human brain studies

Ibarra-Lecue

Pilar-Cuéllar

Muguruza

et al. 2018

Biochemical Pharmacology

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Mental disorders have a high prevalence compared with many other health conditions and are the leading cause of disability worldwide. Several studies performed in the last years support the involvement of the endocannabinoid system in the etiopathogenesis of different mental disorders. The present review will summarize the latest information on the role of the endocannabinoid system in psychiatric disorders, specifically depression, anxiety, and schizophrenia. We will focus on the findings from human brain studies regarding alterations in endocannabinoid levels, cannabinoid receptors and endocannabinoid metabolizing enzymes in patients suffering mental disorders. Studies carried out in humans have consistently demonstrated that the endocannabinoid system is fundamental for emotional homeostasis and cognitive function. Thus, deregulation of the different elements that are part of the endocannabinoid system may contribute to the pathophysiology of several mental disorders. However, the results reported are controversial. In this sense, different alterations in gene and/or protein expression of CB1 receptors have been shown depending on the technical approach used or the brain region studied. Despite the current discrepancies regarding cannabinoid receptors changes in depression and schizophrenia, present findings point to the endocannabinoid system as a pivotal neuromodulatory pathway relevant in the pathophysiology of mental disorders.

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“…An interesting recent study examined circulating endocannabinoid concentrations in individuals who were isolated from family and friends for more than 500 days in a study simulating a trip to Mars (Yi et al, 2016). Individuals in this condition exhibited significant reductions in positive emotions and increased SNS activation.…”

Section: Circulating Endocannabinoids and Chronic Sns Or Hpa Axis Actmentioning

confidence: 99%

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

Hillard

2017

Neuropsychopharmacol.

322

241

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The goal of this review is to summarize studies in which concentrations of circulating endocannabinoids in humans have been examined in relationship to physiological measurements and pathological status. The roles of endocannabinoids in the regulation of energy intake and storage have been well studied and the data obtained consistently support the hypothesis that endocannabinoid signaling is associated with increased consumption and storage of energy. Physical exercise mobilizes endocannabinoids, which could contribute to refilling of energy stores and also to the analgesic and mood-elevating effects of exercise. Circulating concentrations of 2-arachidonoylglycerol are very significantly circadian and dysregulated when sleep is disrupted. Other conditions under which circulating endocannabinoids are altered include inflammation and pain. A second important role for endocannabinoid signaling is to restore homeostasis following stress. Circulating endocannabinoids are stress-responsive and there is evidence that their concentrations are altered in disorders associated with excessive stress, including post-traumatic stress disorder. Although determination of circulating endocannabinoids can provide important information about the state of endocannabinoid signaling and thus allow for hypotheses to be defined and tested, the large number of physiological factors that contribute to their circulating concentrations makes it difficult to use them in isolation as a biomarker for a specific disorder.

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

Cited by 40 publications

References 44 publications

Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome

Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome

The endocannabinoid system in mental disorders: Evidence from human brain studies

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

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