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Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress
Open accessAbstract
Central endocannabinoid signaling is known to be responsive to stressful stimuli; however, there is no research to date characterizing the effects of stress on peripheral endocannabinoid content. The current study examined serum content of the endocannabinoid ligands N-arachidonylethanolamide (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), and the non-cannabinoid N-acyl ethanolamine (NAE) molecules palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) under basal conditions, immediately following the Trier Social Stress Test (TSST), and 30 min thereafter, in 15 medication-free women diagnosed with major depression, and 15 healthy matched controls. Basal serum concentrations of AEA and 2-AG, but not PEA or OEA, were significantly reduced in women with major depression relative to matched controls, indicating a deficit in peripheral endocannabinoid activity. Immediately following the TSST, serum 2-AG concentrations were increased compared to baseline; serum AEA concentration was unchanged at this time point. Serum concentrations of PEA and OEA were significantly lower than baseline 30 min following the cessation of the TSST. The magnitude of these responses did not differ between depressed and control subjects. These are the first data to demonstrate that the peripheral endocannabinoid/NAE system is responsive to exposure to stress.
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“The endocannabinoids anandamide (AEA) and 2arachidonoylglycerol (2AG) are endogenously produced lipids that have been found, for instance, to be elevated in blood in response to psychological stress (Hill et al., 2009;Dlugos et al., 2012).”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Hill et al., 2009
In the citing paper
“Similar effects have been found after acute psychological stress (Hill et al., 2009).”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Hill et al., 2009
In the citing paper
“a number of studies have detected reduced levels of AEA in patients suffering from stress-related psychiatric illnesses, including major depression (Hill et al., 2009) and PTSD (Neumeister et al., 2013).”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Hill et al., 2009
In the citing paper
“two independent studies have now both reported that 2-AG levels are reduced in individuals with major depression (Hill et al., 2008; Hill et al., 2009)”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Hill et al., 2009
In the citing paper
“EC plasma concentrations are also modified by the presence of affective disorders and severe mental illness [7], [8].”
From Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder (2013) · cites this paper as [7]
In the citing paper
“there are a number of recent studies which demonstrated that EC and NAE blood concentrations increase in response to acute stress [7], [10] and that they are higher in individuals who show stress tolerance [10] and lower in patients with depression [18].”
From Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder (2013) · cites this paper as [7]
In the citing paper
“The possible protective effects of an activated EC system are illustrated by the fact that patients with major depression show reduced serum ANA and 2-AG concentrations [7]”
From Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder (2013) · cites this paper as [7]
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Metadata
- Authors
- Hill, M. N., Miller, G. E., Carrier, E. J., Gorzalka, B. B., & Hillard, C. J.
- Affiliations
- University of British Columbia (CA)
- Medical College of Wisconsin (US)
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 34
- Issue
- 8
- Pages
- 1257-1262
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC2716432
- OpenAlex
- W2097199164
- Cited by
- 328
- References
- 30
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 29 · 2023: 19 · 2022: 25 · 2021: 37 · 2020: 23 · 2019: 22 · 2018: 22 · 2017: 17 · 2016: 15 · 2015: 18 · 2014: 8 · 2013: 20 · 2012: 12
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA009155)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- endocannabinoids, N-acylethanolamines, major depressive disorder, social stress, anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, oleoylethanolamide, serum biomarkers, Trier Social Stress Test, women, stress response
- MeSH terms
- Adult, Amides, Arachidonic Acids, Major Depressive Disorder, Ethanolamines, Female, Glycerides, Humans, Oleic Acids, Palmitic Acids, Stress, Psychological, Case-Control Studies, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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