Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress

Matthew N. Hill; Gregory E. Miller; Erica J. Carrier; Boris B. Gorzalka; Cecilia J. Hillard

doi:10.1016/j.psyneuen.2009.03.013

Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress

Matthew N. Hill, Gregory E. Miller, Erica J. Carrier, Boris B. Gorzalka, Cecilia J. Hillard^*

^*Corresponding author for this work

Psychology

Research output: Contribution to journal › Article › peer-review

253 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1257-1262
Number of pages	6
Journal	Psychoneuroendocrinology
Volume	34
Issue number	8
DOIs	https://doi.org/10.1016/j.psyneuen.2009.03.013
State	Published - Sep 2009

Funding

This research was supported by operating grants from the American Heart Association and the Canadian Institutes of Health Research (CIHR) to GEM; a Young Investigator Award from NARSAD and a Michael Smith Foundation for Health Research (MSFHR) Scholar Award to GEM; partial funding was provided by Research for a Healthier Tomorrow, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin (CJH); operating grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and CIHR to BBG; and a MSFHR postgraduate trainee award and a NSERC Canadian Graduate Scholarship to MNH. None of these institutions had any further role in study design, collection, analysis or interpretation of the data nor in the decision to submit this paper for publication.

Keywords

Antidepressant
Cannabinoid
Depression
Metabolic
Stress
Sympathetic

ASJC Scopus subject areas

Endocrine and Autonomic Systems
Psychiatry and Mental health
Biological Psychiatry
Endocrinology
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.psyneuen.2009.03.013

Cite this

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title = "Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress",

abstract = "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.",

keywords = "Antidepressant, Cannabinoid, Depression, Metabolic, Stress, Sympathetic",

author = "Hill, {Matthew N.} and Miller, {Gregory E.} and Carrier, {Erica J.} and Gorzalka, {Boris B.} and Hillard, {Cecilia J.}",

note = "Funding Information: This research was supported by operating grants from the American Heart Association and the Canadian Institutes of Health Research (CIHR) to GEM; a Young Investigator Award from NARSAD and a Michael Smith Foundation for Health Research (MSFHR) Scholar Award to GEM; partial funding was provided by Research for a Healthier Tomorrow, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin (CJH); operating grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and CIHR to BBG; and a MSFHR postgraduate trainee award and a NSERC Canadian Graduate Scholarship to MNH. None of these institutions had any further role in study design, collection, analysis or interpretation of the data nor in the decision to submit this paper for publication. ",

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AU - Carrier, Erica J.

AU - Gorzalka, Boris B.

AU - Hillard, Cecilia J.

N1 - Funding Information: This research was supported by operating grants from the American Heart Association and the Canadian Institutes of Health Research (CIHR) to GEM; a Young Investigator Award from NARSAD and a Michael Smith Foundation for Health Research (MSFHR) Scholar Award to GEM; partial funding was provided by Research for a Healthier Tomorrow, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin (CJH); operating grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and CIHR to BBG; and a MSFHR postgraduate trainee award and a NSERC Canadian Graduate Scholarship to MNH. None of these institutions had any further role in study design, collection, analysis or interpretation of the data nor in the decision to submit this paper for publication.

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N2 - 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.

AB - 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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KW - Depression

KW - Metabolic

KW - Stress

KW - Sympathetic

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Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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