Serum Endocannabinoid Content is Altered in Females with Depressive Disorders: A Preliminary Report
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BACKGROUND: Preclinical research has suggested that the endocannabinoid system may be involved in the etiology and/or treatment of depression; however, there are no published studies examining circulating endocannabinoid content in patients with clinical depression. METHODS: This study examined the endocannabinoids (anandamide; AEA) and 2-arachidonylglycerol (2-AG) in serum from ambulatory, medication-free female patients diagnosed with minor or major depression, and in controls matched for demographic characteristics. RESULTS: Serum 2-AG content was significantly decreased in patients diagnosed with major depression, and this decrease was correlated significantly and negatively with duration of the depressive episode, such that 2-AG content was progressively lower the longer the depressive episode. While AEA was not associated with major depression PER SE, a strong negative correlation was found between serum AEA content and Hamilton ratings for cognitive and somatic anxiety, suggesting that AEA content may relate to the anxiety dimension of affective disorders. In subjects with minor depression, serum AEA was significantly elevated, with 2-AG content demonstrating a similar, but statistically insignificant trend. DISCUSSION: These are the first clinical data to indicate that the endocannabinoid system may be disturbed in affective disease, and suggest that future research is required to determine the relevance of these changes with respect to disease manifestation and pharmacotherapy.
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The finding that circulating AEA is negatively associated with baseline Anxiety is in agreement with a clinical study and with findings in nonhuman models.
“This is in agreement with a clinical study (Hill et al, 2008) as well as with findings in nonhuman models, in which inhibition of AEA metabolism has anxiolytic and antidepressant effects (Bambico et al, 2007;Naidu et al, 2007).”
From Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans (2012) · cites this paper as Hill et al, 2008
AEA levels are reduced in depressed patients with high anxiety scores.
“and depressed patients with high anxiety scores (Hill, Miller, Carrier, Gorzalka, & Hillard, 2009;Hill, Miller, Ho, Gorzalka, & Hillard, 2008).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Hill, Miller, Ho, Gorzalka, & Hillard, 2008
EC and NAE blood concentrations are lower in patients with depression.
“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 [18]
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References 38 · Cited by 292
- Authors
- Hill, M., Miller, G., Ho, W.-S., Gorzalka, B., & Hillard, C.
- Affiliations
- University of British Columbia (CA)
- Medical College of Wisconsin (US)
- Venue
- Pharmacopsychiatry
- Publisher
- Georg Thieme Verlag KG
- Published
- 2008-03
- Volume
- 41
- Issue
- 2
- Pages
- 48-53
- ISSN
- 0176-3679 (ISSN-L)
- 1439-0795
- PMC
- PMC3422568
- OpenAlex
- W2074698946
- Cited by
- 292
- References
- 38
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 21 · 2023: 11 · 2022: 22 · 2021: 27 · 2020: 20 · 2019: 19 · 2018: 15 · 2017: 16 · 2016: 12 · 2015: 16 · 2014: 13 · 2013: 10 · 2012: 13
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacopsychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (DA 16967, R01DA016967)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- endocannabinoid system, depression, anandamide, 2-arachidonoylglycerol, female patients, major depressive disorder, minor depression, anxiety, depressive episode duration, Hamilton Depression Rating Scale
- MeSH terms
- Adult, Anxiety, Arachidonic Acids, Chromatography, High Pressure Liquid, Depressive Disorder, Major, Major Depressive Disorder, Depressive Disorder, Female, Glycerides, Humans, Psychiatric Status Rating Scales, Mass Spectrometry, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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