Regulation of endocannabinoid signaling by stress: Implications for stress-related affective disorders

Gorzalka, Boris B.; Hill, Matthew N.; Hillard, Cecilia J.

doi:10.1016/j.neubiorev.2008.03.004

Cited by 211Cannabis and Cannabinoid ResearchStress Responses and CortisolNeuropeptides and Animal Physiology

Regulation of endocannabinoid signaling by stress: Implications for stress-related affective disorders

Gorzalka, Boris B., Hill, Matthew N., Hillard, Cecilia J.·2008·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2008.03.004

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Abstract

The endocannabinoid system is a widely distributed, neuromodulatory system which serves an integral role in regulating synaptic transmission. The presence of this system in stress-responsive neural circuits suggests that it may play a critical role in regulating neuroendocrine and behavioral responses to stress. Endocannabinoid content in limbic structures which regulate activation of the hypothalamic-pituitary-adrenal (HPA) axis is dynamically regulated by stress. Under conditions of acute stress, the endocannabinoid system tonically constrains activation of the HPA axis. During repeated exposure to aversive stimuli, the endocannabinoid system up-regulates in limbic structures, resulting in dampened neural activity in stress circuits, which could contribute to stress habituation. Disrupted endocannabinoid signaling, on the other hand, is associated with an inability to adapt to chronic stress. Therapeutically, these data suggest that the endocannabinoid system could be dysregulated in affective disorders, such as depression, which are characterized by maladaptive stress coping. In this review, we discuss the evidence demonstrating that the endocannabinoid system is affected by and can oppose the effects of prolonged stress and, as such, represents a potential target for the development of novel antidepressant agents.

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The finding that acute psychosocial stress increases serum NAEs is consistent with other preclinical evidence that the eCB system is involved in the response to acute stress.
“This finding is consistent with other preclinical evidence that the eCB system is involved in the response to acute stress (Gorzalka et al, 2008).”
From Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans (2012) · cites this paper as Gorzalka et al, 2008
Tonic ECB signaling in the BLA and elsewhere is mediated by AEA, whereas phasic ECB responses to robust neuronal activation are sub-served by 2-AG.
“There is growing evidence that tonic ECB signaling in the BLA and elsewhere is mediated by AEA, whereas phasic ECB responses to robust neuronal activation are sub-served by 2-AG [53–56].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [53]
Activating CB1 receptors or increasing AEA signaling prevents some effects of stress in the amygdala and hippocampus and can reduce stress-induced HPA axis activation.
“Several studies have shown that activating CB1 receptors or increasing N-arachidonylethanolamine (AEA) signaling prevents some of the effects of stress in the amygdala and hippocampus and can reduce stress-induced HPA axis activation (Ganon-Elazar and Akirav, 2009;Patel et al, 2004;Gorzalka et al, 2008).”
From Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress (2012) · cites this paper as Gorzalka et al, 2008

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Authors: Gorzalka, B. B., Hill, M. N., & Hillard, C. J.
Affiliations: University of British Columbia (CA)
Medical College of Wisconsin (US)
Corresponding author: Gorzalka, Boris B.
ORCID: Hill, Matthew N.
Hillard, Cecilia J.
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2008-08
Volume: 32
Issue: 6
Pages: 1152-1160
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2008.03.004
OpenAlex: W2017255572
Cited by: 211
References: 104
Citations by year: 2026: 6 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 17 · 2018: 10 · 2017: 11 · 2016: 13 · 2015: 10 · 2014: 15 · 2013: 14 · 2012: 14
FWCI: 2.01
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: endocannabinoid system, stress, hypothalamic-pituitary-adrenal axis, chronic stress, stress habituation, depression, mood disorders, limbic system, neuroendocrine stress response, antidepressant targets, synaptic transmission
MeSH terms: Animals, Humans, Stress, Psychological, Signal Transduction, Mood Disorders, Cannabinoid Receptor Modulators, Endocannabinoids

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Regulation of endocannabinoid signaling by stress: Implications for stress-related affective disorders

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