Functional Interactions between Stress and the Endocannabinoid System: From Synaptic Signaling to Behavioral Output
Open accessAbstract
Endocannabinoid signaling is distributed throughout the brain, regulating synaptic release of both excitatory and inhibitory neurotransmitters. The presence of endocannabinoid signaling within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures such as the amygdala, suggests it may play an important role in regulating the neuroendocrine and behavioral effects of stress. The evidence reviewed here demonstrates that endocannabinoid signaling is involved in both activating and terminating the hypothalamic-pituitary-adrenal axis response to both acute and repeated stress. In addition to neuroendocrine function, however, endocannabinoid signaling is also recruited by stress and glucocorticoid hormones to modulate cognitive and emotional processes such as memory consolidation and extinction. Collectively, these data demonstrate the importance of endocannabinoid signaling at multiple levels as both a regulator and an effector of the stress response.
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Recent preclinical evidence indicates that stress mobilizes the eCB system in both the brain and the periphery, and that the eCB system can modulate behavioral and endocrine responses to both acute and chronic stress.
“Recent preclinical evidence indicates that stress also mobilizes the endocannabinoid (eCB) system in both the brain and the periphery, and that the eCB system can modulate behavioral and endocrine responses to both acute and chronic stress (Hill et al, 2010;Patel and Hillard, 2008).”
From Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans (2012) · cites this paper as Hill et al, 2010
Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA and increase neuronal excitability in the BLA.
“Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA and increase neuronal excitability in a key anxiety-mediating region – the basolateral amygdala (BLA).”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [67]
Stress rapidly mobilizes FAAH, depletes the signaling pool of AEA, and increases BLA excitability to drive anxiety.
“Collectively, these findings support a model in which stress rapidly mobilizes FAAH, depletes the signaling pool of AEA, and increases BLA excitability to drive anxiety [67] (Figure 1).”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [67]
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- Authors
- Hill, M. N., Patel, S., Campolongo, P., Tasker, J. G., Wotjak, C. T., & Bains, J. S.
- Affiliations
- Rockefeller University (US)
- Vanderbilt University (US)
- Sapienza University of Rome (IT)
- Tulane University (US)
- Max Planck Society (DE)
- University of Calgary (CA)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-11-10
- Volume
- 30
- Issue
- 45
- Pages
- 14980-14986
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3073528
- OpenAlex
- W2133859389
- Cited by
- 255
- References
- 57
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 13 · 2023: 11 · 2022: 9 · 2021: 16 · 2020: 9 · 2019: 11 · 2018: 8 · 2017: 19 · 2016: 15 · 2015: 23 · 2014: 21 · 2013: 23 · 2012: 20
- FWCI
- 15.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Tulane University
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Mental Health (MH066958, R01MH066958, K08MH090412)
- 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 › Neuroscience and Neuropharmacology Research
- Keywords
- endocannabinoid system, stress response, hypothalamic-pituitary-adrenal axis, glucocorticoids, amygdala, hypothalamus, memory consolidation, fear extinction, emotional processing, neuroendocrine regulation
- MeSH terms
- Animals, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Hypothalamus, Synaptic Transmission, Pituitary-Adrenal System, Stress, Psychological, Synapses, Cannabinoid Receptor Modulators, Endocannabinoids
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