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Cannabinoid Modulation of Amygdala Reactivity to Social Signals of Threat in Humans
Open accessAbstract
The cannabinoid (CB) system is a key neurochemical mediator of anxiety and fear learning in both animals and humans. The anxiolytic effects of Δ 9 -tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, are believed to be mediated through direct and selective agonism of CB 1 receptors localized within the basolateral amygdala, a critical brain region for threat perception. However, little is known about the effects of THC on amygdala reactivity in humans. We used functional magnetic resonance imaging and a well validated task to probe amygdala responses to threat signals in 16 healthy, recreational cannabis users after a double-blind crossover administration of THC or placebo. We found that THC significantly reduced amygdala reactivity to social signals of threat but did not affect activity in primary visual and motor cortex. The current findings fit well with the notion that THC and other cannabinoids may have an anxiolytic role in central mechanisms of fear behaviors and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid system for disorders of anxiety and social fear.
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“Administration of Δ9-tetrahydrocannabinoid (THC), the main psychoactive constituent of cannabis, reduces amygdala response to social signals of threat, an action that may underlie anxiolytic effects of THC (Phan et al. 2008).”
From Effects of MDMA on sociability and neural response to social threat and social reward (2009) · cites this paper as Phan et al. 2008
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Metadata
- Authors
- Phan, K. L., Angstadt, M., Golden, J., Onyewuenyi, I., Popovska, A., & de Wit, H.
- Affiliations
- University of Michigan (US)
- Howard University (US)
- Amherst College (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-03-05
- Volume
- 28
- Issue
- 10
- Pages
- 2313-2319
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2657360
- OpenAlex
- W2004840573
- Cited by
- 251
- References
- 63
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 3 · 2023: 8 · 2022: 11 · 2021: 22 · 2020: 26 · 2019: 12 · 2018: 13 · 2017: 20 · 2016: 11 · 2015: 19 · 2014: 16 · 2013: 14 · 2012: 20
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH076198, K23MH076198)
- National Institute on Drug Abuse (R03DA024197, DA024197, R90DA023425, DA009133, DA023425, R01DA009133, R01DA002812, DA002812)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- endocannabinoid system, delta-9-tetrahydrocannabinol, THC, amygdala, fear, anxiety, CB1 receptor, anxiolytic effects, cannabis users, fear learning
- MeSH terms
- Adolescent, Adult, Amygdala, Cannabinoids, Double-Blind Method, Fear, Female, Humans, Magnetic Resonance Imaging, Male, Psychomotor Performance, Social Behavior, Dronabinol
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