Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users
Open accessAbstract
Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.
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Adolescent rats treated with THC have fewer synaptic contacts during adulthood and reduced efficiency of hippocampal networks.
“Adolescent rats treated with THC also have fewer synaptic contacts during adulthood and reduced efficiency of hippocampal networks 75”
From Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood (2019) · cites this paper as [75]
The Introduction and Discussion describe THC-related structural changes in rats’ nucleus accumbens, but do not report fewer synaptic contacts in adulthood or reduced hippocampal-network efficiency. Searches for adolescent THC exposure, synaptic contacts, and hippocampal-network efficiency found no passage addressing those outcomes. The Discussion’s report of no hippocampal effects in one rat study does not establish a contradiction for the adolescent-treatment claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe paper gives a weak recommendation against cannabinoids in neuropathic pain, mainly because of negative results and risks of misuse, abuse, diversion, and long-term mental health harm in susceptible people.
“We provide a weak recommendation against the use of cannabinoids in neuropathic pain, mainly because of negative results, potential misuse, abuse, diversion and long term mental health risks particularly in susceptible individuals.66–71”
From Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis (2015) · cites this paper as [70]
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- Authors
- Gilman, J. M., Kuster, J. K., Lee, S., Lee, M. J., Kim, B. W., Makris, N., van der Kouwe, A., Blood, A. J., & Breiter, H. C.
- Affiliations
- Northwestern University (US)
- Harvard University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-04-16
- Volume
- 34
- Issue
- 16
- Pages
- 5529-5538
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3988409
- OpenAlex
- W2030725437
- Cited by
- 250
- References
- 58
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 15 · 2021: 22 · 2020: 30 · 2019: 22 · 2018: 26 · 2017: 26 · 2016: 32 · 2015: 36 · 2014: 11
- FWCI
- 25.51
- 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)
- Funders
- Northwestern University
- Office of National Drug Control Policy (DABK39-03-C-0098)
- National Institutes of Health
- U.S. Public Health Service (NIDA 026104, NIDA 14118, NIDA 026002, NIDA 027804, NINDS 052368, NIDA 034093)
- National Institute on Drug Abuse (K01DA034093)
- National Institute of Neurological Disorders and Stroke (052368)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- cannabis use, nucleus accumbens, amygdala, gray matter density, brain volume, brain shape, reward systems, delta-9-tetrahydrocannabinol, young adults, subcallosal cortex, dendritic branching
- MeSH terms
- Adolescent, Adult, Amygdala, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Marijuana Smoking, Nucleus Accumbens, Organ Size, Severity of Illness Index, Young Adult
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