Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants

Hampson, A. J.; Grimaldi, M.; Axelrod, J.; Wink, D.

doi:10.1073/pnas.95.14.8268

Cited by 850Cannabis and Cannabinoid ResearchNeuroscience and Neuropharmacology ResearchNeurological Disorders and Treatments

Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants

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Hampson, A. J., Grimaldi, M., Axelrod, J., Wink, D.·1998·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.95.14.8268PMC PMC20965

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Abstract

The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (-)Delta9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or alpha-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.

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In rat cortical neurons, CBD prevented NMDA-mediated neurotoxicity and oxidative damage through a cannabinoid receptor-independent mechanism.
“In rat cortical neurons, CBD prevented NMDA-mediated neurotoxicity and oxidative damage in through a cannabinoid receptor-independent mechanism (113).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [113]

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Authors: Hampson, A. J., Grimaldi, M., Axelrod, J., & Wink, D.
Affiliations: National Institutes of Health (US)
ORCID: Hampson, A. J.
Grimaldi, M.
Wink, D.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1998-07-07
Volume: 95
Issue: 14
Pages: 8268-8273
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.95.14.8268
PMC: PMC20965
OpenAlex: W2119898593
Cited by: 850
References: 29
Citations by year: 2026: 13 · 2025: 43 · 2024: 40 · 2023: 41 · 2022: 29 · 2021: 40 · 2020: 52 · 2019: 42 · 2018: 30 · 2017: 41 · 2016: 19 · 2015: 32 · 2014: 20 · 2013: 31 · 2012: 29
FWCI: 11.52
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords: cannabidiol, tetrahydrocannabinol, neuroprotection, glutamate excitotoxicity, antioxidants, NMDA receptor, non-NMDA receptors, voltage-gated calcium channels, Fenton reaction, cerebral ischemia, cortical neurons
MeSH terms: Animals, Antioxidants, Cannabidiol, Cells, Cultured, Drug Antagonism, Neurons, Receptors, Drug, Dronabinol, Cell Death, Rats, Wistar, Oxidative Stress, Glutamic Acid, Receptors, Cannabinoid, Rats

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Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants

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