The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain

Costa, Barbara; Trovato, Anna Elisa; Comelli, Francesca; Giagnoni, Gabriella; Colleoni, Mariapia

doi:10.1016/j.ejphar.2006.11.006

Cited by 396Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsInflammatory mediators and NSAID effects

The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain

Costa, Barbara, Trovato, Anna Elisa, Comelli, Francesca, Giagnoni, Gabriella, Colleoni, Mariapia·2007·European Journal of Pharmacology

DOI 10.1016/j.ejphar.2006.11.006

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Abstract

Cannabidiol, the major psycho-inactive component of cannabis, has substantial anti-inflammatory and immunomodulatory effects. This study investigated its therapeutic potential on neuropathic (sciatic nerve chronic constriction) and inflammatory pain (complete Freund's adjuvant intraplantar injection) in rats. In both models, daily oral treatment with cannabidiol (2.5-20 mg/kg to neuropathic and 20 mg/kg to adjuvant-injected rats) from day 7 to day 14 after the injury, or intraplantar injection, reduced hyperalgesia to thermal and mechanical stimuli. In the neuropathic animals, the anti-hyperalgesic effect of cannabidiol (20 mg/kg) was prevented by the vanilloid antagonist capsazepine (10 mg/kg, i.p.), but not by cannabinoid receptor antagonists. Cannabidiol's activity was associated with a reduction in the content of several mediators, such as prostaglandin E(2) (PGE(2)), lipid peroxide and nitric oxide (NO), and in the over-activity of glutathione-related enzymes. Cannabidiol only reduced the over-expression of constitutive endothelial NO synthase (NOS), without significantly affecting the inducible form (iNOS) in inflamed paw tissues. Cannabidiol had no effect on neuronal and iNOS isoforms in injured sciatic nerve. The compound's efficacy on neuropathic pain was not accompanied by any reduction in nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor alpha (TNFalpha) content. The results indicate a potential for therapeutic use of cannabidiol in chronic painful states.

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Anti-hyperalgesic effects observed with cannabidiol-containing synthetic analogues are likely independent of cannabinoid receptors and may be mediated through TRPV1.
“However, anti-hyperalgesic effects observed with these compounds are likely to be independent of cannabinoid receptors, and may be mediated through TRPV1.”
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Authors: Costa, B., Trovato, A. E., Comelli, F., Giagnoni, G., & Colleoni, M.
Affiliations: University of Milano-Bicocca (IT)
University of Milan (IT)
Corresponding author: Costa, Barbara
ORCID: Costa, Barbara
Venue: European Journal of Pharmacology
Publisher: Elsevier BV
Published: 2007-02
Volume: 556
Issue: 1-3
Pages: 75-83
ISSN: 0014-2999 (ISSN-L)
DOI: 10.1016/j.ejphar.2006.11.006
OpenAlex: W1967303451
Cited by: 395
References: 46
Citations by year: 2026: 22 · 2025: 28 · 2024: 37 · 2023: 42 · 2022: 37 · 2021: 43 · 2020: 35 · 2019: 20 · 2018: 17 · 2017: 16 · 2016: 14 · 2015: 8 · 2014: 9 · 2013: 11 · 2012: 14
FWCI: 4.80
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: European Journal of Pharmacology (publishedVersion)
PubMed (publishedVersion)
BOA (University of Milano-Bicocca) (submittedVersion)
Funders: Ministero dell’Istruzione, dell’Università e della Ricerca
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords: cannabidiol, neuropathic pain, inflammatory pain, chronic constriction injury, complete Freund's adjuvant, hyperalgesia, capsazepine, vanilloid receptor, prostaglandin E2, nitric oxide, endothelial nitric oxide synthase, glutathione, NF-κB, TNF-α, anti-inflammatory activity, oral administration
MeSH terms: Administration, Oral, Animals, Cannabidiol, Cannabis, Capsaicin, Chronic Disease, Freund's Adjuvant, Hyperalgesia, Inflammation, Lipid Peroxides, Male, Nitric Oxide, Pain, Pain Measurement, Tumor Necrosis Factor-alpha, Dinoprostone, NF-kappa B, Rats, Wistar, Nitric Oxide Synthase, Sciatic Neuropathy, Rats, Cannabinoid Receptor Antagonists

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The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain

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