Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved
Abstract
This study aimed to give a rationale for the employment of phytocannabinoid formulations to treat neuropathic pain. It was found that a controlled cannabis extract, containing multiple cannabinoids, in a defined ratio, and other non-cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive efficacy than the single cannabinoid given alone, when tested in a rat model of neuropathic pain. The results also demonstrated that such an antihyperalgesic effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was mediated by vanilloid receptors TRPV1. The non-psychoactive compound, cannabidiol, is the only component present at a high level in the extract able to bind to this receptor: thus cannabidiol was the drug responsible for the antinociceptive behaviour observed. In addition, the results showed that after chronic oral treatment with cannabis extract the hepatic total content of cytochrome P450 was strongly inhibited as well as the intestinal P-glycoprotein activity. It is suggested that the inhibition of hepatic metabolism determined an increased bioavailability of cannabidiol resulting in a greater effect. However, in the light of the well known antioxidant and antiinflammatory properties of terpenes and flavonoids which could significantly contribute to the therapeutic effects, it cannot be excluded that the synergism observed might be achieved also in the absence of the cytochrome P450 inhibition.
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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.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [41]
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- Authors
- Comelli, F., Giagnoni, G., Bettoni, I., Colleoni, M., & Costa, B.
- Affiliations
- University of Milano-Bicocca (IT)
- University of Milan (IT)
- Corresponding author
- Costa, Barbara
- ORCID
- Costa, Barbara
- Venue
- Phytotherapy Research
- Publisher
- Wiley
- Published
- 2008-07-29
- Volume
- 22
- Issue
- 8
- Pages
- 1017-1024
- ISSN
- 0951-418X (ISSN-L)
- 1099-1573
- OpenAlex
- W2044160665
- Cited by
- 103
- References
- 34
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 2 · 2018: 11 · 2017: 6 · 2016: 1 · 2014: 6 · 2013: 6 · 2012: 5
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Phytotherapy Research (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- Sanofi
- GW Pharmaceuticals
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry Medicinal Plant Applications
- Keywords
- Cannabis sativa extract, neuropathic pain, antihyperalgesia, antinociception, cannabidiol, TRPV1, vanilloid receptor, CB1 and CB2 receptors, terpenes, flavonoids, cytochrome P450 inhibition, P-glycoprotein, bioavailability, synergistic effect, phytocannabinoids
- MeSH terms
- Analgesics, Animals, Cannabidiol, Cannabinoids, Cannabis, Cytochrome P-450 Enzyme System, Disease Models, Animal, Hyperalgesia, Liver, Male, Pain, Plant Extracts, Rats, Wistar, Pain Threshold, ATP Binding Cassette Transporter, Subfamily B, Member 1, Sciatic Neuropathy, Receptors, Cannabinoid, TRPV Cation Channels, Rats, Cytochrome P-450 Enzyme Inhibitors
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