Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α2‐adrenoceptor agonists in acute pain models in mice
Open accessAbstract
Cannabinoid receptor agonists elicit analgesic effects in acute and chronic pain states via spinal and supraspinal pathways. We investigated whether the combination of a cannabinoid agonist with other classes of antinociceptive drugs exerted supra‐additive (synergistic) or additive effects in acute pain models in mice. The interactions between the cannabinoid agonist CP55,940, α2‐adrenoceptor agonist dexmedetomidine and μ‐opioid receptor agonist morphine were evaluated by isobolographic analysis of antinociception in hot plate (55°C) and tail flick assays in conscious male Swiss mice. Drug interactions were examined by administering fixed‐ratio combinations of agonists (s.c.) in 1 : 1, 3 : 1 and 1 : 3 ratios of their respective ED 50 fractions. CP55,940, dexmedetomidine and morphine all caused dose‐dependent antinociception. In the hot plate and tail flick assays, ED 50 values (mg kg−1) were CP55,940 1.13 and 0.51, dexmedetomidine 0.066 and 0.023, and morphine 29.4 and 11.3, respectively. Synergistic interactions existed between CP55,940 and dexmedetomidine in the hot plate assay, and CP55,940 and morphine in both assays. Additive interactions were found for CP55,940 and dexmedetomidine in the tail flick assay, and dexmedetomidine and morphine in both assays. Thus, an α2‐adrenoceptor agonist or μ opioid receptor agonist when combined with a cannabinoid receptor agonist showed significant synergy in antinociception in the hot plate test. However, for the tail flick nociceptive response to heat, only cannabinoid and μ opioid receptor antinociceptive synergy was demonstrated. If these results translate to humans, then prudent selection of dose and receptor‐specific agonists may allow an improved therapeutic separation from unwanted side effects. British Journal of Pharmacology (2005) 144, 875–884. doi:10.1038/sj.bjp.0706045
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The combination of CP55,940 and morphine synergistically attenuates thermal nociception in mice.
“For example, the combination of CP55,940 and morphine synergistically attenuates thermal nociception in mice (Tham et al, 2005).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Tham et al, 2005
In preclinical models of acute pain, cannabinoid receptor agonists augment the antinociceptive effects of opioids.
“Cannabinoid receptor agonists augment the antinociceptive effects of opioids in preclinical models of acute pain, suggesting that cannabinoid agonists are opioid-sparing (Mecs et al, 2010;Tham et al, 2005;Tuboly et al, 2009).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Tham et al, 2005
Analyses showed greater than additive results (synergism) for CP55,940 with morphine in the tail-flick and hot plate tests.
“Analyses showed greater than additive results (synergism)”
From Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) · cites this paper as Tham 2005
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- Authors
- Tham, S. M., Angus, J. A., Tudor, E. M., & Wright, C. E.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Wright, Christine E
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2005-03
- Volume
- 144
- Issue
- 6
- Pages
- 875-884
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1576059
- OpenAlex
- W1987722050
- Cited by
- 98
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 2 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 9 · 2012: 9
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
- Keywords
- CP55,940, cannabinoid receptor agonists, mu-opioid receptor agonists, alpha-2 adrenergic agonists, dexmedetomidine, morphine, drug synergy, drug interactions, antinociception, acute pain, hot plate test, tail-flick test, isobolographic analysis, analgesia
- MeSH terms
- Acute Disease, Adrenergic alpha-Agonists, Analgesics, Analgesics, Opioid, Animals, Cannabinoids, Cyclohexanols, Dose-Response Relationship, Drug, Drug Synergism, Injections, Spinal, Male, Morphine, Pain, Pain Measurement, Receptors, Opioid, mu, Analgesics, Non-Narcotic, Dexmedetomidine, Mice
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