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Cited by 105Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsPain Management and Opioid Use

Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine

Roberts, John D., Gennings, Chris, Shih, Margaret·2006·European Journal of Pharmacology
DOI 10.1016/j.ejphar.2005.11.036
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Abstract

Evidence for an analgesic interaction between delta-9-tetrahydrocannabinol (Delta(9)-THC) and morphine was sought using an experimental pain model applied to normal volunteers. The study incorporated a double blinded, four treatment, four period, four sequence, crossover design. Subjects received Delta(9)-THC 5 mg orally or placebo and 90 min later morphine 0.02 mg/kg intravenously or placebo. Fifteen minutes later subjects rated the pain associated with the application of thermal stimuli to skin using two visual analog scales, one for the sensory and one for the affective aspects of pain. Among sensory responses, neither morphine nor Delta(9)-THC had a significant effect at the doses used, and there was no significant interaction between the two. Among affective responses, although neither morphine nor Delta(9)-THC had a significant effect, there was a positive analgesic interaction between the two (p = 0.012), indicating that the combination had a synergistic affective analgesic effect. The surprisingly limited reported experimental experience in humans does not support a role for Delta(9)-THC as an analgesic or as an adjunct to cannabinoid analgesia, except for our finding of synergy limited to the affective component of pain. Comparison of our results with those of others suggests that extrapolation from experimental pain models to the clinic is not likely to be a straight-forward process. Future studies of Delta(9)-THC or other cannabinoids in combination with opiates should focus upon clinical rather than experimental pain.

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Crossref · 10.1016/j.ejphar.2005.11.036

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  • In an experimental pain model involving thermal stimuli applied to normal subjects, the combination of morphine and THC showed an enhanced analgesic effect with respect to the affective component of pain, whereas the doses of morphine or THC used alone did not elicit a significant analgesic effect.

    “In this study, the doses of morphine or THC used alone did not elicit a significant analgesic effect, but combination of the drugs showed an enhanced analgesic effect with respect to the affective component of pain.”

    From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Roberts et al, 2006

  • In Roberts 2006, the combination of delta-9-THC and morphine did not have an effect on pain intensity; the combination resulted in lower ratings of unpleasantness of pain compared with either drug alone.

    “Combination of delta-9-THC and morphine did not have an effect on pain intensity.The combination resulted in lower ratings of unpleasantness of pain compared with either drug alone”

    From Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) · cites this paper as Roberts 2006

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Authors
Roberts, J. D., Gennings, C., & Shih, M.
Affiliations
  • Virginia Commonwealth University (US)
  • Los Angeles County Department of Public Health (US)
Corresponding author
Roberts, John D.
ORCID
Venue
European Journal of Pharmacology
Publisher
Elsevier BV
Published
2006-01
Volume
530
Issue
1-2
Pages
54-58
ISSN
0014-2999 (ISSN-L)
DOI
10.1016/j.ejphar.2005.11.036
OpenAlex
W2145508348
Cited by
103
References
19
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 7 · 2017: 9 · 2016: 1 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 7
FWCI
1.70
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • European Journal of Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords
delta-9-tetrahydrocannabinol, morphine, analgesic interaction, synergistic analgesia, affective pain, sensory pain, experimental pain models, thermal pain
MeSH terms
Adolescent, Adult, Analgesics, Double-Blind Method, Drug Synergism, Female, Hot Temperature, Humans, Injections, Intravenous, Male, Middle Aged, Morphine, Pain, Pain Measurement, Dronabinol, Cross-Over Studies

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