In rats with inflammatory pain, oral THC alone provided dose-dependent pain relief (especially in females), but adding CBD diminished THC's analgesic effects.
Pain researchers, cannabis medicine formulators, and clinicians prescribing cannabinoid-based pain treatments.
CBD diminished THC pain relief when combined, and females responded better to THC than males
What the researchers found
Oral THC dose-dependently decreased hyperalgesia and allodynia in a carrageenan inflammatory pain model, with stronger effects in females than males. The lowest THC dose (1 mg/kg) was actually pro-inflammatory in males. CBD alone did not affect pain sensitivity but had modest anti-inflammatory effects in males. When combined, CBD diminished THC antinociception (subadditive interaction), suggesting THC alone is superior to THC+CBD for acute inflammatory pain.
Why it matters
Many cannabis pain products contain both THC and CBD, assuming they work synergistically. This study challenges that assumption for inflammatory pain, suggesting pure THC formulations may be more effective.
The numbers in context
THC doses: 1, 3, 10 mg/kg oral. CBD doses: 10, 30, 100 mg/kg oral. THC antinociception was greater in females than males. THC 1 mg/kg was pro-inflammatory in males. CBD+THC interaction was subadditive by isobolographic analysis.
How the study worked
Male and female Sprague-Dawley rats (n=10-14 per sex/group) received oral pretreatment with vehicle, THC (1, 3, 10 mg/kg), CBD (10, 30, 100 mg/kg), or THC+CBD combinations 1 hour before carrageenan injection. Edema, thermal hyperalgesia, and mechanical allodynia measured at 1, 3, and 5 hours. Isobolographic and dose addition analyses assessed interaction type.
What this study cannot tell us
Rat model of acute inflammatory pain may not translate to chronic pain conditions. Oral administration through gavage differs from human cannabis consumption. Only acute (pretreatment) effects studied. Specific THC:CBD ratios tested may not reflect commercial product ratios.
How to read the evidence
Well-designed animal study with sex comparisons and isobolographic analysis, but translation to human inflammatory pain conditions is uncertain.
When this study was published
2025 publication.
The bigger picture
The finding that CBD can antagonize THC pain relief contradicts the popular assumption that CBD always enhances or modulates THC effects beneficially. The sex difference in THC pain relief adds to growing evidence that cannabis-based pain treatments may need to be sex-specific.
Questions still open
- Do commercial THC:CBD ratio products underperform compared to pure THC products for inflammatory pain?
- Why are females more responsive to THC analgesia than males?
Read the original research
Cannabidiol interactions with Δ-9-tetrahydrocannabinol on antinociception after carrageenan-induced inflammatory pain in male and female rats.
The Journal of pharmacology and experimental therapeutics, 392(7), 103625
Citation
Jenkins, Bryan W; Moore, Catherine F; Weerts, Elise M. (2025). Cannabidiol interactions with Δ-9-tetrahydrocannabinol on antinociception after carrageenan-induced inflammatory pain in male and female rats.. The Journal of pharmacology and experimental therapeutics, 392(7), 103625. https://doi.org/10.1016/j.jpet.2025.103625
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