Oral THC Modified Some Oral Morphine Outcomes in Mice but Left Withdrawal Diarrhea Unchanged
Oral THC coadministration reduced several morphine-related outcomes in mice, but the benefits were not uniform. Withdrawal jumping decreased while diarrhea remained unchanged, and a very high morphine challenge limited the apparent prevention of antinociceptive tolerance.
The regimen used oral administration
ICR mice received repeated high-dose oral morphine, with some groups also receiving an oral THC dose that was not antinociceptive by itself in the protocol. Morphine tolerance was prevented under several challenge conditions, but not when a very high morphine dose was used. The term low dose in this animal study should not be treated as a human dosing recommendation.
Withdrawal outcomes split apart
Chronic THC coadministration reduced naloxone-precipitated platform jumping but did not reduce diarrhea. Acute THC in morphine-tolerant mice produced a similar distinction. Consequently, a statement that THC eliminated opioid withdrawal would be inconsistent with the measured outcomes.
Cross-tolerance was not observed in the separate test
Morphine-tolerant mice were not cross-tolerant to acute THC antinociception; they were more sensitive in that comparison. This result concerns the direction from prior morphine to later THC and should remain separate from the chronic cotreatment findings.
The study offers an experimental oral-route comparison and preserves an important negative finding. Its suggestion of possible clinical benefit was prospective. It does not establish effective treatment of opioid tolerance or withdrawal in people, and the different challenge results argue against treating the combination as universally protective.
Related: interpreting cannabis tolerance claims.
Research cited
Cichewicz DL; Welch SP. Modulation of oral morphine antinociceptive tolerance and naloxone-precipitated withdrawal signs by oral Delta 9-tetrahydrocannabinol. The Journal of pharmacology and experimental therapeutics (2003). doi:10.1124/jpet.102.046870. Findings discussed from the study abstract.
