Cannabinoid Tolerance in Isolated Guinea-Pig Intestine Was More Selective Than Morphine Tolerance
Intestinal tissue from opioid- and cannabinoid-treated animals did not show the same pattern of reduced drug responsiveness. A guinea-pig study found broader subsensitivity after morphine and more selective changes after WIN55,212-2.
Exposure occurred before the tissue assay
Animals received repeated drug treatment in vivo. Researchers then examined longitudinal muscle and myenteric plexus preparations, measuring inhibition or stimulation of contractions by several test drugs.
The receptor findings differed
Chronic cannabinoid treatment reduced CB1 receptor protein abundance without a corresponding reduction in mu-opioid receptor protein. Repeated morphine did not produce the same protein-abundance pattern, despite broader changes in tissue responsiveness.
Co-localization did not settle function
The distribution and co-localization of the receptors in myenteric neurons were not changed by either treatment. Unchanged anatomical overlap does not establish unchanged signaling, as the contraction and sensitivity findings illustrate.
These were isolated intestinal preparations, not direct measurements of human analgesia, intoxication or withdrawal. A change in the concentration needed to affect a tissue contraction should not be translated into a human dose adjustment. The study is useful for distinguishing cellular adaptation patterns between drug systems while showing why no single receptor-abundance measurement can explain every functional change.
Related: interpreting cannabis tolerance claims.
Research cited
Maguma H; Thayne K; Taylor DA. Characteristics of tolerance in the guinea pig ileum produced by chronic in vivo exposure to opioid versus cannabinoid agonists. Biochemical pharmacology (2010). doi:10.1016/j.bcp.2010.05.005. Findings discussed from the study abstract.
