Rimonabant’s Intestinal Motility Effect Disappeared Rapidly With Repeated Dosing in Mice
Repeated rimonabant dosing produced rapid tolerance to its intestinal motility effect in mice. The result concerns a CB1-blocking drug and a gastrointestinal transit measure, rather than tolerance to cannabis intoxication.
A colored marker measured transit
Mice received rimonabant or control treatment twice daily for up to eight days. On selected days, separate groups received a non-absorbable colored marker into the stomach. Researchers recorded how far the leading edge traveled through the small intestine. The endpoint was physical transit distance, not pain, appetite or a subjective gastrointestinal symptom.
The first-dose effect did not persist
Rimonabant markedly increased intestinal peristalsis on the first treatment day. Complete tolerance to that effect developed by the third day in the protocol described. Because separate groups were used at the measurement points, the design should not be narrated as repeated marker tracking within the same individual mice.
Antagonist tolerance has a specific meaning
Rimonabant blocks CB1 receptors rather than reproducing THC's receptor activation. Adaptation to its prokinetic effect therefore cannot be transferred directly to a claim about how long cannabis tolerance takes to develop. The study also does not show that every physiological effect of rimonabant disappeared on the same schedule.
This experiment is useful for distinguishing acute pharmacology from effects sustained during repeated exposure. A strong first-dose transit response did not guarantee a continuing response. Its historical discussion of possible clinical relevance should not be read as a current recommendation to use rimonabant for gastrointestinal symptoms.
Related: interpreting cannabis tolerance claims.
Research cited
Carai MA; Colombo G; Gessa GL. Rapid tolerance to the intestinal prokinetic effect of cannabinoid CB1 receptor antagonist, SR 141716 (Rimonabant). European journal of pharmacology (2004). doi:10.1016/j.ejphar.2004.05.005. Findings discussed from the study abstract.
