Tolerance to Rimonabant’s Feeding Effect Did Not Remove Its Response to a Hunger Stimulus
Loss of one feeding effect did not mean that CB1 blockade had become inactive. In rats, tolerance to rimonabant's reduction of ordinary intake coexisted with retained suppression of a feeding stimulus.
The study separated baseline intake and challenge
Researchers examined food intake after rimonabant and after hexarelin, a peptide used to stimulate feeding. They then repeated antagonist treatment and administered further challenge tests during the regimen.
The responses adapted differently
The abstract reports early tolerance to the ordinary intake-suppressing effect while body weight remained below the vehicle group. Rimonabant nevertheless continued to suppress the feeding effect of repeated hexarelin challenges.
Different measures answer different questions
Daily intake, body weight and response to a stimulated appetite are not interchangeable. Weight reflects cumulative influences, while a challenge tests the system under an additional perturbation. A diminished baseline effect cannot establish absence of every receptor-related action.
This was an animal receptor-blockade study, not evidence for taking cannabis or an antagonist to control weight. The experiment also does not establish the safety of a treatment or a clinical appetite-management plan. It illustrates why tolerance should be attached to a specified response rather than used as a blanket statement that a drug has stopped working.
Related: interpreting cannabis tolerance claims.
Research cited
Rigamonti AE; Giordani C; Bonomo SM; Cella SG; Müller EE. Early tolerance to the hypophagic effect of the cannabinoid receptor antagonist SR141716 does not impede blockade of an orexigenic stimulus. European journal of pharmacology (2006). doi:10.1016/j.ejphar.2006.05.028. Findings discussed from the study abstract.
