Cyclosporine Affected Developing Cannabinoid Tolerance Differently From Established Tolerance in Mice
In a mouse experiment, cyclosporine reduced the development of tolerance to the synthetic cannabinoid WIN 55,212-2 but did not change the expression of tolerance once established. The distinction concerns experimental timing, not an established treatment for cannabis tolerance.
Two cannabinoid effects adapted at different speeds
WIN 55,212-2 produced dose- and time-dependent antinociceptive effects and catalepsy, a movement-related state. With daily administration, complete tolerance developed within five days for the pain-response measure and nine days for catalepsy. Even within one experiment, there was no single tolerance timeline for every outcome.
Pretreatment and later intervention were different tests
Giving cyclosporine before repeated WIN administration attenuated the development of both forms of tolerance. However, it did not affect expression of existing tolerance. Acute cyclosporine pretreatment also did not change the initial antinociceptive or cataleptic effects of WIN. Chronic cyclosporine alone did not alter the response to an acute WIN challenge.
What the selectivity supports
These comparisons suggest an influence on adaptation during repeated exposure rather than simple amplification of the initial cannabinoid response. They do not identify a universally effective way to reverse tolerance. WIN is a synthetic receptor agonist, and the mice received injections; neither feature reproduces ordinary cannabis consumption.
The study is useful when assessing claims that a compound prevents or reverses cannabis tolerance. Prevention during a dosing regimen, reversal after tolerance develops and improvement in a human clinical outcome require different evidence. This experiment should not be treated as a reason to use cyclosporine for cannabis-related effects.
Related: interpreting cannabis tolerance claims.
Research cited
Banafshe HR; Ghazi-Khansari M; Dehpour AR. The effect of cyclosporine on the development and expression of cannabinoid tolerance in mice. Pharmacology, biochemistry, and behavior (2005). doi:10.1016/j.pbb.2005.11.006. Findings discussed from the study abstract.
