THC Cross-Tolerance to Anandamide Differed Between Body Temperature and Isolated Tissue
THC pretreatment reduced anandamide sensitivity in isolated mouse tissue without producing detected cross-tolerance to anandamide-induced hypothermia. The same exposure history gave different answers depending on the endpoint.
The whole-animal comparison used temperature
After two days of THC pretreatment, mice showed tolerance to THC hypothermia and cross-tolerance to CP55,940 and WIN55,212-2 hypothermia. The same pretreatment did not produce detected cross-tolerance to anandamide's temperature effect. That exception is essential to the result.
The tissue comparison broadened the pattern
Vas deferens preparations from pretreated mice were less sensitive to inhibition of electrically evoked contractions by THC and all three challenge compounds, including anandamide. THC's concentration-response curve also showed reduced maximal inhibition. A curve shift and a lower response ceiling describe different aspects of adaptation.
The discrepancy remained a research question
The authors regarded the tissue preparation as useful for investigating pharmacodynamic tolerance but explicitly called for further work on the anandamide temperature exception. It would be inaccurate to present an established receptor explanation when the supplied material leaves the cause unresolved.
This experiment shows why a general statement about cross-tolerance needs the measured function attached. It does not demonstrate that anandamide is universally exempt from THC-related adaptation or that every tissue response predicts whole-animal behavior. Neither preparation establishes an individual's degree of cannabis impairment.
Related: interpreting cannabis tolerance claims.
Research cited
Pertwee RG; Stevenson LA; Griffin G. Cross-tolerance between delta-9-tetrahydrocannabinol and the cannabimimetic agents, CP 55,940, WIN 55,212-2 and anandamide. British journal of pharmacology (1993). doi:10.1111/j.1476-5381.1993.tb13989.x. Findings discussed from the study abstract.
