Initial THC Sensitivity and Rapid Tolerance Were Different Measurements in Mice
How strongly an animal responds to its first THC exposure is not the same as how much its response changes at the next exposure. A mouse study measured these separately and found different sex- and strain-related patterns.
Two strains and several endpoints
Male and female C57BL/6J and DBA/2J mice received repeated THC or vehicle. Investigators measured temperature, movement and tail withdrawal from a thermal stimulus. Initial sensitivity was defined relative to baseline on the first exposure; rapid tolerance was defined by the change between the first and second exposures.
The pattern depended on the test
Strain differences appeared in movement suppression and antinociception, while females showed greater initial hypothermic responses. Rapid tolerance appeared in temperature and antinociceptive measures, with much less adaptation on the movement-related measure.
Not every apparent sex contrast was significant
For rapid antinociceptive tolerance, the study found a strain effect but no significant main effect of sex or sex-by-strain interaction. Descriptive differences between group averages should not be promoted into a confirmed sex effect on that endpoint.
From a definition to an inference
A baseline-to-first-dose contrast and a first-to-second-dose contrast can vary for different reasons. Neither measurement alone describes long-term dependence or every form of cannabis impairment. The animal strains, injected regimen and brief observation period further restrict transfer to people. For research interpretation, specify how tolerance was calculated rather than assuming that a stronger first response necessarily predicts more or less later tolerance.
Related analysis: evaluating cannabis tolerance claims.
Primary research
Parks C; Jones BC; Moore BM; Mulligan MK. Sex and Strain Variation in Initial Sensitivity and Rapid Tolerance to Δ9-Tetrahydrocannabinol. Cannabis and cannabinoid research (2020). DOI: 10.1089/can.2019.0047.
