THC Hormone Tolerance Spared the Immobilization-Stress Response in Mice
A 1974 mouse study found tolerance to THC-related increases in plasma corticosterone without reducing the response to immobilization stress. The endocrine adaptation was stimulus-specific rather than a demonstrated shutdown of stress responsiveness.
Extract and purified-compound conditions were examined
Cannabis extract and THC increased plasma corticosterone. Prior extract or THC exposure attenuated the later THC-related rise. These plasma hormone measurements were distinct from the study's tissue-weight and catalepsy outcomes.
A separate stressor retained its effect
The extract pretreatment did not reduce the corticosterone increase caused by immobilization. That control helped distinguish tolerance to a drug challenge from a generalized inability to produce the hormone response. It did not establish that every aspect of the stress system remained unchanged.
Temperature helped test another explanation
In a thermoneutral environment, the hormone effect and its tolerance still occurred without hypothermia. Some tissue-weight findings differed with temperature. The corticosterone response therefore could not be attributed solely to drug-induced cooling under the reported conditions.
The experiment illustrates the value of alternative-stimulus and environmental controls. It does not provide a human endocrine diagnosis or show that cannabis protects against stress. Extract composition, old THC nomenclature, injected regimens and mouse physiology all limit translation to modern products and patients.
Related: interpreting cannabis tolerance claims.
Research cited
Pertwee RG. Tolerance to the effect of delta1-tetrahydrocannabinol on corticosterone levels in mouse plasma produced by repeated administration of cannabis extract or delta1-tetrahydrocannabinol. British journal of pharmacology (1974). doi:10.1111/j.1476-5381.1974.tb10674.x. Findings discussed from the study abstract.
