Aged and Adolescent Mice Did Not Show the Same THC Adaptation Pattern

Age changed the observed adaptation pattern in a mouse THC study. Repeated exposure altered movement and hippocampal receptor signaling in adolescent animals without producing the same findings in aged animals.

Behavior and tissue assays were separate

Researchers measured open-field movement after THC and studied cannabinoid-stimulated G-protein activity in hippocampal membranes. They also examined repeated JZL184 treatment and levels of the endogenous cannabinoid 2-arachidonoylglycerol in another age group.

The THC comparison depended on age

Movement suppression was weaker in THC-pretreated than untreated adolescent mice. The corresponding difference was not observed in aged mice. Hippocampal basal and stimulated signaling also decreased after THC pretreatment in adolescents but was not affected in the aged group.

A null adaptation result is not proof of no acute effect

Lack of a pretreatment-related difference does not mean aged animals were unaffected by THC. It concerns whether repeated exposure changed the measured response. Similarly, a hippocampal membrane assay does not describe every brain region or cognitive function.

The JZL184 findings depended on dose and measurement, illustrating another limit on generalizing across interventions that affect the same broad system. These results do not establish cannabis safety for older adults, explain an individual person's tolerance or provide a driving rule. Age, drug, tissue and endpoint must accompany any conclusion about receptor adaptation.

Related: interpreting cannabis tolerance claims.

Research cited

Feliszek M; Bindila L; Lutz B; Zimmer A; Bilkei-Gorzo A; Schlicker E. Lack of hippocampal CB1 receptor desensitization by Δ(9)-tetrahydrocannabinol in aged mice and by low doses of JZL 184. Naunyn-Schmiedeberg's archives of pharmacology (2016). doi:10.1007/s00210-016-1226-6. Findings discussed from the study abstract.