Normalized THC Challenge Curves Did Not Mean Baseline Responding Was Unchanged
A dose–response curve expressed as a percentage of control can coexist with changes in the underlying baseline behavior. A primate THC study reported baseline responding separately from challenge-drug sensitivity.
Two comparisons served different purposes
McMahon’s experiment measured food-maintained and stimulus-shock-termination responding before and during repeated THC. Challenge doses were used to examine sensitivity, while vehicle-session behavior showed how responding itself changed across the treatment history.
The denominator was part of the measurement
The paper reports reduced responding during the early chronic-treatment period and plots vehicle performance across days. A normalized challenge curve describes a dose effect relative to its reference. It does not establish that the reference behavior remained at the original untreated level.
Tolerance does not automatically restore the starting condition
A rightward shift in a challenge curve supports reduced drug sensitivity on that measure. A separate baseline comparison is needed to assess whether ordinary task performance has returned to its earlier level. The response-rate experiment involved three monkeys and injected THC, rather than human driving. The methodological lesson is to retain both absolute or longitudinal baseline behavior and normalized drug effects before describing tolerance as complete behavioral recovery.
Related: Interpreting cannabinoid tolerance evidence.
Research cited
Lance R. McMahon. Chronic Δ9-tetrahydrocannabinol treatment in rhesus monkeys: differential tolerance and cross-tolerance among cannabinoids (2011).
