Cannabinoid Potency and Receptor Efficacy Had Different Rankings in a Primate Study
The dose needed to produce an effect and the ability to activate a receptor are different properties. A rhesus-monkey experiment illustrates why a more potent cannabinoid should not automatically be called a higher-efficacy agonist.
The dose comparison measured potency
McMahon compared THC, CP55,940 and WIN55,212-2 on learned responding. Before chronic THC treatment, CP55,940 was more potent than THC, while WIN55,212-2 was slightly less potent on the measured response-rate outcomes. Those comparisons concern the doses producing a specified effect.
Efficacy supplied a different mechanistic question
The paper discusses evidence of higher CB1 agonist efficacy for WIN55,212-2 and CP55,940 than for THC. Chronic THC produced greater loss of sensitivity to THC than to those higher-efficacy agonists, supporting a receptor-efficacy interpretation of the adaptation. Efficacy and the observed dose ranking were therefore not interchangeable.
The ranking belongs to the assay
The chronic response-rate comparison involved three monkeys receiving controlled injected drugs. It does not provide human intoxication multipliers or dose conversions for cannabis products. Receptor number, coupling and the response measured can affect an agonist’s apparent activity. Describing the actual property—dose potency, receptor efficacy or maximum response—avoids turning one experimental ranking into a universal statement about drug strength.
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).
