The primary psychoactive metabolite of THC (11-OH-THC) was 7 to 31 times more potent than THC across multiple measures in mice, and THC was significantly more potent in female rats than males.
Pharmacologists, cannabis researchers, and clinicians advising on edible cannabis dosing.
11-OH-THC was up to 31x more potent than THC in hypothermia measures
What the researchers found
11-OH-THC showed 7- to 31-fold greater potency than THC for catalepsy and hypothermia in mice and 7- to 9-fold greater potency in drug discrimination. Female rats were significantly more sensitive to THC than males. THC discriminative stimulus effects were stable across 17 months of aging in mice.
Why it matters
When cannabis is eaten rather than smoked, more THC is converted to 11-OH-THC through first-pass liver metabolism. Understanding this metabolite's greater potency helps explain why edibles can produce stronger effects.
The numbers in context
11-OH-THC potency vs. THC: 7-15x for catalepsy, 7-31x for hypothermia, 7-9x in drug discrimination. 11-OH-THC affinity: ~1.5x higher than THC. Aging period: 17 months with stable THC discrimination.
How the study worked
Compared THC and 11-OH-THC using CB1 receptor binding assays, GTPgS functional assays, and in vivo behavioral tests (catalepsy, hypothermia, drug discrimination) across ICR mice, C57Bl/6J mice, and Sprague-Dawley rats of both sexes.
What this study cannot tell us
Animal study using intraperitoneal injection, not oral consumption. Cross-species differences complicate human extrapolation. Limited behavioral measures.
How to read the evidence
Rigorous pharmacological study across multiple species and assays, but animal models have limited direct human applicability.
When this study was published
Published in 2021.
The bigger picture
These findings have direct implications for cannabis edible dosing and may help explain why women often report stronger effects from cannabis than men.
Questions still open
- Do sex differences in THC metabolism explain why women report stronger cannabis effects? Should edible cannabis dosing guidelines account for the potency of 11-OH-THC?
Common questions
Why are cannabis edibles often stronger than smoking?
Are there sex differences in THC sensitivity?
Read the original research
Sex, species and age: Effects of rodent demographics on the pharmacology of ∆9-tetrahydrocanabinol.
Progress in neuro-psychopharmacology & biological psychiatry, 106, 110064
Citation
Wiley, Jenny L; Barrus, Daniel G; Farquhar, Charlotte E; Lefever, Timothy W; Gamage, Thomas F. (2021). Sex, species and age: Effects of rodent demographics on the pharmacology of ∆9-tetrahydrocanabinol.. Progress in neuro-psychopharmacology & biological psychiatry, 106, 110064. https://doi.org/10.1016/j.pnpbp.2020.110064
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