CBDA plasma levels were 14 times higher when administered in a cannabis extract compared to the same dose as an isolated compound, because other cannabinoids blocked the BCRP drug efflux pump that normally limits CBDA absorption.
Cannabis pharmacologists, formulators of cannabinoid medicines, and researchers studying the entourage effect.
14x higher CBDA plasma levels from extract vs. isolated compound
What the researchers found
Plasma CBDA concentrations were 14-fold higher from cannabis extract versus isolated CBDA at the same dose. In vitro testing identified CBDA as a substrate of the BCRP efflux transporter. CBG and THC inhibited BCRP-mediated transport of CBDA. This cannabinoid-cannabinoid pharmacokinetic interaction at intestinal BCRP transporters explains the dramatic increase in absorption.
Why it matters
This is one of the first mechanistic demonstrations of a pharmacokinetic "entourage effect." It means CBDA from whole-plant extracts reaches much higher blood levels than expected from its dose, with implications for both efficacy and dosing.
The numbers in context
CBDA plasma levels 14x higher from extract vs. isolated compound. CBDA identified as BCRP substrate. CBG and THC inhibited BCRP transport of CBDA.
How the study worked
Mouse pharmacokinetic comparison of cannabinoids administered as cannabis extract versus individual compounds at equivalent doses. In vitro BCRP transwell transport assays identified the drug interaction mechanism.
What this study cannot tell us
Mouse pharmacokinetics may differ from humans. Only CBDA absorption was dramatically affected; other cannabinoids may not show the same magnitude of interaction. The clinical significance of elevated CBDA levels depends on CBDA having its own therapeutic effects.
How to read the evidence
Mechanistically elegant study combining in vivo pharmacokinetics with in vitro transporter assays, but mouse-only data.
When this study was published
2021 study. First mechanistic demonstration of a pharmacokinetic cannabinoid-cannabinoid interaction via drug transporters.
The bigger picture
The entourage effect is usually discussed in pharmacodynamic terms (compounds acting together on receptors). This study reveals a pharmacokinetic entourage effect: compounds altering each other's absorption, which could be equally or more important.
Questions still open
- Do other cannabinoid-cannabinoid interactions at drug transporters exist? Could this explain why whole-plant extracts seem more effective than isolated compounds in some studies? Would standardizing cannabinoid ratios in extracts improve dosing predictability?
Common questions
What is the BCRP transporter?
What does this mean for cannabis medicines?
Read the original research
Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations.
Scientific reports, 11(1), 14948
Citation
Anderson, Lyndsey L; Etchart, Maia G; Bahceci, Dilara; Golembiewski, Taliesin A; Arnold, Jonathon C. (2021). Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations.. Scientific reports, 11(1), 14948. https://doi.org/10.1038/s41598-021-94212-6
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