Other cannabinoids in cannabis extract dramatically increased CBDA blood levels by blocking a drug transporter
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.
Quick Facts
What This Study 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.
Key Numbers
CBDA plasma levels 14x higher from extract vs. isolated compound. CBDA identified as BCRP substrate. CBG and THC inhibited BCRP transport of CBDA.
How They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- 14x higher CBDA plasma levels from extract vs. isolated compound
- Evidence Grade:
- Mechanistically elegant study combining in vivo pharmacokinetics with in vitro transporter assays, but mouse-only data.
- Study Age:
- 2021 study. First mechanistic demonstration of a pharmacokinetic cannabinoid-cannabinoid interaction via drug transporters.
- Original Title:
- Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations.
- Published In:
- Scientific reports, 11(1), 14948 (2021)
- Authors:
- Anderson, Lyndsey L(10), Etchart, Maia G, Bahceci, Dilara(3), Golembiewski, Taliesin A, Arnold, Jonathon C
- Database ID:
- RTHC-02969
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is the BCRP transporter?
Breast cancer resistance protein (BCRP) is a drug efflux pump in the intestines that pumps certain substances back into the gut, limiting their absorption. CBDA is normally expelled by BCRP, but other cannabinoids in cannabis extract block this pump.
What does this mean for cannabis medicines?
It means whole-plant cannabis extracts may deliver dramatically different cannabinoid blood levels than expected from isolated compound dosing. This has major implications for product formulation and dosing accuracy.
Read More on RethinkTHC
- CBD-oil-quality-guide
- anxiety-medication-after-quitting-weed
- cannabis-chemotherapy-nausea
- cannabis-chronic-pain-research
- cannabis-epilepsy-CBD-Epidiolex
- cbd-anxiety-research-evidence
- cbd-for-weed-withdrawal
- cbd-vs-thc-difference
- medical-benefits-of-cannabis
- quitting-weed-before-surgery
- quitting-weed-medication-interactions
- quitting-weed-pregnancy
- quitting-weed-pregnant
- seniors-older-adults-cannabis-risks-medications
- weed-breastfeeding-THC-breast-milk
Cite This Study
https://rethinkthc.com/research/RTHC-02969APA
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
MLA
Anderson, Lyndsey L, et al. "Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations.." Scientific reports, 2021. https://doi.org/10.1038/s41598-021-94212-6
RethinkTHC
RethinkTHC Research Database. "Cannabis constituents interact at the drug efflux pump BCRP ..." RTHC-02969. Retrieved from https://rethinkthc.com/research/anderson-2021-cannabis-constituents-interact-at
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.