Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6

@article{Yamaori2011CannabidiolAM,
  title={Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6},
  author={Satoshi Yamaori and Yasuka Okamoto and Ikuo Yamamoto and Kazuhito Watanabe},
  journal={Drug Metabolism and Disposition},
  year={2011},
  volume={39},
  pages={2049 - 2056}
}
Δ9-Tetrahydrocannabinol, cannabidiol (CBD), and cannabinol are the three major cannabinoids contained in marijuana, which are devoid of nitrogen atoms in their structures. In this study, we investigated the inhibitory effects of the major phytocannabinoids on the catalytic activity of human CYP2D6. These major cannabinoids inhibited the 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC) and dextromethorphan O-demethylase activities of recombinant CYP2D6 and pooled human… 

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References

SHOWING 1-10 OF 42 REFERENCES
Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids
TLDR
Results indicated that Δ9-THC, CBD, and CBN showed differential inhibition against CYP2A6 and CyP2B6, and were characterized as mechanism-based inhibitors for CYP 2A6.
The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin.
  • R. Pertwee
  • Biology, Chemistry
    British journal of pharmacology
  • 2008
Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds,
Marijuana extracts possess the effects like the endocrine disrupting chemicals.
The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin
TLDR
This review focuses on the manner with which three of these compounds, (−)‐trans‐Δ 9‐tetrahydrocannabinol (Δ9‐THC), (−]‐cannabidiol (CBD) and (−)-trans‐ Δ9‐TetrahYDrocannabivarin (Γ‐THCV), interact with cannabinoid CB1 and CB2 receptors.
Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman.
TLDR
The results indicate that a member of CYP2C is primarily responsible for the metabolism of the above cannabinoids in the human hepatic microsomes.
Effect of psychotropic drugs on the 21-hydroxylation of neurosteroids, progesterone and allopregnanolone, catalyzed by rat CYP2D4 and human CYP2D6 in the brain.
TLDR
Results indicate that psychotropic drugs including fluoxetine affected the metabolism of neurosteroids, such as PROG and ALLO in the brain, suggesting that the regulation of the neurosteroid levels is modified by central nervous system-active drugs that inhibit brain CYP2D isoforms.
Pharmacokinetics and Pharmacodynamics of Cannabinoids
TLDR
Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.
...
1
2
3
4
5
...