Berberine is an alkaloid found in goldenseal (hydrastis canadensis) at concentrations typically between 2.5-6% dry weight.
Effects On Cytochrome P450 Enzymes
Berberine has been shown to be a very potent CYP2D6 inhibitor. It also strongly inhibits CYP2C9 and weakly inhibits CYP3A4. Goldenseal is known to have no effect on CYP2E1 in humans. Berberine is also likely to have no effect on CYP2E1, but tests in humans using pure berberine appear to be currently lacking.
| Effects On Cytochrome P450 Enzymes | |||
|---|---|---|---|
| Enzyme | Effect | Dosage | Verified In Humans |
| CYP1A2 | no effect [1] | 300 mg for 2 weeks[1] | Yes[1] |
| CYP2A6 | ? | ? | ? |
| CYP2C19 | no effect [1] | 300 mg for 2 weeks[1] | Yes[1] |
| CYP2C9 | inhibition (200% increase in substrates)[1] | 300 mg for 2 weeks[1] | Yes[1] |
| CYP2D6 | inhibition (900% increase in substrates)[1] | 300 mg for 2 weeks[1] | Yes[1] |
| CYP2E1 | ? | ? | ? |
| CYP3A4 | inhibition (40% increase in substrates)[1] | 300 mg for 2 weeks[1] | Yes[1] |
Promising Use In Oilahuasca
THE ANECDOTAL REPORTS IN THIS SECTION REQUIRE FURTHER VALIDATION BEFORE BEING CONSIDERED FACTUAL
Berberine has been tested by several individuals as an oilahuasca admixture. Doses tested were 300 mg and above taken as berberine hydrochloride. In one report as little as 20 mg of elemicin taken together with 1 cup of coffee (caffeine inhibits CYP1A2), 300 mg berberine hydrochloride and 100 mg steviosides, produced effects described as nearly equal to a 50 mg dose of mescaline hydrochloride. Larger doses of elemicin were also tested, with similar results, giving activated elemicin a potency roughly 250% the potency of mescaline.
Berberine is believed to help activate elemicin because it inhibits CYP2D6, CYP3A4 and CYP2C9, while leaving CYP2E1 fully active. CYP2D6, CYP3A4 and CYP2C9 can all theoretically O-demethylate elemicin into methoxyeugenol. By inhibiting these enzymes, elemicin is more likely to be attacked by CYP2E1. CYP2E1 is not known to O-demethylate allylbenzenes, but is known to 1'-hydroxylate them. By shifting attack of elemicin to CYP2E1, it is likely to prevent the formation of methoxyeugenol and favor the formation of 1'-hydroxyelemicin. The metabolite 1'-hydroxyelemicin can then theoretically form 1'-oxoelemicin (by the action of the enzyme Estradiol 17beta-dehydrogenase Type 2), which can then form alkaloids in vivo (see oilahuasca for more details).
Note that in the tests reported CYP1A2 was inhibited by taking the capsules with coffee (caffeine inhibits CYP1A2). UGT2B7 was also potentially inhibited by using 100 mg or more of pure steviosides (isolated sweeteners extracted from the stevia plant). This is done to prevent attack of 1'-hydroxyelemicin by UGT2B7. If 1'-hydroxyelemicin is attacked by UGT2B7 it forms 1'-hydroxyelemicin glucuronide which is not capable of forming alkaloids in vivo. By inhibiting UGT2B7, the metabolite 1'-oxoelemicin is favored over 1'-hydroxyelemicin glucuronide.
Chemical Properties
Synonyms: Berberin; Umbellatine; Berberal; Thalsine
CAS #: 2086-83-1
Molecular Formula: C20H18NO4+
Canonical SMILES: COC1=C(C2=C[N+]3=C(C=C2C=C1)C4=CC5=C(C=C4CC3)OCO5)OC
InChI Key: YBHILYKTIRIUTE-UHFFFAOYSA-N
InChI: InChI=1S/C20H18NO4/c1-22-17-4-3-12-7-16-14-9-19-18(24-11-25-19)8-13(14)5-6-21(16)10-15(12)20(17)23-2/h3-4,7-10H,5-6,11H2,1-2H3/q+1
Molecular Weight: 336.36122 g/mol
XLogP3: 3.6
Melting Point: 145 °C
PubChem CID: 2353