CYP2D6

CYP2D6 is expressed in tissues including the liver, kidney, placenta, brain, breast, lungs, and small intestine. It is expressed at a low level in human liver, accounting for only approximately 3% of total CYP450 protein. In the small intestine, CYP2D6 is expressed in the duodenum and jejunum and not in the ileum and colon.

Approximately 7–10% of the Caucasian population shows an inherited deficiency in this enzyme due to the presence of one or several mutant alleles at the CYP2D6 gene locus.

CYP2D6 Inhibitors and Inducers

Potent Inhibitors	Strength	Dosage	Verified in Humans
9-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-ylnon-8-en-1-one1 (in black pepper)	>50 % inhibition	10 mM[10]	?
Alpha-bisabolol (from German chamomile)	50 % inhibition	IC50 = 2.18 microM[12]	?
Andrographis paniculata	>70% inhibition[11]	IC50 86 μg/ml	?
Benzyl isothiocyanate [6]	?	?	?
Berberine (in goldenseal)[1][15]	Potent inhibition (900% increase in substrates[15])	300 mg for 2 weeks[15]	Yes[15]
Black Cumin seed (Nigella sativa)	99% inhibition2	2.5 g twice daily for seven days	Yes[8]
Black pepper extract	72.8% inhibition[11]	?	?
Cannabidiol (from cannabis)	?	?	?
Catharanthus roseus extract	50% inhibition	IC50=11 microg/ml[11]	?
Chamazulene (from German chamomile)	50 % inhibition	IC50 = 1.06 microM[12]	?
Cinnamomum burmanni	>70% inhibition[11]	IC50 1203 μg/ml	?
Dihydrotanshinone	50% Inhibition	IC50=35.4 μM[9]	?
Goldenseal extract[1][4]	50% Inhibition	1070 mg3, 3 times daily	Yes
Licorice root extract	70% inhibition[11]	IC50= 515 μM/ml	?
Pipercyclobutanamide A4 (in black pepper)	>50 % inhibition	10 mM[10]	?
Pomegranate extract (Punica granatum)	>70% inhibition[11]	IC50 32 μg/ml	?5
Pummelo	?	?	?
Resveratrol	A 70% increase in substrates	1 gram daily for 4 weeks	Yes[14]
Rheum palmatum	>70% inhibition[11]	IC50 385 μg/ml	?
Santalum album	>70% inhibition[11]	IC50 886 μg/ml	?
Star fruit juice	?	?	?
Syzygium aromaticum	>70% inhibition[11]	IC50 249 μg/ml	?
Tinospora crispa	>70% inhibition[11]	IC50 488 μg/ml	?
Zingiber aromaticum	>70% inhibition[11]	IC50 693 μg/ml	?
Moderate Inhibitors	Strength	Dosage	Verified in in Humans
Alpha-asarone (found in Calamus EO) [2]	?	IC50 = 55.2 μg/ml	?
Calamus EO [2]	?	1-3 drops (unverified)	?
Pi. cubeba	?	?	?
Quercetin	?	?	?
Zingiber aromaticum	?	?	?
Weak Inhibitors	Strength	Dosage	Verified in in Humans
Black cohosh [4]	Weak inhibition	?	Yes
Black cohosh extract6 [1]	No effect	40 mg, twice daily	Yes
Capsaicin (found in cayenne pepper, habanero peppers, etc.)	?	?	?
Cayenne pepper	?	?	?
Cryptotanshinone	?	?	?
Curcuma heyneana	?	?	?
Curcumin	?	?	?
German chamomile EO	?	?	?
Habanero pepper	?	?	?
Hydrastine (in goldenseal)[1]	50% Inhibition	(IC50 = 350 μM	?
Safrole	?	?	?
Sage [5]	?	?	?
Tanshinone I	?	?	?
Turmeric	?	?	?
In Vitro Inhibitors Inactive in Humans	Strength	Dosage	Verified in in Humans
Echinacea purpurea extract7 [1]	Inactive	267 mg, three times daily	Yes
Milk Thistle extract8 [1]	Inactive	300 mg, three times daily	Yes
Ginkgo biloba [4]	Inactive	?	Yes
Kava [4]	Inactive	?	Yes
Saint John’s Wort extract9 [1]	Inactive	300 mg, three times daily	Yes
Valerian Root [4]	Inactive	?	Yes
White grapefruit juice [7]	Inactive	3 cups	Yes
In Vitro Inhibitors Inactive in Rats	Strength	Dosage	Verified in Humans
Chamomile [13]	Inactive	?	?
Inducers	Strength	Dosage	Verified in Humans
Valerian root (inhibits then induces)	?	?	?
Valerian root EO	?	2-5 drops (unverified)	?

Bibliography

1. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea.

Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK; PubMed PMID 18214849

2. Fitoterapia. 2011 Apr;82(3):369-74. doi: 10.1016/j.fitote.2010.11.009. Epub 2010 Nov 6;

Metabolism mediated interaction of α-asarone and Acorus calamus with CYP3A4 and CYP2D6; Pandit S, Mukherjee PK, Ponnusankar S, Venkatesh M, Srikanth N; School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India; PubMed PMID 21062640

3.

Clin Pharmacol Ther. 2002 Sep;72(3):276-87. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY.; Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, 72205, USA; PubMed PMID: 12235448

4. Clin Pharmacol Ther. 2005 May;77(5):415-26;

In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes; Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A; Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, 4301 W Markham St, Slot 522, Little Rock, AR 72205, USA; PubMed PMID: 15900287

5. Hellum BH, Nilsen OG;

The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol; Basic Clin Pharmacol Toxicol. 2007 Nov;101(5):350-8; Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

6. Shufeng Zhou, Hwee-Ling Koh, Yihuai Gao,

Zhi-yuan Gong, Edmund Jon Deoon Lee; Herbal bioactivation: The good, the bad and the ugly; Life Sciences 74 (2004) 935 – 968; April 2003; DOI:10.1016/j.lfs.2003.09.035 (Download Attached PDF Document)

7. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB. PubMed PMID: 9153299

8. Effect of black seed on dextromethorphan O- and N-demethylation in human liver microsomes and healthy human subjects.

Al-Jenoobi FI, Al-Thukair AA, Abbas FA, Ansari MJ, Alkharfy KM, Al-Mohizea AM, Al-Suwayeh SA, Jamil S. PubMed PMID: 20201775

9. Molecular docking and enzyme kinetic studies of dihydrotanshinone on metabolism of a model CYP2D6 probe substrate in human liver microsomes.

Zhou X, Wang Y, Or PM, Wan DC, Kwan YW, Yeung JH. PubMed PMID: 22541637

10. Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum.

Subehan, Usia T, Kadota S, Tezuka Y. PubMed PMID: 16808005

11. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants.

Usia T, Iwata H, Hiratsuka A, Watabe T, Kadota S, Tezuka Y. PubMed PMID: 16360935

12. Inhibitory effects of the essential oil of chamomile (Matricaria recutita L.) and its major constituents on human cytochrome P450 enzymes.

Ganzera M, Schneider P, Stuppner H. PubMed PMID: 16137701

13. Effect of herbal teas on hepatic drug metabolizing enzymes in rats.

Maliakal PP, Wanwimolruk S. PubMed PMID: 11697539

14.

Resveratrol Modulates Drug- and Carcinogen-Metabolizing Enzymes in a Healthy Volunteer Study H-H. Sherry Chow, Linda L. Garland, Chiu-Hsieh Hsu, Donna R. Vining, Wade M. Chew, Jessica A. Miller, Marjorie Perloff, James A. Crowell and David S. Alberts; DOI: 10.1158/1940-6207.CAPR-09-0155 Published September 2010; PubMed PMCID: PMC2933312; NIHMSID: NIHMS207754

15. Repeated administration of berberine inhibits cytochromes P450 in humans

Ying Guo, Yao Chen, Zhi-rong Tan, Curtis D. Klaassen, Hong-hao Zhou; Published online 2011 Aug 26.; Eur J Clin Pharmacol. 2012 Feb; 68(2): 213–217.; doi: 10.1007/s00228-011-1108-2; NIHMSID: NIHMS583946; PMCID: PMC4898966

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If an inducer or inhibitor is present on this page and reliable human in vivo studies are available but not shown on this page please leave a comment about it using the Discuss link at the bottom of this page so we can update the inhibitor's data.

Footnotes

1. 9-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-ylnon-8-en-1-one is compound 15 in the PubChem reference's abstract.

2. Black Cumin (also known as (black seed) inhibited the action of CYP2D6 by 80% in vitro using human liver cells. It also potently inhibited CYP2D6 in human test subjects by 99%.[8]

3. The goldenseal extract was standardized to contain 24.1 mg isoquinoline alkaloids per capsule.

4. Pipercyclobutanamide A is compount 17 in the PubChem reference's abstract.

5. Anecdotal reports suggest that pomegranate has no effect in humans on CYP2D6.

6. The black cohosh extract tested was standardized to contain 2.5% triterpene glycosides per 40 mg tablet.

7. The echinacea purpurea extract tested was standardized to contain 2.2 mg isobutylamides per 267 mg capsule

8. The milk thistle extract tested was standardized to contain 80% silymarin.

9. The Saint John’s Wort extract tested was standardized to contain 3% hyperforin.