Evidence map›Paper›PMID 21790905›Full record

ArticleAddiction biology2013

CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction.

Orna Levran, Einat Peles, Sara Hamon, Matthew Randesi, Miriam Adelson, Mary Jeanne Kreek

Open access · greenAbstract read
In one paragraph

Article in Addiction biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 2 pooled it
10.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013
    Trial
  7. Article
  8. Review
  9. Review
  10. Review
  11. Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025
    Review
  12. Article
  13. Article
  14. Influence ofLife (Basel, Switzerland) · 2023
    Article
  15. The Role of Pharmacogenomics in Opioid Prescribing.Current treatment options in oncology · 2022
    Review
  16. Article
  17. Pharmacogenetics of Addiction Therapy.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  18. Article
  19. Novel associations betweenPharmacogenomics · 2021
    Observational
  20. Genetic Vulnerability to Opioid Addiction.Cold Spring Harbor perspectives in medicine · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Orna LevranLaboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. levrano@rockefeller.edu
Einat Peles
Sara Hamon
Matthew Randesi
Miriam Adelson
Mary Jeanne Kreek
Rockefeller University · USTel Aviv Sourasky Medical Center · IL

Funding

ULTRASTUCTURE, RECEPTORS, AND GENE EXPRESSIONP60DA005130 · NIDA · ROCKEFELLER UNIVERSITY · PI KREEK, MARY J · 2002 to 2012
$30.6M
UNIQUE RNA STRUCTURE OF CAUSATIVE AGENT FOR DELTA HEPATITISP50DA005130 · NIDA · ROCKEFELLER UNIVERSITY · PI KREEK, MARY J · 1987 to 2001
$5.0M
NIDA NIH HHS P50 DA005130NIDA NIH HHS P60 DA005130PHS HHS NIDA-P60-05130
6 · The paper itself

Abstract

Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter-individual variability in dose-response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6 and CYP2D6. The CYP2B6*6 allele [single nucleotide polymorphisms (SNPs) 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dose requirement, it was genotyped in a well-characterized sample of 74 Israeli former heroin addicts in MMT. The sample is primarily of Middle Eastern/European ancestry, based on ancestry informative markers (AIMs). Only patients with no major co-medication that may affect methadone metabolism were included. The stabilizing daily methadone dose in this sample ranges between 13 and 260mg (mean 140±52mg). The mean methadone doses required by subjects homozygous for the variant alleles of the CYP2B6 SNPs 785A>G and 516G>T (88, 96mg, respectively) were significantly lower than those of the heterozygotes (133, 129mg, respectively) and the non-carriers (150, 151mg, respectively) (nominal P=0.012, 0.048, respectively). The results remain significant after controlling for age, sex and the ABCB1 SNP 1236C>T (rs1128503), which was previously shown to be associated with high methadone dose requirement in this population (P=0.006, 0.030, respectively). An additional 77 CYP2B6, CYP3A4 and CYP2D6 SNPs were genotyped. Of these, 24 SNPs were polymorphic and none showed significant association with methadone dose. Further studies are necessary to replicate these preliminary findings in additional subjects and other populations.

Indexed as

AdolescentAdultAgedAnalgesics, OpioidAnalysis of VarianceAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2B6Dose-Response Relationship, DrugEthnicityFemaleGene FrequencyHeterozygoteHomozygoteHumansIsraelLinkage DisequilibriumAnalgesics, OpioidAryl Hydrocarbon HydroxylasesCYP2B6 protein, humanCytochrome P-450 CYP2B6MethadoneOxidoreductases, N-Demethylating

Identifiers

PMID21790905
PMCPMC3735354
OpenAlexW1565736591

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.