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Genetic Variant in the CRH-binding Protein Gene (CRHBP) is Associated With Cessation of Cocaine Use in Methadone Maintenance Patients With Opioid Addiction

Peles, Einat PhD; Levran, Orna PhD; Randesi, Matthew BSc; Ott, Jurg PhD; Kreek, Mary Jeanne MD; Adelson, Miriam MD

doi: 10.1097/ADM.0000000000000515
Original Research

Objectives: We have previously shown associations between 4 genetic variants in opioid and stress-related genes (OPRM1, NPYR1/NPYR5, NR3C1, and CRHBP) and prolonged abstinence from heroin without methadone maintenance treatment (MMT). We currently assessed the associations between these variants and MMT patients’ characteristics.

Methods: A non-selective group of 351 patients who stayed at least 1 year in their first admission to MMT were genotyped and their characteristics and substance in urine on admission and after 1 year were studied.

Results: The proportions of patients with both cocaine and benzodiazepine abuse were reduced significantly after 1 year in MMT; however, cocaine abuse cessation was significantly associated with the non-carriers of the CRHBP (corticotrophin releasing hormone binding protein) SNP rs1500 minor C allele (GG genotype) (P = 0.0009, PBonferroni = 0.0221). More carriers of the 2 C alleles (CC genotype) than carriers of the GC and GG genotypes abused cocaine on admission (32.3% vs 19.7%, respectively, P = 0.0414, recessive model), and more of the C allele carriers (GC and CC genotypes) than non-carriers (GG genotype) abused cocaine after 1 year in MMT (25.7% vs 15.8%, respectively, P = 0.0334, dominant model). Abusers of benzodiazepine were more prevalent among carriers of the C allele compared with non-carriers on admission (60.6% vs 45.9%, respectively, P = 0.0080, dominant model), as well as after 1 year in MMT (50.9% vs 39.1%, respectively, P = 0.0362).

Conclusions: Reduction in cocaine abuse among MMT patients may be mediated by a genetic effect in a stress-related gene (CRHBP SNP rs1500 minor C allele). Evaluations of larger samples, additional SNPs, and different populations are needed to support these findings.

Dr Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Tel Aviv Sourasky Medical Center (EP, MA); Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel (EP); The Laboratory of the Biology of Addictive Diseases (OL, MR, MJK, MA); The Laboratory of Statistical Genetics, The Rockefeller University, New York, NY (JO); Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Las Vegas, NV (MA).

Send correspondence to Einat Peles, PhD, Adelson Clinic, Tel Aviv Medical Center, 1 Henrietta Szold St., Tel Aviv 64924, Israel. E-mail:

Received 31 October, 2018

Accepted 14 December, 2018

The authors report no conflicts of interest.

The study was funded by The Dr. Miriam and Sheldon G. Adelson Family Foundation.

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© 2019 American Society of Addiction Medicine