Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene

Purpose The aim of this secondary analysis was to identify prodynorphin ( PDYN ) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). Methods Cocaine-dependent participants ( N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. Results In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group ( P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group ( N = 35) had fewer cocaine-positive urines ( P = 0.0006) than did the PLB group ( N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group ( N = 49) had fewer cocaine-positive urines ( P = 0.0003) than did the PLB group ( N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. Conclusion These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.