Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting.

Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop heroin addiction by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe heroin addicts in methadone treatment, and 184 healthy controls with no history of drug abuse. Nine variants, in six genes, showed the lowest nominal P values in the association tests (P < 0.01). These variants were in noncoding regions of the genes encoding the mu (OPRM1; rs510769 and rs3778151), kappa (OPRK1; rs6473797) and delta (OPRD1; rs2236861, rs2236857 and rs3766951) opioid receptors; the neuropeptide galanin (GAL; rs694066); the serotonin receptor subtype 3B (HTR3B; rs3758987) and the casein kinase 1 isoform epsilon (CSNK1E; rs1534891). Several haplotypes and multilocus genotype patterns showed nominally significant associations (e.g. OPRM1; P 5 0.0006 and CSNK1E; P 5 0.0007). Analysis of a combined effect of OPRM1 and OPRD1 showed that rs510769 and rs2236861 increase the risk of heroin addiction (P 5 0.0005). None of these associations remained significant after adjustment for multiple testing. This study suggests the involvement of several genes and variants in heroin addiction, which is worthy of future study. Heroin addiction is a chronic relapsing disease characterized by compulsive drug seeking, drug abuse, tolerance and physical dependence. It is treated by methadone, buprenorphine and behavioral therapy. Heroin addiction is part of group of addictions (e.g. cocaine, alcohol and nicotine) that constitute a worldwide public health crisis. The genetic contribution to vulnerability to develop heroin addiction is 40-60%, suggesting a complex inheritance mode in which multiple genes exert a small effect, along with the environment (Kendler et al. 2003;Tsuang et al. 1996Tsuang et al. , 1998. ). These include variants in the genes encoding the mu and kappa opioid receptors, dopamine receptors D2 and D4, serotonin receptor 1B, gamma-aminobutryic acid (GABA) receptor subunit gamma 2, catechol-O-methyltransferase, period circadian protein (PER3), proenkephalin, proopiomelanocortin, tryptophan hydroxylase 2 and brain-derived neurotrophic factor.To identify genetic variants that underlie heroin addiction, we performed a candidate gene case-control association study using a single nucleotide polymorphism (SNP) array that was designed by the group of D. Goldman at the National Institute of Alcohol Abuse and Alcoholism (NIAAA). This approach is based on physiological hypotheses and the genes were selected based on their function (e.g. drug receptors, neurotransmitters, transporters and drug metabolism enzymes) and related pathways (e.g. reward modulation, behavioral control, cognitive function, signal transduction and stress response). In order to maximize the power of the study, the cases were selected from the extreme margin of the specific phenotype range (e.g. severe heroin a...

The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy.

EPENDENCE ON OPIOIDS, IN THE form of heroin or prescription pain medications, is a significant health concern. 1-3 Methadone maintenance treatment for opioid dependence reduces morbidity, mortality, and the spread of infectious diseases 4 but is restricted to licensed specialty clinics in the United States, requires frequent clinic visits, and has a risk of mortality with overdose. 5 These issues have led to increased use of buprenorphine, and numerous studies support the efficacy of sublingually administered buprenorphine. 6 In the United States, buprenorphine can be prescribed in office-based physician practice. 7 Because it is a partial agonist, buprenorphine has less risk of overdose than methadone. 8 However, there are concerns about diversion and nonmedical use of sublingual buprenorphine, even when a buprenorphine-naloxone combination (designed to reduce misuse) is used. 9-11 Poor treatment adherence, resulting in craving and withdrawal symptoms that increase the likelihood of relapse, is also a concern with sublingual buprenorphine. 12