Sublingual buprenorphine/naloxone treatment is not affected by OPRM1 A118G and BDNF Va66Met polymorphisms, but alters the plasma beta-endorphin and BDNF levels in individuals with opioid use disorder

The study aimed to examine the genetic contribution to buprenorphine (BUP) treatment in individuals with opioid use disorder (OUD), with a specific focus on BDNF and OPRM1 genes. A total of 113 controls and 111 OUD patients receiving sublingual BUP/naloxone were enrolled. OPRM1 A118G and BDNF Val66Met polymorphisms were investigated by PCR-FRLP. Plasma BDNF and beta-endorphin levels were assessed by ELISA kits in both groups. Blood BUP levels were measured by LC-MS/MS and normalized with daily BUP dose (BUP/D). OPRM1 A118G and BDNF Val66Met polymorphisms didn't have an effect on plasma beta-endorphin and BDNF levels in OUD patients, respectively. Interestingly, OUD patients had significantly higher plasma BDNF and lower beta-endorphin levels compared to the controls (p < 0.001). A negative and significant correlation between plasma BUP/D and BDNF levels was found. Age onset of first use was associated with OPRM1 A118G polymorphism. The findings indicated that sublingual BUP/naloxone may increase plasma BDNF levels, but may decrease beta-endorphin levels in individuals with OUD. Plasma BDNF level seemed to be decreased in a BUP/D concentration-dependent manner. © 2022 Elsevier B.V

How probation affects treatment of opioid use disorders: Comparison of early remission rates between opioid use disorder patients admitted to medical clinic voluntarily and by probation

© 2019, Pacini Editore S.p.A.. All rights reserved.Background: Probation is a well-intentioned approach that aims to bring substance abusers back into the community. In the literature there is a lack of studies dedicated to showing how probation affects the treatment outcomes of opioid use disorders. Aim: This study aims to explore the probation’s impact on treatment outcomes of opioid use disorders by comparing the early remission rates of patients admitted voluntarily and by probation. Methods: 158 convicts on probation and 303 patients with opioid use disorder who applied voluntarily were included in the study. The sociodemographic characteristics and the early remission rates of the patients were compared. Based on DSM-5 criteria, early remission refers to the failure to meet any of the criteria of substance use disorder, other than craving or a strong desire, and the compulsion to use such substances for at least 3 months, but for a time period shorter than 12 months. Results: Early remission rate among patients who applied voluntarily (38.9%) was significantly higher than patients who were referred to us as convicts on probation (26.6%). Independent factors raising the probability of early remission were found to be voluntary referral to outpatient clinics (1.791-fold), being male (4.855-fold) and old age (1.090-fold), while being single (0.508-fold) and a long duration of substance use (0.981-fold) were found to be independent factors lowering the probability of early remission. Conclusion: The findings of the present study demonstrate that in patients suffering from opioid use disorder, the willingness and motivation of the individual to undergo treatment were more effective than motivations based on the threat of legal sanctions

Association of OPRK1 rs963549 and rs997917 polymorphisms with opioid use disorder and related phenotypes

Aim: To evaluate the association between OPRK1 rs963549 and rs997917 and opioid use disorder (OUD) and related phenotypes. Methods: A sample of 208 individuals with (n = 100) and without (n = 108) OUD were enrolled. OPRK1 rs963549 and rs997917 were analyzed by PCR-RFLP. Craving, opioid withdrawal and the intensity of depressive and anxiety symptoms were measured by the appropriate scales. Results:OPRK1 rs963549 variation showed a trend of association with decreased opioid withdrawal. No significant associations were found between OPRK1 rs963549 and rs997917 polymorphisms and craving, depression or anxiety symptoms. Neither single OPRK1 SNPs nor OPRK1 haplotypes were associated with OUD. Conclusion: Our results could be useful for treatment failures of individuals who experience greater opioid withdrawal due to their OPRK1 rs963549 genotypes

Effect of PDYN rs2281285, rs2235749 and rs910080 gene polymorphisms on the intensity of depression symptoms and negative craving in heroin addicts

The present study was undertaken to explore whether prodynorphin (PDYN) polymorphisms have an effect on the intensity of depressive symptoms and negative craving in heroin addicts in a sample of 100 heroin addicts and 108 controls. PDYN rs2281285, rs2225749 and rs910080 polymorphisms were analyzed by PCR-RFLP. Craving and the intensity of depressive symptoms were measured by the Substance Craving Scale and the Beck Depression Inventory-II, respectively. A significant association between depression severity and PDYN rs2281285 (P=0.026) and rs2225749 (P=0.038) polymorphisms was detected. PDYN rs2225749 variation showed a trend association with increased negative craving (P=0.066). We also examined the associations between heroin dependence and PDYN rs2281285, rs2225749 and rs910080 gene polymorphisms at the gene and haplotype levels. The AAA haplotype was more frequent in heroin addicts and shown to be significantly associated with increased risk for heroin dependence (OR, 8.922; 95% CI, 1.116-71.313; P[removed

Association of PDYN 68-bp VNTR polymorphism with sublingual buprenorphine/naloxone treatment and with opioid or alcohol use disorder: Effect on craving, depression, anxiety and age onset of first use

In this case-control study (423 Turkish subjects), the functional pro-dynorphin (PDYN) 68-bp VNTR polymorphism was genotyped in opioid users receiving sublingual buprenorphine/naloxone treatment (SBNT; n = 129, 119 males and 10 females), in opioid users (OUD; n = 99, 90 males and 9 females), in alcohol users (AUD; n = 75, 75 males) and in controls (n = 120, 109 males and 11 females) to determine the effect of this polymorphism on different treatment responses, heroin or alcohol dependence as well as age onset of first use. The PDYN 68-bp alleles were determined based on the number of repeats and genotypes were classified as “short/ short (SS)”, “short-long (SL)” and “long-long (LL)”. The intensity of craving, withdrawal, depression and anxiety were measured by the Substance Craving Scale (SCS), the Clinical Opiate Withdrawal Scale (COWS), the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively. Healthy controls (5.5 ± 5.8) had significantly lower levels of depressive symptoms compared to OUD (25.4 ± 13.5), AUD (22.5 ± 11.3) and SBNT (19.29 ± 12.2) groups. In OUD group, the LL genotype was associated with decreased intensity of anxiety and depressive symptoms than the SS+SL genotype. The BDI-II scores for PDYN VNTR genotypes within the 4 groups were analysed by two-way ANOVA and statistical differences were found for the groups. SBNT group had significantly lower COWS score than OUD group (1.00 versus 3.00). There were statistically significant differences in the median BAI (11 versus 24) and BDI-II scores (17.5 versus 25) between OUD and SBNT groups, supporting the antidepressant and anxiolytic effects of SBNT in persons with OUD

Effects of UGT2B7 rs7662029 and rs7439366 polymorphisms on sublingual buprenorphine metabolism in heroin addicts: An improved PCR-RFLP assay for the detection of rs7662029 polymorphism

This study aimed to determine the effects of UGT2B7 rs7662029 and rs7439366 polymorphisms on plasma buprenorphine (BUP) concentration and different treatment responses in a sample of 109 patients with opioid use disorder (OUD) treated with sublingual BUP/naloxone. Polymorphisms were analysed by PCR-RFLP. Plasma concentrations of BUP and its metabolite norbuprenorphine were detected by LC-MS/MS. Craving, withdrawal, depression and anxiety were measured by appropriate scales. OUD patients with rs7439366 CC or rs7662029 GG genotypes had significantly lower dose-normalized (BUP/D) and dose/kg-normalized BUP (BUP/D.kg(-1)) levels than those who were CT or AA carriers. Significant associations between UGT2B7 rs7662029 and increased craving (p = 0.037) and withdrawal symptoms (p = 0.029) were detected. Our findings were pointing to an important role of UGT2B7 in the metabolism of sublingual BUP/naloxone in the heroin addicts for the first time. A novel PCR-RFLP assay was developed for the determination of UGT2B7 rs7662029 polymorphism, based on utilizing novel restriction enzyme