Polymorphisms in Stress-Related Genes Are Associated with Reduced Cocaine Abuse and Longer Retention in Methadone Maintenance Treatment for Opioid Use Disorder.

BACKGROUND: As CRH-binding protein (CRHBP) SNP rs1500 was associated with reduced cocaine abuse after 1 year in methadone maintenance treatment (MMT) for heroin addiction, we evaluated the association of additional 28 selected SNPs, in 17 stress-related genes, with MMT outcome. METHODS: The distribution of genotypes of each SNP by cocaine abuse after 1 year in MMT was assessed under the dominant and recessive models using χ2. Cumulative retention (up to 26.5 years) was studied using Kaplan-Meier analyses. Logistic regression and Cox model were used for multivariate analyses. RESULTS: Of a nonselective sample of 404 patients, 25 patients with <50% Europeans/Middle Eastern ancestry were excluded. Of the remaining 379 patients, 330 (87.1%) stayed at least 1 year in treatment. Four SNPs were associated with cocaine abuse after 1 year in MMT. A lower proportion of cocaine abusers was found in the groups of subjects with the following genotypes: arginine vasopressin (AVP) SNP rs2282018 CC, CRHBP rs7728378 TT, galanin rs3136541 TT/TC, and neuropeptide Y receptor Y1 (NPY1R) rs4518200 AA. The following independent variables were associated with lack of cocaine in urine after 1 year (multivariate analyses): CRHBP rs7728378 TT, NPY1R rs4518200 AA, no cocaine in urine on admission, as well as opiate and benzodiazepine use after 1 year in MMT. Cumulative retention (n = 379) was longer in carriers of AVP rs2282018 CC (13.7 years, 95% CI 11.1-16.2) versus TT/TC genotypes (10.5, 95% CI 9.4-11.5) (p = 0.0230) Conclusions: The study suggests that a reduction in cocaine abuse and longer retention among MMT patients is mediated in part by variants in stress-related genes and is a step toward precision medicine.

[STIGMA AND MISINFORMATION ABOUT METHADONE MAINTENANCE THERAPY].

INTRODUCTION: Opioids play a key role in managing acute and chronic pain, but at the same time, opioid abuse is a socio-economic and health problem that has been expanding over the past three decades, causing a high rate of morbidity and mortality. Methadone maintenance therapy is the most effective treatment choice (combined with psychosocial therapy) for opioid addiction. However, only a small proportion of people with opioid addiction turn to this treatment. In addition, patients applying for methadone maintenance treatment do so with great delay, after 10 and even 20 years of addiction. A possible explanation for this phenomenon discussed in the medical literature is stigma and misinformation about methadone maintenance therapy in patients with substance use disorder, society, family of patients, and healthcare professionals.

Drug Abuse and Behavioral Transgressions during Methadone Maintenance Treatment (MMT) are Related to High Psychopathy Levels.

Introduction: Studies which used the Psychopathy Checklist-Revised (PCL-R) among methadone maintenance treatment (MMT) patients focused mostly on methodological issues, without addressing its relationship to patients' misconduct during treatment. This paper tests the hypothesis that high PCL-R scores are related to high rates of drug abuse, and high numbers of behavioral transgressions in MMT during a 7-year period. Material and Methods: 107 MMT patients were recruited from a MMT clinic in Israel, and were administered the PCL-R. The questionnaires results as well as routine drug test findings were recorded between 7/2007 and 11/2007. Seven years later (7/2014), repeated drug test results were analyzed, and the number of behavioral transgressions during the entire period was computed. Results: High levels of psychopathy were related to drug test results indicating any illicit drug use, cocaine use and benzodiazepines misuse at the beginning of study, and limited to benzodiazepines misuse among patients who stayed in treatment at the 7-year follow-up. However, higher scores on different PCL-R facets were significantly associated with different types of drugs. The PCL-R's total score and all but the antisociality facet were positively correlated with a higher number of behavioral transgressions (such as, threats and/or verbal and physical aggression). Conclusions: Administration of the PCL-R during MMT may help identify patients with high illicit drug use levels and a higher chance of committing behavioral transgressions during treatment.

Educational lectures enhance knowledge about the human immunodeficiency virus (HIV) and reduce risky behavior and fear among methadone maintenance treatment patients.

Background: The aim of this study was to characterize human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-related knowledge and stigma among methadone maintenance treatment (MMT) patients and evaluate the contribution of an educational lecture in reducing risky behavior and unjustified overprotective behavior due to fear and stigma among MMT patients. Methods: Patients from an MMT clinic within a tertiary medical center were invited to an educational lecture on HIV/AIDS. Seventy participants (of current 330) were chosen by a random sample (December 2015), plus at-risk patients and HIV patients. Attendee compliance and change in scores of questionnaires on knowledge (modified HIV-K-Q-22) and on sexual and injection behaviors were studied. Results: Forty-six patients (65.7% compliance) attended the lecture, and their knowledge and behavior scores improved 2 weeks post-lecture (knowledge: from 14.2 ± 3 to 19.0 ± 2.2 [P < .0005], sexual behavior: from 12.1 ± 2.9 to 8.8 ± 3.0 [P < .0005], and injection behavior: from 7.3 ± 6.2 to 0.2 ± 1.3 [P < .0005]). The unjustified fear of proximity to HIV carriers reported by 50% attendees fell to 35% post-lecture. Eight months post-lecture, the scores on knowledge and risky behavior of 21 randomly chosen attendees were still better than pre-lecture scores (knowledge: 15.4 ± 2.3 vs. 17.2 ± 1.8 [paired t test, P = .001], sexual behavior: 13.2 ± 2.3 vs. 9.7 ± 2.9 [P < .0005], and injection behavior: 9.3 ± 5.6 vs. 2.8 ± 3.1 [P < .0005]). Drug abuse and treatment adherence were not related to intervention and to risky behavior. Conclusions: More knowledge, less fear, and less risky behavior immediately and at 8 months post-lecture reflect the success and importance of the educational intervention. Future efforts are needed in order to reduce ignorance and fear associated with HIV/AIDS.

Outcome of Patients With High Depressive Symptoms on Admission to Methadone Maintenance Treatment.

Objective: Comorbidity of depression among individuals with opioid addiction is highly prevalent, but their outcome in methadone maintenance treatment (MMT) is not well determined.Methods: Characteristics and outcomes (retention until December 2017) of newly admitted and already (5.5 ± 4 years) in MMT patients with available Hamilton Depression Rating Scale (HAM-D) scores on admission were studied.Results: During psychiatric intake on admission, 70 (21.2%) of 330 patients were diagnosed with high depressive symptoms beyond the cutoff (HAM-D scores ≥ 18). Depressed and nondepressed groups had a similar proportion of females (20% and 23.8%) and age at admission (43.0 ± 10.5 and 43.7 ± 10.4 years), but the depressed group had higher Brief Psychiatric Rating Scale (BPRS) scores (21.4 ± 8.6 vs. 7.0 ± 7.3, respectively; p < .0005), a higher proportion of minority (non-Jewish faith; 28.6% vs.15.4%; p =.02), and a higher proportion of positive urine screening results for cocaine (55.7% vs. 34.4%; p = .001) and for benzodiazepines on admission (74.3% vs. 57.5%; p = .01). Retention after 1 year was similar (79% and 80.7%), but depressed patients had higher rates of cocaine (40.8% vs. 25.5%; p = .05) and benzodiazepine use (59.2% vs. 41.8%; p = .04) and a shorter cumulative retention (5.6 years, 95% confidence interval [CI; 4.3, 7.0]) than the nondepressed patients (6.8 years, 95% CI [6.1, 7.5]; p = .05). Of the 263 evaluated while already in MMT, 23.5% were depressed, characterized with more females (43.5% vs. 23.4%) and with a history of rape (34.5% vs. 7.6%).Conclusions: Newly admitted depressed and nondepressed patients succeeded similarly in the first year retention in treatment, despite their cocaine and benzodiazepine co-abuse. The depression was characterized with females and with rape history in those who were already in MMT. Adequate intervention is recommended for both depressed groups to improve long-term retention and outcome.

Characteristics and Outcome of Male and Female Methadone Maintenance Patients: MMT in Tel Aviv and Las Vegas.

To compare in methadone maintenance treatment (MMT) gender characteristics and outcomes, all patients ever admitted to Tel Aviv (TA) MMT clinic (N = 837) (June 1993-December 2014) and Las Vegas (LV) MMT clinic (N = 1256) (February 2000-June 2015) were prospectively followed-up (until June 2016). Drugs in urine on admission and after one year and long-term retention up to 23 and 16 years, respectively, were analyzed. Females in both clinics admitted younger than males and following shorter duration of opioid usage (TA: n = 215, 25.7%, age 35.0 ± 7.9 vs. 40.6 ± 9.8 years, p < .0005, duration 12.4 ± 7.0 vs. 18.1 ± 10 years, p < .0005; LV, n = 494, 39.3%, age 38.0 ± 12.6 vs. 39.2 ± 12.8, p = .08 duration 12.9 ± 11.0 vs. 14.8 ± 12.7 years, p = .008). On admission, higher proportion of female than male had positive urine for cocaine in TA (30.4% vs. 21.8%, p = .02) and for benzodiazepine in LVs (33.9% vs. 26.6%, p = .006). After 1 year, both genders had similar retention rate (TA: 76.1% LV: 49.8%) and opioid abstinence (TA: 67.6%, LV: 74.9%), and cumulative retention (TA: 8.2 years, 95% Confidence-Interval 7.6-8.8; LV 2.2 years, 95% confidence interval 2.0-2.4). CONCLUSIONS: Clinics differed in their characteristics and outcome, however in both clinic similar outcome between genders despite the difference in characteristics on admission was observed, as did the known women "telescoping effect."

Newborn birth-weight of pregnant women on methadone or buprenorphine maintenance treatment: A national contingency management approach trial.

BACKGROUND AND OBJECTIVES: Methadone maintenance treatment (MMT) is the gold standard for pregnant women with opioid use disorders. Still, low birth-weights were reported, in particular of mothers who became pregnant before admission to MMT. We studied whether an escalating incentive contingency-management approach may contribute to better newborn birth-weights. METHODS: A nationwide controlled randomized trial among all Israeli methadone/buprenorphine maintenance treatment (MBMT), newly or already in treatment pregnant women was performed. A modified contingency-management protocol with coupons of escalating value depending upon reduction of drug use, cigarette smoking, and alcohol consumption was compared to standard care arm. Drugs in urine, smoking (Fagerstrom score), alcohol use, and depression were monitored. RESULTS: Thirty-five women had 46 pregnancies. In their first pregnancy, 19 from the contingency-management and 16 from the standard care arms were studied. Contingency-management group as compared to the standard care arm included more newly admitted women (36.8% vs. 6.3%, p = .05), with benzodiazepine and cannabis onset at a younger age, and higher proportion of any drug abuse while pregnant (100% vs. 68.8%, p = .01). Fifteen of the contingency-management and 14 of the control arm gave birth (78.9% vs. 87.5%, p = .3) with similar proportions of normal (>2,500 g) birth-weight (71.4% vs. 61.5%, p = .8). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Newborns' birth-weight was comparable among the two study arms indicating no contribution of the contingency-management approach. Small sample and baseline differences between arms might have influenced results. Intensive intervention should be evaluated on a larger scale of participants. (Am J Addict 2017;26:167-175).

Is a History of Sexual Abuse Related to Poor Sleep Among Former Opioid-Addicted Women With and Without Methadone Maintenance Treatment?

To study whether poor sleep that is known to characterize methadone maintenance treatment (MMT) patients may be related to their past sexual abuse and/or their treatment modality, we compared perceived sleep indices (Pittsburgh Sleep Quality Index (PSQI); Epworth Sleepiness Scale (ESS)) and depression (21-HAM-D) between women with and without sexual abuse history (Childhood Trauma Questionnaire) in MMT and in a non-MMT ("opioid medication-free") in-patient rehabilitation center (MABAT). Twenty-six sexually abused women in MMT had the worst sleep quality scores (PSQI) (10.4 ± 4.2), followed by 15 sexually abused non-MMT women (7.9 ± 4.8), with the lowest score among 13 MMT non-sexually abused women (6.3 ± 4.8, p = 0.03). ESS score and cognitive state scores (Mini Mental State Exam) were similar. Depression (21-HAM-D) score was similar between the two sexually abused (MABAT and MMT) groups (15.3 ± 7.0 and 15.0 ± 6.3, respectively), but was significantly higher than the nonabused MMT group (10.5 ± 6.3, p = 0.03). Logistic regression model for being poor sleeper (PSQI >5), found depression OR = 1.2 (95% CI: 1.1-1.4, p = 0.001), and poor cognitive state (MMSE) OR = 0.6 (95% CI: 0.3-0.9, p = 0.03) to characterize poor sleep. We conclude that poor sleepers were depressed and this characterized sexually abused women in both the MMT and non-MMT groups.

ADHD risk alleles associated with opiate addiction: study of addicted parents and their children.

BACKGROUND: Polymorphisms in genes such as DAT1, 5HTTLPR, D4DR4, and MAO-A have been linked to attention deficit hyperactivity disorder (ADHD) and susceptibility for opiate addiction. We investigated in opiate-addicted parents and their children the rate of ADHD and genetic markers that could predict susceptibility to ADHD and/or opiate addiction. METHODS: We studied 64 heroin-addicted, methadone-maintained parents, and their 94 children who had or had not been exposed prenatally to opiates. DNA extracted from mouthwash was assessed for genetic polymorphism for six polymorphic sites of four different genes. Study subjects also filled a variety of questionnaires assessing the rate of ADHD in the parents and children and the children's intelligence quotient. RESULTS: Children of opiate-dependent mothers had a higher rate of ADHD compared to those of the opiate-dependent fathers. Opiate-dependent parents have a high risk of being carriers of most risk alleles examined except DRD4EX3 (allele 7). There was no difference whether the addicted parents had or did not have ADHD. CONCLUSIONS: Serotonergic and dopaminergic risk alleles seem to be mainly related to opiate dependence with no effect on the occurrence of ADHD. People carrying those polymorphisms are susceptible to opioid addiction and not necessarily to ADHD.

Risk factors for weight gain during methadone maintenance treatment.

BACKGROUND: Weight gain was reported during methadone maintenance treatment (MMT). However, its relation to eating habits and specific risk factors, including methadone dose or serum level, was limited. The aims of this study were to characterize risk factors for weight gain and to study current eating habits, food preferences, and nutrition knowledge. METHODS: Patients with available measures of weight and height (body mass index [BMI]) at admission to MMT and at follow-up, when methadone serum levels were determined (after 1 year or when stabilized) (N = 114), were studied (using the Addiction Severity Index [ASI], drugs in urine, methadone doses, and serum levels). In addition, 109 current patients with available earlier (5.8 ± 2.6 years earlier) BMI completed eating behavior rating and nutrition knowledge questionnaires, and their current and earlier BMI were compared. RESULTS: The BMI of 114 newly admitted patients increased from 22.5 ± 3.8 to 24.4 ± 4.3 (P < .0005). Once stabilized on methadone, BMI increased further (24.3 ± 4.5 to 25.6 ± 5.0; P < .0005; n = 74), with no change in methadone doses (125.6 ± 32.5 to 128.0 ± 34.1; F = 1.4, P = .2) or serum levels (495.6 ± 263.7 to 539.8 ± 306.2; F = 1.3, P = .2). Repeated-measures analyses revealed that BMI elevation was higher among 45 hepatitis C virus seronegative and 46 non-benzodiazepine-abusing on-admission patients. Those who scored lower on knowledge about healthy diet and showed a higher sweet-foods preference had a higher BMI. CONCLUSION: BMI increased over time, but independent of methadone dosage and blood levels. As expected, worse diet habits and a desire for sweet foods are related to higher BMI. Paradoxically, healthier status (i.e., hepatitis C seronegative, no benzodiazepine abuse) at admission is predictive of greater weight gain during MMT. Education about nutrition habits is recommended.

Stroop task among patients with obsessive-compulsive disorder (OCD) and pathological gambling (PG) in methadone maintenance treatment (MMT).

OBJECTIVES: To evaluate the impaired attention selection (Stroop interference effect) and general performance [reaction times (RTs)] on the Stroop task among methadone maintenance treatment (MMT) patients with obsessive compulsive disorder (OCD), pathological gambling (PG), both PG/OCD or none, and the influence if having ADHD. METHODS: Eighty-six patients and 15 control subjects underwent the Stroop task, which measured RTs of condition-related words (color, obsessive compulsive disorder, pathological gambling, addiction) and neutral words. RESULTS: MMT patients had longer RTs on the Stroop task compared with controls. RTs were longer among patients with OCD and in those who abused drugs on the study day. The combined PG/OCD group had the longest RTs, but they were also characterized as abusing more drugs, being older, and having worse cognitive status. Stroop color interference differed only among MMT patients with ADHD, and it was higher among those with OCD than those without OCD. The modified condition-related Stroop did not show any interference effect of OCD, addiction, or gambling words. CONCLUSIONS: MMT patients had generally poorer performance, as indicated by longer RTs, that were related to clinical OCD, drug abuse, poor cognitive state, and older age. Patients with both clinical OCD and ADHD had a higher Stroop interference effect, which is a reflection of an attention deficit. In order to improve clinical approach and treatment of MMT patients, OCD and ADHD should be evaluated (and treated as needed).

Trends in substance abuse and infectious disease over 20 years in a large methadone maintenance treatment (MMT) clinic in Israel.

BACKGROUND: The objective was to study substance abuse, infectious disease, and patient outcomes (retention and substance abuse abstinence) over 2 decades in a large methadone maintenance treatment (MMT) facility within a tertiary-referral medical center. METHODS: Prevalence of substance abuse was determined monthly between 1993 (35 patients) and 2013 (350 patients) based on observed random urine tests. On entry, patients were tested for hepatitis C and human immunodeficiency virus (HIV) antibodies. One-year retention and substance abuse abstinence were calculated. RESULTS: At admission, mean age and rate of cocaine and benzodiazepines abuse increased over the years, with no change in the prevalence of hepatitis C (50%) and HIV (<10%). Retention rate increased (P = .008) (range: 42.9%-92.4%; overall: 76.2%) and opiate abstinence also increased (P = .006) (range: 49.1%-85.7%; overall: 68.1%), reflecting outcome improvement over the years. CONCLUSIONS: Outcome improvement could be attributed to the staff's growing experience and improvements in treatment but also to changes in patient characteristics over the past 2 decades.

Characteristics and outcome of minority group patients in methadone maintenance treatment.

Abstract Minority status is associated with mental and physical morbidity, substance dependence, and poor outcomes. To compare characteristics and treatment outcomes between patients from two minority groups in Israel (Christians and Muslims) and patients from the majority population (Jews) in methadone maintenance treatment (MMT), we prospectively studied all patients admitted to our clinic between 1993 and 2012 and followed up until 2013; 655 Jews, 67 Christians, and 37 Muslims. Christian patients differed from Jews and Muslims by younger age at admission to MMT, greater prevalence of drug injectors, and a higher proportion of Hepatitis-C and HIV sera positive. Muslims had comparatively less education and a lower proportion of females. The three groups had similar rates of one-year retention (75.9%) and opiate abstinence (68.1%). They also did not differ in long-term retention (up to 20 years): Muslims 5.5 years (95%CI 3.6-7.4), Christians 7.5 years (95%CI 6-9.1), and Jews 7.6 years (95%CI 7-8.2, p = .3). The Hepatitis-C incidence, however, was higher among the 21 admitted Hepatitis-C seronegative minorities (5.0/100 person years) than the 207 Hepatitis-C seronegative non-minority patients (1.7/100 person years, p=0.03). All groups had good treatment outcomes, except for Hepatitis-C seroconversion, which necessitates a specific preventive intervention among the minority groups.

The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among methadone maintenance treatment patients.

The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among patients in methadone maintenance treatment (MMT) was examined by the Vulnerable Attachment Style Questionnaire (VASQ), the Symptom Checklist-90 (SCL-90), and drug abuse urine tests. After six years, retention in treatment and repeated urine test results were studied. Patients with vulnerable attachment style (a high VASQ score) had higher rates of drug abuse and higher psychopathology levels compared to patients with secure attachment style, especially on the interpersonal sensitivity, anxiety, hostility, phobic anxiety, and paranoid ideation scales. Drug abstinence at baseline was related to retention in treatment and to higher rates of drug abstinence after six years in MMT, whereas a vulnerable attachment style could not predict drug abstinence and retention in treatment. Clinical Implications concerning treatment of drug abusing populations and methodological issues concerning the VASQ's subscales are also discussed.

Is pain empathy associated with pain indices and trauma history? A comparison between patients receiving methadone maintenance treatment and healthy controls.

BACKGROUND: To study whether pain empathy and theory of mind (ToM) are related to pain indices and trauma experience, we studied opioid users receiving methadone maintenance treatment (MMT), a population with a history of traumas and a high prevalence of chronic pain. METHODS: MMT patients (n = 53), substance abuse-free, with no impaired cognition (Montreal Cognitive Assessment (MoCA) ≥24), were compared to healthy controls (HC) matched by age and gender (n = 66). All participants were assessed using Reading the Mind in the Eyes (RMET) for ToM, empathy (Interpersonal Reactivity Index [IRI], Empathy Quotient Scale for Adults [EQ60]), and Pain Empathy [PE task]). An algometer was used for pain pressure threshold, and supra-pain threshold was rated using a visual analog scale (VAS). Catastrophizing, McGill pain, Negative life events (NLE), and MoCA questionnaires were administered. Substance abuse was tested in the urine of MMT patients and self-reported by HC. RESULTS: MMT, compared to HC, were less educated with more NLE and a lower RMET (logistic regression). Groups had comparable empathy and pain indices, except for higher supra-threshold VAS rating and catastrophizing in univariate analyses. Pain empathy (PE) correlated with NLE in HC, and in MMT, with catastrophizing, which correlated with NLE, perceived stress, and pain intensity. Higher empathy was observed in 18 participants with a history of sexual abuse (83.3 % belong to the MMT group). CONCLUSIONS: Pain Empathy was found to be associated with personal suffering experience in both groups, as reflected by correlations with NLE in HC and with catastrophizing, which correlates with NLE, stress, and pain intensity, in MMT.

Prevalence of high impulsivity and its relation to sleep indices in opioid use disorder patients receiving methadone maintenance treatment.

BACKGROUND: The relation between impulsivity and sleep indices is not well determined in patients receiving methadone maintenance treatment (MMT). AIMS: to evaluate high impulsivity prevalence, its risk factors and relation with sleep indices. METHODS: a random MMT sample (n = 61) plus MMT current cocaine users (n = 20) were assessed for impulsivity (Barratt impulsivity scale [BIS-11] and Balloon Analogue Risk task [BART]), sleep quality (Pittsburg Sleep Quality Index [PSQI]), sleepiness (The Epworth sleepiness scale [ESS]), and substance in urine. RESULTS: 81 patients, aged 56.6 ± 10, 54.3% tested positive to any substance, 53.1% with poor sleep (PSQI>5) and 43.2% with daytime sleepiness (ESS >7) were studied. Impulsivity (BIS-11 ≥ 72) prevalence was 27.9% (of the representative sample), and 30.9% of all participants. These patients characterized with any substance and shorter duration in MMT with no sleep indices or other differences including BART balloon task performance (that was higher only in any substance than non-substance user group). However, impulsive score linearly correlated with daytime sleepiness (R = 0.2, p = 0.05). Impulsivity proportion was lowest among those with no cocaine followed by cocaine use and the highest in those who used cocaine and opiates (20.8%, 33.3% and 60% respectively, p = 0.02), as daily sleep (38.3%, 42.1% and 60%, p = 0.3) although not statistically significant. CONCLUSION: Daytime sleepiness correlated with impulsivity, but cocaine usage is the robust factor. Further follow-up is warranted to determine whether substance discontinuing will lead to a reduction in impulsivity, and improved vigilance. Sleep quality did not relate to daytime sleepiness and impulsivity and need further research.

Fentanyl abuse proportion in methadone maintenance treatment, and patients' knowledge about its risks.

INTRODUCTION: Fentanyl is not yet routinely monitored among methadone maintenance treatment (MMT) patients in Israel. We aimed 1. to evaluate urine fentanyl proportion changes over 3 years and characterize patients' characteristics 2. To study patients' self-report on fentanyl usage, and compare knowledge about fentanyl risk, before and following brief educational intervention. METHODS: Fentanyl in the urine of all current MMT patients was tested every 3 months year between 2021 and 2023, and patients with positive urine fentanyl were characterized. Current patients were interviewed using a fentanyl knowledge questionnaire (effects, indications, and risks) before and following an explanation session. RESULTS: Proportion of fentanyl ranged between 9.8 and 15.1%, and patients with urine positive for fentanyl (September 2023) were characterized as having positive urine for pregabalin, cocaine, and benzodiazepine (logistic regression). Of the current 260 patients (87% compliance), 78(30%) self-reported of fentanyl lifetime use ("Ever"), and 182 "never" use. The "Ever" group had higher Knowledge scores than the "Never", both groups improved following the explanatory session (repeated measure). The "Ever" group patients were found with urine positive for cannabis and benzodiazepine on admission to MMT, they were younger, did not manage to gain take-home dose privileges and had a higher fentanyl knowledge score (logistic regression). CONCLUSIONS: In the absence of routine fentanyl tests, a high knowledge score, shorter duration in MMT, benzodiazepine usage on admission, and current cannabis usage, may hint of the possibility of fentanyl abuse.

Occurrence of hypertension among patients with opioid use disorder in methadone maintenance treatment.

BACKGROUND: Patients in methadone maintenance treatment (MMT) may develop age-related medical problems, but hypertension (HTN) proportion and its occurrence during MMT have not been studied yet. We aimed to evaluate changes in blood pressure (BP) during MMT and characterize current HTN. METHODS: Of all 1098 ever admitted MMT patients, those with ≥2 BP follow-up measures were included ( n  = 516), of them all current patients ( N  = 245) tested for HTN (systolic BP ≥140 mmHg or diastolic BP ≥90 were detected twice (one week apart) were considered as affected with HTN. Current and earliest during the first, and latest year in MMT of body mass index (BMI), BP, methadone dose and serum level, and drugs in urine were analyzed. RESULTS: HTN was detected in 89(36.3%) of the current patients. The HTN and non-HTN groups did not differ by sex ( P  = 0.6), age ( P  = 0.2), and duration in MMT ( P  = 0.6), but had higher BMI (27.9 ±â€Š5.2 vs. 25.6 ±â€Š5.2, respectively, P  = 0.001) and fewer had positive urine test findings for any substance (31.5% vs. 44.9%, P  = 0.04). Comparing their earliest measures (before 11.9 ±â€Š5.8 years), BP and BMI increased more among the hypertensive group, independent of methadone dose and serum levels, which significantly reduced over the years. No drug abuse was associated with increased BMI and BP. CONCLUSIONS: Weight gain was associated with BP elevation and characterized patients who succeeded in drug abstinence during MMT. Healthy nutrition education at admission to MMT may reduce the incidence of weight gain and HTN, therefore identifying HTN and offering treatment for this highly prevalent life-threatening condition among middle-age and older patients in MMT is recommended.

Different characteristics but comparable hypertension rates between two MMT "twin" clinics.

BACKGROUND: Patients in methadone maintenance treatment (MMT) may develop age-related medical problems. Objective: To compare hypertension prevalence and its risk factors between two MMT clinics, having similar treatment guidelines, but different characteristics, one from Tel Aviv (TA) and one from Las Vegas (LV). METHODS: Prevalence of hypertension (systolic ≥140 and or diastolic ≥90 mmHg BP) among all current 291 MMT patients in TA and 180 patients in LV were studied, including body mass index (BMI), drugs in urine, sociodemographic, and addiction history data. RESULTS: Hypertension prevalence was comparable in TA (35.4%) and LV (34.4%), however TA patients were older (55.9 ± 9.5 vs. 45.5 ± 13.3, p < 0.001), with fewer females (22 vs. 42.2%, p < 0.001), fewer obese (BMI ≥30) (24 vs. 40.9%, p < 0.001), higher cocaine (21 vs. 7.8%, p < 0.001), and lower cannabis (14.1 vs. 32.4%, p < 0.001) and amphetamines (0 vs. 33.5%) users. Logistic regression found higher BMI to characterize hypertension in both clinics, but in TA also negative urine cocaine, benzodiazepine, and opioids screen, while in LV older age (≥50 y), male gender, and negative urine cannabis screen. CONCLUSIONS: While TA was characterized with older patients, LV patients had a comparable hypertension rate, as obesity was more prevalent. No drug use was accompanied by higher BMI in TA and therefore associated with hypertension. Weight reduction, hypertension detection and treatment are recommended.

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

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.