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Sample records for 21-day methadone detoxification

  1. Implosive Therapy Treatment of Heroin Addicts during Methadone Detoxification.

    ERIC Educational Resources Information Center

    Hirt, Michael; Greenfield, Heywood

    1979-01-01

    Examined effectiveness of implosive therapy with heroin addicts during detoxification from methadone. Treatment groups received 12 sessions of implosive therapy or eclectic counseling and were followed for a six-week period. The implosive therapy group were the only ones to significantly reduce their methadone level during treatment and follow-up.…

  2. Comparison of methadone and buprenorphine for opiate detoxification (LEEDS trial): a randomised controlled trial

    PubMed Central

    Wright, Nat MJ; Sheard, Laura; Adams, Clive E; Rushforth, Bruno J; Harrison, Wendy; Bound, Nicole; Hart, Roger; Tompkins, Charlotte NE

    2011-01-01

    Background Many opiate users require prescribed medication to help them achieve abstinence, commonly taking the form of a detoxification regime. In UK prisons, drug users are nearly universally treated for their opiate use by primary care clinicians, and once released access GP services where 40% of practices now treat drug users. There is a paucity of evidence evaluating methadone and buprenorphine (the two most commonly prescribed agents in the UK) for opiate detoxification. Aim To evaluate whether buprenorphine or methadone help to achieve drug abstinence at completion of a reducing regimen for heroin users presenting to UK prison health care for detoxification. Design Open-label, pragmatic, randomised controlled trial in three prison primary healthcare departments in the north of England. Method Prisoners (n = 306) using illicit opiates were recruited and given daily sublingual buprenorphine or oral methadone, in the context of routine care, over a standard reduced regimen of not more than 20 days. The primary outcome measure was abstinence from illicit opiates at 8 days post detoxification, as indicated by urine test (self-report/clinical notes where urine sample was not feasible). Secondary outcomes were also recorded. Results Abstinence was ascertained for 73.7% at 8 days post detoxification (urine sample = 52.6%, self report = 15.2%, clinical notes = 5.9%). There was no statistically significant difference in the odds of achieving abstinence between methadone and buprenorphine (odds ratio [OR] = 1.69; 95% confidence interval [CI] = 0.81 to 3.51; P = 0.163). Abstinence was associated solely with whether or not the participant was still in prison at that time (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for lasting abstinence was abstinence at an earlier time point. Conclusion There is equal clinical effectiveness between methadone and buprenorphine in achieving abstinence from opiates at 8 days post detoxification within prison

  3. Self-Efficacy and Illicit Opioid Use in a 180-Day Methadone Detoxification Treatment.

    ERIC Educational Resources Information Center

    Reilly, Patrick M.; And Others

    1995-01-01

    Studied self-efficacy and treatment outcomes in a sample of opioid addicts. Results show self-efficacy influenced subsequent drug use in parallel with previous behavior. Suggests that psychological constructs like self-efficacy may hold promise for understanding and decreasing illicit opioid use during long-term methadone detoxification treatment.…

  4. Major disruptions of sleep during treatment of the opiate withdrawal syndrome: differences between methadone and lofexidine detoxification treatments.

    PubMed

    Beswick, Tracy; Best, David; Rees, Sian; Bearn, Jenny; Gossop, Michael; Strang, John

    2003-03-01

    Sleep disturbance experienced during methadone or lofexidine opiate detoxification was investigated in 118 opiate-dependent patients receiving inpatient detoxification treatment. Sleep was assessed at four time-points during opiate detoxification using a self-report questionnaire. Maximum sleep disruption occurred at completion of detoxification and during the protracted withdrawal period, with patients in the methadone group reporting higher levels of withdrawal symptoms, lower overall sleep, longer sleep latencies and significantly longer periods of time awake than lofexidine patients. Regression analyses demonstrated a significant relationship between sleep disturbance, protracted withdrawal and retention in treatment, in addition to the major treatment benefit of reduced sleep disturbance conferred by lofexidine treatment.

  5. Methadone

    PubMed Central

    Sim, S. K.

    1973-01-01

    Methadone and acetylmethadol, although possessing almost all of morphine's pharmacological properties, differ from other morphine-like drugs in their longer action, more gradual and less intense withdrawal syndrome, and blockade of euphoric effect of other opiates in addicts. A high percentage of patients maintained on methadone are better able to hold employment or to be otherwise socially productive than when dependent on heroin or morphine. A review of published results and procedures used in methadone maintenance treatment programs for heroin dependence is presented. Former heroin addicts are usually maintained on 80 to 120 mg. (high dose) or 20 to 60 mg. (low dose) oral methadone daily. Some programs are reported to have produced 80% success (patients employed or otherwise socially productive). Selection of patients, availability of allied therapeutic and rehabilitative facilities, strict control of supply, record keeping and periodic evaluation are considered essential. Different criteria (“drug-free” vs. “socially productive”) for judging “success” of treatment of heroin-dependent persons by methadone maintenance and administrative problems in large-scale treatment programs constitute the principal aspects of controversy. PMID:4599599

  6. Another Alternative: A 90-Day Contractual Detoxification Treatment Program

    ERIC Educational Resources Information Center

    Kahn, Robert B.; And Others

    1978-01-01

    In May 1974, Fresno County's Narcotic Abuse Treatment Program began a 21-day outpatient methadone detoxification treatment modality. The purpose of this paper is to examine this alternative treatment modality, its characteristics, its therapeutic outcomes and the rationale for its use. (Author)

  7. 21-Day Content Screen

    EPA Pesticide Factsheets

    Under PRIA, EPA has 21 days after it receives the pesticide application and the fee to conduct an initial screen of the application’s contents for completeness and for the applicant to make necessary corrections. This page provides the checklists we use.

  8. Methadone maintenance: some client opinions.

    PubMed

    Brown, B S; Benn, G J; Jansen, D R

    1975-06-01

    The authors found similar attitudes toward methadone and methadone treatment programs in 75 detoxification and 115 methadone maintenance clients. Both groups expressed considerable ambivalence--although they viewed methadone as capable of helping them end their herioin addiction, they were concerned about possible methadone dependence and about side effects, both real and imagined. The authors stress the societal context of such concern and suggest that, althought they are not easily allayed, limiting the duration of methadone maintenace from the outset of treatment may be an ameliorative factor.

  9. Decreasing Methadone Dose Via Anxiety Reduction: A Treatment Manual.

    ERIC Educational Resources Information Center

    Kushner, Marlene; And Others

    This manual describes a Relaxation-Information Presentation program based on the clinical observation that anxiety is a serious barrier to detoxification for many methadone clients, and on experimental evidence indicating that expectations may play a greater role in the discomfort experienced during detoxification than the actual methadone dose.…

  10. Using Acceptance and Commitment Therapy during Methadone Dose Reduction: Rationale, Treatment Description, and a Case Report

    ERIC Educational Resources Information Center

    Stotts, Angela L.; Masuda, Akihiko; Wilson, Kelly

    2009-01-01

    Many clients who undergo methadone maintenance (MM) treatment for heroin and other opiate dependence prefer abstinence from methadone. Attempts at methadone detoxification are often unsuccessful, however, due to distressing physical as well as psychological symptoms. Outcomes from an MM client who voluntarily participated in an Acceptance and…

  11. PRIA 21-Day Content Screen Worksheet

    EPA Pesticide Factsheets

    Under PRIA 3, EPA has 21 days after it receives the application and the fee to conduct an initial screen of the application’s contents for completeness and for the applicant to make any necessary corrections.

  12. Pharmacological strategies for detoxification

    PubMed Central

    Diaper, Alison M; Law, Fergus D; Melichar, Jan K

    2014-01-01

    Detoxification refers to the safe discontinuation from a substance of dependence and is distinct from relapse prevention. Detoxification usually takes between a few days and a few weeks to complete, depending on the substance being misused, the severity of dependence and the support available to the user. Psychosocial therapies alongside pharmacological treatments are essential to improve outcome. The dependencies considered in this overview are detoxification from opioids (with methadone, buprenorphine, α2-adrenoceptor agonists and adjunct medications), alcohol (with benzodiazepines, anti-glutamatergics and γ-aminobutyric acid (GABA)-ergic drugs), stimulants and cannabis (with no clear recommended pharmacological treatments), benzodiazepines (with dose tapering) and nicotine (with nicotine replacement therapy, antidepressants and partial agonists). Evidence is limited by a lack of controlled trials robust enough for review bodies, and more research is required into optimal treatment doses and regimes, alone and in combination. PMID:24118014

  13. Pharmacological strategies for detoxification.

    PubMed

    Diaper, Alison M; Law, Fergus D; Melichar, Jan K

    2014-02-01

    Detoxification refers to the safe discontinuation from a substance of dependence and is distinct from relapse prevention. Detoxification usually takes between a few days and a few weeks to complete, depending on the substance being misused, the severity of dependence and the support available to the user. Psychosocial therapies alongside pharmacological treatments are essential to improve outcome. The dependencies considered in this overview are detoxification from opioids (with methadone, buprenorphine, α2-adrenoceptor agonists and adjunct medications), alcohol (with benzodiazepines, anti-glutamatergics and γ-aminobutyric acid (GABA)-ergic drugs), stimulants and cannabis (with no clear recommended pharmacological treatments), benzodiazepines (with dose tapering) and nicotine (with nicotine replacement therapy, antidepressants and partial agonists). Evidence is limited by a lack of controlled trials robust enough for review bodies, and more research is required into optimal treatment doses and regimes, alone and in combination.

  14. Use of Ultra Rapid Opioid Detoxification in the Treatment of US Military Burn Casualties

    DTIC Science & Technology

    2011-07-01

    results of a modified version of rapid opiate detoxification under general anaesthesia: a prospective study in methadone , heroin, codeine and morphine...van Cauter RM, De Jong CA. Rapid detoxification from opioid dependence under general anes- thesia versus standard methadone tapering: abstinence

  15. Methadone-related deaths. A ten year overview.

    PubMed

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; Pozzi, Fulvia; Groppi, Angelo

    2015-12-01

    Over the last 10 years we have registered in our district (about 500,000 inhabitants) 36 cases of fatal methadone poisoning, involving both patients on treatment and naive subjects: this is a significant increase of deaths due to methadone use, misuse or abuse compared with previous years. Twenty-four patients (66.7%) were on methadone maintenance programs for heroin detoxification, while 12 (33.3%) were taking the drug without a medical prescription. The average blood concentration of methadone in patients undergoing a maintenance program was 1.06 mg/L (0.21-3.37 mg/L), against 0.79 mg/L (0.2-3.15 mg/L) in those taking the non-prescribed drug. Since 111 heroin-related deaths were recorded in our district in the same period, the fact that there appear to be many methadone deaths (about a third of heroin-related deaths) cannot be overlooked. The aim of this work is to understand the possible reasons for such a large number of methadone-related deaths. On this subject, we have noticed that risks associated with methadone intake are often underestimated by clinicians prescribing the drug: sometimes methadone is prescribed without taking into account patient's tolerance to opiates, and a large number of subjects enrolled in methadone maintenance programs in Italy, have also been given take-home doses, thus increasing the risk of abuse and diversion.

  16. Early outcomes following low dose naltrexone enhancement of opioid detoxification.

    PubMed

    Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Gottheil, Edward; Wu, Li-Tzy; Gorelick, David A

    2009-01-01

    Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow-up treatment modalities designed to address opioid dependence.

  17. Satisfaction With Methadone Among Heroin-Dependent Patients With Current Substance Use Disorders During Methadone Maintenance Treatment.

    PubMed

    Perez de Los Cobos, Jose; Trujols, Joan; Siñol, Núria; Duran-Sindreu, Santiago; Batlle, Francesca

    2016-04-01

    Methadone maintenance treatment (MMT) has long been used to treat heroin-dependent patients. However, satisfaction with methadone in this patient population is unknown. The aim of this cross-sectional case-control study was to evaluate satisfaction with methadone in heroin-dependent patients with current substance use disorders (SUDs). Cases included 152 methadone-maintained patients with current SUD, requiring inpatient detoxification treatment, and controls included 33 methadone-maintained patients in sustained full remission for SUD. Satisfaction with methadone as a medication to treat heroin addiction was measured by using the Scale to Assess Satisfaction with Medications for Addiction Treatment-methadone for heroin addiction (SASMAT-METHER). The SASMAT-METHER subscales assess the following domains: personal functioning and well-being, antiaddictive effect on heroin, and antiaddictive effect on other substances. Compared with patients with remitted SUD, patients with current SUD scored lower on all SASMAT-METHER assessments. In such patients, overall SASMAT-METHER scores were independently and negatively associated with downward desired adjustment of methadone dose and days of heroin use during last month; although various sets of factors were independently associated with each of the SASMAT-METHER subscales, the only determinant of dissatisfaction on all subscales was the desire for downward adjustment of methadone dose. In summary, MMT patients with current SUD are less satisfied with methadone than MMT patients with remitted SUD. In patients with current SUD, downward desired adjustment of methadone dose and days of heroin use during last month are independently associated with overall dissatisfaction with methadone.

  18. Diazepam and methadone interactions in methadone maintenance.

    PubMed

    Preston, K L; Griffiths, R R; Stitzer, M L; Bigelow, G E; Liebson, I A

    1984-10-01

    Survey study data and high rates of diazepam use/abuse in methadone maintenance suggest that acute administration of diazepam with daily methadone doses may enhance methadone effects. Acute subjective and physiologic effects of single oral doses of placebo, diazepam (20 and 40 mg), methadone (100%, 150%, and 200% of the maintenance dose), and four diazepam-methadone dose combinations (20 and 40 mg diazepam in combination with 100% and 150% of the maintenance dose) were assessed under double-blind conditions. The subjects were five adult male patients on methadone maintenance with histories of diazepam abuse who were receiving 50 to 60 mg methadone a day. Physiologic measures were continuously monitored for 30 min before and for 2 hr after dosing. Pupil diameter and subjective responses were measured 15 min before dosing and 15, 30, 45, 60, 90, and 120 min after dosing. Methadone induced dose-dependent increases in pupil constriction and scores on a subjective opioid effects rating scale, but diazepam had no significant effect on either. The combination of methadone at 150% of the maintenance dose with 40 mg diazepam induced increases in these measures greater than those induced by either drug dose alone. Drug combinations, however, were more frequently identified as being benzodiazepine/barbiturate-like than as methadone-like. Thus although the subjective effects of the drug combination are distinguishable from those of methadone alone, diazepam with methadone in methadone maintenance appears to increase some physiologic and subjective opioid effects that may be related to the relatively great use/abuse of diazepam in this population.

  19. Determining Effective Methadone Doses for Individual Opioid-Dependent Patients

    PubMed Central

    Trafton, Jodie A; Minkel, Jared; Humphreys, Keith

    2006-01-01

    Background Randomized clinical trials of methadone maintenance have found that on average high daily doses are more effective for reducing heroin use, and clinical practice guidelines recommend 60 mg/d as a minimum dosage. Nevertheless, many clinicians report that some patients can be stably maintained on lower methadone dosages to optimal effect, and clinic dosing practices vary substantially. Studies of individual responses to methadone treatment may be more easily translated into clinical practice. Methods and Findings A volunteer sample of 222 opioid-dependent US veterans initiating methadone treatment was prospectively observed over the year after treatment entry. In the 168 who achieved at least 1 mo of heroin abstinence, methadone dosages on which patients maintained heroin-free urine samples ranged from 1.5 mg to 191.2 mg (median = 69 mg). Among patients who achieved heroin abstinence, higher methadone dosages were predicted by having a diagnosis of posttraumatic stress disorder or depression, having a greater number of previous opioid detoxifications, living in a region with lower average heroin purity, attending a clinic where counselors discourage dosage reductions, and staying in treatment longer. These factors predicted 42% of the variance in dosage associated with heroin abstinence. Conclusions Effective and ineffective methadone dosages overlap substantially. Dosing guidelines should focus more heavily on appropriate processes of dosage determination rather than solely specifying recommended dosages. To optimize therapy, methadone dosages must be titrated until heroin abstinence is achieved. PMID:16448216

  20. Model of methadone-induced hyperalgesia in rats and effect of memantine.

    PubMed

    Hay, Justin L; Kaboutari, Jahangir; White, Jason M; Salem, Abdallah; Irvine, Rod

    2010-01-25

    Methadone used for opioid dependence therapy is associated with increased pain sensitivity. This study aimed to investigate whether methadone administration lowers nociceptive threshold in adult male Sprague-Dawley (SD) rats, and if this threshold could be altered by the NMDA receptor antagonist memantine. Rats were implanted with osmotic pumps delivering 1mg/kg/day methadone (n=6), or saline placebo (n=6) (0.51 microl/h). A separate cohort of rats received either methadone 1mg/kg/day (n=8) or methadone 1mg/kg/day with 20mg/kg/day memantine (n=8). Nociception was measured by the Hargreave's paw withdrawal test. Baseline nociception was measured on day 0 prior to osmotic pump implantation and was measured daily for the following 21 days. Osmotic pumps were removed following nociceptive testing on day 14. Methadone only treated rats had a mean paw withdrawal latency significantly lower than the corresponding values for saline on days 8, 9, 10, 11, 12, 14, and 17 (P<0.05). At all other time points the mean paw withdrawal latency was not significantly different from saline (P>0.05). Paw withdrawal latency of rats treated with methadone co-administered with memantine did not differ significantly compared to methadone only (P>0.05). This demonstrates that methadone induces hyperalgesia in the SD rat yet this hyperalgesia resolves following discontinuation of methadone administration. Furthermore, memantine does not alter the development of methadone-induced hyperalgesia.

  1. Optimum Methadone Compliance Testing

    PubMed Central

    2006-01-01

    and gums for 3 minutes on average. The pad absorbs the oral fluid. After 3 minutes (range 2min-5 min) the collection device is removed from the mouth and the absorbent pad is placed in a small vial which contains 0.8mL of pH-balanced preservative, for transportation to a laboratory for analysis. It is recommended that the person undergoing oral fluid drug testing have nothing to eat or drink for a 10- minute period before the oral fluid specimen is collected. This will remove opportunity for adulteration. Likewise, it is recommended that the person be observed for the duration of the collection period to prevent adulteration of the specimen. An average of 0.4 mL of saliva can be collected. The specimen may be stored at 4C to 37C and tested within 21 days of collection (or within 6 weeks if frozen). The oral fluid specimen must be analyzed in a laboratory setting. There is no point-of-care (POC) oral fluid test kit for drugs of abuse (other than for alcohol). In the laboratory the oral fluid is extracted from the vial after centrifugation and a screening test is completed to eliminate negative specimens. Similar to urinalysis, oral fluid specimens are analyzed first by enzyme immunoassay with positive specimens sent for confirmatory testing. Comparable cut-off values to urinalysis by enzyme immunoassay have been developed for oral fluids Review Strategy   Research Question What is the diagnostic utility of the Intercept oral specimen device? Inclusion criteria: Studies evaluating paired urine and oral fluid specimens from the same individual with the Intercept oral fluid collection device. The population studied includes drug users. Exclusion criteria: Studies testing for marijuana (THC) only. Outcomes: Sensitivity and Specificity of oral fluid testing compared to urinalysis for methadone (methadone metabolite), opiates, cocaine, benzodiazepines, and alcohol. Quality of the Body of Evidence The Grading of Recommendations Assessment, Development and Evaluation (GRADE

  2. Contingent methadone delivery: effects on illicit-opiate use.

    PubMed

    Higgins, S T; Stitzer, M L; Bigelow, G E; Liebson, I A

    1986-07-01

    This study examined the effects of contingent vs. non-contingent delivery of a methadone dose supplement on relapse to illicit opiate use in the context of a methadone outpatient detoxification program. Following a 3-week methadone stabilization period on 30 mg, patients (N = 39) were randomly assigned to a contingent, a non-contingent, or a control treatment group. All patients received identical gradual reductions in their assigned methadone dose. During the dose reduction period (weeks 4-11), members of the contingent (N = 13) and non-contingent groups (N = 13) could obtain daily methadone-dose supplements up to 20 mg, but contingent group members could obtain supplements only if their most recent urinalysis results were opiate negative. Control subjects (N = 13) did not have dose increases available. The contingent group presented significantly lower opiate-positive urines during weeks 8-11 (14% positive) of the detox than the non-contingent (38% positive) or control (50% positive) groups. Additionally, the availability of extra methadone improved treatment retention and increased clinic attendance above levels observed in the control group. The potential for further use of methadone's reinforcing properties in the treatment of opiate dependence is discussed.

  3. Another Alternative: A Ninety-Day Contractual Detoxification Treatment Program

    ERIC Educational Resources Information Center

    Kahn, Robert B.; And Others

    1976-01-01

    In May, 1974, Fresno County's Narcotic Abuse Treatment Program began a twenty-one-day outpatient methadone detoxification treatment modality. The results of the evaluation suggested an alternative treatment modality. The purpose of this paper is to examine this alternative treatment modality, its characteristics, its therapeutic outcomes and the…

  4. The Methadone Illusion

    ERIC Educational Resources Information Center

    Lennard, Henry L.; And Others

    1972-01-01

    Methadone treatment for heroin addiction does not touch the roots of the drug problem" and to think that the use of another drug can solve the profound and complex task facing us is indeed an illusion." (Author/AL)

  5. Revisit the 21-day cumulative irritation test - statistical considerations.

    PubMed

    Zhang, Paul; Li, Qing

    2017-03-01

    The 21-day cumulative irritation test is widely used for evaluating the irritation potential of topical skin-care products. This test consists of clinician's assessment of skin reaction of the patch sites and a classification system to categorize the test product's irritation potential. A new classification system is proposed which enables us to control the estimation error and provides a statistical confidence with regard to the repeatability of the classification.

  6. Methadone Treatment: Overview and Bibliography.

    ERIC Educational Resources Information Center

    Greenfield, Lawrence; Tang, Beth Archibald

    This overview focuses on methadone treatment. Briefly, it describes the clinical uses of methadone for substance abuse treatment, explores dosage guidelines, and discusses counseling components. This overview also reviews research data on the application of methadone treatment to special populations, such as pregnant women, polydrug users, and…

  7. Methadone-induced hypoglycemia.

    PubMed

    Faskowitz, Andrew J; Kramskiy, Vladimir N; Pasternak, Gavril W

    2013-05-01

    To determine if recent observations of hypoglycemia in patients receiving high-dose methadone extended to an animal model, we explored the effects of methadone and other mu-opioids on blood glucose levels in mice. Methadone lowered blood glucose in a dose-dependent manner with 20 mg/kg yielding a nadir in average glucose levels to 55 ± 6 mg/dL from a baseline of 172 ± 7 mg/dL, an effect that was antagonized by naloxone and mu selective antagonists β-funaltrexamine and naloxonazine. The effect was stereoselective and limited to only the l-isomer, while the d-isomer was ineffective. Despite the robust decrease in blood glucose produced by methadone, a series of other mu-opioids, including morphine, fentanyl, levorphanol, oxycodone or morphine-6β-glucuronide failed to lower blood glucose levels. Similar differences among mu-opioid agonists have been observed in other systems, suggesting the possible role of selected splice variants of the mu-opioid receptor gene Oprm1. This mouse model recapitulates our clinical observations and emphasizes the need to carefully monitor glucose levels when using high methadone doses, particularly intravenously, and the need for controlled clinical trials.

  8. Therapeutic and recreational methadone cardiotoxicity.

    PubMed

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2016-04-01

    Several classes of drugs have been associated with an increased risk of cardiovascular disease and occurrence of arrhythmias potentially involved in sudden deaths in chronic users even at therapeutic doses. The study presented herein focuses on pathological changes involving the heart possibly due to methadone use. 60 cases were included in the study in total and were divided into three groups (therapeutic methadone users: 20 cases, recreational methadone users: 20 cases, and sudden death group in subjects who had never taken methadone: 20 cases). Autopsies, histology, biochemistry and toxicology were performed in all cases. Macroscopic and microscopic investigation results in therapeutic methadone users were similar to those observed in sudden, unexpected deaths in non-methadone users. In recreational methadone consumers, macroscopic and microscopic examination of the heart failed to provide results consistent with acute or chronic myocardial or coronary damage, thereby corroborating the hypothesis of death most likely following respiratory depression.

  9. Methadone and prescription drug overdose.

    PubMed

    Hendrikson, Hollie; Hansen, Melissa

    2014-12-01

    (1) Methadone accounted for 2 percent of painkiller prescriptions and more than 30 percent of prescription painkiller deaths in 2009. (2) Data suggest that the rise in deaths from methadone overdose is not related to its use in treating drug abuse but, rather, to its use for pain management. (3) Preferred drug lists in most Medicaid programs identify methadone as a preferred drug for managing chronic pain, but most experts do no recommend it as a first choice.

  10. Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma.

    PubMed

    Holbrook, Amber M

    2015-01-01

    The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States.

  11. Opiate-dependent patients receiving methadone. How physicians should manage therapy.

    PubMed Central

    Kahan, M.; Sutton, N.

    1996-01-01

    Methadone treatment can reduce illicit drug use, needle sharing, and the social costs and health risks of heroin addiction. It is superior to no treatment, detoxification, or treatment programs lasting less than 3 months. For most patients, the optimal methadone dose is 50 to 120 mg daily. Supervised, random urine drug specimens should be collected at least twice weekly. Long-term counseling is essential and should include information on the risks of needle sharing and on screening for HIV and hepatitis B and C. PMID:8828879

  12. Opium tincture versus methadone syrup in management of acute raw opium withdrawal: A randomized, double-blind, controlled trial.

    PubMed

    Tabassomi, Farzaneh; Zarghami, Mehran; Shiran, Mohammad-Reza; Farnia, Samaneh; Davoodi, Mohsen

    2016-01-01

    The aim of this study was to evaluate the effectiveness of opium tincture versus methadone syrup in the management of acute withdrawal syndrome in opium dependent patients during the detoxification period. In this double-blind randomized controlled study, a total of 74 adult male raw opium dependent patients were treated with opium tincture or methadone syrup 2 times daily for 5 consecutive days. Detoxification was initiated by tapered dose reductions to reach abstinence. At the end of the 10th day, the medications were discontinued. The Objective Opioid Withdrawal Scale was used to assess withdrawal symptoms every day. Significant decreases on the Objective Opioid Withdrawal Scale were found for both treatment methods during the study period (p < .0001). However, there was no significant difference between groups on the total Objective Opioid Withdrawal Scale, and adverse effects existed. Opium tincture can be considered as a potential substitute for methadone syrup for suppression of raw opium withdrawal symptoms, with minimal adverse effects.

  13. Determination of methadone and its N-demethylation metabolites in biological specimens by GC-PICI-MS.

    PubMed

    Alburges, M E; Huang, W; Foltz, R L; Moody, D E

    1996-10-01

    Methadone is often invoked for detoxification and maintenance of the opioid addict. We have developed and validated a sensitive and specific method for the analysis of methadone and its metabolites, 2-ethylidene-1,5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP), in human plasma, urine, and liver microsomes. This assay uses a solid-phase extraction. Separation and analysis of the analytes are performed by capillary gas chromatography-positive ion chemical ionization-mass spectrometry. The protonated molecules (MH+) are monitored at m/z 264 and 267 for EMDP-d0 and -d3, m/z 278 and 281 for EDDP-d0 and -d3, and m/z 310 and 313 for methadone-d0 and -d3. The recovery of methadone and its metabolites exceeded 85% in the different matrices analyzed. Linear standard curves in plasma and in urine were obtained over the concentration range of 10-600 ng/mL (coefficients of determination: methadone, > or = 0.995; EMDP, > or = 0.994; and EDDP, > or = 0.996). With plasma and urine fortified at 25, 100, and 300 ng/mL, the assay was precise (intra-assay coefficients of variation [CVs], 2-12%; interassay CVs, 1-15%) and accurate (intra-assay percent of target, 85-107; interassay percent of target, 88-105) for all three analytes. Stability studies indicated that methadone and its metabolites are stable at room temperature in plasma and in urine for at least 1 week and in liver microsomes for at least 24 h. This method has now been shown to be useful for quantitation of methadone, EDDP, and EMDP in human urine and plasma and is also useful for quantitation of the amount of EDDP produced in human liver microsomes incubated with methadone. It provides an accurate and precise analytical tool for further studies on the metabolism of methadone.

  14. The effects of gabapentin on methadone based addiction treatment: a randomized controlled trial.

    PubMed

    Moghadam, Mohsen Saber; Alavinia, Mohammad

    2013-09-01

    Gabapentin is a potentially useful drug in alleviating the hyperexcitatory painful states in the control of opiate dependence in acute detoxification and the stabilization phase. This study aim was to evaluate the effectiveness of gabapentin adds-on methadone therapy on lowering the methadone. This randomized double blind controlled clinical trial conducted at an outpatient rehabilitation clinic. Sixty patients using opium, opium extract and heroin were randomly assigned to two groups (34 in treatment group and 26 in control group); one group was prescribed combination of methadone (40-120 mg) and gabapentin (300 mg) as group A, and the other group was given methadone (40-120) and placebo as group B. The subjects were followed up for three weeks after intervention. There were 60 outpatients including 51 males with the mean age of 40.9±9.2. Daily dose and cumulative dose of methadone during the treatment was found to be significantly higher in group B (73.8±19.5 mg daily vs. 58.9±11 mg daily and cumulatively 1550.7±409.7 mg vs. 238.3±238.2 mg, p= 0.001). When the patients were stratified based on the kind of abused drug, the methadone dose was seen to be significantly reduced in the opium addicted patients in the group A. Group A showed more withdrawal symptoms whereas the most common complain of group B was sedation particularly during the first three days. The results showed that gabapentin is an effective adds-on therapy when is added to methadone. This drug leads to relief of withdrawal symptoms and lower methadone consumption.

  15. Enhanced development of dispositional tolerance to methadone by desipramine given together with methadone

    SciTech Connect

    Liu, S.J.; Wang, R.I.H.

    1985-02-25

    Rats given 2-day oral administration of methadone (15 mg/kg, twice on day 1 and once on day 2) by gastric tube developed dispositional tolerance to methadone analgesia as demonstrated by a decrease in analgesic response and by an increase in methadone metabolism. The increased metabolism of methadone was evidenced by a decrease in brain concentration of /sup 14/C-methadone and increases in the percentages of total /sup 14/C in liver or urine as /sup 14/C-water-soluble metabolites (/sup 14/C-WSM) after the rats were challenged with a test dose of /sup 14/C-methadone. Two-day pretreatment with a combination of desipramine (DMI) (10 mg/kg, ip) and methadone (15 mg/kg, po) enhanced the development of dispositional tolerance to methadone analgesia which was evidenced by a greater decrease in the brain concentration of methadone and a greater increase in methadone metabolism as compared to those changes in rats pretreated with only methadone. Repeated treatment with DMI alone neither decreased the analgesic effect of methadone nor stimulated methadone metabolism. It is suggested that DMI given together with methadone promoted the induction of methadone metabolism in the liver by prolonging the enzyme-stimulating state of methadone, thus enhancing the development of dispositional tolerance to methadone. 20 references, 1 figure, 1 table.

  16. Uses of diverted methadone and buprenorphine by opioid-addicted individuals in Baltimore, Maryland

    PubMed Central

    Mitchell, Shannon Gwin; Kelly, Sharon M.; Brown, Barry S.; Reisinger, Heather Schacht; Peterson, James A.; Ruhf, Adrienne; Agar, Michael H.; O'Grady, Kevin E.; Schwartz, Robert P.

    2009-01-01

    This study examined the uses of diverted methadone and buprenorphine among opiate-addicted individuals recruited from new admissions to methadone programs and from out-of-treatment individuals recruited from the streets. Self-report data regarding diversion were obtained from surveys and semi-structured qualitative interviews. Approximately 16% (n=84) of the total sample (N=515) reported using diverted (street) methadone 2–3 times per week for six months or more, and for an average of 7.8 days (SD=10.3) within the past month. The group reporting lifetime use of diverted methadone as compared to the group that did not report such use was less likely to use heroin and cocaine in the 30 days prior to admission (ps < .01) and had lower ASI Drug Composite scores (p < .05). Participants in our qualitative sub-sample (n=22) indicated that street methadone was more widely used than street buprenorphine and that both drugs were largely used as self-medication for detoxification and withdrawal symptoms. Participants reported using low dosages and no injection of either medication was reported. PMID:19874152

  17. Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial.

    PubMed

    Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathi; Gorelick, David A; Wu, Li-Tzy; Gottheil, Edward

    2009-04-01

    Although current treatments for opioid detoxification are not always effective, medical detoxification remains a required step before long-term interventions. The use of opioid antagonist medications to improve detoxification has produced inconsistent results. Very low dose naltrexone (VLNTX) was recently found to reduce opioid tolerance and dependence in animal and clinical studies. We decided to evaluate safety and efficacy of VLNTX adjunct to methadone in reducing withdrawal during detoxification. In a multi-center, double-blind, randomized study at community treatment programs, where most detoxifications are performed, 174 opioid-dependent subjects received NTX 0.125 mg, 0.250 mg or placebo daily for 6 days, together with methadone in tapering doses. VLNTX-treated individuals reported attenuated withdrawal symptoms [F = 7.24 (2,170); P = 0.001] and reduced craving [F = 3.73 (2,107); P = 0.03]. Treatment effects were more pronounced at discharge and were not accompanied by a significantly higher retention rate. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Further studies should explore the use of VLNTX, combined with full and partial opioid agonist medications, in detoxification and long-term treatment of opioid dependence.

  18. Methadone Recycling Sustains Drug Reservoir in Tissue.

    PubMed

    Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie; Schiesser, William E; Boston, Raymond C

    2015-09-01

    We hypothesize that there is a tissue store of methadone content in humans that is not directly accessible, but is quantifiable. Further, we hypothesize the mechanism by which methadone content is sustained in tissue stores involves methadone uptake, storage, and release from tissue depots in the body (recycling). Accordingly, we hypothesize that such tissue stores, in part, determine plasma methadone levels. We studied a random sample of six opioid-naïve healthy subjects. We performed a clinical trial simulation in silico using pharmacokinetic modeling. We found a large tissue store of methadone content whose size was much larger than methadone's size in plasma in response to a single oral dose of methadone 10 mg. The tissue store measured 13-17 mg. This finding could only be explained by the contemporaneous storage of methadone in tissue with dose recycling. We found that methadone recycles 2-5 times through an inaccessible extravascular compartment (IAC), from an accessible plasma-containing compartment (AC), before exiting irreversibly. We estimate the rate of accumulation (or storage) of methadone in tissue was 0.029-7.29 mg/h. We predict 39 ± 13% to 83 ± 6% of methadone's tissue stores "spillover" into the circulation. Our results indicate that there exists a large quantifiable tissue store of methadone in humans. Our results support the notion that methadone in humans undergoes tissue uptake, storage, release into the circulation, reuptake from the circulation, and re-release into the circulation, and that spillover of methadone from tissue stores, in part, maintain plasma methadone levels in humans.

  19. Methadone and alcohol.

    PubMed

    Freedman, L Z

    1976-01-01

    We have demonstrated the dangers of alcoholism that complicate methadone treatment of heroin addiction. In future papers, we will attempt to identify contributory factors and suggest interventionist techniques. In the final analysis, however, rehabilitation programs, vocational programs, and, above all, alleviation of the dreadful socioeconomic deprivations related to, among other factors, the racial bias under which most of these people have been born and have suffered during their lives will, in the long run, prove the most satisfactory means of reducing the heroin problem, except for a minority whose psychologic problems will then provide the irreducible minimum from which the majority of the addicts will come. As has so often been stated, the great drug problem in this country is alcoholism. We know that legal prohibition does not prevent the rise of alcoholism, and we know to our sorrow that not only does it give rise to enormous wealth and power to criminals and criminal gangs but that some of them are now also profiting from the great wealth to be made by dealing in heroin.

  20. Pharmacokinetic interaction between telaprevir and methadone.

    PubMed

    van Heeswijk, Rolf; Verboven, Peter; Vandevoorde, Ann; Vinck, Petra; Snoeys, Jan; Boogaerts, Griet; De Paepe, Els; Van Solingen-Ristea, Rodica; Witek, James; Garg, Varun

    2013-05-01

    Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of R- and S-methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative subjects on stable, individualized methadone therapy. Unbound R-methadone was measured in predose plasma samples before and during telaprevir coadministration. Safety and symptoms of opioid withdrawal were evaluated throughout the study. In total, 18 subjects were enrolled; 2 discontinued prior to receiving telaprevir. The minimum plasma concentration in the dosing interval (C(min)), the maximum plasma concentration (Cmax), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC(0-24)) for R-methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir. The AUC0-24 ratio of S-methadone/R-methadone was not altered. The median unbound percentage of R-methadone increased by 26% in the presence of telaprevir. The R-methadone median (absolute) unbound C(min) values in the absence (10.63 ng/ml) and presence (10.45 ng/ml) of telaprevir were similar. There were no symptoms of opioid withdrawal and no discontinuations due to adverse events. In summary, exposure to total R-methadone was reduced by approximately 30% in the presence of telaprevir, while the exposure to unbound R-methadone was unchanged. No symptoms of opioid withdrawal were observed. These results suggest that dose adjustment of methadone is not required when initiating telaprevir treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT00933283.).

  1. Drug Abuse: Methadone Becomes the Solution and the Problem

    ERIC Educational Resources Information Center

    Bazell, Robert J.

    1973-01-01

    Methadone is used to divert heroin addicts from using stronger drugs. Rate of crimes committed by drug addicts has fallen considerably after putting them on methadone. Despite criticisms, methadone use seems to be encouraging for the future. (PS)

  2. Foucault on methadone: beyond biopower.

    PubMed

    Keane, Helen

    2009-09-01

    This essay reviews four texts which critically analyse methadone maintenance therapy using Foucault as a key theoretical framework: [Friedman, J., & Alicea, M. (2001). Surviving heroin: Interviews with women in methadone clinics. Florida: University Press of Florida], [Bourgois, P. (2000). Disciplining addictions: The bio-politics of methadone and heroin in the United States. Culture Medicine and Psychiatry, 24, 165-195], [Bull, M. (2008). Governing the heroin trade: From treaties to treatment. Ashgate: Aldershot], and [Fraser, S., & valentine, k. (2008). Substance & substitution: Methadone subjects in liberal societies. New York: Palgrave Macmillan]. Taken together these works demonstrate one trajectory in the development of critical drug studies over the past decade. While all four view MMT as a regulatory technology which aims to create productive and obedient subjects, their understandings of the power relations of the clinic are quite distinct. The first two texts emphasise the social control of drug users, the third, issues of governmentality and liberal political practice, while the fourth engages with ontological questions about substances themselves. Thus while Foucauldian analysis has become familiar in social studies of drugs and alcohol, new uses for its conceptual tools continue to emerge.

  3. Prescription opioid dependence and treatment with methadone in pregnancy.

    PubMed

    Sander, Stephanie C Eken; Hays, Lon R

    2005-01-01

    Prescription opioids are used medically to treat pain, but their diversion and abuse continues to escalate in the United States. Abuse of OxyContin (Purdue Pharma LP, Stamford, CT), a timed-release form of oxycodone, is a major focus of public health and law enforcement agencies. The rise in opioid abuse may lead to an increase in opioid dependence in pregnancy, which was a focus of this study. Our retrospective chart review examined the demographics and patterns of opioid addiction of pregnant women admitted to an inpatient psychiatric unit in an academic medical center in central Kentucky. Charts of 94 women admitted from January 2001 to May 2004 were reviewed. Information obtained included demographics and details of their opioid use, including the specific opioid(s) used, route of administration, and duration of use. Treatment information included length of hospital stay, stabilizing dose of methadone, comorbid drug use, and concomitant Axis I diagnoses. Most women were in their mid-twenties and in the second trimester of pregnancy when they sought treatment. Benzodiazepines were the most common comorbid drugs of abuse and the most frequent medical complication of their drug use was hepatitis C, newly diagnosed in 11 patients. This study demonstrates the need for further research in prescription opioid dependency in pregnancy, methadone maintenance therapy, the safety of detoxification, and neonatal outcomes.

  4. Methadone-Induced Toxic Brain Damage

    PubMed Central

    Corré, Jérôme; Pillot, Jérôme; Hilbert, Gilles

    2013-01-01

    A 29-year-old man presented with comatose after methadone intoxication. Cerebral tomography only showed cortico-subcortical hypodense signal in the right cerebellar hemisphere. Brain MRI showed a rare imaging of FLAIR and DWI hyperintensities in the two cerebellar hemispheres as well as basal ganglia (globi pallidi), compatible with methadone overdose. To our knowledge this is the first reported case of both cerebellar and basal ganglia involvement in methadone overdose. PMID:23762729

  5. Methadone induced lysis of mammalian cells.

    PubMed

    Will, P C; Noteboom, W D

    1978-08-01

    Methadone induced lysis of human erythrocytes and mouse leukemic cells was studied. The cells lyse without prior swelling that is a necessary step of colloid osmotic lysis. Methadone is accumulated by both cell types, and is widely distributed intracellurly in mouse leukemic cells. The maximum lytic rate is roughly proportional to the amount of methadone uptake and the Q10 for lysis is equal to the Q10 for methadone partitioning between octanol and water. It is concluded that the cells lyse as a result of a non-specific disruption of the plasma membrane.

  6. Reduced methadone clearance during aromatase inhibition.

    PubMed

    Lu, Wenjie Jessie; Thong, Nancy; Flockhart, David A

    2012-08-01

    Methadone is increasingly used in pain management and is a cornerstone in the treatment of opiate withdrawal. It is subject to highly variable clearance among patients. The complete metabolic disposition of methadone is likely to involve a number of enzymes, including specifically CYP2B6. Previous studies in vitro suggest that metabolism by aromatase may also contribute. Single-dose methadone pharmacokinetics (2 mg, intravenous) were studied in 15 healthy postmenopausal women in the presence and absence of a potent aromatase inhibitor, letrozole. A sequential design was used, involving a control period followed by treatment with letrozole (2.5 mg/d, 11 days), in which each subject served as her own control. On average, letrozole treatment reduced methadone systemic clearance by 22% (P = 0.001), increased methadone AUC by 23% (P = 0.007), and increased elimination half-life by 21% (P = 0.042). The plasma parent-to-metabolite ratio also increased (P = 0.009), and there was a linear relationship (R2 = 0.74) between change in this plasma ratio and change in methadone AUC0-∞. In contrast, there was no such association with change in apparent urinary methadone clearance. Letrozole did not change methadone distribution half-life or its volume of distribution. Overall, these data demonstrate a significant decrease in methadone clearance during coadministration of letrozole, consistent with decreased metabolism brought about by aromatase inhibition. An involvement of aromatase in the disposition of methadone may help explain the difficulty in methadone dosing and suggests a broader role for this catalyst of endogenous steroid metabolism in xenobiotic drug disposition.

  7. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  8. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  9. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  10. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  11. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  12. Experience-Seeking Characteristics of Methadone Clients.

    ERIC Educational Resources Information Center

    Kohn, Paul M.; And Others

    1979-01-01

    Methadone clients scored higher than controls on measures reflecting boredom, desire for change and attraction to physically thrilling activities. Correlations of these measures with length of most recent dependency before treatment, time on program, and time since initial dependency suggest peculiarities of methadone clients antedated involvement…

  13. Methadone Medical Maintenance: An Early 21st-Century Perspective.

    PubMed

    Novick, David M; Salsitz, Edwin A; Joseph, Herman; Kreek, Mary Jeanne

    2015-01-01

    Methadone medical maintenance is the treatment of stable methadone-maintained patients in primary care physicians' offices under an exemption from federal methadone regulations. Reports from seven such programs in six states show high retention and low frequencies of illicit drug use. Patients and physicians indicate high levels of satisfaction. Although methadone maintenance has a long history of safety and efficacy, most methadone medical maintenance programs are no longer operating or accepting new patients. Federal regulations for standard methadone clinics allow some features of methadone medical maintenance, and advocacy for state approval of these changes is strongly recommended.

  14. Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series

    PubMed Central

    2011-01-01

    Introduction The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics, and unpredictable side effects that include sedation, respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here, to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding, a new potential mechanism for drug interactions with methadone. Case presentation We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman (aged 59) experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone, while the other (aged 49) did not. To understand the etiology of this event, we measured methadone pharmacokinetics in both patients. In our affected patient only, a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient, but the percentage of unbound methadone in the plasma decreased 3.7-fold. As a result, the volume of distribution of methadone decreased approximately fourfold. The increased plasma binding in our affected patient was consistent with observed increases in plasma protein concentrations. Conclusions The marked increase in the total plasma methadone concentration observed in our patient, and the enhanced pharmacodynamic

  15. Methadone's effect on nAChRs--a link between methadone use and smoking?

    PubMed

    Talka, Reeta; Tuominen, Raimo K; Salminen, Outi

    2015-10-15

    Methadone is a long-acting opioid agonist that is frequently prescribed as a treatment for opioid addiction. Almost all methadone maintenance patients are smokers, and there is a correlation between smoking habit and use of methadone. Methadone administration increases tobacco smoking, and heavy smokers use higher doses of methadone. Nevertheless, methadone maintenance patients are willing to quit smoking although their quit rates are low. Studies on nicotine-methadone interactions provide an example of the bedside-to-bench approach, i.e., observations in clinical settings have been studied experimentally in vivo and in vitro. In vivo studies have revealed the interplay between nicotine and the endogenous opioid system. At the receptor level, methadone has been shown to be an agonist of human α7 nAChRs and a non-competitive antagonist of human α4β2 and α3* nAChRs. These drugs do not have significant interactions at the level of drug metabolism, and thus the interaction is most likely pharmacodynamic. The net effect of the interaction may depend on individual characteristics because pharmacogenetic factors influence the disposition of both methadone and nicotine.

  16. Methadone and buprenorphine toxicity in children.

    PubMed

    Boyer, Edward W; McCance-Katz, Elinore F; Marcus, Steven

    2010-01-01

    Recent years have seen very large increases in the prescribing of methadone and buprenorphine formulations for treatment of opioid addiction as well as the increasing utilization of methadone for the treatment of chronic pain. Coincident with the rise in the prescribing of these drugs has been a substantial increase in pediatric opioid toxicities and adverse events. This review will address the current state of methadone- and buprenorphine-related adverse events in children in the United States. We will also discuss treatment of opioid toxicity in pediatric populations and make recommendations aimed at reducing these occurrences.

  17. Forensic Investigation of Methadone Concentrations in Deceased Breastfed Infants.

    PubMed

    Madadi, Parvaz; Kelly, Lauren E; Ross, Colin J; Kepron, Charis; Edwards, James N; Koren, Gideon

    2016-03-01

    There is a paucity of data to aid in assessing whether postmortem methadone findings in breastfed infants are clinically and/or toxicologically significant. Two cases are reported in which methadone was detected in deceased neonates whose mothers were enrolled in methadone maintenance programs and were breastfeeding. In addition to a complete autopsy and toxicological testing for alcohol, prescription medications, and drugs of abuse, pharmacogenetic analysis was performed for variants in genes related to methadone metabolism and response. In both cases, the postmortem methadone concentration measured in neonatal heart blood was higher than the maximum serum methadone concentration reported in living breastfed infants whose mothers were receiving methadone. However, additional analysis of antemortem blood indicated postmortem redistribution of methadone. Pharmacogenetic results were suggestive of a potential predisposition to methadone toxicity based on studies in adults; the significance of these findings in breastfed neonates requires further research. The medical cause of death was unascertained in both cases.

  18. Methadone for the treatment of Prescription Opioids Dependence. A retrospective chart review.

    PubMed

    Barrio, Pablo; Ezzeldin, Mohamed; Bruguera, Pol; Pérez, Ana; Mansilla, Sara; Fàbrega, Marina; Lligoña, Anna; Mondón, Sílvia; Balcells, Mercè

    2016-06-14

    Prescription opioids (PO) addiction is increasing to an epidemic level. Few studies exist regarding its treatment. Although buprenorphine has been the mainstay so far, other treatment options might be considered, such as methadone. We conducted a retrospective assessment of all patients admitted to a psychiatry ward for PO detoxification using methadone between 2010 and 2013. The assessment and description was carried out during a 3-month follow-up period after their discharge. Although this is a retrospective chart review, our exploration included sociodemographic and treatment variables in addition to the abstinence rates for the whole sample. Eleven patients were included, mostly women (81.8%), with a median age of 50 years. The median duration of dependence was 8 years. Dependence on other substances and psychiatric comorbidities were high. Eight patients were monitored during three months. Of these, 7 (87.5%) were abstinent after that period. The results suggest that methadone deserves further exploration as a potentially efficacious treatment option for PO dependence.

  19. Methadone Maintenance as Law and Order

    ERIC Educational Resources Information Center

    Heyman, Florence

    1972-01-01

    Argues that substitution of methadone for heroin would not rehabilitate the drug addict, but it may be used as a method of tranquilizing a potentially troublesome ghetto and poor white population. (RJ)

  20. Changes in intervertebral disc morphology persist 5 mo after 21-day bed rest.

    PubMed

    Belavý, Daniel L; Bansmann, P Martin; Böhme, Gisela; Frings-Meuthen, Petra; Heer, Martina; Rittweger, Jörn; Zange, Jochen; Felsenberg, Dieter

    2011-11-01

    As part of the nutrition-countermeasures (NUC) study in Cologne, Germany in 2010, seven healthy male subjects underwent 21 days of head-down tilt bed rest and returned 153 days later to undergo a second bout of 21-day bed rest. As part of this model, we aimed to examine the recovery of the lumbar intervertebral discs and muscle cross-sectional area (CSA) after bed rest using magnetic resonance imaging and conduct a pilot study on the effects of bed rest in lumbar muscle activation, as measured by signal intensity changes in T(2)-weighted images after a standardized isometric spinal extension loading task. The changes in intervertebral disc volume, anterior and posterior disc height, and intervertebral length seen after bed rest did not return to prebed-rest values 153 days later. While recovery of muscle CSA occurred after bed rest, increases (P ≤ 0.016) in multifidus, psoas, and quadratus lumborum muscle CSA were seen 153 days after bed rest. A trend was seen for greater activation of the erector spinae and multifidus muscles in the standardized loading task after bed rest. Greater reductions of multifidus and psoas CSA muscle and greater increases in multifidus signal intensity with loading were associated with incidence of low back pain in the first 28 days after bed rest (P ≤ 0.044). The current study contributes to our understanding of the recovery of the lumbar spine after 21-day bed rest, and the main finding was that a decrease in spinal extensor muscle CSA recovers within 5 mo after bed rest but that changes in the intervertebral discs persist.

  1. [Breast feeding during methadon- and buprenorphin therapy].

    PubMed

    Müller, M J; Lange, M; Paul, T; Seeliger, S

    2011-12-01

    The number of opiate addicted patients treated with opioid replacement therapy is continuously increasing. In Germany, 57.7% of these patients are treated with methadone and 18.6% with buprenorphine. This maintenance therapy provides several advantages while addicted pregnant women and their foetus have a high benefit from appropriate replacement therapy. However, the recommendations concerning breast feeding during an opioid replacement therapy are discussed controversially, because methadone as well as buprenorphine accumulate in breast milk. This accumulation might cause damages to the newborn's health; so, child benefits of breast feeding have to be balanced with possible health risks.This review provides an overview of a selective literature search based on the PubMed-database and german consensus recommendations. Used search terms included: (methadone*) AND (breastfeeding OR lactation), (methadone*) AND (human milk), (buprenorphine*) AND (breastfeeding OR lactation) and (buprenorphine*) AND (human milk).According to the available literature, addicted women, substinated with methadone or buprenorphine are allowed to breast feed their newborns. The advantages of breast feeding prevail the risks of an infant opiate intoxication caused by methadone or buprenorphine.

  2. Manifest and Latent Components in Methadone Maintenance: The Methadone Maintenance Game

    ERIC Educational Resources Information Center

    King, Charles H.

    1975-01-01

    This paper discusses various difficulties which arise when the staff of a methadone maintenance clinic must come to grips with the manifest and latent issues in service delivery. A solution is suggested which involves severing the tie between methadone and the behaviors which are reinforced by its use. (Author)

  3. Changes in attitude toward methadone.

    PubMed

    Brown, B S; Jansen, D R; Benn, G J

    1975-02-01

    Staff and client attitudes toward heroin users and toward maintenance and abstient clients were assessed in 1970 and again in 1973. On each occasion there was striking agreement between the ratings made by staff and client groups. Abstinent clients were rated by all groups as significantly more effective and more responsible than either maintance clients or heroin users; maintenance clients were rated as more conservative, self-conscious, and self-effacing than were the other groups. While heroin users and abstinent clients were characterized similarly in the two rating periods, raters in the 1973 survey viewed methadone hydrochloride clients as more passive and less inclined to undertake adult responsibilities than was true of raters in the 1970 survey.

  4. Methadone

    MedlinePlus

    ... were addicted to opiate drugs by producing similar effects and preventing withdrawal symptoms in people who have ... your medications or monitor you carefully for side effects.tell your doctor what herbal products you are ...

  5. Intradialytic clearance of opioids: methadone versus hydromorphone.

    PubMed

    Perlman, Ryan; Giladi, Hili; Brecht, Krista; Ware, Mark A; Hebert, Terence E; Joseph, Lawrence; Shir, Yoram

    2013-12-01

    Opioids are commonly prescribed to patients with chronic pain associated with end-stage renal disease requiring hemodialysis. The stability of opioid analgesia during dialysis may vary among different opioids. No studies to date have corroborated this clinical observation by directly comparing plasma concentrations of different opioids during dialysis. We compared changes in peridialysis plasma concentrations of 2 pharmacokinetically distinct opioids, methadone and hydromorphone (HM). Fourteen dialysis patients with chronic pain received either methadone or HM for at least 2 weeks before beginning the study. Blood samples were obtained immediately before, during, and after hemodialysis in 2 separate dialysis sessions, 1 week apart, and were analyzed for opioid concentrations. Methadone plasma concentrations were more stable during hemodialysis compared to HM: the mean percent change of methadone plasma levels was 14.9% ± 8.2% (± SD) compared with 55.1% ± 8.1% in the HM treatment group, a difference of 40.2% (95% confidence interval 17.14 to 63.14). The mean plasma clearance of methadone was 19.9 ± 8.5 mL/min (± SD) compared with 105.7 ± 8.3 mL/min for HM, a difference of 85.7 mL/min (95% confidence interval 61.9 to 109.1). There were no differences between the 2 opioid groups in pain scores, side effect profile, and quality of life. Methadone therapy was not associated with an increased rate of adverse events. If confirmed by larger clinical studies, methadone could be considered as one of the opioids of choice in dialysis patients.

  6. Work Adjustment of the Methadone-Maintained Corporate Employee

    ERIC Educational Resources Information Center

    Yankowitz, Robert; Randell, Joan

    1977-01-01

    The work adjustment of 26 methadone-maintained corporate employees was evaluated. Results indicated: (a) relative to their nonmethadone-maintained coworkers, the methadone-maintained employees had comparable job performance and superior punctuality and attendance; and (b) the methadone-maintained skilled laborers were satisfied with their…

  7. Going Through the Changes: Methadone in New York City

    ERIC Educational Resources Information Center

    Agar, Michael

    1977-01-01

    Methadone has been defined as an agent to draw addicts out of the street life into "straight" society. However, the complementary perspective of the streets sees methadone as a new, widely available drug to be integrated into a subculture previously dominated by heroin. This article discusses the adaptation to methadone and its…

  8. A 21-day-old boy with an annular eruption. Tinea faciei / Tinea capitis.

    PubMed

    Berry, Adam; Abramovici, Gil; Chamlin, Sarah L

    2014-01-01

    A healthy 21-day-old black male was referred to pediatric dermatology for evaluation of a facial and scalp eruption that had been present for less than 1 week. The child's parents had applied a topical corticosteroid cream for several days without any improvement noted. The child was otherwise well and thriving. Review of systems was negative. Family history was unremarkable for autoimmune or infectious skin diseases. On physical examination the patient was alert, active, and vigorous. He had multiple 1 to 2.5-cm erythematous annular, scaly plaques with pustules on the periphery on his upper cheeks, forehead, and anterior scalp (Figures 1-2). No alopecia was noted. Occipital and neck lymph nodes were not palpable. A potassium hydroxide skin preparation was negative for fungal elements and a fungal culture was performed. Serum laboratory testing was also performed.

  9. Dose finding in a low-dose 21-day combined oral contraceptive containing gestodene.

    PubMed

    Lüdicke, F; Sullivan, H; Spona, J; Elstein, M

    2001-10-01

    An open label, non-comparative study was carried out in 22 women over a total of five cycles. After an untreated cycle, oral administration of 20 microg ethinyl estradiol (EE) with 50 microg gestodene (GST) (tablets taken daily for 21 days with a break of 7 days) was commenced, and three treatment cycles were followed by an untreated follow-up control cycle. The ability of this formulation to inhibit ovulation and suppress ovarian activity was assessed by using hormonal parameters and ultrasound. One ovulation occurred during treatment. Luteinized unruptured follicles were observed in three cases in the second treatment cycle and in one case during the third treatment cycle. Follicle-like structures larger than 13 mm associated with a serum estradiol level of more than 30 pg/mL were noted in 19% of the women in the first treatment cycle. The rate of active follicle-like structures was 43% in the second treatment cycle and 28% in the third treatment cycle. The results were compared with previously reported findings of a preparation containing 20 microg EE and 75 microg GST. With regard to ovarian grading and endogenous hormone secretion, considerably more residual ovarian activity, with all parameters examined, was found in the 20 microg EE and 50 microg GST preparation compared to the 20 microg EE and 75 microg GST preparation. It was concluded that the 20 microg EE and 50 microg GST preparation administered for 21 days does not meet the requirements of a combined oral contraceptive with respect to ovulation inhibition.

  10. Investigation of the interactions between methadone and elvitegravir-cobicistat in subjects receiving chronic methadone maintenance.

    PubMed

    Bruce, R Douglas; Winkle, P; Custodio, J M; Wei, X; Rhee, M S; Kearney, B P; Ramanathan, S; Friedland, Gerald H

    2013-12-01

    Interactions between HIV and opioid dependence therapies are known to occur. We sought to determine if such interactions occurred between methadone and elvitegravir boosted with cobicistat (EVG/COBI). We performed a within-subject open-label pharmacokinetic and pharmacodynamic study of 11 HIV-seronegative subjects stabilized on at least 2 weeks of methadone. Subjects underwent baseline and steady-state evaluation of the effect of elvitegravir 150 mg once a day (QD) boosted with 150 mg QD of cobicistat (EVG/COBI) on methadone pharmacokinetic parameters. Safety and pharmacodynamics were monitored throughout the study. Compared to baseline values, the R-methadone mean area under the concentration-time curve to the end of the dosing period (AUCtau) (5,550 versus 6,210 h · ng/ml) and mean maximum concentration of drug in serum (Cmax) (316 versus 337 ng/ml) did not significantly increase in the presence of EVG/COBI. Compared to baseline values, the S-methadone mean AUCtau (7,040 versus 7,540 h · ng/ml) and mean Cmax (446 versus 452 ng/ml) did not significantly increase in the presence of EVG/COBI. The AUCtau, Cmax, and Ctau of elvitegravir and cobicistat did not significantly differ from those of historical controls. Opioid withdrawal or overdose was not observed among subjects in this study. The addition of EVG/COBI to stabilized patients receiving methadone did not affect methadone pharmacokinetics and pharmacodynamics. These two agents can be safely coadministered.

  11. [Fatal methadone poisoning of a child].

    PubMed

    Klupp, N; Risser, D; Stichenwirth, M; Hönigschnabl, S; Stimpfl, T; Bauer, G

    2000-04-21

    The substance methadone is used for substitution therapy since the 1960s in the U.S. Mainly because of the endemic spread of HIV-1 infections among intravenous drug abusers methadone was made legally available through medical prescription in Austria in 1987. Legal authorities today also allow the patient to take home the necessary daily consumption for weekends or public holidays. The drug is distributed as a watery solution in tiny bottles, which are fitted with an ordinary screw cap. This kind of distribution may, however, have fatal consequences. This is demonstrated in the following case of accidental poisoning of an infant: A two-year-old girl whose parents were both participating in the substitution scheme was found dead in her bed in Vienna in 1997. Forensic autopsy revealed a methadone concentration in the liver tissue of 640 ng/g. The criminal investigation determined that the girl had opened a bottle of methadone solution and subsequently had taken the drug. Considering the circumstances of this accident, from the medical point of view safety devices for the screw caps of the methadone bottles should be required by law, in order to avoid future accidental poisoning.

  12. Body Composition Changes Associated With Methadone Treatment

    PubMed Central

    Sadek, Gamal E.; Chiu, Simon; Cernovsky, Zack Z.

    2016-01-01

    Background: Methadone is associated with a statistically significant increase in BMI in the first 2 years of treatment. Objectives: To evaluate the changes of body composition (bone mass, % fat, % muscle mass, % water, and basal metabolic rate) related to this increase. Patients and Methods: Changes in body composition were monitored, via bioelectrical impedance, in 29 patients in methadone treatment for opiate dependency (age 18 to 44, mean = 29.3, SD = 7.0, 13 men, 16 women). Results: Within one year from admission to treatment, a statistically significant (t-tests, P < 0.05) increase was noted in their body mass index (BMI), % of body fat, average body mass, and average basal metabolic rate, and relative decrease in their % of muscle mass and % of bone mass. Neither absolute bone mass nor muscle mass changed significantly. Conclusions: Physicians involved in care of methadone patients should recommend dietary and lifestyle changes to improve their overall health. PMID:27162765

  13. Pharmacogenomics of methadone maintenance treatment.

    PubMed

    Somogyi, Andrew A; Barratt, Daniel T; Ali, Robert L; Coller, Janet K

    2014-05-01

    Methadone is the major opioid substitution therapy for opioid dependence. Dosage is highly variable and is often controlled by the patient and prescriber according to local and national policy and guidelines. Nevertheless many genetic factors have been investigated including those affecting its metabolism (CYP2B6-consistent results), efflux transport (P-gp-inconsistent results), target μ-opioid receptor (μ-opioid receptor-inconsistent results) and a host of other receptors (DRD2) and signaling elements (GIRK2 and ARRB2; not replicated). None by themselves have been able to substantially explain dosage variation (the major but not sole end point). When multiple genes have been combined such as ABCB1, CYP2B6, OPRM1 and DRD2 a greater contribution to dosage variation was found but not as yet replicated. As stabilization of dosage needs to be made rapidly, it is imperative that larger internationally based studies be instigated so that genetic contribution to dosage can be properly assessed, which may or may not tailor to different ethnic groups and each country's policy towards an outcome that benefits all.

  14. Knowledge and stigma regarding methadone maintenance treatment among personnel of methadone maintenance treatment and non-methadone maintenance treatment addiction facilities in Israel.

    PubMed

    Shidlansik, Lia; Adelson, Miriam; Peles, Einat

    2017-01-01

    Stigma attached to methadone maintenance treatment is very common. The objective of the current article is to evaluate the presence of stigma and its relation to the extent of knowledge about methadone maintenance treatment. The authors conducted a survey among methadone maintenance treatment and non-methadone maintenance treatment addiction therapists from different treatment centers in Israel, including methadone maintenance treatment clinics (Ministry of Health) and non-methadone maintenance treatment addiction facilities (Ministry of Social Services), using an anonymous questionnaire about methadone maintenance treatment stigma and knowledge. There were 63 therapists from methadone maintenance treatment clinics (63%) and 46 therapists from the social services department (SSD) non-methadone maintenance treatment addiction facilities (9.2%) who responded. Methadone maintenance treatment versus social services department personnel were older (42.7 ± 12.8 versus 37.5 ± 8.2 years; p = 0.03), with fewer females (48 versus 75%; p = 0.006), and 50% were social workers compared to 100% social workers in the SSD group (p < 0.0005). Stigma score was lower among methadone maintenance treatment personnel compared to the social services department personnel (3 ± 2.5 versus 5.0 ± 3.5; p = 0.0001), while the knowledge score about methadone maintenance treatment was higher among the methadone maintenance treatment personnel (10.3 ± 2.9 versus 7.7 ± 2.8; p < 0.0005). The difference in both the stigma and knowledge scores remained significant after controlling for age, gender, and profession. There was a negative correlation between the stigma and knowledge scores among both the methadone maintenance treatment (R = -0.5, p < 0.0005) and the social services department personnel (R = -0.33, p = 0.03). These results revealed a significant correlation between the presence of stigma and the extent of education and knowledge about methadone maintenance treatment, with ignorance

  15. Methylene blue photodynamic therapy in rats' wound healing: 21 days follow-up

    NASA Astrophysics Data System (ADS)

    Carneiro, Vanda Sanderana Macêdo; Catao, Maria Helena Chaves de Vasconcelos; Menezes, Rebeca Ferraz; Araújo, Natália Costa; Gerbi, Marleny Elizabeth Martinez

    2015-06-01

    The experimental evaluated the photodynamic therapy (PDT) in wound healing. It used 60 male rats, making two circular wounds at each animal. They were treated at 48hs intervals, with methylene blue (MB), low level laser treatment (LLLT) or both, thus resulting in PDT. The wounds were observed 01, 03, 07, 14 and 21 days after and then processed and subjected to HE staining to analyze granulation tissue, necrosis, epithelialization and collagen. After day 1, wounds treated with MB showed necrosis less intense than other groups, and the PDT group showed more intense granulation tissue. At day 3, reepithelialization was absent for half of injuries in the PDT group, and this group was also with lower collagen. However, at day 7, this same group presented reepithelialization more advanced than control group, which did not happen with those treated with MB or LLLT (p = 0.015). The results allow us to conclude that PDT difficulted reepithelization at 7th day and interfered in standard healing. However, when used separately, MB and LLLT interfered significantly compared to the control group, which did not happened to the PDT group. There was no significant difference between the treatment groups in other analysed times.

  16. Use of population modeling to interpret a 21-day sediment elutriate bioassay with Daphnia magna

    SciTech Connect

    Bridges, T.S.; Gibson, A.B.; Wright, R.B.; Gray, B.R.; Gamble, V.E.

    1994-12-31

    Sediment contamination was evaluated in 17 Great Lakes sediments using a 21-day sediment elutriate bioassay with D. magna. Sediment type had a significant effect on survival at the conclusion of the test, age at first reproduction, the number of broods produced, and the total number of young produced per adult. Sediments producing low survivorship also had negative effects on reproduction. However, a broad range of reproductive responses were found among sediments with high survivorship. To integrate all of these results a stochastic matrix population model was constructed for each of the sediment treatments. Survivorship, age at first reproduction, and total fecundity were all important determinants of population growth. However, modeling results indicated that independent examination of the endpoints measured during the test does not accurately reflect effects at the population level; i.e., no one endpoint appeared to have an overriding effect on population growth. The amount of total suspended solids (TSS) in the elutriates had a strong effect on the reproductive endpoints measured; TSS was negatively correlated with age at first reproduction and positively correlated with per brood fecundity and measures of population growth. Demographic modeling appears to be a useful method for integrating the effects of multiple endpoints and for providing ecologically relevant interpretive guidance.

  17. Evaluation of dual-tip micromanometers during 21-day implantation in goats

    NASA Technical Reports Server (NTRS)

    Reister, C. A.; Koenig, S. C.; Schaub, J. D.; Ewert, D. L.; Swope, R. D.; Latham, R. D.; Fanton, J. W.; Convertino, V. A. (Principal Investigator)

    1998-01-01

    Investigative research efforts using a cardiovascular model required the determination of central circulatory haemodynamic and arterial system parameters for the evaluation of cardiovascular performance. These calculations required continuous beat-to-beat measurement of pressure within the four chambers of the heart and great vessels. Sensitivity and offset drift, longevity, and sources of error for eight 3F dual-tipped micromanometers were determined during 21 days of implantation in goats. Subjects were instrumented with pairs of chronically implanted fluid-filled access catheters in the left and right ventricles, through which dual-tipped (test) micromanometers were chronically inserted and single-tip (standard) micromanometers were acutely inserted. Acutely inserted sensors were calibrated daily and measured pressures were compared in vivo to the chronically inserted sensors. Comparison of the pre- and post-gain calibration of the chronically inserted sensors showed a mean sensitivity drift of 1.0 +/- 0.4% (99% confidence, n = 9 sensors) and mean offset drift of 5.0 +/- 1.5 mmHg (99% confidence, n = 9 sensors). Potential sources of error for these drifts were identified, and included measurement system inaccuracies, temperature drift, hydrostatic column gradients, and dynamic pressure changes. Based upon these findings, we determined that these micromanometers may be chronically inserted in high-pressure chambers for up to 17 days with an acceptable error, but should be limited to acute (hours) insertions in low-pressure applications.

  18. Quantitation of methadone and metabolite in patients under maintenance treatment.

    PubMed

    Diong, Shiau Hui; Mohd Yusoff, Nor Shuhadah; Sim, Maw Shin; Raja Aziddin, Raja Elina; Chik, Zamri; Rajan, Poppy; Abdul Rashid, Rusdi; Chemi, Norliza; Mohamed, Zahurin

    2014-01-01

    Gas chromatography-mass spectrometry quantitative method was developed to monitor concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in plasma and urine of patients. The developed method was simple, accurate and reproducible to quantify methadone and EDDP in plasma and urine samples in the concentration range of 15-1,000 and 50-2,000 ng/mL, respectively. The proposed analytical method was applied to plasma and urine samples obtained from 96 patients undergoing methadone maintenance treatment (MMT) with daily methadone doses of 2-120 mg/day. Urinary methadone excretion was observed to be significantly affected by pH, in which the ratio of methadone to EDDP was two times higher in acidic urine (P = 0.029). The findings of this study further enhance the guidelines for monitoring of methadone treatment among outpatients. Methadone-to-EDDP ratio in urine was found to be consistent at 24 and 4 h, hence suggesting the possibility that outpatients may be monitored with single urine sample in order to check for compliance. This study which provides data on peak concentrations of methadone and EDDP as well as the ratio of both compounds has added to the body of knowledge regarding pharmacokinetic properties of methadone among heroin-dependent patients under MMT.

  19. Methadone maintenance and drug-related crime.

    PubMed

    Bell, J; Mattick, R; Hay, A; Chan, J; Hall, W

    1997-01-01

    Using data from an evaluation of methadone maintenance treatment, this study investigated factors associated with continued involvement in crime during treatment, and in particular whether there appeared to be differences in effectiveness of treatment between different methadone clinics. The methodology was an observational study, in which 304 patients attending three low-intervention, private methadone clinics in Sydney were interviewed on three occasions over a twelve month period. Outcome measures were self-reported criminal activity and police department records of convictions. By self-report, crime dropped promptly and substantially on entry to treatment, to a level of acquisitive crime about one-eighth that reported during the last addiction period. Analysis of official records indicated that rates of acquisitive convictions were significantly lower in the in-treatment period compared to prior to entry to treatment, corroborating the changes suggested by self-report. Persisting involvement in crime in treatment was predicted by two factors: the cost of persisting use of illicit drugs, particularly cannabis, and ASPD symptom count. Treatment factors also were independently predictive of continued involvement in crime. By both self-report and official records, and adjusting for subject factors, treatment at one clinic was associated with greater involvement in crime. This clinic operated in a chaotic and poorly organized way. It is concluded that crime during methadone treatment is substantially lower than during street addiction, although the extent of reduction depends on the quality of treatment being delivered.

  20. Methadone Maintenance: The Addict's Family Recreated.

    ERIC Educational Resources Information Center

    Schwartzman, John; Bokos, Peter

    1979-01-01

    A study of four methadone clinics, the addicts treated at these clinics, and their families, reveals basic dissonances in treatment ideology and professional-paraprofessional relationships which, combined with the addict's particular mode of functioning, make significant change in his behavior improbable. (Author)

  1. Employment Patterns of Methadone Maintenance Clients

    ERIC Educational Resources Information Center

    Bloch, Harriet I.; And Others

    1977-01-01

    Analysis of employment patterns of methadone maintenance clients had indicated that the majority were not employed at time of program admission. At time of evaluation, 70 percent of the sample were employed; 88 percent of these clients had previous work histories and brought marketable skills with them. (Author)

  2. Conglomerate pulmonary disease: a form of talcosis in intravenous methadone abusers.

    PubMed

    Sieniewicz, D J; Nidecker, A C

    1980-10-01

    A program of detoxification of heroin addicts by the use of oral methadone produced a series of patients who developed pulmonary granulomatous mass lesions as the result of the intravenous use of the oral form of the drug. Talc, used in the preparation of the tablet, seems to be the offending substance. Besides producing a diffuse interstitial granulomatous reaction, conglomerate masses in the upper lung zones were also noted. This radiographic pattern can occur rather rapidly from the background of fine diffuse interstitial micronodularity. The latter may be subtle, but can change to mass lesions associated with lung contraction, volume loss in the upper lung zones, and hyperinflation in the lower lungs. The mechanism of formation of mass lesions is unknown, but individual host reaction and immunologic mechanisms probably play a role. The development and progress of such a process is described in four heroin addicts.

  3. Methadone Maintenance Therapy in Vietnam: An Overview and Scaling-Up Plan

    PubMed Central

    Nguyen, Tam T. M.; Nguyen, Long T.; Pham, Manh D.; Vu, Hoang H.; Mulvey, Kevin P.

    2012-01-01

    Vietnam is among the countries with the highest rate of HIV transmission through injecting drug users. HIV prevalence among injecting drug users is 20% and up to 50% in many provinces. An estimated number of drug users in the country by the end of 2011 were 171,000 in which the most common is heroin (85%). Detoxification at home, community, and in rehabilitation centers have been the main modalities for managing heroin addiction until Methadone Maintenance Treatment (MMT) was piloted in 2008. Recent reports have demonstrated positive treatment outcomes. Incidence of HIV was found remarkably low among patients on MMT. Treatment has significantly improved the quality of life as well as stability for society. The government has granted the Ministry of Health (MoH) to expand Methadone treatment to at least 30 provinces to provide treatment for more than 80,000 drug users by 2015. The Vietnam Administration for HIV/AIDS Control (VAAC) and MOH have outlined the role and responsibility of key departments at the central and local levels in implementing and maintaining MMT treatment. This paper will describe the achievements of the MMT pilot program and the scaling-up plan as well as strategies to ensure quality and sustainability and to overcome the challenges in the coming years. PMID:23227351

  4. Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: I. Evidence against CYP3A mediation of methadone clearance.

    PubMed

    Kharasch, E D; Bedynek, P S; Park, S; Whittington, D; Walker, A; Hoffer, C

    2008-10-01

    Ritonavir diminishes methadone plasma concentrations, an effect attributed to CYP3A induction, but the actual mechanisms are unknown. We determined ritonavir effects on stereoselective methadone pharmacokinetics and clinical effects (pupillary miosis) in healthy human immunodeficiency virus-negative volunteers. Subjects received intravenous plus oral (deuterium-labeled) racemic methadone after no ritonavir, short-term (3-day) ritonavir, and steady-state ritonavir. Acute and steady-state ritonavir, respectively, caused 1.5- and 2-fold induction of systemic and apparent oral R- and S-methadone clearances. Ritonavir increased renal clearance 40-50%, and stereoselectively (S > R) increased hepatic methadone N-demethylation 50-80%, extraction twofold, and clearance twofold. Bioavailability was unchanged despite significant inhibition of intestinal P-glycoprotein. Intestinal and hepatic CYP3A was inhibited > 70%. Ritonavir shifted methadone plasma concentration-miosis curves leftward and upward. Rapid ritonavir induction of methadone clearance results from increased renal clearance and induced hepatic metabolism. Induction of methadone metabolism occurred despite profound CYP3A inhibition, suggesting no role for CYP3A in clinical methadone metabolism and clearance. Ritonavir may alter methadone pharmacodynamics.

  5. Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment.

    PubMed

    Meini, Milo; Moncini, Marco; Daini, Laura; Giarratana, Tania; Scaramelli, Daniela; Chericoni, Silvio; Stefanelli, Fabio; Rucci, Paola

    2015-08-05

    This study evaluated the relationship between the plasma concentration of l-methadone and response to methadone in real-world patients, in order to identify a minimum plasma concentration above which methadone treatment is effective. Ninety-four patients with opioid dependence under maintenance methadone treatment were consecutively recruited. Response was defined as negative urine analyses in the three weeks prior to the blood sampling. The percentage of participants with a plasma l-methadone concentration between 100 and 250 ng/ml was 54.2% among those with a methadone dosage ≥60 mg/day. Plasma l-methadone concentrations were significantly higher in patients with negative urine analyses compared with those with positive urine analyses (median 93 vs. 77 ng/ml, Mann-Whitney test, P<0.05). Above plasma l-methadone concentrations of 200 ng/ml no heroin use was reported and urine analyses were negative. Moreover, above concentrations of 250 ng/ml craving was absent. Examination of demographic correlates of treatment outcome indicated that older age, a stable job and being married were protective against the use of heroin. Mean plasma l-methadone concentration was significantly lower in patients who used cannabis compared with those who did not use cannabis, after adjusting for methadone dosage. In conclusion our results identify specific cut-offs for plasma l-methadone concentrations about which therapeutic response is observed and provide new evidence that therapeutic response is associated with patient׳s demographic characteristics. This underscores the need to monitor plasma methadone concentrations as part of Drug Addiction Services routine practice, in order to provide an objective framework for changing the methadone dosage.

  6. Characteristics of methadone-related fatalities in Norway.

    PubMed

    Bernard, Jean-Paul; Khiabani, Hassan Z; Hilberg, Thor; Karinen, Ritva; Slørdal, Lars; Waal, Helge; Mørland, Jørg

    2015-11-01

    There are currently over 7000 patients enrolled in opioid maintenance treatment (OMT) programs in Norway. A rise in methadone-related deaths proportional to increasing methadone sales over the period 2000-2006 has been observed, but the causative factors for these fatalities have been elusive. In the present study, individual characteristics, methadone concentrations and additional toxicological findings were analyzed. Methadone intoxication deaths (n = 264) were divided into 3 groups according to toxicological findings in whole blood: group 1 - methadone detected alone, or together with one additional drug at low or therapeutic levels, or a low concentration of ethanol (<1 g/L) (n = 21); group 2 - multiple additional drugs/substances detected below lethal levels (n = 175); group 3 - one or more additional drugs/substances detected at lethal levels, or ethanol >3 g/L (n = 55). Methadone blood concentrations in decedents who had been enrolled in OMT were higher than for decedents not in treatment, in all groups. Blood methadone concentrations around 1 mg/L were present in fatal multi-drug intoxications in OMT patients. Results suggest that some patients may be at risk of dying when combining therapeutic concentrations of methadone with other psychoactive substances. Somatic disease was a common finding among deceased OMT patients. Concentrations in methadone users not enrolled in OMT were predominantly between 0.3 and 0.4 mg/L and were not related to the presence of other drugs. However, methadone concentrations below 0.1 mg/L may be associated with intoxication following methadone use, both alone and in combination with other drugs. Younger male users (mean age 34 years) seemed to have a higher susceptibility to methadone intoxication.

  7. Lung function measurements over 21 days shiftwork in steelworkers from a strandcasting department.

    PubMed Central

    Nemery, B; Van Leemputten, R; Goemaere, E; Veriter, C; Brasseur, L

    1985-01-01

    On the assumption that short term changes in lung function may reflect the potential for a long term decline the evolution of lung function indices in 25 steelworkers from a strandcasting department and in 11 comparable steelworkers not exposed to dust was investigated over an almost uninterrupted 21 day working period and over three different workshifts. The mean total dust level in the strandcasting department, assessed by personal sampling, was 11.8 mg/m3. All subjects were examined at the beginning, in the middle, and at the end of their first (day 1) morning shift (0600 to 1400), their last (day 14) afternoon shift (1400 to 2200), and their last (day 21) night shift (2200 to 0600). Indices measured were vital capacity (VC), forced expiratory volume in one second (FEV1) and in three seconds (FEV3), forced expiratory flow over the middle half of the forced vital capacity (FEF25-75), peak expiratory flow rate (PEFR), the slope of the N2 plateau (delta N2) and the closing volume (CV) of the single breath oxygen test. Differences in indices between initial values (0600 on day 1) and final values (0500 on day 21) were not significant in the control group (except delta N2 which became lower); in the casting group there were significant (p less than 0.05) decreases in FEF25-75 and FEV3, but these decreases were not significantly greater than in the control group. Lung function changes were not significant in either group over the morning shift. During the afternoon there were significant decreases in spirometric indices in the casting group, with no significant decreases in the control group, but the interactions between exposure and time were generally not significant. During the night shift, however, the decreases in FEV1 and FEF25-75 observed in the strandcasting group were significantly more pronounced than in the control group. The single breath test, which many subjects failed to perform correctly on each occasion, showed no significant changes in closing

  8. 26 CFR 301.6332-3 - The 21-day holding period applicable to property held by banks.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... deposits at the end of the 21-day holding period (or at the end of any longer period that has been... not include any interest on the deposits at the end of the holding period, or any extension thereof... the end of the holding period, or any extension thereof, is treated as a payment to the...

  9. Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics.

    PubMed

    Kharasch, E D; Whittington, D; Ensign, D; Hoffer, C; Bedynek, P S; Campbell, S; Stubbert, K; Crafford, A; London, A; Kim, T

    2012-04-01

    Mechanisms by which efavirenz diminishes methadone plasma concentrations are unknown. This investigation determined efavirenz influence on clinical methadone disposition and miosis, intravenous and oral alfentanil clearance (hepatic and intestinal cytochrome P450 3A4/5 (CYP3A4/5) activity), fexofenadine disposition (intestinal transporters activity), and efavirenz clearance and 8-hydroxylation (CYP2B6 activity), and human hepatocyte effects. Efavirenz induced systemic and oral alfentanil clearances two- to fivefold and induced efavirenz 8-hydroxylation. Efavirenz stereoselectively decreased methadone plasma concentrations 50-70%. Methadone systemic and oral clearances, hepatic clearance and extraction ratio, N-demethylation, and metabolite formation clearance were stereoselectively increased two- to threefold. Bioavailability decreased. Efavirenz shifted methadone concentration-miosis curves leftward and upward. Efavirenz induced hepatocyte CYP2B6 and CYP3A4 expression, activity, and methadone N-demethylation. Results show that efavirenz coinduced hepatic CYP2B6 and CYP3A4/5, coinduced hepatic and intestinal CYP3A4/5, and coinduced gastrointestinal CYP3A4/5 and efflux transporters. Methadone disposition was most consistent with efavirenz induction of hepatic CYP2B6-mediated methadone N-demethylation. Efavirenz may alter methadone pharmacodynamics.

  10. Pharmacotherapy in the Treatment of Addiction: Methadone

    PubMed Central

    Kreek, Mary Jeanne; Borg, Lisa; Ducat, Elizabeth; Ray, Brenda

    2010-01-01

    Methadone maintenance treatment is the most widely available pharmacotherapy for opioid addiction and has been shown over a period of 40 years to be an effective and safe treatment. While women comprise approximately 40% of clients currently being treated in MMT programs, comparatively little research geared specifically toward this group has been published. This article begins with an overview of neurobiological studies on opioid addiction, including a discussion of gender differences, followed by a review of the pharmacology of methadone The authors then examine the particular needs and differences of women being treated in MMTs, including co-dependence with other substances, women’s health issues and psychosocial needs unique to this population. In conclusion, research shows that women have different substance abuse treatment needs in comparison to their male counterparts. One New York City MMT program that has attempted to address these differences is highlighted. PMID:20407977

  11. Methadone Anonymous: A 12-Step Program for Methadone Maintained Heroin Addicts.

    PubMed

    Gilman, Stephen M.; Galanter, Marc; Dermatis, Helen

    2001-12-01

    Methadone Anonymous (MA) is a new 12-step fellowship developed for methadone maintained heroin addicts. A total of 53 MA members completed a survey assessing factors related to methadone maintenance treatment program (MMTP) entry, drug use, MA participation, beliefs concerning effectiveness of MMTP and MA, and level of social cohesiveness. Length of time in MA was associated with a decreased use of alcohol, cocaine, and marijuana. Clients rated components of MA to be significantly more helpful to recovery than MMTP treatment components. Affiliation to five MA members known best by the respondents was significantly greater than affiliation to non-MA members. Length of time in MA was positively associated with MA affiliation. Social affiliation and endorsement of 12-step principles were positively correlated. These findings suggest that MA participation has benefits not available in professionally driven MMTP, and should be further studied.

  12. Enzyme therapeutics for systemic detoxification.

    PubMed

    Liu, Yang; Li, Jie; Lu, Yunfeng

    2015-08-01

    Life relies on numerous biochemical processes working synergistically and correctly. Certain substances disrupt these processes, inducing living organism into an abnormal state termed intoxication. Managing intoxication usually requires interventions, which is referred as detoxification. Decades of development on detoxification reveals the potential of enzymes as ideal therapeutics and antidotes, because their high substrate specificity and catalytic efficiency are essential for clearing intoxicating substances without adverse effects. However, intrinsic shortcomings of enzymes including low stability and high immunogenicity are major hurdles, which could be overcome by delivering enzymes with specially designed nanocarriers. Extensive investigations on protein delivery indicate three types of enzyme-nanocarrier architectures that show more promise than others for systemic detoxification, including liposome-wrapped enzymes, polymer-enzyme conjugates, and polymer-encapsulated enzymes. This review highlights recent advances in these nano-architectures and discusses their applications in systemic detoxifications. Therapeutic potential of various enzymes as well as associated challenges in achieving effective delivery of therapeutic enzymes will also be discussed.

  13. Trends in Methadone Distribution for Pain Treatment, Methadone Diversion, and Overdose Deaths - United States, 2002-2014.

    PubMed

    Jones, Christopher M; Baldwin, Grant T; Manocchio, Teresa; White, Jessica O; Mack, Karin A

    2016-07-08

    Use of the prescription opioid methadone for treatment of pain, as opposed to treatment of opioid use disorder (e.g., addiction), has been identified as a contributor to the U.S. opioid overdose epidemic. Although methadone accounted for only 2% of opioid prescriptions in 2009 (1), it was involved in approximately 30% of overdose deaths. Beginning with 2006 warnings from the Food and Drug Administration (FDA), efforts to reduce methadone use for pain have accelerated (2,3). The Office of the Assistant Secretary for Planning and Evaluation of the U.S. Department of Health and Human Services and CDC analyzed methadone distribution, reports of diversion (the transfer of legally manufactured methadone into illegal markets), and overdose deaths during 2002-2014. On average, the rate of grams of methadone distributed increased 25.1% per year during 2002-2006 and declined 3.2% per year during 2006-2013. Methadone-involved overdose deaths increased 22.1% per year during 2002-2006 and then declined 6.5% per year during 2006-2014. During 2002-2006, rates of methadone diversion increased 24.3% per year; during 2006-2009, the rate increased at a slower rate, and after 2009, the rate declined 12.8% per year through 2014. Across sex, most age groups, racial/ethnic populations, and U.S. Census regions, the methadone overdose death rate peaked during 2005-2007 and declined in subsequent years. There was no change among persons aged ≥65 years, and among persons aged 55-64 years the methadone overdose death rate continued to increase through 2014. Additional clinical and public health policy changes are needed to reduce harm associated with methadone use for pain, especially among persons aged ≥55 years.

  14. Human Methadone Self-Administration and the Generalized Matching Law

    ERIC Educational Resources Information Center

    Spiga, Ralph; Maxwell, R. Stockton; Meisch, Richard A.; Grabowski, John

    2005-01-01

    The present study examined whether in humans the generalized matching law described the relation between relative responding and relative drug intake by humans under concurrent variable interval variable interval (conc VI VI) schedules of drug reinforcement. Methadone-maintained patients, stabilized on 80 mg per day of methadone, were recruited…

  15. The metabolism of methadone by cultured mammalian cells.

    PubMed

    Will, P C; Noteboom, W D

    1978-02-15

    Rat hepatoma tissue culture cells and mouse leukemic cells were found to metabolize [1-3H] methadone to at least 2 unidentified radioactive compounds. These results suggest that cultured cells may be useful models for studying methadone metabolism by specific cell types.

  16. Factors Associated with Illegal Drug Use among Older Methadone Clients

    ERIC Educational Resources Information Center

    Rosen, Daniel

    2004-01-01

    Purpose. The overall aims of this study are to describe the life stressors of, exposure to illegal drug use of, and illegal drug use by older methadone clients. Design and Methods. The current study focuses on a sub-sample of the larger administrative data of a methadone clinic that is limited to African American and White clients over the age of…

  17. Methadone Diversion: Experiences and Issues. Services Research Monograph Series.

    ERIC Educational Resources Information Center

    Inciardi, James A.

    This report is a description of the phenomenon of methadone diversion as it exists now and places it in the context of prior research in this area. The intent here is to clarify issues around methadone diversion and to provide guidance to treatment administrators and program planners regarding efforts they can initiate to monitor this significant…

  18. Multimodality Approach to Methadone Treatment of Narcotic Addicts

    ERIC Educational Resources Information Center

    Brill, Leon; Chambers, Carl D.

    1971-01-01

    This multimodality approach is geared primarily to the goal of abstinence. For addicts who cannot achieve this goal, methadone maintenance is suggested as the next step. The modalities described range from low-dose maintenance for clinic outpatients to intensive rehabilitation in a methadone maintenance residential center facility. (Author)

  19. Inflammatory response in heroin addicts undergoing methadone maintenance treatment.

    PubMed

    Chan, Yuan-Yu; Yang, Szu-Nian; Lin, Jyh-Chyang; Chang, Junn-Liang; Lin, Jaung-Geng; Lo, Wan-Yu

    2015-03-30

    Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation.

  20. Methadone-related deaths in Palm Beach County.

    PubMed

    Wolf, Barbara C; Lavezzi, Wendy A; Sullivan, Linda M; Flannagan, Lisa M

    2004-03-01

    The authors reviewed cases investigated by the Palm Beach Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of methadone over the period from 1998 to 2002, to examine the role of the drug in these deaths. There were 139 methadone-positive cases, including 75 in which the death was attributed to combined drug toxicity and 23 to methadone toxicity alone. Methadone was most frequently used in conjunction with other prescription or illicit drugs, most commonly benzodiazepines and/or cocaine. There was considerable overlap in the postmortem blood methadone concentrations among the groups. Concentrations ranged from 0.114 mg/L-1.939 mg/L (mean .0559 mg/L) in cases where death was attributed to methadone toxicity; 0.050 mg/L-1.903 mg/L (mean 0.411 mg/L) in cases of combined drug toxicity; 0.069 mg/L-0.644 mg/L (mean 0.224 mg/L) in deaths attributed to other drugs; 0.062 mg/L-1.090 mg/L (mean 0.344 mg/L) among deaths attributed to natural causes and 0.072 mg/L-2.7 mg/L (mean 0.605 mg/L) among deaths due to trauma. The concentrations of methadone detected indicate that it may not be possible to establish a lethal methadone range because some deaths occurred at methadone concentrations below previously reported lethal ranges, and because of the presence of other drugs. Determining the cause of death in methadone-positive cases necessitates correlation with autopsy results and investigative findings.

  1. Decontamination and detoxification of mycotoxins.

    PubMed

    Jemmali, M

    1990-01-01

    Product decontamination and chemical detoxification are needed because preventive measures are not fully able to avoid contamination by mycotoxins. Criteria for safety evaluation studies of decontaminated products have to be established. Few chemical methods are available on an industrial scale; among them, ammoniation and the mixture monomethylamine-calcium hydroxide treatments show greatest promise of short-term application to oilseed cakes. Technical, economic, and public health aspects of these treatments are considered. Other decontamination techniques are briefly reviewed.

  2. Takotsubo cardiomyopathy due to iatrogenic methadone withdrawal.

    PubMed

    Saiful, Faisal B; Lafferty, James; Jun, Chin Hee; Teli, Sumaya; Duvvuri, Srinivas; Khattri, Saakshi; Bhat, Tariq

    2011-01-01

    Takotsubo cardiomyopathy is a syndrome characterized by transient apical ballooning or reversible midventricular systolic dysfunction. Most cases occur in postmenopausal women and are typically triggered by an acute medical illness or emotional or physical stress. Its presentation is highly suggestive of myocardial ischemia, but there is little or no evidence of epicardial coronary artery disease. To our knowledge there are only three reported cases in the literature of Takotsubo cardiomyopathy induced by opioid agonist withdrawal in adults; ours is the first reported case of iatrogenic methadone withdrawal leading to Takotsubo cardiomyopathy.

  3. Detoxification reactions: relevance to aging

    PubMed Central

    Zimniak, Piotr

    2008-01-01

    It is widely (although not universally) accepted that organismal aging is the result of two opposing forces: (i) processes that destabilize the organism and increase the probability of death, and (ii) longevity assurance mechanisms that prevent, repair, or contain damage. Processes of the first group are often chemical and physico-chemical in nature, and are either inevitable or only under marginal biological control. In contrast, protective mechanisms are genetically determined and are subject to natural selection. Life span is therefore largely dependent on the investment into protective mechanisms which evolve to optimize reproductive fitness. Recent data indicate that toxicants, both environmental and generated endogenously by metabolism, are major contributors to macromolecular damage and physiological dysregulation that contribute to aging; electrophilic carbonyl compounds derived from lipid peroxidation appear to be particularly important. As a consequence, detoxification mechanisms, including the removal of electrophiles by glutathione transferase-catalyzed conjugation, are major longevity assurance mechanisms. The expression of multiple detoxification enzymes, each with a significant but relatively modest effect on longevity, is coordinately regulated by signaling pathways such as insulin/insulin-like signaling, explaining the large effect of such pathways on life span. The major aging-related toxicants and their cognate detoxification systems are discussed in this review. PMID:18547875

  4. HIV transmission and the cost-effectiveness of methadone maintenance.

    PubMed Central

    Zaric, G S; Barnett, P G; Brandeau, M L

    2000-01-01

    OBJECTIVES: This study determined the cost-effectiveness of expanding methadone maintenance treatment for heroin addiction, particularly its effect on the HIV epidemic. METHODS: We developed a dynamic epidemic model to study the effects of increased methadone maintenance capacity on health care costs and survival, measured as quality-adjusted life-years (QALYs). We considered communities with HIV prevalence among injection drug users of 5% and 40%. RESULTS: Additional methadone maintenance capacity costs $8200 per QALY gained in the high-prevalence community and $10,900 per QALY gained in the low-prevalence community. More than half of the benefits are gained by individuals who do not inject drugs. Even if the benefits realized by treated and untreated injection drug users are ignored, methadone maintenance expansion costs between $14,100 and $15,200 per QALY gained. Additional capacity remains cost-effective even if it is twice as expensive and half as effective as current methadone maintenance slots. CONCLUSIONS: Expansion of methadone maintenance is cost-effective on the basis of commonly accepted criteria for medical interventions. Barriers to methadone maintenance deny injection drug users access to a cost-effective intervention that generates significant health benefits for the general population. PMID:10897189

  5. A systematic review of the cardiotoxicity of methadone

    PubMed Central

    Alinejad, Samira; Kazemi, Toba; Zamani, Nasim; Hoffman, Robert S.; Mehrpour, Omid

    2015-01-01

    Methadone is one of the most popular synthetic opioids in the world with some favorable properties making it useful both in the treatment of moderate to severe pain and for opioid addiction. Increased use of methadone has resulted in an increased prevalence of its toxicity, one aspect of which is cardiotoxicity. In this paper, we review the effects of methadone on the heart as well as cardiac concerns in some special situations such as pregnancy and childhood. Methods: We searched for the terms methadone, toxicity, poisoning, cardiotoxicity, heart, dysrhythmia, arrhythmia, QT interval prolongation, torsade de pointes, and Electrocardiogram (ECG) in bibliographical databases including TUMS digital library, PubMed, Scopus, and Google Scholar. This review includes relevant articles published between 2000 and 2013. The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases. The aim of this paper is to inform physicians and health care staff about these adverse effects. Effectiveness of methadone in the treatment of pain and addiction should be weighed against these adverse effects and physicians should consider the ways to lessen such undesirable effects. This article presents some recommendations to prevent heart toxicity in methadone users. PMID:26869865

  6. Methadone-induced respiratory depression in the neonatal guinea pig.

    PubMed

    Nettleton, Rosemary T; Ransom, Ty A; Abraham, Stephanie L; Nelson, Cole S; Olsen, George D

    2007-12-01

    Respiratory depression, the most serious side-effect of opioid treatment, is well documented for morphine, the most commonly used opioid in neonatal care. Less is known about methadone, a clinically relevant opioid analgesic, especially during neonatal development. This study was undertaken to determine the neonatal respiratory effects of methadone. We hypothesize that methadone is equipotent to morphine, compared to our previous morphine results in the same animal model, but has a much longer duration of action, due to its longer elimination half-life. Neonatal guinea pigs (3-14 days old) randomly received a single subcutaneous dose of methadone or saline. Using a non-invasive plethysmographic method, we measured ventilatory and metabolic parameters before injection and at intervals for 32 hr after injection while pups breathed "room air" or 5% CO(2) gas mixtures. Methadone-induced depression of ventilation was most evident during 5% CO(2) challenge. The onset of drug effects was within 15 min for all ages and doses, but the duration of action decreased with age. While the depth of methadone-induced respiratory depression did not depend on pup age, the control of breathing was different in 3-day-old pups, where inspiratory time increased fourfold; twice that of older pups. We conclude that methadone induces a naloxone reversible respiratory depression in guinea pig neonates and, in the very young, causes an abnormal breathing pattern due to changes in respiratory timing. Methadone is more potent than morphine with respect to neonatal respiratory depression, but surprisingly, the duration of methadone action was not longer than morphine.

  7. [Ultra-fast opiate detoxification under general anesthesia: preliminary results of the Liege protocol].

    PubMed

    Pinto, E; Reggers, J; Delhez, M; Fuchs, S; Venneman, I; Lamy, M; Ansseau, M

    2001-08-01

    Many studies support the hypothesis of a substantial benefit in inducing an Opiate Receptor Blockade through a Rapid Opiate Detoxification under general Anaesthesia (RODA) in opiate dependent patients. However, prospective studies and long term evaluation of the technique are lacking. In order to evaluate long-term abstinence rates after a RODA among a sample of opiate addicts, a study was started in March 1999 at the University of Liège. To date, 45 patients were evaluated (mean age: 29 +/- 5 years) with a mean opiate dependence duration of 8 +/- 4 years. Most of them were both heroin and methadone dependent; 42.2% of them were included while 31.1% did not complete the whole inclusion procedure and 26.7% were excluded. None experienced severe withdrawal symptoms. At six months, abstinence rate was 67% and 46% at one year. These preliminary results suggest the interest of the procedure in carefully selected patients.

  8. Opioid addiction and abuse in primary care practice: a comparison of methadone and buprenorphine as treatment options.

    PubMed

    Bonhomme, Jean; Shim, Ruth S; Gooden, Richard; Tyus, Dawn; Rust, George

    2012-01-01

    Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care.

  9. The effect of parole on methadone patient behavior.

    PubMed

    Anglin, M D; McGlothlin, W H; Speckart, G

    1981-01-01

    A 7-year followup of three male samples of 1971-1973 methadone maintenance admissions was conducted: a random sample of 100; a sample of 136 who had a minimum of 30 months remaining on civil addict parole status at the time of methadone entry; and a matched sample of 136 not on parole. Ninety percent of those not decreased were interviewed. The overall sample spent 58% of the nonincarcerated follow-up interval on methadone. This resulted in a large decline in daily heroin use and associated criminal behavior measures. The addition of parole supervision with urine testing resulted in only marginal improvements in behavior over that attributable to maintenance alone; however, the parole status did significantly reduce the length of intervals of daily heroin use both prior and subsequent to methadone entry.

  10. Differences in Methadone Metabolism by CYP2B6 Variants.

    PubMed

    Gadel, Sarah; Friedel, Christina; Kharasch, Evan D

    2015-07-01

    Methadone is a long-acting opioid with considerable unexplained interindividual variability in clearance. Cytochrome P450 2B6 (CYP2B6) mediates clinical methadone clearance and metabolic inactivation via N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). Retrospective studies suggest that individuals with the CYP2B6*6 allelic variant have higher methadone plasma concentrations. Catalytic activities of CYP2B6 variants are highly substrate- and expression-system dependent. This investigation evaluated methadone N-demethylation by expressed human CYP2B6 allelic variants in an insect cell coexpression system containing P450 reductase. Additionally, the influence of coexpressing cytochrome b5, whose role in metabolism can be inhibitory or stimulatory depending on the P450 isoform and substrate, on methadone metabolism, was evaluated. EDDP formation from therapeutic (0.25-1 μM) R- and S-methadone concentrations was CYP2B6.4 ≥ CYP2B6.1 ≥ CYP2B6.5 > CYP2B6.9 ≈ CYP2B6.6, and undetectable from CYP2B6.18. Coexpression of b5 had small and variant-specific effects at therapeutic methadone concentrations but at higher concentrations stimulated EDDP formation by CYP2B6.1, CYP2B6.4, CYP2B6.5, and CYP2B6.9 but not CYP2B6.6. In vitro intrinsic clearances were generally CYP2B6.4 ≥ CYP2B6.1 > CYP2B6.5 > CYP2B6.9 ≥ CYP2B6.6. Stereoselective methadone metabolism (S>R) was maintained with all CYP2B6 variants. These results show that methadone N-demethylation by CYP2B6.4 is greater compared with CYP2B6.1, whereas CYP2B6.9 and CYP2B6.6 (which both contain the 516G>T, Q172H polymorphism), are catalytically deficient. The presence or absence of b5 in expression systems may explain previously reported disparate catalytic activities of CYP2B6 variants for specific substrates. Differences in methadone metabolism by CYP2B6 allelic variants provide a mechanistic understanding of pharmacogenetic variability in clinical methadone metabolism and clearance.

  11. Are empty methadone bottles empty? An analytic study

    PubMed Central

    2014-01-01

    Background Methadone maintenance treatment is the most widely prescribed treatment for opiate dependence with proven benefits for patients. In naïve users or in case of recreational misuse, methadone can be a source of potentially lethal intoxications, resulting in fatal overdoses. A few cases of infantile intoxications have been described in the literature, some of which resulted in death. Nowadays, more than 50,000 bottles are used every day in France, most of which are thrown away in the bin. Relatives at home, especially children, can have access to these empty bottles. This study aims to determine whether the residual quantity of methadone in the bottles is associated with a risk of intoxication for someone who has a low tolerance to opiates, such as a child. Methods The methadone dosage left in a sample of 175 bottles recapped after use by the patients taking their maintenance treatment in an addiction treatment program centre was analysed during a 2-week period in March 2013. Results The mean residual quantity of methadone left in each bottle after use is 1.9 ± 1.8 mg and 3.3 ± 2.4 mg in the sample of 60 mg bottles. Conclusions There is a potential danger of accidental overdose with empty bottles of methadone syrup, especially for children. To take into account this hazard, several harm reduction strategies can be proposed, such as favouring the taking of the treatment within the delivery centres rather than the ‘take home’ doses, asking methadone users to bring back their used bottles, and raising patients’ awareness of the intoxication risks and the necessary everyday precautions. For stable patients with take home methadone, the use of capsules could be considered. PMID:24990630

  12. Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy

    PubMed Central

    Graziani, Manuela; Nisticò, Robert

    2015-01-01

    Gender-related differences in the pharmacological effects of drug are an emerging topic. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of methadone, a long-acting opioid agonist that is prescribed as a treatment for opioid dependence and the management of chronic pain. Method: We performed a search in the Medline database from 1990 to 2014 in order to find published literature related to gender differences in pharmacokinetics (PK) and pharmacodynamics (PD) of methadone. Results: None of the studies were carried out with the primary or secondary aim to identify any gender differences in the pharmacokinetic profile of methadone. Importantly; high inter-subjects variability in PK parameters was found also intra female population. The reported differences in volume of distribution could be ascribed to the physiological differences between men and women in body weight and composition, taking into account that the dose of methadone was established irrespective of body weight of patients (Peles and Adelson, 2006). On the other hand, the few studies present in literature found no gender difference in some direct pharmacodynamic parameters. Some reports have suggested that female gender is associated with an increased risk for long-QT-related cardiac arrhythmias in methadone maintenance subjects. Conclusion: Even though it may be too simplistic to expect variability only in one parameter to explain inter-individual variation in methadone response, we believe that a better knowledge of gender-related differences might have significant implications for better outcomes in opioid dependence substitution therapy in women. PMID:26106330

  13. [Fatal methadone poisoning: observations at the CHU of Liege].

    PubMed

    Denooz, R; Charlier, C

    2006-01-01

    All methadone-associated deaths from October 2002 to April 2005 are analysed. A regular increase in these fatal intoxications has been recorded, in Belgium as in other countries, due, in particular, to an intensified prescription of this product, of which illicit use as street dope becomes problematic. Over the 30 months period covered by the study, 26 deaths related to methadone were listed, of which 3 occurred in accidental circumstances. In the other 23 cases, methadone can be found, yet always associated with psychotropic substances, mainly benzodiazepines (18 cases), narcotics (15 cases) and finally alcohol (5 cases). Based upon the nature of the products combined with methadone, records have been divided in two groups: In the first group (17 observations), xenobiotics at (infra)therapeutic levels are detected. In the other group (6 observations), xenobiotics at high and toxic levels are detected. Blood methadone concentrations are not so different between the 2 groups of individuals since the median values and the extreme values are worth respectively 308, and 110-11300 microg/L, for the first group and 776 and 93-2080 microg/L for the second group. There is thus an important overlap between the therapeutic blood methadone concentrations (150-400 microg/L) and blood concentrations observed in fatalities.Thus, it is necessary that all information and post-mortem results must be examined in a critical way to identify and justify cause of the death.

  14. The Source of Methadone in Overdose Deaths in Western Virginia in 2004

    PubMed Central

    Weimer, Melissa B.; Korthuis, P. Todd; Behonick, George S.; Wunsch, Martha J.

    2011-01-01

    Objectives Methadone-related overdose deaths increased in the United States by 468% from 1999 to 2005. Current studies associate the nonmedical use of methadone with methadone-related deaths. This study describes medical examiner cases in rural Virginia in 2004 with methadone identified by toxicology and compares cases according to source of methadone. Methods In 2004, all intentional and unintentional poisoning deaths from the Office of The Chief Medical Examiner, Western District of Virginia, were reviewed to identify cases in which methadone was a direct or contributing cause of death. The Virginia Prescription Monitoring Program was reviewed for prescription opioids in the name of these identified decedents. Decedent participation in local opioid treatment programs (OTP) was also assessed. Results The source of methadone in the 61 methadone-related overdose deaths was mostly nonprescribed (67%), although 28% of decedents were prescribed methadone for analgesia. Only 5% of decedents were actively enrolled in an OTP. The majority of deaths were attributed to polysubstance overdose. Conclusions The majority of methadone overdose deaths in this study were related to illicit methadone use, rather than prescribed or OTP uses. Interventions to decrease methadone-related deaths should focus on reduction of nonprescription use of methadone. PMID:21844834

  15. A 21 day Daniel Fast improves selected biomarkers of antioxidant status and oxidative stress in men and women

    PubMed Central

    2011-01-01

    Background Dietary modification via both caloric and nutrient restriction is associated with multiple health benefits, some of which are related to an improvement in antioxidant status and a decrease in the production of reactive oxygen species. The Daniel Fast is based on the Biblical book of Daniel, is commonly partaken for 21 days, and involves food intake in accordance with a stringent vegan diet. The purpose of the present study was to determine the effect of a 21 day Daniel Fast on biomarkers of antioxidant status and oxidative stress. Methods 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day Daniel Fast following the guidelines provided by investigators. Subjects reported to the lab in a 12 hour post-absorptive state both pre fast (day 1) and post fast (day 22). At each visit, blood was collected for determination of malondialdehyde (MDA), hydrogen peroxide (H2O2), nitrate/nitrite (NOx), Trolox Equivalent Antioxidant Capacity (TEAC), and Oxygen Radical Absorbance Capacity (ORAC). Subjects recorded dietary intake during the 7 day period immediately prior to the fast and during the final 7 days of the fast. Results A decrease was noted in MDA (0.66 ± 0.0.03 vs. 0.56 ± 0.02 μmol L-1; p = 0.004), while H2O2 demonstrated a trend for lowering (4.42 ± 0.32 vs. 3.78 ± 0.21 μmol L-1; p = 0.074). Both NOx (18.79 ± 1.92 vs. 26.97 ± 2.40 μmol L-1; p = 0.003) and TEAC (0.47 ± 0.01 vs. 0.51 ± 0.01 mmol L-1; p = 0.001) increased from pre to post fast, while ORAC was unchanged (5243 ± 103 vs. 5249 ± 183 μmol L-1 TE; p = 0.974). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total calorie intake (2185 ± 94 vs. 1722 ± 85). Conclusion Modification of dietary intake in accordance with the Daniel Fast is associated with an improvement in selected biomarkers of antioxidant status and oxidative stress, including metabolites of nitric oxide (i.e., NOx). PMID:21414232

  16. Recreational drugs, methadone and protease inhibitors.

    PubMed

    Timour, K

    1998-01-01

    The Treatment Education Project, an initiative of the Staten Island AIDS Task Force, often responds to requests for information on the effects of recreational drugs on people taking anti-HIV medications. There is very little research on the topic because the drugs are illegal and the effects tested with chemically pure street drugs are not likely to mirror those in the population using varied strengths and qualities of the drugs. There have been some controlled studies with methadone, and there is a trial underway to test the use of Marinol and marijuana with Crixivan. The Treatment Education Project also provides counseling, maintains Internet sites in both English and Spanish, and sets up treatment libraries. They also provide workshops for social service agencies and staff.

  17. Detection of clinical interactions between methadone and anti-retroviral compounds using an enantioselective capillary electrophoresis for methadone analysis.

    PubMed

    Esteban, Javier; de la Cruz Pellín, María; Gimeno, Carmen; Barril, José; Mora, Eva; Giménez, Jesús; Vilanova, Eugenio

    2004-06-15

    A capillary electrophoresis method was developed to detect interactions between methadone and anti-retroviral compounds. Eight subjects, who underwent methadone maintenance treatment in the Province of Alicante (Spain), consented to participate in the present study. Of those, one subject was followed up for 123 days to detect drug-drug interactions. The enantiomers of methadone and those of its main metabolite were conveniently resolved within 4 min using a chiral electrophoresis buffer mixture which consisted of phosphate buffer, pH 5, plus 0.2% highly sulphated-(beta)-cyclodextrin. The effective mobility of the analytes was in the 0.061-0.140 cm(2)/(kV s) range at pH 5. The R-methadone plasma concentration range for seven patients was 91-318 ng/mL, it decreased from 186 to 46 ng/mL in a patient followed-up on commencement of the anti-retroviral therapy, returning to the previous higher levels after progressive dose increases. We conclude that monitoring R-methadone plasma levels can be a useful tool for the dose adjustment of methadone.

  18. Methadone maintenance in general practice: patients, workload, and outcomes.

    PubMed Central

    Wilson, P.; Watson, R.; Ralston, G. E.

    1994-01-01

    OBJECTIVE--To assess recruitment to and work-load associated with methadone maintenance clinics in general practice; to investigate the characteristics of patients and outcomes associated with treatment. DESIGN--Study of case notes. SETTING--Methadone maintenance clinics run jointly by general practitioners and drug counsellors in two practices in Glasgow. PARTICIPANTS--46 injecting drug users receiving methadone maintenance during an 18 month period, 31 of whom were recruited to clinic based methadone maintenance treatment and 15 of whom were already receiving methadone maintenance treatment from the general practitioners. Mean (SD) age of patients entering treatment was 29.6 (5.5) years; 29 were male. They had been injecting opiates for a mean 9.9 (5.1) years, and most had a concurrent history of benzodiazepine misuse. Average reported daily intake of heroin was approximately 0.75 g. Participants in treatment had high levels of preexisting morbidity, and most stated that they committed crime daily. RESULTS--2232 patient weeks of treatment were studied. Mean duration of treatment during the study period was 50.7 (21.1) weeks and retention in treatment at 26 weeks was 83%. No evidence of illicit opiate use was obtained at an average of 78% of patients' consultations where methadone had been prescribed in the previous week; for opiate injection the corresponding figure was 86%. CONCLUSIONS--Providing methadone maintenance in general practice is feasible. Although costs are considerable, the reduction in drug use, especially of intravenous opiates, is encouraging. Attending clinics also allows this population, in which morbidity is considerable, to receive other health care. PMID:8086989

  19. Pain Among High-Risk Patients on Methadone Maintenance Treatment.

    PubMed

    Voon, Pauline; Hayashi, Kanna; Milloy, M-J; Nguyen, Paul; Wood, Evan; Montaner, Julio; Kerr, Thomas

    2015-09-01

    The complexity of treating concurrent pain and opioid dependence among many methadone-maintained individuals presents a major challenge in many clinical settings. Furthermore, recent expert guidelines have called for increased research on the safety of methadone in the context of chronic pain. This study explores the prevalence and correlates of pain among a prospective cohort of people who use illicit drugs in Vancouver, British Columbia, Canada, who reported enrollment in methadone maintenance treatment (MMT) between 2011 and 2014. Among the 823 participants eligible for this analysis, 338 (40.9%) reported moderate pain and 91 (11.1%) reported extreme pain at the first study visit. In multivariable, generalized, linear mixed model analyses, higher pain severity was positively and independently associated with self-managing pain (adjusted odds ratio [AOR] 2.15, 95% confidence interval [CI] 1.77-2.60), patient perception of methadone dose being too low (AOR 1.82, 95% CI 1.41-2.34), older age (AOR 1.31, 95% CI 1.13-1.51), having a physical disability (AOR 4.59, 95% CI 3.73-5.64), having ever been diagnosed with a mental illness (AOR 1.44, 95% CI 1.13-1.84), white ethnicity (AOR 1.42, 95% CI 1.10-1.83), and marijuana use (AOR 1.25, 95% CI 1.02-1.52). These findings suggest several areas for clinical intervention, particularly related to patient education and alternative analgesic approaches for MMT patients experiencing pain. Perspective: To better understand the complexity of concurrent pain and opioid dependency among individuals on methadone maintenance treatment, this article describes the prevalence and correlates of higher pain severity among methadone-maintained people who use illicit drugs. Patients on methadone with comorbid pain may benefit from education and alternative analgesic approaches.

  20. Cause of death conundrum with methadone use: a case report.

    PubMed

    Letsky, Michael C; Zumwalt, Ross E; Seifert, Steven A; Benson, Blaine E

    2011-06-01

    Deaths caused by a methadone intoxication or overdose are becoming more frequent. We report a case involving a patient who had extremely high methadone blood concentrations but whose cause of death may have been unrelated to the drug. A 51-year-old woman was found deceased in bed by her daughter. At the scene were numerous bottles of methadone, with the chronic dosage of 240 mg 3 times a day. There was no history of prior suicide attempts, there were no reports of suicidal ideation having been voiced and there was no suicide note. At autopsy, there were no pills found in the stomach. Microscopic tissue examination revealed lobar pneumonia of the right lower lobe. Postmortem lung cultures grew out Streptococcus pneumoniae. Femoral blood contained methadone, 5.7 mg/L; EDDP, 2.1 mg/L; oxycodone, 0.017 mg/L; doxylamine, 0.022 mg/L; and ethanol, 13.0 mg/dL. The postmortem methadone concentration was consistent with her known dose, plausible pharmacokinetics and conditions of discovery. Various causes of death, such as a methadone-related arrhythmia from QTc prolongation or the contribution of methadone to the development of the pneumonia, cannot be ruled out and may well have caused or contributed to death, but the pneumonia was felt to be a competent cause of death. Ultimately, the most likely cause(s) of death, is a decision left to the individual medical examiner. This case is illustrative of the growing number of similar cases facing forensic pathologists. The cause of death cannot be solely based on drug concentrations and it may not be possible to come to a conclusion as to "the" cause of death and the forensic pathologist must be content with "a" cause of death.

  1. Methadone disposition in oral fluid during pharmacotherapy for opioid-dependence

    PubMed Central

    Gray, Teresa R.; Dams, Riet; Choo, Robin E.; Jones, Hendree E.; Huestis, Marilyn A.

    2010-01-01

    Introduction Oral fluid testing is widely used for detecting drug exposure, but data describing methadone and metabolites in oral fluid during pharmacotherapy for opioid-dependence are relatively limited. Method 414 oral fluid specimens from 16 opioid-dependent pregnant women receiving daily methadone were analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and methadol by liquid chromatography-mass spectrometry. Results All oral fluid specimens contained methadone greater than 1 ng/mL; 88% were positive for EDDP and 12% for methadol. Over 95% of oral fluid specimens exceeded the 20 ng/mL methadone cutoff set by the European Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) study. Methadone and EDDP oral fluid concentrations were highly variable within and between participants, did not predict methadone dose, but were negatively correlated with pH. Conclusion Methadone was readily identified in oral fluid at concentrations greater than 20 ng/mL following daily 30–110 mg/day methadone pharmacotherapy. As no specimens contained only EDDP or methadol, there was no advantage to including these analytes for identification of methadone exposure. As nearly all oral fluid specimens from methadone-maintained patients exceeded the DRUID guideline, the 20 ng/mL cutoff appears to be sensitive enough to detect daily methadone exposure; however, additional indicators of behavioral and/or motor impairment would be necessary to provide evidence of driving impairment. PMID:20667673

  2. Methadone Maintenance: The Experience of Four Programs. The Drug Abuse Council Manuscript Series, No. 1.

    ERIC Educational Resources Information Center

    Danaceau, Paul

    Methadone maintenance is a relatively new method for treating heroin addiction. Controversy and questions remain about the drug itself and its use of methadone. The author was engaged by The Drug Abuse Council to prepare these descriptions of four methadone programs and the accompanying summary. The evolution of these programs is examined, and the…

  3. Detoxification in Naturopathic Medicine: A Survey

    PubMed Central

    Montalto, Melissa; Lovejoy, Jennifer; Weber, Wendy

    2011-01-01

    Abstract Objectives This study sought to assess the use of clinical detoxification therapies used by licensed naturopathic doctors (NDs) in the United States. Design This was a qualitative, descriptive, online survey of a convenience sample of NDs. Methods An online survey was conducted of NDs who were licensed in the United States. Responses were analyzed descriptively regarding the use of clinical detoxification therapies. Respondents were recruited from a membership list provided by the American Association of Naturopathic Physicians, and from alumni e-mail lists of Council of Naturopathic Medical Education accredited naturopathic medical schools. Results Surveys were sent out to 1442 e-mail addresses (261 were returned to sender); a total of 196 respondents completed the survey (16.6%). Ninety-two percent (92%) of respondents reported using clinical detoxification therapies. Over 75% of respondents utilized detoxification therapies primarily to treat patients for environmental exposures, general cleansing/preventive medicine, gastrointestinal disorders, and autoimmune disease. Regarding methods used, >75% reported using dietary measures, reducing environmental exposures, and using botanicals as detoxification therapies. Eighty-three percent (83%) of NDs surveyed reported using follow-up measurements to determine efficacy of detoxification therapies. The most common were patient symptom questionnaires (66%), patient medical histories (54%), and urinary provocative challenge testing (53%). Conclusions The majority of NDs responding to this survey reported routine use of clinical detoxification therapies to treat a range of medical conditions utilizing multiple therapeutic approaches. Although the majority of NDs reported using some follow-up measurements after detoxification therapy, few of these are an objective means to determine treatment efficacy. Further research is needed in the field of complementary and alternative medicine clinical detoxification to

  4. Increases in body mass index following initiation of methadone treatment.

    PubMed

    Fenn, Jennifer M; Laurent, Jennifer S; Sigmon, Stacey C

    2015-04-01

    Despite the clear efficacy of methadone for opioid dependence, one less desirable phenomenon associated with methadone may be weight gain. We examined changes in body mass index (BMI) among patients entering methadone treatment. A retrospective chart review was conducted for 96 patients enrolled in an outpatient methadone clinic for ≥ 6 months. The primary outcome of BMI was assessed at intake and a subsequent physical examination approximately 1.8 ± 0.95 years later. Demographic, drug use and treatment characteristics were also examined. There was a significant increase in BMI following intake (p<0.001). Mean BMIs increased from 27.2 ± 6.8 to 30.1 ± 7.7 kg/m(2), translating to a 17.8-pound increase (10% increase in body weight) in the overall patient sample. Gender was the strongest predictor of BMI changes (p < 0.001), with significantly greater BMI increases in females than males (5.2 vs. 1.7 kg/m(2), respectively). This translates to a 28-pound (17.5%) increase in females vs. a 12-pound (6.4%) increase in males. In summary, methadone treatment enrollment was associated with clinically significant weight gain, particularly among female patients. This study highlights the importance of efforts to help patients mitigate weight gain during treatment, particularly considering the significant health and economic consequences of obesity for individuals and society more generally.

  5. Interim versus standard methadone treatment: a benefit-cost analysis.

    PubMed

    Schwartz, Robert P; Alexandre, Pierre K; Kelly, Sharon M; O'Grady, Kevin E; Gryczynski, Jan; Jaffe, Jerome H

    2014-03-01

    A benefit-cost analysis was conducted as part of a clinical trial in which newly-admitted methadone patients were randomly assigned to interim methadone (IM; methadone without counseling) for the first 4 months of 12 months of methadone treatment or 12 months of methadone with one of two counseling conditions. Health, residential drug treatment, criminal justice costs, and income data in 2010 dollars were obtained at treatment entry, and 4- and 12-month follow-up from 200 participants and program costs were obtained. The net benefits of treatment were greater for the IM condition but controlling for the baseline variables noted above, the difference between conditions in net monetary benefits was not significant. For the combined sample, there was a pre- to post-treatment net benefit of $1470 (95% CI: -$625; $3584) and a benefit-cost ratio of 1.5 (95% CI: 0.8, 2.3), but using our conservative approach to calculating benefits, these values were not significant.

  6. Methadone in healthy goats - pharmacokinetics, behaviour and blood pressure.

    PubMed

    Olsén, L; Olsson, K; Hydbring-Sandberg, E; Bondesson, U; Ingvast-Larsson, C

    2013-08-01

    The pharmacokinetics and effects of the opioid methadone on behaviour, arterial blood pressure, heart rate and haematocrit were studied in goats. Two goats received methadone (0.2mg/kg) intravenously and the terminal half-life was 88 and 91 min, the volume of distribution 8.4 and 6.1L/kg, and clearance 86 and 123 mL/min/kg. In a crossover study eight goats received methadone (0.6 mg/kg) or 0.15M NaCl subcutaneously (SC). After SC administration bioavailability was complete and the terminal half-life was 215 ± 84 min (mean ± SD), Tmax 31 ± 15 min and Cmax 45 ±11 ng/mL. Blood pressure and haematocrit increased while heart rate did not change. The goats did not ruminate and they climbed, scratched, gnawed and showed tail-flicking after SC methadone in contrast to NaCl administration. The use of methadone in goats may be restricted due to the inhibition of rumination and the rather short half-life.

  7. Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans

    PubMed Central

    Zwart, S. R.; Crawford, G. E.; Gillman, P. L.; Kala, G.; Rodgers, A. S.; Rogers, A.; Inniss, A. M.; Rice, B. L.; Ericson, K.; Coburn, S.; Bourbeau, Y.; Hudson, E.; Mathew, G.; DeKerlegand, D. E.; Sams, C. F.; Heer, M. A.; Paloski, W. H.; Smith, S. M.

    2009-01-01

    Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum α- and γ-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma β-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest. PMID:19074571

  8. Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses.

    PubMed

    Crosignani, N; Luna, S P; Dalla Costa, T; Pimenta, E L; Detoni, C B; Guterres, S S; Puoli Filho, J N; Pantoja, J C; Pigatto, M C

    2017-01-16

    We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6 h after dosing for plasma drug quantification by LC-MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vdss /F) and increased mean residence time (MRT) for NANO. One-compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone.

  9. ETS: DEVELOPMENT OF A PHOTOTHERMAL DETOXIFICATION UNIT

    EPA Science Inventory

    There has long been interest in utilizing photochemical methods for destroying hazardous organic materials. Unfortunately, the direct application of classic, low temperature photochemical processes to hazardous waste detoxification is often too slow to be practical for wide spre...

  10. Esterase detoxification of acetylcholinesterase inhibitors by ...

    EPA Pesticide Factsheets

    Organophosphate (OP) and N-methylcarbamate pesticides inhibit acetylcholinesterase (AChE), but differences in metabolism and detoxification can influence potency of these pesticides across and within species. Carboxylesterase (CaE) and A-esterase (paraoxonase, PON) are considered factors underlying age-related sensitivity differences. We used an in vitro system to measure detoxification of AChE-inhibiting pesticides mediated via these esterases. Recombinant human AChE was used as a bioassay of inhibitor concentration following incubation with detoxifying tissue: liver plus Ca+2 (to stimulate PONs, measuring activity of both esterases) or EGTA (to inhibit PONs, thereby measuring CaE activity). Inhibitory concentrations of aldicarb, chlorpyrifos oxon, malaoxon, methamidophos, oxamyl, paraoxon, and methyl paraoxon were incubated with liver from adult male rat or one of 20 commercially provided human (11-83 years of age) liver samples. Detoxification was the difference in inhibition produced by the pesticide alone or in combination with liver plus Ca+2 or EGTA. Generally, rat liver produced more detoxification than did the human samples. There were large detoxification differences, which were not correlated with age or sex, across human samples for some pesticides (especially malaoxon, chlorpyrifos oxon) but not for others (e.g., aldicarb, methamidophos). Chlorpyrifos oxon was detoxified only in the presence of Ca+2 in both rat and human livers. Detoxification of pa

  11. Bacterial detoxification of diisopropyl fluorophosphate.

    PubMed Central

    Attaway, H; Nelson, J O; Baya, A M; Voll, M J; White, W E; Grimes, D J; Colwell, R R

    1987-01-01

    The ability of 18 gram-negative bacterial isolates to detoxify diisopropyl fluorophosphate, a structural analog of the agents soman and sarin, was investigated. Detoxification by both frozen cell sonicates and acetone powders was assayed by two methods, i.e., the hydrolytic release of fluoride, measured by a fluoride-specific ion electrode, and the disappearance of acetylcholinesterase inhibition in vitro. Frozen cell sonicates for all strains exhibited some activity (F- ion release). In general, acetone powder preparations produced higher activity than frozen cell sonicates did, and the highest activities were exhibited by strains with known parathion hydrolase activity. Two ranges in activity were observed, low level, ranging from 0.1 to 7.0 mumol/min per g of protein, and high level, detected only in parathion hydrolase-producing strains, from 47 to greater than 300 mumol/min per g of protein. Results indicate that parathion hydrolase was nonspecific in phosphoesterase activity. Also, it was an effective detoxicant at low concentrations and near-neutral pH. PMID:3662511

  12. Peroxide detoxification by brain cells.

    PubMed

    Dringen, Ralf; Pawlowski, Petra G; Hirrlinger, Johannes

    Peroxides are generated continuously in cells that consume oxygen. Among the different peroxides, hydrogen peroxide is the molecule that is formed in highest quantities. In addition, organic hydroperoxides are synthesized as products of cellular metabolism. Generation and disposal of peroxides is a very important process in the human brain, because cells of this organ consume 20% of the oxygen used by the body. To prevent cellular accumulation of peroxides and damage generated by peroxide-derived radicals, brain cells contain efficient antioxidative defense mechanisms that dispose of peroxides and protect against oxidative damage. Cultured brain cells have been used frequently to investigate peroxide metabolism of neural cells. Efficient disposal of exogenous hydrogen peroxide was found for cultured astrocytes, oligodendrocytes, microglial cells, and neurons. Comparison of specific peroxide clearance rates revealed that cultured oligodendrocytes dispose of the peroxide quicker than the other neural cell cultures. Both catalase and the glutathione system contribute to the clearance of hydrogen peroxide by brain cells. For efficient glutathione-dependent reduction of peroxides, neural cells contain glutathione in high concentration and have substantial activity of glutathione peroxidase, glutathione reductase, and enzymes that supply the NADPH required for the glutathione reductase reaction. This article gives an overview on the mechanisms involved in peroxide detoxification in brain cells and on the capacity of the different types of neural cells to dispose of peroxides.

  13. METODO, a prospective observational study to assess the efficacy and tolerability of methadone in heroin-addicted patients undergoing a methadone maintenance treatment: preliminary results at baseline evaluation.

    PubMed

    D'Egidio, Pietro Fausto; Bignamini, Emanuele; De Vivo, Enrico; Leonardi, Claudio; Pieri, Maria Chiara; González-Saiz, Francisco; Lucchini, Alfio

    2013-12-01

    METODO (methadone efficacy therapy optimization dosage on-going) is a prospective observational study to assess the efficacy and tolerability of methadone in 500 heroin-addicted patients taking a methadone maintenance treatment, enrolled through 2010 to 2011 in five Italian sites, observed over 2 years. The Opiate Dosage Adequacy Scale has been used for the evaluation of the "adequacy" of the methadone dosage and to stratify patients in adequate and not adequate groups. The treatment efficacy has been evaluated in correlation to the dosage adequacy during the visits. Moreover, patients have been evaluated according to the retention rate and duration of retention in treatment and a series of questionnaires.

  14. Quantitation of methadone enantiomers in humans using stable isotope-labeled (2H3)-, (2H5)-, and (2H8)Methadone

    SciTech Connect

    Nakamura, K.; Hachey, D.L.; Kreek, M.J.; Irving, C.S.; Klein, P.D.

    1982-01-01

    A new technique for simultaneous stereoselective kinetic studies of methadone enantiomers was developed using three deuterium-labeled forms of methadone and GLC-chemical-ionization mass spectrometry. A racemic mixture (1:1) of (R)-(-)-(2H5)methadone (l-form) and (S)-(R)-(2H3)methadone (d-form) was administered orally in place of a single daily dose of unlabeled (+/-)-(2H0)methadone in long-term maintenance patients. Racemic (+/-)-(2H8)methadone was used as an internal standard for the simultaneous quantitation of (2H0)-, (2H3)-, and (2H5)methadone in plasma and urine. A newly developed extraction procedure, using a short, disposable C18 reversed-phase cartridge and improved chemical-ionization procedures employing ammonia gas, resulted in significant reduction of the background impurities contributing to the ions used for isotopic abundance measurements. These improvements enabled the measurement of labeled plasma methadone levels for 120 hr following a single dose. This methodology was applied to the study of methadone kinetics in two patients; in both patients, the analgesically active l-enantiomer of the drug had a longer plasma elimination half-life and a smaller area under the plasma disappearance curve than did the inactive d-form.

  15. Route of administration influences substitution patterns in rats trained to discriminate methadone vs. vehicle.

    PubMed

    Vann, Robert E; Wise, Laura E; Varvel, Stephen A; Philibin, Scott D; Walentiny, D Matthew; Porter, Joseph H

    2009-08-01

    Replacement therapy with the synthetic mu-opioid agonist methadone is an efficacious treatment for opioid abuse. While much is known about methadone's pharmacology, its discriminative stimulus properties remain largely unexplored. The present study sought to establish methadone discrimination in rats. Moreover, some research suggests that route of administration alters the discriminative stimulus of methadone. Thus, the present study also compared intraperitoneal (i.p.) and subcutaneous (s.c.) routes of administration. Male Sprague-Dawley rats were trained to discriminate 3.0mg/kg methadone (i.p.) from vehicle in a two-lever discrimination procedure. Generalization tests were conducted with a variety of compounds administered i.p. and s.c. Methadone fully substituted for itself, yielding ED(50)s of 1.5mg/kg (i.p.) and 0.2mg/kg (s.c.). Naltrexone (i.p.), an opioid antagonist produced a dose-dependent reduction in methadone-appropriate responding. The methadone stereoisomers fully substituted for methadone when given s.c.; however, when administered i.p., (+) and (-) methadone produced partial and no substitution, respectively. Heroin fully generalized to methadone regardless of administration route, while morphine fully substituted when given s.c., but not i.p. The kappa-agonist U50-488 failed to generalize to methadone with either route of administration. These results demonstrated that methadone's discriminative stimulus is mediated through mu-opioid receptor activity and is similar to that of commonly abused opioids (heroin, morphine). Additionally, route of administration produced differential results for many of the drugs tested, suggesting decreased drug bioavailability following i.p. administration due to hepatic first pass metabolism. Taken together, these results suggest that methadone's shared subjective effects with abused opioids, as well as its unique metabolic properties contribute to its efficacy in opioid maintenance therapy.

  16. Use of the cytosensor microphysiometer to predict results of a 21-day cumulative irritation patch test in humans.

    PubMed

    Landin, Wendell E; Mun, Greg C; Nims, Raymond W; Harbell, John W

    2007-09-01

    The cytosensor microphysiometer (mu phi) was investigated as a rapid, relatively inexpensive test to predict performance of skin cleansing wipes on the human 21-day cumulative irritation patch test (21CIPT). It indirectly measures metabolic rate changes in L929 cells as a function of test article dose, by measuring the acidification rate in a low-buffer medium. The dose producing a 50% reduction in metabolic rate (MRD50), relative to the baseline rate, is used as a measure of toxicity. The acute toxicity of the mu phi assay can be compared to the chronic toxicity of the 21CIPT, which is based largely on the exposure of test agents to the epidermal cells, resulting in damage and penetration of the stratum corneum leading to cell toxicity. Two series of surfactant-based cleansing wipe products were tested via the mu phi assay and 21CIPT. The first series, consisting of 20 products, was used to determine a prediction model. The second series of 38 products consisted of routine product development formulas or marketed products. Comparing the results from both tests, samples with an MRD50 greater than 50 mg/ml provided a 21CIPT score consistent with a product that performs satisfactorily in the market. When the MRD50 was greater than 78 mg/ml, the 21CIPT score was usually zero. The mu phi may be more sensitive than the 21CIPT for ranking minimally irritating materials. The mu phi assay is useful as a screen for predicting the performance of a wet wipes formula on the 21CIPT, and concurrently reduces the use of animals for safety testing in a product development program for cleansing wipes.

  17. [Clinical study of modified M-VAC therapy with one 21-day cycle for advanced urothelial cancer].

    PubMed

    Nakanishi, Shinichi; Matsuzaki, Masato; Morikawa, Hiroshi; Nakano, Masahiro; Komatsu, Hideki

    2004-10-01

    Although M-VAC therapy is a standard chemotherapy for advanced transitional cell carcinoma, the treatment schedule has to be delayed or cancelled in many patients because of the toxicity. To reduce the toxicity we modified the treatment schedule of M-VAC treatment. The dosages of this simplified M-VAC therapy were 30 mg/m2 methotrexate (on day 1), 3 mg/m2 vinblastine (on day 2), 30 mg/m2 doxorubicin (on day 2) and 70 mg/m2 cisplatin (on day 2), with courses repeated every 21 days for four cycles as a principle. Seventeen patients with histologically proven advanced transitional cell carcinoma were treated with this simplified M-VAC therapy without dose modification or delay. The median number of cycles was 4. Neutropenia, anemia and thrombopenia (grade 4) was observed in 2, 1 and 2 patients respectively, but no drug-related deaths were observed. Complete response and partial response were achieved in 2 (12%) and 10 (59%) patients respectively. Of 2 complete responders one patient was alive without evidence of disease at 12 months and another patient died of the disease at 42 months. Of 10 partial responders 6 patients underwent the additional surgical resection of residual tumors. Of these 6 patients 3 patients are alive without evidence of disease at 6, 30 and 31 months. The remaining 3 developed recurrence and 2 died of the disease at 13 and 29 months. Five non-responders died of the disease at 5 months after the start of the therapy. Response rate of simplified M-VAC therapy was excellent and treatment duration was short. However, relapses were commonly observed as well as the original M-VAC treatment.

  18. Pineal 'synaptic ribbons' and serum melatonin levels in the rat following the pulse action of 52-Gs (50-Hz) magnetic fields: an evolutive analysis over 21 days.

    PubMed

    Martínez Soriano, F; Giménez González, M; Armañazas, E; Ruiz Torner, A

    1992-01-01

    In continuation of earlier studies, we have investigated the influence of 52-Gs (50-Hz) magnetic fields on the evolution of pinealocyte 'synaptic ribbons' and serum melatonin levels in rats, following 30 min daily exposure. The animals were sacrificed after 1, 3, 7, 15 and 21 days. A significant decrease in the number of synaptic ribbons was observed after 15 and 21 days, together with a significant drop in serum melatonin concentrations after 15 days. The mediating role of the retina in these modifications and magnetic field effects is discussed.

  19. Utilization and outcomes of detoxification and maintenance treatment for opioid dependence in publicly-funded facilities in California, US: 1991-2012*

    PubMed Central

    Nosyk, Bohdan; Li, Libo; Evans, Elizabeth; Urada, Darren; Huang, David; Wood, Evan; Rawson, Richard; Hser, Yih-Ing

    2015-01-01

    Background California treats the largest population of opioid dependent individuals in the US and is among a small group of states that applies regulations for opioid treatment that are more stringent than existing federal regulations. We aim to characterize changes in patient characteristics and treatment utilization over time, and identify determinants of successful completion of detoxification and MMT retention in repeated attempts. Methods State-wide administrative data was obtained from California Outcome Measurement System during the period: January 1st, 1991 to March 31st, 2012. Short-term detoxification treatment and long-term maintenance treatment, primarily with methadone, was available to study participants. Mixed effects regression models were used to define determinants of successful completion of the detoxification treatment protocol (as classified by treatment staff) and duration of maintenance treatment. Results The study sample consisted of 237,709 unique individuals and 885,971 treatment episodes; 83.7% were detoxification treatment episodes in 1994, dropping to 40.5% in 2010. Among individuals accessing only detoxification, the adjusted odds of success declined with each successive attempt (vs. 1st attempt: 2nd: OR: 0.679; 95% CI (0.610, 0.755); 3rd: 0.557 (0.484, 0.641); 4th: 0.526 (0.445, 0.622); 5th: 0.407 (0.334, 0.497); ≥6th: 0.339 (0.288, 0.399). For those ever accessing maintenance treatment, later subsequent attempts were longer in duration, and those with two or more prior attempts at detoxification had marginally longer subsequent maintenance episodes (hazard ratio: 0.97; 95% CI: 0.95, 0.99). Finally, only 10.9% of all detoxification episodes were followed by admission into maintenance treatment within 14 days. Conclusions This study has revealed high rates of detoxification treatment for opioid dependence in California throughout the study period, and decreasing odds of success in repeated attempts at detoxification. PMID:25110333

  20. Interaction of different antidepressants with acute and chronic methadone in mice, and possible clinical implications.

    PubMed

    Schreiber, Shaul; Barak, Yonatan; Hostovsky, Avner; Baratz-Goldstein, Renana; Volis, Ina; Rubovitch, Vardit; Pick, Chaim G

    2014-04-01

    We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p < 0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn.

  1. Dose, Plasma Level, and Treatment Outcome Among Methadone Patients in Shanghai, China.

    PubMed

    Jiang, Haifeng; Hillhouse, Maureen; Du, Jiang; Pan, Shujun; Alfonso, Ang; Wang, Jun; Zhou, Zhirong; Yuan, Weijun; Ling, Walter; Zhao, Min

    2016-12-01

    The purpose of this study was to investigate the blood levels of methadone in participants receiving methadone for the treatment of opioid dependence. After stabilization on methadone for four weeks, blood samples from 95 participants were collected between treatment weeks 4 and 12, before and after receiving doses of methadone, and its blood levels were measured. A multiple linear regression model was used to examine the association between methadone blood levels and the outcomes of methadone maintenance treatment (MMT). Outcome differences between participants who had high (≥2) or low (<2) peak-to-trough ratios were also compared using an independent sample t-test. The blood level of methadone was not correlated with the clinical outcome of MMT with the moderate range of doses given. However, the retention of patients who had a free peak-to-trough ratio >2 was significantly poorer than those whose ratio was <2. Thus, monitoring plasma methadone levels is unlikely to be effective for guiding dosing decisions in situations where compliance with MMT is already very high or when the methadone dose is no longer the dominant factor in determining the clinical outcome. However, monitoring plasma methadone levels is still helpful for guiding the dosage for patients with a rapid metabolism.

  2. A case of serotonin syndrome associated with methadone overdose.

    PubMed

    Martinez, Terry T; Martinez, Daniel N

    2008-01-01

    A chronic pain patient prescribed 20 mg of methadone per day was seen at the Emergency Department within one hour following a witnessed intentional 200 mg ingestion. In addition, he was taking the serotonin re-uptake inhibitor antidepressant drugs, sertraline and venlafaxine as prescribed. Methadone is also a serotonin re-uptake inhibitor which has been involved in serotonin toxicity reactions. Initially, no symptoms of narcotic overdose (depressed central nervous system, respiration, or blood pressure) could be distinguished, and the standard narcotic urine screen was negative. No decontamination or antagonist therapy was given, and the patient was discharged to a psychiatric unit for observation. At 5 hours post-ingestion he presented in a panic with hallucinations and elevated blood pressure, pulse, and respiration. These symptoms are characteristic of serotonin syndrome which is often described as mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. At 10 hours post-ingestion the patient was found unconscious. He had aspirated stomach contents into his lungs. His respiration, blood pressure, and pulse were all severely depressed. He never regained conciousness, and he died 5 days later. The medical examiner's finding was probable acute methadone intoxication. In this case serotonin syndrome appears to have opposed and delayed typical narcotic symptoms. Methadone has additional pharmacologic and toxicologic properties which may complicate the assessment and treatment in overdose situations.

  3. Topical methadone and meperidine analgesic synergy in the mouse.

    PubMed

    Kolesnikov, Yuri A; Oksman, Galina; Pasternak, Gavril W

    2010-07-25

    Topical analgesics have many potential advantages over systemic administration. Prior work has shown potent analgesic activity of a number of topical opioids in the radiant heat tail-flick assay. The current study confirms the analgesic activity of morphine and extends it to two other mu opioids, methadone and meperidine. Combinations of topical morphine and lidocaine are synergistic. Similarly, the combination of methadone and lidocaine is synergistic. While there appeared to be some potentiation with the combination of meperidine and lidocaine, it did not achieve significance. Systemically, prior studies have shown that co-administration of morphine and methadone was synergistic. The combination of morphine and methadone was also synergistic when given topically. In contrast, the combination of morphine and meperidine was not synergistic systemically and it was not synergistic topically. Thus, the pharmacology of topical opioids mimics that seen with systemic administration. Their activity in the topical model supports their potential utility while the local limitation of their actions offers the possibility of a reduced side-effect profile.

  4. Attitudes of Employers toward Hiring Methadone Maintenance Patients.

    ERIC Educational Resources Information Center

    Pugliese, Anthony

    1978-01-01

    Results of this study indicate that at present employers are not ready to accept methadone maintained patients into their firms. The stigma placed on heroin addicts by employers is a very important issue when the treated patient tries to make it in the employment field. More employer education is needed. (Author)

  5. Integrating Fieldwork into Employment Counseling for Methadone-Treatment Patients

    ERIC Educational Resources Information Center

    Blankertz, Laura; Spinelli, Michael; Magura, Stephen; Bali, Priti; Madison, Elizabeth M.; Staines, Graham L.; Horowitz, Emily; Guarino, Honoria; Grandy, Audrey; Fong, Chunki; Gomez, Augustin; Dimun, Amy; Friedman, Ellen

    2005-01-01

    An innovative employment counseling model, Customized Employment Supports, was developed for methadone-treatment patients, a population with historically low employment rates. The effectiveness of a key component of the model, "vocational fieldwork," the delivery of services in the community rather than only within the clinic, was assessed through…

  6. Changing Needle Practices in Community Outreach and Methadone Treatment.

    ERIC Educational Resources Information Center

    Wechsberg, Wendee M.; And Others

    1994-01-01

    This pretest/posttest study used two samples of injecting drug users (184 from street outreach and 103 from a methadone program) to assess drug use and human immunodeficiency virus risk practices. The improvement in risk behaviors at posttest suggests that intervention programs were agents of change. (SLD)

  7. Cost Analysis of Training and Employment Services in Methadone Treatment.

    ERIC Educational Resources Information Center

    French, Michael T.; And Others

    1994-01-01

    A cost analysis is presented for developing a training and employment (TEP) program at four methadone treatment centers in a quasi-experimental pilot study. Average annual costs for TEP per client were derived. The methodology can be used in other projects to compare standard and TEP-enhanced substance-abuse treatment. (SLD)

  8. Counseling with Methadone Clients: A Review of Recent Research

    ERIC Educational Resources Information Center

    Powers, Robert J.; Powers, Henrietta B.

    1978-01-01

    A review of studies on counseling with methadone clients affirmed the importance of counseling services. Support was found for analytic therapy, T-group therapy, behavioral training, reality therapy, and family therapy. There was evidence of client resistance to group therapy. (Author)

  9. Physician Peer Assessments for Compliance with Methadone Maintenance Treatment Guidelines

    ERIC Educational Resources Information Center

    Strike, Carol; Wenghofer, Elizabeth; Gnam, William; Hillier, Wade; Veldhuizen, Scott; Millson, Margaret

    2007-01-01

    Introduction: Medical associations and licensing bodies face pressure to implement quality assurance programs, but evidence-based models are lacking. To improve the quality of methadone maintenance treatment (MMT), the College of Physicians and Surgeons of Ontario, Canada, conducts an innovative quality assurance program on the basis of peer…

  10. Tandem DART™ MS Methods for Methadone Analysis in Unprocessed Urine.

    PubMed

    Beck, Rachel; Carter, Patrick; Shonsey, Erin; Graves, David

    2016-03-01

    Current methods of methadone analysis in untreated urine are traditionally limited to enzyme immunoassays (EIA) while confirmation techniques require specimen processing (i.e., sample clean-up) before analyzing by gas or liquid chromatography coupled with mass spectrometry (GC-MS or LC-MS-MS). EIA and traditional confirmation techniques can be costly and, at times inefficient. As an alternative approach, we present Direct Analysis in Real Time (DART™) coupled with both time-of-flight and triple quadrupole linear ion trap (Q-TRAP™) mass spectrometers for screening and confirming methadone in untreated urine specimens. These approaches require neither expensive kits nor sample clean-up for analysis. More importantly, the total combined analysis time for both screening and confirmation methods was <5 min per sample; in contrast to the 3-5 day process required by traditional EIA, GC-MS and LC-MS-MS techniques. To examine the fundamental protocol and its applicability for routine drug screening, studies were performed that included limits of detection, precision, selectivity and specificity, sample recovery and stability and method robustness. The methods described in this report were determined to be highly specific and selective; allowing for detection of methadone at 250 ng/mL, consistent with cutoffs for current EIA techniques (300 ng/mL). The results reported here demonstrate the DART™ MS platform provides rapid and selective methadone analysis and the potential for providing savings of both time and resources compared with current analysis procedures.

  11. Prozac affects stickleback nest quality without altering androgen, spiggin or aggression levels during a 21-day breeding test.

    PubMed

    Sebire, Marion; Elphinstone Davis, Jessica; Hatfield, Robert; Winberg, Svante; Katsiadaki, Ioanna

    2015-11-01

    Pharmaceuticals are increasingly being used in human and veterinary medicine, and their presence in the aquatic environment may present a threat to non-target aquatic organisms. The selective serotonin reuptake inhibitor fluoxetine (Prozac) has been reported to affect diverse behaviours (feeding, aggression, and reproduction) and also the endocrine system (steroid biosynthesis pathway) in fish. To investigate these claims further, and in particular effects on androgen synthesis, male three-spined sticklebacks (Gasterosteus aculeatus) were exposed to fluoxetine at 0, 3.2, 10 and 32μg/L in a flow-through system for 21 days. Their sex was determined prior to exposure using a non-invasive method to collect DNA for determining the genetic sex, reported here for the first time. This was necessary as the exposure required males of a non-breeding status which had not developed secondary characteristics. Post exposure a number of biochemical (serotonin, steroid and spiggin levels) and apical (aggressive behaviour) endpoints were measured. No effects were detected on morphometric parameters, spiggin or androgen (11-ketotestosterone) levels. However, all fluoxetine-exposed male fish had higher cortisol levels in comparison to the control fish, although this effect only persisted throughout the whole exposure duration at the highest concentration (32μg/L). In addition, the ratio of 5-HIAA/5-HT (serotonin metabolite/serotonin) was significantly lower in the brains of males exposed to fluoxetine at all concentrations tested. Although we found no differences in the number of nests built by the males, the quality of the nests produced by the fluoxetine-exposed males was generally inferior consisting only of a basic, rudimentary structure. Males exposed to 32μg/L of fluoxetine displayed a delayed response to a simulated threat (rival male via own mirror image) and were less aggressive (number of bites and attacks) toward their mirror image, but these differences were not

  12. Cytochrome P4503A does not mediate the interaction between methadone and ritonavir-lopinavir.

    PubMed

    Kharasch, Evan D; Stubbert, Kristi

    2013-12-01

    Plasma concentrations of orally administered methadone are reduced by the human immunodeficiency virus protease inhibitor combination ritonavir and lopinavir, but the mechanism is unknown. Methadone metabolism, clearance, and drug interactions have been attributed to CYP3A4, but this remains controversial. This investigation assessed the effects of acute (2 days) and steady-state (2 weeks) ritonavir-lopinavir on intravenous and oral methadone metabolism and clearance, hepatic and intestinal CYP3A4/5 activity (using the probe substrate intravenous and oral alfentanil), and intestinal transporter activity (using oral fexofenadine) in healthy volunteers. Plasma and urine concentrations of methadone and metabolite enantiomers, and other analytes, were determined by mass spectrometry. Acute and chronic ritonavir-lopinavir reduced plasma methadone enantiomer concentrations in half, with an average 2.6- and 1.5-fold induction of systemic and apparent oral methadone clearances. Induction was attributable to stereoselectively increased hepatic methadone N-demethylation, hepatic extraction, and hepatic clearance, and there was a strong correlation between methadone N-demethylation and clearance. Methadone renal clearance was unchanged. Alfentanil's systemic clearance and hepatic extraction, apparent oral clearance, and intestinal extraction were reduced to 25%, 16%, and 35% of control, indicating strong inhibition of hepatic and intestinal CYP3A activities. Ritonavir-lopinavir (acute > chronic) increased fexofenadine exposure, suggesting intestinal P-glycoprotein inhibition. No correlation was found between methadone clearance and CYP3A activity. Acute and steady-state ritonavir-lopinavir stereoselectively induced methadone N-demethylation and clearance, despite significant inhibition of hepatic and intestinal CYP3A activity. Ritonavir-lopinavir inhibited intestinal transporters activity but had no effect on methadone bioavailability. These results do not support a

  13. Cross-reactivity of tapentadol specimens with DRI methadone enzyme immunoassay.

    PubMed

    Collins, Ayodele A; Merritt, A Paola; Bourland, James A

    2012-10-01

    A substantial incidence of positive methadone screens for pain management urine specimens using a commercial enzyme immunoassay (EIA) was observed in the absence of a methadone prescription, with negative methadone confirmation by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS). Tapentadol was the only common prescription among the investigated specimens. Tapentadol or one of its three major metabolites was tested at various concentrations (100-200,000 ng/mL) against the DRI EIAs for methadone and methadone metabolite, to evaluate cross-reactivity. Ninety-seven authentic tapentadol urine specimens that produced false-positive methadone EIA results (cutoff = 130 ng/mL) were analyzed for methadone and tapentadol in compound-specific UPLC-MS-MS confirmation tests. Tapentadol, tapentadol glucuronide, tapentadol sulfate and N-desmethyltapentadol exhibited cross-reactivity with the methadone EIA at 6,500 (2.2%), 25,000 (0.6%), 3,000 (4.4%) and 20,000 ng/mL (0.9%), respectively. No cross-reactivity was observed with the methadone metabolite 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine EIA. All authentic urine specimens were confirmed to be negative for methadone, but positive for tapentadol and all monitored metabolites. Individual concentrations indicated that separate or combined urinary concentrations of tapentadol and its conjugates may produce false-positive methadone screens through cross-reactivity with the methadone immunoassay. The potential for false-positive results for methadone EIA screening of urine specimens associated with tapentadol prescriptions should be considered when interpreting results.

  14. Nutritional aspects of detoxification in clinical practice.

    PubMed

    Cline, John C

    2015-01-01

    Detoxification is a vital cellular task that, if lacking, can lead to early morbidity and mortality. The process of detoxification involves the mobilization, biotransformation, and elimination of toxicants of exogenous and endogenous origin. This article discusses the phase I and phase II detoxification and biotransformation pathways and promotes using food to support these highly complex processes. The author identifies the comprehensive elimination diet as a useful therapeutic tool for clinicians and patients to use to achieve detoxification. Using this diet, the patient removes the most common allergenic foods and beverages from the diet and replaces them with nonallergenic choices for a period of 4 wk, gradually adding back the eliminated foods and observing their effects. Another effective clinical tool that the author discusses is the detox-focused core food plan, which identifies the variety of foods required to supply key nutrients that can maximize the effectiveness of detoxification. Finally, the author provides a case study in which these tools were used to help a patient suffering from major, debilitating illnesses that resulted from exposure to malathion, including severe vomiting and diarrhea, headaches, night sweats, severe arthralgias and myalgias, episcleritis, and shortness of breath. The article details the interventions used and the clinical results (ie, successful resolution of most issues after 3 mo).

  15. Tissue-specific copper concentrations in red drum Sciaenops ocellatus following long-term sublethal waterborne copper exposure and a 21-day withdrawal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Juvenile red drum Sciaenops ocellatus were exposed to sublethal waterborne copper (Cu) concentrations (0.25-0.35 mg/L Cu) using a chelated Cu compound for 242 days as a prophylactic treatment to control ectoparasites followed by a 21-day withdrawal period in two 43 m3 recirculating aquaculture syste...

  16. Tissue-specific copper concentrations in red drum after long-term exposure to sublethal levels of waterborne copper and a 21-day withdrawal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Juvenile red drum Sciaenops ocellatus were exposed to sublethal waterborne copper (Cu) concentrations (0.25-0.35 mg/L Cu) using a chelated Cu compound for 242 days as a prophylactic treatment to control ectoparasites followed by a 21-day withdrawal period in two 43 m3 recirculating aquaculture syste...

  17. Predictors of Opioid-Related Death During Methadone Therapy.

    PubMed

    Leece, Pamela; Cavacuiti, Christopher; Macdonald, Erin M; Gomes, Tara; Kahan, Meldon; Srivastava, Anita; Steele, Leah; Luo, Jin; Mamdani, Muhammad M; Juurlink, David N

    2015-10-01

    We aimed to examine pharmacologic, demographic and medical comorbidity risk factors for opioid-related mortality among patients currently receiving methadone for an opioid use disorder. We conducted a population-based, nested case-control study linking healthcare and coroner's records in Ontario, Canada, from January 31, 1994 to December 31, 2010. We included social assistance recipients receiving methadone for an opioid use disorder. Within this group, cases were those who died of opioid-related causes. For each case, we identified up to 5 controls matched on calendar quarter. The primary analysis examined the association between use of psychotropic drugs (benzodiazepines, antidepressants or antipsychotics) and opioid-related mortality. Secondary analyses examined the associations between baseline characteristics, health service utilization, comorbidities and opioid-related mortality. Among 43,545 patients receiving methadone for an opioid use disorder, we identified 175 (0.4%) opioid-related deaths, along with 873 matched controls. Psychotropic drug use was associated with a two fold increased risk of opioid-related death (adjusted odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2 to 3.5). Specifically, benzodiazepines (adjusted OR 1.6; 95% CI 1.1 to 2.5) and antipsychotics (adjusted OR 2.3; 95% CI 1.5 to 3.5) were independently associated with opioid-related death. Other associated factors included chronic lung disease (adjusted OR 1.7; 95% CI 1.2 to 2.6), an alcohol use disorder (adjusted OR 1.9; 95% CI 1.2 to 3.2), mood disorders (adjusted OR 1.8; 95% CI 1.0 to 3.2), and a history of heart disease (adjusted OR 5.3; 95% CI 2.0 to 14.0). Psychotropic drug use is associated with opioid-related death in patients receiving methadone. Mindfulness of these factors may reduce the risk of death among methadone recipients.

  18. Methadone-induced Damage to White Matter Integrity in Methadone Maintenance Patients: A Longitudinal Self-control DTI Study

    PubMed Central

    Li, Wei; Li, Qiang; Wang, Yarong; Zhu, Jia; Ye, Jianjun; Yan, Xuejiao; Li, Yongbin; Chen, Jiajie; Liu, Jierong; Li, Zhe; Wang, Wei; Liu, Yijun

    2016-01-01

    Methadone maintenance treatment (MMT) can induce impairments in brain function and structure, despite its clinical effectiveness. However, the effect of chronic MMT on brain white matter (WM) is not fully known. Thirty-three MMT patients underwent diffusion tensor imaging (DTI) twice – at the start of the study (Scan1) and one year later (Scan2). Tract-based spatial statistics were used to investigate changes in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) between the two scans. The correlations between DTI indices and methadone consumption and neuropsychological status were analysed. We found significantly decreased FA, decreased AD and increased RD in Scan2 in extensive WM regions; overlapping regions were found in the left posterior limb and the retrolenticular part of internal capsule, superior and posterior corona radiata, bilateral external capsule and the right superior longitudinal fasciculus. In addition, the change of FA in the overlapping regions was positively correlated with the accumulated dosage of methadone use, the RD value in Scan2 and non-planning impulsiveness (NPI) measured at follow-up. The results suggest that methadone has damaging effects on WM integrity. The dose-dependent pattern and characteristics of the impairment may suggest new strategies for MMT. PMID:26794650

  19. Rotation to methadone after opioid dose escalation: How should individualization of dosing occur?

    PubMed

    Zimmermann, Camilla; Seccareccia, Dori; Booth, Christopher M; Cottrell, Wayne

    2005-01-01

    Methadone is a synthetic opioid agonist and N-methyl-D-aspartate (NMDA) receptor antagonist that is being increasingly used in pain management, particularly for pain that is resistant to conventional opioids. We describe two patients with neurotoxic side effects on escalating doses of parenteral hydromorphone with uncontrolled cancer pain who were successfully converted to oral methadone at a dose much smaller than predicted. The phenomenon of increasing pain despite opioid dose escalation is discussed and the rationale for the use of methadone in this situation is described. While methadone is useful for patients with unremitting pain on another opioid, existing conversion regimens do not specifically take into account the setting of dose escalation. Clinical guidelines for rotation to methadone after dose escalation of the previous opioid are needed to avoid toxicity including respiratory depression. A possible conversion method for rotation to methadone for patients with escalating pain and opioid use is suggested.

  20. Successful transition to buprenorphine in a patient with methadone-induced torsades de pointes.

    PubMed

    Esses, Jason Levi; Rosman, Jonathan; Do, Lien Thanh; Schweitzer, Paul; Hanon, Sam

    2008-11-01

    A 56-year-old-man presented with syncope and torsades de pointes secondary to methadone-induced QT prolongation. After transition from methadone to buprenorphine, a partial mu-opiate-receptor agonist and a kappa-opiate-receptor antagonist, the QT normalized and ventricular arrhythmias resolved. Buprenorphine should be used for opiate dependence and chronic pain in patients with methadone-induced QT prolongation and as first line therapy in patients with risk factors for torsades de pointes.

  1. Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

    PubMed

    Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang

    2016-01-01

    Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p < .001) and had ever received methadone maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p < .01) were more likely to enter methadone maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may

  2. A phase I study of D-methadone in patients with chronic pain.

    PubMed

    Moryl, Natalie; Tamasdan, Cristina; Tarcatu, Dana; Thaler, Howard T; Correa, Denise; Steingart, Richard; Payne, Richard; Obbens, Eugenie

    2016-01-01

    D-Methadone is the d optical isomer of racemic mixture (DL-methadone) used clinically to treat pain and addiction in the United States. D-Methadone is practically devoid of opioid activity but maintains N-methyl-D-aspartate (NMDA) receptor antagonism. Evidence from extensive preclinical studies suggests that NMDA receptor antagonists attenuate neuronal plasticity, reverse opioid analgesic tolerance, and alleviate chronic pain states. The authors conducted a phase I open label study of D-methadone administered for the first time to patients with chronic pain to determine the safety and tolerability of D-methadone. In addition to their long-term regimen of opioids, the patients received 40 mg of D-methadone twice daily for 12 days. Analgesia and toxicity were recorded by the patients in a daily diary and assessed in clinic on days 1, 8, and 12. Eight patients of the 10 enrolled completed the study. Pain scores on Edmonton Symptom Assessment System (ESAS) did not change between days 1 and 12, but five of eight patients (62.5 percent) characterized D-methadone as moderately or very effective in relieving pain on the Global Assessment for pain. Five of the eight patients (62.5 percent) who completed the study requested to start treatment with commercially available methadone (DL-racemic methadone) after completing the study. D-Methadone at the dose of 40 mg PO Q 12 hours was well tolerated. Perspective: This is the first clinical study of D-methadone in patients suffering from chronic pain. Additional phase I and phase II studies are needed to confirm its safety and analgesic effects. If D-methadone is well tolerated, it is likely to become a useful adjuvant to the treatment of a wide spectrum of pain syndromes.

  3. Methadone Maintenance: Some Treatment Programs are Not Effective; Greater Federal Oversight Needed

    DTIC Science & Technology

    1990-03-01

    Mr. Chairman: In response to your request, we reviewed the activities of a number of methadone maintenance treatment programs. This report focuses on...the (1) extent of drug use by patients in methadone maintenance treatment programs; (2) the goals, objectives, and approaches of the treatment...treatment programs and the status of proposed regulations to allow methadone to be dispensed without counseling or other supportive services that are

  4. Gulf War Illness - Evaluation of an Innovative Detoxification Program

    DTIC Science & Technology

    2013-12-01

    innovative detoxification program PRINCIPAL INVESTIGATOR: David O. Carpenter, MD...2. REPORT TYPE Final 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Gulf War Illness – Evaluation of an innovative detoxification program...SUPPLEMENTARY NOTES 14. ABSTRACT This project is to determine whether a widely used detoxification protocol that utilizes exercise, sauna therapy

  5. Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity

    SciTech Connect

    Kaufmann, C.A.; Kreek, M.J.; Raghunath, J.; Arns, P.

    1983-09-01

    Narcotic withdrawal is often accompanied by an atypical depression which responds to resumption of narcotics. It was hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined /sub 3/H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24 hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.

  6. Clinical Signs and Symptoms and Laboratory Findings of Methadone Poisoning in Children

    PubMed Central

    Sharif, Mohammad Reza; Nouri, Saeed

    2015-01-01

    Background: Poisoning accounts for about 7% of all accidents in children under 5 years and is implicated in over 5% of all childhood deaths in developing countries. Objectives: Due to the potential risks of methadone poisoning in children and increased cases of methadone poisoning among Iranian children, this study was conducted to investigate the clinical signs and symptoms and laboratory findings of methadone toxicity in children. Patients and Methods: The present retrospective, descriptive, cross-sectional study describes the clinical symptoms and signs and laboratory findings of methadone poisoning in children under 12 years old in Shahid Beheshti Hospital, Kashan, during the years 2009 to 2013. Results: Of 58 patients, 33 (56.9%) were male and 25 (43.1%) female (P = 0.294). The mean age of patients was 5.2 ± 1.0 years. All the cases of poisoning happened with methadone syrup, due to unsafe keeping of methadone in mineral water bottles and containers of other drugs. Signs and symptoms included drowsiness (91.4 %), miosis (75.9%), vomiting (69.0%), ineffective breathing (any kind of breathing problem except apnea) (62.1%), apnea (53.4%), cyanosis (43.1%), seizure (8.6%), ataxia (6.9%) and delirium (3.4%). Conclusions: Keeping methadone in appropriate containers and warning methadone consumers about the dangerous side effects of its consumption and the symptoms of methadone poisoning in children may minimize the occurrence of this form of poisoning and its complications in children. PMID:26199683

  7. Evaluation of poly-drug use in methadone-related fatalities using segmental hair analysis.

    PubMed

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

    2015-03-01

    In Denmark, fatal poisoning among drug addicts is often related to methadone. The primary mechanism contributing to fatal methadone overdose is respiratory depression. Concurrent use of other central nervous system (CNS) depressants is suggested to heighten the potential for fatal methadone toxicity. Reduced tolerance due to a short-time abstinence period is also proposed to determine a risk for fatal overdose. The primary aims of this study were to investigate if concurrent use of CNS depressants or reduced tolerance were significant risk factors in methadone-related fatalities using segmental hair analysis. The study included 99 methadone-related fatalities collected in Denmark from 2008 to 2011, where both blood and hair were available. The cases were divided into three subgroups based on the cause of death; methadone poisoning (N=64), poly-drug poisoning (N=28) or methadone poisoning combined with fatal diseases (N=7). No significant differences between methadone concentrations in the subgroups were obtained in both blood and hair. The methadone blood concentrations were highly variable (0.015-5.3, median: 0.52mg/kg) and mainly within the concentration range detected in living methadone users. In hair, methadone was detected in 97 fatalities with concentrations ranging from 0.061 to 211ng/mg (median: 11ng/mg). In the remaining two cases, methadone was detected in blood but absent in hair specimens, suggesting that these two subjects were methadone-naive users. Extensive poly-drug use was observed in all three subgroups, both recently and within the last months prior to death. Especially, concurrent use of multiple benzodiazepines was prevalent among the deceased followed by the abuse of morphine, codeine, amphetamine, cannabis, cocaine and ethanol. By including quantitative segmental hair analysis, additional information on poly-drug use was obtained. Especially, 6-acetylmorphine was detected more frequently in hair specimens, indicating that regular abuse of

  8. Evaluating the relationship of methadone concentrations and EDDP formation in chronic pain patients.

    PubMed

    Leimanis, Edijs; Best, Brookie M; Atayee, Rabia S; Pesce, Amadeo J

    2012-05-01

    Methadone is used to treat moderate to severe pain in patients not responsive to non-narcotic analgesics and for maintenance treatment of opioid addiction. Methadone is primarily metabolized by N-demethylation to an inactive metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP) by CYP3A4 and CYP2B6. Establishing expected concentrations for metabolism of methadone to EDDP using urine excretion data may be useful for monitoring "medications" and toxicity. Urine specimens from chronic pain patients were collected during routine clinic visits. Methadone and EDDP were quantified by liquid chromatography-tandem mass spectrometry. Approximately 8,000 subjects who reported taking methadone had creatinine concentrations ≥20 mg/dL, and excreted concentrations of methadone and EDDP above ≥100 ng/mL were selected. The median methadone urine concentration was 3.03 mg/g cr. Ninety-five percent of the population had concentrations between 0.175 and 20.9 mg/g cr. EDDP was, on average, twice the methadone concentration. The wide variance in relationship of methadone to its metabolite was not concentration-dependent. Variability between subjects was larger than variability within subjects. As the urinary pH increased, the proportion of excreted EDDP increased, implying a preferred excretion of EDDP.

  9. Role of cytochrome P4502B6 in methadone metabolism and clearance.

    PubMed

    Kharasch, Evan D; Stubbert, Kristi

    2013-03-01

    Methadone N-demethylation in vitro is catalyzed by hepatic cytochrome P4502B6 (CYP2B6) and CYP3A4, but clinical disposition is often attributed to CYP3A4. This investigation tested the hypothesis that CYP2B6 is a prominent CYP isoform responsible for clinical methadone N-demethylation and clearance, using the in vivo mechanism-based CYP2B6 inhibitor ticlopidine, given orally for 4 days. A preliminary clinical investigation with the CYP3A4/5 substrate probe alfentanil established that ticlopidine did not inhibit intestinal or hepatic CYP3A4/5. Subjects received intravenous plus oral (deuterium-labeled) racemic methadone before and after ticlopidine. Ticlopidine significantly and stereoselectively (S > R) inhibited methadone N-demethylation, decreasing plasma metabolite/methadone area under the curve ratios and metabolite formation clearances. Ticlopidine also significantly increased the dose-adjusted plasma area under the curve for R- and S-methadone by 20% and 60%, respectively, after both intravenous and oral dosing. CYP2B6 inhibition reduces methadone N-demethylation and clearance, and alters methadone concentrations, demonstrating an important role for CYP2B6 in clinical methadone disposition.

  10. Sex trading and psychological distress among women on methadone.

    PubMed

    El-Bassel, N; Simoni, J M; Cooper, D K; Gilbert, L; Schilling, R F

    2001-09-01

    This study examined the relationship between sex trading and psychological distress among a nonrandom sample of women recruited from 3 methadone maintenance clinics in New York City. Face-to-face interviews with 280 women (M age = 40.7) revealed that 32% had traded sex for money or drugs in the previous year. Compared to other participants, these women reported less education and higher rates of incarceration in the past year, sexually transmitted diseases, childhood sexual abuse, partner abuse, and current regular crack/cocaine and alcohol use. Hierarchical multiple regression analysis indicated that sex traders scored 0.41 units higher than non-sex traders on the General Severity Index of the Brief Symptom Inventory after controlling for all relevant covariates. The findings emphasize the need to consider the interrelation of psychological distress, abuse, and addiction in designing public health interventions addressing methadone maintained women.

  11. Provider-Client Interaction in Methadone Treatment Clinics in China.

    PubMed

    Li, Li; Wu, Zunyou; Cao, Xiaobin; Zhang, Linglin

    2012-04-01

    This study examines provider-client interactions in the context of methadone maintenance treatment (MMT) in China. Service providers were recruited from six methadone clinics. A total of 41 providers were enrolled in the study and participated in an assessment from February to March 2010. Descriptive and multiple regression analyses were performed. Providers with a higher level of negative attitude toward drug users were less likely than others to interact with clients. Female providers were less likely to have negative attitudes toward drug users as compared with their male counterparts. Doctors were more likely than others to have negative attitudes toward drug users. Knowledge of MMT was not related to either negative attitude toward drug users or to provider-client interaction. The findings indicate an urgent need to address the issue of provider attitudes, which can impact interactions with clients and influence efforts to maintain treatment retention and outcomes for drug users.

  12. Renal lipidosis in patients enrolled in a methadone substitution program.

    PubMed

    Porubsky, Stefan; Kuppe, Christoph; Maier, Tanja; Birk, Horst-Walter; Wörnle, Markus; Moeller, Marcus J; Floege, Jürgen; Gröne, Hermann-Josef

    2014-05-01

    Kidney biopsies often show accumulation of lipids or lipidlike material. Evidence has been provided that lipids can directly initiate and contribute to the progression of glomerular and tubulointerstitial lesions. In this study we describe a renal lipidosis occurring in patients with a positive history of narcotic abuse who were enrolled in a methadone substitution program. All 3 patients presented with proteinuria (2.5-20 g/d) and impaired renal function. Renal biopsy revealed a pronounced extracellular and intracellular deposition of lipidlike material in the glomerular, interstitial, and tubular compartments. Known causes of lipid storage could be excluded clinically and morphologically. We consider this to be a distinct renal lipidosis associated with narcotic abuse, methadone intake, or intravenous abuse thereof.

  13. Brain development in male rats subjected to early weaning and treated with diet containing flour or flaxseed oil after 21 days until 60 days.

    PubMed

    Pessanha, C R; da Camara Boueri, B Ferolla; da Costa, L Rodrigues; Ferreira, M Rocha; Melo, H Saldanha; de Abreu, M Duque Coutinho; Pessoa, L Rozeno; da Silva, P C Alves; Pereira, A D'Avila; Ribeiro, D Cavalcante; de Meneses, J Azevedo; da Costa, C A Soares; Boaventura, G T

    2015-08-01

    The precocious interruption of lactation is a prime factor for developmental plasticity. Here we analyzed whether flour or flaxseed oil treatment contributes to body and brain mass in male rats subjected to early weaning. Pups were weaned for separation from their mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, some of the pups were evaluated (C21 v. EW21). After 21 days, control pups (C60) were fed a control diet. EW pups were divided into those fed a control diet (EWC60), those given flaxseed flour (EWFF60), and those given flaxseed oil (EWFO60) until 60 days. EW21 showed lower body and absolute brain mass and higher relative brain mass. At 60 days, EWC60 and EWFO60 had lower body mass. With regard to relative brain mass, EWC60 was heavier; EWFO60 had lower values compared with EWC60 and higher values compared with C60 and EWFF60. These results indicated that flaxseed flour, in comparison with flaxseed oil, contributes to brain development after EW.

  14. Body composition in male rats subjected to early weaning and treated with diet containing flour or flaxseed oil after 21 days until 60 days.

    PubMed

    Ferolla da Camara Boueri, B; Ribeiro Pessanha, C; Rodrigues da Costa, L; Ferreira, M R; Saldanha Melo, H; Duque Coutinho de Abreu, M; Rozeno Pessoa, L; Alves da Silva, P C; Pereira, A D; Cavalcante Ribeiro, D; de Meneses, J A; Soares da Costa, C A; Teles Boaventura, G

    2015-12-01

    The aim of this study was analyzed if the flour or flaxseed oil treatment contributes to body composition in male rats subjected to early weaning. Pups were weaned for separation from mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, part of the pups was evaluated (C21 v. EW21). After 21 days, control (C60) was fed with control diet. EW was divided in control (EWC60); flaxseed flour (EWFF60); flaxseed oil (EWFO60) diets until 60 days. Body mass, length and body composition by dual-energy X-ray absorptiometry were determined. EW21 (v. C21) and EWC60 (v. C60 and EWFF60) showed lower (P<0.05) mass, length and body composition. EWFO60 (v. C60 and EWFF60) showed lower (P<0.05) body mass and length, body and trunk lean mass, bone mineral density and content and bone area. Flaxseed flour, in comparison with flaxseed oil, contributes to recovery of body composition after early weaning.

  15. Respiratory Variability during Sleep in Methadone Maintenance Treatment Patients

    PubMed Central

    Nguyen, Chinh D.; Kim, Jong Won; Grunstein, Ronald R.; Thamrin, Cindy; Wang, David

    2016-01-01

    Study Objectives: Methadone maintenance treatment (MMT) patients have a high prevalence of central sleep apnea and ataxic breathing related to damage to central respiratory rhythm control. However, the quantification of sleep apnea indices requires laborious manual scoring, and ataxic breathing pattern is subjectively judged by visual pattern recognition. This study proposes a semi-automated technique to characterize respiratory variability in MMT patients. Methods: Polysomnography, blood, and functional outcomes of sleep questionnaire (FOSQ) from 50 MMT patients and 20 healthy subjects with matched age, sex, and body mass index, were analyzed. Inter-breath intervals (IBI) were extracted from the nasal cannula pressure signal. Variability of IBI over 100 breaths was quantified by standard deviation (SD), coefficient of variation (CV), and scaling exponent (α) from detrended fluctuation analysis. The relationships between these variability measures and blood methadone concentration, central sleep apnea index (CAI), apnea-hypopnea index (AHI), and clinical outcome (FOSQ), were then examined. Results: MMT patients had significantly higher SD and CV during all sleep stages. During NREM sleep, SD and CV were correlated with blood methadone concentration (Spearman R = 0.52 and 0.56, respectively; p < 0.01). SD and CV were also correlated with CAI (R = 0.63 and 0.71, p < 0.001, respectively), and AHI (R = 0.45 and 0.58, p < 0.01, respectively). Only α showed significant correlation with FOSQ (R = −0.33, p < 0.05). Conclusions: MMT patients have a higher respiratory variability during sleep than healthy controls. Semi-automated variability measures are related to apnea indices obtained by manual scoring and may provide a new approach to quantify opioid-related sleep-disordered breathing. Citation: Nguyen CD, Kim JW, Grunstein RR, Thamrin C, Wang D. Respiratory variability during sleep in methadone maintenance treatment patients. J Clin Sleep Med 2016;12(4):607–616

  16. Determination of methadone in exhaled breath condensate by liquid chromatography-tandem mass spectrometry.

    PubMed

    Beck, Olof; Sandqvist, Sören; Eriksen, Paul; Franck, Johan; Palmskog, Göran

    2011-04-01

    Within the field of toxicology exhaled breath is used as specimen only for determination of alcohol. However, it was recently discovered that when using sensitive liquid chromatography-mass spectrometry (LC-MS) technique, amphetamine, methamphetamine, and methadone are detectable in exhaled breath following intake by drug addicts. We therefore undertook to develop a method for determination of methadone in exhaled breath condensate from patients undergoing methadonemaintenance treatment. Exhaled breath condensate was collected from 14 patients after intake of the daily methadone dose. The exhaled breath condensate was collected for 10 min using an Ecoscreen instrument. After extraction of any trapped methadone from the condensate by solid-phase extraction, the final extract was analyzed by a combined LC-MS-MS method. Recovery of methadone from breath condensate in the solid-phase extraction was 104%, no significant matrix effects were observed, and the quantification using methadone-d(3) as internal standard was accurate (10% bias) and precise (coefficient of variation 6.2%). Methadone was indisputably identified by means of the MS technique in exhaled breath condensate from all 14 patients. Identification was based on monitoring two product ions in selected reaction monitoring mode with correct relative ratio (± 20%) and correct retention time. Excretion rates ranged from 23.6 to 275 pg/min. No methadone was detected in five control subjects (< 2 pg/min). This finding confirms that methadone is present in exhaled breath from patients in methadone treatment. Collection of exhaled breath specimen is likely to be complementary to other matrices presently in use in testing for drugs-of-abuse.

  17. Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist

    PubMed Central

    Doi, Seira; Mori, Tomohisa; Uzawa, Naoki; Arima, Takamichi; Takahashi, Tomoyuki; Uchida, Masashi; Yawata, Ayaka; Narita, Michiko; Uezono, Yasuhito; Suzuki, Tsutomu

    2016-01-01

    Background Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we further investigated the pharmacological profile of methadone compared to those of fentanyl and morphine as measured mainly by the discriminative stimulus effect and in vitro assays for NMDA receptor binding, µ-opioid receptor-internalization, and µ-opioid receptor-mediated β-arrestin recruitment. Results We found that fentanyl substituted for the discriminative stimulus effects of methadone, whereas a relatively high dose of morphine was required to substitute for the discriminative stimulus effects of methadone in rats. Under these conditions, the non-competitive NMDA receptor antagonist MK-801 did not substitute for the discriminative stimulus effects of methadone. In association with its discriminative stimulus effect, methadone failed to displace the receptor binding of MK801 using mouse brain membrane. Methadone and fentanyl, but not morphine, induced potent µ-opioid receptor internalization accompanied by the strong recruitment of β-arrestin-2 in µ-opioid receptor-overexpressing cells. Conclusions These results suggest that methadone may, at least partly, produce its pharmacological effect as a β-arrestin-biased µ-opioid receptor agonist, similar to fentanyl, and NMDA receptor blockade is not the main contributor to the pharmacological profile of methadone. PMID:27317580

  18. Methadone: a substrate and mechanism-based inhibitor of CYP19 (aromatase).

    PubMed

    Lu, Wenjie Jessie; Bies, Robert; Kamden, Landry K; Desta, Zeruesenay; Flockhart, David A

    2010-08-01

    The peripheral conversion of testosterone to estradiol by aromatase is the primary source of endogenous estrogen in postmenopausal women. Studies indicating that placental aromatase is able to metabolize methadone to its primary metabolite, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidin (EDDP), led us to test the hypothesis that methadone is able to act as an inhibitor of aromatase. Using recombinant human CYP19, we examined the ability of methadone to bring about either reversible or mechanism-based inhibition of the conversion of testosterone to estradiol. To test for reversible inhibition, racemic methadone or its metabolite EDDP or 2-ethyl-5-methyl-3, 3-diphenylpyrroline (EMDP) was incubated for 30 min with testosterone at the K(m) (4 microM). To test for mechanism-based inhibition, microsomal preincubations were performed for up to 30 min using racemic methadone (1-1000 microM), R- or S-methadone (0.5-500 microM), or EDDP or EMDP (10 and 100 microM) followed by incubation with testosterone at a V(max) concentration (50 microM). Racemic methadone, EDDP, and EMDP did not act as competitive inhibitors of CYP19. Preincubation of methadone, EDDP, or EMDP with CYP19 resulted in time- and concentration-dependent inhibition, indicating a mechanism-based reaction that destroys CYP19 activity. The K(I) and k(inact) values for racemic methadone were calculated to be 40.6 +/- 2.8 microM and 0.061 +/- 0.001 min(-1), respectively. No stereoselectivity was observed. Methadone is metabolized by CYP19 and may act as a potent inhibitor of CYP19 in vivo. These findings may contribute to variability in methadone clearance, to drug-drug interactions, and to side effects observed in individual patients.

  19. Methadone treatment, bruxism, and temporomandibular disorders among male prisoners.

    PubMed

    Enguelberg-Gabbay, Judith V; Schapir, Lior; Israeli, Yair; Hermesh, Haggai; Weizman, Abraham; Winocur, Ephraim

    2016-06-01

    There is little information on bruxism related to illicit drug use. Prolonged drug use may damage the stomatognathic system via oral motor overactivity. The aim of the present study was to compare the rates of bruxism and temporomandibular disorders (TMDs) between prisoners with and without drug-use disorders, to evaluate the association between methadone treatment and bruxism and to assess the possible relationship between bruxism and pain. The sample included 152 male prisoners, 69 of whom were drug users maintained on methadone. All prisoners were examined by an experienced dentist and completed a questionnaire on their oral habits, with the aim of detecting signs or symptoms of TMD and/or bruxism. Additional data were collected from medical files. The prevalence of sleep bruxism and awake bruxism, but not of TMDs, was significantly higher among drug-user than non-drug user prisoners (52.2% vs. 34.9% for sleep bruxism, 59.7% vs. 30.1% for awake bruxism, and 46.3% vs. 25.6% for TMDs, respectively). Participants with awake bruxism were statistically more sensitive to muscle palpation compared with participants with sleep bruxism [rating scores (mean ± SD): 0.32 ± 0.21 vs. 0.19 ± 0.28, respectively]. An association was found between sleep bruxism and awake bruxism. It seems that there is a direct or an indirect association between methadone maintenance treatment and sleep bruxism or awake bruxism in male prisoners.

  20. Surveillance of methadone-related adverse drug events using multiple public health data sources.

    PubMed

    Sims, Shannon A; Snow, Laverne A; Porucznik, Christina A

    2007-08-01

    Healthcare safety and quality surveillance is increasingly conducted by public health agencies. We describe a biomedical informatics method that uses multiple public health data sources to perform surveillance of methadone-related adverse drug events. Data from Utah medical examiner records, vital statistics, emergency department encounter administrative data and a database of controlled substances prescriptions are used to examine trends in state-wide adverse events related to methadone. From 1997 to 2004, population-adjusted methadone prescriptions increased 727%, with evidence to suggest the rise in the methadone prescription rate is for treatment of pain, not addiction therapy. During the same period of time, population adjusted, accidental methadone-related deaths in medical examiner data increased 1770%. Population adjusted methadone-related emergency department encounters rose 612% from 1997 to 2003. Our results suggest that the increase in methadone prescription rates from 1997 to 2004 was accompanied by a concurrent increase in methadone-related morbidity and mortality. Although patient data is not linked between data sources, our results demonstrate that utilizing multiple public health data sources captures more cases and provides more clinical detail than individual data sources alone. Our approach is a successful biomedical informatics approach for surveillance of adverse events and utilizes widely available public health data sources, as well as an emerging source of public health data, controlled substance prescription registries.

  1. Addict Descriptions of Therapeutic Community, Multimodality, and Methadone Maintenance Treatment Clients and Staff.

    ERIC Educational Resources Information Center

    Stuker, Patricia B.; And Others

    1978-01-01

    Compared the Adjective Check List descriptions of addicts in treatment toward methadone maintenance, multimodality, and therapeutic community clients and program staff. Results indicate client pessimism regarding methadone maintenance. Results suggest addict opinions represent a valuable source for evaluating treatment approaches and identifying…

  2. Access to Care for Methadone Maintenance Patients in the United States

    ERIC Educational Resources Information Center

    Hettema, Jennifer E.; Sorensen, James L.

    2009-01-01

    This policy commentary addresses a significant access to care issue that faces methadone maintenance patients seeking residential treatment in the United States. Methadone maintenance therapy (MMT) has demonstrated strong efficacy in the outpatient treatment of opiate dependence. However, many opiate dependent patients are also in need of more…

  3. Dyads at Risk: Methadone-Maintained Women and Their Four-Month-Old Infants.

    ERIC Educational Resources Information Center

    Jeremy, Rita Jeruchimowicz; Bernstein, Victor J.

    1984-01-01

    Compares 17 methadone-exposed and 23 control four-month-old infants in interactions with their mothers. Results indicate that methadone is only one of several risk factors affecting interaction. Mothers rated poor in communication have poor psychosocial and psychological resources, and infants rated poor in communication showed problematic motor…

  4. Evaluation of Drug Abuse Treatment: A Repeated Measures Design Assessing Methadone Maintenance.

    ERIC Educational Resources Information Center

    Hser, Yih-Ing; And Others

    1988-01-01

    A repeated measures design was used to evaluate methadone maintenance (MM) treatment effects for 720 heroin addicts who entered MM in Southern California in 1971-1978. Compared to pretreatment measures, results show significant improvement for methadone users. Level of improvement was affected by sex, ethnicity, and treatment duration. (TJH)

  5. Developing Training and Employment Programs to Meet the Needs of Methadone Treatment Clients.

    ERIC Educational Resources Information Center

    Dennis, Michael L.; And Others

    1993-01-01

    Research on vocational services for methadone clients is reviewed, and preliminary results of an evaluation of a training and employment program for 249 methadone treatment clients in 3 community-based programs are presented. Results suggest the usefulness of vocational services in increasing training access and use. (SLD)

  6. Children of Methadone-Maintained Mothers: Three-Year Follow-Up.

    ERIC Educational Resources Information Center

    Johnson, Helen L.; And Others

    The physical and neurobehavioral findings at 3 years of age for 39 children born to mothers on methadone- maintenance and 23 children born to drug-free comparison mothers are reported. The methadone children had a higher incidence of head circumferences less than the third percentile, nystagmus/strabismus, and otitis media. No differences were…

  7. Contingent Take-Home Incentive: Effects on Drug Use of Methadone Maintenance Patients.

    ERIC Educational Resources Information Center

    Stitzer, Maxine L.; And Others

    1992-01-01

    Examined contingent methadone take-home privileges for effectiveness in reducing supplemental drug use of methadone maintenance patients. Assigned 53 new intakes to begin receiving take-home privileges after 2 consecutive weeks of drug-free urines or to noncontingent procedure in which take-homes were delivered independently of urine results.…

  8. Fatal methadone toxicity: potential role of CYP3A4 genetic polymorphism.

    PubMed

    Richards-Waugh, Lauren L; Primerano, Donald A; Dementieva, Yulia; Kraner, James C; Rankin, Gary O

    2014-10-01

    Methadone is difficult to administer as a therapeutic agent because of a wide range of interindividual pharmacokinetics, likely due to genetic variability of the CYP450 enzymes responsible for metabolism to its principal metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). CYP3A4 is one of the primary CYP450 isoforms responsible for the metabolism of methadone to EDDP in humans. The purpose of this study was to evaluate the role of CYP3A4 genetic polymorphisms in accidental methadone fatalities. A study cohort consisting of 136 methadone-only and 92 combined methadone/benzodiazepine fatalities was selected from cases investigated at the West Virginia and Kentucky Offices of the Chief Medical Examiner. Seven single nucleotide polymorphisms (SNPs) were genotyped within the CYP3A4 gene. Observed allelic and genotypic frequencies were compared with expected frequencies obtained from The National Center for Biotechnology Information dbSNP database. SNPs rs2242480 and rs2740574 demonstrated an apparent enrichment within the methadone-only overdose fatalities compared with the control group and the general population. This enrichment was not apparent in the methadone/benzodiazepine cases for these two SNPs. Our findings indicate that there may be two or more SNPs on the CYP3A4 gene that cause or contribute to the methadone poor metabolizer phenotype.

  9. The glycosylation of AGP and its associations with the binding to methadone.

    PubMed

    Behan, Jennifer L; Cruickshank, Yvonne E; Matthews-Smith, Gerri; Bruce, Malcolm; Smith, Kevin D

    2013-01-01

    Methadone remains the most common form of pharmacological therapy for opioid dependence; however, there is a lack of explanation for the reports of its relatively low success rate in achieving complete abstinence. One hypothesis is that in vivo binding of methadone to the plasma glycoprotein alpha-1-acid glycoprotein (AGP), to a degree dependent on the molecular structure, may render the drug inactive. This study sought to determine whether alterations present in the glycosylation pattern of AGP in patients undergoing various stages of methadone therapy (titration < two weeks, harm reduction < one year, long-term > one and a half years) could affect the affinity of the glycoprotein to bind methadone. The composition of AGP glycosylation was determined using high pH anion exchange chromatography (HPAEC) and intrinsic fluorescence analysed to determine the extent of binding to methadone. The monosaccharides galactose and N-acetyl-glucosamine were elevated in all methadone treatment groups indicating alterations in AGP glycosylation. AGP from all patients receiving methadone therapy exhibited a greater degree of binding than the normal population. This suggests that analysing the glycosylation of AGP in patients receiving methadone may aid in determining whether the therapy is likely to be effective.

  10. The Costs of Pursuing Accreditation for Methadone Treatment Sites: Results from a National Study

    ERIC Educational Resources Information Center

    Zarkin, Gary A.; Dunlap, Laura J.; Homsi, Ghada

    2006-01-01

    The use of accreditation has been widespread among medical care providers, but accreditation is relatively new to the drug abuse treatment field. This study presents estimates of the costs of pursuing accreditation for methadone treatment sites. Data are from 102 methadone treatment sites that underwent accreditation as part of the Center for…

  11. Biohazard Detoxification Method Utilizing Magnetic Particles

    DTIC Science & Technology

    2007-05-01

    developing a detoxification system for the human blood that is based on magnetic nanoparticles . A key component of the proposed system is a portable...Targeting of Functionalized Nanoparticles ," Argonne National Laboratory Report ANL-CMT-04/02, September 2004. 7. M. D. Kaminski and A. J. Rosengart...Finck, S. Guy, and A.J. Rosengart, "In Vitro Studies of Functionalized Magnetic Nanoparticles for Selective Removal of a Simulant Biotoxin," J. Magn. Magn

  12. Chemical Detoxification of Polychlorinated Biphenyls (PCBs).

    DTIC Science & Technology

    The present invention relates to the chemical detoxification of polychlorinated biphenyls by converting them to non-hazardous substances. In...particular, the invention relates to chemically destroying polychlorinated biphenyls on site for decontamination purposes without creating pollution or...hazardous situations. The invention provides a two-step process where polychlorinated biphenyls (PCBs), i.e. biphenyl having 2 to 10 chlorine atoms, are

  13. Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations.

    PubMed

    Manfredi, P L; Borsook, D; Chandler, S W; Payne, R

    1997-03-01

    Methadone is a very effective second-line opioid for treatment of cancer pain. However, the starting doses of methadone indicated on opioid conversion charts may over-estimate the dose of intravenous (i.v.) methadone needed. In this report, we describe four patients with cancer-related pain treated with continuous i.v. morphine and hydromorphone. Because of persistent pain and opioid side effects limiting increases in opioid dose, each patient was switched to i.v. methadone. All four patients had excellent pain relief without significant side effects at a dose that, according to the available conversion charts, was approximately 3% of the calculated equianalgesic dose of hydromorphone. When converting from continuous i.v. hydromorphone to continuous i.v. methadone, much lower doses than those suggested by the opioid conversion charts should be used as starting doses.

  14. Pharmacokinetic-pharmacodynamic modeling of mood and withdrawal symptoms in relation to plasma concentrations of methadone in patients undergoing methadone maintenance treatment.

    PubMed

    Shiran, Mohammad-Reza; Lennard, Martin S; Iqbal, Mohammad-Zafar; Lagundoye, Olawale; Seivewright, Nicholas; Tucker, Geoffrey T; Rostami-Hodjegan, Amin

    2012-10-01

    The aims of the present study were to characterize the relationship between plasma racemic methadone and its enantiomers' concentrations with respect to their pharmacodynamic effects and to investigate the influence of potential covariates on the pharmacodynamic parameters in patients on methadone maintenance treatment (MMT). Eighty-eight regular subjects at the Sheffield Care Trust Substance Misuse Services were studied. Samples of blood and urine were collected before the daily dose of methadone. Blood samples were taken up to 5 hours after dose. Total plasma concentrations of (RS)-methadone and total and unbound plasma concentrations of both enantiomers were measured by liquid chromatography-mass spectrometry. The Total Mood Disturbance Score (TMDS), the Objective Opioid Withdrawal Scale (OOWS), and the Subjective Opioid Withdrawal Scale (SOWS) were used as measures of mood and withdrawal. Population pharmacokinetic/pharmacodynamic analysis and subsequent multiple regression analysis were used to determine the factors influencing the pharmacodynamic effects of methadone. Significant decreases (P ≤ 0.04) were observed in the scores for the TMDS, SOWS, and OOWS for 5 hours after methadone dosage. The TMDS had returned to baseline by 10 hours after dose (P = 0.98), at which time the SOWS remained significantly below baseline (P = 0.001). Multiple regression analysis revealed that 33% of the overall variation in unbound (R)-methadone EC50 was explained by 3 variables, namely CYP3A activity (9%), age (16%), and sex (8%). Age also accounted for 8% and 9% of the variation in total (rac)- and (R)-methadone EC50. The present study has confirmed that the duration of mood change in the present study was shorter than the effect of methadone in stabilizing withdrawal symptoms. Thus, it is likely that a once-daily dose of methadone, albeit effective for preventing withdrawal, may not be sufficient to improve mood in some patients. Finally, it was established that CYP3A

  15. The impact of cocaine and heroin on the placental transfer of methadone

    PubMed Central

    Malek, Antoine; Obrist, Cristina; Wenzinger, Silvana; von Mandach, Ursula

    2009-01-01

    Background Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine) which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods Placentae (n = 24) were ex-vivo perfused with medium (m) (control, n = 6), m plus methadone (n = 6), m plus methadone and cocaine (n = 6) or m plus methadone and heroin (n = 6). Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin), microparticles release and the expression of P-glycoprotein were analysed. Results Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/- SD, P < 0.01), whereas the combination with cocaine or heroin increased it (0.56 +/- 0.08 to 0.68 +/- 0.13, P = 0.03 and 0.58 +/- 0.21 to 0.71 +/- 0.24; P = 0.18). Microparticles (MPs) released from syncytiotrophoblast into maternal circuit increased by 30% after cocaine or heroin (P < 0.05) and the expression of P-glycoprotein in the tissue increased by ≥ 49% after any drug (P < 0.05). All other measured parameters did not show any significant effect when methadone was combined with cocaine or heroine. Conclusion The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast. PMID:19519880

  16. Methadone induces CAD degradation and AIF-mediated necrotic-like cell death in neuroblastoma cells.

    PubMed

    Perez-Alvarez, Sergio; Iglesias-Guimarais, Victoria; Solesio, María E; Melero-Fernandez de Mera, Raquel María; Yuste, Víctor J; Galindo, María F; Jordán, Joaquín

    2011-04-01

    Methadone (d,l-methadone hydrochloride) is a full-opioid agonist, originally developed as a substitution for heroin or other opiates abusers. Nowadays methadone is also being applied as long-lasting analgesics in cancer, and it is proposed as a promising agent for leukemia therapy. Previously, we have demonstrated that high concentrations of methadone (0.5mM) induced necrotic-like cell death in SH-SY5Y cells. The pathway involved is caspase-independent but involves impairment of mitochondrial ATP synthesis and mitochondrial cytochrome c release. However, the downstream mitochondrial pathways remained unclear. Here, we studied the participation of apoptosis inducing factor (AIF) in methadone-induced cell death. Methadone resulted in a translocation of AIF from mitochondria to the nucleus. Translocation was inhibited by cyclosporine A, but not by lack of Bax protein. Therefore the effect seems mediated by the formation of the mitochondrial transition pore, but is apparently independent of Bax. Furthermore, methadone-treated SH-SY5Y nuclei show characteristics that are typical for stage I nuclear condensation. Methadone did not induce degradation of DNA into oligonucleosomal fragments or into high molecular weight DNA fragments. Absence of DNA fragmentation coincided with a considerable decrease in the levels of the caspase-actived endonuclase DNase and its chaperone-inhibitor ICAD. In conclusion, our results provide mechanistic insights into the molecular mechanisms that underlie methadone-induced cell death. This knowledge may prove useful to develop novel strategies to prevent toxic side-effects of methadone thereby sustaining its use as therapeutical agent against tumors.

  17. Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction--a 21-day treatment-randomized clinical trial.

    PubMed

    Paulson, Daniel M; Kennedy, Daniel T; Donovick, Roger A; Carpenter, Randall L; Cherubini, Maryann; Techner, Lee; Du, Wei; Ma, Yuju; Schmidt, William K; Wallin, Bruce; Jackson, David

    2005-03-01

    Alvimopan has been shown to reverse the inhibitory effect of opioids on gastrointestinal transit without affecting analgesia. We evaluated oral alvimopan, 0.5 or 1 mg, versus placebo, once daily for 21 days, in 168 patients with opioid-induced bowel dysfunction (OBD) who were receiving chronic opioid therapy (minimum, 1 month) for nonmalignant pain (n = 148) or opioid dependence (n = 20). The primary outcome was the proportion of patients having at least one bowel movement (BM) within 8 hours of study drug on each day during the 21-day treatment period. Averaged over the 21-day treatment period, 54%, 43%, and 29% of patients had a BM within 8 hours after alvimopan 1 mg, 0.5 mg, or placebo, respectively (P < .001). Secondary outcomes of median times to first BM were 3, 7, and 21 hours after initial doses of 1 mg, 0.5 mg, and placebo, respectively (P < .001; 1 mg vs placebo). Weekly BMs and overall patient satisfaction were increased after the 1-mg dose (P < .001 at weeks 1 and 2 vs placebo, and P = .046, respectively). Treatment-emergent adverse events were primarily bowel-related, occurred during the first week of treatment, and were of mild to moderate severity. Alvimopan was generally well tolerated and did not antagonize opioid analgesia. Patients treated with chronic opioid therapy often experience opioid-induced bowel dysfunction as a result of undesirable effects on peripheral opioid receptors located in the gastrointestinal tract. Alvimopan, a novel peripheral opioid mu-receptor antagonist, has demonstrated significant efficacy for the management of opioid-induced bowel dysfunction without compromise of centrally mediated opioid-induced analgesia.

  18. Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment

    PubMed Central

    Posa, Luca; Accarie, Alison; Marie, Nicolas

    2016-01-01

    Background: Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin reduces tolerance to morphine. So far, no studies have been conducted to evaluate the ability of methadone to reduce morphine tolerance in morphine-pretreated animals, a treatment sequence that could be encountered in opiate rotation protocol. We investigated the ability of methadone (a mu opioid receptor internalizing agonist used in therapy) to reverse morphine tolerance and the associated cellular mechanisms in the periaqueductal gray matter, a region involved in pain control. Methods: We measured analgesic response following a challenge dose of morphine in the hot plate test and investigated regulation of mu opioid receptor (coupling and endocytosis) and some cellular mechanisms involved in tolerance such as adenylate cyclase superactivation and changes in N-methyl-d-aspartate receptor subunits expression and phosphorylation state. Results: A chronic treatment with morphine promoted tolerance to its analgesic effects and was associated with a lack of mu opioid receptor endocytosis, adenylate cyclase overshoot, NR2A and NR2B downregulation, and phosphorylation of NR1. We reported that a methadone treatment in morphine-treated mice reversed morphine tolerance to analgesia by promoting mu opioid receptor endocytosis and blocking cellular mechanisms of tolerance. Conclusions: Our data might lead to rational strategies to tackle opiate tolerance in the frame of opiate rotation. PMID:26390873

  19. Buprenorphine and methadone for opioid addiction during pregnancy.

    PubMed

    Mozurkewich, Ellen L; Rayburn, William F

    2014-06-01

    Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians.

  20. Factors associated with methadone treatment among injection drug users in Bangkok, Thailand.

    PubMed

    Fairbairn, Nadia; Hayashi, Kanna; Kaplan, Karyn; Suwannawong, Paisan; Qi, Jiezhi; Wood, Evan; Kerr, Thomas

    2012-07-01

    Little is known about the characteristics of injection drug users (IDU) who take methadone treatment in Thailand. We examined prevalence and correlates of methadone treatment among a community-recruited sample of IDU in Bangkok, Thailand. Among 273 participants, 143 (52.4%) reported accessing methadone treatment within the previous 6 months. Older age (adjusted odds ratio [AOR] = 1.90, 95% confidence interval [CI] = 1.10-3.30) and more than weekly midazolam injection (AOR = 1.85, 95% CI = 1.04-3.29) were positively associated, whereas alcohol use (AOR = 0.34, 95% CI = 0.18-0.63) and noninjection methamphetamine use (AOR = 0.49, 95% CI = 0.29-0.85) were negatively associated with methadone treatment. In subanalyses, 98.6% of IDU on methadone continued to inject drugs, and the most common reason for stopping methadone was becoming incarcerated (49%). Evidence-based addiction treatment in the form of methadone maintenance therapy, with attention paid to concomitant midazolam injection in this setting, should be implemented.

  1. False-positive methadone urine drug screen in a patient treated with quetiapine.

    PubMed

    Lasić, Davor; Uglesić, Boran; Zuljan-Cvitanović, Marija; Supe-Domić, Daniela; Uglesić, Lovro

    2012-06-01

    We present a case of T.M. admitted to University Department of Psychiatry, Split University Hospital Center, in Croatia, because of the acute psychotic reaction (F23.9). The patient's urine tested positive for methadone without a history of methadone ingestion. Urine drug screen was performed with the COBAS Integra Methadone II test kit (kinetic interaction of microparticles in solution /KIMS/ methodology) by Roche. Drugs that have been shown to cross-react with methadone feature a tricyclic structure with a sulfur and nitrogen atom in the middle ring, which is common for both quetiapine and methadone. Therefore, it is plausible that this structural similarity between quetiapine and methadone could underlie the cross-reactivity on methadone drug screen. Besides quetiapine, a number of routinely prescribed medications have been associated with triggering false-positive urine drug screen results. Verification of the test results with a different screening test or additional analytical tests should be performed to avoid adverse consequences for the patients.

  2. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats.

    PubMed

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-Kang; Chen, Shao-Tsu

    2015-01-01

    Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3-20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light-dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light-dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders.

  3. Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

    SciTech Connect

    Amirshahrokhi, K.; Dehpour, A.R.; Hadjati, J.; Sotoudeh, M.; Ghazi-Khansari, M.

    2008-10-01

    Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of {beta} cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a {mu}-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1{beta}, tumor necrosis factor-{alpha} and interferon-{gamma}] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of {beta} cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of {beta} cells and insulitis in the MLDS model of type 1 diabetes.

  4. A Retrospective Evaluation of Inpatient Transfer from High-Dose Methadone to Buprenorphine Substitution Therapy.

    PubMed

    Oretti, Rossana

    2015-10-01

    The product license of buprenorphine/naloxone for opioid substitution therapy indicates reducing methadone concentrations to 30 mg or less per day for a minimum of 1 week before transferring patients to buprenorphine and no sooner than 24 hours after the last methadone dose, because of the risk of precipitated withdrawal and a corresponding high risk of relapse to opioid use. There are few studies describing high-dose methadone transfers. This retrospective case review assessed the feasibility of transferring patients on methadone doses above 30 mg/day to buprenorphine or buprenorphine/naloxone in the inpatient setting. Six of seven patients on 60-120 mg/day of methadone successfully completed the transfer, and four cases tested negative for opiates at long-term follow-up (6-15 months). This suggests that methadone transfer to buprenorphine can be performed rapidly without the need to taper methadone doses in patients indicated for a therapeutic switch. This small study is hypothesis-generating; larger, well-designed trials are needed to define a protocol that can be used routinely to improve and widen transfers to buprenorphine when indicated.

  5. Respiratory effects of chronic in utero methadone or morphine exposure in the neonatal guinea pig.

    PubMed

    Nettleton, Rosemary T; Wallisch, Michael; Olsen, George D

    2008-01-01

    This study uses a neonatal guinea pig model to compare the effects of in utero methadone or morphine exposure upon breathing control. We hypothesize that in utero methadone exposure will result in similar respiratory disturbances to those seen in morphine exposed neonates, but that the onset will be slower and the duration longer, due to methadone's longer elimination half-life. Pregnant Dunkin-Hartley guinea pigs received once-daily injections of methadone, morphine, or vehicle (saline) during the last half of gestation and pups were studied 3, 7, or 14 days after birth. In utero methadone or morphine exposure resulted in decreased birth weight compared to vehicle, and pups experienced a withdrawal syndrome which included increased locomotor activity and respiratory disturbances but no change in rectal temperature. Both opioid exposures increased inspiratory minute ventilation during CO(2) challenge at 3 days after birth, but only in morphine exposed pups was this withdrawal effect still present on day 7. Surprisingly, only morphine exposure increased inspiratory minute ventilation during room air breathing. We conclude that in utero methadone exposure is not equivalent to in utero morphine exposure. With respect to neonatal respiratory control, methadone-induced changes in respiration are only apparent during hypercapnia.

  6. The effect of P-glycoprotein on methadone hydrochloride flux in equine intestinal mucosa.

    PubMed

    Linardi, R L; Stokes, A M; Andrews, F M

    2013-02-01

    Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a transmembrane protein, P-glycoprotein, present in different tissues including the small intestine in other species. This study aims to determine the effect of the P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator of in vivo drug absorption. Jejunum tissues from five horses were placed into the Ussing chambers and exposed to methadone solution in the presence or absence of Rhodamine 123 or verapamil. Electrical measurements demonstrated tissue viability for 120 min, and the flux of methadone across the jejunal membrane (mucosal to submucosal direction) was calculated based on the relative drug concentration measured by ELISA. The flux of methadone was significantly higher only in the presence of verapamil. P-glycoprotein was immunolocalized in the apical membrane of the jejunal epithelial cells (enterocytes), mainly located in the tip of the villi compared to cells of the crypts. P-glycoprotein is present in the equine jejunum and may possibly mediate the intestinal transport of methadone. This study suggests that P-glycoprotein may play a role in the poor intestinal absorption of methadone in vivo.

  7. Plasma catecholamines during an ultrarapid heroin detoxification.

    PubMed

    Macedo, T R; Relvas, J; Fontes Ribeiro CA; Pacheco, F; Morgadinho, M T; Pinto, C M; Gomes, P C; Ventura, M; Henriques, V; Nunes, S V; Ruis, G R; Ramalheira, C; Boto, I; Vale, L L

    2000-09-01

    The adrenergic system has long been known to be activated in a situation of stress and thus during opiate withdrawal. A method for detoxification that decreases the stimulation of the sympathetic nervous system will prevent changes of catecholamine levels. Some of such methods have been developed. One of them uses direct transition from heroin to oral naltrexone after deep sedation with midazolam in conjunction with naloxone, droperidol, ondansetron, and clonidine treatment for 24 hours. Can such method prevent adrenergic changes? Moreover, 5-HT has been related to mood disorders. This study aims to determine plasma catecholamines and 5-HT before heroin withdrawal, during the day of the withdrawal, and at the ends of the first day, the first week, and the first 6 months. Forty-three patients with more than 6 years of drug abuse volunteered to seek help to detoxify. After clinical evaluation, blood samples were taken. Plasma catecholamines were isolated by standard alumina procedures and measured by high-performance liquid chromatography with electrochemical detection. Only for NE was there a significant decrease in the day of heroin withdrawal with deep sedation, followed the next day by an increase. During the following days, NE plasma concentrations returned slowly to basal levels. Epinephrine and dopamine plasma levels did not significantly change. Platelet 5-HT levels progressively decreased from the day before detoxification until the last period of observation. We also found that there were no abrupt changes in cardiovascular functions. In conclusion, our results suggest that this type of ultrarapid opiate detoxification prevents the dramatic activation of the autonomic nervous system.

  8. There is no age limit for methadone: a retrospective cohort study

    PubMed Central

    2011-01-01

    Background Data from the US indicates that methadone-maintained populations are aging, with an increase of patients aged 50 or older. Data from European methadone populations is sparse. This retrospective cohort study sought to evaluate the age trends and related developments in the methadone population of Basel-City, Switzerland. Methods The study included methadone patients between April 1, 1995 and March 31, 2003. Anonymized data was taken from the methadone register of Basel-City. For analysis of age distributions, patient samples were split into four age categories from '20-29 years' to '50 years and over'. Cross-sectional comparisons were performed using patient samples of 1996 and 2003. Results Analysis showed a significant increase in older patients between 1996 and 2003 (p < 0.001). During that period, the percentage of patients aged 50 and over rose almost tenfold, while the proportion of patients aged under 30 dropped significantly from 52.8% to 12.3%. The average methadone dose (p < 0.001) and the 1-year retention rate (p < 0.001) also increased significantly. Conclusions Findings point to clear trends in aging of methadone patients in Basel-City which are comparable, although less pronounced, to developments among US methadone populations. Many unanswered questions on medical, psychosocial and health economic consequences remain as the needs of older patients have not yet been evaluated extensively. However, older methadone patients, just as any other patients, should be accorded treatment appropriate to their medical condition and needs. Particular attention should be paid to adequate solutions for persons in need of care. PMID:21592331

  9. Genetic influence on methadone treatment outcomes in patients undergoing methadone maintenance treatment for opioid addiction: a pilot study

    PubMed Central

    Samaan, Zainab; Bawor, Monica; Dennis, Brittany B; Plater, Carolyn; Varenbut, Michael; Daiter, Jeffrey; Worster, Andrew; Marsh, David C; Tan, Charlie; Desai, Dipika; Thabane, Lehana; Pare, Guillaume

    2014-01-01

    Introduction Treatment of opioid addiction with methadone is effective; however, it is known to produce interindividual variability. This may be influenced in part by genetic variants, which can increase the initial risk of developing opioid addiction as well as explain differences in response to treatment. This pilot study aimed to assess the feasibility of conducting a full-scale genetic analysis to identify genes that predict methadone treatment outcomes in this population. Methods This was a cross-sectional observational study of patients admitted to a methadone maintenance treatment program for opioid addiction. We obtained demographic and clinical characteristics in addition to blood and urine samples, for the assessment of treatment outcomes. Results The recruitment process yielded 252 patients, representing a 20% recruitment rate. We conducted genetic testing based on a 99.6% rate of provision of DNA samples. The average retention in treatment was 3.4 years, and >50% of the participants reported psychiatric and medical comorbidities. BDNF rs6265 and DRD2 rs1799978 were the common single nucleotide polymorphisms (SNPs) selected for the feasibility study. Discussion This study met our predetermined feasibility criteria; recruitment, response rates, and genetic testing were feasible; treatment duration was sufficient for follow up; and the prevalence of comorbid conditions indicated the need for reliable psychiatric and chronic pain measures. The study strengths included effective collaboration with clinics and the generalizability of sample population. Key learning points show the need for assessment of treatment outcomes on multiple domains, implementation of follow up, and the development of standardized training for the study clinical staff. PMID:25187714

  10. Performance modeling of nonconcentrating solar detoxification systems

    SciTech Connect

    March, M.; Martin, A.; Saltiel, C.

    1995-03-01

    A detailed simulation model is developed for predicting the performance of solar detoxification systems. Concentration profiles are determined via a method of lines approach during sunlight hours for acquired and synthetic (simulating clear and cloudy days) ultraviolet radiation intensity data. Verification of the model is performed with comparison against indoor laboratory and outdoor field test results. Simulations are performed over a range of design parameters to examine system sensitivity. Discussions are focused on the determination of optimal sizing and operating conditions. 17 refs., 8 figs.

  11. Bioconversion of lignocellulose: inhibitors and detoxification

    PubMed Central

    2013-01-01

    Bioconversion of lignocellulose by microbial fermentation is typically preceded by an acidic thermochemical pretreatment step designed to facilitate enzymatic hydrolysis of cellulose. Substances formed during the pretreatment of the lignocellulosic feedstock inhibit enzymatic hydrolysis as well as microbial fermentation steps. This review focuses on inhibitors from lignocellulosic feedstocks and how conditioning of slurries and hydrolysates can be used to alleviate inhibition problems. Novel developments in the area include chemical in-situ detoxification by using reducing agents, and methods that improve the performance of both enzymatic and microbial biocatalysts. PMID:23356676

  12. A Pilot Study of the Nutritional Status of Opiate Abusing Pregnant Women on Methadone Maintenance Therapy

    PubMed Central

    Tomedi, Laura E.; Bogen, Debra; Hanusa, Barbara H.; Wisner, Katherine L.; Bodnar, Lisa M.

    2011-01-01

    Pregnant women in methadone maintenance therapy may have poor nutrition during pregnancy. In 2006–2008, methadone treated pregnant women (n = 22) were recruited at an urban academic medical center and compared with non-drug using pregnant women (n = 119) at 20–35 weeks gestation. We measured adiposity using pre-pregnancy body mass index (BMI), dietary intake using a food frequency questionnaire, and micronutrient and essential fatty acid status using biomarkers. Methadone treated women had lower BMI, consumed more calories, had lower serum carotenoid concentrations and higher plasma homocysteine concentrations than controls. The study’s limitations and implications for future research are discussed. PMID:22217127

  13. Influence of HIV antiretrovirals on methadone N-demethylation and transport.

    PubMed

    Campbell, Scott D; Gadel, Sarah; Friedel, Christina; Crafford, Amanda; Regina, Karen J; Kharasch, Evan D

    2015-05-15

    Drug interactions involving methadone and/or HIV antiretrovirals can be problematic. Mechanisms whereby antiretrovirals induce clinical methadone clearance are poorly understood. Methadone is N-demethylated to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) by CYP2B6 and CYP3A4 in vitro, but by CYP2B6 in vivo. This investigation evaluated human hepatocytes as a model for methadone induction, and tested the hypothesis that methadone and EDDP are substrates for human drug transporters. Human hepatocyte induction by several antiretrovirals of methadone N-demethylation, and CYP2B6 and CYP3A4 transcription, protein expression and catalytic activity, and pregnane X receptor (PXR) activation were evaluated. Methadone and EDDP uptake and efflux by overexpressed transporters were also determined. Methadone N-demethylation was generally not significantly increased by the antiretrovirals. CYP2B6 mRNA and activity (bupropion N-demethylation) were induced by several antiretrovirals, as were CYP3A4 mRNA and protein expression, but only indinavir increased CYP3A activity (alfentanil dealkylation). CYP upregulation appeared related to PXR activation. Methadone was not a substrate for uptake (OCT1, OCT2, OCT3, OATP1A2, OATP1B1, OATP1B3, OATP2B1) or efflux (P-gp, BCRP) transporters. EDDP was a good substrate for P-gp, BCRP, OCT1, OCT3, OATP1A2, and OATP1B1. OATP1A2- and OCT3-mediated EDDP uptake, and BCRP-mediated EDDP efflux transport, was inhibited by several antiretrovirals. Results show that hepatocyte methadone N-demethylation resembles expressed and liver microsomal metabolism more than clinical metabolism. Compared with clinical studies, hepatocytes underreport induction of methadone metabolism by HIV drugs. Hepatocytes are not a good predictive model for clinical antiretroviral induction of methadone metabolism and not a substitute for clinical studies. EDDP is a transporter substrate, and is susceptible to transporter-mediated interactions.

  14. Visual evoked potentials in infants exposed to methadone in utero.

    PubMed

    McGlone, L; Mactier, H; Hamilton, R; Bradnam, M S; Boulton, R; Borland, W; Hepburn, M; McCulloch, D L

    2008-09-01

    We investigated the effects of maternal drug misuse on neonatal visual evoked potentials (VEPs). Flash VEPs were recorded within 4 days of birth from 21 term infants of mothers misusing drugs and prescribed substitute methadone and 20 controls. Waveforms were classified as typical, atypical, immature or non-detectable, and amplitude and latencies were measured. VEPs from drug-exposed infants were less likely to be of typical waveform and more likely to be immature or non-detectable (p<0.01) than those of control infants. They were also smaller in amplitude (median 10.8 vs 24.4 microV, p<0.001). VEPs of drug-exposed infants had matured after 1 week but remained of lower amplitude than VEPs of newborn controls (p<0.01) and were non-detectable in 15%. Flash VEPs differ between maternal drug-exposed and non-drug-exposed newborns. Future research should address the specific effects of maternal methadone and/or other illicit drug misuse on infant VEPs, and associations between neonatal VEPs and subsequent visual development.

  15. Correlates of Alcohol Use among Methadone-Maintained Adults

    PubMed Central

    Nyamathi, Adeline; Cohen, Allan; Marfisee, Mary; Shoptaw, Steven; Greengold, Barbara; de Castro, Viviane; George, Daniel; Leake, Barbara

    2009-01-01

    This prospective study (n = 190) examined correlates of alcohol use from baseline data of a longitudinal trial conducted among moderate and heavy alcohol users receiving methadone maintenance therapy (MMT). The sample included MMT clients who were 18-55 years of age, and were receiving MMT from five large methadone maintenance clinics in the Los Angeles area. Half of the sample were heavy drinkers and nearly half (46%) reported heroin use. Using a structured questionnaire, correlates of heavy alcohol use included White and Hispanic ethnicity, and fair or poor physical health combined with older age (≥ 50 years). We also found that MMT clients who were younger than 50 years, regardless of health status, were more likely to be heavy drinkers. Compared with moderate alcohol consumers, a greater number of heavy alcohol users also experienced recent victimization. To optimize MMT, alcohol screening should be part of routine assessment and alcohol treatment should be made available within MMT programs. Moreover, special consideration should be provided to the most vulnerable clients, such as the younger user, those with a long-term and current history of heavy drug use, and those victimized and reporting fair or poor health. In addition, promoting attention to general physical and mental health problems within MMT programs may be beneficial in enhancing health outcomes of this population. PMID:19081204

  16. Methadone Prescribing and Overdose and the Association with Medicaid Preferred Drug List Policies - United States, 2007-2014.

    PubMed

    Faul, Mark; Bohm, Michele; Alexander, Caleb

    2017-03-31

    Drug overdose is a leading cause of injury death in the United States; 47,055 fatal drug overdoses were reported in 2014, a 6.5% increase from the previous year (1), driven by opioid use disorder (2,3). Methadone is an opioid prescribed for pain management and is also provided through opioid treatment programs to treat opioid use disorders. Because methadone might remain in a person's system long after the pain-relieving benefits have been exhausted, it can cause slow or shallow breathing and dangerous changes in heartbeat that might not be perceived by the patient (4,5). In December 2006, the Food and Drug Administration issued a Public Health Advisory that alerted health care professionals to reports of death and life-threatening adverse events, such as respiratory depression and cardiac arrhythmias, in patients receiving methadone (4); in January 2008, a voluntary manufacturer restriction limited distribution of the 40 mg formulation of methadone.* CDC analyzed state mortality and health care data and preferred drug list (PDL) policies to 1) compare the percentage of deaths involving methadone with the rate of prescribing methadone for pain, 2) characterize variation in methadone prescribing among payers and states, and 3) assess whether an association existed between state Medicaid reimbursement PDL policies and methadone overdose rates. The analyses found that, from 2007 to 2014, large declines in methadone-related overdose deaths occurred. Prescriptions for methadone accounted for 0.85% of all opioid prescriptions for pain in the commercially insured population and 1.1% in the Medicaid population. In addition, an association was observed between Medicaid PDLs requiring prior authorization for methadone and lower rates of methadone overdose among Medicaid enrollees. PDL policies requiring prior authorization might help to reduce the number of methadone overdoses.

  17. Occurrence, detection and detoxification of mycotoxins.

    PubMed

    Aiko, Visenuo; Mehta, Alka

    2015-12-01

    Mycotoxins have been identified as important toxins affecting animal species and humans ever since the discovery of aflatoxin B1 in 1960. Mycotoxigenic fungi are ubiquitous in nature and are held responsible for economic loss as they decrease crop yield and quality of food. The presence of fungi and their mycotoxins are reported not only in food grains but also in medicinal herbs and processed foods. Since prevention is not always possible, detoxification of mycotoxins have been attempted using several means; however, only few have been accepted for practical use, e.g. ammonia in the corn industry. Organizations such as the World Health Organization, US Food and Drug Administration and European Union have set regulations and safety limits of important mycotoxins, viz. aflatoxins, fusarium toxins, ochratoxin, patulin zearalenone, etc., to ensure the safety of the consumers. This review article is a brief and up-to-date account of the occurrence, detection and detoxification of mycotoxins for those interested in and considering research in this area.

  18. Yeast metallothionein function in metal ion detoxification.

    PubMed

    Ecker, D J; Butt, T R; Sternberg, E J; Neeper, M P; Debouck, C; Gorman, J A; Crooke, S T

    1986-12-25

    A genetic approach was taken to test the function of yeast metallothionein in metal ion detoxification. A yeast strain was constructed in which the metallothionein locus was deleted (cup1 delta). The cup1 delta strain was complemented with normal or mutant metallothionein genes under normal or constitutive regulatory control on high copy episomal plasmids. Metal resistance of the cup1 delta strain with and without the metallothionein-expressing vectors was analyzed. The normally regulated metallothionein gene conferred resistance only to copper (1000-fold); constitutively expressed metallothionein conferred resistance to both copper (500-fold) and cadmium (1000-fold), but not to mercury, zinc, silver, cobalt, nickel, gold, platinum, lanthanum, uranium, or tin. Two mutant versions of the metallothionein gene were constructed and tested for their ability to confer metal resistance in the cup1 delta background. The first had a deletion of a highly conserved amino acid sequence (Lys-Lys-Ser-Cys-Cys-Ser). The second was a hybrid gene consisting of the sequences coding for the first 20 amino acids of the yeast protein fused to the monkey metallothionein gene. Expression of these genes under the CUP1 promoter provided significant protection from copper, but none of the other metals tested. These results demonstrate that there is significant flexibility in the structural requirements for metallothionein to function in copper detoxification and that yeast metallothionein is also capable of detoxifying cadmium under conditions of constitutive expression.

  19. The detoxification process, bioaccumulation and damage effect in juvenile white shrimp Litopenaeus vannamei exposed to chrysene.

    PubMed

    Ren, Xianyun; Pan, Luqing; Wang, Lin

    2015-04-01

    This study aimed to evaluate the effect of chrysene (CHR) on detoxification enzymes, bioaccumulation and effect of CHR on biomolecule damage in different organs of the juvenile white shrimp Litopenaeus vannamei. In this study, juvenile white shrimp L. vannamei were exposed to CHR for 21 days at four different concentrations as 0, 0.3, 2.1 and 14.7 μg/L. Results showed that CHR bioaccumulation increased rapidly at first then reached a plateau. The activities of aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin O-deethylase (EROD), epoxide hydrolase (EH), glutathione-S-transferase (GST), sulfotransferase (SULT) and uridinediphosphate glucuronyltransferase (UGT) were induced and then became stable gradually. Moreover, 2.1 and 14.7 μg/L CHR treatments increased activity of superoxide dismutase (SOD) in gills and hepatopancreas, while total antioxidant capacity (T-AOC) and GSH/GSSG were suppressed after CHR exposure. Additionally, lipid peroxidation (LPO) levels, protein carbonyl (PC) contents and DNA damage were induced throughout the exposure period, and different trends were detected with time of exposure. Overall, these novel findings of CHR bioaccumulation and resulted toxicity demonstrate that CHR could affect the physical status of L. vannamei. This study will form a solid basis for a realistic extrapolation scientific data for aquaculture water monitoring and food security.

  20. Cumulated activities determined from biodistribution data in pregnant rats ranging from 13 to 21 days gestation. I. Tc-99m pertechnetate.

    PubMed

    Wegst, A V; Goin, J E; Robinson, R G

    1983-01-01

    Cumulated activity estimates for Tc-99m pertechnetate were determined using biodistribution data from pregnant and nonpregnant rats. The pregnant rats were studied at 13, 15, 17, 19, and 21 days gestation. The results indicate that maternal organ cumulated activities are not a simple function of gestational age. The organs into which Tc-99m pertechnetate enters through passive diffusion follow the pattern established by the blood, generally resulting in an increase from the 13th through the 17th day with a decrease on the 19th and 21st day. The organs dominated by active transport follow unique and different patterns. The fetal cumulated activity estimates increased exponentially with gestational age and the placental estimates increased linearly.

  1. Older adults prescribed methadone: a review of the literature across the life span from opiate initiation to methadone maintenance treatment.

    PubMed

    Doukas, Nick

    2014-01-01

    Professionals currently working with methadone patients are facing challenges with the rise of polydrug use, HIV and Hepatitis epidemics, and treating a large volume of individuals who are older than ever before, presenting for the first time in their 50's, 60's and 70's. There have been two literature reviews conducted on this older population, but they can only provide a snap-shot view on the later stage of life of this unique group. A longitudinal literature review of the long-term opiate abuser who has transitioned into opiate replacement therapy will provide depth and illustrate the complexity of interrelated factors that have been affected throughout their life span. This paper reviews the literature conducted on opiate addicts from their earlier stages of substance use to older adulthood where many have chosen to enter into a methadone maintenance program. The paper will also take a biopsychosocial approach when reviewing the literature because of how these three domains are deeply affected and interrelated with this population.

  2. QT Interval Screening in Methadone Maintenance Treatment: Report of a SAMHSA Expert Panel

    PubMed Central

    Martin, Judith A.; Campbell, Anthony; Killip, Thomas; Kotz, Margaret; Krantz, Mori J.; Kreek, Mary Jeanne; McCarroll, Brian A.; Mehta, Davendra; Payte, J. Thomas; Stimmel, Barry; Taylor, Trusandra; Wilford, Bonnie B.

    2014-01-01

    In an effort to enhance patient safety in Opioid Treatment Programs (OTPs), the Substance Abuse and Mental Health Services Administration (SAMHSA) convened a multi-disciplinary Expert Panel on the Cardiac Effects of Methadone. Panel members reviewed the literature, regulatory actions, professional guidances, and OTPs’ experiences regarding adverse cardiac events associated with methadone. The Panel concluded that, to the extent possible, every OTP should have a universal Cardiac Risk Management Plan (incorporating clinical assessment, ECG assessment, risk stratification, and prevention of drug interactions) for all patients, and should strongly consider patient-specific risk minimization strategies (such as careful patient monitoring, obtaining ECGs as indicated by a particular patient’s risk profile, and adjusting the methadone dose as needed) for patients with identified risk factors for adverse cardiac events. The Panel also suggested specific modifications to informed consent documents, patient education, staff education, and methadone protocols. PMID:22026519

  3. Sex effects in cocaine using methadone patients randomized to contingency management interventions

    PubMed Central

    Burch, Ashley E.; Rash, Carla J.; Petry, Nancy M.

    2015-01-01

    Contingency management (CM) is an effective treatment for promoting cocaine abstinence in patients receiving methadone maintenance. However, few studies have examined the effect of sex on treatment outcomes in this population. This study evaluated the impact of sex on longest duration of abstinence (LDA) and percent negative urine samples in 323 cocaine-using methadone patients from four randomized clinical trials comparing CM to standard methadone care. Overall, women had better treatment outcomes compared to men, demonstrated by an increase in both LDA and percentages of negative samples. Patients receiving CM also had significantly higher LDA and percentages of negative samples compared to patients receiving standard care, but sex by treatment condition effects were not significant. These data suggest that cocaine using methadone patients who are women have better substance use outcomes than men in interventions that regularly monitor cocaine use, and CM is equally efficacious regardless of sex. PMID:26237326

  4. Economic Cost of the Therapeutic Workplace Intervention Added to Methadone Maintenance

    PubMed Central

    Knealing, Todd W.; Roebuck, M. Christopher; Wong, Conrad J.; Silverman, Kenneth

    2008-01-01

    The therapeutic workplace is a novel intervention that uses access to paid training and employment to reinforce drug abstinence within the context of standard methadone maintenance. We used the Drug Abuse Treatment Cost Analysis Program as a standard method of estimating the economic costs of this intervention. Over a one-year period, the therapeutic workplace served 122 methadone maintenance clients who had a median length of stay of 22 weeks. The workplace maintained a mean daily census of 48 clients. The combined cost of methadone maintenance and the therapeutic workplace was estimated at $362 per week. This cost is less than other treatments that might be used to promote abstinence in individuals who continue to use drugs during methadone treatment. Given prior evidence of effectiveness, these cost data may be useful to policymakers, social service agencies, and researchers interested in using or further developing the therapeutic workplace intervention. PMID:17614239

  5. Assessing the spatial distribution of methadone clinic clients and their access to treatment

    PubMed Central

    2010-01-01

    Using Geographic Information System (GIS), the spatial distribution of methadone clinic clients and their utilization of a treatment service in Hong Kong was analysed. A majority (93.7%) of the 63 methadone users recruited were residing in the same district, of which 84.1% spent not more than 15 minutes for traveling. Walking (55.6%) was the commonest transport mode followed by cycling (30.2%). There was no distance decay effect on traveling time, but an association between distance and transport selection could be demonstrated. The residence locations displayed a compact distribution, merging with the general population without any evidence of clustering. Though the distribution of methadone users could have been shaped by the location of clinic, it can also be concluded that methadone clinics at convenient locations are needed if maintenance is a key determinant of service effectiveness. PMID:20602756

  6. Use of hair testing to determine methadone exposure in pediatric deaths.

    PubMed

    Tournel, Gilles; Pollard, Jocelyn; Humbert, Luc; Wiart, Jean-François; Hédouin, Valéry; Allorge, Delphine

    2014-09-01

    A case of death attributed to methadone acute poisoning in an infant aged 11 months is reported. A sudden infant death syndrome (SIDS) was suspected, whereas a traumatic cause of death was excluded regarding autopsy findings. Specimens were submitted to a large toxicological analysis, which included ethanol measurement by HS-GC-FID, a targeted screening for drugs of abuse and various prescription drug classes followed by quantification using UPLC-MS/MS methods. Methadone and its metabolite (EDDP) were detected in all the tested fluids, as well as in hair, with a blood concentration of methadone considered as lethal for children (73 ng/mL). The cause of death was determined to be acute "methadone poisoning", and the manner of death was "accidental". A discussion of the case circumstances, the difficulties with the interpretation of toxicological findings in children (blood concentration and hair testing), and the origin of exposure are discussed.

  7. The use of token economy to reduce illicit drug use among methadone maintenance clients.

    PubMed

    Glosser, D S

    1983-01-01

    The effects of a token economy in modifying the illicit polydrug use of 97 methadone maintenance clients was investigated over a period of two and a half years. Subjects' drug-free urinalysis reports were reinforced with points which could be redeemed to obtain methadone. Each subject's daily dose level varied with the point balance. A multiple baseline analysis showed that when methadone acquisition was in part made contingent upon drug-free urinalyses, illicit drug use declined rapidly. After six months, the token economy group's urines were 14% positive for illicit drugs compared to 39% in the traditional treatment group. As time in treatment increased, illicit drug use further declined. These results suggest a more effective and practical strategy for the treatment of polydrug abusing methadone maintenance clients than has previously been available.

  8. Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial

    PubMed Central

    Rich, Josiah D; McKenzie, Michelle; Larney, Sarah; Wong, John B; Tran, Liem; Clarke, Jennifer; Noska, Amanda; Reddy, Manasa; Zaller, Nickolas

    2015-01-01

    Summary Background Methadone is an effective treatment for opioid dependence. When people who are receiving methadone maintenance treatment for opioid dependence are incarcerated in prison or jail, most US correctional facilities discontinue their methadone treatment, either gradually, or more often, abruptly. This discontinuation can cause uncomfortable symptoms of withdrawal and renders prisoners susceptible to relapse and overdose on release. We aimed to study the effect of forced withdrawal from methadone upon incarceration on individuals’ risk behaviours and engagement with post-release treatment programmes. Methods In this randomised, open-label trial, we randomly assigned (1:1) inmates of the Rhode Island Department of Corrections (RI, USA) who were enrolled in a methadone maintenance-treatment programme in the community at the time of arrest and wanted to remain on methadone treatment during incarceration and on release, to either continuation of their methadone treatment or to usual care—forced tapered withdrawal from methadone. Participants could be included in the study only if their incarceration would be more than 1 week but less than 6 months. We did the random assignments with a computer-generated random permutation, and urn randomisation procedures to stratify participants by sex and race. Participants in the continued-methadone group were maintained on their methadone dose at the time of their incarceration (with dose adjustments as clinically indicated). Patients in the forced-withdrawal group followed the institution’s standard withdrawal protocol of receiving methadone for 1 week at the dose at the time of their incarceration, then a tapered withdrawal regimen (for those on a starting dose >100 mg, the dose was reduced by 5 mg per day to 100 mg, then reduced by 3 mg per day to 0 mg; for those on a starting dose ≤100 mg, the dose was reduced by 3 mg per day to 0 mg). The main outcomes were engagement with a methadone maintenance

  9. Effect of prenatal methadone on reinstated behavioral sensitization induced by methamphetamine in adolescent rats.

    PubMed

    Wong, Chih-Shung; Lee, Yih-Jing; Chiang, Yao-Chang; Fan, Lir-Wan; Ho, Ing-Kang; Tien, Lu-Tai

    2014-01-01

    It has been known that methadone maintenance treatment is the standard treatment of choice for pregnant opiate addicts. However, there are few data on newborn outcomes especially in the cross talk with other addictive agents. The present study was to investigate the effect of prenatal exposure to methadone on methamphetamine (METH)-induced behavioral sensitization as an indicator of drug addiction in later life. Pregnant rats received saline or methadone (7 mg/kg, s.c.) twice daily from E3 to E20. To induce behavioral sensitization, offspring (5 weeks old) were treated with METH (1mg/kg, i.p.) or saline once daily for 5 consecutive days. Ninety-six hours (day 9) after the 5th treatment with METH or saline, animals received a single dose of METH (1mg/kg, i.p.) or saline to induce the reinstated behavioral sensitization. Prenatal methadone treatment enhanced the level of development of locomotor behavioral sensitization to METH administration in adolescent rats. Prenatal methadone treatment also enhanced the reinstated locomotor behavioral sensitization in adolescent rats after the administration had ceased for 96 h. These results indicate that prenatal methadone exposure produces a persistent lesion in the dopaminergic system, as indicated by enhanced METH-induced locomotor behavioral sensitization (before drug abstinence) and reinstated locomotor behavioral sensitization (after short term drug abstinence) in adolescent rats. These findings show that prenatal methadone exposure may enhance susceptibility to the development of drug addiction in later life. This could provide a reference for drug usage such as methamphetamine in their offspring of pregnant woman who are treating with methadone.

  10. An Ageing Methadone Population: A Challenge to Aged Persons' Mental Health Services?

    PubMed

    Searby, Adam; Maude, Phil; McGrath, Ian

    2015-01-01

    Oral administration of methadone has been used as a treatment strategy for opiate addiction for many years. The state of Victoria, Australia, has a long-running methadone program with a large number of participants. Accordingly, a growing number of adults have utilised methadone maintenance treatment for a number of years and are now moving into older age due to advances in medical treatment and harm reduction initiatives. The objective of this review is to examine the literature pertaining to co-occurring mental illness in older methadone treatment participants and to explore the future challenges this growing cohort of ageing adults pose to aged persons’ psychiatry services. As part of a broader study into dual diagnosis in older adults, a search of the Scopus, ProQuest, and CINAHL journal databases was performed. Twenty abstracts from literature published within the previous 15 years (1999–2014) were identified that explored methadone maintenance programs and the older adults maintained on them. A number of researchers have identified the ageing methadone population to have a high degree of comorbid mental illness and psychological distress. Studies also indicate that individuals enrolled in methadone maintenance programs may engage in a degree of continual substance use, potentially leading to deleterious effects on their psychosocial function. An ageing methadone population experiencing a high degree of comorbid mental illness is likely to challenge aged persons’ psychiatry services. These services are likely to be increasingly called on to manage these individuals, particularly within Victoria where few substance use services exist for those over the age of 65. It is essential that aged persons’ psychiatry services prepare to provide care for these individuals in a responsive manner that is inclusive of both their mental health and substitution pharmacotherapy.

  11. Trends in Reporting Methadone-Associated Cardiac Arrhythmia, 1997–2011

    PubMed Central

    Kao, David; Bartelson, Becki Bucher; Khatri, Vaishali; Dart, Richard; Mehler, Philip S.; Katz, David; Krantz, Mori J.

    2013-01-01

    Background: Long-acting opioids are a leading cause of accidental death in the United States, and methadone is associated with greater mortality rates. Whether this increase is related to the proarrhythmic properties of methadone is unclear. Objective: To describe methadone-associated arrhythmia events reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Design: Description of national adverse event registry data before and after publication of a 2002 report describing an association between methadone and arrhythmia. Setting: FAERS, November 1997 and June 2011. Patients: Adults with QTc prolongation or torsade de pointes and ventricular arrhythmia or cardiac arrest. Measurements: FAERS reports before and after the 2002 report. Results: 1646 cases of ventricular arrhythmia or cardiac arrest and 379 cases of QTc prolongation or torsade de pointes were associated with methadone. Monthly reports of QTc prolongation or torsade de pointes increased from a mean of 0.3 (95% CI, 0.1 to 0.5) before the 2002 publication to a mean of 3.5 (CI, 2.5 to 4.8) after it. After 2000, methadone was the second-most common primary suspect in cases of QTc prolongation or torsade de pointes after dofetilide (a known proarrhythmic drug) and was associated with disproportionate reporting similar to that of antiarrhythmic agents known to promote torsade de pointes. Antiretroviral drugs for HIV were the most common coadministered drugs. Limitation: Reports to FAERs are voluntary and selective, and incidence rates cannot be determined from spontaneously reported data. Conclusion: Since 2002, reports to FAERS of methadone-associated arrhythmia have increased substantially and are disproportionately represented relative to other events with the drug. Coadministration of methadone with antiretrovirals in patients with HIV may pose particular risk. Primary Funding Source: Colorado Clinical and Translational Sciences Institute, National Institutes of Health, and

  12. Highly selective electrode for potentiometric analysis of methadone in biological fluids and pharmaceutical formulations.

    PubMed

    Ardeshiri, Moslem; Jalali, Fahimeh

    2016-06-01

    In order to develop a fast and simple procedure for methadone analysis in biological fluids, a graphite paste electrode (GPE) was modified with the ion-pair of methadone-phosphotungstic acid, and multiwalled carbon nanotubes (MWCNTs). Optimized composition of the electrode with respect to graphite powder:paraffin oil:MWCNTs:ion pair, was 58:30:8:4 (w/w%). The electrode showed a near-Nernstian slope of 58.9 ± 0.3 mV/decade for methadone in a wide linear range of 1.0 × 10(-8)-4.6 × 10(-3)M, with a detection limit of 1.0 × 10(-8)M. The electrode response was independent of pH in the range of 5-11, with a fast response time (~4s) at 25 °C. The sensor showed high selectivity and was successfully applied to the determination of sub-micromolar concentrations of methadone in human blood serum and urine samples, with recoveries in the range of 95-99.8%. The average recovery of methadone from tablets (5 mg/tablet) by using the proposed method was 98%. The life time of the modified electrode was more than 5 months, due to the characteristic of GPE which can be cut off and fresh electrode surface be available. A titration procedure was performed for methadone analysis by using phosphotungstic acid, as titrating agent, which showed an accurate end point and 1:1 stoichiometry for the ion-pair formed (methadone:phosphotungstic acid). The simple and rapid procedure as well as excellent detection limit and selectivity are some of the advantages of the proposed sensor for methadone.

  13. Aggressive responding of male heroin addicts under methadone treatment: psychometric and neuroendocrine correlates.

    PubMed

    Gerra, G; Zaimovic, A; Raggi, M A; Giusti, F; Delsignore, R; Bertacca, S; Brambilla, F

    2001-12-01

    Objective measures of experimentally-induced aggressiveness were evaluated in 20 methadone-treated heroin addicts, in comparison to 20 normal healthy male subjects. All the subjects were submitted to preliminary DSM IV interviews, Buss Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the point subtraction aggression paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money, which was attributed to a fictitious other participants. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response), or protecting their counter (escape response). Money-earning responses were significantly lower (t=4.38, P<0.001) and aggressive responses significantly higher (t=5.45; P<0.001) in methadone patients in comparison to controls. During the experimentally-induced aggressiveness, plasma adrenocorticotropic hormone (ACTH), cortisol (CORT) and growth hormone (GH) concentrations increased significantly less and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), significantly more in methadone subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamines changes, BDHI 'direct' and 'irritability' scores, MMPI 'psychopathic deviate' scores both in methadone subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between methadone doses, or exposure extent, and aggressiveness levels. Our findings suggest that heroin dependent patients have higher outward-directed aggressiveness than healthy subjects, in relationship with monoamines hyper-reactivity, also under methadone medication. Aggressiveness in methadone patients seems to be related more to the personality traits than to drug effects. Hypothalamus-pituitary-adrenal (HPA) axis responses, unexpectedly dissociated from catecholamines rise

  14. Prevalence of pulmonary edema among the deceased cases with acute Methadone poisoning: A report from Iran

    PubMed Central

    Eizadi-Mood, Nastaran; Naeini, Seyed Amir Hossein Madani; Hedaiaty, Mahrang; Sabzghabaee, Ali Mohammad; Moudi, Maryam

    2016-01-01

    Objective: Methadone poisoning is common in our society, mainly in drug addicts. One of its lethal complications is pulmonary edema. Therefore, we evaluated the prevalence of pulmonary edema in the deceased cases with methadone poisoning and its possible relationship with some medical variables. Methods: In this cross-sectional study which was done in 2014, we have investigated the deceased patients with methadone toxicity who underwent autopsy at Isfahan Forensic Medicine Department (Iran). All variables including age, gender, and autopsy findings were recorded and analyzed. Demographic characteristics and medical complications of the patients were compared between the patients with or without pulmonary edema in the autopsy findings. Findings: There were 64 cases who died with methadone poisoning during the 1-year study period. The average age of cases (±standard deviation) was 32.1 ± 10.29 years, among which 92.2% were male. Based on the autopsy findings, 64.1% were diagnosed with pulmonary edema. There was no statistically significant relationship between pulmonary edema and age, gender, history of addiction, and hepatic or cardiovascular complications. Conclusion: Pulmonary edema is a common finding in deceased methadone poisoning cases and must be considered and ruled out in patients with acute methadone toxicity. PMID:27843967

  15. Predisposing Factors for Methadone Poisoning in Children Hospitalized at Kerman Afzalipour Hospital, Iran

    PubMed Central

    Hosseininasab, Ali; Vahidi, Aliasghar; Bagheri-Charouk, Fatemeh

    2016-01-01

    Background Methadone is a synthetic opioid that has been used to relieve severe pain in addiction withdrawal. Unfortunately, due to non-standard supply and storage, the incidence of poisoning and deaths caused by this drug is increasing daily. The purpose of this study was to determine the underlying causes of methadone poisoning in children admitted to Kerman Afzalipour Hospital, Kerman University of Medical Sciences, Iran, during 2012. Methods This cross-sectional study was performed on 105 children diagnosed with methadone poisoning and admitted to the pediatric emergency ward at Kerman Afzalipour Hospital. The required information was recorded through interviews with parents, patient examination, and if necessary telephone calls with the parents. The data were analyzed using SPSS software. Findings Mean age of children was 3.9 ± 2.4 years and 59.0% of them were boys. Most parents had a high school diploma or a lower level of education. In all cases, a family member or relative, or at least one person in a party they attended was an addict. In most cases, methadone was fed to the child by mistake instead of water or other drugs. Parental substance abuse, employment status, and family income were significantly associated with methadone poisoning. Conclusion Training of methadone storage in individuals who need to use this drug can help to prevent accidental ingestion and poisoning of children. PMID:27274794

  16. Effects of regulation on methadone and buprenorphine provision in the wake of Hurricane Sandy.

    PubMed

    McClure, Bridget; Mendoza, Sonia; Duncan, Laura; Rotrosen, John; Hansen, Helena

    2014-10-01

    Hurricane Sandy led to the closing of many major New York City public hospitals including their substance abuse clinics and methadone programs, and the displacement or relocation of thousands of opioid-dependent patients from treatment. The disaster provided a natural experiment that revealed the relative strengths and weaknesses of methadone treatment in comparison to physician office-based buprenorphine treatment for opioid dependence, two modalities of opioid maintenance with markedly different regulatory requirements and institutional procedures. To assess these two modalities of treatment under emergency conditions, semi-structured interviews about barriers to and facilitators of continuity of care for methadone and buprenorphine patients were conducted with 50 providers of opioid maintenance treatment. Major findings included that methadone programs presented more regulatory barriers for providers, difficulty with dose verification due to impaired communication, and an over reliance on emergency room dosing leading to unsafe or suboptimal dosing. Buprenorphine treatment presented fewer regulatory barriers, but buprenorphine providers had little to no cross-coverage options compared to methadone providers, who could refer to alternate methadone programs. The findings point to the need for well-defined emergency procedures with flexibility around regulations, the need for a central registry with patient dose information, as well as stronger professional networks and cross-coverage procedures. These interventions would improve day-to-day services for opioid-maintained patients as well as services under emergency conditions.

  17. A Meta-Analysis of Retention in Methadone Maintenance by Dose and Dosing Strategy

    PubMed Central

    Bao, Yan-ping; Liu, Zhi-min; Epstein, David H.; Du, Cun; Shi, Jie; Lu, Lin

    2013-01-01

    Objective To estimate, via meta-analysis, the influence of different methadone dose ranges and dosing strategies on retention rates in methadone maintenance treatment (MMT). Methods A systematic literature search identified 18 randomized controlled trials (RCTs) evaluating methadone dose and retention. Retention was defined as the percentage of patients remaining in treatment at a specified time point. After initial univariate analyses of retention by Pearson chi-squares, we used multilevel logistic regression to calculate summary odds ratios (ORs) and 95% confidence intervals for the effects of methadone dose (above or below 60 mg/day), flexible vs. fixed dosing strategy, and duration of follow-up. Results The total number of opioid-dependent participants in the 18 studies was 2831, with 1797 in MMT and 1034 receiving alternative mediations or placebo. Each variable significantly predicted retention with the other variables controlled for. Retention was greater with methadone doses ≥ 60 than with doses <60 (OR: 1.74, 95% CI: 1.43–2.11). Similarly, retention was greater with flexible-dose strategies than with fixed-dose strategies (OR: 1.72, 95% CI: 1.41–2.11). Conclusions Higher doses of methadone and individualization of doses are each independently associated with better retention in MMT. PMID:19152203

  18. Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice.

    PubMed

    Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura; Whistler, Jennifer L

    2012-02-01

    Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

  19. Potential P-glycoprotein pharmacokinetic interaction of telaprevir with morphine or methadone.

    PubMed

    Fudin, Jeffrey; Fontenelle, Dania Vanesta; Fudin, Hannah Rebecca; Carlyn, Cynthia; Hinden, Debra Ann; Ashley, Christopher C

    2013-08-01

    Telaprevir (TVR) effects on P-glycloprotein and cytochrome P450 (CYP) may significantly elevate serum levels of morphine and methadone. Recent literature points to major interactions when combining TVR with warfarin or rifampin. Opioid interactions are especially dangerous in hepatitis C patients, as coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs in 50-90% of HIV-infected drug users that are prescribed opioids for chronic pain and/or methadone for maintenance. TVR has been shown to significantly inhibit the active transport enzyme pGP and may therefore increase intestinal morphine absorption. TVR also inhibits hepatic CYP3A4 that are responsible for metabolizing methadone. Patients requiring opioid analgesics must be carefully monitored because of potential for elevated opioid levels and overdose risk. Current recommendations minimize potential drug interactions between telaprevir and opioids, especially methadone, based on a single 7-day trial. We outline the various pharmacokinetic mechanisms involved when combining TVR with methadone or morphine and recommend that current data are not sufficiently robust to minimize the potentially significant interaction with opioids, especially methadone. Clinicians must be mindful of these understated interactions, know that the opioid dose may need to be significantly increased or reduced, and use caution during upward titration of opioids affected by these enzyme systems.

  20. Forskolin stimulates detoxification of brefeldin A.

    PubMed

    Nickel, W; Helms, J B; Kneusel, R E; Wieland, F T

    1996-07-05

    Forskolin has been shown to prevent the effects brefeldin A (BFA) exerts on many mammalian cells with respect to the disassembly of the Golgi apparatus as well as an increase of sphingomyelin synthesis (Lippincott, S. J., Glickman, J., Donaldson, J. G., Robbins, J., Kreis, T. E., Seamon, K. B., Sheetz, M. P., and Klausner, R. D. (1991) J. Cell Biol. 112, 567-577). It has been speculated that forskolin interferes with the action of BFA by competition for the binding of BFA to its target protein, which is most likely the Golgi-localized nucleotide exchange factor specific for ADP-ribosylation factor 1. Here we show that in vitro forskolin does not prevent inhibition of Golgi-catalyzed nucleotide exchange by BFA. Therefore it appears unlikely that forskolin and BFA bind to the same target protein. Using [3H]BFA we have measured detoxification of BFA by Chinese hamster ovary (CHO) cells. BFA is secreted from CHO cells as cysteine and glutathione conjugates (Brüning, A., Ishikawa, T., Kneusel, R. E., Matern, U., Lottspeich, F., and Wieland, F. T. (1992) J. Biol. Chem. 267, 7726-7732). We present evidence that forskolin treatment of CHO cells results in increased levels of Cys-BFA, the major BFA conjugate secreted by CHO cells, in the medium. Elevated levels of Cys-BFA are also found intracellularly. The effect of forskolin is shown to be independent of its ability to raise the intracellular concentration of cyclic AMP. Therefore, we suggest that the effect of forskolin on BFA-induced disassembly of the Golgi apparatus might be due to an enhanced detoxification of the drug.

  1. Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response

    PubMed Central

    Fonseca, Francina; de la Torre, Rafael; Díaz, Laura; Pastor, Antonio; Cuyàs, Elisabet; Pizarro, Nieves; Khymenets, Olha; Farré, Magí; Torrens, Marta

    2011-01-01

    Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements. PMID:21589866

  2. Rationale and design of a randomized controlled trial of varenicline directly observed therapy delivered in methadone clinics

    PubMed Central

    2014-01-01

    Background Tobacco cessation medication adherence is one of the few factors shown to improve smoking cessation rates among methadone-maintained smokers, but interventions to improve adherence to smoking cessation medications have not yet been tested among methadone treatment patients. Methadone clinic-based, directly observed therapy (DOT) programs for HIV and tuberculosis improve adherence and clinical outcomes, but have not been evaluated for smoking cessation. We describe a randomized controlled trial to evaluate whether a methadone clinic-based, directly observed varenicline therapy program increases adherence and tobacco abstinence among opioid-dependent drug users receiving methadone treatment. Methods/Design We plan to enroll 100 methadone-maintained smokers and randomize them to directly observed varenicline dispensed with daily methadone doses or treatment as usual (self-administered varenicline) for 12 weeks. Our outcome measures are: 1) pill count adherence and 2) carbon monoxide-verified tobacco abstinence. We will assess differences in adherence and abstinence between the two treatment arms using repeated measures models. Discussion This trial will allow for rigorous evaluation of the efficacy of methadone clinic-based, directly observed varenicline for improving adherence and smoking cessation outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs and can guide protocols for studies among opioid-dependent smokers receiving methadone treatment. Trial Registration clinicaltrials.gov NCT01378858 PMID:24928218

  3. Expression patterns of antioxidant genes in human SH-SY5Y cells after treatment with methadone.

    PubMed

    Saify, Khyber; Saadat, Mostafa

    2015-11-30

    The expression levels of nine antioxidant genes in SH-SY5Y cells exposed to methadone (final concentrations 1-20µM) were investigated. Based on this study the genes could be categorized on three different groups. The number of down-regulated genes were increased as a function of exposure time (P=0.004). The methadone associated mRNA alterations were modulated by N-acetyl-cysteine. These findings suggested that different pathways for regulation of antioxidant genes could be active after exposing of SH-SY5Y cells to methadone; and also suggested that methadone might act by inducing the reactive oxygen species.

  4. Double-blind, multicenter comparison of efficacy, cycle control, and tolerability of a 23-day versus a 21-day low-dose oral contraceptive regimen containing 20 microg ethinyl estradiol and 75 microg gestodene.

    PubMed

    Endrikat, J; Cronin, M; Gerlinger, C; Ruebig, A; Schmidt, W; Düsterberg, B

    2001-08-01

    This prospective, double-blind, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day versus a 21-day oral contraceptive regimen containing 20 microg ethinyl estradiol and 75 microg gestodene. Participants took trial medication daily for 28 days, either 23 tablets with active substances plus 5 placebo tablets or 21 tablets with active substances plus 7 placebo tablets. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 4,878 treatment cycles (23-day regimen: 2,362 cycles; 21-day regimen: 2,516 cycles) were obtained from 703 participants (23-day regimen, n = 342; 21-day regimen, n = 361). Both preparations proved to be effective contraceptives and provided good cycle control. One pregnancy because of method failure was recorded in each treatment group. This resulted in a study Pearl Index of 0.5 for each treatment. For the 23-day regimen, 36.0% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 37.1% in the 21-day regimen. In the 23-day regimen group, intracyclic bleeding episodes were reported by 42.4% of the participants in Cycle 1 but only in 14% in Cycle 7 and in the 21-day regimen group by 44.6% in Cycle 1 and only 17.3% in Cycle 7. Overall, intracyclic bleeding was reported in 21.9% of the 23-day regimen cycles and in 22.7% of the 21-day regimen cycles.A greater number of 23-day regimen participants had shorter withdrawal bleeding periods than with the 21-day regimen. In significantly (p <0.0001) more cycles in the 23-day regimen group, participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day regimen group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day regimen group was 4 days and in the 21-day regimen group 5 days. Both preparations were well tolerated and showed a similar

  5. Characteristics of opiate users leaving detoxification treatment against medical advice.

    PubMed

    Kenne, Deric R; Boros, Alec P; Fischbein, Rebecca L

    2010-07-01

    Substance-dependent patients leaving against medical advice (AMA) pose a unique challenge to detoxification programs. Most notably, AMA patients fail to access residential or outpatient treatment needed after detoxification and often return to detoxification treatment multiple times which has deleterious results for the patient and is taxing to the healthcare system. Using retrospective data from 89 daily opiate-using detoxification patients completing detoxification and 95 patients leaving AMA, we sought to identify patient characteristics useful in predicting AMA discharges from detoxification. Bivariate analyses indicated that AMA patients reported drug use did not impair their health, were injection drug users, younger and had fewer previous treatment admissions. Binomial logistic regression indicated that AMA patients were more likely to be unemployed and report that drug use did not impair their health. Patients completing detoxification were less likely to be injection drug users and less likely to be self-referred to treatment. Identifying patients at risk of leaving AMA provides an opportunity for clinicians to intervene in an effort to increase treatment engagement for these patients.

  6. Pulmonary 'mainline' granulomatosis: talcosis of intravenous methadone abuse.

    PubMed

    Paré, J A; Fraser, R G; Hogg, J C; Howlett, J G; Murphy, S B

    1979-05-01

    Seventeen intravenous abusers of methadone underwent clinical, roentgenologic and physiologic assessment. Two complained of dyspnea on exertion and two had cor pulmonale. Of 15 patients whose fundi were examined, nine had talc particles in their retinal vessels. The chest roentgenograms of seven showed a diffuse pin-point micronodular pattern and two of the seven also manifested volume loss, one with coalescence of opacities simulating progressive massive fibrosis. Twelve patients had some degree of pulmonary dysfunction, 10 with lowered steady state diffusing capacity and 11 with decreased flow rates (FEV1 and MMF). There was no hyperinflation, but two showed an increase in residual volume. Corticosteroid therapy was attempted on two and was ineffective. Necropsy on the one patient who died revealed severe pulmonary fibrosis and talc granulomas in lungs, liver, kidneys and lymph nodes.

  7. Methodology for the Randomised Injecting Opioid Treatment Trial (RIOTT): evaluating injectable methadone and injectable heroin treatment versus optimised oral methadone treatment in the UK

    PubMed Central

    Lintzeris, Nicholas; Strang, John; Metrebian, Nicola; Byford, Sarah; Hallam, Christopher; Lee, Sally; Zador, Deborah

    2006-01-01

    Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding the safety, efficacy and cost effectiveness of this treatment approach remains equivocal. Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high-quality oral methadone treatment who continue to regularly inject heroin, and that treatment be initiated in newly-developed supervised injecting clinics. The Randomised Injectable Opioid Treatment Trial (RIOTT) is a multisite, prospective open-label randomised controlled trial (RCT) examining the role of treatment with injected opioids (methadone and heroin) for the management of heroin dependence in patients not responding to conventional substitution treatment. Specifically, the study examines whether efforts should be made to optimise methadone treatment for such patients (e.g. regular attendance, supervised dosing, high oral doses, access to psychosocial services), or whether such patients should be treated with injected methadone or heroin. Eligible patients (in oral substitution treatment and injecting illicit heroin on a regular basis) are randomised to one of three conditions: (1) optimized oral methadone treatment (Control group); (2) injected methadone treatment; or (3) injected heroin treatment (with access to oral methadone doses). Subjects are followed up for 6-months, with between-group comparisons on an intention-to-treat basis across a range of outcome measures. The primary outcome is the proportion of patients who discontinue regular illicit heroin use (operationalised as providing >50% urine drug screens negative for markers of

  8. Evaluation of ongoing oxycodone abuse among methadone-maintained patients.

    PubMed

    Dunn, Kelly E; Sigmon, Stacey C; McGee, Mark R; Heil, Sarah H; Higgins, Stephen T

    2008-12-01

    Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges.

  9. Gulf War Illness - Evaluation of an Innovative Detoxification Program

    DTIC Science & Technology

    2014-10-01

    clinical chemistry analysis before and after undergoing the detoxification program. The GWI veterans will be studied at several time points, before the detoxification, immediately after and three months after completing the program. The goal of the study is to determine whether this method of detoxification results in reduction of the symptoms of GWI. Because of delays in obtaining human subjects approval, this project has only recently begun. All final IRB and DOD approvals were received in late 2013. However we have not yet received funding for the second and third

  10. Use of Methadone for Prevention of Opioid Withdrawal in Critically Ill Children

    PubMed Central

    Jeffries, Sonia A; McGloin, Rumi; Pitfield, Alexander F; Carr, Roxane R

    2012-01-01

    Background Opioids are commonly administered to critically ill children for analgesia and sedation, but many patients experience opioid withdrawal upon discontinuation. The authors’ institution developed a protocol for using methadone to prevent opioid withdrawal in children who have received morphine by continuous IV infusion for 5 days or longer in the pediatric intensive care unit (PICU). Objectives The primary objectives were to determine if opioids were tapered according to the protocol and to determine the conversion ratio for IV morphine to oral methadone that was used. Secondary objectives were to describe the methadone dosage used and the clinical outcomes, to evaluate adjustments to methadone dosing, and to report the incidence of adverse effects. Methods A retrospective analysis of charts was conducted for pediatric patients who had received morphine by continuous IV infusion for 5 days or longer followed by methadone in the PICU between May 2008 and August 2009. Validated scoring systems (the Withdrawal Assessment Tool and the State Behavioral Scale) were used to assess symptoms of withdrawal and degree of sedation, respectively. Results Forty-three patients were included in the study, with median age of 8 months (range 0.25–201 months). For 31 patients (72%), the protocol was not used, and there were no patients for whom the protocol was followed to completion. The median duration of weaning was 10 days (range 0–91 days). The conversion ratio for IV morphine to oral methadone was 1:0.78 for anticipated 5-day weaning and 1:0.98 for anticipated 10-day weaning. During the first 10 days of weaning, 18 patients (42%) experienced withdrawal symptoms. The methadone dose was increased for 11 (26%) of the 43 patients. Patients were sedated for a median of 1 day (range 0–9 days), were comfortable for a median of 6.5 days (range 1–64 days), and were agitated for a median of 2.5 days (range 0–23 days). Naloxone was required for 2 patients. Conclusions

  11. Sexual Dysfunction in Men Receiving Methadone Maintenance Treatment: Clinical History and Psychobiological Correlates.

    PubMed

    Gerra, Gilberto; Manfredini, Matteo; Somaini, Lorenzo; Maremmani, Icro; Leonardi, Claudio; Donnini, Claudia

    2016-01-01

    A variety of studies evidenced a relationship between drug use disorders and sexual dysfunction. In particular, heroin and opioid agonist medications to treat heroin dependence have been found to be associated with erectile dysfunction and reduced libido. Controversial findings also indicate the possibility of factors other than the pharmacological effects of opioid drugs concurring to sexual dysfunction. With the present study, we investigated the link between sexual dysfunction and long-term exposure to opioid receptor stimulation (heroin dependence, methadone maintenance treatment, methadone dosage), the potentially related hormonal changes reflecting hypothalamus-pituitary-gonadal axis function and prolactin (PRL) pituitary release, the role of adverse childhood experiences in the clinical history and the concomitant symptoms of comorbid mental health disorders in contributing to sexual problems. Forty male patients participating in a long-term methadone treatment program were included in the present study and compared with 40 healthy control subjects who never used drugs nor abused alcohol. All patients and controls were submitted to the Arizona Sexual Experiences Scale (ASEX), Child Experiences of Care and Abuse-Questionnaire (CECA-Q) and the Symptom Check List-90 Scale. A blood sample for testosterone and PRL assays was collected. Methadone dosages were recorded among heroin-dependent patients on maintenance treatment. Methadone patients scored significantly higher than controls on the 5-item rating ASEX scale, on CECA-Q and on Symptoms Check List 90 (SCL 90) scale. Testosterone plasma levels were significantly lower and PRL levels significantly higher in methadone patients with respect to the healthy control group. ASEX scores reflecting sexual dysfunction were directly and significantly correlated with CECA-Q neglect scores and SCL 90 psychiatric symptoms total score. The linear regression model, when applied only to addicted patients, showed that

  12. Methadone induction in primary care (ANRS-Methaville): a phase III randomized intervention trial

    PubMed Central

    2012-01-01

    Background In France, the rapid scale-up of buprenorphine, an opioid maintenance treatment (OMT), in primary care for drug users has led to an impressive reduction in HIV prevalence among injecting drug users (IDU) but has had no major effect on Hepatitis C incidence. To date, patients willing to start methadone can only do so in a methadone clinic (a medical centre for drug and alcohol dependence (CSAPA) or a hospital setting) and are referred to primary care physicians after dose stabilization. This study aims to assess the effectiveness of methadone in patients who initiated treatment in primary care compared with those who initiated it in a CSAPA, by measuring abstinence from street opioid use after one year of treatment. Methods/Design The ANRS-Methaville study is a randomized multicenter non-inferiority control trial comparing methadone induction (lasting approximately 2 weeks) in primary care and in CSAPA. The model of care chosen for methadone induction in primary care was based on study-specific pre-training of all physicians, exclusion criteria and daily supervision of methadone during the initiation phase. Between January 2009 and January 2011, 10 sites each having one CSAPA and several primary care physicians, were identified to recruit patients to be randomized into two groups, one starting methadone in primary care (n = 147), the other in CSAPA (n = 48). The primary outcome of the study is the proportion of participants abstinent from street opioids after 1 year of treatment i.e. non-inferiority of primary care model in terms of the proportion of patients not using street opioids compared with the proportion observed in those starting methadone in a CSAPA. Discussion The ANRS-Methaville study is the first in France to use an interventional trial to improve access to OMT for drug users. Once the non-inferiority results become available, the Ministry of Health and agency for the safety of health products may change the the New Drug Application

  13. Gas chromatography-mass spectrometry method for the determination of methadone and 2-ethylidene-1,5-dimethyl-3, 3-diphenylpyrrolidine (EDDP).

    PubMed

    Snozek, Christine L H; Bjergum, Matthew W; Langman, Loralie J

    2010-01-01

    Methadone is a synthetic opioid used to relieve pain, treat opioid withdrawal, and wean heroin addicts. Measurement of methadone and its major metabolite EDDP in urine is useful for assessing compliance with addiction rehabilitation and pain management programs. This method quantitatively measures methadone and its metabolite EDDP in urine. Methadone and EDDP are recovered from urine by solid phase extraction at pH 6.0. Analysis is performed by gas chromatography with mass spectrometry detection, using selective ion monitoring.

  14. Resonance enhancement in the accelerator transmutation of 1.3-day {sup 232}Pa and 2.1-day {sup 238}Np

    SciTech Connect

    Moore, M. S.; Danon, Y.

    1995-09-15

    The suggestion that the transmutation of actinide waste into fission products might best be done with thermalized spallation neutrons and odd-odd target materials such as {sup 238}Np has been studied. During the 1993 LAMPF/PSR cycle, we measured the fission cross section of 1.3-day {sup 232}Pa and 2.1-day {sup 238}Np from 0.01 eV to 40 keV at the LANSCE facility, and have carried out a preliminary resonance analysis of the observed structure and of the thermal region, with a 1/v representation above a few eV. In the present study, we calculate the reaction rates of these two species and {sup 247}Cm in a 'resonance reactor', an accelerator-driven assembly whose slowing-down properties are well known. Our model is a 1.8 m{sup 3} block of lead with a helium-cooled tungsten target in the center, i.e., the Rensselaer Intense Neutron Source (RINS). We include the effects of adding moderator outside an idealized lead slowing-down assembly, giving resonance enhancement factors for {sup 232}Pa and {sup 238}Np, and present parameters for the accelerator required to drive such an assembly to accomplish actinide burnup of these species.

  15. Parathyroid hormone blocks the stimulatory effect of insulin-like growth factor-I on collagen synthesis in cultured 21-day fetal rat calvariae

    SciTech Connect

    Kream, B.E.; Petersen, D.N.; Raisz, L.G. )

    1990-01-01

    We examined the interaction of parathyroid hormone (PTH) and recombinant human insulin-like growth factor I (IGF-I) on collagen synthesis in 21-day fetal rat calvariae as assessed by measuring the incorporation of ({sup 3}H)proline into collagenase-digestible protein. After 96 hours of culture, 10 nM PTH antagonized the stimulation of collagen synthesis and partially blocked the increase in dry weight produced by 10 nM IGF-I. The effect of PTH to block IGF-I stimulated collagen synthesis was observed in the central bone of calvariae and was mimicked by forskolin and phorbol 12-myristate 13-acetate, but not by 1,25-dihydroxyvitamin D3, transforming growth factor-alpha or dexamethasone. Our data are consistent with the concept that the direct effect of PTH is to inhibit basal CDP labeling and fully oppose IGF-I stimulated CDP labeling. The finding that this effect of PTH is mimicked by forskolin and PMA suggests that this block in IGF-I stimulation of CDP labeling involves both cAMP and protein kinase C mediated pathways.

  16. Cholesterol reduction and lack of genotoxic or toxic effects in mice after repeated 21-day oral intake of lemongrass (Cymbopogon citratus) essential oil.

    PubMed

    Costa, Celso A R A; Bidinotto, Lucas T; Takahira, Regina K; Salvadori, Daisy M F; Barbisan, Luís F; Costa, Mirtes

    2011-09-01

    Cymbopogon citratus (lemongrass) is currently used in traditional folk medicine. Although this species presents widespread use, there are no scientific data on its efficacy or safety after repeated treatments. Therefore, this work investigated the toxicity and genotoxicity of this lemongrass's essential oil (EO) in male Swiss mice. The single LD(50) based on a 24h acute oral toxicity study was found to be around 3500 mg/kg. In a repeated-dose 21-day oral toxicity study, mice were randomly assigned to two control groups, saline- or Tween 80 0.01%-treated groups, or one of the three experimental groups receiving lemongrass EO (1, 10 or 100mg/kg). No significant changes in gross pathology, body weight, absolute or relative organ weights, histology (brain, heart, kidneys, liver, lungs, stomach, spleen and urinary bladder), urinalysis or clinical biochemistry were observed in EO-treated mice relative to the control groups. Additionally, blood cholesterol was reduced after EO-treatment at the highest dose tested. Similarly, data from the comet assay in peripheral blood cells showed no genotoxic effect from the EO. In conclusion, our findings verified the safety of lemongrass intake at the doses used in folk medicine and indicated the beneficial effect of reducing the blood cholesterol level.

  17. Interactions on mixing diazepam with methadone or buprenorphine in maintenance patients.

    PubMed

    Lintzeris, Nicholas; Mitchell, Timothy B; Bond, Alyson; Nestor, Liam; Strang, John

    2006-06-01

    Benzodiazepine use by patients in methadone and buprenorphine substitution treatment is common, despite safety concerns regarding these drug interactions. The relative safety of diazepam use by methadone- or buprenorphine-treated patients has not been systematically examined. This study aimed to examine the effect of single diazepam doses, within normal therapeutic range (doses: 0, 10, and 20 mg), upon physiological, subjective, and performance measures in stable methadone and buprenorphine-treated patients. In a double-blind, randomized crossover design, methadone- or buprenorphine-treated patients were administered their normal opioid dose and either placebo, 10-, or 20-mg diazepam, in balanced order over 3 sessions. Eight methadone- and 8 buprenorphine-prescribed patients with no concurrent benzodiazepine dependence or significant comorbidity were recruited from an outpatient addiction clinic in London. Measures were taken at baseline and for 6 hours after dosing, and included physiological responses (pulse rate, blood pressure, pupil size, respiratory rate, and peripheral pO2), subjective drug effects (Addiction Research Center Inventory subscales, visual analog scales of strength of drug effect, drug-liking, and sedation), and performance measures (simple reaction time, cancellation task, digit symbol substitution task, and balance). The 10- and 20-mg diazepam doses resulted in comparable subjective experiences of greater sedation and strength of drug effects in both patient groups, and had minimal impact on physiological parameters. However, diazepam had greater peak effects on performance measures (simple reaction time, digit symbol substitution task, and cancellation time) in methadone-treated than in buprenorphine-treated patients. Diazepam may significantly alter the response to opioid substitution treatment with methadone or buprenorphine.

  18. Contrasting cardiovascular properties of the µ-opioid agonists morphine and methadone in the rat.

    PubMed

    Tung, Kenneth H; Angus, James A; Wright, Christine E

    2015-09-05

    Morphine and methadone share the property of μ-opioid receptor agonism yet have markedly different cardiovascular actions suggesting additional properties are at play. We investigated the i.v. dose-response relationships of the opioids on cardiovascular metameters in anaesthetised rats in the absence or presence of H1- and H2-receptor antagonism and the μ-opioid antagonist naloxone. In vitro tissue assays were employed to define more clearly cardiac and vascular mechanisms of action. Morphine (9, 30, 90mg/kg i.v.) decreased heart rate (HR) and mean arterial pressure (MAP) - responses that were blocked by naloxone pretreatment (10mg/kg i.v.). In contrast, methadone (3, 10, 30mg/kg i.v.) caused dramatic short-lived (1-3min) bradycardia, hypotension and lengthening of the QT interval before stabilising 5min after i.v. dosing. Only the steady-state responses of HR and MAP were blocked by naloxone. Mepyramine (10mg/kg i.v.) and cimetidine (100mg/kg i.v.) also blocked the naloxone-sensitive components. In isolated small mesenteric arteries precontracted by K(+) 62mM or endothelin-1, methadone (1-30μM) relaxed vessels while morphine (1-100μM) had no effect. Pretreatment with naloxone (10μM), indomethacin (30μM) or nitro-l-arginine (100μM) did not affect the relaxation to methadone. In rat isolated left atria, morphine and methadone inhibited inotropic responses at high concentrations (100μM). In rat papillary muscle and right atria, methadone was more than 30 times more potent at lengthening the refractory period and slowing the atrial rate than morphine. We conclude that methadone is a potent vasodilator agent, possibly through blocking L-type calcium channels.

  19. EMERGING TECHNOLOGY REPORT: DEVELOPMENT OF A PHOTOTHERMAL DETOXIFICATION UNIT

    EPA Science Inventory

    There has long been interest in utilizing photochemical methods for destroying hazardous organic materials. Unfortunately, the direct application of classic, low temperature photochemical processes to hazardous waste detoxification are often too slow to be practical for wide spr...

  20. Steroid toxicity and detoxification in ascomycetous fungi.

    PubMed

    Cvelbar, Damjana; Zist, Vanja; Kobal, Katja; Zigon, Dušan; Zakelj-Mavrič, Marija

    2013-02-25

    In the last couple of decades fungal infections have become a significant clinical problem. A major interest into fungal steroid action has been provoked since research has proven that steroid hormones are toxic to fungi and affect the host/fungus relationship. Steroid hormones were found to differ in their antifungal activity in ascomycetous fungi Hortaea werneckii, Saccharomyces cerevisiae and Aspergillus oryzae. Dehydroepiandrosterone was shown to be the strongest inhibitor of growth in all three varieties of fungi followed by androstenedione and testosterone. For their protection, fungi use several mechanisms to lower the toxic effects of steroids. The efficiency of biotransformation in detoxification depended on the microorganism and steroid substrate used. Biotransformation was a relatively slow process as it also depended on the growth phase of the fungus. In addition to biotransformation, steroid extrusion out of the cells contributed to the lowering of the active intracellular steroid concentration. Plasma membrane Pdr5 transporter was found to be the most effective, followed by Snq2 transporter and vacuolar transporters Ybt1 and Ycf1. Proteins Aus1 and Dan1 were not found to be involved in steroid import. The research of possible targets of steroid hormone action in fungi suggests that steroid hormones inhibit ergosterol biosynthesis in S. cerevisiae and H. werneckii. Results of this inhibition caused changes in the sterol content of the cellular membrane. The presence of steroid hormones most probably causes the degradation of the Tat2 permease and impairment of tryptophan import.

  1. Chronic pain and ultrarapid opioid detoxification.

    PubMed

    Kaye, Alan D; Banister, Ron E; Hoover, Jason M; Baluch, Amir R; Jacobs, Scott; Shah, Rinoo V

    2005-03-01

    Availability of opiate substances through physicians and on the street has led to a rise in dependence and in addiction resulting in countless numbers of people hooked on these drugs. Long-term use of these agents results in reduction of endogenous supply of opiate replaced by these exogenous compounds. A technique known as Ultrarapid Detoxification (UROD) has been developed and appears more promising than conventional modalities. UROD has been modified over 3 decades resulting in a safe and an effective general anesthetic that results in hemodynamically stable withdrawal without manifestation of central nervous system hyperarousal. A cornerstone of this technique involves clonidine, which stimulates reuptake of catecholamines and allows for large doses of opioid antagonist to be delivered without significant changes in heart rate or blood pressure, displacing the opiate. Though techniques vary from center to center, safety should be paramount with the technique performed in an intensive care unit with trained professional anesthesiologists. Psychosocial issues should be evaluated by a trained addictionalist and most people will succeed from the UROD procedure without experiencing the horrible withdrawal syndrome. Patients must have realistic goals and be prepared to deal with psychosocial issues post-procedure.

  2. Engineered photocatalysts for detoxification of waste water

    SciTech Connect

    Majumder, S.A.; Prairie, M.R.; Shelnutt, J.A.; Khan, S.U.M.

    1996-12-01

    This report describes progress on the development of engineered photocatalysts for the detoxification of water polluted with toxic organic compounds and heavy metals. We examined a range of different oxide supports (titania, alumina, magnesia and manganese dioxide) for tin uroporphyrin and investigated the efficacy of a few different porphyrins. A water-soluble octaacetic-acid-tetraphenylporphyrin and its derivatives have been synthesized and characterized in an attempt to design a porphyrin catalyst with a larger binding pocket. We have also investigated photocatalytic processes on both single crystal and powder forms of semiconducting SiC with an ultimate goal of developing a dual-semiconductor system combining TiO{sub 2} and SiC. Mathematical modeling was also performed to identify parameters that can improve the efficiency of SiC-based photocatalytic systems. Although the conceptual TiO{sub 2}/SiC photodiode shows some promises for photoreduction processes, SiC itself was found to be an inefficient photocatalyst when combined with TiO{sub 2}. Alternative semiconductors with bandgap and band potentials similar to SiC should be tested in the future for further development and a practical utilization of the dual photodiode concept.

  3. Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats

    PubMed Central

    Fadaei-Kenarsary, Meisam; Farbood, Yaghoob; Taghi Mansouri, Seyed Mohammad; Fathi Moghaddam, Hadi

    2015-01-01

    Introduction: Methadone has been used as a drug to detoxify opioid tolerance. Naloxane precipitated morphine withdrawal behaviours were attenuated by venlafaxine as an antidepressant. On the contrary, after detoxifying the opioids, spontaneous withdrawal syndrome may occur with pain sensitivity. Therefore the present study aimed to examine the effects of chronic methadone (70 mg/kg, in drinking water, 7 days), venlafaxine (80 mg/kg/day, intraperitoneally, 7 days) and their combinations with the spontaneous morphine withdrawal syndrome and pain sensitivity. Methods: Twenty eight young male Sprague-Dawley rats were randomly divided into 4 groups: control, venlafaxine treated, methadone treated and venlafaxine + methadone treated. Morphine sulfate (10 mg/kg/day, subcutaneously, 4 days) was injected to all animals. Then primary withdrawal behaviours and tail flick test were performed. The test was then followed by methadone or its vehicle administration. Second intervention was venlafaxine or its vehicle injection. Then final withdrawal behaviours and tail flick test were performed. Results: Combination of chronic methadone substitution and venlafaxine administration, significantly reduced freezing behaviour of spontaneous morphine withdrawal syndrome (P<0.01, 379±144%). Chronic methadone administration (P<0.05, 35±8% difference with venlafaxine treated group) induced hyperalgesia. A positive correlation (P=0.001, +63%) was observed between the animals final freezing scores and their response latencies to the painful stimulus. Discussion: Combination of chronic methadone and venlafaxine administrations reduces freezing withdrawal behaviour. Further investigations on analgesic interventions are needed to overcome this hyperalgesia. PMID:27504153

  4. "I Kicked the Hard Way. I Got Incarcerated." Withdrawal from Methadone During Incarceration and Subsequent Aversion to Medication Assisted Treatments.

    PubMed

    Maradiaga, Jeronimo A; Nahvi, Shadi; Cunningham, Chinazo O; Sanchez, Jennifer; Fox, Aaron D

    2016-03-01

    Incarceration is a common experience for individuals with opioid use disorder, including those receiving medication assisted treatments (MAT), such as buprenorphine or methadone. In the United States, MAT is rarely available during incarceration. We were interested in whether challenges with methadone maintenance treatment during incarceration affected subsequent attitudes toward MAT following release. We conducted semi-structured interviews with 21 formerly incarcerated individuals with opioid use disorder in community substance abuse treatment settings. Interviews were audio recorded, transcribed, and analyzed using a grounded theory approach. Themes that emerged upon iterative readings of transcripts were discussed by the research team. The three main themes relating to methadone were: 1) rapid dose reduction during incarceration; 2) discontinuity of methadone during incarceration; and 3) post incarceration aversion to methadone. Participants who received methadone maintenance treatment prior to incarceration reported severe and prolonged withdrawal symptoms from rapid dose reductions or disruption of their methadone treatment during incarceration. The severe withdrawal during incarceration contributed to a subsequent aversion to methadone and adversely affected future decisions regarding reengagement in MAT. Though MAT is the most efficacious treatment for opioid use disorder, current penal policy, which typically requires cessation of MAT during incarceration, may dissuade individuals with opioid use disorder from considering and engaging in MAT after release from incarceration.

  5. Antinociceptive effects of high-dose remifentanil in male methadone-maintained patients.

    PubMed

    Hay, Justin L; White, Jason M; Bochner, Felix; Somogyi, Andrew A

    2008-10-01

    The treatment of acute pain in patients maintained on methadone is difficult due to increased pain sensitivity (hyperalgesia) and cross-tolerance to other opioids. This study aimed to investigate whether remifentanil elicits antinociception in methadone-maintained subjects in a dose-dependent manner. Eight chronic methadone-maintained subjects attended the testing session approximately 20 h after their normal methadone dose (range 50-110 mgday(-1)). Following a 20 min saline infusion, subjects were administered intravenous remifentanil in seven increasing doses ranging from 0.5 to 3.5 microgkg(-1)min(-1), each for 2 0min. Testing was performed in the last 10 min of each infusion. The testing measures included nociception, as measured by the cold pressor test, withdrawal using the subjective opiate withdrawal scale (SOWS), and subjective opioid effects using the morphine-benzedrine group scale (MBG). Results showed dose-dependent increase in cold pressor tolerance time from baseline of 15.6+/-3.5 (mean+/-SEM)s up to 77.3+/-24.7s during this dosing protocol. During the infusion typical mu-opioid receptor agonist side effects were observed, but with no withdrawal. Methadone-maintained patients demonstrate significant tolerance to remifentanil and may require opioid doses 20-30 higher than required for the treatment of acute pain in opioid-naïve patients.

  6. Impulsivity in men with prescription of benzodiazepines and methadone in prison.

    PubMed

    Moreno-Ramos, Luis; Fernández-Serrano, María José; Pérez-García, Miguel; Verdejo-García, Antonio

    2016-06-14

    Benzodiazepines and methadone use has been associated with various neuropsychological impairments. However, to the best of our knowledge, no studies have been carried out on the effect of these substances (either separately or combined) on impulsive personality, including studies in prisoners. The aim of this study is to examine the impulsive personality of a sample of 134 male prisoners using the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (Torrubia, Avila, Molto, & Caseras, 2001) and the UPPS-P Scale (Cyders et al., 2007). Some of these were methadone users, methadone and benzodiazepines users, polydrug users in abstinence and non-dependent drug users. The results showed that drug users have greater sensitivity to reward, positive urgency, negative urgency and sensation seeking than non-dependent users. Methadone users showed more sensitivity to punishment and lack of perseverance with respect to other users. No differences were found between methadone+benzodiazepines users and other groups. The secondary aim is to examine which impulsive personality dimensions are related to the two motivational systems proposed by Gray (BIS-BAS) using exploratory factor analysis. Results showed two different components. One component was defined by the subscales sensitivity to reinforcement, positive urgency, negative urgency and sensation seeking. The second component was defined by the subscales sensitivity to punishment, lack of perseverance and lack of premeditation.

  7. Methadone diversion as a protective strategy: the harm reduction potential of 'generous constraints'.

    PubMed

    Harris, Magdalena; Rhodes, Tim

    2013-11-01

    Methadone maintenance treatment is evidenced as a successful harm reduction initiative in regard to the prevention of blood borne viruses and other injecting related harms. This is attributable to reductions in heroin use and injecting equipment sharing incidents, yet the means by which these are achieved are rarely elaborated. Methadone diversion is predominantly presented in a negative light; associated with overdose and other harms. In our qualitative London-based study with 37 people who inject drugs, 35 on substitution therapies, we found that methadone self regulation and diversion played a prominent role in helping participants to manage their drug use, prevent withdrawal, cement social relationships, and inadvertently protect against hepatitis C transmission. The ability of participants to enact these 'indigenous harm reduction strategies' was constrained to various degrees by their treatment dosing protocols. In this article we explore the strategies participants enacted with methadone, the role of 'generous constraints' in this enactment and the associated production and reduction of risk. In order to reengage people who inject drugs with harm reduction interventions, it is necessary for initiatives to take stock of the indigenous strategies that individuals are already utilising and - in the case of methadone self regulation - support them by the implementation of more generous constraints.

  8. The comparative toxicology and major organ pathology of fatal methadone and heroin toxicity cases.

    PubMed

    Darke, Shane; Duflou, Johan; Torok, Michelle

    2010-01-01

    In order to determine the comparative toxicology and systemic disease of cases of death due to methadone and heroin toxicity, 1193 coronial cases of opioid overdose that occurred in New South Wales, Australia between 1 January 1998 and 31 December 2007 were inspected. These comprised 193 cases in which cause of death involved methadone toxicity (METH) and 1000 cases in which cause of death involved heroin toxicity in the absence of methadone (HER). METH cases were significantly more likely to have benzodiazepines (63.7% vs. 32.2%), and less likely to have alcohol (23.6% vs. 42.7%) detected. METH cases were significantly more likely to be diagnosed with pre-existing systemic pathology (94.3% vs. 79.9%), and multiple organ system pathology (68.8% vs. 41.4%). Specifically, METH cases were more likely to have cardiac (58.9% vs. 34.5%), pulmonary (53.6% vs. 30.9%), hepatic (80.7% vs. 62.8%) and renal (25.0% vs. 9.5%) disease. Given the notable differences in toxicology and disease patterns, great caution appears warranted in prescribing benzodiazepines to methadone users, and regular physical examinations of methadone treatment patients would appear clinically warranted.

  9. Methadone N-demethylation by the common CYP2B6 allelic variant CYP2B6.6.

    PubMed

    Gadel, Sarah; Crafford, Amanda; Regina, Karen; Kharasch, Evan D

    2013-04-01

    The long-acting opioid methadone displays considerable unexplained interindividual pharmacokinetic variability. Methadone metabolism clinically occurs primarily by N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), catalyzed predominantly by CYP2B6. Retrospective studies suggest that the common allele variant CYP2B6*6 may influence methadone plasma concentrations. The catalytic activity of CYP2B6.6, encoded by CYP2B6*6, is highly substrate-dependent. This investigation compared methadone N-demethylation by CYP2B6.6 with that by wild-type CYP2B6.1. Methadone enantiomer and racemate N-demethylation by recombinant-expressed CYP2B6.6 and CYP2B6.1 was determined. At substrate concentrations (0.25-2 µM) approximating plasma concentrations occurring clinically, rates of methadone enantiomer N-demethylation by CYP2B6.6, incubated individually or as the racemate, were one-third to one-fourth those by CYP2B6.1. For methadone individual enantiomers and metabolism by CYP2B6.6 compared with CYP2B6.1, Vmax was diminished, Ks was greater and the in vitro intrinsic clearance was diminished 5- to 6-fold. The intrinsic clearance for R- and S-EDDP formation from racemic methadone was diminished approximately 6-fold and 3-fold for R- and S-methadone, respectively. Both CYP2B6.6 and CYP2B6.1 showed similar stereoselectivity (S>R-methadone). Human liver microsomes with diminished CYP2B6 content due to a CYP2B6*6 allele had lower rates of methadone N-demethylation. Results show that methadone N-demethylation catalyzed by CYP2B6.6, the CYP2B6 variant encoded by the CYP2B6*6 polymorphism, is catalytically deficient compared with wild-type CYP2B6.1. Diminished methadone N-demethylation by CYP2B6.6 may provide a mechanistic explanation for clinical observations of altered methadone disposition in individuals carrying the CYP2B6*6 polymorphism.

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

    PubMed

    Levran, Orna; Peles, Einat; Hamon, Sara; Randesi, Matthew; Adelson, Miriam; Kreek, Mary Jeanne

    2013-07-01

    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.

  11. Current knowledge of detoxification mechanisms of xenobiotic in honey bees.

    PubMed

    Gong, Youhui; Diao, Qingyun

    2017-01-01

    The western honey bee Apis mellifera is the most important managed pollinator species in the world. Multiple factors have been implicated as potential causes or factors contributing to colony collapse disorder, including honey bee pathogens and nutritional deficiencies as well as exposure to pesticides. Honey bees' genome is characterized by a paucity of genes associated with detoxification, which makes them vulnerable to specific pesticides, especially to combinations of pesticides in real field environments. Many studies have investigated the mechanisms involved in detoxification of xenobiotics/pesticides in honey bees, from primal enzyme assays or toxicity bioassays to characterization of transcript gene expression and protein expression in response to xenobiotics/insecticides by using a global transcriptomic or proteomic approach, and even to functional characterizations. The global transcriptomic and proteomic approach allowed us to learn that detoxification mechanisms in honey bees involve multiple genes and pathways along with changes in energy metabolism and cellular stress response. P450 genes, is highly implicated in the direct detoxification of xenobiotics/insecticides in honey bees and their expression can be regulated by honey/pollen constitutes, resulting in the tolerance of honey bees to other xenobiotics or insecticides. P450s is also a key detoxification enzyme that mediate synergism interaction between acaricides/insecticides and fungicides through inhibition P450 activity by fungicides or competition for detoxification enzymes between acaricides. With the wide use of insecticides in agriculture, understanding the detoxification mechanism of insecticides in honey bees and how honeybees fight with the xenobiotis or insecticides to survive in the changing environment will finally benefit honeybees' management.

  12. Indicators of Buprenorphine and Methadone Use and Abuse: What Do We Know?

    PubMed Central

    Maxwell, Jane Carlisle; McCance-Katz, Elinore F.

    2013-01-01

    Abuse of prescription opioids is a growing problem. The number of methadone pain pills distributed now exceeds liquid methadone used in opioid treatment, and the increases in buprenorphine indicators provide evidence of the need to monitor and intervene to decrease the abuse of this drug. The need for additional and improved data to track trends is discussed, along with findings as to the characteristics of the users and combinations of drugs. Data on toxicities related to methadone or buprenorphine, particularly in combination with other prescribed drugs, are presented and clinical implications and considerations are offered. These findings underscore the need for physicians to be aware of potential toxicities and to educate their patients regarding these issues. PMID:20132124

  13. [Accidental ingestion of methadone by children and suggestions for better prevention].

    PubMed

    Hein, Henrik; Püschel, Klaus; Schaper, Andreas; Iwersen-Bergmann, Stefanie

    2016-01-01

    Despite the medial attention attracted by the presented case in January 2012 and the determined measures taken to minimize the risk of accidental poisoning for children in the direct surroundings of substituted persons, we recently faced two more cases of methadone-intoxicated children in Hamburg. We believe that the most important step to increase awareness of the dangerous effects of methadone for children might be the storage of methadone in lockable boxes, which would make it safe from access by children and third parties. Moreover this way of storing reminds the patients of the risks resulting from their medication. Repeated and comprehensive instruction appears to be the best protection against cases like this to counteract careless handling of the substitution medication.

  14. A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction.

    PubMed

    Neumann, Anne M; Blondell, Richard D; Jaanimägi, Urmo; Giambrone, Amanda K; Homish, Gregory G; Lozano, Jacqueline R; Kowalik, Urszula; Azadfard, Mohammadreza

    2013-01-01

    Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction.

  15. Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis.

    PubMed

    Perez-Alvarez, Sergio; Cuenca-Lopez, Maria D; de Mera, Raquel M Melero-Fernández; Puerta, Elena; Karachitos, Andonis; Bednarczyk, Piotr; Kmita, Hanna; Aguirre, Norberto; Galindo, Maria F; Jordán, Joaquin

    2010-11-01

    Methadone is a widely used therapeutic opioid in narcotic addiction and neuropathic pain syndromes. Oncologists regularly use methadone as a long-lasting analgesic. Recently it has also been proposed as a promising agent in leukemia therapy, especially when conventional therapies are not effective. Nevertheless, numerous reports indicate a negative impact on human cognition with chronic exposure to opiates. Thus, clarification of methadone toxicity is required. In SH-SY5Y cells we found that high concentrations of methadone were required to induce cell death. Methadone-induced cell death seems to be related to necrotic processes rather than typical apoptosis. Cell cultures challenged with methadone presented alterations in mitochondrial outer membrane permeability. A mechanism that involves Bax translocation to the mitochondria was observed, accompanied with cytochrome c release. Furthermore, no participation of known protein regulators of apoptosis such as Bcl-X(L) and p53 was observed. Interestingly, methadone-induced cell death took place by a caspases-independent pathway; perhaps due to its ability to induce a drastic depletion in cellular ATP levels. Therefore, we studied the effect of methadone on isolated rat liver mitochondria. We observed that methadone caused mitochondrial uncoupling, coinciding with the ionophoric properties of methadone, but did not cause swelling of the organelles. Overall, the effects observed for cells in the presence of supratherapeutic doses of methadone may result from a "bioenergetic crisis." A decreased level of cellular energy may predispose cells to necrotic-like cell death.

  16. Promethazine Misuse among Methadone Maintenance Patients and Community-Based Injection Drug Users

    PubMed Central

    Shapiro, Brad J.; Lynch, Kara L.; Toochinda, Tab; Lutnick, Alexandra; Cheng, Helen Y.; Kral, Alex H.

    2013-01-01

    Objective Promethazine has been reported to be misused in conjunction with opioids in several settings. Promethazine misuse by itself or in conjunction with opioids may have serious adverse health effects. To date, no prevalence data for the nonmedical use of promethazine has been reported. This study examines the prevalence and correlates of promethazine use in two different populations in San Francisco, California, USA: methadone maintenance clinic patients and community-based injection drug users (IDUs). Methods We analyzed urine samples for the presence of promethazine and reviewed the clinical records for 334 methadone maintenance patients at the county methadone clinic. Separately, we used targeted sampling methods to recruit and survey 139 community-based opioid IDUs about their use of promethazine. We assessed prevalence and factors associated with promethazine use with bivariate and multivariate statistics. Results The prevalence of promethazine positive urine samples among the methadone maintenance patients was 26 percent. Only 15 percent of promethazine positive patients had an active prescription for promethazine. Among IDUs reporting injection of opiates in the community-based survey, 17 percent reported having used promethazine in the past month; 24 percent of the IDUs who reported being enrolled in methadone treatment reported using promethazine in the past month. Conclusions The finding that one quarter of methadone maintenance patients in a clinic or recruited in community settings have recently used promethazine provides compelling evidence of significant nonmedical use of promethazine in this patient population. Further research is needed to establish the extent and nature of nonmedical use of promethazine. PMID:23385449

  17. Emergence of Methadone as a Street Drug in St. Petersburg, Russia

    PubMed Central

    Heimer, Robert; Lyubimova, Aleksandra; Barbour, Russell; Levina, Olga S.

    2015-01-01

    Background The syndemic of opioid addiction, HIV, hepatitis, tuberculosis, imprisonment, and overdose in Russia has been worsened by the illegality of opioid substitution therapy. As part of on-going serial studies, we sought to explore the influence of opioid availability on aspects of the syndemic as it has affected the city of St. Petersburg. Methods We employed a sequential approach in which quantitative data collection and statistical analysis were followed by a qualitative phase. Quantitative data were obtained from a respondent-driven sample (RDS) of people who inject drugs (PWID) obtained in 2012–13. Individuals recruited by RDS were tested for antibodies to HIV and interviewed about drug use and injection practices, sociodemographics, health status, and access to medical care. Subsequently, we collected in-depth qualitative data on methadone use, knowledge, and market availability from PWID recruited at nine different locations within St. Petersburg. Results Analysis of interview data from the sample revealed he percentage of PWID injecting methadone in the 30 days prior to interview increased from 3.6% in 2010 to 53.3% in 2012–13. Injection of only methadone, as compared to injecting only heroin or both drugs, was associated with less frequent injection and reduced HIV-related injected risk, especially a lower rate of injecting with a previously used syringe. In-depth questioning of methadone injectors corroborated the finding from serial quantitative surveys of PWID that methadone’s black market availability is a recent phenomenon. Spatial analysis revealed widespread methadone availability but no concentration in any specific districts of the city. Conclusion Despite the prohibition of substitution therapy and demonization of methadone, the drug has emerged to rival heroin as the most commonly available opioid in St. Petersburg. Ironically, its use is associated with reduced injection-related HIV risk even when its use is illegal. PMID:26573380

  18. Functional impact of ABCB1 variants on interactions between P-glycoprotein and methadone.

    PubMed

    Hung, Chin-Chuan; Chiou, Mu-Han; Teng, Yu-Ning; Hsieh, Yow-Wen; Huang, Chieh-Liang; Lane, Hsien-Yuan

    2013-01-01

    Methadone is a widely used substitution therapy for opioid addiction. Large inter-individual variability has been observed in methadone maintenance dosages and P-glycoprotein (P-gp) was considered to be one of the major contributors. To investigate the mechanism of P-gp's interaction with methadone, as well as the effect of genetic variants on the interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established in the present study. The RNA and protein expression levels of human P-gp were confirmed by real-time quantitative RT-PCR and western blot, respectively. Utilizing rhodamine 123 efflux assay and calcein-AM uptake study, methadone was demonstrated to be an inhibitor of wild-type human P-gp via non-competitive kinetic (IC50 = 2.17±0.10 µM), while the variant-type human P-gp, P-gp with 1236T-2677T-3435T genotype and P-gp with 1236T-2677A-3435T genotype, showed less inhibition potency (IC50 = 2.97±0.09 µM and 4.43±1.10 µM, respectively) via uncompetitive kinetics. Methadone also stimulated P-gp ATPase and inhibited verapamil-stimulated P-gp ATPase activity under therapeutic concentrations. These results may provide a possible explanation for higher methadone dosage requirements in patients carrying variant-type of P-gp and revealed the possible drug-drug interactions in patients who receive concomitant drugs which are also P-gp substrates.

  19. Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity

    PubMed Central

    Mouly, Stéphane; Bloch, Vanessa; Peoc'h, Katell; Houze, Pascal; Labat, Laurence; Ksouda, Kamilia; Simoneau, Guy; Declèves, Xavier; Bergmann, Jean Francois; Scherrmann, Jean-Michel; Laplanche, Jean-Louis; Lepine, Jean-Pierre; Vorspan, Florence

    2015-01-01

    Aims Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients. Methods Eighty-one stable patients (60 men and 21 women, 43.7 ± 8.1 years old, 63.1 ± 50.9 mg day−1 methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, R,S-methadone trough concentration and clinically significant polymorphisms of the OPRM1, DRD2, COMT, ABCB1, CYP2B6, CYP3A5, CYP2C19 and CYP2D6 genes. Results Methadone maintenance dose was correlated to the highest dose ever used (r2 = 0.57, P < 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27–18.6, P = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01–2.44, P = 0.04), history of cocaine dependence (80 vs. 44 mg day−1 in never-addict patients, P = 0.005) and ethnicity (Asian > Caucasian > African, P = 0.04) were independently associated with high-dose methadone in multiple regression analysis. A modest correlation was observed between liver/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [rs] = 0.21, P = 0.06) but not with highest dose ever used (rs = 0.15, P = 0.18) or dose-normalized R,S-methadone trough concentrations (rs = −0.05, P = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and R,S-methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose. Conclusions Methadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver/intestinal CYP

  20. Opiate-addicted parents in methadone treatment: long-term recovery, health, and family relationships.

    PubMed

    Skinner, Martie L; Haggerty, Kevin P; Fleming, Charles B; Catalano, Richard F; Gainey, Randy R

    2011-01-01

    Few studies follow the lives of opiate-addicted parents. The authors examined a 12-year follow-up of 144 parents in methadone treatment and their 3- to 14-year-old children. Parent mortality was high. Among survivors, drug use and treatment, incarceration, residential and family disruptions, and health problems were common. Moderate and long-term recovery were associated with consistent methadone treatment, further education, employment, and fewer relationship disruptions. Earlier depression, deviant friends, and poor coping skills predicted continued drug problems. Thus, interventions should include treatment for depression and build skills for avoiding and refusing drugs, coping with stress, and maintaining recovery-supportive friendships.

  1. The effect of maternal methadone use on the fetal heart pattern: a computerised CTG analysis.

    PubMed

    Navaneethakrishnan, R; Tutty, S; Sinha, C; Lindow, S W

    2006-08-01

    Using a computerised analysis, the cardiotocograph (CTG) from women who use methadone (n= 25) when compared with women who do not use methadone (n= 25) showed a significant reduction in the fetal heart baseline rate, with a significant reduction in number of accelerations and episodes of high variation. The short-term variation, number of decelerations and episodes of low variation were not different between the two groups. The time taken to meet the standardised criteria was not different, and it is possible that a computer-assisted CTG analysis could be more accurate than a naked eye interpretation.

  2. Opiate-addicted Parents in Methadone Treatment: Long-term Recovery, Health and Family Relationships

    PubMed Central

    Skinner, Martie L.; Haggerty, Kevin P.; Fleming, Charles B.; Catalano, Richard F.; Gainey, Randy R.

    2011-01-01

    Few studies follow the lives of opiate-addicted parents. We examine a 12-year follow-up of 144 parents in methadone treatment and their 3- to 14-year-old children. Parent mortality was high. Among survivors, drug use and treatment, incarceration, residential and family disruptions, and health problems were common. Moderate and long-term recovery were associated with consistent methadone treatment, further education, employment, and fewer relationship disruptions. Earlier depression, deviant friends, and poor coping skills predicted continued drug problems. Thus, interventions should include treatment for depression and build skills for avoiding and refusing drugs, coping with stress, and maintaining recovery-supportive friendships. PMID:21218307

  3. Voucher-based contingent reinforcement of smoking abstinence among methadone-maintained patients: a pilot study.

    PubMed

    Dunn, Kelly E; Sigmon, Stacey C; Thomas, Colleen S; Heil, Sarah H; Higgins, Stephen T

    2008-01-01

    This study evaluated the efficacy of a contingency management (CM) intervention to promote smoking cessation in methadone-maintained patients. Twenty participants, randomized into contingent (n=10) or noncontingent (n=10) experimental conditions, completed the 14-day study. Abstinence was determined using breath carbon monoxide and urine cotinine levels. Contingent participants received voucher-based incentives for biochemical evidence of smoking abstinence. Noncontingent participants earned vouchers independent of smoking status. Contingent participants achieved significantly more smoking abstinence and longer durations of continuous smoking abstinence than did noncontingent participants. These results support the potential efficacy of using voucher-based CM to promote smoking cessation among methadone-maintained patients.

  4. Open, multicenter comparison of efficacy, cycle control, and tolerability of a 23-day oral contraceptive regimen with 20 microg ethinyl estradiol and 75 microg gestodene and a 21-day regimen with 20 microg ethinyl estradiol and 150 microg desogestrel.

    PubMed

    Endrikat, J; Cronin, M; Gerlinger, C; Ruebig, A; Schmidt, W; Düsterberg, B

    2001-09-01

    This prospective, open, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day regimen with 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) and a 21-day regimen with 20 microg EE and 150 microg desogestrel (DSG). Participants took either 23 tablets with active substances plus 5 placebo tablets (23-day EE/GSD) or 21 tablets with active substances followed by 7 days without pill-taking (21-day EE/DSG). Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 5967 treatment cycles (23-day EE/GSD: 2975 cycles; 21-day EE/DSG: 2992 cycles) were obtained from 890 participants (445 in each group). Both preparations proved to be effective contraceptives and provided good cycle control. No pregnancy during treatment was recorded. This resulted in a study Pearl Index of 0.0 for both treatments. For 23-day EE/GSD, 32.4% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 31.5% for 21-day EE/DSG. In the 23-day EE/GSD group, intracyclic bleeding episodes were reported by 48.8% of the participants in Cycle 1 but in only 15.1% in Cycle 7, and in the 21-day regimen group by 43.4% in Cycle 1 and only 14.2% in Cycle 7. Overall, intracyclic bleeding was reported in 20.9% of cycles for both treatments.A greater number of 23-day EE/GSD participants had shorter withdrawal bleeding periods than with 21-day EE/DSG. In significantly (p <0.0001) more cycles in the 23-day EE/GSD group participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day EE/DSG group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day EE/GSD group was 4 days and in the 21-day EE/DSG group 5 days. Both preparations were well tolerated and showed a similar adverse events pattern. The discontinuation rate because of adverse events was

  5. Application of electrolysis for detoxification of an antineoplastic in urine.

    PubMed

    Kobayashi, Toyohide; Hirose, Jun; Sano, Kouichi; Kato, Ryuji; Ijiri, Yoshio; Takiuchi, Hiroya; Tanaka, Kazuhiko; Goto, Emi; Tamai, Hiroshi; Nakano, Takashi

    2012-04-01

    Antineoplastics in excreta from patients have been considered to be one of the origins of cytotoxic, carcinogenic, teratogenic, and mutagenic contaminants in surface water. Recent studies have demonstrated that antineoplastics in clinical wastewater can be detoxified by electrolysis. In this study, to develop a method for the detoxification of antineoplastics in excreta, methotrexate solution in the presence of human urine was electrolyzed and evaluated. We found that urine inhibits detoxification by electrolysis; however, this inhibition decreased by diluting urine. In urine samples, the concentrations of active chlorine generated by anodic oxidation from 0.9% NaCl solution for inactivation of antineoplastics increased in dilution-dependent and time-dependent manner. These results indicate that electrolysis with platinum-based iridium oxide composite electrode is a possible method for the detoxification of a certain antineoplastic in urine.

  6. A novel nonconcentrating reactor for solar water detoxification

    SciTech Connect

    Well, M. van; Dillert, R.H.G.; Bahnemann, D.W.; Benz, V.W.; Mueller, M.A.

    1997-05-01

    The photocatalytic degradation of organic compounds using titanium dioxide is a promising method for the clean up of polluted water, especially if the sun is used as the light source. In this paper a novel double-skin sheet reactor made of Plexiglas{reg_sign}, able to use diffuse as well as direct sunlight, is introduced. To characterize this novel photochemical reactor for solar water detoxification, degradation experiments were performed using dichloroacetic acid as a model compound and varying the type of catalyst and its concentration. Moreover, the content of molecular oxygen of the suspension was varied systematically. Photonic efficiencies up to 13% were achieved in these experiments in very good agreement with those of corresponding experiments performed under idealized laboratory conditions. Photocatalytic detoxification experiments with ground water contaminated with nitro aromatic compounds from a World War II ammunition plant proved that this reactor can indeed be employed for the solar detoxification of realistic contaminated water.

  7. Microsomal detoxification enzymes in yam bean [Pachyrhizus erosus (L.) urban].

    PubMed

    Belford, Ebenezer J D; Dörfler, Ulrike; Stampfl, Andreas; Schröder, Peter

    2004-01-01

    Cytochrome P450s and glutathione-S-transferases (GSTs) constitute two of the largest groups of enzyme families that are responsible for detoxification of exogenous molecules in plants. Their activities differ from plant to plant with respect to metabolism and substrate specificity which is one of the reasons for herbicide selectivity. In the tuber forming yam bean, the legume Pachyrhizus erosus, their activities at the microsomal level were investigated to determine the detoxification status of the plant. The breakdown of the herbicide isoproturon (IPU) to two distinct metabolites, 1-OH-IPU and monodesmethyl-IPU, was demonstrated. GST activity was determined with model substrates, but also by the catalysed formation of the fluorescent glutathione bimane conjugate. This study demonstrates for the first time microsomal detoxification activity in Pachyrhizus and the fluorescence image description of microsomal GST catalysed reaction in a legume.

  8. Quality of Life in Methadone Maintenance Treated Patients in Iran

    PubMed Central

    Aghayan, Shahrokh; Amiri, Mohammad; Chaman, Reza; Khosravi, Ahmad

    2015-01-01

    Background: Measurement of life quality as an index of health status has a widespread application in health care domain. Objectives: The current study aimed to determine the quality of life of referents to addiction cessation centers of Iran. Patients and Methods: In this cross-sectional study, 988 addicts who had referred to addiction cessation centers in Shahroud were studied through SF-36 questionnaire. The data were analyzed using linear regression in structural equation modeling and STATA 12 statistical software. Results: The mean ± SD age of the participants was 41.2 ± 11.8 years. Most of the referents used smoking followed by eating method of opium abuse. The mean ± SD score of life quality was 67.8 ± 17.2, the mean ± SD score of life quality in physical health dimension was 76.9 ± 26.7, and the mean ± SD score in mental health dimension was 64.5 ± 18.4. Univariate analysis showed a significant relationship between life quality and gender, place of residence, education, occupation, marital status, and income (P ≤ 0.05). However, in multivariate analysis a significant relationship was observed only between gender, socioeconomic status, and quality of life score. Conclusions: Although most studies have reported low and weak quality of life in addicts, the findings of this study shows that the life quality score of addicts is rather good. It seems that the maintenance treatment that addicts receive in addiction cessation centers has been effective in improving the quality of life of the patients. Hence, expanding methadone treatment centers can play a leading role in the improvement of life quality in addicts. PMID:26870708

  9. [Postpartum risk factors in the development of children born to opiate-addicted mothers; comparison between mothers with and without methadone substitution].

    PubMed

    Ziegler, M; Poustka, F; von Loewenich, V; Englert, E

    2000-09-01

    In a retrospective case control study at the University of Frankfurt, Germany, 101 babies born to opiate-addicted mothers were identified from birth charts from 1988 to 1995. After birth, they developed a withdrawal syndrome (neonatal abstinence syndrome). Fifty control infants and their mothers were selected from neonatal wards. The group of opiate-exposed babies was subdivided into a group born to mothers without methadone treatment (n = 48) and a group born to mothers who were enrolled in a methadone program (n = 51). The methadone infants had a significantly higher mean birth weight (2822 g) than children in the group without methadone (2471 g). The abstinence syndrome was much more intense in the methadone group (convulsions 47.1%) than in heroin-exposed babies without methadone treatment (convulsions 27.1%). Women in methadone maintenance programs lived in more stable socioeconomic conditions than opiate-addicted women without methadone substitution. Moreover, they cared significantly better for their babies: 81.3% of the methadone mothers visited their children on a regular basis and 90.9% cared adequately. The data emphasize the need in future research to look more closely at the role of methadone treatment programs in the development of opiate-exposed babies.

  10. Decreased maternal-fetal attachment in methadone-maintained pregnant women: a preliminary study.

    PubMed

    Mikhail, M S; Youchah, J; DeVore, N; Ho, G Y; Anyaegbunam, A

    1995-01-01

    Maternal-fetal attachment represents the mother's affiliation and interaction with her unborn fetus. It develops during pregnancy and may be critical to successful mother-infant adaptation. The purpose of this study was to investigate maternal-fetal attachment in methadone-maintained pregnant women. We studied a cross-sectional sample of women (n = 67), 15 to 35 years of age, with uncomplicated, singleton pregnancies, at 28 to 37 weeks of gestation. The study population comprised two groups: group 1 consisted of 17 women enrolled in a substance abuse program who were using methadone, 40 to 80 mg a day, for a period of more than 3 months; group 2 included 50 women with no history of substance abuse. The Cranley 24-item scale was used as a measure of maternal-fetal attachment. Methadone-maintained pregnant women had diminished maternal-fetal attachment scores compared with controls (P < .05). This may be attributed to methadone use or to behavior characteristics of women with substance abuse. In either case, decreased maternal-fetal attachment may conceivably reduce women's compliance with prenatal health care, interfere with maternal adjustment during pregnancy, and/or have negative long-term effects on mother-child attachment.

  11. Respiratory consequences of methadone: the response to added resistance to breathing.

    PubMed

    Santiago, T V; Goldblatt, K; Winters, K; Pugliese, A C; Edelman, N H

    1980-10-01

    Respiratory responses to hypercapnia and added airway resistance were studied before and after methadone intake in 7 normal subjects (Group I) and 7 subjects receiving chronic methadone maintenance therapy (Group II). Before taking the drug, both groups exhibited similar ventilatory responses to CO2 without the resistance and equivalent augmentation of the airway occlusion pressure or "respiratory drive" responses to CO2 with the resistance. In Group I subjects, analgesic dosages of methadone depressed ventilation and ventilatory responsiveness to hypercapnia, and abolished the increase in respiratory drive elicited by the resistance. In contrast, patients receiving methadone maintance therapy exhibited no changes in either ventilatory responses or respiratory drive after intake of their daily doses of the drug. The data show that narcotic drugs may abolish the respiratory compensation, i.e., the enhanced ventilatory drive that accompanies increased airway resistance, although tolerance develops with chronic use. Because this compensation has been reported to play an important role in the respiratory response to diffuse obstructive disease, the findings suggested a mechanism for the frequent inordinate respiratory depressant effects of narcotic drugs in such diseases.

  12. Retention in publicly funded methadone maintenance treatment in two Western States.

    PubMed

    Deck, Dennis; Carlson, Matthew J

    2005-01-01

    This study examined individual and system characteristics associated with retention in methadone maintenance treatment among Medicaid-eligible adults in treatment for opiate use in Oregon and Washington. Logistic regression was used to examine the contributions of predisposing, need, and enabling characteristics on 365 day retention in methadone maintenance treatment. Older patients, patients with a history of methadone maintenance treatment, and persons with stable Medicaid eligibility had higher rates of retention than did patients with disabilities, polysubstance users, and those with an arrest record. In Oregon, which delivers methadone maintenance treatment through managed care, retention rose sharply from 28% to 51% between 1994 and 1998 and then leveled off. During the same time period, retention in Washington State grew from 28% to 34%. The higher rates of retention in Oregon, in part, can be explained by differences in service delivery influenced by financing. Faced with long waiting lists, Washington providers were more than twice as likely to administratively discharge patients for rule violations as their Oregon counterparts. Given the importance of retention, policies and practices that influence retention should be carefully considered. Because Medicaid eligibility has a dramatic impact on retention, policies that help extend eligibility or stabilize eligibility among individuals actively engaged in treatment should be carefully considered.

  13. Disaccharides in urine samples as markers of intravenous abuse of methadone and buprenorphine.

    PubMed

    Jungen, Hilke; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie

    2013-01-01

    Methadone and buprenorphine are commonly used as oral substitutes in opiate maintenance programs to treat persons who are dependent on heroin. During these programs, patients are not allowed to continue using illicit drugs. Abstinence can easily be monitored by urine tests with immunochemical methods. It is well known that the intravenous abuse of heroin substitutes like methadone or buprenorphine has become common as well. The methadone-prescribing physician has no opportunity to check whether the opiate maintenance treatment patient takes his substitution medicines orally as intended or continues with his intravenous misuse now substituting the methadone instead of injecting heroin. In Germany, substitutes are available as liquids and tablets that contain carbohydrates as adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is needed for pressing tablets (e.g., Methaddict® and Subutex®). In case of oral ingestion, disaccharides are broken down into monosaccharides by disaccharidases in the small intestine. These monosaccharides are absorbed into the blood stream by special monosaccharide transporters. Disaccharidases do not exist in blood, thus sucrose and lactose are not split if substitute medicines are injected intravenously. Our assumption, therefore, was that they are excreted unchanged in urine. We investigated a method for the detection of disaccharides in urine as markers of intravenous abuse of substitutes. Urine samples of 26 intravenous substitute abusers showed all positive results for lactose (76.9%) and/or sucrose (73.1%). The method is assumed to be useful to detect intravenous abuse of substitutes.

  14. Patterns in admission delays to outpatient methadone treatment in the United States.

    PubMed

    Gryczynski, Jan; Schwartz, Robert P; Salkever, David S; Mitchell, Shannon Gwin; Jaffe, Jerome H

    2011-12-01

    Waiting lists for methadone treatment have existed in many U.S. communities, but little is known nationally about what patient and service system factors are related to admission delays that stem from program capacity shortfalls. Using a combination of national data sources, this study examined patterns in capacity-related admission delays to outpatient methadone treatment in 40 U.S. metropolitan areas (N = 28,920). Patient characteristics associated with admission delays included racial/ethnic minority status, lower education, criminal justice referral, prior treatment experience, secondary cocaine or alcohol use, and co-occurring psychiatric problems. Injection drug users experienced fewer delays, as did self-pay patients and referrals from health care and addiction treatment providers. Higher community-level utilization of methadone treatment was associated with delay, whereas delays were less common in communities with higher utilization of alternative modalities. These findings highlight potential disparities in timely admission to outpatient methadone treatment. Implications for improving treatment access and service system monitoring are discussed.

  15. Characterizing Pain and Associated Coping Strategies in Methadone and Buprenorphine Maintained Patients

    PubMed Central

    Dunn, Kelly E.; Finan, Patrick H.; Tompkins, D. Andrew; Fingerhood, Michael; Strain, Eric C.

    2015-01-01

    Background Chronic pain is common among patients receiving opioid maintenance treatment (OMT) for opioid use disorder. To aid development of treatment recommendations for coexisting pain and opioid use disorder, it is necessary to characterize pain treatment needs and assess whether needs differ as a function of OMT medication. Methods A point-prevalence survey assessing pain and engagement in coping strategies was administered to 179 methadone and buprenorphine-maintained patients. Results Forty-two percent of participants were categorized as having chronic pain. Methadone patients had greater severity of pain relative to buprenorphine patients, though both groups reported high levels of interference with daily activities, and participants with pain attended the emergency room more frequently relative to participants without pain. Only 2 coping strategies were being utilized by more than 50% of participants (over-the-counter medication, prayer). Conclusions Results indicate that pain among OMT patients is common, severe, and of significant impairment. Methadone patients reported greater severity pain, particularly worse pain in the past 24 hours, though interference from pain in daily activities did not vary as a function of OMT. Most participants with pain were utilizing few evidenced-based pain coping strategies. Increasing OMT patient access to additional pain treatment strategies is an opportunity for immediate intervention, and similarities across OMT type suggest interventions do not need to be customized to methadone vs. buprenorphine patients. PMID:26518253

  16. Prize Reinforcement Contingency Management for Cocaine Dependence: Integration with Group Therapy in a Methadone Clinic

    ERIC Educational Resources Information Center

    Petry, Nancy M.; Martin, Bonnie; Simcic, Francis

    2005-01-01

    In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes…

  17. Impact of a methadone maintenance program on an Aboriginal community: a qualitative study

    PubMed Central

    Landry, Michel; Veilleux, Nadia; Arseneault, Julie-Eve; Abboud, Saneea; Barrieau, André; Bélanger, Mathieu

    2016-01-01

    Background: Methadone maintenance treatment programs implemented in Aboriginal communities have proven to be beneficial for the control of opioid addiction and its associated consequences, but the perceptions and opinions of different community members about these programs remain elusive. The goal of this study was to determine the perceptions of members of a First Nation community in New Brunswick, Canada, on the implementation of a methadone maintenance treatment program and its effects on the community. Methods: We conducted a qualitative study using semistructured focus group discussions with 3 distinct groups composed of health care professionals and influential community members, patients in the methadone maintenance treatment program and community members at large. Thematic analysis of discussion transcripts was performed. Results: A total of 22 partipants were included in the 3 focus groups. All groups of participants expressed that patients in the program are stigmatized and marginalized. Discussions also revealed widespread misconceptions about the program. Participants associated the program with improvements in community-level outcomes and in parenting abilities of patients, but also with difficulties preserving family unity. Interpretation: Despite being culturally adapted to the community, elements surrounding the methadone maintenance treatment program in this First Nation community appear to be misunderstood and stigmatized. It may be beneficial to provide community education on these programs to assure community buy-in for the successful implementation of harm reduction programs in Aboriginal communities. PMID:27730106

  18. The Relationship between Sugar-Containing Methadone and Dental Caries: A Systematic Review

    ERIC Educational Resources Information Center

    Tripathee, Sheela; Akbar, Tahira; Richards, Derek; Themessl-Huber, Markus; Freeman, Ruth

    2013-01-01

    Objectives: To review the evidence of a relationship between sugar-containing methadone and dental caries. Data sources: A systematic search of Cochrane Library, PubMed, PsychINFO, EMBASE, MEDLINE, Current Controlled Trials, WHO, OHRN, SIGLE and ERIC databases was conducted from January 1978 up to June 2010. Study selection: Articles were assessed…

  19. Pharmacogenomics study on cadherin 2 network with regard to HIV infection and methadone treatment outcome

    PubMed Central

    Kuo, Hsiang-Wei; Shih, Chia-Lung; Tsung, Jieh-Hen; Liu, Sheng-Wen; Chu, Shih-Kai; Yang, Hsin-Chou; Tsou, Hsiao-Hui; Wang, Zih-Hsiang; Chen, Andrew C. H.; Liu, Yu-Li

    2017-01-01

    Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study. We found significant correlations among HIV infection status, plasma levels of CDH2, cytokine IL-7, ADAM10, and the treatment responses to methadone. Two single nucleotide polymorphisms located within CDH2 gene showed associations with blood pressure and plasma CDH2 concentration. Plasma concentration of CDH2 showed correlations with the level of cytokine IL-7, status of HIV infection, and urine morphine test result. Plasma level of IL-7 was correlated with corrected QT interval (QTc) and gooseflesh skin withdrawal symptom score, while level of ADAM10 was correlated with plasma concentrations of vitamin D metabolite, nicotine metabolite, and R-methadone. The results suggest a novel network involving HIV infection and methadone treatment outcome. PMID:28358908

  20. The 2-Year Test-Retest Reliability of the Psychopathy Checklist-Revised in Methadone Patients.

    ERIC Educational Resources Information Center

    Rutherford, Megan; Cacciola, John S.; Alterman, Arthur I.; McKay, James R.; Cook, Terry G.

    1999-01-01

    Examined the two-year test-retest reliability of the Psychopathy Checklist-Revised (R. Hare, 1991)(PCL-R) in 200 men and 25 women methadone patients. Stability of the PCL-R was generally good, but the measure was somewhat more reliable as a continuous measure than a dichotomous measure. (SLD)

  1. Resting EEG and ERPs findings in methadone-substituted opiate users: a review.

    PubMed

    Wang, Grace Y; Kydd, Robert; Russell, Bruce R

    2015-12-01

    Methadone has been used to treat opiate dependence since the mid-1960s. Despite its clinical effectiveness there is evidence from neuropsychological studies demonstrating that its long-term use might have negative effects on cognition. Nevertheless, it remains uncertain whether the observed cognitive impairments in patients undertaking methadone maintenance treatment (MMT) are solely attributable to the pharmacological effects of methadone, as suggested by some researchers. Determining the effects of MMT on neuropsychological function using electroencephalography (EEG) combined with event-related potentials (ERP) has been used infrequently. However EEG and ERP provide a means of closely examining information processing to determine whether MMT induces any deficits. The purpose of this review was to investigate whether psychophysiological evidence supports cognitive impairment in association with MMT by focusing on research using EEG and ERPs. The findings of EEG studies to date appear not support the notion that cognitive impairments are attributable to the specific pharmacological effects of methadone suggested by some neuropsychological studies. However, due to the methodological deficits and limited number of the studies, any conclusion based on the findings of the existing EEG studies should be avoided.

  2. Psychological Symptoms in Methadone Maintenance Patients: Prevalence and Change over Treatment.

    ERIC Educational Resources Information Center

    Corty, Eric; And Others

    1988-01-01

    Twice interviewed methadone maintenance patients in three cities using Addiction Severity Index. Of subjects followed, 35.4 percent reported having experienced recent psychological symptoms. Found no relation between length of time in treatment at first interview and psychiatric severity. Over one-year period, treatment that subjects received from…

  3. Impact of a Vocational Counselor on Employment-Related Outcomes among Methadone Patients.

    ERIC Educational Resources Information Center

    Appel, P. W.; Smith, R.; Schmeidler, J. B.; Randell, J.

    2000-01-01

    Studied the effects of placement of a vocational rehabilitation counselor (VRC) in methadone maintenance clinics for 333 and 358 patients. Results suggest that placement of a VRC in clinic settings is a cost effective change to vocational and educational services. (SLD)

  4. Evidence-Based Drug Treatment Practice and the Child Welfare System: The Example of Methadone

    ERIC Educational Resources Information Center

    Lundgren, Lena M.; Schilling, Robert F.; Peloquin, Susan D.

    2005-01-01

    This article examined the extent to which methadone maintenance (MM) is considered a treatment alternative for drug-dependent parents, as reflected in the social work and child welfare literature and in child welfare policies. Findings were derived from a review of 15 social work journals published from 1996 through 2002 and from a review of child…

  5. Methadone: The Drug and Its Therapeutic Uses In the Treatment of Addiction. Series 31, No. 1.

    ERIC Educational Resources Information Center

    Gamage, James R.; Zerkin, E. Lief

    This fact sheet from the National Clearinghouse for Drug Abuse Information discusses methadone, a therapeutic drug for the treatment of narcotic addiction. It reviews the pharmacology of the drug as well as physiological and psychological effects, patterns of use, and adverse effects (toxicity and poisoning). It examines the success rates of…

  6. Intervention for Infants and Toddlers Exposed to Methadone in Utero: Three Case Studies.

    ERIC Educational Resources Information Center

    Burns, M. Susan; And Others

    1996-01-01

    Three case studies describe intervention with infants/toddlers who were exposed to methadone in utero. Intervention included providing therapeutic nursery services and addressing developmental and mental health needs of the children and the high-risk family systems, including parents' knowledge of child development and parents' emotional support…

  7. Randomized Trial of Contingent Prizes versus Vouchers in Cocaine-Using Methadone Patients

    ERIC Educational Resources Information Center

    Petry, Nancy M.; Alessi, Sheila M.; Hanson, Tressa; Sierra, Sean

    2007-01-01

    Contingency management (CM) interventions frequently utilize vouchers as reinforcers, but a prize-based system is also efficacious. This study compared these approaches. Seventy-four cocaine-dependent methadone outpatients were randomly assigned to standard treatment (ST), ST plus a maximum of $585 in contingent vouchers, or ST plus an expected…

  8. Voucher-Based Contingent Reinforcement of Smoking Abstinence among Methadone-Maintained Patients: A Pilot Study

    ERIC Educational Resources Information Center

    Dunn, Kelly E.; Sigmon, Stacey C.; Thomas, Colleen S.; Heil, Sarah H.; Higgins, Stephen T.

    2008-01-01

    This study evaluated the efficacy of a contingency management (CM) intervention to promote smoking cessation in methadone-maintained patients. Twenty participants, randomized into contingent (n = 10) or noncontingent (n = 10) experimental conditions, completed the 14-day study. Abstinence was determined using breath carbon monoxide and urine…

  9. Contracting for Treatment Termination to Reduce Illicit Drug Use among Methadone Maintenance Treatment Failures.

    ERIC Educational Resources Information Center

    Dolan, Michael P.; And Others

    1985-01-01

    Evaluated the effectiveness of a contingency contracting intervention on reducing illicit drug use by methadone maintenance outpatients. Illicit drug use was significantly reduced during the 30-day intervention and remained below baseline levels during 60-day follow-up. (Author/MCF)

  10. Use of methadone in a highly tolerant patient receiving parenteral hydromorphone.

    PubMed

    Thomas, Z; Bruera, E

    1995-05-01

    A 59-year-old woman with metastatic breast cancer experienced a poor response to increasing doses of hydromorphone, possibly related to the neuropathic nature of her pain. Ultimately, the cost of this treatment was more than $1000 per day. Administration of methadone, initially as an adjuvant and eventually as the sole analgesic, at a much smaller dose than expected resulted in very satisfactory analgesia, without the development of serious side effects. In addition, the cost of treatment decreased to less than $25 per day. This case illustrates the rationale and advantages for the use of methadone. Intraindividual variability in the response to various opioids is a factor to be considered when selecting analgesics. Methadone is a useful second-line or third-line opioid for the patient who is highly tolerant to other opioids, as it may demonstrate incomplete cross-tolerance with other agonist opioids. Switching of the opioid to methadone may be a worthwhile option to consider in managing patients who are highly tolerant to other opioids.

  11. UHPLC-MS/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma.

    PubMed

    Kyle, Amy Redmond; Carmical, Jennifer; Shah, Darshan; Pryor, Jason; Brown, Stacy

    2015-10-01

    Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC-MS/MS method using solid-phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were <15% for each validated concentration. Our data establishes a 2 week maximum freezer storage window in order to achieve the most accurate cord plasma concentrations of these analytes. Additionally, we found that the umbilical cord tissue analysis was less sensitive compared with analysis with umbilical cord blood plasma, indicating that this may be a more appropriate matrix for determination of buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy.

  12. Methadone, Buprenorphine and Preferences for Opioid Agonist Treatment: A Qualitative Analysis

    PubMed Central

    Yarborough, Bobbi Jo H.; Stumbo, Scott P.; McCarty, Dennis; Mertens, Jennifer; Weisner, Constance; Green, Carla A.

    2016-01-01

    Background Patients and clinicians have begun to recognize the advantages and disadvantages of buprenorphine relative to methadone, but factors that influence choices between these two medications remain unclear. For example, we know little about how patients’ preferences and previous experiences influence treatment decisions. Understanding these issues may enhance treatment engagement and retention. Methods Adults with opioid dependence (n = 283) were recruited from two integrated health systems to participate in interviews focused on prior experiences with treatment for opioid dependence, knowledge of medication options, preferences for treatment, and experiences with treatment for chronic pain in the context of problems with opioids. Interviews were audio-recorded, transcribed verbatim, and coded using Atlas.ti. Results Our analysis revealed seven areas of consideration for opioid agonist treatment decision-making: 1) awareness of treatment options; 2) expectations and goals for duration of treatment and abstinence; 3) prior experience with buprenorphine or methadone; 4) need for accountability and structured support; 5) preference to avoid methadone clinics or associated stigma; 6) fear of continued addiction and perceived difficulty of withdrawal; and 7) pain control. Conclusion The availability of medication options increases the need for clear communication between clinicians and patients, for additional patient education about these medications, and for collaboration and patient influence over choices in treatment decision-making. Our results suggest that access to both methadone and buprenorphine will increase treatment options and patient choice and may enhance treatment adherence and outcomes. PMID:26796596

  13. Mathematical model insights into arsenic detoxification

    PubMed Central

    2011-01-01

    Background Arsenic in drinking water, a major health hazard to millions of people in South and East Asia and in other parts of the world, is ingested primarily as trivalent inorganic arsenic (iAs), which then undergoes hepatic methylation to methylarsonic acid (MMAs) and a second methylation to dimethylarsinic acid (DMAs). Although MMAs and DMAs are also known to be toxic, DMAs is more easily excreted in the urine and therefore methylation has generally been considered a detoxification pathway. A collaborative modeling project between epidemiologists, biologists, and mathematicians has the purpose of explaining existing data on methylation in human studies in Bangladesh and also testing, by mathematical modeling, effects of nutritional supplements that could increase As methylation. Methods We develop a whole body mathematical model of arsenic metabolism including arsenic absorption, storage, methylation, and excretion. The parameters for arsenic methylation in the liver were taken from the biochemical literature. The transport parameters between compartments are largely unknown, so we adjust them so that the model accurately predicts the urine excretion rates of time for the iAs, MMAs, and DMAs in single dose experiments on human subjects. Results We test the model by showing that, with no changes in parameters, it predicts accurately the time courses of urinary excretion in mutiple dose experiments conducted on human subjects. Our main purpose is to use the model to study and interpret the data on the effects of folate supplementation on arsenic methylation and excretion in clinical trials in Bangladesh. Folate supplementation of folate-deficient individuals resulted in a 14% decrease in arsenicals in the blood. This is confirmed by the model and the model predicts that arsenicals in the liver will decrease by 19% and arsenicals in other body stores by 26% in these same individuals. In addition, the model predicts that arsenic methyltransferase has been

  14. Methadone Induction in Primary Care for Opioid Dependence: A Pragmatic Randomized Trial (ANRS Methaville)

    PubMed Central

    Carrieri, Patrizia Maria; Michel, Laurent; Lions, Caroline; Cohen, Julien; Vray, Muriel; Mora, Marion; Marcellin, Fabienne; Spire, Bruno; Morel, Alain; Roux, Perrine

    2014-01-01

    Objective Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC. Methods In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively. Results In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively). Conclusions Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and

  15. 42 CFR 2.34 - Disclosures to prevent multiple enrollments in detoxification and maintenance treatment programs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... detoxification and maintenance treatment programs. 2.34 Section 2.34 Public Health PUBLIC HEALTH SERVICE... detoxification and maintenance treatment programs. (a) Definitions. For purposes of this section: Central... information about individuals applying for maintenance treatment or detoxification treatment for the...

  16. Sex differences in outcomes of methadone maintenance treatment for opioid addiction: a systematic review protocol

    PubMed Central

    2014-01-01

    Background Use of methadone for the treatment of opioid addiction is an effective harm-reduction approach, although variability in treatment outcomes among individuals has been reported. Men and women with opioid addiction have been known to differ in factors such as opioid use patterns and characteristics at treatment entry; however, little has been reported about differences in methadone treatment outcomes between men and women. Therefore, we present a protocol for a systematic review which aims to provide a summary of existing literature on sex differences in outcomes of methadone treatment for opioid addiction. Methods/Design Electronic search of PubMed/MEDLINE, EMBASE, PsycINFO, and CINAHL databases will be conducted using a priori defined search strategy. Two authors (MB and BBD) will independently screen potential articles for eligibility using pre-determined inclusion and exclusion criteria and extract key information using a data extraction form designed for this study. Discrepancies will be resolved using a third party (ZS). The primary outcome will be sex differences in response to treatment defined as abstinence from illicit opioid use. We will also assess sex differences in treatment outcomes including treatment retention, remission status post-treatment, polysubstance abuse, methadone dose, drug-related adverse events, health status, psychological status, mortality, criminal activity, high risk sexual behavior, social support/relations, and employment. A meta-analysis will be conducted if possible; risk of bias and overall quality of evidence will be assessed to determine confidence in the estimates. Discussion We anticipate that this review will highlight how men and women differ in methadone treatment outcomes and allow us to generate conclusions that can be applied to treatment in a clinical setting. Systematic review registration PROSPERO CRD42013006549 PMID:24887111

  17. Feasibility of Promoting Smoking Cessation Among Methadone Users Using Multimedia Computer-Assisted Education

    PubMed Central

    Lapshin, Oleg; Cha, Eunme

    2008-01-01

    Background The prevalence of smoking is very high among methadone users. As a method of delivering health education, computers can be utilized effectively. However computer-assisted education in methadone users has not been evaluated systematically. Objective This study was aimed at assessing feasibility and patient acceptance of an interactive educational module of a multi-component smoking cessation counseling computer program for former illicit drug users treated in an outpatient methadone clinic. Methods The computer-mediated education for hazards of smoking utilized in this study was driven by major constructs of adult learning theories. The program interface was tailored to individuals with minimal computer experience and was implemented on a touch screen tablet PC. The number of consecutive methadone-treated current smokers enrolled in the study was 35. After providing socio-demographic and smoking profiles, the patients were asked to use the educational program for 40 minutes. The impact of the computer-mediated education was assessed by administering a pre- and post-intervention Hazards of Smoking Knowledge Survey (HSKS). An attitudinal survey and semi-structured qualitative interview were used after the educational session to assess the opinions of participants about their educational experience. Results The computer-mediated education resulted in significant increase of HSKS scores from 60.5 ± 16.3 to 70.4 ± 11.7 with t value 3.69 and P < .001. The majority of the patients (78.8%) felt the tablet PC was easy to use, and most of the patients (91.4%) rated the educational experience as good or excellent. After controlling for patient baseline characteristics, the effect of computer-mediated education remained statistically significant. Conclusions Computer-assisted education using tablet PCs was feasible, well-accepted, and an effective means of providing hazards of smoking education among methadone users. PMID:18984556

  18. Improvement of saccadic functions after dosing with methadone in opioid addicted individuals.

    PubMed

    Gorzelańczyk, Edward Jacek; Walecki, Piotr; Feit, Julia; Kunc, Marek; Fareed, Ayman

    2016-01-01

    In the current experiment, we used the saccadometric test to study the effect of a single therapeutic dose of methadone on the integrity of cortico-subcortical brain functioning. In this prospective study, we used the Saccadometer System (Advanced Clinical Instrumentation, Cambridge, UK). The saccadometric test was performed before and 1.5 hours after methadone dosing. We analyzed the following saccadic parameters: latency, duration, amplitude, average and peak velocity, and processing performance (promptness) as well as a number of different types of saccades (like correct/incorrect, under/overshoot, and left-sided/right-sided). The sample consists of 40 subjects with an average 18 years of opioid addiction. The mean age is 35.3 ± 7 (80% males and 20% females). The mean period of heroin dependence is 15.3 ± 6.3 years. The mean daily dose of methadone in substitution therapy is 90 ± 26.5 mg. After administration of a single therapeutic dose of methadone, there were statistically significant differences in the values of saccade duration and latency when compared to the values before the drug administration. Average duration of saccade was significantly longer [51.40 ± 8.75 ms versus 48.93 ± 6.91 ms, z = 2.53, p = .01] and average latency was significantly longer [198.85 ± 52.57 ms versus 183.05 ± 30.95 ms, z = 2.09 p < .03]. This is the first study to test the therapeutic effect of daily methadone dosing on the integrity of the cortico-subcortical brain functions as measured by the saccadometry. More research is needed to explore the effect of illicit opioid use on the integrity of brain structures and functions, and the protective effect of opioid agonist therapy on reversing the damaging effects of illicit opioid use.

  19. Shear stress activation of nuclear receptor PXR in endothelial detoxification.

    PubMed

    Wang, Xiaohong; Fang, Xi; Zhou, Jing; Chen, Zhen; Zhao, Beilei; Xiao, Lei; Liu, Ao; Li, Yi-Shuan J; Shyy, John Y-J; Guan, Youfei; Chien, Shu; Wang, Nanping

    2013-08-06

    Endothelial cells (ECs) are constantly exposed to xenobiotics and endobiotics or their metabolites, which perturb EC function, as well as to shear stress, which plays a crucial role in vascular homeostasis. Pregnane X receptor (PXR) is a nuclear receptor and a key regulator of the detoxification of xeno- and endobiotics. Here we show that laminar shear stress (LSS), the atheroprotective flow, activates PXR in ECs, whereas oscillatory shear stress, the atheroprone flow, suppresses PXR. LSS activation of PXR in cultured ECs led to the increased expression of a PXR target gene, multidrug resistance 1 (MDR1). An in vivo study using rats showed that the expression of MDR1 was significantly higher in the endothelium from the descending thoracic aorta, where flow is mostly laminar, than from the inner curvature of aortic arch, where flow is disturbed. Functionally, LSS-activated PXR protects ECs from apoptosis triggered by doxorubicin via the induction of MDR1 and other detoxification genes. PXR also suppressed the expression of proinflammatory adhesion molecules and monocyte adhesion in response to TNF-α and lipopolysaccharide. Overexpression of a constitutively active PXR in rat carotid arteries potently attenuated proinflammatory responses. In addition, cDNA microarray revealed a large number of the PXR-activated endothelial genes whose products are responsible for major steps of detoxification, including phase I and II metabolizing enzymes and transporters. These detoxification genes in ECs are induced by LSS in ECs in a PXR-dependent manner. In conclusion, our results indicate that PXR represents a flow-activated detoxification system to protect ECs against damage by xeno- and endobiotics.

  20. Widespread Chemical Detoxification of Alkaloid Venom by Formicine Ants.

    PubMed

    LeBrun, Edward G; Diebold, Peter J; Orr, Matthew R; Gilbert, Lawrence E

    2015-10-01

    The ability to detoxify defensive compounds of competitors provides key ecological advantages that can influence community-level processes. Although common in plants and bacteria, this type of detoxification interaction is extremely rare in animals. Here, using laboratory behavioral assays and analyses of videotaped interactions in South America, we report widespread venom detoxification among ants in the subfamily Formicinae. Across both data sets, nine formicine species, representing all major clades, used a stereotyped grooming behavior to self-apply formic acid (acidopore grooming) in response to fire ant (Solenopsis invicta and S. saevissima) venom exposure. In laboratory assays, this behavior increased the survivorship of species following exposure to S. invicta venom. Species expressed the behavior when exposed to additional alkaloid venoms, including both compositionally similar piperidine venom of an additional fire ant species and the pyrrolidine/pyrroline alkaloid venom of a Monomorium species. In addition, species expressed the behavior following exposure to the uncharacterized venom of a Crematogaster species. However, species did not express acidopore grooming when confronted with protein-based ant venoms or when exposed to monoterpenoid-based venom. This pattern, combined with the specific chemistry of the reaction of formic acid with venom alkaloids, indicates that alkaloid venoms are targets of detoxification grooming. Solenopsis thief ants, and Monomorium species stand out as brood-predators of formicine ants that produce piperidine, pyrrolidine, and pyrroline venom, providing an important ecological context for the use of detoxification behavior. Detoxification behavior also represents a mechanism that can influence the order of assemblage dominance hierarchies surrounding food competition. Thus, this behavior likely influences ant-assemblages through a variety of ecological pathways.

  1. Shear stress activation of nuclear receptor PXR in endothelial detoxification

    PubMed Central

    Wang, Xiaohong; Fang, Xi; Zhou, Jing; Chen, Zhen; Zhao, Beilei; Xiao, Lei; Liu, Ao; Li, Yi-Shuan J.; Shyy, John Y.-J.; Guan, Youfei; Chien, Shu; Wang, Nanping

    2013-01-01

    Endothelial cells (ECs) are constantly exposed to xenobiotics and endobiotics or their metabolites, which perturb EC function, as well as to shear stress, which plays a crucial role in vascular homeostasis. Pregnane X receptor (PXR) is a nuclear receptor and a key regulator of the detoxification of xeno- and endobiotics. Here we show that laminar shear stress (LSS), the atheroprotective flow, activates PXR in ECs, whereas oscillatory shear stress, the atheroprone flow, suppresses PXR. LSS activation of PXR in cultured ECs led to the increased expression of a PXR target gene, multidrug resistance 1 (MDR1). An in vivo study using rats showed that the expression of MDR1 was significantly higher in the endothelium from the descending thoracic aorta, where flow is mostly laminar, than from the inner curvature of aortic arch, where flow is disturbed. Functionally, LSS-activated PXR protects ECs from apoptosis triggered by doxorubicin via the induction of MDR1 and other detoxification genes. PXR also suppressed the expression of proinflammatory adhesion molecules and monocyte adhesion in response to TNF-α and lipopolysaccharide. Overexpression of a constitutively active PXR in rat carotid arteries potently attenuated proinflammatory responses. In addition, cDNA microarray revealed a large number of the PXR-activated endothelial genes whose products are responsible for major steps of detoxification, including phase I and II metabolizing enzymes and transporters. These detoxification genes in ECs are induced by LSS in ECs in a PXR-dependent manner. In conclusion, our results indicate that PXR represents a flow-activated detoxification system to protect ECs against damage by xeno- and endobiotics. PMID:23878263

  2. Towards "evidence-making intervention" approaches in the social science of implementation science: The making of methadone in East Africa.

    PubMed

    Rhodes, Tim; Closson, Elizabeth F; Paparini, Sara; Guise, Andy; Strathdee, Steffanie

    2016-04-01

    In this commentary, we take the recent introduction of methadone treatment in response to emerging problems of HIV linked to heroin addiction in Kenya as a case for reflecting on the social science of implementation science. We offer a framework of 'evidence-making intervention' which we hold as distinct from mainstream 'evidence-based intervention' approaches. Whilst accepting that interventions are shaped in their contexts, evidence-based intervention approaches tend to imagine a stable intervention object with universal effect potential. By contrast, an evidence-making intervention approach investigates how an intervention, and the knowledge which constitutes it, is made locally, through its processes of implementation. Drawing on qualitative research generated in Kenya prior to (2012-2013) and during (2014-2015) the implementation of methadone treatment, we explore the making of 'methadone promise' as a case of evidence-making intervention. We show how enactments of methadone promise make multiple methadones, through which a binary is negotiated between the narratives of methadone as hope for addiction recovery and methadone as hope for HIV prevention. Addiction recovery narratives predominate, despite methadone's incorporation into policy via its globally supported HIV prevention evidence-base. Key practices in the making of methadone promise in Kenya include its medicalization, and renaming, as 'medically assisted treatment' - or simply 'MAT' - which distance it from prior constitutions elsewhere as a drug of substitution, and the visualisation of its effects wherein unhealthy people can be seen and shown to have become well. We also show how actors seek to protect the story of methadone promise from counter narratives, including through mass media projects. We conclude that there is no single biomedical object of methadone intervening on a single biological body across contexts, and no single universe of evidence. By giving weight to local rather than

  3. Mechanism-Based Inactivation of Cytochrome P450 2B6 by Methadone through Destruction of Prosthetic Heme

    PubMed Central

    Amunugama, Hemali T.; Zhang, Haoming

    2012-01-01

    Methadone is a μ-opioid receptor agonist widely used in the treatment of narcotic addiction and chronic pain conditions. Methadone is metabolized predominantly in the liver by cytochromes P450 to its pharmacologically inactive primary metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. Initial in vitro data suggested that CYP3A4 is the major isoform responsible for the in vivo clearance of methadone in humans. However, recent clinical data have indicated that CYP2B6 is actually the major isoform responsible for methadone metabolism and clearance in vivo. In this study, methadone was shown to act as a mechanism-based inactivator of CYP2B6. Methadone inactivates CYP2B6 in a time-, concentration-, and NADPH-dependent manner with a KI = 10.0 μM and kinact = 0.027 min−1. The loss of CYP2B6 activity in the presence of methadone and NADPH occurred with concomitant loss of the reduced CO spectrum of the P450. Moreover, there was good correlation between the loss of CYP2B6 activity and the loss of the CO-binding spectrum. High-performance liquid chromatography analysis of the native heme of the inactivated CYP2B6 demonstrated that approximately 75% loss of heme was accompanied by comparable inactivation of CYP2B6. Liquid chromatography-mass spectrometry analysis did not reveal the formation of a protein adduct during the inactivation. The evidence strongly suggests that destruction of prosthetic heme is the underlying mechanism leading to the inactivation of CYP2B6 by methadone. PMID:22685215

  4. Mechanism-based inactivation of cytochrome P450 2B6 by methadone through destruction of prosthetic heme.

    PubMed

    Amunugama, Hemali T; Zhang, Haoming; Hollenberg, Paul F

    2012-09-01

    Methadone is a μ-opioid receptor agonist widely used in the treatment of narcotic addiction and chronic pain conditions. Methadone is metabolized predominantly in the liver by cytochromes P450 to its pharmacologically inactive primary metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. Initial in vitro data suggested that CYP3A4 is the major isoform responsible for the in vivo clearance of methadone in humans. However, recent clinical data have indicated that CYP2B6 is actually the major isoform responsible for methadone metabolism and clearance in vivo. In this study, methadone was shown to act as a mechanism-based inactivator of CYP2B6. Methadone inactivates CYP2B6 in a time-, concentration-, and NADPH-dependent manner with a K(I) = 10.0 μM and k(inact) = 0.027 min⁻¹. The loss of CYP2B6 activity in the presence of methadone and NADPH occurred with concomitant loss of the reduced CO spectrum of the P450. Moreover, there was good correlation between the loss of CYP2B6 activity and the loss of the CO-binding spectrum. High-performance liquid chromatography analysis of the native heme of the inactivated CYP2B6 demonstrated that approximately 75% loss of heme was accompanied by comparable inactivation of CYP2B6. Liquid chromatography-mass spectrometry analysis did not reveal the formation of a protein adduct during the inactivation. The evidence strongly suggests that destruction of prosthetic heme is the underlying mechanism leading to the inactivation of CYP2B6 by methadone.

  5. Factors associated with frequent utilization of crisis substance use detoxification services.

    PubMed

    Carrier, Emily; McNeely, Jennifer; Lobach, Iryna; Tay, Shane; Gourevitch, Marc N; Raven, Maria C

    2011-04-01

    Previous research suggests that some substance users have multiple crisis detoxification visits and never access rehabilitation care. This care-seeking pattern leads to poorer outcomes and higher costs. The authors aimed to identify predictors of repeat detoxification visits by analyzing state-level data routinely collected at the time of substances use services admission. Repeat detoxification clients were more likely to be homeless, city-dwelling fee-for-service Medicaid recipients. Repeat detoxification clients were less likely than those with one admission to enter rehabilitation within 3 days. Treatment providers should aim for rapid transfer to rehabilitation and consider expanding detoxification intake data to improve risk stratification.

  6. Functional Genetic Polymorphisms in CYP2C19 Gene in Relation to Cardiac Side Effects and Treatment Dose in a Methadone Maintenance Cohort

    PubMed Central

    Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C.H.; Chang, Yao-Sheng

    2013-01-01

    Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations. PMID:24016178

  7. Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.

    PubMed

    Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C H; Chang, Yao-Sheng; Liu, Yu-Li

    2013-10-01

    Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.

  8. A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

    PubMed Central

    GORDON, MICHAEL S.; KINLOCK, TIMOTHY W.; COUVILLION, KATHRYN A.; SCHWARTZ, ROBERT P.; O’GRADY, KEVIN

    2014-01-01

    The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone. The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference. PMID:25392605

  9. Active heroin injectors' perceptions and use of methadone maintenance treatment: cynical performance or self-prescribed risk reduction?

    PubMed

    Koester, S; Anderson, K; Hoffer, L

    1999-12-01

    In addition to the numerous heroin users who voluntarily enter methadone treatment as a way to free themselves from illicit drug addiction and those ordered to do so by the courts, there are a large number of opioid users who enter methadone treatment with other objectives in mind. These include shorter-term goals that users do not necessarily equate with complete heroin abstinence. In this paper we report the results of a qualitative study designed to identify and describe the motivations active heroin users have for entering methadone treatment, and to suggest that many of these short-term methadone episodes may operate as self-prescribed attempts at risk reduction, and act as pilot tests for users considering or anticipating entering treatment to quit the use of illicit drugs. We argue that heroin users' motivations, perceptions about methadone, and the strategies they devise for adapting methadone treatment for their own needs should be recognized for their value in reducing the multiple risks associated with drug use.

  10. Detoxification of organophosphate residues using phosphotriesterase and their evaluation using flow based biosensor.

    PubMed

    Mishra, Rupesh K; Istamboulie, George; Bhand, Sunil; Marty, Jean-Louis

    2012-10-01

    Among known pesticide groups, organophosphates (OPs) have grasped attention due to their hazardous nature and their applications as pesticides and chemical weapons. This work presents the development of cost-effective column based biosensor for detoxification of OPs in water and milk. Enzyme phosphotriesterase (PTE) was immobilized on an activated Sepharose 4B via covalent coupling using an Omnifit glass column. Three different OPs, ethyl paraoxon (EPOx), malaoxon (MAO) and chlorpyriphos-oxon (CPO) were spiked in water and milk to test the detoxification of OPs. Mixtures of these pesticides were also tested to check the cumulative detoxification in the real samples. The efficiency of detoxification was evaluated using a highly sensitive acetylcholinesterase (AChE) B394 biosensor based flow system. The column conditions were optimized for the detoxification studied. The method was shown to be promising when we tested real milk samples spiked with OPs. Detoxification obtained in milk was up to 86% whereas in water, 100% detoxification was obtained.

  11. The impact of recent cocaine use on plasma levels of methadone and buprenorphine in patients with and without HIV-infection.

    PubMed

    Tetrault, Jeanette M; McCance-Katz, Elinore F; Moody, David E; Fiellin, David A; Lruie, Bonnie S; DInh, An T; Fiellin, Lynn E

    2015-04-01

    Cocaine decreases methadone and buprenorphine plasma concentrations. HIV infection and/or antiretroviral medication use may impact these relationships. We sought to determine the association between recent cocaine use and methadone and buprenorphine concentrations in HIV-infected and uninfected subjects in clinical care. R- and S-methadone or buprenorphine and norbuprenorphine concentrations were assessed at 0.5, 1, 2, and 24 hours after dosing in subjects with confirmed cocaine use and abstinence. We compared methadone and buprenorphine concentrations for cocaine use vs. abstinence, by HIV status in 16 subjects receiving methadone (6 HIV-infected) and 17 receiving buprenorphine (8 HIV-infected). With recent cocaine use, peak R-methadone (244 vs. 297 ng/mL, p = 0.03) and peak S-methadone (285 vs. 339 ng/mL); p = 0.03 concentrations were lower in HIV-uninfected subjects only. Peak buprenorphine and norbuprenorphine concentrations were unchanged regardless of cocaine use or HIV status. Cocaine may decrease methadone concentrations in HIV-uninfected subjects. HIV infection or its treatment may attenuate cocaine's effect on methadone.

  12. Comparison of sedation scores and propofol induction doses in dogs after intramuscular administration of dexmedetomidine alone or in combination with methadone, midazolam, or methadone plus midazolam.

    PubMed

    Canfrán, S; Bustamante, R; González, P; Cediel, R; Re, M; de Segura, I A Gómez

    2016-04-01

    The objectives of this study were to determine: (1) the sedative effects of dexmedetomidine in combination with methadone, midazolam, or both, and (2) the propofol dose required to achieve endotracheal intubation in healthy dogs. Seven healthy Beagle dogs were included in a prospective experimental, crossover, randomised and masked design. All dogs received four treatments IM, with at least 1 week between sessions, as follows: dexmedetomidine 5 µg/kg (D) alone, or combined with methadone 0.3 mg/kg (DMe), midazolam 0.3 mg/kg (DMi), or both (DMeMi). The degree of sedation was evaluated using a numerical scale (maximum 15 points). The dose of propofol required for intubation was also calculated for each group. Recovery time and quality were determined. Statistical analysis was performed using parametric (ANOVA) and nonparametric tests (Friedman, Cochran Q), as appropriate. The degree of sedation obtained with DMe and DMeMi (13, [7-14]; 13, [6-14], respectively) was significantly higher than in the control group (2, [1-4]; P = 0.023, P = 0.006, respectively). The required dose of propofol was lower in all groups (DMi, 1.5 ± 0.5 mg/kg, P = 0.002; DMe, 1.2 ± 0.5 mg/kg, P <0.001; DMeMi, 0.9 ± 0.3 mg/kg) than in the control group (2.9 ± 0.9 mg/kg; P <0.001). Recovery quality was not different between groups (P = 0.137). In healthy dogs, the addition of midazolam did not enhance the sedative effects of dexmedetomidine or a dexmedetomidine-methadone combination at the doses studied, and propofol requirements were reduced. The sedative effect of dexmedetomidine was enhanced with methadone, and the required dose of propofol was reduced.

  13. Detoxification mechanism of asbestos materials by microwave treatment.

    PubMed

    Yoshikawa, N; Kashimura, K; Hashiguchi, M; Sato, M; Horikoshi, S; Mitani, T; Shinohara, N

    2015-03-02

    The detoxification mechanism of asbestos materials was investigated through simulations and experiments. The permittivities of pure CaO and Mg3Si4O12, as quasi-asbestos materials, were measured using the cavity perturbation method. The real and imaginary parts of the relative permittivity (ɛr' and ɛr″) of CaO are functions of temperature, and numerical simulations revealed the thermal distributions in an electromagnetic field with respect to both asbestos shape and material configuration based on permittivity. Optical microscopic observation revealed that the thickness of chrysotile fibers decreased as a result of CaO heating. The heating mechanism of asbestos materials has been determined using CaO phase, and the detoxification mechanism of asbestos materials was discussed based on the heating mechanism.

  14. Detoxification of acidic catalyzed hydrolysate of Kappaphycus alvarezii (cottonii).

    PubMed

    Meinita, Maria Dyah Nur; Hong, Yong-Ki; Jeong, Gwi-Taek

    2012-01-01

    Red seaweed, Kappaphycus alvarezii, holds great promise for use in biofuel production due to its high carbohydrate content. In this study, we investigated the effect of fermentation inhibitors to the K. alvarezii hydrolysate on cell growth and ethanol fermentation. In addition, detoxification of fermentation inhibitors was performed to decrease the fermentation inhibitory effect. 5-Hydroxymethylfurfural and levulinic acid, which are liberated from acidic hydrolysis, was also observed in the hydrolysate of K. alvarezii. These compounds inhibited ethanol fermentation. In order to remove these inhibitors, activated charcoal and calcium hydroxide were introduced. The efficiency of activated charcoals was examined and over-liming was used to remove the inhibitors. Activated charcoal was found to be more effective than calcium hydroxide to remove the inhibitors. Detoxification by activated charcoal strongly improved the fermentability of dilute acid hydrolysate in the production of bioethanol from K. alvarezii with Saccharomyces cerevisiae. The optimal detoxifying conditions were found to be below an activated charcoal concentration of 5%.

  15. Oxidation and detoxification of pentachlorophenol in aqueous phase by ozonation.

    PubMed

    Anotai, Jin; Wuttipong, Rosawan; Visvanathan, Chettiyappan

    2007-10-01

    The degradation and detoxification performance of ozonation in treating pentachlorophenol (PCP) contaminated wastewater was determined. All experiments were conducted in a bench scale glass column equipped with ceramic diffuser and a lab-scale ozone generator under ambient temperature and pH 7. The decomposition rate of PCP in this study was primarily controlled by the ozone mass transfer rate from gas to liquid phases. Principal intermediates found were 2,3,4,6- and 2,3,5,6-tetrachlorophenols (TeCP) and phenol. PCP seems to be more vulnerable to ozone than its intermediates. A bioluminescence technique was used to evaluate the toxicity of PCP with Vibrio fisheri NRRL B-11177 as the test bacterium, and the EC(50) of PCP was found to be 1.0 mg l(-1). Detoxification occurred as the PCP and TeCP reacted with ozone and decomposed to less chlorinated congeners and phenol.

  16. Methadone use in a male with the FMRI premutation and FXTAS.

    PubMed

    Muzar, Zukhrofi; Lozano, Reymundo; Schneider, Andrea; Adams, Patrick E; Faradz, Sultana M H; Tassone, Flora; Hagerman, Randi J

    2015-06-01

    The fragile X-associated tremor ataxia syndrome (FXTAS) is caused by the premutation in FMR1 gene. Recent reports of environmental toxins appear to worsen the progression of FXTAS. Here we present a case of male adult with FXTAS and a long history of methadone use. The patient shows a faster progression in both symptoms of disease and MRI changes compared to what is typically seen in FXTAS. There has been no research regarding the role of narcotics in onset, progression, and severity of FXTAS symptoms. However, research has shown that narcotics can have a negative impact on several neurodegenerative diseases, and we hypothesize that in this particular case, methadone may have contributed to a faster progression of FXTAS as well as exacerbating white matter disease through RNA toxicity seen in premutation carriers.

  17. Methadone Use in a Male With the FMR1 Premutation and FXTAS

    PubMed Central

    Muzar, Zukhrofi; Lozano, Reymundo; Schneider, Andrea; Adams, Patrick E.; Faradz, Sultana M.H.; Tassone, Flora; Hagerman, Randi J.

    2016-01-01

    The fragile X-associated tremor ataxia syndrome (FXTAS) is caused by the premutation in FMR1 gene. Recent reports of environmental toxins appear to worsen the progression of FXTAS. Here we present a case of male adult with FXTAS and a long history of methadone use. The patient shows a faster progression in both symptoms of disease and MRI changes compared to what is typically seen in FXTAS. There has been no research regarding the role of narcotics in onset, progression, and severity of FXTAS symptoms. However, research has shown that narcotics can have a negative impact on several neurodegenerative diseases, and we hypothesize that in this particular case, methadone may have contributed to a faster progression of FXTAS as well as exacerbating white matter disease through RNA toxicity seen in premutation carriers. PMID:25900641

  18. Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone.

    PubMed

    Syed, Husnain; Som, Sumit; Khan, Nazia; Faltas, Wael

    2009-01-01

    The present report highlights the possible adverse effects of doxylamine, a common over the counter sleep aid. Doxylamine is an antihistamine that at toxic doses can cause anticholinergic effects, including seizures, rhabdomyolysis and death. The following case describes a patient with doxylamine toxicity who presented with seizure and confusion. Our patient was managed symptomatically, and remained otherwise stable throughout his hospitalisation. This case is atypical in terms of a delayed rhabdomyolysis and a false positive urine drug screen test for methadone. There is evidence that doxylamine at toxic levels can lead to false positives for methadone and phencyclidine testing using immunoassay-based urine drug screen kits. Urine drug screen testing on patients who are hospitalised is typically performed using immunoassays. However, in certain cases confirmatory secondary testing may be required. Doxylamine is prone to abuse and knowledge of the clinical presentation of its toxicity and the management of acute overdose can be life-saving.

  19. Plasmodium infection alters Anopheles gambiae detoxification gene expression

    PubMed Central

    2010-01-01

    Background Anopheles gambiae has been shown to change its global gene expression patterns upon Plasmodium infection. While many alterations are directly related to the mosquito's innate immune response, parasite invasion is also expected to generate toxic by-products such as free radicals. The current study aimed at identifying which loci coding for detoxification enzymes are differentially expressed as a function of Plasmodium berghei infection in midgut and fat body tissues. Results Using a custom-made DNA microarray, transcript levels of 254 loci primarily belonging to three major detoxification enzyme families (glutathione S-transferases, cytochrome P450 monooxygenases and esterases) were compared in infected and uninfected mosquitoes both during ookinete invasion and the release of sporozoites into the hemocoel. The greatest changes in gene expression were observed in the midgut in response to ookinete invasion. Interestingly, many detoxification genes including a large number of P450s were down-regulated at this stage. In the fat body, while less dramatic, gene expression alterations were also observed and occurred during the ookinete invasion and during the release of sporozoites into the hemocoel. While most gene expression changes were tissue-related, CYP6M2, a CYP previously associated with insecticide resistance, was over-expressed both in the midgut and fat body during ookinete invasion. Conclusions Most toxicity-related reactions occur in the midgut shortly after the ingestion of an infected blood meal. Strong up-regulation of CYP6M2 in the midgut and the fat body as well as its previous association with insecticide resistance shows its broad role in metabolic detoxification. PMID:20482856

  20. Detoxification: A Novel Function of BRCA1 in Tumor Suppression?

    PubMed Central

    Kang, Hyo Jin; Hong, Young Bin; Kim, Hee Jeong; Rodriguez, Olga C.; Nath, Raghu G.; Tilli, Elena M.; Albanese, Christopher; Chung, Fung-Lung; Kwon, Sang Hoon; Bae, Insoo

    2011-01-01

    Our studies found that BRCA1 levels negatively correlate with DNA adducts induced by Benzo(a)pyrene (BaP). Pulse-chase experiments showed that the increase in BaP-induced DNA adducts in BRCA1 knockdown cells may not be associated with BRCA1’s function in nucleotide excision repair activity; rather, it may be associated with its function in modulating transcriptional regulation. BRCA1 knockdown in MCF-10A cells significantly attenuated the induction of CYP1A1 following BaP treatment indicating that the increase in BaP-induced adducts in BRCA1 knockdown cells is not CYP1A1 dependent. However, our study shows that BRCA1 defective cells may still be able to biotransform BaP by regulating other CYP enzymes, including CYP1B1. Knockdown of BRCA1 also severely affected the expression levels of two types of uridine diphosphate glucorunyltransferase (UGT1A1 and UGT1A9) and NRF2. Both UGTs are known as BaP-specific detoxification enzymes, and NRF2 is a master regulator of antioxidant and detoxification genes. Thus, we concluded that the increased amount of BaP-induced DNA adducts in BRCA1 knockdown cells is strongly associated with its loss of functional detoxification. Chromatin immunoprecipitation assay revealed that BRCA1 is recruited to the promoter/enhancer sequences of UGT1A1, UGT1A9, and NRF2. Regulation of UGT1A1 and UGT1A9 expression showed that the induction of DNA adducts by BaP is directly affected by their expression levels. Finally, overexpression of UGTs, NRF2, or ARNT significantly decreased the amount of BaP-induced adducts in BRCA1-deficient cells. Overall, our results suggest that BRCA1 protects cells by reducing the amount of BaP-induced DNA adducts possibly via transcriptional activation of detoxification gene expression. PMID:21507987

  1. Is arsenic biotransformation a detoxification mechanism for microorganisms?

    PubMed

    Rahman, M Azizur; Hassler, Christel

    2014-01-01

    Arsenic (As) is extremely toxic to living organisms at high concentration. In aquatic systems, As exists in different chemical forms. The two major inorganic As (iAs) species are As(V), which is thermodynamically stable in oxic waters, and As(III), which is predominant in anoxic conditions. Photosynthetic microorganisms (e.g., phytoplankton and cyanobacteria) take up As(V), biotransform it to As(III), then biomethylate it to methylarsenic (MetAs) forms. Although As(III) is more toxic than As(V), As(III) is much more easily excreted from the cells than As(V). Therefore, majority of researchers consider the reduction of As(V) to As(III) as a detoxification process. The biomethylation process results in the conversion of toxic iAs to the less toxic pentavalent MetAs forms (monomethylarsonate; MMA(V), dimethylarsonate; DMA(V), and trimethylarsenic oxide; TMAO(V)) and trimethylarsine (TMAO(III)). However, biomethylation by microorganisms also produces monomethylarsenite (MMA(III)) and dimethylarsenite (DMA(III)), which are more toxic than iAs, as a result of biomethylation by the microorganisms, demonstrates the need to reconsider to what extent As biomethylation contributes to a detoxification process. In this review, we focused on the discussion of whether the biotransformation of As species in microorganisms is really a detoxification process with recent data.

  2. Rice transcriptome analysis to identify possible herbicide quinclorac detoxification genes

    PubMed Central

    Xu, Wenying; Di, Chao; Zhou, Shaoxia; Liu, Jia; Li, Li; Liu, Fengxia; Yang, Xinling; Ling, Yun; Su, Zhen

    2015-01-01

    Quinclorac is a highly selective auxin-type herbicide and is widely used in the effective control of barnyard grass in paddy rice fields, improving the world's rice yield. The herbicide mode of action of quinclorac has been proposed, and hormone interactions affecting quinclorac signaling has been identified. Because of widespread use, quinclorac may be transported outside rice fields with the drainage waters, leading to soil and water pollution and other environmental health problems. In this study, we used 57K Affymetrix rice whole-genome array to identify quinclorac signaling response genes to study the molecular mechanisms of action and detoxification of quinclorac in rice plants. Overall, 637 probe sets were identified with differential expression levels under either 6 or 24 h of quinclorac treatment. Auxin-related genes such as GH3 and OsIAAs responded to quinclorac treatment. Gene Ontology analysis showed that genes of detoxification-related family genes were significantly enriched, including cytochrome P450, GST, UGT, and ABC and drug transporter genes. Moreover, real-time RT-PCR analysis showed that top candidate genes of P450 families such as CYP81, CYP709C, and CYP72A were universally induced by different herbicides. Some Arabidopsis genes of the same P450 family were up-regulated under quinclorac treatment. We conducted rice whole-genome GeneChip analysis and the first global identification of quinclorac response genes. This work may provide potential markers for detoxification of quinclorac and biomonitors of environmental chemical pollution. PMID:26483837

  3. Impact of food processing and detoxification treatments on mycotoxin contamination.

    PubMed

    Karlovsky, Petr; Suman, Michele; Berthiller, Franz; De Meester, Johan; Eisenbrand, Gerhard; Perrin, Irène; Oswald, Isabelle P; Speijers, Gerrit; Chiodini, Alessandro; Recker, Tobias; Dussort, Pierre

    2016-11-01

    Mycotoxins are fungal metabolites commonly occurring in food, which pose a health risk to the consumer. Maximum levels for major mycotoxins allowed in food have been established worldwide. Good agricultural practices, plant disease management, and adequate storage conditions limit mycotoxin levels in the food chain yet do not eliminate mycotoxins completely. Food processing can further reduce mycotoxin levels by physical removal and decontamination by chemical or enzymatic transformation of mycotoxins into less toxic products. Physical removal of mycotoxins is very efficient: manual sorting of grains, nuts, and fruits by farmers as well as automatic sorting by the industry significantly lowers the mean mycotoxin content. Further processing such as milling, steeping, and extrusion can also reduce mycotoxin content. Mycotoxins can be detoxified chemically by reacting with food components and technical aids; these reactions are facilitated by high temperature and alkaline or acidic conditions. Detoxification of mycotoxins can also be achieved enzymatically. Some enzymes able to transform mycotoxins naturally occur in food commodities or are produced during fermentation but more efficient detoxification can be achieved by deliberate introduction of purified enzymes. We recommend integrating evaluation of processing technologies for their impact on mycotoxins into risk management. Processing steps proven to mitigate mycotoxin contamination should be used whenever necessary. Development of detoxification technologies for high-risk commodities should be a priority for research. While physical techniques currently offer the most efficient post-harvest reduction of mycotoxin content in food, biotechnology possesses the largest potential for future developments.

  4. Sulfide Intrusion and Detoxification in the Seagrass Zostera marina.

    PubMed

    Hasler-Sheetal, Harald; Holmer, Marianne

    2015-01-01

    Gaseous sulfide intrusion into seagrasses growing in sulfidic sediments causes little or no harm to the plant, indicating the presence of an unknown sulfide tolerance or detoxification mechanism. We assessed such mechanism in the seagrass Zostera marina in the laboratory and in the field with scanning electron microscopy coupled to energy dispersive X-ray spectroscopy, chromatographic and spectrophotometric methods, and stable isotope tracing coupled with a mass balance of sulfur compounds. We found that Z. marina detoxified gaseous sediment-derived sulfide through incorporation and that most of the detoxification occurred in underground tissues, where sulfide intrusion was greatest. Elemental sulfur was a major detoxification compound, precipitating on the inner wall of the aerenchyma of underground tissues. Sulfide was metabolized into thiols and entered the plant sulfur metabolism as well as being stored as sulfate throughout the plant. We conclude that avoidance of sulfide exposure by reoxidation of sulfide in the rhizosphere or aerenchyma and tolerance of sulfide intrusion by incorporation of sulfur in the plant are likely major survival strategies of seagrasses in sulfidic sediments.

  5. Detoxification of dilute acid hydrolysates of lignocellulose with lime.

    PubMed

    Martinez, A; Rodriguez, M E; Wells, M L; York, S W; Preston, J F; Ingram, L O

    2001-01-01

    The hydrolysis of hemicellulose to monomeric sugars by dilute acid hydrolysis is accompanied by the production of inhibitors that retard microbial fermentation. Treatment of hot hydrolysate with Ca(OH)(2) (overliming) is an effective method for detoxification. Using ethanologenic Escherichia coli LY01 as the biocatalyst, our results indicate that the optimal lime addition for detoxification varies and depends on the concentration of mineral acids and organic acids in each hydrolysate. This optimum was shown to be readily predicted on the basis of the titration of hydrolysate with 2 N NaOH at ambient temperature to either pH 7.0 or pH 11.0. The average composition of 15 hydrolysates prior to treatment was as follows (per L): 95.24 +/- 7.29 g sugar, 5.3 +/- 2.99 g acetic acid, 1.305 +/- 0.288 g total furans (furfural and hydroxymethylfurfural), and 2.86 +/- 0.34 g phenolic compounds. Optimal overliming resulted in a 51 +/- 9% reduction of total furans, a 41 +/- 6% reduction in phenolic compounds, and a 8.7 +/- 4.5% decline in sugar. Acetic acid levels were unchanged. Considering the similarity of microorganisms, it is possible that the titration method described here may also prove useful for detoxification and fermentation processes using other microbial biocatalysts.

  6. TRAZODONE FOR SLEEP DISTURBANCE DURING METHADONE MAINTENANCE: A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

    PubMed Central

    Stein, Michael D.; Kurth, Megan E.; Sharkey, Katherine M; Anderson, Bradley J.; Corso, Richard P; Millman, Richard P

    2011-01-01

    BACKGROUND To test whether trazodone, one of the most commonly prescribed medications for treatment of insomnia, improves subjective and/or objective sleep among methadone-maintained persons with sleep complaints, we performed a randomized, double-blind, placebo-controlled trial with six month follow-up. METHODS From eight methadone maintenance programs in the northeastern United States, we recruited 137 persons receiving methadone for at least one month who reported a Pittsburgh Sleep Quality Index (PSQI) score of six or higher. Two-night home polysomnography (PSG) was completed at baseline and one month later, with morning surveys and urine drug toxicologies. Interviews assessed sleep over the past 30 days at baseline and 1-, 3-, and 6- month follow-ups. RESULTS Participants averaged 38 years of age, were 47% male, and had a mean PSQI total score of 12.9 (± 3.1). At baseline, intervention groups did not significantly differ on 10 PSG-derived objective sleep measures and 11 self-reported measures. Over 88% (n = 121) of participants completed the PSG at 1-month. Without adjusting p-values for multiple comparisons, only 1 of 21 sleep measure comparisons was statistically significant (p<.05). The effect of trazodone on mean PSQI scores during the six-month follow-up was not statistically significant (p = .10). Trazodone neither significantly increased nor decreased illicit drug use relative to placebo. CONCLUSIONS Trazodone did not improve subjective or objective sleep in methadone-maintained persons with sleep disturbance. Other pharmacologic and non-pharmacologic treatments should be investigated for this population with high rates of insomnia. PMID:21798674

  7. Topiramate impairs cognitive function in methadone-maintained individuals with concurrent cocaine dependence

    PubMed Central

    Rass, Olga; Umbricht, Annie; Bigelow, George E.; Strain, Eric C.; Johnson, Matthew W.; Mintzer, Miriam Z.

    2014-01-01

    Topiramate is being investigated as a potential pharmacotherapy for the treatment of addictive disorders. However, its cognitive side effects raise concerns about its use, especially in populations with cognitive impairment, such as persons with chronic substance use disorders. This study investigated the topiramate's cognitive effects in individuals dually dependent on cocaine and opioids as part of a double-blind, randomized, controlled trial of topiramate for the cocaine dependence treatment. Following five weeks of stabilization on daily oral methadone (M=96 mg), participants were randomized to topiramate (n=18) or placebo (n=22). Cognitive testing took place at two time points: study weeks 4-5 to assess baseline performance and 10-13 weeks later to assess performance during stable dosing (300 mg topiramate or placebo). All participants were maintained on methadone at both testing times, and testing occurred two hours after the daily methadone plus topiramate/placebo administration. The topiramate and placebo groups did not differ on sex, level of education, premorbid intelligence, methadone dose, or illicit drug use. Topiramate slowed psychomotor and information processing speed, worsened divided attention, reduced n-back working memory accuracy, and increased the false alarm rate in recognition memory. Topiramate had no effects on visual processing, other measures of psychomotor function, risk-taking, self-control, Sternberg working memory, free recall, and metamemory. These findings indicate that topiramate may cause cognitive impairment in this population. This effect may limit its acceptability and use as a treatment in individuals with chronic opiate and cocaine use disorders, among whom pre-existing cognitive impairments are common. PMID:25365653

  8. Effect of Methadone Maintenance Therapy on Anthropometric Indices in Opioid Dependent Patients

    PubMed Central

    Montazerifar, Farzaneh; Karajibani, Mansour; Lashkaripour, Kobra

    2012-01-01

    Background Opium abuse significantly affects the nutritional status of users and frequently leads to undernourishment. Methadone maintenance therapy has been used as one of the possible ways to prevent of infection diseases such as HIV and hepatitis B and C and improve the quality of life in opioid-dependent patients. Objectives The aim of this study was to assess the anthropometric and socio-demographic characteristics of opium addicted persons before and after 8 weeks of methadone maintenance therapy (MMT). Patients and Methods A clinical cross-sectional study was carried out on 55 opium users (15 women and 40 men; mean aged 31.6 ± 10 years), dependent on opium and its derivatives at the Addiction Treatment Clinic of the Baharan psychiatric Hospital, Zahedan, Sistan and Baluchistan Province, Iran, in 2011. The patients were examined before and after 8 weeks MMT. Weight and height of participants were taken and the body mass index (BMI) was calculated. Results Body weight increased significantly from 61.4 ± 14.4 to 65.3 ± 14.2 kg and BMI from 21.4 ± 4.2 to 23 ± 5.6 (kg/m2) after 8 weeks of methadone maintenance therapy in opium users (P < 0.01). The percentages of underweight, overweight and obese patients were; 27.3%, 18.2% and 3.6%, respectively pre-MMT, and 12.7%, 18.2% and 7.2%, respectively after MMT. Conclusions The study shows that methadone Maintenance Therapy led to improvements in nutritional status. PMID:24971244

  9. Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment

    PubMed Central

    Yee, Anne; Danaee, Mahmoud; Loh, Huai Seng; Sulaiman, Ahmad Hatim; Ng, Chong Guan

    2016-01-01

    Introduction Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT). The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients. Methods Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15), and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders. Results The study population consisted of 171 patients (71.8%) on MMT and 67 (28.2%) on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012) and overall satisfaction (p = 0.043) domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008) compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026) and overall satisfaction (p = 0.039) were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables. Conclusions Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus

  10. Bioavailability of morphine, methadone, hydromorphone, and oxymorphone following buccal administration in cats.

    PubMed

    Pypendop, B H; Ilkiw, J E; Shilo-Benjamini, Y

    2014-06-01

    Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time-concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean ± SE (range) bioavailability was 36.6 ± 5.2 (12.7-49.5), 44.2 ± 7.9 (18.7-70.5), 22.4 ± 6.9 (6.4-43.4), and 18.8 ± 2.0 (12.9-23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone.

  11. Effects of Methadone on the Minimum Anesthetic Concentration of Isoflurane, and Its Effects on Heart Rate, Blood Pressure and Ventilation during Isoflurane Anesthesia in Hens (Gallus gallus domesticus)

    PubMed Central

    Pypendop, Bruno Henri; Zangirolami Filho, Darcio; Sousa, Samuel Santos; Valadão, Carlos Augusto Araújo

    2016-01-01

    The aim of this study was to measure the temporal effects of intramuscular methadone administration on the minimum anesthetic concentration (MAC) of isoflurane in hens, and to evaluate the effects of the isoflurane-methadone combination on heart rate and rhythm, blood pressure and ventilation. Thirteen healthy adult hens weighing 1.7 ± 0.2 kg were used. The MAC of isoflurane was determined in each individual using the bracketing method. Subsequently, the reduction in isoflurane MAC produced by methadone (3 or 6 mg kg-1, IM) was determined by the up-and-down method. Stimulation was applied at 15 and 30 minutes, and at 45 minutes if the bird had not moved at 30 minutes. Isoflurane MAC reduction was calculated at each time point using logistic regression. After a washout period, birds were anesthetized with isoflurane and methadone, 6 mg kg-1 IM was administered. Heart rate and rhythm, respiratory rate, blood gas values and invasive blood pressure were measured at 1.0 and 0.7 isoflurane MAC, and during 45 minutes after administration of methadone once birds were anesthetized with 0.7 isoflurane MAC. Fifteen minutes after administration of 3 mg kg-1 of methadone, isoflurane MAC was reduced by 2 (-9 to 13)% [logistic regression estimate (95% Wald confidence interval)]. Administration of 6 mg kg-1 of methadone decreased isoflurane MAC by 29 (11 to 46)%, 27 (-3 to 56)% and 10 (-8 to 28)% after 15, 30 and 45 minutes, respectively. Methadone (6 mg kg-1) induced atrioventricular block in three animals and ventricular premature contractions in two. Methadone caused an increase in arterial blood pressure and arterial partial pressure of carbon dioxide, while heart rate and pH decreased. Methadone, 6 mg kg-1 IM significantly reduced isoflurane MAC by 30% in hens 15 minutes after administration. At this dose, methadone caused mild respiratory acidosis and increase in systemic blood pressure. PMID:27018890

  12. Effects of Methadone on the Minimum Anesthetic Concentration of Isoflurane, and Its Effects on Heart Rate, Blood Pressure and Ventilation during Isoflurane Anesthesia in Hens (Gallus gallus domesticus).

    PubMed

    Escobar, André; da Rocha, Rozana Wendler; Pypendop, Bruno Henri; Zangirolami Filho, Darcio; Sousa, Samuel Santos; Valadão, Carlos Augusto Araújo

    2016-01-01

    The aim of this study was to measure the temporal effects of intramuscular methadone administration on the minimum anesthetic concentration (MAC) of isoflurane in hens, and to evaluate the effects of the isoflurane-methadone combination on heart rate and rhythm, blood pressure and ventilation. Thirteen healthy adult hens weighing 1.7 ± 0.2 kg were used. The MAC of isoflurane was determined in each individual using the bracketing method. Subsequently, the reduction in isoflurane MAC produced by methadone (3 or 6 mg kg(-1), i.m.) was determined by the up-and-down method. Stimulation was applied at 15 and 30 minutes, and at 45 minutes if the bird had not moved at 30 minutes. Isoflurane MAC reduction was calculated at each time point using logistic regression. After a washout period, birds were anesthetized with isoflurane and methadone, 6 mg kg(-1) i.m. was administered. Heart rate and rhythm, respiratory rate, blood gas values and invasive blood pressure were measured at 1.0 and 0.7 isoflurane MAC, and during 45 minutes after administration of methadone once birds were anesthetized with 0.7 isoflurane MAC. Fifteen minutes after administration of 3 mg kg(-1) of methadone, isoflurane MAC was reduced by 2 (-9 to 13)% [logistic regression estimate (95% Wald confidence interval)]. Administration of 6 mg kg(-1) of methadone decreased isoflurane MAC by 29 (11 to 46)%, 27 (-3 to 56)% and 10 (-8 to 28)% after 15, 30 and 45 minutes, respectively. Methadone (6 mg kg(-1)) induced atrioventricular block in three animals and ventricular premature contractions in two. Methadone caused an increase in arterial blood pressure and arterial partial pressure of carbon dioxide, while heart rate and pH decreased. Methadone, 6 mg kg(-1) i.m. significantly reduced isoflurane MAC by 30% in hens 15 minutes after administration. At this dose, methadone caused mild respiratory acidosis and increase in systemic blood pressure.

  13. Comparison of the effects of epidural or intravenous methadone on the minimum alveolar concentration of isoflurane in dogs.

    PubMed

    Campagnol, Daniela; Teixeira-Neto, Francisco J; Peccinini, Rosangela G; Oliveira, Flávia A; Alvaides, Renata K; Medeiros, Luiza Q

    2012-06-01

    The effects of epidural and intravenous (IV) methadone (0.5mg/kg) on the minimum alveolar concentration of isoflurane (ISO(MAC)) were compared in dogs. Six dogs (16.5 ± 2.5 kg bodyweight) received three treatments in random order during isoflurane anaesthesia, with a 7 day washout interval between each study. Methadone was injected via a lumbosacral epidural catheter introduced 10 cm cranially into the epidural canal and the electrical stimulation for ISO(MAC) determination was applied either to the thoracic (EP(T) treatment) or to the pelvic limb (EP(P) treatment) during separate study days. In the IV treatment, ISO(MAC) was determined via electrical stimulation of the pelvic limb. Variables were recorded before (baseline), 2.5 and 5h after drug injection. The ISO(MAC) decreased significantly (P<0.05) from baseline at 2.5 and 5h after methadone in all treatments. At 2.5h, the magnitude of ISO(MAC) reduction did not differ between treatments (mean decreases from baseline: 30-33%). The ISO(MAC) reduction lasted longer following epidural methadone in the thoracic limb (decreases from baseline: 30% at 5h in the EP(T) treatment vs. 19% and 16% in the EP(P) and IV treatments, respectively). Although the isoflurane sparing effect provided by epidural methadone was not significantly greater than IV methadone during the initial stage (2.5h), it was more prolonged than the IV route in specific dermatomes (5h in the thoracic limb) with the epidural technique employed. Methadone may therefore provide a greater isoflurane sparing effect when administered epidurally, compared to IV, when noxious stimulation occurs in specific dermatomes.

  14. Effect of prenatal methadone and ethanol on opioid receptor development in rats

    SciTech Connect

    Peters, M.A.; Braun, R.L. )

    1991-03-11

    The current literature shows that the offspring of female rats exposed to methadone or ethanol display similar neurochemical and neurobehavioral alterations, and suggests that these drugs may be operating through a common mechanism. If this hypothesis is true, their effect on the endogenous opioid systems should be qualitatively similar. In this study virgin females were treated with methadone or 10% ethanol oral solution starting prior to conception and continued throughout gestation. When the offspring had reached 15 or 30 days of age they were sacrificed, the brain was removed and prepared for opioid receptor binding studies. ({sup 3}H)DAGO and ({sup 3}H)DADLE were used as ligands for the mu and delta receptors, respectively. These studies show significant treatment-related differences in both the number of mu and delta binding sites as well as in apparent receptor affinity. Significant sex- and age-related differences between treatments were also observed. These data show that methadone and ethanol, while manifesting some similar neurochemical and behavioral effects, have unique effects on opioid receptor binding, suggesting that they may be acting by different mechanisms.

  15. Scaling up the national methadone maintenance treatment program in China: achievements and challenges

    PubMed Central

    Yin, Wenyuan; Hao, Yang; Sun, Xinhua; Gong, Xiuli; Li, Fang; Li, Jianhua; Rou, Keming; Sullivan, Sheena G; Wang, Changhe; Cao, Xiaobin; Luo, Wei; Wu, Zunyou

    2010-01-01

    China’s methadone maintenance treatment program was initiated in 2004 as a small pilot project in just eight sites. It has since expanded into a nationwide program encompassing more than 680 clinics covering 27 provinces and serving some 242 000 heroin users by the end of 2009. The agencies that were tasked with the program’s expansion have been confronted with many challenges, including high drop-out rates, poor cooperation between local governing authorities and poor service quality at the counter. In spite of these difficulties, ongoing evaluation has suggested reductions in heroin use, risky injection practices and, importantly, criminal behaviours among clients, which has thus provided the impetus for further expansion. Clinic services have been extended to offer clients a range of ancillary services, including HIV, syphilis and hepatitis C testing, information, education and communication, psychosocial support services and referrals for treatment of HIV, tuberculosis and sexually transmitted diseases. Cooperation between health and public security officials has improved through regular meetings and dialogue. However, institutional capacity building is still needed to deliver sustainable and standardized services that will ultimately improve retention rates. This article documents the steps China made in overcoming the many barriers to success of its methadone program. These lessons might be useful for other countries in the region that are scaling-up their methadone programs. PMID:21113034

  16. THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats.

    PubMed

    Wakley, Alexa A; Craft, Rebecca M

    2011-09-01

    This study examined cannabinoid-opioid interactions within the same subjects on measures of discrimination, antinociception, horizontal locomotion, and catalepsy. Male Sprague-Dawley rats were trained to discriminate Δ(9)-tetrahydrocannabinol (THC, 3 mg/kg) from vehicle. THC alone (0.32-10 mg/kg) dose-dependently increased THC-appropriate lever responding and decreased response rate. THC alone also produced paw pressure antinociception and decreased locomotor activity, but did not produce catalepsy. Methadone (0.32-5.6 mg/kg) and naltrexone (0.32-3.2 mg/kg) alone produced low THC-appropriate lever responding up to doses that decreased response rate. When combined with THC, methadone (1.0 mg/kg) flattened the THC discrimination curve, but did not affect antinociceptive or motoric effects of THC. Naltrexone did not alter any effects of THC. In rats that were not trained to discriminate THC from vehicle, 1.0 mg/kg methadone did enhance THC antinociception. These results suggest that μ-opioid receptor agonists can disrupt the discriminative stimulus effects of cannabinoids while not significantly altering their antinociceptive or motoric effects, in chronically drug-exposed subjects. Further research is required to determine whether opioid enhancement of cannabinoid antinociception is limited to acute exposure, or simply requires higher doses in chronically drug-exposed subjects.

  17. Scaling up the national methadone maintenance treatment program in China: achievements and challenges.

    PubMed

    Yin, Wenyuan; Hao, Yang; Sun, Xinhua; Gong, Xiuli; Li, Fang; Li, Jianhua; Rou, Keming; Sullivan, Sheena G; Wang, Changhe; Cao, Xiaobin; Luo, Wei; Wu, Zunyou

    2010-12-01

    China's methadone maintenance treatment program was initiated in 2004 as a small pilot project in just eight sites. It has since expanded into a nationwide program encompassing more than 680 clinics covering 27 provinces and serving some 242 000 heroin users by the end of 2009. The agencies that were tasked with the program's expansion have been confronted with many challenges, including high drop-out rates, poor cooperation between local governing authorities and poor service quality at the counter. In spite of these difficulties, ongoing evaluation has suggested reductions in heroin use, risky injection practices and, importantly, criminal behaviours among clients, which has thus provided the impetus for further expansion. Clinic services have been extended to offer clients a range of ancillary services, including HIV, syphilis and hepatitis C testing, information, education and communication, psychosocial support services and referrals for treatment of HIV, tuberculosis and sexually transmitted diseases. Cooperation between health and public security officials has improved through regular meetings and dialogue. However, institutional capacity building is still needed to deliver sustainable and standardized services that will ultimately improve retention rates. This article documents the steps China made in overcoming the many barriers to success of its methadone program. These lessons might be useful for other countries in the region that are scaling-up their methadone programs.

  18. Serotonin syndrome caused by fentanyl and methadone in a burn injury.

    PubMed

    Hillman, Ashley D; Witenko, Corey J; Sultan, Said M; Gala, Gary

    2015-01-01

    Serotonin syndrome is a syndrome identified by a triad of altered mental status, neuromuscular overactivity, and autonomic instability caused by the overstimulation of serotonin in the central nervous system and periphery. Serotonin syndrome may be provoked with the addition or increase in serotonergic agents such as selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors as well as other agents with serotonergic properties. Some narcotics, including fentanyl and methadone, have these properties and may be associated with the development of serotonin syndrome when used in conjunction with other agents. Currently, there are no identified case reports of narcotics as the sole agent causing serotonin syndrome. This report provides a brief overview of serotonin syndrome, particularly with cases involving administration of narcotics such as fentanyl and methadone. The case described is the first report associated with fentanyl and methadone without the coadministration of other serotonergic agents, and a possible drug interaction with voriconazole is discussed. This raises awareness of using multiple serotonergic narcotics and the potential precipitation of serotonin syndrome.

  19. Quality of life among former Soviet Union and Israeli origin methadone users.

    PubMed

    Isralowitz, Richard; Reznik, Alexander; Pruginin, Itay

    2016-01-01

    A common treatment intervention for heroin addiction is methadone maintenance. In recent years a wider perspective has been adapted to understand and evaluate addiction through quality of life. This article examines quality of life conditions of 170 male former Soviet Union and Israeli origin drug users in methadone maintenance and provides an understanding of conditions linked to the World Health Organization Quality of Life project's best available techniques reference document. Having a partner or spouse and less chronic illness are positive factors affecting quality of life regardless of country of origin. Israeli born drug users reported better quality of life based on their psychological health and environment domain responses; no difference was found for the physical health and social relationship domains of the Israeli and former Soviet Union origin males. Because heroin addiction is a chronic and relapsing illness, one of the goals of methadone maintenance is to address patients' health status from a broad perspective. Based on clinical observations, the treatment of special populations may be enhanced if their particular needs are considered and met. Quality of life factors are relevant for assessing high risk groups, including those from different ethnic origins, in poor physical and psychological health, their treatment and personal adjustment, and their service personnel training needs.

  20. Concurrent Alcohol Dependence Among Methadone-Maintained Cocaine Abusers Is Associated with Greater Abstinence

    PubMed Central

    Byrne, Shannon A.; Petry, Nancy M.

    2011-01-01

    Concurrent alcohol dependence (AD) among polysubstance abusers has been associated with negative consequences, although it may not necessarily lead to poor treatment outcomes. One of the most efficacious treatments for cocaine abuse is contingency management (CM), but little research has explored the impact of AD on abstinence outcomes, particularly among patients in methadone maintenance. Using data from three trials of CM for cocaine use, we compared baseline characteristics and post-treatment and follow-up cocaine outcomes between methadone maintained, cocaine dependent patients (N=193) with and without concurrent AD, randomized to standard care (SC) with or without CM. Patients with and without concurrent AD had similar baseline characteristics, with the exception that AD patients reported more alcohol use. AD patients achieved longer durations of cocaine abstinence and were more likely to submit a cocaine negative sample at follow-up than non-AD patients. Patients randomized to CM achieved better outcomes than those randomized to SC, but there was no interaction between treatment condition and AD status. These findings suggest that cocaine using methadone patients with AD achieve greater cocaine abstinence than their non-AD counterparts and should not be necessarily viewed as more difficult to treat. PMID:21463068

  1. Detoxification of azo dyes in the context of environmental processes.

    PubMed

    Rawat, Deepak; Mishra, Vandana; Sharma, Radhey Shyam

    2016-07-01

    Azo dyes account for >70% of the global industrial demand (∼9 million tons). Owing to their genotoxic/carcinogenic potential, the annual disposal of ∼4,500,000 tons of dyes and/or degraded products is an environmental and socio-economic concern. In comparison to physico-chemical methods, microbe-mediated dye degradation is considered to be low-input, cost-effective and environmentally-safe. However, under different environmental conditions, interactions of chemically diverse dyes with metabolically diverse microbes produce metabolites of varying toxicity. In addition, majority of studies on microbial dye-degradation focus on decolorization with least attention towards detoxification. Therefore, the environmental significance of microbial dye detoxification research of past >3 decades is critically evaluated with reference to dye structure and the possible influence of microbial interactions in different environments. In the absence of ecosystem-based studies, the results of laboratory-based studies on dye degradation, metabolite production and their genotoxic impact on model organisms are used to predict the possible fate and consequences of azo dyes/metabolites in the environment. In such studies, the predominance of fewer numbers of toxicological assays that too at lower levels of biological organization (molecular/cellular/organismic) suggests its limited ecological significance. Based on critical evaluation of these studies the recommendations on inclusion of multilevel approach (assessment at multiple levels of biological organization), multispecies microcosm approach and native species approach in conjunction with identification of dye metabolites have been made for future studies. Such studies will bridge the gap between the fundamental knowledge on dye-microbe-environment interactions and its application to combat dye-induced environmental toxicity. Thus an environmental perspective on dye toxicity in the background of dye structure and effects of

  2. Are methadone counselors properly equipped to meet the palliative care needs of older adults in methadone maintenance treatment? Implications for training.

    PubMed

    Doukas, Nick

    2014-01-01

    Today's methadone patients differ greatly from those of the past. Because of the rise of polydrug use and the HIV and hepatitis epidemics, treatment has become much more complex, which multiply the concerns and complexities of treatment. Patients entering methadone programs are also more commonly presenting at ages well into their 50s, 60s, and 70s; and this phenomenon of high rates continues to grow. The majority of these individuals in treatment have presented with a number of significant comorbid medical conditions that will progress and eventually lead to death. This aging cohort must be approached with a modified treatment plan that focuses on management and promoting healthy aging, while attending to their maximum delay of illness, disease, and disability. This article argues that it is necessary for counselors working with this group to adopt a palliative care philosophy. This article also makes recommendations in areas that counselors need to be knowledgeable and skilled in to provide appropriate palliative services specific to this aging population with multiple needs as they near end of life.

  3. Bio-inspired detoxification using 3D-printed hydrogel nanocomposites

    NASA Astrophysics Data System (ADS)

    Gou, Maling; Qu, Xin; Zhu, Wei; Xiang, Mingli; Yang, Jun; Zhang, Kang; Wei, Yuquan; Chen, Shaochen

    2014-05-01

    Rationally designed nanoparticles that can bind toxins show great promise for detoxification. However, the conventional intravenous administration of nanoparticles for detoxification often leads to nanoparticle accumulation in the liver, posing a risk of secondary poisoning especially in liver-failure patients. Here we present a liver-inspired three-dimensional (3D) detoxification device. This device is created by 3D printing of designer hydrogels with functional polydiacetylene nanoparticles installed in the hydrogel matrix. The nanoparticles can attract, capture and sense toxins, while the 3D matrix with a modified liver lobule microstructure allows toxins to be trapped efficiently. Our results show that the toxin solution completely loses its virulence after treatment using this biomimetic detoxification device. This work provides a proof-of-concept of detoxification by a 3D-printed biomimetic nanocomposite construct in hydrogel, and could lead to the development of alternative detoxification platforms.

  4. Bio-inspired detoxification using 3D-printed hydrogel nanocomposites.

    PubMed

    Gou, Maling; Qu, Xin; Zhu, Wei; Xiang, Mingli; Yang, Jun; Zhang, Kang; Wei, Yuquan; Chen, Shaochen

    2014-05-08

    Rationally designed nanoparticles that can bind toxins show great promise for detoxification. However, the conventional intravenous administration of nanoparticles for detoxification often leads to nanoparticle accumulation in the liver, posing a risk of secondary poisoning especially in liver-failure patients. Here we present a liver-inspired three-dimensional (3D) detoxification device. This device is created by 3D printing of designer hydrogels with functional polydiacetylene nanoparticles installed in the hydrogel matrix. The nanoparticles can attract, capture and sense toxins, while the 3D matrix with a modified liver lobule microstructure allows toxins to be trapped efficiently. Our results show that the toxin solution completely loses its virulence after treatment using this biomimetic detoxification device. This work provides a proof-of-concept of detoxification by a 3D-printed biomimetic nanocomposite construct in hydrogel, and could lead to the development of alternative detoxification platforms.

  5. Bio-inspired detoxification using 3D-printed hydrogel nanocomposites

    PubMed Central

    Gou, Maling; Qu, Xin; Zhu, Wei; Xiang, Mingli; Yang, Jun; Zhang, Kang; Wei, Yuquan; Chen, Shaochen

    2014-01-01

    Rationally designed nanoparticles that can bind toxins show great promise for detoxification. However, the conventional intravenous administration of nanoparticles for detoxification often leads to nanoparticle accumulation in the liver, posing a risk of secondary poisoning especially in liver-failure patients. Here we present a liver-inspired three-dimensional (3D) detoxification device. This device is created by 3D printing of designer hydrogels with functional polydiacetylene nanoparticles installed in the hydrogel matrix. The nanoparticles can attract, capture and sense toxins, while the 3D matrix with a modified liver lobule microstructure allows toxins to be trapped efficiently. Our results show that the toxin solution completely loses its virulence after treatment using this biomimetic detoxification device. This work provides a proof-of-concept of detoxification by a 3D-printed biomimetic nanocomposite construct in hydrogel, and could lead to the development of alternative detoxification platforms. PMID:24805923

  6. Arrhythmia Associated with Buprenorphine and Methadone Reported to the Food and Drug Administration

    PubMed Central

    Kao, David P; Haigney, Mark CP; Mehler, Philip S; Krantz, Mori J

    2015-01-01

    Aim To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, QTc prolongation, or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone. Design Retrospective pharmacoepidemiologic study Setting Adverse drug events spontaneously reported to the FDA between 1969-June 2011 originating in 196 countries (71% events from the US). Cases Adverse event cases mentioning methadone (n=14,915) or buprenorphine (n=7,283) were evaluated against all other adverse event cases (n= 4,796,141). Measurements The primary outcome was the composite of ventricular arrhythmia or cardiac arrest. The secondary outcome was the composite of QTc prolongation or torsade de pointes. The proportional reporting ratio (PRR) was used to identify disproportionate reporting defined as a PRR>2, χ2 error>4, with ≥3 cases. Findings There were 132 (1.8%) ventricular arrhythmia/cardiac arrest and 19 (0.3%) QTc prolongation/torsade de pointes cases associated with buprenorphine compared with 1729 (11.6%) ventricular arrhythmia/cardiac arrest and 390 (2.6%) QTc prolongation/torsade de pointes cases involving methadone. PRRs associated with buprenorphine were not significant for ventricular arrhythmia/cardiac arrest (1.1 95% confidence interval (CI) 0.9–1.3, χ2=1.2) or QTc prolongation/torsade de pointes (1.0 95% CI 0.7–1.9, χ2=0.0006), but were for methadone (7.2 95% CI 6.9–7.5, χ2=9160; 10.6 95% CI 9.7–11.8, χ2=3305, respectively). Conclusion In spontaneously reported adverse events, methadone is associated with disproportionate reporting of cardiac arrhythmias, whereas buprenorphine is not. Although these findings probably reflect clinically relevant differences, a causal connection cannot be presumed and disproportionality analysis cannot quantify absolute risk per treatment episode. Population-based studies to definitively quantify differential incidence rates are warranted. PMID:26075588

  7. The effect of changes in gastric pH induced by omeprazole on the absorption and respiratory depression of methadone.

    PubMed

    de Castro, J; Aguirre, C; Rodríguez-Sasiaín, J M; Gómez, E; Garrido, M J; Calvo, R

    1996-10-01

    The effect of omeprazole (2 mg kg-1 i.v.) on respiratory depression induced in rats by acute oral methadone administration (5 mg kg-1) was examined and compared with control animals that only received methadone. Quantitative assessments of arterial Pco2,Po2, pH, and respiratory rate were employed as criteria for evaluation. Intragastric pH was measured in each rat immediately before and 2 h after methadone. Plasma concentration of methadone was measured for 3 h. The relationship between drug effect and the systemic bioavailability of methadone, measured as the area under the plasma concentration-time curve (AUC0-180), was also evaluated. The intensity of the methadone-induced respiratory depression was significantly greater in the omeprazole group than in control rats. A significant variation (p < 0.01) in all respiratory parameters was detected from 30 to 120 min after methadone. Omeprazole caused a significant increase in methadone levels (Cmax = 156 +/- 6.5 ng mL-1 against 51 +/- 5.8 ng mL-1 in control; p < 0.05). AUC0-180 was higher (p < 0.05) after omeprazole treatment (18.6 +/- 1.4 micrograms mL-1 min) than in control (6.8 +/- 0.6 microgram mL-1 min). Two hours after treatment with omeprazole, intragastric pH values were significantly elevated (4.7 +/- 0.1 against 2.2 +/- 0.04) and continued increasing, being 6.4 +/- 0.1 at the end of the experiment. Correlation was observed between intragastric pH and the area under the effect- (respiratory depression-) time curve (r = 0.74; p < 0.001). A relationship between plasma methadone levels at 120 min and gastric pH (r = 0.92; p < 0.001) was detected. A significant correlation between the area under the effect-time curve (0-120 min) and AUC0-180 has been also observed (r = 0.90; p < 0.01). These pharmacokinetic and pharmacodynamic changes could be gastric pH dependent because they were mimicked when gastric pH was experimentally modified by bicarbonate whereas opposite results were obtained with acidic pH2 solution.

  8. “I kicked the hard way. I got incarcerated.” Withdrawal from methadone during incarceration and subsequent aversion to medication assisted treatments

    PubMed Central

    Maradiaga, Jeronimo A.; Nahvi, Shadi; Cunningham, Chinazo O.; Sanchez, Jennifer; Fox, Aaron D.

    2016-01-01

    Incarceration is a common experience for individuals with opioid use disorder, including those receiving medication assisted treatments (MAT), such as buprenorphine or methadone. In the United States, MAT is rarely available during incarceration. We were interested in whether challenges with methadone maintenance treatment during incarceration affected subsequent attitudes toward MAT following release. We conducted semi-structured interviews with 21 formerly incarcerated individuals with opioid use disorder in community substance abuse treatment settings. Interviews were audio recorded, transcribed, and analyzed using a grounded theory approach. Themes that emerged upon iterative readings of transcripts were discussed by the research team. The three main themes relating to methadone were: 1) rapid dose reduction during incarceration; 2) discontinuity of methadone during incarceration; and 3) post incarceration aversion to methadone. Participants who received methadone maintenance treatment prior to incarceration reported severe and prolonged withdrawal symptoms from rapid dose reductions or disruption of their methadone treatment during incarceration. The severe withdrawal during incarceration contributed to a subsequent aversion to methadone and adversely affected future decisions regarding reengagement in MAT. Though MAT is the most efficacious treatment for opioid use disorder, current penal policy, which typically requires cessation of MAT during incarceration, may dissuade individuals with opioid use disorder from considering and engaging in MAT after release from incarceration. PMID:26747509

  9. Psychiatric comorbidity and additional abuse of drugs in maintenance treatment with L- and D,L-methadone.

    PubMed

    Wedekind, Dirk; Jacobs, Stefan; Karg, Iris; Luedecke, Christel; Schneider, Udo; Cimander, Konrad; Baumann, Pierre; Ruether, Eckart; Poser, Wolfgang; Havemann-Reinecke, Ursula

    2010-03-01

    Sixty D,L- or L-methadone treated patients in maintenance therapy were interviewed for additional drug abuse and psychiatric comorbidity; 51.7% of the entire population had a comorbid Axis-I disorder, with a higher prevalence in females (P=0.05). Comorbid patients tended to have higher abuse of benzodiazepines, alcohol, cannabis, and cocaine, but not of heroin. They had received a significantly lower D,L- (P<0.05) and L-methadone dose than non-comorbid subjects. The duration of maintenance treatment showed an inverse relationship to frequency of additional heroin intake (P<0.01). Patients with additional heroin intake over the past 30 days had been treated with a significantly lower L-methadone dosage (P<0.05) than patients without. Axis-I comorbidity appears to be decreased when relatively higher dosages of D,L- (and L-methadone) are administered; comorbid individuals, however, were on significantly lower dosages. Finally, L-, but not D,L-methadone seems to be more effective in reducing additional heroin abuse.

  10. Detoxification of lantana hepatotoxin, lantadene A, using Alcaligenes faecalis.

    PubMed

    Singh, A; Sharma, O P; Kurade, N P; Ojha, S

    2001-01-01

    Detoxification of lantadene A (LA), the hepatotoxin from Lantana camara var. aculeata, by the bacterial strain Alcaligenes faecalis has been investigated. Lantadene A induced hepatotoxicity concomitant with increases in plasma bilirubin, blood plasma enzymes and histopathological lesions that typify lantana toxicity. The extract of fermentation broth in which LA was incubated with A. faecalis did not elicit any alterations in blood enzyme prolife or liver histopathology, which were comparable with the control group. It is concluded that A. faecalis detoxified LA and no noxious product was formed on incubation of LA with A. faecalis.

  11. The psychometric properties of the iowa personality disorder screen in methadone-maintained patients: an initial investigation.

    PubMed

    Beitel, Mark; Peters, Skye; Savant, Jonathan D; Cutter, Christopher J; Cecero, John J; Barry, Declan T

    2015-02-01

    The psychometric properties of the Iowa Personality Disorder Screen (IPDS) were examined in 150 methadone-maintained patients who completed measures of demographic, psychopathology, substance use, pain, and methadone maintenance treatment (MMT) characteristics. An exploratory factor analysis revealed a two-factor solution that explained 45% of the scale variance. The first factor captured internalizing tendencies, such as inhibition and hypersensitivity to others. The second factor comprised externalizing tendencies, such as impulsivity and insensitivity to others. The IPDS item subsets, derived factors, and the total score were significantly related to race/ethnicity but not sex. The effects of race/ethnicity were controlled statistically when the IPDS was compared to other measures of psychopathology, self-reported substance use, pain variables, and MMT characteristics. In general, the IPDS appears to be reliable and valid for use with methadone-maintained patients. The two-factor structure found in this study may have clinical utility and merits further investigation in other MMT samples.

  12. Clinical Presentation and the Outcome of Therapy in a Cohort of Patients with Methadone Toxicity in Iran

    PubMed Central

    Eizadi-Mood, Nastaran; Yaraghi, Ahmad; Sharifian, Zahra; Feizi, Awat; Hedaiaty, Mahrang; Sabzghabaee, Ali Mohammad

    2015-01-01

    Background: Agonist maintenance therapy with methadone is amongst the preferred remedies for treating opioid dependence and is increasingly supported by the regional governments in this part of the world. In this study we have investigated the clinical manifestations and factors affecting the outcome of therapy in patients with methadone poisoning in a Middle-Eastern (Iranian) referral tertiary care University hospital. Methods: In this prospective and descriptive-analytic study which was done in a tertiary care and referral University hospital in Iran (2012-2013) all of the admitted patients with a clear and reliable history of methadone poisoning (n=433) were included and demographic data, Clinical status on admission including Glasgow Coma Scale (GCS) score, time elapsed from ingestion to hospital admission, average dose of naloxone used, any history of psychiatric disorder, type of toxic exposure, co ingestion of other medication, hospitalization time and the outcome were recorded and statistically analyzed. Results: The average length of hospital stay was 33 ± 26 hours. 80.1% of patients had ingested methadone alone, and 90.3% survived. Complications were pulmonary edema (7%), aspiration pneumonia (1.4%), generalized tonic colonic seizure (0.9%), and renal failure (0.5%). GCS, systolic blood pressure and respiratory rate were lower in fatal cases and GCS had prognostic value for the outcome of therapy in methadone intoxicated patients. Patients with higher GCS on admission had better outcome [OR =0.47 (95% CI: 0.38-0.580); P value< 0.0001]. Conclusion: Admission time GCS score maybe considered as an important predictor for the outcome of therapy in methadone poisoning. PMID:26543423

  13. Post-prison Release HIV-Risk Behaviors in a Randomized Trial of Methadone Treatment for Prisoners

    PubMed Central

    Wilson, Monique E.; Kinlock, Timothy W.; Gordon, Michael S.; O’Grady, Kevin E.; Schwartz, Robert P.

    2012-01-01

    Background This secondary analysis examined the impact of methadone initiated in prison on post-release HIV risk behaviors. The parent study was a three-group randomized clinical trial in which participants received drug abuse counseling in prison and were randomly assigned to: (1) passive referral to substance abuse treatment upon release; (2) guaranteed methadone treatment admission upon release; and (3) methadone in prison and guaranteed continuation of methadone upon release. Methods Participants were 211 adult males with pre-incarceration histories of opiate dependence. The AIDS Risk Assessment was administered at baseline (in prison) and at 1-, 3-, 6-, and 12-months post-release. Data were analyzed for the entire sample (N = 211) as well as the subsamples who reported injecting drugs in the 30 days prior to incarceration (n = 131) and who reported having unprotected sex in that time frame (n = 144) using generalized linear mixed model on an intent-to-treat basis. Results There were no significant changes in sex- or drug-risk by Condition over Time. There were significant Time and Condition main effects for the total sample as well as the injector subsample for drug-risk behaviors. There were no significant Condition main effects for HIV sex–risk behaviors, but there were significant Time main effects. Conclusions Methadone initiated in prison or immediately post-release is associated with reduced HIV drug-risk compared to counseling in prison without methadone and passive referral to treatment at release. Participation in several drug- and sex-risk behaviors also showed significant declines during the post-release time periods. PMID:22882399

  14. Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients.

    PubMed

    Yang, Hsin-Chou; Chu, Shih-Kai; Huang, Chieh-Liang; Kuo, Hsiang-Wei; Wang, Sheng-Chang; Liu, Sheng-Wen; Ho, Ing-Kang; Liu, Yu-Li

    2016-03-01

    Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new

  15. Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients

    PubMed Central

    Yang, Hsin-Chou; Chu, Shih-Kai; Huang, Chieh-Liang; Kuo, Hsiang-Wei; Wang, Sheng-Chang; Liu, Sheng-Wen; Ho, Ing-Kang; Liu, Yu-Li

    2016-01-01

    Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10−8), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new

  16. Identification of glucuronide metabolites of d- and 1-methadone in bile from the isolated perfused rat liver.

    PubMed

    Lynn, R K; Leger, R M; Gerber, N

    1976-09-01

    Three hydroxylated metabolites of methadone, 2-ethyl-3-(dihydroxyphenyl)-5-methyl-3-phenylpyrroline (di-HO-EMDP), 2-ethyl-3-(hydroxy-methoxy-phenyl)-5-methyl-3-phenylpyrroline (HO-MeO-EMDP) and 2-ethyl-3-(hydroxy-phenyl)-5-methyl-3-phenylpyrroline (HO-EMDP) were excreted as O-glucuronide conjugates in bile from the isolated perfused rat liver following the addition of either d- or 1-methadone to the perfusate. These glucuronide metabolites were identified as intact molecules by combined gas chromatographic-mass spectrometric (GC-MS) analysis of their permethylated derivatives.

  17. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

    PubMed Central

    Wurst, Keele E.; Zedler, Barbara K.; Joyce, Andrew R.; Sasinowski, Maciek; Murrelle, E. Lenn

    2016-01-01

    BACKGROUND Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father. CONCLUSIONS An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment

  18. Nitric oxide detoxification in the rhizobia-legume symbiosis.

    PubMed

    Sánchez, Cristina; Cabrera, Juan J; Gates, Andrew J; Bedmar, Eulogio J; Richardson, David J; Delgado, María J

    2011-01-01

    NO (nitric oxide) is a signal molecule involved in diverse physiological processes in cells which can become very toxic under certain conditions determined by its rate of production and diffusion. Several studies have clearly shown the production of NO in early stages of rhizobia-legume symbiosis and in mature nodules. In functioning nodules, it has been demonstrated that NO, which has been reported as a potent inhibitor of nitrogenase activity, can bind Lb (leghaemoglobin) to form LbNOs (nitrosyl-leghaemoglobin complexes). These observations have led to the question of how nodules overcome the toxicity of NO. On the bacterial side, one candidate for NO detoxification in nodules is the respiratory Nor (NO reductase) that catalyses the reduction of NO to nitrous oxide. In addition, rhizobial fHbs (flavohaemoglobins) and single-domain Hbs which dioxygenate NO to form nitrate are candidates to detoxify NO under free-living and symbiotic conditions. On the plant side, sHbs (symbiotic Hbs) (Lb) and nsHbs (non-symbiotic Hbs) have been proposed to play important roles as modulators of NO levels in the rhizobia-legume symbiosis. In the present review, current knowledge of NO detoxification by legume-associated endosymbiotic bacteria is summarized.

  19. Biodegradation and detoxification of chloronitroaromatic pollutant by Cupriavidus.

    PubMed

    Tiwari, Jyoti; Naoghare, Pravin; Sivanesan, Saravanadevi; Bafana, Amit

    2017-01-01

    Current study reports isolation of Cupriavidus strain a3 which can utilize 2-chloro-4-nitrophenol (C4NP) as sole source of carbon and nitrogen, leading to its detoxification. Degradation process was initiated by release of nitrite ion resulting in the formation of 2-chlorohydroquinone as intermediate. The nitrite releasing activity was also evident in the cell free protein extract. Different parameters for 2C4NP biodegradation were optimized. The degradation pattern followed Haldane substrate inhibition model with maximum specific degradation rate (qmax) of 0.13/h, half saturation constant (Ks) of 0.05mM, and 2C4NP inhibition constant (Ki) of 0.64mM. The isolate was successfully applied to remediation of 2C4NP-contaminated soil in microcosm study. 2-Dimensional protein electrophoresis analysis showed that growth of the isolate in the presence of 2C4NP resulted in modification of membrane permeability and induction of signal transduction protein. In our knowledge, this is the first study reporting degradation and detoxification of 2C4NP by Cupriavidus.

  20. N-Acetylcysteine boosts xenobiotic detoxification in shellfish.

    PubMed

    Peña-Llopis, Samuel; Serrano, Roque; Pitarch, Elena; Beltrán, Eduardo; Ibáñez, María; Hernández, Félix; Peña, Juan B

    2014-09-01

    Water pollution represents a threat of increasing importance to human health. Bivalve mollusks are filter-feeding organisms that can accumulate chemical and microbiological contaminants in their tissues from very low concentrations in the water or sediments. Consumption of contaminated shellfish is one of the main causes of seafood poisoning. Thus, marine bivalves are normally depurated in sterilized seawater for 48 h to allow the removal of bacteria. However, this depuration time might be insufficient to eliminate chemical contaminants from their tissues. We have developed a novel technology that accelerates up to fourfold the excretion rate of xenobiotics in bivalves by treatment with the antioxidant and glutathione (GSH) pro-drug N-acetylcysteine (NAC) during the depuration period. NAC improved dose-dependently the detoxification of the organophosphate (OP) pesticide fenitrothion in the mussel Mytilus galloprovincialis, diminishing its levels up to nearly a hundred fold compared to conventional depuration, by enhancing the glutathione S-transferase (GST) activity and inducing the GSH anabolism (GSH synthesis and reduction by glutathione reductase). Notably, this induction in GSH anabolism and GST activity was also observed in uncontaminated bivalves treated with NAC. As the GSH pathway is involved in the detoxification of many pollutants and biotoxins from harmful algal blooms, we validated this proof of principle in king scallops (Pecten maximus) that naturally accumulated the amnesic shellfish poisoning (ASP) toxin domoic acid. We illustrate here a method that enhances the elimination of organic contaminants in shellfish, opening new avenues of depuration of marine organisms.

  1. Detoxification of Dissolved SO2 (Bisulfite) by Terricolous Mosses

    PubMed Central

    BHARALI, BHAGAWAN; BATES, JEFFREY W.

    2006-01-01

    • Background and Aims The widespread calcifuge moss Pleurozium schreberi is moderately tolerant of SO2, whereas Rhytidiadelphus triquetrus is limited to calcareous soils in regions of the UK that were strongly affected by SO2 pollution in the 20th century. The proposition that tolerance of SO2 by these terricolous mosses depends on metabolic detoxification of dissolved bisulfite was investigated. • Methods The capacities of the two mosses to accelerate loss of bisulfite from aqueous solutions of NaHSO3 were studied using DTNB [5, 5-dithio-(2-nitrobenzoic acid)] to assay bisulfite, and HPLC to assay sulfate in the incubation solutions. Incubations were performed for different durations, in the presence and absence of light, at a range of solution pH values, in the presence of metabolic inhibitors and with altered moss apoplastic Ca2+ and Fe3+ levels. • Key Results Bisulfite disappearance was markedly stimulated in the light and twice as great for R. triquetrus as for P. schreberi. DCMU, an inhibitor of photosynthetic electron chain transport, significantly reduced bisufite loss. • Conclusions Bisulfite (SO2) tolerance in these terricolous mosses involves extracellular oxidation using metabolic (photo-oxidative) energy, passive oxidation by adsorbed Fe3+ (only available to the calcifuge) and probably also internal metabolic detoxification. PMID:16319108

  2. DETOXIFICATION OF OUTFALL WATER USING NATURAL ORGANIC MATTER

    SciTech Connect

    Halverson, N.; Looney, B.; Millings, M.; Nichols, R.; Noonkester, J.; Payne, B.

    2010-07-13

    To protect stream organisms in an ephemeral stream at the Savannah River Site, a proposed National Pollutant Discharge Elimination System (NPDES) permit reduced the copper limit from 25 {micro}g/l to 6 {micro}g/l at Outfall H-12. Efforts to reduce copper in the wastewater and stormwater draining to this outfall did not succeed in bringing copper levels below this limit. Numerous treatment methods were considered, including traditional methods such as ion exchange and natural treatment alternatives such as constructed wetlands and peat beds, all of which act to remove copper. However, the very low target metal concentration and highly variable outfall conditions presented a significant challenge for these treatment technologies. In addition, costs and energy use for most of these alternatives were high and secondary wastes would be generated. The Savannah River National Laboratory developed an entirely new 'detoxification' approach to treat the outfall water. This simple, lower-cost detoxification system amends outfall water with natural organic matter to bind up to 25 {micro}g/l copper rather than remove it, thereby mitigating its toxicity and protecting the sensitive species in the ecosystem. The amendments are OMRI (Organic Materials Review Institute) certified commercial products that are naturally rich in humic acids and are commonly used in organic farming.

  3. Metal bioaccumulation and detoxification processes in cephalopods: A review.

    PubMed

    Penicaud, Virginie; Lacoue-Labarthe, Thomas; Bustamante, Paco

    2017-05-01

    In recent decades, cephalopods have been shown to have very high capacities to accumulate most trace elements, regardless of whether they are essential (e.g., Cu and Zn) or non-essential (e.g., Ag and Cd). Among the different pathways of exposure to trace elements, the trophic pathway appears to be the major route of assimilation for numerous metals, including Cd, Co, Hg and Zn. Once assimilated, trace elements are distributed in the organism, accumulating in storage organs. The digestive gland is the main organ in which many trace elements accumulate, whichever of the exposure pathway. For example, this organ can present Cd concentrations reaching hundreds to thousands of ppm for some species, even though the digestive gland represents only a small proportion of the total mass of the animal. Such a specific organotropism towards the digestive gland of both essential and non-essential elements, regardless of the exposure pathway, poses the question of the detoxification processes evolved by cephalopods in order to sustain these high concentrations. This paper reviews the current knowledge on the bioaccumulation of trace elements in cephalopods, the differences in pharmaco-dynamics between organs and tissues, and the detoxification processes they use to counteract trace element toxicity. A peculiar focus has been done on the bioaccumulation within the digestive gland by investigating the subcellular locations of trace elements and their protein ligands.

  4. Biocatalytic nerve agent detoxification in fire fighting foams.

    PubMed

    LeJeune, K E; Russell, A J

    1999-03-20

    Current events across the globe necessitate rapid technological advances to combat the epidemic of nerve agent chemical weapons. Biocatalysis has emerged as a viable tool in the detoxification of organophosphorus neurotoxins, such as the chemical weapons VX and sarin. Efficient detoxification of contaminated equipment, machinery, and soils are of principal concern. This study describes the incorporation of a biocatalyst (organophosphorus hydrolase, E.C. 3.1.8.1) into conventional formulations of fire fighting foam. The capacity of fire fighting foams to decrease volatilization of contained contaminants, increase surface wettability, and control the rate of enzyme delivery to large areas makes them useful vehicles for enzyme application at surfaces. The performance of enzyme containing foams has been shown to be not only reproducible but also predictable. An empirical model provides reasonable estimations for the amounts of achievable surface decontamination as a function of the important parameters of the system. Theoretical modeling illustrates that the enzyme-containing foam is capable of extracting agent from the surface and is catalytically active at the foam-surface interface and throughout the foam itself. Biocatalytic foam has proven to be an effective, "environmentally friendly" means of surface and soil decontamination.

  5. Optimality in the zonation of ammonia detoxification in rodent liver.

    PubMed

    Bartl, Martin; Pfaff, Michael; Ghallab, Ahmed; Driesch, Dominik; Henkel, Sebastian G; Hengstler, Jan G; Schuster, Stefan; Kaleta, Christoph; Gebhardt, Rolf; Zellmer, Sebastian; Li, Pu

    2015-11-01

    The rodent liver eliminates toxic ammonia. In mammals, three enzymes (or enzyme systems) are involved in this process: glutaminase, glutamine synthetase and the urea cycle enzymes, represented by carbamoyl phosphate synthetase. The distribution of these enzymes for optimal ammonia detoxification was determined by numerical optimization. This in silico approach predicted that the enzymes have to be zonated in order to achieve maximal removal of toxic ammonia and minimal changes in glutamine concentration. Using 13 compartments, representing hepatocytes, the following predictions were generated: glutamine synthetase is active only within a narrow pericentral zone. Glutaminase and carbamoyl phosphate synthetase are located in the periportal zone in a non-homogeneous distribution. This correlates well with the paradoxical observation that in a first step glutamine-bound ammonia is released (by glutaminase) although one of the functions of the liver is detoxification by ammonia fixation. The in silico approach correctly predicted the in vivo enzyme distributions also for non-physiological conditions (e.g. starvation) and during regeneration after tetrachloromethane (CCl4) intoxication. Metabolite concentrations of glutamine, ammonia and urea in each compartment, representing individual hepatocytes, were predicted. Finally, a sensitivity analysis showed a striking robustness of the results. These bioinformatics predictions were validated experimentally by immunohistochemistry and are supported by the literature. In summary, optimization approaches like the one applied can provide valuable explanations and high-quality predictions for in vivo enzyme and metabolite distributions in tissues and can reveal unknown metabolic functions.

  6. Detoxification of sulphidic African shelf waters by blooming chemolithotrophs

    NASA Astrophysics Data System (ADS)

    Lavik, Gaute; Stührmann, Torben; Brüchert, Volker; van der Plas, Anja; Mohrholz, Volker; Lam, Phyllis; Mußmann, Marc; Fuchs, Bernhard M.; Amann, Rudolf; Lass, Ulrich; Kuypers, Marcel M. M.

    2009-01-01

    Coastal waters support ~90 per cent of global fisheries and are therefore an important food reserve for our planet. Eutrophication of these waters, due to human activity, leads to severe oxygen depletion and the episodic occurrence of hydrogen sulphide-toxic to multi-cellular life-with disastrous consequences for coastal ecosytems. Here we show that an area of ~7,000km2 of African shelf, covered by sulphidic water, was detoxified by blooming bacteria that oxidized the biologically harmful sulphide to environmentally harmless colloidal sulphur and sulphate. Combined chemical analyses, stoichiometric modelling, isotopic incubations, comparative 16S ribosomal RNA, functional gene sequence analyses and fluorescence in situ hybridization indicate that the detoxification proceeded by chemolithotrophic oxidation of sulphide with nitrate and was mainly catalysed by two discrete populations of γ- and ɛ-proteobacteria. Chemolithotrophic bacteria, accounting for ~20 per cent of the bacterioplankton in sulphidic waters, created a buffer zone between the toxic sulphidic subsurface waters and the oxic surface waters, where fish and other nekton live. This is the first time that large-scale detoxification of sulphidic waters by chemolithotrophs has been observed in an open-ocean system. The data suggest that sulphide can be completely consumed by bacteria in the subsurface waters and, thus, can be overlooked by remote sensing or monitoring of shallow coastal waters. Consequently, sulphidic bottom waters on continental shelves may be more common than previously believed, and could therefore have an important but as yet neglected effect on benthic communities.

  7. Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa.

    PubMed

    Levitt, M D; Furne, J; Springfield, J; Suarez, F; DeMaster, E

    1999-10-01

    Colonic bacteria liberate large quantities of the highly toxic gases hydrogen sulfide (H(2)S) and methanethiol (CH(3)SH). The colonic mucosa presumably has an efficient means of detoxifying these compounds, which is thought to occur through methylation of H(2)S to CH(3)SH and CH(3)SH to dimethylsulfide (CH(3)SCH(3)). We investigated this detoxification pathway by incubating rat cecal mucosal homogenates with gas containing H(2)S, CH(3)SH, or CH(3)SCH(3). Neither CH(3)SH nor CH(3)SCH(3) was produced during H(2)S catabolism, whereas catabolism of CH(3)SH liberated H(2)S but not CH(3)SCH(3). Thus, H(2)S and CH(3)SH are not detoxified by methylation to CH(3)SCH(3). Rather, CH(3)SH is demethylated to H(2)S, and H(2)S is converted to nonvolatile metabolites. HPLC analysis of the homogenate showed the metabolite to be primarily thiosulfate. Analysis of cecal venous blood obtained after intracecal instillation of H(2)(35)S revealed that virtually all absorbed H(2)S had been oxidized to thiosulfate. The oxidation rate of H(2)S by colonic mucosa was 10,000 times greater than the reported methylation rate. Conversion to thiosulfate appears to be the mechanism whereby the cecal mucosa protects itself from the injurious effects of H(2)S and CH(3)SH, and defects in this detoxification possibly could play a role in colonic diseases such as ulcerative colitis.

  8. THE IMPACT OF LOW-THRESHOLD METHADONE MAINTENANCE TREATMENT ON MORTALITY IN A CANADIAN SETTING

    PubMed Central

    Nolan, Seonaid; Hyashi, Kanna; Milloy, M-J; Kerr, Thomas; Dong, Huiru; Lima, Viviane Dias; Lappalainen, Leslie; Montaner, Julio; Wood, Evan

    2015-01-01

    Background Methadone maintenance therapy (MMT) is among the most effective treatment modalities available for the management of opioid use disorder. However, the effect of MMT on mortality, and optimal strategies for delivering methadone are less clear. This study sought to estimate the effect of low-threshold MMT and its association with all-cause mortality among persons who inject drugs (PWID) in a setting where methadone is widely available through primary care physicians and community pharmacies at no cost through the setting’s universal medical insurance plan. Methods Between May, 1996 and December, 2011 data were collected as part of two prospective cohort studies of PWID in Vancouver, Canada, and were linked to the provincial vital statistics database to ascertain rates and causes of death. The association of MMT with all-cause mortality was estimated using multivariable extended Cox regression with timedependent variables. Results Of 2335 PWID providing 15027 person-years of observation, 511 deaths were observed for a mortality rate of 3.4 (95% Confidence Interval [CI]: 3.1 – 3.7) deaths per 100 person-years. After adjusting for potential confounders including age and HIV seropositivity, MMT enrolment was found to be associated with lower mortality (adjusted hazard ratio [AHR] = 0.73, 95% CI: 0.61 – 0.88). Conclusions While observed all-cause mortality rates among PWID in this setting were high, participation in low-threshold MMT was significantly associated with improved survival. These findings add to the known benefits of providing low-threshold MMT on reducing the harms associated with injection drug use. PMID:26455554

  9. Recovery from Mu-opioid Receptor Desensitization following Chronic Treatment with Morphine and Methadone

    PubMed Central

    Quillinan, Nidia; Lau, Elaine; Virk, Michael; von Zastrow, Mark; Williams, John T

    2011-01-01

    Chronic treatment with morphine results in a decrease in mu-opioid receptor sensitivity, an increase in acute desensitization and a reduction in the recovery from acute desensitization in locus coeruleus neurons. With acute administration, morphine is unlike many other opioid agonists in that it does not mediate robust acute desensitization or induce receptor trafficking. This study compares mu-opioid receptor desensitization and trafficking in brain slices taken from rats treated for 6–7 days with a range of doses of morphine (60, 30, 15 mg/kg/day) and methadone (60, 30, 5 mg/kg/day) applied by subcutaneous implantation of osmotic mini pumps. Mice were treated with 45 mg/kg/day. In morphine treated animals, recovery from acute [Met]5enkephalin-induced desensitization and receptor recycling was diminished. In contrast, recovery and recycling were unchanged in slices from methadone treated animals. Remarkably the reduced recovery from desensitization and receptor recycling found in slices from morphine treated animals were not observed in animals lacking β-arrestin2. Further, pharmacological inhibition of GRK2, while not affecting the ability of [Met]5enkephalin to induce desensitization, acutely reversed the delay in recovery from desensitization produced by chronic morphine treatment. These results characterize a previously unidentified function of the GRK/arrestin system in mediating opioid regulation in response to chronic morphine administration. They also suggest that the GRK/arrestin system, rather then serving as a primary mediator of acute desensitization, controls recovery from desensitization by regulating receptor reinsertion to the plasma membrane after chronic treatment with morphine. The sustained GRK/arrestin dependent desensitization is another way in which morphine and methadone are distinguished. PMID:21430144

  10. 21 CFR 1304.24 - Records for maintenance treatment programs and detoxification treatment programs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Records for maintenance treatment programs and detoxification treatment programs. 1304.24 Section 1304.24 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION... treatment programs and detoxification treatment programs. (a) Each person registered or authorized...

  11. 21 CFR 1304.24 - Records for maintenance treatment programs and detoxification treatment programs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Records for maintenance treatment programs and detoxification treatment programs. 1304.24 Section 1304.24 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION... treatment programs and detoxification treatment programs. (a) Each person registered or authorized...

  12. 21 CFR 1304.24 - Records for maintenance treatment programs and detoxification treatment programs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Records for maintenance treatment programs and detoxification treatment programs. 1304.24 Section 1304.24 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION... treatment programs and detoxification treatment programs. (a) Each person registered or authorized...

  13. Client Impact Study of Six Detoxification Centers ("Sub-Acute Receiving Centers").

    ERIC Educational Resources Information Center

    Mayer, Steven E.; And Others

    Results are reported of a study to determine the effects of detoxification centers on the people who use their services. A detoxification center is "a social rehabilitation facility established for the purpose of facilitating access into care and rehabilitation by detoxifying and evaluating the person and providing entrance into the continuum…

  14. Is Internet Addiction Prevalent Among Methadone Maintenance Treatment Patients? Data from Las Vegas and Tel Aviv.

    PubMed

    Peles, Einat; Linzy, Shirley; Sason, Anat; Tene, Oren; Adelson, Miriam

    2015-01-01

    Internet addiction is known to be associated with depression. The Internet Addiction Test (IAT) and the Center for Epidemiologic Studies Depression scale (CES-D) for depression were studied among non-selective methadone maintenance treatment patients from the United States (n = 164) and Israel (n = 113). Thirty percent were not exposed to the internet, and 2.9% (n = 8) had an "occasional/frequent problem." The IAT and CES-D scores correlated significantly (p = .03). The non-exposed group was older, less educated, and had more benzodiazepine abusers. Unlike other behavioral addictions that characterized these patients, the internet addiction problem is rare, but should not be ignored.

  15. In silico ordinary differential equation/partial differential equation hemodialysis model estimates methadone removal during dialysis

    PubMed Central

    Linares, Oscar A; Schiesser, William E; Fudin, Jeffrey; Pham, Thien C; Bettinger, Jeffrey J; Mathew, Roy O; Daly, Annemarie L

    2015-01-01

    Background There is a need to have a model to study methadone’s losses during hemodialysis to provide informed methadone dose recommendations for the practitioner. Aim To build a one-dimensional (1-D), hollow-fiber geometry, ordinary differential equation (ODE) and partial differential equation (PDE) countercurrent hemodialyzer model (ODE/PDE model). Methodology We conducted a cross-sectional study in silico that evaluated eleven hemodialysis patients. Patients received a ceiling dose of methadone hydrochloride 30 mg/day. Outcome measures included: the total amount of methadone removed during dialysis; methadone’s overall intradialytic mass transfer rate coefficient, km; and, methadone’s removal rate, jME. Each metric was measured at dialysate flow rates of 250 mL/min and 800 mL/min. Results The ODE/PDE model revealed a significant increase in the change of methadone’s mass transfer with increased dialysate flow rate, %Δkm=18.56, P=0.02, N=11. The total amount of methadone mass transferred across the dialyzer membrane with high dialysate flow rate significantly increased (0.042±0.016 versus 0.052±0.019 mg/kg, P=0.02, N=11). This was accompanied by a small significant increase in methadone’s mass transfer rate (0.113±0.002 versus 0.014±0.002 mg/kg/h, P=0.02, N=11). The ODE/PDE model accurately predicted methadone’s removal during dialysis. The absolute value of the prediction errors for methadone’s extraction and throughput were less than 2%. Conclusion ODE/PDE modeling of methadone’s hemodialysis is a new approach to study methadone’s removal, in particular, and opioid removal, in general, in patients with end-stage renal disease on hemodialysis. ODE/PDE modeling accurately quantified the fundamental phenomena of methadone’s mass transfer during hemodialysis. This methodology may lead to development of optimally designed intradialytic opioid treatment protocols, and allow dynamic monitoring of outflow plasma opioid concentrations for model

  16. AAS and AES determination of furaltadone, methadone and trazodone in pharmaceutical formulations.

    PubMed

    Khalil, S; El-Ries, M A

    2002-01-01

    Ion-associate complexes of furaltadone, methadone and trazodone hydrochlorides with [Cd(SCN)(4)](2-) and [Zn(SCN)(4)](2-) were precipitated and the excess unreacted cadmium or zinc complex was determined. A new method using atomic emission and atomic absorption spectrometry for the determination of the above drugs in pure solutions and in pharmaceutical preparations is given. The drugs can be determined by the affort method in the ranges 7.2-72.16, 6.9-69.18 and 8.1-81.6 microg/ml solutions of the three drugs, respectively.

  17. Lipid signalling couples translational surveillance to systemic detoxification in Caenorhabditis elegans

    PubMed Central

    Govindan, J. Amaranath; Jayamani, Elamparithi; Zhang, Xinrui; Breen, Peter; Larkins-Ford, Jonah; Mylonakis, Eleftherios

    2015-01-01

    Translation in eukaryotes is surveilled to detect toxins and virulence factors and coupled to the induction of defense pathways. C. elegans germline-specific mutations in translation components are detected by this system to induce detoxification and immune responses in distinct somatic cells. An RNAi screen revealed gene inactivations that act at multiple steps in lipid biosynthetic and kinase pathways that act upstream of MAP kinase to mediate the systemic communication of translation-defects to induce detoxification genes. Mammalian bile acids can rescue the defect in detoxification gene induction caused by C. elegans lipid biosynthetic gene inactivations. Extracts prepared from C. elegans with translation deficits but not from wild type can also rescue detoxification gene induction in lipid biosynthetic defective strains. These eukaryotic antibacterial countermeasures are not ignored by bacteria: particular bacterial species suppress normal C. elegans detoxification responses to mutations in translation factors. PMID:26322678

  18. Treatment-like steady-state methadone in rats interferes with incubation of cocaine sensitization and associated alterations in gene expression☆

    PubMed Central

    Leri, Francesco; Zhou, Yan; Carmichael, Brendan; Cummins, Erin; Kreek, Mary Jeanne

    2013-01-01

    In a previous study, steady-state methadone treatment was found to prevent associative cocaine learning, as well as related decreases in mRNA expression of preprohypocretin/preproorexin (ppHcrt) in the lateral hypothalamus (LH) and dopamine D2 receptor (DR2) in the caudate-putamen (CP), and increases in mu-opioid receptor in the ventral striatum of rats. To investigate whether the same regimen of methadone exposure could prevent the incubation of cocaine sensitization and related alterations in gene expression, male Sprague–Dawley rats received 45 mg/kg/day steadydose “binge” cocaine administration (IP) for 14 days followed by mini-pumps releasing 30 mg/kg/day methadone (SC). After 14 days of methadone, and a subsequent 10-day drug-free period, all rats were tested for sensitization (cocaine test dose: 15 mg/kg) and brain tissue was collected to quantify mRNA expression. Rats exposed to cocaine displayed cocaine-induced stereotypy at test, as well as enhanced ppHcrt mRNA in the LH and reduced DR2 mRNA in the CP. Importantly, these alterations were significantly reduced in rats treated with methadone following cocaine. These results suggest that steady-state methadone can interfere with the incubation of neuroadaptations underlying changes in behavioral responses to cocaine and cocaine-associated stimuli, and that these effects can be observed even after withdrawal from methadone. PMID:21745729

  19. Treatment-like steady-state methadone in rats interferes with incubation of cocaine sensitization and associated alterations in gene expression.

    PubMed

    Leri, Francesco; Zhou, Yan; Carmichael, Brendan; Cummins, Erin; Kreek, Mary Jeanne

    2012-02-01

    In a previous study, steady-state methadone treatment was found to prevent associative cocaine learning, as well as related decreases in mRNA expression of preprohypocretin/preproorexin (ppHcrt) in the lateral hypothalamus (LH) and dopamine D2 receptor (DR2) in the caudate-putamen (CP), and increases in mu-opioid receptor in the ventral striatum of rats. To investigate whether the same regimen of methadone exposure could prevent the incubation of cocaine sensitization and related alterations in gene expression, male Sprague-Dawley rats received 45 mg/kg/day steady-dose "binge" cocaine administration (IP) for 14 days followed by mini-pumps releasing 30 mg/kg/day methadone (SC). After 14 days of methadone, and a subsequent 10-day drug-free period, all rats were tested for sensitization (cocaine test dose: 15 mg/kg) and brain tissue was collected to quantify mRNA expression. Rats exposed to cocaine displayed cocaine-induced stereotypy at test, as well as enhanced ppHcrt mRNA in the LH and reduced DR2 mRNA in the CP. Importantly, these alterations were significantly reduced in rats treated with methadone following cocaine. These results suggest that steady-state methadone can interfere with the incubation of neuroadaptations underlying changes in behavioral responses to cocaine and cocaine-associated stimuli, and that these effects can be observed even after withdrawal from methadone.

  20. Disentangling Detoxification: Gene Expression Analysis of Feeding Mountain Pine Beetle Illuminates Molecular-Level Host Chemical Defense Detoxification Mechanisms

    PubMed Central

    Robert, Jeanne A.; Pitt, Caitlin; Bonnett, Tiffany R.; Yuen, Macaire M. S.; Keeling, Christopher I.; Bohlmann, Jörg; Huber, Dezene P. W.

    2013-01-01

    The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae) that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq) of mountain pine beetle male and female adults either starved or fed in male-female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S-transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle. PMID:24223726

  1. Single and Repeated Ultra-Rapid Detoxification Prevents Cognitive Impairment in Morphine Addicted Rats: A Privilege for Single Detoxification

    PubMed Central

    Ghamati, Leila; Hajali, Vahid; Sheibani, Vahid; Esmaeilpour, Khadijeh; Sepehri, Gholamreza; Shojaee, Mojtaba

    2014-01-01

    Background Opioids have been shown to affect learning and memory processes. Different protocols of morphine withdrawal can substantially vary in their success to prevent opioid induced impairments of cognitive performance. In the present study, we report the effects of single and repetitive ultra-rapid detoxification (URD) on spatial learning and memory in morphine addicted rats. Methods Morphine (10 mg/kg) was intraperitoneally (IP) injected in male rats once a day over one week and after which they were detoxified with naloxone administration under anesthesia. For the repetitive procedure, a second one week morphine treatment with a second subsequent detoxification was performed. Control groups received an equivalent volume of saline injections. Spatial learning and memory was evaluated using the Morris water maze (MWM) task. Findings Both protocols of morphine administration resulted in a severe spatial memory impairment that could be significantly prevented by both single and repetitive URD. However, memory abilities in animals treated with repetitive URD were still significantly lower than in animals of the corresponding control group. Alterations in motor activity or sensory-motor coordination between morphine treated and control animals could be ruled out by comparing swimming speed and visible platform performances that were not different between groups. Thus, URD and, specifically single URD, can prevent the spatial memory impairments in addicted rats. Conclusion As opioid addiction is an extending and serious concern in many societies, these findings may have clinical values and therapeutic implications for patients who experience multiple opioid relapses. PMID:25140218

  2. Disentangling detoxification: gene expression analysis of feeding mountain pine beetle illuminates molecular-level host chemical defense detoxification mechanisms.

    PubMed

    Robert, Jeanne A; Pitt, Caitlin; Bonnett, Tiffany R; Yuen, Macaire M S; Keeling, Christopher I; Bohlmann, Jörg; Huber, Dezene P W

    2013-01-01

    The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae) that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq) of mountain pine beetle male and female adults either starved or fed in male-female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S-transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle.

  3. Effects of high-dose methadone maintenance on cocaine place conditioning, cocaine self-administration, and mu-opioid receptor mRNA expression in the rat brain.

    PubMed

    Leri, Francesco; Zhou, Yan; Goddard, Benjamin; Cummins, Erin; Kreek, Mary Jeanne

    2006-07-01

    Methadone maintenance at appropriate doses can effectively reduce cocaine abuse in heroin-dependent individuals. In the present studies, we investigated the effect of high-dose methadone maintenance cocaine conditioned place preference (CPP) and cocaine intravenous self-administration. Rats implanted with methadone-filled osmotic mini-pumps (20 and 55 mg/kg/day, SC) and conditioned with cocaine (1, 5, and 20 mg/kg, i.p.) did not express cocaine CPP. Similarly, rats implanted with methadone pumps (55 mg/kg/day) after cocaine conditioning (20 mg/kg) displayed neither spontaneous nor cocaine-precipitated (20 mg/kg, i.p.) CPP. In contrast, methadone maintenance (30 and 55 mg/kg/day, SC) did not alter the intravenous self-administration (continuous schedule of reinforcement) of various doses of cocaine (0.1, 0.5, and 2.0 mg/kg/inf). To explore neuropharmacological interactions between methadone maintenance and cocaine conditioning, we quantitatively measured mRNA levels of mu-opioid receptor (MOR) and proopiomelanocortin genes 10 days after methadone maintenance. MOR mRNA levels in both the nucleus accumbens core and frontal cortex were significantly elevated in rats exposed to cocaine during CPP conditioning. However, upregulation of MOR mRNA levels in the nucleus accumbens core were reduced by methadone maintenance in a dose-dependent manner. In conclusion, our results suggest that high-dose methadone maintenance does not alter the direct reinforcing effect of cocaine, but blocks spontaneous and cocaine-precipitated cocaine-seeking, possibly by preventing MOR alterations in the nucleus accumbens core induced by cocaine conditioning.

  4. Standard magnitude prize reinforcers can be as efficacious as larger magnitude reinforcers in cocaine-dependent methadone patients

    PubMed Central

    Petry, Nancy M.; Alessi, Sheila M.; Barry, Danielle; Carroll, Kathleen M.

    2014-01-01

    Objective Contingency management (CM) reduces cocaine use in methadone patients, but only about 50% of patients respond to CM interventions. This study evaluated whether increasing magnitudes of reinforcement will improve outcomes. Methods Cocaine-dependent methadone patients (N = 240) were randomized to one of four 12-week treatment conditions: usual care (UC), UC plus “standard” prize CM in which average expected prize earnings were about $300, UC plus high magnitude prize CM in which average expected prize earnings were about $900, or UC plus voucher CM with an expected maximum of about $900 in vouchers. Results All three CM conditions yielded significant reductions in cocaine use relative to UC, with effect sizes (d) ranging from 0.38 to 0.59. No differences were noted between CM conditions, with at least 55% of patients in each CM condition achieving one week or more of cocaine abstinence versus 35% in UC. During the 12 weeks after the intervention ended, CM increased time until relapse relative to UC, but the effects of CM were no longer significant at a 12-month follow-up. Conclusions Providing the standard magnitude of $300 in prizes was as effective as larger magnitude CM in cocaine-dependent methadone patients in this study. Given its strong evidence base and relatively low costs, standard magnitude prize CM should be considered for adoption in methadone clinics to encourage cocaine abstinence, but new methods need to be developed to sustain abstinence. PMID:25198284

  5. Prolonged Exposure for Treating PTSD Among Female Methadone Patients Who Were Survivors of Sexual Abuse in Israel.

    PubMed

    Schiff, Miriam; Nacasch, Nitsa; Levit, Shabtay; Katz, Noam; Foa, Edna B

    2015-01-01

    The aims of this pilot study were: (a) to test the feasibility of prolonged exposure (PE) therapy conducted by a social worker staff on female patients in methadone program clinics who were survivors of child sexual abuse or rape and (b) to examine preliminary outcomes of PE on posttraumatic stress disorder (PTSD), depression, and illicit drug use at pre- and posttreatment, and up to 12-month follow-ups. Twelve female methadone patients who were survivors of child sexual abuse or rape diagnosed with PTSD were enrolled in 13-19 weekly individual PE sessions. Assessments were conducted at pre-, mid-, and posttreatment, as well as at 3, 6, and 12-month follow-ups. The treatment outcomes measures included PTSD symptoms, depressive symptoms, and illicit drug use. Ten of the 12 study patients completed treatment. PTSD and depressive symptoms showed significant reduction. No relapse to illicit drug use was detected. These preliminary results suggest that PE may be delivered by methadone social workers with successful outcomes. Further research should test the efficacy of PE among methadone patients in a randomized control trial with standard care as the control condition.

  6. A Randomized Trial of Long-Term Reinforcement of Cocaine Abstinence in Methadone-Maintained Patients Who Inject Drugs

    ERIC Educational Resources Information Center

    Silverman, Kenneth; Robles, Elias; Mudric, Timothy; Bigelow, George E.; Stitzer, Maxine L.

    2004-01-01

    This study determined whether long-term abstinence reinforcement could maintain cocaine abstinence throughout a yearlong period. Patients who injected drugs and used cocaine during methadone treatment (n = 78) were randomly assigned to 1 of 2 abstinence-reinforcement groups or to a usual care control group. Participants in the 2…

  7. Attendance Rates in a Workplace Predict Subsequent Outcome of Employment-Based Reinforcement of Cocaine Abstinence in Methadone Patients

    ERIC Educational Resources Information Center

    Donlin, Wendy D.; Knealing, Todd W.; Needham, Mick; Wong, Conrad J.; Silverman, Kenneth

    2008-01-01

    This study assessed whether attendance rates in a workplace predicted subsequent outcome of employment-based reinforcement of cocaine abstinence. Unemployed adults in Baltimore methadone programs who used cocaine (N = 111) could work in a workplace for 4 hr every weekday and earn $10.00 per hour in vouchers for 26 weeks. During an induction…

  8. A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

    ERIC Educational Resources Information Center

    Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin

    2012-01-01

    The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…

  9. Cumulative versus Stabilizing Effects of Methadone Maintenance: A Quasi-Experimental Study Using Longitudinal Self-Report Data.

    ERIC Educational Resources Information Center

    Powers, Keiko Ichikawa; Anglin, M. Douglas

    1993-01-01

    Whether methadone maintenance treatment demonstrates cumulative (rehabilitative) or stabilizing effects on behavior of narcotics addicts over multiple treatment episodes was studied involving 993 addicts in a quasi-experimental design. Observed behavioral changes and longitudinal self-reports indicate stabilizing, but not cumulative, effects. (SLD)

  10. Use of a low-cost incentive intervention to improve counseling attendance among methadone-maintained patients.

    PubMed

    Sigmon, Stacey C; Stitzer, Maxine L

    2005-12-01

    Despite the importance of counseling in methadone maintenance treatment, many patients do not take advantage of these services. Incentives for attending group counseling were offered to methadone-maintained patients during an orientation phase of treatment or during required attendance at a relapse group later in treatment. Upon attending each counseling session, patients could draw for prizes under an escalating draw system with a 50% probability that draws would result in a prize. Incentives included small (1dollar), moderate (5 dollars), and large (20 dollars) prizes, with chances of winning inversely related to prize costs, and a maximum possible total of 160 dollars per patient. It was anticipated that this policy would provide a relatively low-cost approach to improving counseling attendance in our methadone clinic. The incentive policy significantly increased the percent of counseling sessions attended (52% vs. 76%) and promoted periods of continuous attendance. These data further support the effectiveness of low-cost incentive programs in enhancing counseling attendance among methadone patients.

  11. Distribution of enantiomers of methadone and its main metabolite EDDP in human tissues and blood of postmortem cases.

    PubMed

    Holm, Karen Marie Dollerup; Linnet, Kristian

    2015-01-01

    Knowledge concerning the distribution of methadone in postmortem human tissue and the effect of postmortem redistribution on methadone is today limited making the choice of a suitable substitute for femoral blood difficult when this is not available. Cardiac blood, femoral blood, muscle, and brain tissue concentrations of the enantiomers of methadone and its metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were recorded for 155 postmortem cases. Brain and muscle tissue concentrations exceeded the femoral blood concentrations with a median fold of 2.3 and 1.6, respectively, but both had a better correlation than cardiac blood to femoral blood concentrations. The Kruskal-Wallis test showed a significant dependency on time and body mass index for some of the matrix ratios over femoral blood. We conclude brain or muscle tissue may constitute a better alternative for measurement of methadone than cardiac blood for situations in which femoral blood is not available, despite concentrations in both matrices being systematically higher.

  12. Revisiting the effectiveness of methadone treatment on crime reductions in the 1990s.

    PubMed

    Rothbard, A; Alterman, A; Rutherford, M; Liu, F; Zelinski, S; McKay, J

    1999-06-01

    This study examines the relationship between methadone treatment and the criminal activity of 126 individuals participating in treatment during the early 1990s. The primary question addressed is to what extent is methadone maintenance treatment associated with reductions in crime? Although prior studies in the 1970s and early 1980s showed significant decreases in crime for individuals in treatment programs, criteria for remaining in this treatment modality have changed in recent years, particularly with the advent of acquired immune deficiency syndrome and the need to reduce intravenous drug use. A pre-post study design is employed spanning a 6-year time period of subject recruitment and follow-up (1987-1993). Uniform administrative records on arrests are used for the analyses. A multiple regression model is employed to explain the variance in the number of arrests 2 years following program admission, with prior criminal history, prior and current drug treatment, and current cocaine use employed as explanatory variables. Results indicate that treatment retention has only a slight, though significant, effect on reducing criminal activity during treatment. Two other factors that appear to increase arrest activity are the use of cocaine and prior criminal history. The fact that arrests did not decrease during a treatment period of 18 months on average requires more investigation in light of the increase in cocaine use in this population.

  13. The Mediating Role of Parenting Stress in Methadone-Maintained Mothers’ Parenting

    PubMed Central

    Suchman, Nancy E.; Luthar, Suniya S.

    2007-01-01

    SYNOPSIS Objective To (1) examine the subjective experience of parenting stress as a mediator between 2 distal stressors (sociodemographic risk and global psychological maladjustment), and examine the parenting of methadone-maintained mothers, and (2) identify maladaptive and adaptive parenting correlates of specific types of parenting stress. Design We analyzed baseline data from interviews conducted with 74 methadone-maintained mothers who expressed interest in a randomized clinical trial study testing the efficacy of a relational parenting intervention. Baseline measures included questionnaires on maternal psychological maladjustment, parenting stress, parenting problems, and children’s maladjustment. Three series of hierarchical linear regressions were conducted to test the mediation model and specificity of associations. Results Parenting stress mediated the associations between sociodemographic risk and 2 maladaptive parenting domains (aggression and neglect) and between psychological maladjustment and all 5 parenting domains examined (aggression, neglect, affective interactions, limit setting, and autonomy), although correlations were modest. Child-focused stress was associated with higher levels of aggression, limit-setting problems, and restricted autonomy. Stress derived from the mother – child relationship was associated with higher levels of neglect and affective withdrawal. Conclusions Although preliminary in nature, results of this study indicate the importance of understanding the role of internal mechanisms (e.g., parenting stress) in the parenting processes of addicted women and examining specific correlates of their parenting problems. PMID:17710214

  14. Comparison of the transcriptional responses induced by acute morphine, methadone and buprenorphine.

    PubMed

    Belkaï, Emilie; Crété, Dominique; Courtin, Cindie; Noble, Florence; Marie-Claire, Cynthia

    2013-07-05

    Despite their widespread use in opioid maintenance treatment and pain management, little is known about the intracellular effectors of methadone and buprenorphine and the transcriptional responses they induce. We therefore studied the acute effects of these two opioids in rats, comparing our observations with those for the reference molecule, morphine. We determined the analgesic ED50 of the three molecules in the tail flick test, to ensure that transcriptional effects were compared between doses of equivalent analgesic effect. We analysed changes in gene expression over time in three cerebral structures involved in several opioid behaviours-the dorsal striatum, thalamus and nucleus accumbens-by real-time quantitative PCR. We analysed the expression of genes encoding proteins of the endogenous opioid system in parallel with that of Fos, a marker of neuronal activation. The acute transcriptional effects of methadone resembled those of morphine more closely than did those of buprenorphine, in terms of kinetics and intensities. Our results provide the first evidence that these two drugs widely used in pain management and opioid maintenance treatment can disturb the regulation of endogenous opioid system genes and induce molecular outcomes different from those observed with morphine.

  15. Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment.

    PubMed

    Housová, J; Wilczek, H; Haluzík, M M; Kremen, J; Krízová, J; Haluzík, M

    2005-01-01

    Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.

  16. Differences in methylphenidate abuse rates among methadone maintenance treatment patients in two clinics.

    PubMed

    Peles, Einat; Schreiber, Shaul; Linzy, Shirley; Domani, Yoav; Adelson, Miriam

    2015-07-01

    Methylphenidate, an amphetamine-like prescription medication for attention deficit hyperactivity disorder (ADHD) was suspected as being abused among methadone maintenance treatment (MMT) patients. We tested its presence in the routine urine monitoring of all patients in both Tel Aviv and Las Vegas MMT clinics. Data on demographic and addiction history, ADHD (Wender Utah Rating Scale), cognitive impairment (Mini Mental State Exam), and lifetime DSM-IV-TR psychiatric diagnosis from admission were retrieved, and retention following 6 months. None of the 190 patients in Las Vegas tested positive for methylphenidate, while 14.7% (45/306) did in Tel Aviv. Abusers were less educated (p = 0.01), had higher ADHD scores (p = 0.02), lower cognitive scores (p = 0.05), and a higher benzodiazepine (BDZ) abuse rate (p < 0.0005), with no difference in age, gender, duration in MMT, cannabis, opiates, and cocaine abuse and infectious disease. Of the methylphenidate abuse 42.2% have take-home methadone dose privileges. Not like opiate use, being methylphenidate positive did not relate to 6-months retention. Compared to Tel Aviv, Las Vegas patients were more educated, with lower BDZ, and cocaine abuse. The greater abuse of methylphenidate among ADHD subjects might indicate their using it as self-medication, raising a possible indication for its prescription for that subgroup of MMT patients. The high rate of methylphenidate abuse in Israel needs future study.

  17. Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

    PubMed Central

    Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

    2014-01-01

    The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence. PMID:23145768

  18. Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls

    PubMed Central

    Yang, Jin; Li, Jifeng; Xu, Guanyi; Zhang, Jing; Chen, Zheng; Lu, Zuhong; Deng, Huihua

    2016-01-01

    Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic–pituitary–adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity. PMID:27010803

  19. Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls.

    PubMed

    Yang, Jin; Li, Jifeng; Xu, Guanyi; Zhang, Jing; Chen, Zheng; Lu, Zuhong; Deng, Huihua

    2016-01-01

    Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic-pituitary-adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.

  20. Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

    PubMed

    Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

    2014-02-01

    The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence.

  1. A randomized controlled trial of the effects of working memory training in methadone maintenance patients

    PubMed Central

    Rass, Olga; Schacht, Rebecca L.; Buckheit, Katherine; Johnson, Matthew W.; Strain, Eric C.; Mintzer, Miriam Z.

    2015-01-01

    Objective Working memory impairment in individuals with chronic opioid dependence can play a major role in cognitive and treatment outcomes. Cognitive training targeting working memory shows promise for improved function in substance use disorders. To date, cognitive training has not been incorporated as an adjunctive treatment for opioid dependence. Methods Methadone maintenance patients were randomly assigned to experimental (n = 28) or active control (n = 28) 25-session computerized training and run in parallel. Cognitive and drug use outcomes were assessed before and after training. Results Participants in the experimental condition showed performance improvements on two of four working memory measures, and both groups improved on a third measure of working memory performance. Less frequent drug use was found in the experimental group than in the control group post-training. In contrast to previous findings with stimulant users, no significant effect of working memory training on delay discounting was found using either hypothetical or real rewards. There were no group differences on working memory outcome measures that were dissimilar from the training tasks, suggesting that another mechanism (e.g., increased distress tolerance) may have driven drug use results. Conclusions Working memory training improves performance on some measures of working memory in methadone maintenance patients, and may impact drug use outcomes. Working memory training shows promise in patients with substance use disorders; however, further research is needed to understand the mechanisms through which performance is improved and drug use outcomes are impacted. PMID:26404954

  2. Antioxidant efficiency and detoxification enzymes in spotted dogfish Scyliorhinus canicula.

    PubMed

    Gorbi, Stefania; Pellegrini, David; Tedesco, Sara; Regoli, Francesco

    2004-01-01

    Although elasmobranchs are widely distributed species, commonly found on sandy, gravely or muddy bottoms, several biological aspects of their metabolism still remain poorly investigated. In this work the efficiency of antioxidant system and detoxification enzymes were investigated in the coastal spotted dogfish Scyliorhinus canicula and in the red mullet Mullus barbatus for comparison with a teleost species. Organisms were sampled during a bottom trawl survey and analyzed for the biotransformation activity (EROD), levels of metallothioneins, catalase, glutathione S-transferases and total oxyradical scavenging capacity (TOSC) toward peroxyl radicals and hydroxyl radicals. EROD activity in the elasmobranchs was more than one order of magnitude lower than in the red mullets, while similar levels of metallothioneins were measured in these species. S. canicula showed significantly lower antioxidant enzymes and a more reduced efficiency in neutralizing *OH; on the other hand the scavenging capability toward ROO* was comparable in S. canicula and M. barbatus.

  3. Detoxification of organophosphate nerve agents by bacterial phosphotriesterase

    SciTech Connect

    Ghanem, Eman; Raushel, Frank M. . E-mail: raushel@tamu.edu

    2005-09-01

    Organophosphates have been widely used as insecticides and chemical warfare agents. The health risks associated with these agents have necessitated the need for better detoxification and bioremediation tools. Bacterial enzymes capable of hydrolyzing the lethal organophosphate nerve agents are of special interest. Phosphotriesterase (PTE) isolated from the soil bacteria Pseudomonas diminuta displays a significant rate enhancement and substrate promiscuity for the hydrolysis of organophosphate triesters. Directed evolution and rational redesign of the active site of PTE have led to the identification of new variants with enhanced catalytic efficiency and stereoselectivity toward the hydrolysis of organophosphate neurotoxins. PTE has been utilized to protect against organophosphate poisoning in vivo. Biotechnological applications of PTE for detection and decontamination of insecticides and chemical warfare agents are developing into useful tools. In this review, the catalytic properties and potential applications of this remarkable enzyme are discussed.

  4. Functional Nanoparticles Activate a Decellularized Liver Scaffold for Blood Detoxification.

    PubMed

    Xu, Fen; Kang, Tianyi; Deng, Jie; Liu, Junli; Chen, Xiaolei; Wang, Yuan; Ouyang, Liang; Du, Ting; Tang, Hong; Xu, Xiaoping; Chen, Shaochen; Du, Yanan; Shi, Yujun; Qian, Zhiyong; Wei, Yuquan; Deng, Hongxin; Gou, Maling

    2016-04-01

    Extracorporeal devices have great promise for cleansing the body of virulence factors that are caused by venomous injuries, bacterial infections, and biological weaponry. The clinically used extracorporeal devices, such as artificial liver-support systems that are mainly based on dialysis or electrostatic interaction, are limited to remove a target toxin. Here, a liver-mimetic device is shown that consists of decellularized liver scaffold (DLS) populated with polydiacetylene (PDA) nanoparticles. DLS has the gross shape and 3D architecture of a liver, and the PDA nanoparticles selectively capture and neutralize the pore-forming toxins (PFTs). This device can efficiently and target-orientedly remove PFTs in human blood ex vivo without changing blood components or activating complement factors, showing potential application in antidotal therapy. This work provides a proof-of-principle for blood detoxification by a nanoparticle-activated DLS, and can lead to the development of future medical devices for antidotal therapy.

  5. Limits for alkaline detoxification of dilute-acid lignocellulose hydrolysates.

    PubMed

    Nilvebrant, Nils-Olof; Persson, Per; Reimann, Anders; De Sousa, Filipe; Gorton, Lo; Jönsson, Leif J

    2003-01-01

    In addition to fermentable sugars, dilute-acid hydrolysates of lignocellulose contain compounds that inhibit fermenting microorganisms, such as Saccharomyces cerevisiae. Previous results show that phenolic compounds and furan aldehydes, and to some extent aliphatic acids, act as inhibitors during fermentation of dilute-acid hydrolysates of spruce. Treatment of lignocellulose hydrolysates with alkali, usually in the form of overliming to pH 10.0, has been frequently employed as a detoxification method to improve fermentability. A spruce dilute-acid hydrolysate was treated with NaOH in a factorial design experiment, in which the pH was varied between 9.0 and 12.0, the temperature between 5 and 80 degrees C, and the time between 1 and 7 h. Already at pH 9.0, >25% of the glucose was lost when the hydrolysate was treated at 80 degrees C for 1 h. Among the monosaccharides, xylose was degraded faster under alkaline conditions than the hexoses (glucose, mannose, and galactose), which, in turn, were degraded faster than arabinose. The results suggest that alkali treatment of hydrolysates can be performed at temperatures below 30 degrees C at any pH between 9.0 and 12.0 without problems with sugar degradation or formation of inhibiting aliphatic acids. Treatment with Ca(OH)2 instead of NaOH resulted in more substantial degradation of sugars. Under the harsher conditions of the factorial design experiment, the concentrations of furfural and 5-hydroxymethylfurfural decreased while the total phenolic content increased. The latter phenomenon was tentatively attributed to fragmentation of soluble aromatic oligomers in the hydrolysate. Separate phenolic compounds were affected in different ways by the alkaline conditions with some compounds showing an increase in concentration while others decreased. In conclusion, the conditions used for detoxification with alkali should be carefully controlled to optimize the positive effects and minimize the degradation of fermentable sugars.

  6. Sulfurtransferases and cyanide detoxification in mouse liver, kidney, and brain.

    PubMed

    Wróbel, M; Jurkowska, H; Sliwa, L; Srebro, Z

    2004-01-01

    The activity of rhodanese, 3-mercaptopyruvate sulfurtransferase (MPST) and cystathionase in mouse liver, kidney, and four brain regions: tele-, meso-, di- and rhombencephalon was studied 30 min and 2 h following a sublethal dose of cyanide (4 mg/ kg body weight) intraperitoneal injection. Simultaneously, sulfane sulfur levels and total sulfur content, a direct or indirect source of sulfur for CN(-) conversion to SCN(-), were also investigated in these tissues. In the liver this dose of cyanide seemed to impair the process of cyanide detoxification by MPST, as well as rhodanese inhibition. The effects of cyanide administration to mice proved to be totally different in the liver and kidney. In the kidney, a significant increase in the rhodanese activity was observed as early as 30 min following cyanide intoxication, and an elevated cystathionase activity after 2 h was detected. This suggests the involvement of cystathionase in cyanide detoxification in the kidney. The activity of MPST remained at the same level as in the control group. In the rhombencephalon, similarly as in the kidney, L-cysteine desulfuration pathways, which generate sulfane sulfur and sulfurtransferases that transfer sulfane sulfur atoms to CN(-), seemed to play an important role as a defense system against cyanide. The stable level of sulfane sulfur and total sulfur content was accompanied in the rhombencephalon by an increased activity of MPST, cystathionase and rhodanese. In other brain regions the role of these three sulfurtransferases was not so clear and it seemed that in the telencephalon, where the total sulfur content, but not the sulfane sulfur level, was significantly increased, some sulfur-containing compounds, such as GSH and/or cysteine, appeared in response to cyanide.

  7. Selenium detoxification by volatilization and precipitation in aquatic plants

    SciTech Connect

    Fan, T.W.M.; Higashi, R.M.

    1995-12-31

    The narrow margin of requirement and toxicity for selenium makes it a difficult pollution problem to solve. Selenium bioaccumulation has been a major threat to wildlife in California and is becoming a major concern in the San Francisco Bay/Estuaries. Despite the past efforts in Se nutrition, chemistry, and remediation, its toxicity and detoxification mechanism(s) in wildlife, particularly primary producers, is still unclear, due to a lack of understanding in Se biochemistry. This is becoming a critical issue in assessing Se risk and remediation. To address this gap, the authors have been characterizing Se speciation and its linkage to detoxification mechanism(s) of two indigenous aquatic plants, duckweed (Lemna minor) and a microphyte (Chlorella). Using GT-MS analysis, they found that Chlorella monocultures transformed Se oxyanions into volatile dimethylselenide and dimethyidiselenide and into insoluble So at extremely high Se (up to 750 ppm) concentrations. This alga did not accumulate selenomethionine which is among the most toxic forms of Se to wildlife. Dimethylsulfide was also volatilized, consistent with the hypothesis that dimethylsulfide/dimethylselenide emissions share a similar biochemical pathway. Se-treated Chlorella biomass released dimethylsulfide/dimethylselenide upon alkaline hydrolysis, suggesting the presence of dimethylsulfonium and dimethylselenonium propionates. Dimethylsulfoniumpropionate is known as an osmoprotectant in marine phytoplankton and as a major contributor to global biogenic dimethylsulfide emissions. Dimethylselenoniumpropionate has not been identified previously and may be a byproduct of dimethylsulfoniumpropionate synthesis. The unusual Se tolerance of Chlorella may be due to its ability to volatilize and precipitate Se. Such activities may be utilized for in situ Se bioremediation. Similar investigations with duckweed is underway.

  8. Process evaluation of an out-patient detoxification service.

    PubMed

    Sannibale, Claudia; Fucito, Lisa; O'Connor, Danny; Curry, Kenneth

    2005-11-01

    This paper describes the process evaluation of an out-patient detoxification service (ODS) established by Drug Health Services (DHS) to increase the supervised withdrawal options for substance users in a Sydney metropolitan Area Health Service. The ODS aimed to provide a safe and effective supervised withdrawal to substance users who were at low risk of severe withdrawal, engage those with severe dependence in further treatment and increase the involvement of general practitioners (GPs) in the medical care of ODS clients. During its first 10 months of operation, the ODS received 199 inquiries, assessed 82 individuals and admitted 76 clients for detoxification. Withdrawal treatment proceeded without complications and within the expected time frames. Fifty-four clients completed withdrawal, 10 ceased treatment, 10 remained in treatment without completing withdrawal and two were transferred elsewhere. Clients who injected substances (mainly heroin) daily at admission, compared to others, were less likely to complete withdrawal and more likely to use a range of non-prescribed substances during withdrawal. One-fifth of clients went on to further treatment with DHS, attending at least once. Overall, the ODS met its goals, providing a safe and effective supervised withdrawal to local residents, especially women, young people and those withdrawing from benzodiazepines who had significant substance dependence, impairment and previous alcohol and other drug (AOD) treatment. Non-injecting substance users benefited most from the ODS in terms of withdrawal completion and ongoing treatment. The level of GP involvement in the conjoint care of ODS clients remained constant over time. The development and expansion of the ODS are discussed.

  9. Mothers' experiences of their children's detoxification in the home: results from a pilot study.

    PubMed

    Van Hout, Marie Claire; Bingham, Tim

    2012-07-01

    Detoxification from alcohol and/or drugs and the achievement of abstinence without formal treatment is often preferred using community-based supports from local GPs and family. Family members are often involved in the sourcing of information on detoxification and treatment options, user advocacy and provision of remedial supports while detoxifying within the family home. The aim of the research was to describe and explore family experiences of self-detoxification processes from the perspectives of mothers in the Mid West of Ireland. A convenience sample of adult mothers who had experienced their child detoxifying in the home (n=9) were interviewed. The findings illustrated varied personal definitions of detoxification. Addiction stigma and costly experiences of treatment and after care pathways facilitated home detoxification attempts. A lack of GP advice, support and information around safe home detoxification was observed to contribute to information and support seeking from friends, family and community members with home detoxification experience. Self-medication of both licit and illicit substances while detoxifying, and relapse cycles were common. The research highlights the need for inclusive health and social supports provided by GPs, community nurses, RGNs and district nurses for families and individuals detoxifying in the home setting.

  10. Energy cost of intracellular metal and metalloid detoxification in wild-type eukaryotic phytoplankton.

    PubMed

    Lavoie, Michel; Raven, John A; Jones, Oliver A H; Qian, Haifeng

    2016-10-01

    Microalgae use various cellular mechanisms to detoxify both non-essential and excess essential metals or metalloids. There exists however, a threshold in intracellular metal(loid) concentrations beyond which detoxification mechanisms are no longer effective and inhibition of cell division inevitably occurs. It is therefore important to determine whether the availability of energy in the cell could constrain metal(loid) detoxification capacity and to better define the thresholds beyond which a metal(loid) becomes toxic. To do this we performed the first extensive bioenergetics analysis of intracellular metal(loid) detoxification mechanisms (e.g., metal-binding peptides, polyphosphate granules, metal efflux, metal and metalloid reduction, metalloid methylation, enzymatic and non-enzymatic antioxidants) in wild-type eukaryotic phytoplankton based on the biochemical mechanisms of each detoxification strategy and on experimental measurements of detoxifying biomolecules in the literature. The results show that at the onset of metal(loid) toxicity to growth, all the detoxification strategies considered required only a small fraction of the total cellular energy available for growth indicating that intracellular detoxification ability in wild-type eukaryotic phytoplankton species is not constrained by the availability of cellular energy. The present study brings new insights into metal(loid) toxicity mechanisms and detoxification strategies in wild-type eukaryotic phytoplankton.

  11. Characteristics of Veterans Receiving Buprenorphine vs. Methadone for Opioid Use Disorder Nationally in the Veterans Health Administration

    PubMed Central

    Manhapra, Ajay; Quinones, Lantie; Rosenheck, Robert

    2016-01-01

    BACKGROUND The advent of buprenorphine as an alternative to methadone has dramatically shifted the landscape of opioid agonist therapy (OAT) for opioid use disorder (OUD). However, there is limited US national level data describing the differences between patients who are prescribed these two OAT options. METHODS From veterans with OUD diagnosis who used Veterans Health Administration services in 2012, we identified 3 mutually exclusive groups: those who received (1) buprenorphine only (n=5,670); (2) methadone only (n=6,252); or (3) both buprenorphine and methadone in the same year (n=2513). We calculated the bi-varate effect size differences (risk ratios and Cohen's d) for characteristics that differentiated these groups. Logistic regression analysis was then used to identify factors independently differentiating the groups. RESULTS Ten year increment in age (OR 0.67; 95% CI 0.64-0.70), urban residence (OR 0.26; 95% CI 0.25-0.33), and black race (OR 0.39; 95% CI 0.35-0.43) were strongly and negatively associated with odds of receiving buprenorphine compared to methadone, while medical and psychiatric comorbidities or receipt of other psychiatric medications did not demonstrate substantial differences between groups. CONCLUSIONS Differences between veterans receiving buprenorphine or methadone based OAT seems to be largely shaped by demographic characteristics rather than medical or psychiatric or service use characteristics. A clearer understanding of the reasons for racial differences could be helpful in assuring that black OUD patients are not denied the opportunity to receive buprenorphine if that is their preference. PMID:26804898

  12. Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia

    PubMed Central

    Vijay, Aishwarya; Bazazi, Alexander R.; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L.

    2016-01-01

    Background Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. Methods In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experience with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Results All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (p<0.01), needle/syringe exchange programs (p<0.005), or be of Indian ethnicity (p<0.001). Past use of methadone (p<0.01), older age (p<0.001), stress symptom severity (p<0.001), and sharing of needles or syringes (p<0.05) were associated with higher treatment readiness scores. Conclusion There are suboptimal levels of OMT experience among people who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics

  13. An Intervention Targeting Service Providers and Clients for Methadone Maintenance Treatment in China: A Cluster-randomized Trial

    PubMed Central

    Li, Li; Wu, Zunyou; Liang, Li-Jung; Lin, Chunqing; Zhang, Linglin; Guo, Sam; Rou, Keming; Li, Jianhua

    2012-01-01

    Aims This study examines the preliminary outcomes of an intervention targeting service providers in methadone maintenance therapy clinics in China. The intervention effects on both service providers and clients are reported. Design The MMT CARE intervention pilot was developed and implemented collaboratively with local health educators. After three group intervention sessions, trained providers in intervention clinics delivered two individual motivational interviewing sessions with their clients. Settings Six clinics in Sichuan, China, were randomized to either the MMT CARE intervention condition or a standard care condition. Participants A total of 41 providers and 179 clients were sampled from the six clinics. Measurements At baseline and 3-, 6-, and 9-month assessments, providers completed self-administrated paper/pencil questionnaires regarding provider-client interaction, methadone maintenance therapy knowledge, perceived job-related stigma, and clinic support. Clients completed a face-to-face survey about their concurrent drug use and drug avoidance self-efficacy. Mixed-effects regression models with clinic-level random effect were used to assess the intervention effects. Findings Significant intervention effects for providers were found in improved methadone maintenance therapy knowledge, provider-client interaction, and perceived clinic support. For clients, better improvements in drug avoidance self-efficacy and reduced concurrent drug use were observed for the intervention compared to the standard care group. Conclusions The methadone maintenance therapy CARE intervention targeting providers in methadone maintenance clinics can improve providers’ treatment knowledge and their interaction with clients. The intervention can also reduce clients’ drug using behavior through motivational interviewing sessions conducted by trained providers. PMID:22788780

  14. Twelve-Month Prevalence of DSM-5 Gambling Disorder and Associated Gambling Behaviors Among Those Receiving Methadone Maintenance.

    PubMed

    Himelhoch, Seth S; Miles-McLean, Haley; Medoff, Deborah; Kreyenbuhl, Julie; Rugle, Loreen; Brownley, Julie; Bailey-Kloch, Marie; Potts, Wendy; Welsh, Christopher

    2016-03-01

    This study sought to: (1) determine the prevalence of gambling disorder using the Diagnostic and Statistical Manual of Mental Disorders Version 5 (DSM-5; American Psychiatric Association in Diagnostic and statistical manual of mental disorders, American Psychiatric Publishing, Arlington, 2013) criteria; (2) identify the frequency and amount of money spent on gambling behaviors; and (3) determine demographic and treatment related predictors associated with gambling disorder in a substance using population. People receiving methadone maintenance treatment (N = 185) in an urban medical center consented to participate in the study. We used DSM-5 criteria to assess the 12-month prevalence of gambling disorder. Questions adapted from a previously developed measure were used to identify, describe and quantify the frequency of use and amount of money spent on gambling behaviors. Most participants were African-American (71.4 %), male (54.1 %), unmarried (76.8 %), unemployed (88.1 %) and had an income of <$20,000 (88.5 %). On average, participants were receiving 81.0 mg of methadone (SD: 22.8) daily. Nearly half (46.2 %) of participants met DSM-5 criteria for gambling disorder. Compared to those without gambling disorder, those with gambling disorder did not differ significantly with respect to demographic characteristics nor methadone dose. However, those with gambling disorder had been in methadone maintenance treatment for significantly less time. Those with gambling disorder were significantly more likely to report engaging in a variety of gambling behaviors. Given that the 12-month prevalence of DSM-5 defined gambling disorder was nearly 50 % future efforts to screen and treat gambling disorder in the context of methadone maintenance treatment are clearly warranted.

  15. Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

    PubMed Central

    Wright, Nat MJ; Sheard, Laura; Tompkins, Charlotte NE; Adams, Clive E; Allgar, Victoria L; Oldham, Nicola S

    2007-01-01

    Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49). Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens. PMID:17210079

  16. A review of engineering development of aqueous phase solar photocatalytic detoxification and disinfection processes

    SciTech Connect

    Goswami, D.Y.

    1997-05-01

    Scientific research on photocatalytic oxidation of hazardous chemicals has been conducted extensively over the last three decades. Use of solar radiation in photocatalytic detoxification and disinfection has only been explored in the last decade. Developments of engineering scale systems, design methodologies, and commercial and industrial applications have occurred even more recently. A number of reactor concepts and designs including concentrating and nonconcentrating types and methods of catalyst deployment have been developed. Some commercial and industrial field tests of solar detoxification systems have been conducted. This paper reviews the engineering developments of the solar photocatalytic detoxification and disinfection processes, including system design methodologies.

  17. Development and validation of a liquid chromatography mass spectrometry assay for the simultaneous quantification of methadone, cocaine, opiates and metabolites in human umbilical cord.

    PubMed

    de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M; Huestis, Marilyn A

    2009-10-01

    A liquid chromatography mass spectrometric selected reaction monitoring mode (SRM) method for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), 6-acetylmorphine, morphine and codeine quantification in human umbilical cord was developed and fully validated. Analytes were extracted from homogenized tissue (1g) by solid phase extraction. Linearity was 2.5-500ng/g, except for methadone (10-2000ng/g). Method imprecision was <12.7%CV with analytical recovery 85.9-112.7%, extraction efficiency >59.2%, matrix effect 4.5-39.5%, process efficiency 48.6-92.6% and stability >84.6%. Analysis of an umbilical cord following controlled methadone administration and illicit drug use contained in ng/g, 40.3 morphine, 3.6 codeine, 442 BE, 186 methadone and 45.9 EDDP.

  18. Methadone but not morphine inhibits lubiprostone-stimulated Cl- currents in T84 intestinal cells and recombinant human ClC-2, but not CFTR Cl- currents.

    PubMed

    Cuppoletti, John; Chakrabarti, Jayati; Tewari, Kirti; Malinowska, Danuta H

    2013-05-01

    In clinical trials, methadone, but not morphine, appeared to prevent beneficial effects of lubiprostone, a ClC-2 Cl(-) channel activator, on opioid-induced constipation. Effects of methadone and morphine on lubiprostone-stimulated Cl(-) currents were measured by short circuit current (Isc) across T84 cells. Whole cell patch clamp of human ClC-2 (hClC-2) stably expressed in HEK293 cells and in a high expression cell line (HEK293EBNA) as well as human CFTR (hCFTR) stably expressed in HEK293 cells was used to study methadone and morphine effects on recombinant hClC-2 and hCFTR Cl(-) currents. Methadone but not morphine inhibited lubiprostone-stimulated Isc in T84 cells with half-maximal inhibition at 100 nM. Naloxone did not affect lubiprostone stimulation or methadone inhibition of Isc. Lubiprostone-stimulated Cl(-) currents in hClC-2/HEK293 cells, but not forskolin/IBMX-stimulated Cl(-) currents in hCFTR/HEK293 cells, were inhibited by methadone, but not morphine. HEK293EBNA cells expressing hClC-2 showed time-dependent, voltage-activated, CdCl2-inhibited Cl(-) currents in the absence (control) and the presence of lubiprostone. Methadone, but not morphine, inhibited control and lubiprostone-stimulated hClC-2 Cl(-) currents with half-maximal inhibition at 100 and 200-230 nM, respectively. Forskolin/IBMX-stimulated hClC-2 Cl(-) currents were also inhibited by methadone. Myristoylated protein kinase inhibitor (a specific PKA inhibitor) inhibited forskolin/IBMX- but not lubiprostone-stimulated hClC-2 Cl(-) currents. Methadone caused greater inhibition of lubiprostone-stimulated currents added before patching (66.1 %) compared with after patching (28.7 %). Methadone caused inhibition of lubiprostone-stimulated Cl(-) currents in T84 cells and control; lubiprostone- and forskolin/IBMX-stimulated recombinant hClC-2 Cl(-) currents may be the basis for reduced efficacy of lubiprostone in methadone-treated patients.

  19. Esterase detoxification of acetylcholinesterase inhibitors by human or rat liver in vitro

    EPA Science Inventory

    Organophosphate (OP) and N-methylcarbamate pesticides inhibit acetylcholinesterase (AChE), but differences in metabolism and detoxification can influence potency of these pesticides across and within species. Carboxylesterase (CaE) and A-esterase (paraoxonase, PON) are considered...

  20. Celecoxib enhances the detoxification of diethylnitrosamine in rat liver cancer

    PubMed Central

    Salcido-Neyoy, Martha Estela; Sierra-Santoyo, Adolfo; Beltrán-Ramírez, Olga; Macías-Pérez, José Roberto; Villa-Treviño, Saúl

    2009-01-01

    AIM: To study the effect of celecoxib (CXB) on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model. METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into five groups, a non-treated group (NT), a diethylnitrosamine-treated group (DEN), a DEN+CXB-treated group (DEN+CXB), and CXB 8 d-treated and CXB 32 d-treated groups. The effects of celecoxib on the enzymatic activities of CYP1A1, 2A, 2B1/2, and 2E1 were assessed in hepatic microsomes 24 h after DEN administration. Changes in CYP1A1 and CYP2B1/2 protein expression were also evaluated. The rate of DEN metabolism was measured by the production of the deethylation metabolite acetaldehyde, and the denitrosation metabolite nitrite. RESULTS: DEN+CXB administration produced a significant increase in the enzymatic activities of CYP2B1/2 and 1A1, whereas it did not change the activities of CYP2A and 2E1, compared to that of the DEN group. CXB treatment for eight days did not produce a significant effect on enzymatic activity when compared to the NT group; however, when it was administered for prolonged times (CXB 32 d group), the enzymatic activities were increased in a similar pattern to those in the DEN+CXB group. The observed increase in the enzymatic activities in the DEN+CXB group was accompanied by an increase in the CYP2B1/2 protein levels; no changes were observed in the levels of CYP1A1. In vitro, CXB increased the denitrosation of DEN, a pathway of metabolic detoxification. The addition of SKF-525A, a preferential inhibitor of CYP2B, abrogated the denitrosation of DEN. CONCLUSION: These results suggest that the mechanism of action of CXB involves enhancement of the detoxification of DEN by an increasing denitrosation via CYP2B1/2. PMID:19452576

  1. Criminal Justice Involvement and Service Need among Men on Methadone who Have Perpetrated Intimate Partner Violence.

    PubMed

    Wu, Elwin; El-Bassel, Nabila; Gilbert, Louisa; Sarfo, Bright; Seewald, Randy

    2010-07-01

    Perpetrators of male-to-female intimate partner violence (IPV) may be likely to have multiple service needs, the extent of which may vary with respect to criminal justice involvement. The salience of the criminal justice system and the potential impact on service needs due to arrest and incarceration is underscored given the association between substance use and IPV. This study utilized a sample of men in methadone treatment who perpetrated male-to-female IPV in order to examine associations between criminal justice involvement and perceived additional service need(s). Results indicate that the likelihood of having a service need(s) significantly increased as time since most recent arrest or incarceration decreased. These findings highlight the need and potential benefit that can be derived from greater coordination amongst the criminal justice, IPV prevention, and drug treatment systems and service providers.

  2. Prize reinforcement contingency management for cocaine dependence: integration with group therapy in a methadone clinic.

    PubMed

    Petry, Nancy M; Martin, Bonnie; Simcic, Francis

    2005-04-01

    In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes ranging from $1 to $100 for submitting cocainenegative samples and attending therapy. Patients in the CM condition submitted more cocaine-negative samples and attended more groups than patients in standard treatment. The best predictor of cocaine abstinence at follow-up was duration of abstinence during treatment. On average, patients in the CM condition earned $117 in prizes. Data from this study suggest that some aspects of reinforcement can be implemented in group therapy in community-based clinics.

  3. Effect of CBT on Depressive Symptoms in Methadone Maintenance Patients Undergoing Treatment for Hepatitis C

    PubMed Central

    Ramsey, Susan E.; Engler, Patricia A.; Stein, Michael D.; Brown, Richard A.; Cioe, Patricia; Kahler, Christopher W.; Promrat, Kittichai; Rose, Jennifer; Anthony, Jennifer; Solomon, David A.

    2011-01-01

    To examine the efficacy of a cognitive-behavioral intervention (CBT) to prevent depression among methadone maintenance patients undergoing antiviral treatment for hepatitis C (HCV), 29 patients beginning HCV treatment were randomized to CBT or standard care (SC). Study participants did not meet criteria for major depressive disorder at the time of study recruitment. CBT did not result in less depression-related antiviral treatment failure, better adherence to antiviral treatment, or better HCV RNA outcomes. There were no significant treatment group differences on depressive symptoms over time. The CBT group did display a greater and more consistent decline in both BDI-II and HAM-D scores over time (d=.85 on the BDI-II; d=.72 on the HAM-D). PMID:21743837

  4. B vitamins status: effect of prolonged heroin addiction and methadone treatment.

    PubMed

    Prayurahong, B; Migasena, P; Pongpaew, P; Vudhivai, N; Busapathumrong, P

    1991-03-01

    Vitamin B1, B2 and B6 status were determined in 90 male heroin addicts admitted to Pramongkutklao Army Hospital. Their age (Mean +/- S.D.) was 25.5 +/- 7.8 years. Their activation coefficients of the enzyme transketolase, glutathione oxidoreductase and aspartate aminotransferase (ETK AC, EGR AC and EAST AC respectively) were significantly increased for addicts who were on drugs for a long time which indicated a biochemical deficiency. In addition, 26 follow-up cases treated with methadone for a period of one and two weeks were compared before and after treatment and it was found that ETK AC, EGR AC, and EAST AC were significantly decreased. This means that improvement in the vitamin B1, B2 and B6 status was obtained during admission.

  5. Chiral analysis of amphetamines, methadone and metabolites in biological samples by electrodriven methods.

    PubMed

    Mandrioli, Roberto; Mercolini, Laura; Raggi, Maria A

    2011-10-01

    Amphetamines and methadone are synthetic chiral drugs with a high potential for abuse. As such, several analytical methods have been developed for their enantioseparation and analysis in biological tissues, and some of these are based on electrodriven techniques. In this review, the most important and recent of these latter methods are reviewed and their main advantages and disadvantages are discussed. Particular attention is paid to the suitability of each method for the application to the biological matrix of interest: while all methods have been successfully applied for one or more biological tissues, to reach this goal they must overcome the sensitivity problem that is common to almost all capillary electrophoretic techniques. Most methods use one or more cyclodextrin derivatives as the chiral selector, thus the separation mechanism is not particularly complicated or unusual.

  6. A pilot trial of a videogame-based exercise program for methadone maintained patients.

    PubMed

    Cutter, Christopher J; Schottenfeld, Richard S; Moore, Brent A; Ball, Samuel A; Beitel, Mark; Savant, Jonathan D; Stults-Kolehmainen, Matthew A; Doucette, Christopher; Barry, Declan T

    2014-10-01

    Few studies have examined exercise as a substance use disorder treatment. This pilot study investigated the feasibility and acceptability of an exercise intervention comprising the Wii Fit Plus™ and of a time-and-attention sedentary control comprising Wii™ videogames. We also explored their impact on physical activity levels, substance use, and psychological wellness. Twenty-nine methadone-maintained patients enrolled in an 8-week trial were randomly assigned to either Active Game Play (Wii Fit Plus™ videogames involving physical exertion) or Sedentary Game Play (Wii™ videogames played while sitting). Participants had high satisfaction and study completion rates. Active Game Play participants reported greater physical activity outside the intervention than Sedentary Game Play participants despite no such differences at baseline. Substance use decreased and stress and optimism improved in both conditions. Active Game Play is a feasible and acceptable exercise intervention, and Sedentary Game Play is a promising time-and-attention control. Further investigations of these interventions are warranted.

  7. Sleep Disorders in Methadone Maintenance Treatment Volunteers and Opium-dependent Patients

    PubMed Central

    Khazaie, Habibolah; Najafi, Farid; Ghadami, Mohammad Rasoul; Azami, Atena; Nasouri, Marzieh; Tahmasian, Masoud; Khaledi-Paveh, Behnam

    2016-01-01

    Background The relationship between substance use and sleep is bidirectional. Substance use directly causessleep disturbances, and sleep problems are a critical factor in substance-use relapse. Methods This study evaluated sleep disorders in 65 methadone maintenance treatment (MMT) patients, and61 opium-dependent patients who did not receive any treatment between September 2011 and July 2012 inKermanshah, Iran. Both groups filled out the Pittsburgh Sleep Quality Index (PSQI) and Global SleepAssessment Questionnaire (GSAQ). Findings Sleep disorders were remarkably similar in both groups: 78.5% of MMT patients and 87.7% ofopium-dependent patients suffered from sleep problems. Sleep disorders in the opium-dependent groupwere remarkably higher and more prominent. Conclusion Compared to opium, MMT does not have as many negative effects on sleep and is more effectivein mitigating sleep problems. PMID:27882205

  8. The 2-year test-retest reliability of the Psychopathy Checklist Revised in methadone patients.

    PubMed

    Rutherford, M; Cacciola, J S; Alterman, A I; McKay, J R; Cook, T G

    1999-09-01

    The 2-year test-retest reliability of the Psychopathy Checklist-Revised (PCL-R) was examined in 200 men and 25 women methadone patients. Stability of the PCL-R was generally good whether it was evaluated as a dichotomous or dimensional measure. Utilizing a diagnostic cutoff score of 25 or more the intraclass correlation coefficients (ICCs) were.48 for men and.67 for women. For the Total PCL-R score ICCs were.60 and.65 for men and women, respectively. Factor 1 was more reliably measured in women compared to men (.63 vs.43). For men, Factor 1 was significantly less reliable than Factor 2 or the Total score. For women, Factor 2 was significantly less reliable than the Total PCL-R score or Factor 1.

  9. Retention and HIV seroconversion among drug users on methadone maintenance treatment in Yunnan, China

    PubMed Central

    Duo, L.; Kumar, A. M. V.; Achanta, S.; Xue, H-M.; Satyanarayana, S.; Ananthakrishnan, R.; Srivastava, S.; Qi, W.; Hu, S-Y.

    2014-01-01

    Setting: Thirteen methadone maintenance treatment (MMT) clinics across Yunnan, the province with the highest human immunodeficiency virus (HIV) burden in China. Objectives: To determine, among HIV-negative participants on MMT, the proportion lost to follow-up (defined as those who missed the 6-monthly follow-up examination), factors associated with loss to follow-up (LFU), HIV seroconversion rate and factors associated with seroconversion. Design: Prospective cohort study from October 2008 to April 2011. All participants were administered a pre-tested structured questionnaire to capture associated factors and offered HIV testing every 6 months. χ2 test and log-binomial regression were used for data analysis. Results: Of 1146 participants, 541 (47%) were lost to follow-up in 2.5 years. Factors associated with higher LFU proportion include <6 months of previous MMT, inconvenient location of the MMT clinic and average methadone dose ⩽60 mg/day, with adjusted relative risks (RRs) of respectively 1.4 (95%CI 1.2–1.5), 1.2 (95%CI 1.0–1.4) and 1.1 (95%CI 1.0–1.3). The overall HIV seroconversion rate was 6.6 (95%CI 3.7–11.0) per 1000 person-years. Not living with a partner contributed to higher HIV rates, with an adjusted RR of 3.6 (95%CI 1.0–12.8). Conclusion: The retention rate of MMT participants in Yunnan was not satisfactory. Decentralising service delivery in the community and making directly observed treatment more convenient has the potential to improve retention. PMID:26423758

  10. Integrated internist - addiction medicine - hepatology model for hepatitis C management for individuals on methadone maintenance.

    PubMed

    Martinez, A D; Dimova, R; Marks, K M; Beeder, A B; Zeremski, M; Kreek, M J; Talal, A H

    2012-01-01

    Despite a high prevalence of hepatitis C virus (HCV) among drug users, HCV evaluation and treatment acceptance are extremely low among these patients when referred from drug treatment facilities for HCV management. We sought to increase HCV treatment effectiveness among patients from a methadone maintenance treatment program (MMTP) by maintaining continuity of care. We developed, instituted and retrospectively assessed the effectiveness of an integrated, co-localized care model in which an internist-addiction medicine specialist from MMTP was embedded in the hepatitis clinic. Methadone maintenance treatment program patients were referred, evaluated by the internist and hepatologist in hepatitis clinic and provided HCV treatment with integration between both sites. Of 401 evaluated patients, anti-HCV antibody was detected in 257, 86% of whom were older than 40 years. Hepatitis C virus RNA levels were measured in 222 patients, 65 of whom were aviremic. Of 157 patients with detectable HCV RNA, 125 were eligible for referral to the hepatitis clinic, 76 (61%) of whom accepted and adhered with the referral. Men engaged in MMTP <36 months were significantly less likely to be seen in hepatitis clinic than men in MMTP more than 36 months (odds ratio = 7.7; 95% confidence interval 2.6-22.9) or women. We evaluated liver histology in 63 patients, and 83% had moderate to advanced liver disease. Twenty-four patients initiated treatment with 19 completing and 13 (54%) achieving sustained response. In conclusion, integrated care between the MMTP and the hepatitis clinic improves adherence with HCV evaluation and treatment compared to standard referral practices.

  11. Detoxification of Arsenic by Phytochelatins in Plants1

    PubMed Central

    Schmöger, Marcus E.V.; Oven, Matjaz; Grill, Erwin

    2000-01-01

    As is a ubiquitous element present in the atmosphere as well as in the aquatic and terrestrial environments. Arsenite and arsenate are the major forms of As intoxication, and these anions are readily taken up by plants. Both anions efficiently induce the biosynthesis of phytochelatins (PCs) ([γ-glutamate-cysteine]n-glycine) in vivo and in vitro. The rapid induction of the metal-binding PCs has been observed in cell suspension cultures of Rauvolfia serpentina, in seedlings of Arabidopsis, and in enzyme preparations of Silene vulgaris upon challenge to arsenicals. The rate of PC formation in enzyme preparations was lower compared with Cd-induced biosynthesis, but was accompanied by a prolonged induction phase that resulted finally in higher peptide levels. An approximately 3:1 ratio of the sulfhydryl groups from PCs to As is compatible with reported As-glutathione complexes. The identity of the As-induced PCs and of reconstituted metal-peptide complexes has unequivocally been demonstrated by electrospray ionization mass spectroscopy. Gel filtration experiments and inhibitor studies also indicate a complexation and detoxification of As by the induced PCs. PMID:10712543

  12. Detoxification and mineral supplementation as functions of geophagy

    SciTech Connect

    Johns, T.; Duquette, M. )

    1991-02-01

    Clays employed historically in the consumption of astringent acorns plus seven edible clays from Africa were examined in relation to the functional significance of human geophagy. On the basis of sorptive maxima for tannic acid ranging from 5.6 to 23.7 mg/g, we conclude that adsorption of tannic acid in traditional acorn preparation methods in California and Sardinia helped make these nuts palatable. Calcium available in solution at pH 2.0 and 0.1 mol NaCl/L was 2.10 and 0.71 mg/g for the Sardinian and Californian clays, respectively. The African clays released calcium, copper, iron, magnesium, manganese, or zinc in amounts of nutritional significance from some clays but not from others. A clay recovered from an archaeological site occupied by Homo erectus and early H. sapiens was indistinguishable mineralogically, in detoxification capacity and in available minerals, from clays used in Africa today. We suggest that the physiological significance of geophagy made it important in the evolution of human dietary behavior.

  13. Enhancement of processes for solar photocatalytic detoxification of water

    SciTech Connect

    Pacheco, J.E.; Tyner, C.E.

    1990-01-01

    A solar-driven photocatalytic process is being developed to destroy low levels of toxic organics in water. Parabolic troughs with a glass pipe reactor and heliostats (large tracking mirrors) with a falling-film reactor were used to conduct engineering-scale solar detoxification of water experiments. We have assessed the effect of catalyst (titanium dioxide) loading and hydrogen peroxide concentration on the destruction of a model organic compound, salicylic acid. We found the optimal catalyst loading to be 0.1% for the conditions of 30 ppM salicylic acid and 300 ppM hydrogen peroxide. Hydrogen peroxide affected the reaction rates significantly, increasing the reaction rate over 4 times for stoichiometric amounts and more than 19 times for 10 times the stoichiometric amount. Destruction rates appear to be linearly proportional to the ultraviolet light intensity, though more data are needed to fully establish the relation. Initial tests with an actual water pollutant, trichloroethylene, demonstrated destruction from 1.2 ppM to less than 50 ppB in less than 5 minutes of exposure with a trough system. 15 refs., 6 figs.

  14. Mechanistic Insight into the Biosynthesis and Detoxification of Fumonisin Mycotoxins.

    PubMed

    Burgess, Kevin M N; Renaud, Justin B; McDowell, Tim; Sumarah, Mark W

    2016-09-16

    Fumonisins, notably FB1, FB2, FB3, and FB4, are economically important mycotoxins produced by a number Fusarium sp. that occur on corn, rice, and sorghum as well as by Aspergillus sp. on grapes. The fumonisin scaffold is comprised of a C18 polyketide backbone functionalized with two tricarballylic esters and an alanine derived amine. These functional groups contribute to fumonisin's ability to inhibit sphingolipid biosynthesis in animals, plants, and yeasts. We report for the first time the isolation and structure elucidation of two classes of nonaminated fumonisins (FPy and FLa) produced by Aspergillus welwitschiae. Using a Lemna minor (duckweed) bioassay, these new compounds were significantly less toxic in comparison to the fumonisin B mycotoxins, providing new insight into the mechanism of fumonisin toxicity. Time course fermentations monitoring the production of FB4, FPy4, and FLa4, as well as (13)C and (15)N stable isotope incorporation, suggest a novel postbiosynthetic oxidative deamination process for fumonisins. This pathway was further supported by a feeding study with FB1, a fumonisin not produced by Aspergillus sp., which resulted in its transformation to FPy1. This study demonstrates that Aspergillus have the ability to produce enzymes that could be used for fumonisin detoxification.

  15. Detoxification of olive mill wastewaters by Moroccan yeast isolates.

    PubMed

    Ben Sassi, A; Ouazzani, N; Walker, G M; Ibnsouda, S; El Mzibri, M; Boussaid, A

    2008-06-01

    A total of 105 yeast strains were isolated from Moroccan olive oil production plants and evaluated for their ability to grow in olive oil mill wastewaters (OMW). The 9 isolates that grew best on OMW were selected for further study to evaluate their effect on removal of organic pollutants and OMW phytotoxicity (barley seed germination test). The results showed that at least four yeast isolates effectively lowered the toxicity of this effluent in addition to providing very useful materials in terms of both yeast biomass (6 g/l DW) and an irrigation fluid. This group of yeast isolates significantly reduced the concentration of total phenols (44% removal) and Chemical Oxygen Demand, COD (63% removal). The best germination rate of 80% for undiluted OMW was obtained for strain Candida holstii that also increased the pH from 4.76 to 6.75. Principal component analysis of the results obtained for the best yeast strains confirmed the importance of COD and total phenol reduction along with increase of organic nitrogen and final pH for the improvement of germination rates and phytotoxic reduction. This study has highlighted the potential of indigenous yeasts in detoxification of olive mill wastewaters.

  16. Antioxidant and drug detoxification potentials of Hibiscus sabdariffa anthocyanin extract.

    PubMed

    Ajiboye, Taofeek O; Salawu, Nasir A; Yakubu, Musa T; Oladiji, Adenike T; Akanji, Musbau A; Okogun, Joseph I

    2011-04-01

    The antioxidant and drug metabolizing potentials of Hibiscus anthocyanin extract in CCl(4)- induced oxidative damage of rat liver was investigated. Hibiscus anthocyanin extract effectively scavenge α-diphenyl-β-picrylhydrazyl (DPPH) radical, superoxide ion, and hydrogen peroxide. It produced a 92% scavenging effect of DPPH radical at a concentration of 2.0 mg/mL. Hibiscus anthocyanin extract produced a 69 and 90% scavenging effect on superoxide ion and hydrogen peroxide, respectively, at 1.0 mg/mL, which compared favorably with the synthetic antioxidant (butylated hydroanisole and α-tocopherol). A reducing power of this anthocyanin was examined using K(3)Fe(CN)(6). Hibiscus anthocyanin extract has reducing power that is approximately 2-fold that of the synthetic antioxidant, butylated hydroanisole. Hibiscus anthocyanin extract produced a significantly increase and completely attenuated the CCl(4)-mediated decrease in antioxidant enzymes (e.g., catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase). However, the level of nonenzymic antioxidant molecules (i.e., vitamins C and E) were significant preserved by Hibiscus anthocyanin extract. There was an induction of phase II drug-detoxifying enzymes: glutathione S-transferase, NAD(H):quinone oxidoreductase, and uridyl diphosphoglucuronosyl transferase by 65, 45, and 57%, respectively. In view of these properties, Hibiscus sabdariffa anthocyanin extract can act as a prophylactic by intervening as a free radical scavenger both in vitro and in vivo as well as inducing the phase II drug detoxification enzymes.

  17. Aflatoxin detoxification by manganese peroxidase purified from Pleurotus ostreatus

    PubMed Central

    Yehia, Ramy Sayed

    2014-01-01

    Manganese peroxidase (MnP) was produced from white rot edible mushroom Pleurotus ostreatus on the culture filtrate. The enzyme was purified to homogeneity using (NH4)2SO4 precipitation, DEAE-Sepharose and Sephadex G-100 column chromatography. The final enzyme activity achieved 81 U mL−1, specific activity 78 U mg−1 with purification fold of 130 and recovery 1.2% of the crude enzyme. SDS-PAGE indicated that the pure enzyme have a molecular mass of approximately 42 kDa. The optimum pH was between 4–5 and the optimum temperature was 25 °C. The pure MnP activity was enhanced by Mn2+, Cu2+, Ca2+ and K+ and inhibited by Hg+2 and Cd+2. H2O2 at 5 mM enhanced MnP activity while at 10 mM inhibited it significantly. The MnP-cDNA encoding gene was sequenced and determined (GenBank accession no. AB698450.1). The MnP-cDNA was found to consist of 497 bp in an Open Reading Frame (ORF) encoding 165 amino acids. MnP from P. ostreatus could detoxify aflatoxin B1 (AFB1) depending on enzyme concentration and incubation period. The highest detoxification power (90%) was observed after 48 h incubation at 1.5 U mL−1 enzyme activities. PMID:24948923

  18. Comparative insecticide susceptibility and detoxification enzyme activities among pestiferous blattodea.

    PubMed

    Valles, S M; Koehler, P G; Brenner, R J

    1999-11-01

    Topical bioassays using propoxur, chlorpyrifos, and lambda-cyhalothrin were conducted on eight cockroach species. Based on lethal dose values, the relative toxicities of the insecticide classes were generally pyrethroid > carbamate > organophosphorous. Lambda-Cyhalothrin and propoxur were more toxic toward the Blattidae as compared with the Blattellidae. The order of lambda-cyhalothrin toxicity was Periplaneta americana > Periplaneta brunnea = Periplaneta australasiae = Periplaneta fuliginosa = Blatta orientalis > Blattella asahinai = Blattella germanica > Blattella vaga. The order of propoxur toxicity was B. orientalis > P. americana > P. brunnea = P. australasiae > B. asahinai > P. fuliginosa = B. germanica > B. vaga. The order of chlorpyrifos toxicity was P. americana > B. asahinai = B. vaga > B. orientalis = P. australasiae = P. brunnea > B. germanica = P. fuliginosa. Detoxification enzyme activities for each species also were measured and compared with insecticide toxicity. Propoxur LD50 was significantly (P = 0.01; r = 0.81) correlated with glutathione S-transferase activity. Lambda-Cyhalothrin LD50 correlated with methoxyresorufin O-demethylase activity (P = 0.01; r = 0.81), carboxylesterase activity (P = 0.03; r = - 0.75), general esterase activity (P = 0.02; r = - 0.79), and cockroach weight (P = 0.01; r = -0.95).

  19. A ferritin from Dendrorhynchus zhejiangensis with heavy metals detoxification activity.

    PubMed

    Li, Chenghua; Li, Zhen; Li, Ye; Zhou, Jun; Zhang, Chundan; Su, Xiurong; Li, Taiwu

    2012-01-01

    Ferritin, an iron homeostasis protein, has important functions in transition and storage of toxic metal ions. In this study, the full-length cDNA of ferritin was isolated from Dendrorhynchus zhejiangensis by cDNA library and RACE approaches. The higher similarity and conserved motifs for ferritin were also identified in worm counterparts, indicating that it belonged to a new member of ferritin family. The temporal expression of worm ferritin in haemocytes was analyzed by RT-PCR, and revealed the ferritin could be induced by Cd(2+), Pb(2+) and Fe(2+). The heavy metal binding activity of recombinant ferritin was further elucidated by atomic force microscopy (AFM). It was observed that the ferritin protein could form a chain of beads with different size against three metals exposure, and the largest one with 35~40 nm in height was identified in the Cd(2+) challenge group. Our results indicated that worm ferritin was a promising candidate for heavy metals detoxification.

  20. A Ferritin from Dendrorhynchus zhejiangensis with Heavy Metals Detoxification Activity

    PubMed Central

    Li, Chenghua; Li, Zhen; Li, Ye; Zhou, Jun; Zhang, Chundan; Su, Xiurong; Li, Taiwu

    2012-01-01

    Ferritin, an iron homeostasis protein, has important functions in transition and storage of toxic metal ions. In this study, the full-length cDNA of ferritin was isolated from Dendrorhynchus zhejiangensis by cDNA library and RACE approaches. The higher similarity and conserved motifs for ferritin were also identified in worm counterparts, indicating that it belonged to a new member of ferritin family. The temporal expression of worm ferritin in haemocytes was analyzed by RT-PCR, and revealed the ferritin could be induced by Cd2+, Pb2+ and Fe2+. The heavy metal binding activity of recombinant ferritin was further elucidated by atomic force microscopy (AFM). It was observed that the ferritin protein could form a chain of beads with different size against three metals exposure, and the largest one with 35∼40 nm in height was identified in the Cd2+ challenge group. Our results indicated that worm ferritin was a promising candidate for heavy metals detoxification. PMID:23284696

  1. Drug Addiction Stigma in the Context of Methadone Maintenance Therapy: An Investigation into Understudied Sources of Stigma.

    PubMed

    Earnshaw, Valerie; Smith, Laramie; Copenhaver, Michael

    2013-02-01

    Experiences of stigma from others among people with a history of drug addiction are understudied in comparison to the strength of stigma associated with drug addiction. Work that has studied these experiences has primarily focused on stigma experienced from healthcare workers specifically even though stigma is often experienced from other sources as well. Because stigma has important implications for the mental health and recovery efforts of people in treatment, it is critical to better understand these experiences of stigma. Therefore, we characterize drug addiction stigma from multiple sources using qualitative methodology to advance understandings of how drug addiction stigma is experienced among methadone maintenance therapy patients and from whom. Results demonstrate that methadone maintenance therapy patients experience prejudice, stereotypes, and discrimination from friends and family, coworkers and employers, healthcare workers, and others. Discussion highlights similarities and differences in stigma experienced from these sources.

  2. Comparison of methods for detoxification of spruce hydrolysate for bacterial cellulose production

    PubMed Central

    2013-01-01

    Background Bacterial cellulose (BC) is a nanostructured material with unique properties and wide applicability. In order to decrease the production cost of bacterial cellulose, lignocellulose-based media have considerable potential as alternative cost-effective feedstocks. However, pretreatment and enzymatic hydrolysis of lignocellulose to sugars also generate fermentation inhibitors. Detoxification of lignocellulosic hydrolysates is needed to achieve efficient production of BC. In this investigation, different methods for detoxification of spruce hydrolysate prior to production of BC were compared with respect to effects on potential inhibitors and fermentable sugars, sugar consumption, BC yield, and cell viability. The objectives were to identify efficient detoxification methods and to achieve a better understanding of the role played by different inhibitors in lignocellulosic hydrolysates. Results In a first series of experiments, the detoxification methods investigated included treatments with activated charcoal, alkali [sodium hydroxide, calcium hydroxide (overliming), and ammonium hydroxide], anion and cation ion-exchange resins, and reducing agents (sodium sulfite and sodium dithionite). A second series of detoxification experiments included enzymatic treatments (laccase and peroxidase). The potential inhibitors studied included aliphatic acids, furan aldehydes, and phenolic compounds. The best effects in the first series of detoxification experiments were achieved with activated charcoal and anion exchanger. After detoxification with activated charcoal the BC yield was 8.2 g/L, while it was 7.5 g/L in a reference medium without inhibitors. Treatments with anion exchanger at pH 10 and pH 5.5 gave a BC yield of 7.9 g/L and 6.3 g/L, respectively. The first series of experiments suggested that there was a relationship between the BC yield and phenolic inhibitors. Therefore, the second series of detoxification experiments focused on treatments with phenol

  3. NEGOTIATING STRUCTURAL VULNERABILITY FOLLOWING REGULATORY CHANGES TO A PROVINCIAL METHADONE PROGRAM IN VANCOUVER, CANADA: A QUALITATIVE STUDY

    PubMed Central

    McNeil, Ryan; Kerr, Thomas; Anderson, Solanna; Maher, Lisa; Keewatin, Chereece; Milloy, MJ; Wood, Evan; Small, Will

    2015-01-01

    While regulatory frameworks governing methadone maintenance therapy (MMT) require highly regimented treatment programs that shape treatment outcomes, little research has examined the effects of regulatory changes to these programs on those receiving treatment, and located their experiences within the wider context of socialstructural inequities. In British Columbia (BC), Canada, provincial regulations governing MMT have recently been modified, including: replacing the existing methadone formulation with Methadose® (pre-mixed and 10 times more concentrated); prohibiting pharmacy delivery of methadone; and, prohibiting pharmacies incentives for methadone dispensation. We undertook this study to examine the impacts of these changes on a structurally vulnerable population enrolled in MMT in Vancouver, BC. Qualitative interviews were conducted with 34 people enrolled in MMT and recruited from two ongoing observational prospective cohort studies comprised of drug-using individuals in the six-month period in 2014 following these regulatory changes. Interview transcripts were analyzed thematically, and by drawing on the concept of ‘structural vulnerability’. Findings underscore how these regulatory changes disrupted treatment engagement, producing considerable health and social harms. The introduction of Methadose® precipitated increased withdrawal symptoms. The discontinuation of pharmacy delivery services led to interruptions in MMT and codispensed HIV medications due to constraints stemming from their structural vulnerability (e.g., poverty, homelessness). Meanwhile, the loss of pharmacy incentives limited access to material supports utilized by participants to overcome barriers to MMT, while diminishing their capacity to assert some degree of agency in negotiating dispensation arrangements with pharmacies. Collectively, these changes functioned to compromise MMT engagement and increased structural vulnerability to harm, including re-initiation of injection drug

  4. Negotiating structural vulnerability following regulatory changes to a provincial methadone program in Vancouver, Canada: A qualitative study.

    PubMed

    McNeil, Ryan; Kerr, Thomas; Anderson, Solanna; Maher, Lisa; Keewatin, Chereece; Milloy, M J; Wood, Evan; Small, Will

    2015-05-01

    While regulatory frameworks governing methadone maintenance therapy (MMT) require highly regimented treatment programs that shape treatment outcomes, little research has examined the effects of regulatory changes to these programs on those receiving treatment, and located their experiences within the wider context of social-structural inequities. In British Columbia (BC), Canada, provincial regulations governing MMT have recently been modified, including: replacing the existing methadone formulation with Methadose(®) (pre-mixed and 10 times more concentrated); prohibiting pharmacy delivery of methadone; and, prohibiting pharmacies incentives for methadone dispensation. We undertook this study to examine the impacts of these changes on a structurally vulnerable population enrolled in MMT in Vancouver, BC. Qualitative interviews were conducted with 34 people enrolled in MMT and recruited from two ongoing observational prospective cohort studies comprised of drug-using individuals in the six-month period in 2014 following these regulatory changes. Interview transcripts were analysed thematically, and by drawing on the concept of 'structural vulnerability'. Findings underscore how these regulatory changes disrupted treatment engagement, producing considerable health and social harms. The introduction of Methadose(®) precipitated increased withdrawal symptoms. The discontinuation of pharmacy delivery services led to interruptions in MMT and co-dispensed HIV medications due to constraints stemming from their structural vulnerability (e.g., poverty, homelessness). Meanwhile, the loss of pharmacy incentives limited access to material supports utilized by participants to overcome barriers to MMT, while diminishing their capacity to assert some degree of agency in negotiating dispensation arrangements with pharmacies. Collectively, these changes functioned to compromise MMT engagement and increased structural vulnerability to harm, including re-initiation of injection drug

  5. The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data

    PubMed Central

    Farid, W.O; Dunlop, S.A; Tait, R.J; Hulse, G.K

    2008-01-01

    Most women using heroin are of reproductive age with major risks for their infants. We review clinical and experimental data on fetal, neonatal and postnatal complications associated with methadone, the current “gold standard”, and compare these with more recent, but limited, data on developmental effects of buprenorphine, and naltrexone. Methadone is a µ-opioid receptor agonist and is commonly recommended for treatment of opioid dependence during pregnancy. However, it has undesired outcomes including neonatal abstinence syndrome (NAS). Animal studies also indicate detrimental effects on growth, behaviour, neuroanatomy and biochemistry, and increased perinatal mortality. Buprenorphine is a partial µ-opioid receptor agonist and a κ-opioid receptor antagonist. Clinical observations suggest that buprenorphine during pregnancy is similar to methadone on developmental measures but is potentially superior in reducing the incidence and prognosis of NAS. However, small animal studies demonstrate that low doses of buprenorphine during pregnancy and lactation lead to changes in offspring behaviour, neuroanatomy and biochemistry. Naltrexone is a non-selective opioid receptor antagonist. Although data are limited, humans treated with oral or sustained-release implantable naltrexone suggest outcomes potentially superior to those with methadone or buprenorphine. However, animal studies using oral or injectable naltrexone have shown developmental changes following exposure during pregnancy and lactation, raising concerns about its use in humans. Animal studies using chronic exposure, equivalent to clinical depot formulations, are required to evaluate safety. While each treatment is likely to have maternal advantages and disadvantages, studies are urgently required to determine which is optimal for offspring in the short and long term. PMID:19305793

  6. Methadone overdose

    MedlinePlus

    ... if known) Time it was swallowed Amount swallowed Poison Control Your local poison center can be reached directly by calling the national toll-free Poison Help hotline (1-800-222-1222) from anywhere ...

  7. Is slow-onset long-acting monoamine transport blockade to cocaine as methadone is to heroin? Implication for anti-addiction medications.

    PubMed

    Peng, Xiao-Qing; Xi, Zheng-Xiong; Li, Xia; Spiller, Krista; Li, Jie; Chun, Lauren; Wu, Kuo-Ming; Froimowitz, Mark; Gardner, Eliot L

    2010-12-01

    The success of methadone in treating opiate addiction has suggested that long-acting agonist therapies may be similarly useful for treating cocaine addiction. Here, we examined this hypothesis, using the slow-onset long-acting monoamine reuptake inhibitor 31,345, a trans-aminotetralin analog, in a variety of addiction-related animal models, and compared it with methadone's effects on heroin's actions in the same animal models. Systemic administration of 31,345 produced long-lasting enhancement of electrical brain-stimulation reward (BSR) and extracellular nucleus accumbens (NAc) dopamine (DA). Pretreatment with 31,345 augmented cocaine-enhanced BSR, prolonged cocaine-enhanced NAc DA, and produced a long-term (24-48  h) reduction in cocaine self-administration rate without obvious extinction pattern, suggesting an additive effect of 31,345 with cocaine. In contrast, methadone pretreatment not only dose-dependently inhibited heroin self-administration with an extinction pattern but also dose-dependently inhibited heroin-enhanced BSR and NAc DA, suggesting functional antagonism by methadone of heroin's actions. In addition, 31,345 appears to possess significant abuse liability, as it produces dose-dependent enhancement of BSR and NAc DA, maintains a low rate of self-administration behavior, and dose-dependently reinstates drug-seeking behavior. In contrast, methadone only partially maintains self-administration with an extinction pattern, and fails to induce reinstatement of drug-seeking behavior. These findings suggest that 31,345 is a cocaine-like slow-onset long-acting monoamine transporter inhibitor that may act as an agonist therapy for cocaine addiction. However, its pattern of action appears to be significantly different from that of methadone. Ideal agonist substitutes for cocaine should fully emulate methadone's actions, that is, functionally antagonizing cocaine's action while blocking monoamine transporters to augment synaptic DA.

  8. DOSE-RESPONSE RELATIONSHIP BETWEEN METHADONE DOSE AND ADHERENCE TO ANTIRETROVIRAL THERAPY AMONG HIV-POSITIVE PERSONS WHO USE ILLICIT OPIOIDS

    PubMed Central

    Lappalainen, Leslie; Nolan, Seonaid; Dobrer, Sabina; Puscas, Cathy; Montaner, Julio; Ahamad, Keith; Dong, Huiru; Kerr, Thomas; Wood, Evan; Milloy, M-J

    2015-01-01

    Background and Aims For HIV-positive individuals who use illicit opioids, engagement in methadone maintenance therapy (MMT) can contribute to improved HIV treatment outcomes. However, to our knowledge, the role of methadone dosing in adherence to antiretroviral therapy (ART) has not yet been investigated. We sought to examine the relationship between methadone dose and ART adherence among a cohort of persons who use illicit opioids. Design and Setting We used data from the ACCESS study, an ongoing prospective observational cohort of HIV-positive persons who use illicit drugs in Vancouver, Canada, confidentially linked to comprehensive HIV treatment data in a setting of universal no-cost medical care including medications. We evaluated the longitudinal relationship between methadone dose and the likelihood of ≥ 95% adherence to ART among ART-exposed participants during periods of engagement in MMT. Participants 297 ART-exposed individuals on MMT were recruited between December 2005 and May 2013 and followed for a median of 42.1 months. Measurements We measured methadone dose at ≥ 100 vs < 100 mg/day and the likelihood of ≥ 95% adherence to ART. Findings In adjusted generalized estimating equation (GEE) analyses, MMT dose ≥ 100 mg/day was independently associated with optimal adherence to ART (adjusted odds ratio [AOR] = 1.38; 95% confidence interval [CI]: 1.08 – 1.77, p = 0.010). In a sub-analysis, we observed a dose-response relationship between increasing MMT dose and ART adherence (AOR = 1.06 per 20 mg/day increase, 95% CI: 1.00 – 1.12, p = 0.041). Conclusion Among HIV-positive individuals in methadone maintenance therapy, those receiving higher doses of methadone (≥ 100 mg/day) are more likely to achieve ≥ 95% adherence to antiretroviral therapy than those receiving lower doses. PMID:25940906

  9. Precise simultaneous quantification of methadone and cocaine in rat serum and brain tissue samples following their successive i.p. administration.

    PubMed

    Nakhla, David S; Hussein, Lobna A; Magdy, N; Abdallah, Inas A; Hassan, Hazem E

    2017-03-24

    A sensitive high-performance liquid chromatography (HPLC) assay with dual UV detection has been developed and validated for the simultaneous quantification of methadone and cocaine in rat serum and brain tissue samples. Liquid-liquid extraction using hexanes was applied for samples extraction with Levo-Tetrahydropalmatine (L-THP) as the internal standard. Chromatographic separation of the analytes was achieved on a reversed-phase Waters Symmetry(®) C18 column (150mm×4.6mm, 5μm). A gradient elution was employed with a mobile phase consisting of 5mM potassium phosphate containing 0.1% triethylamine (pH=6.5) (A) and acetonitrile (B) with a flow rate of 1mL/min. UV detection was employed at 215nm and 235nm for the determination of methadone and cocaine, respectively. The calibration curves were linear over the range of 0.05-10μg/mL for both methadone and cocaine. The assay was validated according to FDA guidelines for bioanalytical method validation and results were satisfactory and met FDA criteria. Inter-day accuracy values of serum and brain samples ranged from 96.97 to 105.59% while intra-day accuracy values ranged from 91.49 to 111.92%. Stability assays showed that both methadone and cocaine were stable during sample storage, preparation, and analytical procedures. The method was successfully used to analyze biological samples obtained from a drug- drug interaction pharmacokinetics (PK) study conducted in rats to investigate the effect of methadone on cocaine PK. Our method not only can be used for bioanalysis of samples obtained from rats but also can potentially be applied to human biological serum samples to monitor compliance to methadone maintenance therapy (MMT) and to detect possible cocaine-methadone co-abuse.

  10. “Can’t you initiate me here?”: Challenges to timely initiation on antiretroviral therapy among methadone clients in Dar es Salaam, Tanzania

    PubMed Central

    Saleem, Haneefa T.; Mushi, Dorothy; Hassan, Saria; Bruce, R. Douglas; Cooke, Alexis; Mbwambo, Jessie; Lambdin, Barrot H.

    2016-01-01

    Background Despite dramatic improvement in antiretroviral therapy (ART) access globally, people living with HIV who inject drugs continue to face barriers that limit their access to treatment. This paper explores barriers and facilitators to ART initiation among clients attending a methadone clinic in Dar es Salaam, Tanzania. Methods We interviewed 12 providers and 20 clients living with HIV at the Muhimbili National Hospital methadone clinic between January and February 2015. We purposively sampled clients based on sex and ART status and providers based on job function. To analyze interview transcripts, we adopted a content analysis approach. Results Participants identified several factors that hindered timely ART initiation for clients at the methadone clinic. These included delays in CD4 testing and receiving CD4 test results; off-site HIV clinics; stigma operating at the individual, social and institutional levels; insufficient knowledge of the benefits of early ART initiation among clients; treatment breakdown at the clinic level possibly due to limited staff; and initiating ART only once one feels physically ill. Participants perceived social support as a buffer against stigma and facilitator of HIV treatment. Some clients also reported that persistent monitoring and follow-up on their HIV care and treatment by methadone clinic providers led them to initiate ART. Conclusion Health system factors, stigma and limited social support pose challenges for methadone clients living with HIV to initiate ART. Our findings suggest that on-site point-of-care CD4 testing, a peer support system, and trained HIV treatment specialists who are able to counsel HIV-positive clients and initiate them on ART at the methadone clinic could help reduce barriers to timely ART initiation for methadone clients. PMID:26831364

  11. Voucher-based reinforcement of cocaine abstinence in treatment-resistant methadone patients: effects of reinforcement magnitude.

    PubMed

    Silverman, K; Chutuape, M A; Bigelow, G E; Stitzer, M L

    1999-09-01

    Voucher-based reinforcement of cocaine abstinence has been one of the most effective means of treating cocaine abuse in methadone patients, but it has not been effective in all patients. This study was designed to determine if we could promote cocaine abstinence in a population of treatment-resistant cocaine abusing methadone patients by increasing the magnitude of voucher-based abstinence reinforcement. Participants were 29 methadone patients who previously failed to achieve sustained cocaine abstinence when exposed to an intervention in which they could earn up to $1155 in vouchers (exchangeable for goods/services) for providing cocaine-free urines. Each patient was exposed in counterbalanced order to three 9-week voucher conditions that varied in magnitude of voucher reinforcement. Patients were exposed to a zero, low and high magnitude condition in which they could earn up to $0, $382, or $3480 in vouchers for providing cocaine-free urines. Analyses for 22 patients exposed to all three conditions showed that increasing voucher magnitude significantly increased patients' longest duration of sustained cocaine abstinence (P<0.001) and percent of cocaine-free urines (P<0.001), and significantly decreased patients' reports of cocaine injections (P=0.024). Almost half (45%) of the patients in the high magnitude condition achieved >/=4 weeks of sustained cocaine abstinence, whereas only one patient in the low and none in the zero magnitude condition achieved more than 2 weeks. Reinforcement magnitude was a critical determinant of the effectiveness of this abstinence reinforcement intervention.

  12. A comparison of HCV antibody testing in drug-free and methadone maintenance treatment programs in the United States.

    PubMed

    Strauss, Shiela M; Astone, Janetta M; Jarlais, Don Des; Hagan, Holly

    2004-03-08

    Drug treatment programs are uniquely situated to screen patients for antibodies for hepatitis C virus (HCV), an infectious disease that has reached epidemic proportions among drug users. This paper compares the accessibility and patients' use of opportunities for HCV antibody testing in a large sample of methadone and drug-free treatment programs (N=256) in the US, and reports programs' recent changes and future plans concerning it. Results indicate that almost all methadone and about two-thirds of drug-free programs in the sample provided HCV antibody screening to at least some patients in 2001. While about two-thirds of the methadone and close to one-third of the drug-free programs offered this service to all patients, these programs report that only about 3/5 of their patients actually provided specimens for testing for HCV antibodies. Some drug treatment programs were planning to increase the availability and accessibility of HCV antibody screening, but others were planning to cut back on these services, primarily due to limited resources. These results can inform policymakers who advocate for increased HCV antibody screening in drug treatment programs about the current level and future plans for implementing these services, illuminating where resources and motivational efforts need to be targeted.

  13. Absence of neurocognitive impairment in a large Chinese sample of HCV-infected injection drug users receiving methadone treatment

    PubMed Central

    Gupta, Saurabh; Iudicello, Jennifer E.; Shi, Chuan; Letendre, Scott; Knight, Adam; Li, Jianhua; Riggs, Patricia K.; Franklin, Donald R.; Duarte, Nichole; Jin, Hua; Atkinson, J. Hampton; Yu, Xin; Wu, Zunyou; Grant, Igor; Heaton, Robert K.

    2014-01-01

    Background Prior research has demonstrated neuropsychological (NP) impairment in persons with histories of injection drug use (IDU), hepatitis C virus (HCV) infection, and methadone maintenance treatment (MMT), individually, but little is known about the NP effects of these three risk factors in combination. This issue is particularly important in China, which is addressing its highly HCV-comorbid IDU epidemic with widespread government sponsored MMT, especially in light of recent evidence suggesting that methadone may be neuroprotective in some circumstances. Methods We administered a comprehensive NP test battery to 195 Chinese heroin IDU individuals taking MMT (IDU+ group), the majority of whom were also HCV+ (87%; n = 169), and compared their NP performance to that of 198 demographically comparable, non-IDU Chinese controls (IDU− group). All participants in both groups tested negative for HIV infection, which is also a common comorbidity in the Chinese IDU population. Results The IDU+ group did not have an increased rate of global NP impairment, or perform significantly worse on any individual NP test measure. Within the IDU+ group, liver disease characteristics and reported details of heroin use were not significantly associated with NP performance. Conclusion Failure to detect NP impairment in IDU+ subjects with or without HCV infection was surprising, particularly considering the previously demonstrated sensitivity of our NP battery to neurocognitive disorders associated with HIV infection in China. One possible explanation, which should be explored in future research, is the potential neuroprotective effect of methadone in the context of HCV infection and/or heroin withdrawal. PMID:24508003

  14. The Psychometric Properties of the Iowa Personality Disorder Screen in Methadone-Maintained Patients: An Initial Investigation

    PubMed Central

    Beitel, Mark; Peters, Skye; Savant, Jonathan D.; Cutter, Christopher J.; Cecero, John J.; Barry, Declan T.

    2012-01-01

    The psychometric properties of the Iowa Personality Disorder Screen (IPDS) were examined in 150 methadone-maintained patients who completed measures of demographic, psychopathology, substance use, pain, and methadone maintenance treatment (MMT) characteristics. An exploratory factor analysis revealed a two-factor solution that explained 45 percent of the scale variance. The first factor captured internalizing tendencies, such as inhibition and hypersensitivity to others. The second factor comprised externalizing tendencies, such as impulsivity and insensitivity to others. The IPDS item subsets, derived factors, and the total score were significantly related to race/ethnicity but not sex. The effects of race/ethnicity were controlled statistically when the IPDS was compared to other measures of psychopathology, self-reported substance use, pain variables, and MMT characteristics. In general, the IPDS appears to be reliable and valid for use with methadone-maintained patients. The two-factor structure found in this study may have clinical utility and merits further investigation in other MMT samples. PMID:23398100

  15. BOA detoxification of four summer weeds during germination and seedling growth.

    PubMed

    Schulz, Margot; Marocco, Adriano; Tabaglio, Vincenzo

    2012-07-01

    A recent greenhouse study revealed a significant reduction of germination and growth of redroot pigweed (Amaranthus retroflexus) and common purslane (Portulaca oleracea) by rye mulch, whereas velvetleaf (Abutilon theophrasti) and common lambsquarters (Chenopodium album) were not suppressed. Since BOA detoxification by metabolic alteration may influence the relation between the benzoxazinoid content of the soil mulch and weed suppression, we tested the dynamics in BOA detoxification in different plant organs of three and 10-day-old seedlings of four warm season weeds incubated with five BOA concentrations (4, 20, 40, 80, and 200 μmol g(-1) fresh weight). In addition, germination and length of 3-day-old seedlings were measured after exposure to 0, 0.3, 1.5, 3, 6, and 15 μmol BOA. Finally, we tested the influence of the MDR translocator inhibitors verapamil, nifedipine, and the GST inhibitor ethycrynic acid on BOA accumulation and detoxification activity. Due to BOA-detoxification, all weeds were able to grow in environments with low BOA contents. At higher contents, Abutilon theophrasti and Chenopodium album had a better chance to survive because of highly active mechanisms that avoided the uptake of BOA (A. theophrasti) and of efficient detoxification activities in youngest seedlings (C. album). The interpretation of all of the data gave the following sequence of increasing sensitivity: A. theophrasti < C. album < P. oleracea ≤ A. retroflexus. The results were in agreement with recent findings of the suppression of these weeds by rye mulches and their benzoxazinoid contents. Our studies demonstrate for the first time that the detoxification of BOA influences the survival of certain weeds in environments enriched with this allelochemical. Therefore, detoxification processes affect the potential for weed suppression by soil allelochemicals in sustainable weed management.

  16. Detoxification and elimination of nicotine by nectar-feeding birds.

    PubMed

    Lerch-Henning, S; Du Rand, E E; Nicolson, S W

    2017-02-01

    Many dilute nectars consumed by bird pollinators contain secondary metabolites, potentially toxic chemicals produced by plants as defences against herbivores. Consequently, nectar-feeding birds are challenged not only by frequent water excess, but also by the toxin content of their diet. High water turnover, however, could be advantageous to nectar consumers by enabling them to excrete secondary metabolites or their transformation products more easily. We investigated how the alkaloid nicotine, naturally present in nectar of Nicotiana species, influences osmoregulation in white-bellied sunbirds Cinnyris talatala and Cape white-eyes Zosterops virens. We also examined the metabolic fate of nicotine in these two species to shed more light on the post-ingestive mechanisms that allow nectar-feeding birds to tolerate nectar nicotine. A high concentration of nicotine (50 µM) decreased cloacal fluid output and increased its osmolality in both species, due to reduced food intake that led to dehydration. White-eyes excreted a higher proportion of the ingested nicotine-containing diet than sunbirds. However, sugar concentration did not affect nicotine detoxification and elimination. Both species metabolised nicotine, excreting very little unchanged nicotine. Cape white-eyes mainly metabolised nicotine through the cotinine metabolic pathway, with norcotinine being the most abundant metabolite in the excreta, while white-bellied sunbirds excreted mainly nornicotine. Both species also utilized phase II conjugation reactions to detoxify nicotine, with Cape white-eyes depending more on the mercapturic acid pathway to detoxify nicotine than white-bellied sunbirds. We found that sunbirds and white-eyes, despite having a similar nicotine tolerance, responded differently and used different nicotine-derived metabolites to excrete nicotine.

  17. Detoxification of olive mill wastewater using superabsorbent polymers.

    PubMed

    Davies, L C; Novais, J M; Martins-Dias, S

    2004-01-01

    The detoxification of agro-industrial effluents using superabsorbent polymers is a new and innovative process. Olive mill wastewater constitutes a major environmental problem in Mediterranean countries due to the large volumes generated, the seasonality of the industry, and the high content of polyphenols and organic matter. The application of superabsorbent polymers allows olive mill wastewater to be used as a fertilizer, as it is immobilized, increasing the biological activity that decreases its phytotoxicity, thus making its water, organic matter and mineral content usable for plant nutrition. Various parameters that characterise olive mill wastewater were evaluated after absorption in 2 different superabsorbent polymers (SAP1 and SAP2). The organic matter was equally distributed in both phases, while there was a concentration of protein and sodium in solution. The K:Na ratio decreased from 70:1 to 2:1. The polyphenol desorption from the gel into solution was found to follow Fick's law. The mass transfer coefficients were 0.147 min(-1) and 0.0085 min(-1) for SAP1 and SAP2, respectively. Phytotoxicity tests were carried out with SAP2. Olive mill wastewater in SAP2 with polyphenol concentrations up to 200 mg l(-1) revealed no phytotoxicity, and even stimulated Lepidium sativum growth, while olive mill wastewater without superabsorbent polymer revealed growth inhibition for all concentrations tested. Caffeic acid degradation by the immobilised biomass followed zero order kinetics. Degradation constants of 0.087 mg l(-1) min(-1) gSAP2(-1) and 1.156 mg l(-1) min(-1) gSAP2(-1) were found. Fungi that developed in the plant growth medium were identified as Aspergillus sp. and Penicillium sp.

  18. Dihydroxyacetone detoxification in Saccharomyces cerevisiae involves formaldehyde dissimilation.

    PubMed

    Molin, Mikael; Blomberg, Anders

    2006-05-01

    To investigate Saccharomyces cerevisiae physiology during growth on the conditionally toxic triose dihydroxyacetone (DHA), protein expression was studied in strains overexpressing either of the two dihydroxyacetone kinase isogenes, DAK1 or DAK2, that grow well utilizing DHA as a carbon and energy source. DHA metabolism was found mostly similar to ethanol utilization, involving a strong component of glucose derepression, but also involved DHA-specific regulatory changes. A specific and strong (10- to 30-fold induction of formaldehyde dehydrogenase, Fdhlp, indicated activation of the formaldehyde dissimilation pathway in DHA medium. The importance of this pathway was further supported by impaired adaptation to DHA growth and DHA survival in a glutathione-dependent formaldehyde dehydrogenase (SFA1) deletion mutant. Glutathione synthase (GSH1) deletion led to decreased DHA survival in agreement with the glutathione cofactor requirement for the SFA1-encoded activity. DHA toxicity did, however, not solely appear related to formaldehyde accumulation, because SFA1 overexpression only enhanced formaldehyde but not DHA tolerance. In further agreement with a low DHA-to-formaldehyde flux, GSH supplements in the low microM range also fully suppressed the DHA sensitivity of a gsh1Delta strain. Under growth reduction on high (100 mM) DHA medium we report increased levels of advanced glycation end-product (AGE) formation on total protein. Under these high-DHA conditions expression of several stress-related proteins, e.g. a heat-shock protein (Hsp104p) and the oxidative stress indicator, alkyl hydroperoxide reductase (Ahp1p) was also found induced. However, hallmark determinants of oxidative stress tolerance (e.g. YAP1, SKN7, HYR1/GPX3 and SOD2) were redundant for DHA tolerance, thus indicating mechanisms of DHA toxicity largely independent of central oxidative stress defence mechanisms. We conclude that mechanisms for DHA growth and detoxification appear complex and that the

  19. Comparison of hepatic-like cell production from human embryonic stem cells and adult liver progenitor cells: CAR transduction activates a battery of detoxification genes.

    PubMed

    Funakoshi, Natalie; Duret, Cédric; Pascussi, Jean-Marc; Blanc, Pierre; Maurel, Patrick; Daujat-Chavanieu, Martine; Gerbal-Chaloin, Sabine

    2011-09-01

    In vitro production of human hepatocytes is of primary importance in basic research, pharmacotoxicology and biotherapy of liver diseases. We have developed a protocol of differentiation of human embryonic stem cells (ES) towards hepatocyte-like cells (ES-Hep). Using a set of human adult markers including CAAT/enhancer binding protein (C/EBPalpha), hepatocyte nuclear factor 4/7 ratio (HNF4alpha1/HNF4alpha7), cytochrome P450 7A1 (CYP7A1), CYP3A4 and constitutive androstane receptor (CAR), and fetal markers including alpha-fetoprotein, CYP3A7 and glutathione S-transferase P1, we analyzed the expression of a panel of 41 genes in ES-Hep comparatively with human adult primary hepatocytes, adult and fetal liver. The data revealed that after 21 days of differentiation, ES-Hep are representative of fetal hepatocytes at less than 20 weeks of gestation. The glucocorticoid receptor pathway was functional in ES-Hep. Extending protocols of differentiation to 4 weeks did not improve cell maturation. When compared with hepatocyte-like cells derived from adult liver non parenchymal epithelial (NPE) cells (NPE-Hep), ES-Hep expressed several adult and fetal liver makers at much greater levels (at least one order of magnitude), consistent with greater expression of liver-enriched transcription factors Forkhead box A2, C/EBPalpha, HNF4alpha and HNF6. It therefore seems that ES-Hep reach a better level of differentiation than NPE-Hep and that these cells use different lineage pathways towards the hepatic phenotype. Finally we showed that lentivirus-mediated expression of xenoreceptor CAR in ES-Hep induced the expression of several detoxification genes including CYP2B6, CYP2C9, CYP3A4, UDP-glycosyltransferase 1A1, solute carriers 21A6, as well as biotransformation of midazolam, a CYP3A4-specific substrate.

  20. Factors associated with HCV risk practices in methadone-maintained patients: the importance of considering the couple in prevention interventions

    PubMed Central

    2014-01-01

    Background One important public health issue associated with opioid use today is the risk of hepatitis C (HCV) infection. Although methadone maintenance may help to decrease HCV-related risk practices, HCV risk behaviors persist and are strongly associated with specific substance use patterns, mental status and social context. The ANRS-Methaville study gave us the opportunity to better disentangle the different relationships between these various factors and HCV risk practices. Methods The ANRS-Methaville multisite randomized trial was designed to assess the feasibility of initiating methadone in primary care by comparing it with methadone initiation in specialized centers. This study recruited 195 participants initiating methadone maintenance and followed up for 12 months. Longitudinal data from this trial was used to acquire a greater understanding of HCV risk practices and their pattern of correlates in this population. We selected 176 patients who had data on HCV risk practices at M0 and M12, accounting for 312 visits. HCV risk practices were defined as follows: sharing needles or syringes, sharing drug paraphernalia, getting a tattoo or having a piercing in a non-professional context, sharing toiletry items. To identify factors associated with HCV risk practices, we performed a mixed logistic regression analysis. Results HCV risk practices were reported by 19% and 15% of participants at baseline and M12, respectively. After adjustment for age, cocaine use and alcohol dependence as well as suicidal risk, living in a couple with a non-drug user and in a couple with a drug user were both independent predictors of HCV risk practices (OR[CI95%] = 4.16 [1.42-12.12]; OR[CI95%] = 9.85 [3.13-31.06], respectively). Conclusions Identifying individuals at risk of HCV transmission during methadone treatment such as stimulant users, alcohol dependent individuals, and those at suicidal risk is necessary to optimize response to treatment. Innovative prevention

  1. Contrasting metal detoxification in polychaetes, bivalves and fish from a contaminated bay.

    PubMed

    Fan, Wenhong; Xu, Zhizhen; Wang, Wen-Xiong

    2015-02-01

    Jinzhou Bay in Bohai, Northern China, is historically contaminated with metals, but the organisms living in such contaminated environments are much less well studied. In this study, we contrasted the different subcellular and detoxification responses of polychaetes, bivalves and fish collected from different contaminated sites in Jinzhou Bay. In polychaete Neanthes japonica, metal-rich granule (MRG) was the main biologically detoxified metal compartment, and metallothionein-like protein (MTLP) detoxified a relatively smaller fraction of accumulated metals. The importance of MRG increased whereas that of MTLP decreased with increasing metal bioaccumulation. Detoxification in the two bivalves was similar to that in the polychaetes. However, the MRG appeared to play only a minor role in metal binding and detoxification in the gills and livers of fish, whereas MTLP was the dominating detoxification pool. Cellular debris was an important pool binding with metals in the three marine animals. Our study highlighted the contrasting cellular binding and detoxification among different marine organisms living in contaminated environments.

  2. Relationship between knockdown resistance, metabolic detoxification and organismal resistance to pyrethroids in Anopheles sinensis.

    PubMed

    Zhong, Daibin; Chang, Xuelian; Zhou, Guofa; He, Zhengbo; Fu, Fengyang; Yan, Zhentian; Zhu, Guoding; Xu, Tielong; Bonizzoni, Mariangela; Wang, Mei-Hui; Cui, Liwang; Zheng, Bin; Chen, Bin; Yan, Guiyun

    2013-01-01

    Anopheles sinensis is the most important vector of malaria in Southeast Asia, including China. Currently, the most effective measure to prevent malaria transmission relies on vector control through the use of insecticides, primarily pyrethroids. Extensive use of insecticides poses strong selection pressure on mosquito populations for resistance. Resistance to insecticides can arise due to mutations in the insecticide target site (target site resistance), which in the case of pyrethroids is the para-type sodium channel gene, and/or the catabolism of the insecticide by detoxification enzymes before it reaches its target (metabolic detoxification resistance). In this study, we examined deltamethrin resistance in An. sinensis from China and investigated the relative importance of target site versus metabolic detoxification mechanisms in resistance. A high frequency (>85%) of nonsynonymous mutations in the para gene was found in populations from central China, but not in populations from southern China. Metabolic detoxification as measured by the activity of monooxygenases and glutathione S-transferases (GSTs) was detected in populations from both central and southern China. Monooxygenase activity levels were significantly higher in the resistant than the susceptible mosquitoes, independently of their geographic origin. Stepwise multiple regression analyses in mosquito populations from central China found that both knockdown resistance (kdr) mutations and monooxygenase activity were significantly associated with deltamethrin resistance, with monooxygenase activity playing a stronger role. These results demonstrate the importance of metabolic detoxification in pyrethroid resistance in An. sinensis, and suggest that different mechanisms of resistance could evolve in geographically different populations.

  3. Detoxification of aflatoxin B1 by an aqueous extract from leaves of Adhatoda vasica Nees.

    PubMed

    Vijayanandraj, S; Brinda, R; Kannan, K; Adhithya, R; Vinothini, S; Senthil, K; Chinta, Ramakoteswara Rao; Paranidharan, V; Velazhahan, R

    2014-04-01

    The effectiveness of aqueous extracts of various medicinal plants in detoxification of aflatoxin B1 (AFB1) was tested in vitro by thin-layer chromatography and enzyme-linked immunosorbent assay (ELISA). Among the different plant extracts, the leaf extract of Vasaka (Adhatoda vasica Nees) showed the maximum degradation of AFB1 (≥ 98%) after incubation for 24h at 37 °C. The aflatoxin detoxifying activity of the A. vasica leaf extract was significantly reduced by heating to 100 °C for 10 min or autoclaving at 121 °C for 20 min. Dialysis had no effect on aflatoxin detoxifying ability of A. vasica extract and the dialyzed extract showed similar level of detoxification of AFB1 as that of the untreated extract. A time course study of aflatoxin detoxification by A. vasica extract showed that 69% of the toxin was degraded within 6h and ≥ 95% degradation was observed after 24h of incubation. Detoxification of AFB1 by A. vasica extract was further confirmed by liquid chromatography-mass spectrometry (LC-MS) analysis. Phytochemical analysis revealed the presence of alkaloids in methanolic extract of A. vasica leaves. A partially purified alkaloid from A. vasica leaves by preparative TLC exhibited strong AFB1 detoxification activity.

  4. Molecularly imprinted polymer-sol-gel tablet toward micro-solid phase extraction: I. Determination of methadone in human plasma utilizing liquid chromatography-tandem mass spectrometry.

    PubMed

    El-Beqqali, Aziza; Abdel-Rehim, Mohamed

    2016-09-14

    In the present work molecularly imprinted sol-gel tablet (MIP-Tablet) was prepared. The MIP-sol-gel was prepared as a thin layer on polyethylene material in a tablet form. Methadone-d9 was selected as the template and 3-(propylmethacrylate)-trimethoxysilane was used as precursor. MIP-Tablet was applied for micro-solid phase extraction (μ-SPE). The MIP-Tablet was used for the determination of methadone in human plasma samples utilizing liquid chromatography-tandem mass spectrometry; and each tablet could be used twenty times. The extraction time was 10 min while desorption time was 6 min. Factors affecting the extraction efficiency such as desorption solvents, sample pH, salt addition, extraction time, desorption time and adsorption capacity were investigated. The calibration curves were obtained within the range of 5-5000 ng/mL using methadone in human plasma samples. The coefficients of determination (r(2)) values were ≥0.999 for all runs and the extraction recovery was >80%. The accuracy values for quality control samples varied from +3.6 to +9.7% and the inter-day precision (RSD %) values were ranged from 5.0 to 8.0%. The limit of detection was 1.0 ng/mL and the lower limit of quantification was 5 ng/mL utilizing methadone in human plasma samples.

  5. Differential involvement of P-glycoprotein (ABCB1) in permeability, tissue distribution, and antinociceptive activity of methadone, buprenorphine, and diprenorphine: in vitro and in vivo evaluation.

    PubMed

    Hassan, Hazem E; Myers, Alan L; Coop, Andrew; Eddington, Natalie D

    2009-12-01

    Conclusions based on either in vitro or in vivo approach to evaluate the P-gp affinity status of opioids may be misleading. For example, in vitro studies indicated that fentanyl is a P-gp inhibitor while in vivo studies indicated that it is a P-gp substrate. Quite the opposite was evident for meperidine. The objective of this study was to evaluate the P-gp affinity status of methadone, buprenorphine and diprenorphine to predict P-gp-mediated drug-drug interactions and to determine a better candidate for management of opioid dependence. Two in vitro (P-gp ATPase and monolayer efflux) assays and two in vivo (tissue distribution and antinociceptive evaluation in mdr1a/b (-/-) mice) assays were used. Methadone stimulated the P-gp ATPase activity only at higher concentrations, while verapamil and GF120918 inhibited its efflux (p < 0.05). The brain distribution and antinociceptive activity of methadone were enhanced (p < 0.05) in P-gp knockout mice. Conversely, buprenorphine and diprenorphine were negative in all assays. P-gp can affect the PK/PD of methadone, but not buprenorphine or diprenorphine. Our report is in favor of buprenorphine over methadone for management of opioid dependence. Buprenorphine most likely is not a P-gp substrate and concerns regarding P-gp-mediated drug-drug interaction are not expected.

  6. Moving toward Personalized Medicine in the Methadone Maintenance Treatment Program: A Pilot Study on the Evaluation of Treatment Responses in Taiwan

    PubMed Central

    Lee, Hsin-Ya; Li, Jih-Heng; Sheu, Yuh-Ling; Tang, Hsin-Pei; Chang, Wei-Chiao; Tang, Tze-Chun; Yeh, Yi-Chun; Wang, Shing-Yaw; Liu, Ray-H.

    2013-01-01

    This pilot study simultaneously evaluated the effects of various factors, including genetic variations of CYP2B6, CYP2C19, and ABCB1, demographic characteristics, disease states, methadone-drug interactions (MDIs), and poly-substance use, on the treatment responses among non-HIV patients in the methadone maintenance treatment program (MMTP) in Taiwan. A total of 178 patients were recruited from two major hospitals that provided MMTP services in southern Taiwan, and information regarding concomitant medications and diseases was acquired from the National Health Insurance (NHI) program. The results demonstrated that the methadone maintenance dose, CYP2B6 785G allele, and ABCB1 2677T allele have positive effects on the methadone plasma concentration. In contrast, patients with HCV coinfection, alcohol problems, and psychiatric diseases may have a negative response to treatment. Thus, a comprehensive evaluation of treatment responses in the MMTP should include not only genetic polymorphisms in methadone metabolism and transporter proteins, but also concomitant diseases, MDIs, and poly-substance use. The results also suggest that personalized medicine may be indispensable for a better outcome of the MMTP. PMID:24455721

  7. Moving toward personalized medicine in the methadone maintenance treatment program: a pilot study on the evaluation of treatment responses in Taiwan.

    PubMed

    Lee, Hsin-Ya; Li, Jih-Heng; Sheu, Yuh-Ling; Tang, Hsin-Pei; Chang, Wei-Chiao; Tang, Tze-Chun; Yeh, Yi-Chun; Wang, Shing-Yaw; Liu, Ray-H

    2013-01-01

    This pilot study simultaneously evaluated the effects of various factors, including genetic variations of CYP2B6, CYP2C19, and ABCB1, demographic characteristics, disease states, methadone-drug interactions (MDIs), and poly-substance use, on the treatment responses among non-HIV patients in the methadone maintenance treatment program (MMTP) in Taiwan. A total of 178 patients were recruited from two major hospitals that provided MMTP services in southern Taiwan, and information regarding concomitant medications and diseases was acquired from the National Health Insurance (NHI) program. The results demonstrated that the methadone maintenance dose, CYP2B6 785G allele, and ABCB1 2677T allele have positive effects on the methadone plasma concentration. In contrast, patients with HCV coinfection, alcohol problems, and psychiatric diseases may have a negative response to treatment. Thus, a comprehensive evaluation of treatment responses in the MMTP should include not only genetic polymorphisms in methadone metabolism and transporter proteins, but also concomitant diseases, MDIs, and poly-substance use. The results also suggest that personalized medicine may be indispensable for a better outcome of the MMTP.

  8. Evaluation of Serum Adiponectin Concentrations Among Drug Abusers on Methadone Maintenance Treatment

    PubMed Central

    Montazerifar, Farzaneh; Karajibani, Mansour; Lashkaripour, Kobra; Yousefi, Maryam

    2013-01-01

    Background: Adiponectin, an adipocyte-derived protein, modulates a number of metabolic processes. Methadone maintenance treatment (MMT) changes the level of hormones produced by adipose tissue in addicts. However, current data remains contradictory. Objectives: The aim of this study was to evaluate the effect of MMT on serum adiponectin levels in drug addicts. Materials and Methods: Twenty-five drug abusers with a mean age of 37.4 ± 8.7 years were referred to the Baharan Hospital, Zahedan, and 22 healthy age-matched control subjects wi