Bup Feeds

Liver enzyme levels in adolescent patients treated with buprenorphine and additional psychotropic agents.

Buprenorphine Research (PubMed) - Wed, 12/10/2014 - 6:30am

Liver enzyme levels in adolescent patients treated with buprenorphine and additional psychotropic agents.

Am J Drug Alcohol Abuse. 2015 Jan;41(1):107-113

Authors: Ciftci Demirci A, Gunes H, Adaletli H, Bulanik E, Erdogan A

Abstract
Abstract Background: There are limited efficacy and safety data for buprenorphine/naloxone treatment in adolescents, and little is known about the incidence and prevalence of liver function abnormalities in young patients using buprenorphine/naloxone. Objectives: To assess the changes in liver enzyme levels associated with buprenorphine/naloxone treatment and co-medication with psychotropic agents among opioid dependent subjects aged 15-18 years. Methods: Liver enzyme levels (ALT and AST) were evaluated among 59 adolescent subjects before and following eight weeks of buprenorphine/naloxone treatment. Results: The frequency of additional psychotropic use was 60%. The patients' mean liver enzyme levels at weeks 2 and 4 were significantly higher than the baseline (ALT: p < 0.0001 and p = 0.003, and AST: p < 0.0001 and p = 0.016, respectively). However, there was no statistically significant difference in AST and ALT levels between the baseline and week 8. The majority of the abnormalities seen were clinically nonsignificant elevations (less than two times the upper limit of normal). It is plausible that the abnormalities in liver enzymes could have been mediated by the use of psychotropic medications. Conclusions: Buprenorphine/naloxone was well tolerated in most adolescent patients, besides clinically nonsignificant liver enzyme elevations. Psychotropic medications may have been associated with the liver enzyme changes early in the course of treatment. Nevertheless, given the relatively small number of adolescents studied to date with buprenorphine/naloxone, additional studies evaluating liver enzymes in young patients receiving buprenorphine/naloxone (and no other psychotropics) are needed.

PMID: 25490611 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Association between hepatitis C virus and opioid use while in buprenorphine treatment: preliminary findings.

Buprenorphine Research (PubMed) - Wed, 12/10/2014 - 6:30am

Association between hepatitis C virus and opioid use while in buprenorphine treatment: preliminary findings.

Am J Drug Alcohol Abuse. 2015 Jan;41(1):88-92

Authors: Murphy SM, Dweik D, McPherson S, Roll JM

Abstract
Abstract Background: The prevalence of hepatitis-C-virus (HCV) infections is high among opioid-dependent individuals. Prior research on the simultaneous treatment of both conditions has primarily assessed success as it pertains to HCV. However, it has been noted that favorable substance use therapy outcomes may improve the likelihood of HCV-treatment initiation and success. Therefore, current guidelines for the treatment of HCV among illicit drug users suggest that treatment for addiction be given the highest priority. Objectives: To determine whether opioid-dependent participants in a clinical trial of buprenorphine-treatment tapering regimens, who tested positive for the HCV antibody, experienced significantly different levels of opioid abstinence than those not infected. Methods: Data came from the National Drug Abuse Treatment Clinical Trial Network study 0003. 516 eligible opioid-dependent participants were randomized to either a 7-day or 28-day buprenorphine tapering schedule following a 4-week buprenorphine stabilization period. Generalized estimating equations were used to test the research question. Results: Participants with the HCV antibody were significantly less likely to submit opioid-negative urine analyses during and/or immediately following active treatment [OR = 0.69; CI = 0.51-0.93], indicating a higher rate of opioid use among this group. Conclusion: Individualized opioid-dependence treatment strategies may be required for opioid-dependent individuals who test positive for the HCV antibody in order to ensure resources for both opioid-dependence and HCV therapies are used efficiently.

PMID: 25490610 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation.

Buprenorphine Research (PubMed) - Wed, 12/10/2014 - 6:30am
Related Articles

Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation.

Lab Anim. 2014 Dec 8;

Authors: Jirkof P, Tourvieille A, Cinelli P, Arras M

Abstract
Sustained-release formulations of analgesic drugs are promising alternatives to repeated drug injections. Here, we compared a sustained-release formulation of buprenorphine (SB, 2.2 mg/kg) with a standard protocol of three injections of buprenorphine (Temgesic, 0.1 mg/kg/8 h) in mice. Buprenorphine serum concentration and analgesic action (thermal sensitivity) were determined in healthy mice. Additionally, the pain relief properties of both protocols were assessed after laparotomy using physiological and ethological measures of pain and recovery. Serum concentrations and thermal sensitivity tests indicated duration of action of at least 4 h (but less than 8 h) with the Temgesic protocol, and 24-48 h with SB. Behavioural and clinical parameters indicated at least partial pain relief after surgery for both protocols. Observed side-effects of buprenorphine independent of the protocol were increased activity, disturbed circadian rhythm and several abnormal behaviours. A tendency for decreased food and water intake as well as body weight reduction was also seen. Body weight decreased significantly in animals that received three injections of Temgesic, regardless of whether surgery was performed or not (P = 0.015; P = 0.023), hinting at a stress response towards this repeated intervention. In conclusion, an application interval of 8 h (Temgesic) appears too long and might lead to repeated periods with insufficient analgesia in animals undergoing lasting and/or substantial pain after surgery. In comparison to the standard protocol, SB provided a long-lasting, assured analgesia without possible stressful repeated injections in a standard surgical model, with only limited and acceptable behavioural side-effects.

PMID: 25488320 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Hyperalgesia and increased sevoflurane minimum alveolar concentration induced by opioids in the rat: A randomised experimental study.

Buprenorphine Research (PubMed) - Tue, 12/09/2014 - 6:30am

Hyperalgesia and increased sevoflurane minimum alveolar concentration induced by opioids in the rat: A randomised experimental study.

Eur J Anaesthesiol. 2014 Dec 5;

Authors: Abreu M, Aguado D, Benito J, García-Fernández J, Segura IA

Abstract
BACKGROUND: Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia.
OBJECTIVES: To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia.
DESIGN: A prospective, randomised, experimental study.
SETTING: Experimental Surgery, La Paz University Hospital, Madrid, Spain.
ANIMALS: Seventy-nine adult male Wistar rats.
INTERVENTIONS: Sevoflurane minimum alveolar concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 μg kg h, buprenorphine 150 μg kg, methadone 8 mg kg or morphine 10 mg kg. The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg kg on remifentanil-induced hyperalgesia.
MAIN OUTCOME MEASURES: The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA).
RESULTS: All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine.
CONCLUSION: Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.

PMID: 25485881 [PubMed - as supplied by publisher]

Categories: Bup Feeds

E-cigarette knowledge, attitudes, and use in opioid dependent smokers.

Buprenorphine Research (PubMed) - Tue, 12/09/2014 - 6:30am
Related Articles

E-cigarette knowledge, attitudes, and use in opioid dependent smokers.

J Subst Abuse Treat. 2014 Nov 20;

Authors: Stein MD, Caviness CM, Grimone K, Audet D, Borges A, Anderson BJ

Abstract
Individuals in treatment for opioid dependence have smoking rates 3-5 times greater than the U.S. prevalence rate. Traditional smoking cessation strategies have been ineffective in this population. Novel approaches are needed as well as harm reduction avenues. E-cigarettes (e-cigs) may provide such a novel harm reduction and cessation opportunity, but little is known about the knowledge of, attitudes about, and usage of e-cigs in opioid dependent smokers. The current study enrolled 315 opioid dependent smokers (164 methadone, 151 buprenorphine), treated in the same health system in Fall River, Massachusetts. The sample was 49.7% male and 85.1% non-Latino White. Overall 98.7% had heard of e-cigs, 73.0% had ever tried e-cigs, and 33.8% had used e-cigs in the past 30days. The most common reasons for use were curiosity (41.4%) and to quit all nicotine (26.0%). The proportion of opioid dependent smokers that had ever tried e-cigs and used them in the past month was substantially greater than that found in recent general population surveys. While e-cigs have been used to quit smoking, how to optimize their utility as a cessation tool remains undefined. E-cigs should be a part of smoking cessation discussions with this vulnerable, difficult-to-treat population.

PMID: 25483740 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Lifetime history of heroin use is associated with greater drug severity among prescription opioid abusers.

Buprenorphine Research (PubMed) - Mon, 12/08/2014 - 7:30am

Lifetime history of heroin use is associated with greater drug severity among prescription opioid abusers.

Addict Behav. 2014 Nov 18;42C:189-193

Authors: Meyer AC, Miller ME, Sigmon SC

Abstract
BACKGROUND: While research suggests primary prescription opioid (PO) abusers may exhibit less severe demographic and drug use characteristics than primary heroin abusers, less is known about whether a lifetime history of heroin use confers greater severity among PO abusers.
OBJECTIVE: In this secondary analysis, we examined demographic and drug use characteristics as a function of lifetime heroin use among 89 PO-dependent adults screened for a trial evaluating the relative efficacy of buprenorphine taper durations. Exploratory analyses also examined contribution of lifetime heroin use to treatment response among a subset of participants who received a uniform set of study procedures.
METHODS: Baseline characteristics were compared between participants reporting lifetime heroin use ≥5 (H(+); n=41) vs. <5 (H(-); n=48) times. Treatment response (i.e., illicit opioid abstinence and treatment retention at end of study) was examined in the subset of H(+) and H(-) participants randomized to receive the 4-week taper condition (N=22).
RESULTS: H(+) participants were significantly older and more likely to be male. They reported longer durations of illicit opioid use, greater alcohol-related problems, more past-month cocaine use, greater lifetime IV drug use, and greater lifetime use of cigarettes, amphetamines and hallucinogens. H(+) participants also had lower scores on the Positive Symptom Distress and Depression subscales of the Brief Symptom Inventory. Finally, there was a trend toward poorer treatment outcomes among H(+) participants.
CONCLUSION: A lifetime history of heroin use may be associated with elevated drug severity and unique treatment needs among treatment-seeking PO abusers.

PMID: 25481453 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Refinement of analgesia following thoracotomy and experimental myocardial infarction using the Mouse Grimace Scale.

Buprenorphine Research (PubMed) - Sun, 12/07/2014 - 8:00am

Refinement of analgesia following thoracotomy and experimental myocardial infarction using the Mouse Grimace Scale.

Exp Physiol. 2014 Dec 5;

Authors: Faller KM, McAndrew DJ, Schneider JE, Lygate CA

Abstract
The Mouse Grimace Scale (MGS) was developed for assessing pain severity, but the general applicability to complex post-surgical pain has not been established. We sought to determine whether the MGS provides benefits over and above a standard welfare scoring system for identifying pain in mice following experimental myocardial infarction. Female C57BL/6 mice (n = 60), anaesthetized with isoflurane, were subjected to thoracotomy with ligation of a coronary artery or sham procedure. A single subcutaneous dose of buprenorphine (1.1 mg/kg) was given at time of surgery and pain assessed at 24 hours by MGS and a procedure-specific welfare scoring system. In some animals, a second dose of 0.6 mg/kg buprenorphine was given and pain assessment repeated after 30 min. MGS was scored from multiple photographs by two independent blinded observers with good correlation (r = 0.98). Using the average MGS score of both observers, we identified a subset of mice with low scores that were not considered in pain by the welfare scoring system or by single observer MGS. These mice showed a significant improvement with additional analgesia, suggesting that this low-level pain is real. Pain attributable to the myocardial injury, as opposed to thoracotomy, only persisted at 24 hours in mice with large infarcts >40%. In conclusion, the use of a multi-observer, post-hoc, version of the MGS is a sensitive tool to assess efficacy of post-surgical analgesic protocols. Following surgical myocardial infarction, we identified a significant proportion of mice that were in low-level pain at 24 hours that were not identified by other assessment methods. This article is protected by copyright. All rights reserved.

PMID: 25480160 [PubMed - as supplied by publisher]

Categories: Bup Feeds

The impact of recent cocaine use on plasma levels of methadone and buprenorphine in patients with and without HIV-infection.

Buprenorphine Research (PubMed) - Sun, 12/07/2014 - 8:00am

The impact of recent cocaine use on plasma levels of methadone and buprenorphine in patients with and without HIV-infection.

J Subst Abuse Treat. 2014 Nov 5;

Authors: Tetrault JM, McCance-Katz EF, Moody DE, Fiellin DA, Lruie BS, DInh AT, Fiellin LE

Abstract
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 24hours 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. 297ng/mL, p=0.03) and peak S-methadone (285 vs. 339ng/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.

PMID: 25480096 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Predictors of buprenorphine initial outpatient maintenance and dose taper response among non-treatment-seeking heroin dependent volunteers.

Buprenorphine Research (PubMed) - Sun, 12/07/2014 - 8:00am

Predictors of buprenorphine initial outpatient maintenance and dose taper response among non-treatment-seeking heroin dependent volunteers.

Drug Alcohol Depend. 2014 Nov 26;

Authors: Woodcock EA, Lundahl LH, Greenwald MK

Abstract
BACKGROUND: Buprenorphine (BUP) is effective for treating opioid use disorder. Individuals' heroin-use characteristics may predict their responses to BUP, which could differ during maintenance and dose-taper phases. If so, treatment providers could use pre-treatment characteristics to personalize level of individual care and possibly improve treatment outcomes.
METHODS: Non-treatment-seeking heroin-dependent volunteers (N=34) initiated outpatient BUP maintenance (8-mg/day) and submitted urine samples thrice weekly tested for opioids (non-contingent result). After completing three programmatically-related inpatient behavioral pharmacology experiments (while maintained on 8-mg/day BUP), participants were discharged and underwent a double-blind BUP dose taper (4-mg/day, 2-mg/day and 0-mg/day during weeks 1-3, respectively) with an opioid-abstinence incentive ($30 per consecutive opioid-negative urine specimen, obtained thrice weekly).
RESULTS: Participants who reported less pre-study (past-month) heroin use and shorter lifetime duration of heroin use were more likely to submit an opioid-negative urine sample during initial outpatient BUP maintenance. Participants who reported more lifetime heroin-quit attempts and provided any opioid-free urine sample during initial outpatient maintenance sustained longer continuous opioid-abstinence during the BUP dose taper. Participants who reported >3 lifetime quit attempts abstained from opioid use nearly one week longer (14 days vs. 8 days to opioid-lapse) and nearly half (46.7%) refrained from opioid use during dose taper.
CONCLUSIONS: Number of prior heroin quit attempts may predict BUP dose taper response and provide a metric for stratifying heroin-dependent individuals by relative risk for opioid lapse. This metric may inform personalized relapse prevention care and improve treatment outcomes.

PMID: 25479914 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Etanercept ameliorates inflammation and pain in a novel mono-arthritic multi-flare model of streptococcal cell wall induced arthritis.

Buprenorphine Research (PubMed) - Sat, 12/06/2014 - 8:00am

Etanercept ameliorates inflammation and pain in a novel mono-arthritic multi-flare model of streptococcal cell wall induced arthritis.

BMC Musculoskelet Disord. 2014 Dec 4;15(1):409

Authors: Chakravarthy K, Faltus R, Robinson G, Sevilla R, Shin J, Zielstorff M, Byford A, Leccese E, Caniga MJ, Hseih S, Zhang S, Chiu CS, Zhang-Hoover J, Moy LY, McLeod RL, Stoffregen D, Zhang W, Murtaza A, Cicmil M

Abstract
BACKGROUND: The impact of anti-TNF, corticosteroid and analgesic therapy on inflammation and pain was evaluated in a novel mono-arthritic multi-flare rat Streptococcal Cell Wall (SCW) model using Etanercept, Dexamethasone and Buprenorphine.
METHODS: Multiple flares of arthritis were induced with an intra-articular injection of SCW in the hind ankle on day 1, followed by intravenous challenges on days 21 and 42. Inflammation and pain were monitored in the hind paws. Cytokine profiling, cell phenotyping, bioluminescence imaging and histopathological evaluation were also performed.
RESULTS: Local injection of SCW caused a rapid onset of inflammation and pain in the injected ankle which resolved within 4 days (Flare 1). Intravenous injection 20 days after sensitization resulted in an increase in ankle diameter and pain, which partially resolved in 8 days (Flare 2). The subsequent intra-venous injection in the same animals 14 days after resulted in a more chronic disease with inflammation and pain persisting over a period of 10 days (Flare 3). In Flare 2, therapeutic administration of Dexamethasone inhibited paw swelling (95%; P<0.001) and pain (55%; P<0.05). Therapeutic administration of Buprenorphine inhibited pain (80%; P<0.001) without affecting paw swelling (0%). Prophylactic administration of Etanercept in Flare 2 inhibited paw swelling (>=60%; P<0.001) and pain by >=30%. Expression of IL-1beta, IL-6, MCP-1 and CINC was reduced by >50% (P<0.001). Treatment with Etanercept in Flare 3 inhibited paw swelling by 60% (P<0.001) and pain by 25%. Prior treatment with Etanercept in Flare 2 followed by re-administration in Flare 3 led to a complete loss in the efficacy of Etanercept. Systemic exposure of Etanercept corroborated with lack of efficacy. Dexamethasone inhibited inflammation and pain in both Flares 2 and 3 (P<0.001).
CONCLUSIONS: We established a novel multi-flare SCW arthritis model enabling drug intervention in different stages of disease. We show for the first time the evaluation of inflammation and pain simultaneously in this model. Etanercept and Dexamethasone inhibited inflammation, pain and proinflammatory cytokines in this model. Taken together, this model facilitates the assessment of anti-rheumatic agents targeting inflammation and pain in the multiple flare paradigm and offers a powerful tool for drug discovery.

PMID: 25477192 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Crushed and Injected Buprenorphine Tablets: Characteristics of Princeps and Generic Solutions.

Buprenorphine Research (PubMed) - Fri, 12/05/2014 - 8:30am

Crushed and Injected Buprenorphine Tablets: Characteristics of Princeps and Generic Solutions.

PLoS One. 2014;9(12):e113991

Authors: Bouquié R, Wainstein L, Pilet P, Mussini JM, Deslandes G, Clouet J, Dailly E, Jolliet P, Victorri-Vigneau C

Abstract
Self-injection of high-dose buprenorphine is responsible for well-described complications. In 2011, we have been alerted by unusual but serious cutaneous complication among injection buprenorphine users. A prospective data collection identified 30 cases of necrotic cutaneous lesions after injection of filtered buprenorphine solution, among which 25 cases occurred following injection of buprenorphine generics. The main goal of our study was to put forward particularities that could explain the cutaneous complications, by qualitatively and quantitatively confronting particles present in Subutex and generics solutions. We used the same protocol that injected-buprenorphine users: generic or subutex tablets were crushed in sterile water and filtered through 2 filters commonly used (cotton-pad and sterifilt). Solutions were analyzed by laser granulometry, flow cytometry and scanning electron microscopy. We have highlighted the wide variation of the quantity and the size of the particles present in solution between the two drugs after cotton-pad filtration. The proportion of particles <10 µm is systematically higher in the generic solutions than with Subutex. All of the insoluble particles found in generic solutions contain silica, whereas non- organic element was to be identified in the insoluble particles of Subutex. One skin biopsy obtained from one patient who developed a necrotic lesion after intravenous injection of filtrated solution of buprenorphine generic, shows non-organic elements. Identification of particles in situ enables us to confirm the presence of silica in the biopsy. Actually the monitoring of patient receiving generic of buprenorphine must be strengthened.

PMID: 25474108 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Diversion of methadone and buprenorphine by patients in opioid substitution treatment in Sweden: Prevalence estimates and risk factors.

Buprenorphine Research (PubMed) - Thu, 12/04/2014 - 8:30am

Diversion of methadone and buprenorphine by patients in opioid substitution treatment in Sweden: Prevalence estimates and risk factors.

Int J Drug Policy. 2014 Oct 30;

Authors: Johnson B, Richert T

Abstract
BACKGROUND: Diversion-patients who sell or share their medication-is a hotly debated but relatively unresearched phenomenon. We have investigated the prevalence of self-reported diversion of methadone and buprenorphine at OST programs in Sweden. We have also examined if demographic, treatment, and social factors can be associated with an increased risk of diversion.
METHODS: Structured interviews were conducted with 411 patients from eleven OST programs. A standardized questionnaire with 106 close- and five open-ended questions were used. 280 interviews were done on site, by the researchers, while 131 interviews were conducted by specially trained patients through privileged access interviewing. The data were analyzed through frequency- and averages-calculations, cross-tabulations, and logistic regression analysis.
RESULTS: In total, 24.1% (n=99) of the patients reported diversion in the past month. 67.6% (n=277) stated that they had diverted at some point. The peer interviews showed significantly higher levels of diversion (37.4% past month) compared with the researcher interviews (17.2%). Neither demographic factors, dosages, nor collection routines were associated with diversion. The likelihood of diversion was higher for patients on mono-buprenorphine (OR=5.64) and buprenorphine-naloxone (OR=2.10), than among methadone patients. Other factors which increased the likelihood of diversion were current illicit drug use (OR=5.60), having had patients as a primary source of illicit methadone or buprenorphine prior to treatment (OR=3.39), and mainly socializing with active drug users (OR=2.12).
CONCLUSION: Self-reported diversion was considerably higher than in previous studies. This is most likely due to the new methodological strategy we used, but may also partly be explained by low availability of OST in Sweden, leading to a high demand for the substances by heroin users outside treatment. Efforts to decrease diversion should primarily focus on psychosocial and lifestyle-changing interventions, and expanded access to treatment, rather than on control measures.

PMID: 25465344 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Generic on-line solid phase extraction sample preparation strategies for the analysis of drugs in biological matrices by LC-MS/MS.

Buprenorphine Research (PubMed) - Wed, 12/03/2014 - 6:30am

Generic on-line solid phase extraction sample preparation strategies for the analysis of drugs in biological matrices by LC-MS/MS.

J Pharm Biomed Anal. 2014 Sep 30;102C:290-298

Authors: Bourgogne E, Grivet C, Varesio E, Hopfgartner G

Abstract
In the present work we investigate the integration of a single hardware platform (Prospekt-2) allowing on-line SPE with pre-/post-trapping dilution and direct injection of plasma extracts, and also compare the benefits and challenges of the different approaches for pharmaceutical drugs with heterogeneous physicochemical properties. In the first part, the generic use of on-line SPE with direct plasma injection or after protein precipitation was investigated for the quantitative analysis of talinolol. In the second part, pre-trapping and post-trapping dilution for on-line SPE is discussed for generic method development on an oxadiazole and its major metabolite. Finally, the difference of performance between direct plasma injection vs. off-line liquid-liquid extraction is also described for the quantification of buprenorphine and naltrexone down to 50 and 100pg/ml using a 0.25ml plasma aliquot. All assays were in human plasma and detection was performed by mass spectrometry detection either on simple or triple stage quadrupoles. Regardless of the tested strategy, assays were found linear, with precision and accuracy with <15% for all quality controls samples and <20% for lower limit of quantitation.

PMID: 25459926 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain.

Buprenorphine Research (PubMed) - Wed, 12/03/2014 - 6:30am

Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain.

Drug Alcohol Depend. 2014 Dec 1;145C:143-149

Authors: Wachholtz A, Gonzalez G

Abstract
INTRODUCTION: Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation.
METHOD: 120 Individuals with chronic pain were recruited in 4 groups (N=30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M=121 weeks; SD=23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses.
RESULTS: A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank=15.50; p<.001) and tolerance (log rank=20.11; p<.001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's<.01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p<.05), with the highest tolerance found among opioid naïve control group participants (p's<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R=.37; p<.05); but duration of abstinence did not alter sensitivity (ns).
CONCLUSION: Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed.

PMID: 25456326 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Opioid Addicted Buprenorphine Injectors: Drug Use During and After 12-Weeks of Buprenorphine-Naloxone or Methadone in the Republic of Georgia.

Buprenorphine Research (PubMed) - Wed, 12/03/2014 - 6:30am

Opioid Addicted Buprenorphine Injectors: Drug Use During and After 12-Weeks of Buprenorphine-Naloxone or Methadone in the Republic of Georgia.

J Subst Abuse Treat. 2014 Oct 22;

Authors: Piralishvili G, Otiashvili D, Sikharulidze Z, Kamkamidze G, Poole S, Woody GE

Abstract
AIMS: The aim of this study is to assess the prevalence of non-opioid drug use among opioid-addicted, buprenorphine injecting individuals in Georgia, during and after a 12-week course of buprenorphine-naloxone (Suboxone®) or methadone.
METHODS: Randomized controlled trial with daily observed Suboxone® or methadone and weekly counseling, urine tests and timeline followback (TLFB) in weeks 0-12 and 20, and the Addiction Severity Index (ASI) at weeks 0, 4, 8, 12, 20.
RESULTS: Of the 80 patients (40/group, 4 women), 68 (85%) completed the 12-weeks of study treatment and 66 (82.5%) completed the 20-week follow-up. At baseline, injecting more than one drug in the last 30days was reported by 68.4% of patients in the methadone and 72.5% in the Suboxone® groups. Drug use was markedly reduced in both treatment conditions but there were significant differences in the prevalence of specific drugs with more opioid (1.5 vs. 0.2%; p=0.03), less amphetamine (0.2 vs. 2.8%; p<0.001) and less marijuana (1.7 vs. 10.2%; p<0.001) positive urine tests in the methadone vs. Suboxone® groups. At the 20-week follow-up, TLFB results on the 34 that continued methadone or the 3 on Suboxone® showed less opioid (5.6 vs. 27.6%; p<0.001), illicit buprenorphine (2.7 vs. 13.8%; p=0.005), benzodiazepine (13.5 vs. 34.5%; p<0.001), and marijuana (2.8 vs. 20.7%; p<0.001) use than the 29 who did not continue opioid substitution therapy.
CONCLUSIONS: Despite small but significant differences in opioid and other drug use, both treatments were highly effective in reducing opioid and non-opioid drug use.

PMID: 25456093 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Assessing craving and its relationship to subsequent prescription opioid use among treatment-seeking prescription opioid dependent patients.

Buprenorphine Research (PubMed) - Wed, 12/03/2014 - 6:30am

Assessing craving and its relationship to subsequent prescription opioid use among treatment-seeking prescription opioid dependent patients.

Drug Alcohol Depend. 2014 Dec 1;145C:121-126

Authors: McHugh RK, Fitzmaurice GM, Carroll KM, Griffin ML, Hill KP, Wasan AD, Weiss RD

Abstract
BACKGROUND: Craving is viewed as a core feature of substance use disorders and has been shown to predict future drug use, particularly over the short term. Accordingly, craving is often assessed in treatment settings as a marker of risk for subsequent drug use. The identification of the briefest measure that maintains predictive validity is of particular value for both clinical and research settings to minimize assessment burden while maintaining utility for the prediction of use.
METHODS: Data from a multi-site clinical trial of treatment for prescription opioid dependence were examined to evaluate whether a brief, 3-item craving scale administered each week predicted urine-confirmed self report of prescription opioid use in the subsequent week. Logistic regression models examining the association between craving and presence or absence of opioid use in the following week were conducted, controlling for opioid use in the previous week, treatment condition, and lifetime history of heroin use.
RESULTS: Greater craving was associated with a higher odds of prescription opioid use in the following week. For each one-unit increase on this 10-point scale, the odds of using opioids in the subsequent week was 17% higher. In addition to an item assessing urges, items assessing cue-induced craving and perceived likelihood of relapse in an environment where drugs were previously used contributed uniquely to this association.
CONCLUSIONS: A brief measure of prescription opioid craving predicted prescription opioid use among individuals in treatment. This measure offers an efficient strategy to inform the assessment of risk for use in this population.

PMID: 25454409 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Antidepressant-like effects of buprenorphine in rats are strain dependent.

Buprenorphine Research (PubMed) - Wed, 12/03/2014 - 6:30am

Antidepressant-like effects of buprenorphine in rats are strain dependent.

Behav Brain Res. 2014 Oct 18;278C:385-392

Authors: Browne CA, van Nest DS, Lucki I

Abstract
The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting a drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains.

PMID: 25453747 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Drug analysis of residual content of used syringes: A new approach for improving knowledge of injected drugs and drug user practices.

Buprenorphine Research (PubMed) - Wed, 12/03/2014 - 6:30am

Drug analysis of residual content of used syringes: A new approach for improving knowledge of injected drugs and drug user practices.

Int J Drug Policy. 2014 Oct 2;

Authors: Néfau T, Charpentier E, Elyasmino N, Duplessy-Garson C, Levi Y, Karolak S

Abstract
BACKGROUND: Since their inception, harm reduction services, including needle exchange programs, have aimed to improve and update knowledge about illicit drug consumption and injection practices in order to assess and regularly revise the effectiveness of preventive strategies.
METHODS: In this paper we describe the development of a scientific approach to obtaining this type of information through analysis of the residual content of used syringes. This was done using a validated liquid chromatography method with mass spectrometry detection to identify different molecules. Used syringes were collected from automatic injection kit dispensers at 17 sites in Paris and the surrounding suburbs each month for one year.
RESULTS: In total, 3489 syringes were collected. No compounds were detected in 245 syringes. Heroin was the most commonly observed compound (42%), followed by cocaine (41%), buprenorphine (29%) and 4-methylethylcathinone (23%). These analyses also showed the increased appearance of 4-methylethylcathinone between the summer and winter of 2012.
CONCLUSIONS: Despite the bias involved in this approach, the method can provide rapid data on patterns of drug consumption for specific time periods and for well-defined locations. This kind of analysis enables the detection of new substances being injected and thus enables harm reduction services to revise and adapt prevention strategies.

PMID: 25449054 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Prescription opioid abuse based on representative postmortem toxicology.

Buprenorphine Research (PubMed) - Wed, 12/03/2014 - 6:30am

Prescription opioid abuse based on representative postmortem toxicology.

Forensic Sci Int. 2014 Oct 24;245C:121-125

Authors: Häkkinen M, Vuori E, Ojanperä I

Abstract
Opioids are important medications for pain and opioid maintenance treatment. Increasing use and abuse of prescription opioids has, however, caused worldwide concern. Our aim was to estimate the ratio between prescription opioid abuse and total use, based on representative postmortem toxicology. Our material included all the medico-legally examined deaths in Finland during 2010-2011 involving positive findings involving buprenorphine, codeine, fentanyl, methadone, oxycodone, or tramadol. We studied drug abuse by age group, with "abuse" meaning licit opioids used illicitly as narcotics. Drug-abuse history, drug injecting, or laboratory findings of illicit drugs defined an abuser case. We then compared abuser cases and other opioid-related cases between the opioids with the number of fatal poisonings, accidents, suicides, alcohol findings, concomitant opioid use, and median postmortem blood opioid concentrations. Opioid findings numbered 2499 in 2088 cases. Drug abuse involved 545 opioid-positive cases, which in Finland represented 0.5% of those deceased. The proportion of abuser cases among all opioid-related cases for buprenorphine was 85.5%, for methadone 82.4%, for tramadol 29.4%, for codeine 16.3%, for fentanyl 14.5%, and for oxycodone 6.9%. Abuse in age-groups >60 was rare. Concomitant other opioid findings were more frequent in abuser- than in other cases for codeine, oxycodone, and tramadol, whereas alcohol findings were more frequent in buprenorphine, codeine, and fentanyl abuse. Buprenorphine and methadone were most often related to drug abuse. Every other opioid studied involved some abuse, and especially tramadol. Abuse and fatal poisonings were concentrated in men aged 20-49.

PMID: 25447184 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Management of opioid painkiller dependence in primary care: ongoing recovery with buprenorphine/naloxone.

Buprenorphine Research (PubMed) - Sun, 11/30/2014 - 7:00am

Management of opioid painkiller dependence in primary care: ongoing recovery with buprenorphine/naloxone.

BMJ Case Rep. 2014;2014

Authors: Hard B

Abstract
Opioid painkiller dependence is a growing problem and best-practice management is not well defined. We report a case of a young woman exhibiting dependence on codeine, originally prescribed for myalgic encephalopathy, after escalating use over a 10-year period. In 2012, a consultation with a new general practitioner, who had extensive experience of patients with substance abuse, revealed the underlying dependence. After building trust for 6 months, she was able to admit to medication abuse, and was referred to the community drug and alcohol team. On presentation to the team, the patient had no pain issues and the dihydrocodeine use-600 tablets/week-solely reflected her dependence. The patient successfully underwent rapid induction with buprenorphine/naloxone as opioid substitution treatment over 2 days. She is currently stable, engaged with recovery support services and psychosocial counselling, and has just returned to work. She is maintained on a therapeutic dose of buprenorphine 10 mg/naloxone 2.5 mg.

PMID: 25432908 [PubMed - as supplied by publisher]

Categories: Bup Feeds

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