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Opioid Abuse [keywords]
- Synthesis and Kappa Opioid Receptor Activity of Furan-Substituted Salvinorin A Analogues. [JOURNAL ARTICLE]
- J Med Chem 2014 Nov 26.
The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent kappa opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semi-synthetic studies have been performed to elucidate structure-activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin A has prevented a thorough understanding of its role in binding to the kappa opioid receptor. Herein we report the synthesis of several salvinorin A derivatives with modified furan rings. Evaluation of these compounds in a functional assay indicated that sterically less demanding substitutions are preferred suggesting the furan ring is bound in a congested portion of the binding pocket. The most potent of the analogues successfully reduced drug-seeking behavior in an animal model of drug-relapse without producing the sedation observed with other kappa opioid agonists.
- Zopiclone: Is there cause for concern in addiction services and general practice? [Journal Article]
- Int J Risk Saf Med 2014 Jan 1; 26(4):183-9.
To examine the research on the dependence and abuse potential of zopiclone and the concerns that may be raised for addiction treatment services and General Practice. The focus is on four main areas: Problems that may arise from recommended use; Driving; Issues relating to dependence, and Abuse or recreational misuse.Internet-based searches were carried out using the key descriptors of zopiclone and driving, road traffic accidents, dependence, withdrawal, abuse, misuse and overdose.Problems arising from recommended use are rare and almost always confined to common side-effects. Driving-related studies indicate the potential for driving impairment for up to 12 hours following use and this has clear implications for both addiction services and general practice. The likelihood of dependence increases once recommended doses and time-frames are exceeded and vulnerable populations such as psychiatric patients and those with addiction problems are at risk.Somewhat contrary to impressions that Zopiclone has little or no abuse potential, there is evidence that this medication is prescribed at higher than recommended doses and for longer than recommended. It can also be obtained readily other than by prescription. The potential for deliberate abuse may now be regarded as established, albeit at low levels compared to the benzodiazepines and this requires a degree of vigilance by prescribers and care managers.
- The role of opioidergic genes in the treatment outcome of drug addiction pharmacotherapy: A systematic review. [JOURNAL ARTICLE]
- Am J Addict 2014 Nov 21.
Drug addiction is a serious illness with deleterious functional and social consequences for both the affected individuals, their families, and society at large. In spite of the abundant research on substance dependence, there are few effective treatments for this disease. Given the crucial role of the endogenous opioid system in the development and maintenance of substance abuse disorders, this review focuses on the opioidergic system and examines the role of opioidergic genes in the treatment outcome of pharmacotherapies of alcohol, opioid, and cocaine addiction.Scopus (all databases) and Pubmed were systematically searched with no language or year restrictions, up to July 2014, for studies that focused on the relationship between polymorphisms of opioidergic genes and the treatment outcome of pharmacotherapies of alcohol, opioid, and cocaine addictions. Selected search terms were opioid, gene, polymorphism, drug therapy, substance abuse, and response.The genetic variability of μ-, δ- and κ-opioid receptors genes OPRM1, OPRD1, and OPRK1 modulates the efficacy of opioid antagonist treatments such as naltrexone and methadone, as well as the cocaine vaccine. Despite the number of promising reports, data from additional cohorts are needed to substantiate these findings.Gene variant profiling could help predict treatment response and assist in developing effective treatments for alcohol, opioid, and cocaine addiction. (Am J Addict 2014;XX:1-15).
- Enhancing motivation within a rapid opioid substitution treatment feasibility RCT: a nested qualitative study. [Journal Article]
- Subst Abuse Treat Prev Policy 2014; 9(1):44.
Opioid substitution treatment (OST) has multiple benefits for heroin injectors and is an evidence-based major component of international treatment. The current qualitative study sought to explore participants' attitudes to and reasons for participating in a feasibility randomised trial in primary care offering 'same day' OST (methadone) for injecting heroin users compared to usual care.Twenty injecting heroin users (8 intervention and 12 controls; 16 males and 4 females) were interviewed; purposive sampling was used to select a maximum variation sample from those who agreed; and analysis used thematic methods.Motivation to join the trial included the need to secure treatment set against some ambivalence due to previous negative experiences of trying to obtain OST. Positive effects of securing methadone via the trial, included self-reported improvements in health and self-care; reduction in crime, stress and drug use. Completing the baseline questionnaires at recruitment appeared to enhance motivation for treatment for all participants. For some control participants, this motivation seemed to increase a sense of self-efficacy and cognitive dissonance generated was resolved by seeking treatment from their GP. Self-determination theory suggests that behaviour change may have been initiated during the recruitment appointment, resulting in an increased determination to seek treatment amongst control participants.Taking part in the 'script in a day' trial enabled participants in the intervention arm to gain same-day access to methadone and reduce their drug use. For those in the control arm, completing the baseline questionnaires at recruitment appeared to create cognitive dissonance between their current health state and own aspirations, so increasing motivation for treatment. Over 50% obtained and were still in receipt of OST (methadone or buprenorphine) at the 3 month follow-up. We suggest that a regular 'health evaluation' for injecting heroin users not in treatment, paired with low-barrier access to treatment, may be a way of exploring this and encouraging more into obtaining OST more quickly and at the best time for them. This intervention should be delivered without pressure for change.This trial is registered with International Standard Randomised Controlled Trial Number Register: SCript In a Day for injecting drug users: feasibility trial: ISRCTN16846554.
- Opioid Abuse and Dependence during Pregnancy: Temporal Trends and Obstetrical Outcomes. [Journal Article]
- Anesthesiology 2014 Dec; 121(6):1158-65.
The authors investigated nationwide trends in opioid abuse or dependence during pregnancy and assessed the impact on maternal and obstetrical outcomes in the United States.Hospitalizations for delivery were extracted from the Nationwide Inpatient Sample from 1998 to 2011. Temporal trends were assessed and logistic regression was used to examine the associations between maternal opioid abuse or dependence and obstetrical outcomes adjusting for relevant confounders.The prevalence of opioid abuse or dependence during pregnancy increased from 0.17% (1998) to 0.39% (2011) for an increase of 127%. Deliveries associated with maternal opioid abuse or dependence compared with those without opioid abuse or dependence were associated with an increased odds of maternal death during hospitalization (adjusted odds ratio [aOR], 4.6; 95% CI, 1.8 to 12.1, crude incidence 0.03 vs. 0.006%), cardiac arrest (aOR, 3.6; 95% CI, 1.4 to 9.1; 0.04 vs. 0.01%), intrauterine growth restriction (aOR, 2.7; 95% CI, 2.4 to 2.9; 6.8 vs. 2.1%), placental abruption (aOR, 2.4; 95% CI, 2.1 to 2.6; 3.8 vs. 1.1%), length of stay more than 7 days (aOR, 2.2; 95% CI, 2.0 to 2.5; 3.0 vs. 1.2%), preterm labor (aOR, 2.1; 95% CI, 2.0 to 2.3; 17.3 vs. 7.4%), oligohydramnios (aOR, 1.7; 95% CI, 1.6 to 1.9; 4.5 vs. 2.8%), transfusion (aOR, 1.7; 95% CI, 1.5 to 1.9; 2.0 vs. 1.0%), stillbirth (aOR, 1.5; 95% CI, 1.3 to 1.8; 1.2 vs. 0.6%), premature rupture of membranes (aOR, 1.4; 95% CI, 1.3 to 1.6; 5.7 vs. 3.8%), and cesarean delivery (aOR, 1.2; 95% CI, 1.1 to 1.3; 36.3 vs. 33.1%).Opioid abuse or dependence during pregnancy is associated with considerable obstetrical morbidity and mortality, and its prevalence is dramatically increasing in the United States. Identifying preventive strategies and therapeutic interventions in pregnant women who abuse drugs are important priorities for clinicians and scientists.
- Effectiveness of local anesthesia with lidocaine in chronic opium abusers. [Journal Article]
- J Emerg Trauma Shock 2014 Oct; 7(4):301-4.
It had been demonstrated that chronic opium abusers have lower pain thresholds compared with than non-abusers.This study aimed to compare the required dose of lidocaine, a common local anesthetic drug, with regard to the onset of anesthesia in opium abusers with that in non-abusers undergoing similar suturing of minor hand lacerations.In this study, 109 opium abusers and 91 non-abusers underwent similar suturing for hand lacerations known as digital block. We explained the patients that their case records would remain confidential and admitting to any history of opioid abuse could assist in alleviating any pain associated with the procedure.There was no statistically significant difference between the two groups with regard to age, gender, and cause of injury (P > 0.05). We found a significantly longer duration of onset of analgesia in nonopioid abusers (5.42 ± 1.93 min) than that in abusers (10.30 ± 1.79 min) (P < 0.001). In addition, the lidocaine dose administered to abusers (6.67 ± 1.21 ml) was higher (4.07 ± 1.26) as well as statistically significant (P < 0.001) than that in non-abusers.The findings from this study suggest a longer duration of onset of anesthesia and requirement of a higher lidocaine dose in opium abusers compared with nonopioid abuser. Moreover, chronic opium abusers (4-5 years) experienced significantly higher time of onset of anesthesia compared with nonchronic abusers. This outcome may be useful in selecting a more suitable local anesthetic protocol in such patients.
- Impact of abuse-deterrent OxyContin on prescription opioid utilization. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Nov 13.
We quantified the degree to which the August 2010 reformulation of abuse-deterrent OxyContin affected its use, as well as the use of alternative extended-release and immediate-release opioids.We used the IMS Health National Prescription Audit, a nationally representative source of prescription activity in the USA, to conduct a segmented time-series analysis of the use of OxyContin and other prescription opioids. Our primary time period of interest was 12 months prior to and following August 2010. We performed model checks and sensitivity analyses, such as adjusting for marketing and promotion, using alternative lag periods, and adding extra observation points.OxyContin sales were similar before and after the August 2010 reformulation, with approximately 550 000 monthly prescriptions. After adjusting for declines in the generic extended-release oxycodone market, the formulation change was associated with a reduction of approximately 18 000 OxyContin prescription sales per month (p = 0.02). This decline corresponded to a change in the annual growth rate of OxyContin use, from 4.9% prior to the reformulation to -23.8% during the year after the reformulation. There were no statistically significant changes associated with the sales of alternative extended-release (p = 0.42) or immediate-release (p = 0.70) opioids. Multiple sensitivity analyses supported these findings and their substantive interpretation.The market debut of abuse-deterrent OxyContin was associated with declines in its use after accounting for the simultaneous contraction of the generic extended-release oxycodone market. Further scrutiny into the effect of abuse-deterrent formulations on medication use and health outcomes is vital given their popularity in opioid drug development. Copyright © 2014 John Wiley & Sons, Ltd.
- Opiate dependence in schizophrenia: case presentation and literature review. [Journal Article]
- J Dual Diagn 2014 Jan-Mar; 10(1):52-7.
In the past decade opioid pain reliever misuse among the U.S. population has increased to epidemic proportions. While the U.S. has only 4% of the world's population, Americans consume 86% of the world's opioids. In 2011, approximately 13 million people (5% of the U.S. population) reported nonmedical use of prescription opioids, which are now the second most commonly abused class of drug behind cannabis. There has been little in the way of formal study examining the association between mental illness and prescription opiate abuse, but preliminary evidence suggests a strong association. Neurobiological processes involved in psychosis and opiate abuse may partially explain this association. Despite compelling evidence of the growth in opiate misuse and the potential relationship with mental illness, patients with mental disorders and/or substance abuse are routinely excluded from randomized trials, making it impossible to better understand these phenomena. Treatment guidelines, especially regarding opioid agonists such as methadone and buprenorphine for people with mental illness, are woefully inadequate. We present the case of a young man with schizoaffective disorder who sustained an injury and developed chronic back pain. Opioids were prescribed and he quickly progressed to abusing increasing doses of opioids, which eventually led to daily heroin use. The young man struggled with repeated relapses, serious use-related consequences and suicide attempts. This case highlights the role of chronic pain and opioid prescribing, the segue from prescribed use to abuse and dependence, and the transition to heroin use. It demonstrates the difficulty patients may have in obtaining adequate treatment for co-occurring mental illness and substance abuse and how outcomes are improved when treatment is integrated to address both disorders. Comprehensive treatment must involve a combination of case management and medical management, including possible opioid replacement therapy.
- Stimulant medication for ADHD in opioid maintenance treatment. [Journal Article]
- J Dual Diagn 2014 Jan-Mar; 10(1):32-8.
The use of central stimulant medication in adults with attention deficit hyperactivity disorder (ADHD) who receive opioid maintenance treatment remains controversial and empirical evidence is limited. Because of the abuse potential of stimulant drugs, Norway has restrictions on prescribing central stimulants to individuals who have substance use disorders or who are on opioid maintenance treatment. In this naturalistic study, we describe experiences from a program through which central stimulant medication was administered to patients with ADHD receiving opioid maintenance treatment.This report is based on a program evaluation of a combined treatment project designed to provide stimulant medication to patients with adult ADHD who were receiving opioid maintenance treatment. As part of the clinical treatment, patients were monitored closely for any medical issues or adverse medication reactions and provided regular urine samples for analysis and information regarding demographics, treatment goals, legal involvement, diagnoses, substance abuse, and ADHD symptoms. Monitoring occurred at baseline, at 2 months (after patients being stabilized on the central stimulant), and again at 3, 6 and 24 months.Among 42 patients initially offered the combined treatment, 24 were actually eligible, 20 started the combined treatment, and 10 stayed in the program. We were not able to identify a single major cause of treatment dropout. Patients reported significantly fewer symptoms of ADHD at the 6- to 8-week point, regardless of whether the data were analyzed using an intent-to-treat (all participants) or per-protocol (only those with complete data at all points) method. Even though self-assessed ADHD scores dropped significantly during treatment, the scores still remained fairly high, suggesting persistent functional impairment. Neither severe complications nor increase in substance abuse were observed during treatment with central stimulants.These findings show some promise with regard to the safety and utility of central stimulant medications for patients with ADHD who are receiving opioid maintenance treatment. Our study has methodological limitations, and systematic, well-designed clinical investigations are needed to increase the knowledge base.
- Non-medical prescription opioid use and violent behaviour among adolescents. [Journal Article]
- J Child Adolesc Ment Health 2014 Jul; 26(1):35-47.
Objective A pharmacological explanation for the observed positive association between opioid abuse and violence does not appear to exist. Several explanations have therefore been posited. This study attempted to shed additional light on the latent factors linking opioid abuse and adolescent violence. To the best of our knowledge, this is the first investigation to examine this relationship while distinguishing between adolescents who misused their own versus a diverted prescription. A secondary objective was to compare the estimated effects of opioid abuse to those of other substances. Method The 2008 Washington State Healthy Youth Survey data were analysed. A full information maximum likelihood multiple regression was used to account for missing data. Results Diverted- and own-prescription opioid abuse among adolescents were evidenced to be relatively strong predictors of violent thoughts and subsequent violent behaviour. Conclusions These findings, in conjunction with our unique operationalisation of violence, help us draw inferences about the true source of the relationship between opioid abuse and violence. The results also indicate that opioid abuse is a potentially modifiable risk factor for violence. The fact that this negative outcome was observed for youths abusing their own prescription is further cause for concern given the recent surge in opioid prescriptions.