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Opioid Abuse [keywords]
- Sex Differences Among Opioid-Abusing Patients With Chronic Pain in a Clinical Trial. [JOURNAL ARTICLE]
- J Addict Med 2014 Oct 16.
The characteristics of patients with co-occurring chronic pain and prescription opioid abuse have not been well described, and even less is known about differences between men and women in this population.This study evaluated sex differences in the demographic, diagnostic, and behavioral attributes of patients with chronic pain and opioid abuse.Data were collected via self-report and semistructured clinical interviews from 162 patients (120 men and 42 women) who screened for a study investigating the abuse liability of prescription opioids.There were no differences between men and women in age, race, education, marital status, or employment status. Participants had used prescription opioids for 5.4 ± 6.7 years. The majority of participants (60%) had low back pain in addition to opioid dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. More women reported more arthritic pain than men, but otherwise there were no differences in types of pain. Pain exerted a greater effect in women on mood, walking ability, and social relations. Men reported more of certain aberrant behaviors, including abuse of alcohol or illicit drugs, unauthorized dose increases, contact with street culture, and being arrested by police. Women were more depressed than men.The demographic profile of opioid-abusing patients with chronic pain presenting for treatment in a clinical trial was similar between sexes; however, some important differences were observed. Women reported more psychiatric comorbidity and endorsed greater pain-related physical and social impairment. Men reported more aberrant behaviors. These differences suggest that men with chronic pain and opioid abuse/dependence may benefit by closer monitoring of aberrant behaviors whereas women may benefit from closer attention paid to physical and psychological effects of pain.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
- Opioid Neonatal Abstinence Syndrome: controversies and implications for practice. [JOURNAL ARTICLE]
- Curr Drug Abuse Rev 2014 Oct 15.
The Opioid Neonatal Abstinence Syndrome (NAS) is a term used to describe a cluster of signs and symptoms seen in infants experiencing withdrawal from opioid drugs. Despite a substantial literature the relationship between maternal methadone dose, NAS and the method of assessment of NAS symptoms has not been agreed. The following review will address current and historical controversies surrounding these issues and will examine the evidence concerned with the evaluation of neonates exposed to methadone in utero. The key findings are as follows: A variety of NAS scales are used to assess the severity of neonatal withdrawal symptoms including locally adapted validated tools. Inconsistencies in the use of NAS scales have included the timing, duration and frequency of administration; the degree to which observers were trained to reliability; the use of NAS scales designed for term neonates to assess pre-term neonates who may have a qualitatively different expression of abstinence symptoms and; the research setting in which the tool was administered. There is a lack of research investigating the observant bias' effect upon scoring NAS, the basis for treatment decisions and the influence of concomitant maternal use of non-opioid drugs late in pregnancy. We also discuss the implications of the lack of recognition of NAS symptoms leading to possible under reporting and inappropriate, early neonatal discharge from hospital. In addition, this paper also discusses the merits and problems of conducting research in this area and highlights gaps in our knowledge and areas for further research.
- Disposing of Medicines Safely. [JOURNAL ARTICLE]
- Am J Public Health 2014 Oct 16.:e1-e2.
We read with great interest the systematic review by King et al. analyzing opioid-related mortality in North America.(1) We believe pharmacy take-back programs are an approach that could help address this daunting epidemic. Inappropriate medicine use often arises from improper access. Most adolescents who abuse prescription drugs report obtaining them for free from a friend or relative, often without that person's knowledge.(2) To reduce access, we must remove unused and unneeded medicines from circulation and safely dispose of them. (Am J Public Health. Published online ahead of print October 16, 2014: e1-e2. doi:10.2105/AJPH.2014.302296).
- The G-protein biased k-opioid receptor agonist RB-64 is analgesic with a unique spectrum of activities in vivo. [JOURNAL ARTICLE]
- J Pharmacol Exp Ther 2014 Oct 15.
The hypothesis that functionally selective GPCR agonists may have enhanced therapeutic benefits has revitalized interest for many GPCR targets. In particular, although κ-opioid receptor (KOR) agonists are analgesic with a low risk of dependence and abuse, their utility is limited by a propensity to induce sedation, motor incoordination, hallucinations and dysphoria-like states. Several labs have produced a body of work implying that G-protein biased KOR agonists might be analgesic with fewer side-effects. Although this has been an intriguing hypothesis, suitably KOR selective and G-protein biased agonists have not been available to test this idea. Here we provide data using a G-protein biased agonist RB-64 which suggests that KOR-mediated G protein signaling induces analgesia and aversion, whereas β-arrestin 2 signaling may be associated with motor incoordination. Additionally, unlike unbiased KOR agonists, the G protein-biased ligand RB 64 does not induce sedation and does not have anhedonia-like actions, suggesting that a mechanism other than G protein signaling mediates these effects. Our findings provide the first evidence with a highly selective and G-protein biased tool compound that many, but not all, of the negative side effects of KOR agonists can be minimized by creating G protein biased KOR agonists.
- Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment. [JOURNAL ARTICLE]
- J Addict Med 2014 Oct 13.
Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
- Buprenorphine/Naloxone Dose and Pain Intensity Among Individuals Initiating Treatment for Opioid Use Disorder. [JOURNAL ARTICLE]
- J Subst Abuse Treat 2014 Sep 26.
Opioid use disorder and pain often co-occur, complicating the treatment of each condition. Owing to its partial agonist properties, buprenorphine/naloxone (BUP/NX) may confer advantages over full agonist opioids for treatment of both conditions. The optimal dose of BUP/NX for comorbid pain is not known. We examined dose and other factors associated with pain intensity among patients initiating BUP/NX for opioid use disorder.We studied 1106 patients initiating BUP/NX treatment for opioid use disorder from 2003 to 2010. Information on pain level, diagnoses, and treatment were extracted from medical records. Eligible patients had at least one self-reported pain intensity numerical rating score (NRS) within 30days before BUP/NX initiation (baseline) and at least one between 15 and 90days after BUP/NX initiation (during treatment). The primary outcome was NRS decrease (2 or greater) from baseline to during treatment. We used generalized estimating equations to model odds of the primary outcome with BUP/NX dose as the independent variable of interest in the subset of patients with a baseline NRS≥2.The sample was 94% male and 73% White. Mean age was 50. Psychiatric and non-opioid substance use comorbidities were common. The following demographic and clinical correlates were associated with a decrease in pain intensity: age 18-29 (compared to 30-39 and 40-49); absence of PTSD diagnosis and absence of a chronic pain diagnosis. BUP/NX dose was not associated with decreased pain intensity in bivariate or multivariable analysis.BUP/NX maintenance treatment was generally consistent with improvements in pain intensity; however, factors other than BUP/NX dose contribute to improved pain intensity among those initiating the medication.
- PPARγ Activation Attenuates Opioid Consumption and Modulates Mesolimbic Dopamine Transmission. [JOURNAL ARTICLE]
- Neuropsychopharmacology 2014 Oct 14.
PPARγ is one of the three isoforms identified for the Peroxisome Proliferator-Activated Receptors (PPARs) and is the receptor for the thiazolidinedione class of anti-diabetic medications including pioglitazone. PPARγ has been long studied for its role in adipogenesis and glucose metabolism, but the discovery of the localization in ventral tegmental area (VTA) neurons opens new vistas for a potential role in the regulation of reward processing and motivated behavior in drug addiction. Here we demonstrate that activation of PPARγ by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. These effects are associated with a marked reduction of heroin-induced increase phosphorylation of DARPP-32 protein in the nucleus accumbens (NAc) and with a marked and selective reduction of acute heroin-induced elevation of extracellular dopamine (DA) levels in the NAc shell, as measured by in vivo microdialysis. Through ex vivo electrophysiology in acute midbrain slices, we also show that stimulation of PPARγ attenuates opioid-induced excitation of VTA DA neurons via reduction of presynaptic GABA release from the rostromedial tegmental nucleus (RMTg). Consistent with this finding site-specific microinjection of pioglitazone into the RMTg but not into the VTA reduced heroin taking. Our data illustrate that activation of PPARγ may represent a new pharmacotherapeutic option for the treatment of opioid addiction.Neuropsychopharmacology accepted article preview online, 14 October 2014. doi:10.1038/npp.2014.268.
- A cluster randomized trial of an organizational linkage intervention for offenders with substance use disorders: study protocol. [JOURNAL ARTICLE]
- Health Justice 2013 Dec 19; 1(6)
Substance use disorders are highly prevalent in community correctional populations, yet these settings frequently are ill-equipped to identify and refer offenders to community-based treatment services. In particular, community corrections staff are often opposed to the use of medication in addiction treatment because of inadequate knowledge, resources, and organizational structures to facilitate client linkages to evidence-based services.Each of the NIDA-funded Research Centers recruited 2 criminal justice agencies to participate in the study. Eligibility rules required study sites that were focused on community corrections (i.e., probation or parole), had few or no formal relationships with treatment providers for referring clients to medication-assisted treatment, and had no state or local policies prohibiting such relationships. Sites under the oversight of the same parent agency were eligible only if they were in geographically distinct catchment areas, and could be assigned to different study arms without cross-contamination at any level. The 18 clusters consisted of community corrections officers and their offender caseloads nested within agencies, each of which was partnered with at least one community-based substance abuse treatment program. Randomization was blocked by Research Center, within which one cluster was randomly assigned to a training-only condition (comparison) and the other to training followed by a strategic organizational linkage process (intervention). Line staff received a scientifically-grounded, systematically-delivered training session that addresses gaps in existing knowledge, perceptions, and information about medication-assisted treatment (MAT) and local availability of MAT services. Key decision-makers subsequently were asked to collaborate in a strategic planning process to enhance formal and informal linkages between criminal justice agencies and local MAT providers. It was hypothesized that the two implementation intervention components together would be more likely than staff training alone to improve the process of referring opioid- and alcohol-dependent adults under community supervision to appropriate addiction pharmacotherapy. Outcomes were measured at the client (referrals), line staff (attitudes), and organizational (linkage) levels.Through closer collaboration among criminal justice agencies and treatment providers, improved linkages to effective substance abuse treatment should yield significant clinical, public health and public safety benefits.
- Effects of the Mu Opioid Receptor Polymorphism (OPRM1 A118G) on Pain Regulation, Placebo Effects and Associated Personality Trait Measures. [JOURNAL ARTICLE]
- Neuropsychopharmacology 2014 Oct 13.
Mu-opioid receptors (MOPRs) are critically involved in the modulation of pain and analgesia, and represent a candidate mechanism for the development of biomarkers of pain conditions and their responses to treatment. To further understand the human implications of genetic variation within the opioid system in pain and opioid-mediated placebo responses, we investigated the association between the functional single nucleotide polymorphism (SNP) in the μ-opioid receptor gene (OPRM1), A118G, and psychophysical responses, personality traits and neurotransmitter systems [dopamine (DA), opioid] related to pain and placebo analgesia. OPRM1 G carriers, compared to AA homozygotes, showed an overall reduction of baseline μ-opioid receptor availability in regions implicated in pain and affective regulation. In response to a sustained painful stimulus, we found no effect of A118G on pain-induced endogenous opioid release. Instead, AA homozygotes showed a blunted DA response in the nucleus accumbens (NAc) in response to the pain challenge. After placebo administration, G carriers showed more pronounced mood disturbances and lower placebo-induced μ-opioid system activation in the anterior insula (aINS), the amygdala (AMY), the NAc, the thalamus (THA), and the brainstem, as well as lower levels of DA D2/3 activation in the NAc. At a trait level, G carriers reported higher NEO-Neuroticism scores; a personality trait previously associated with increased pain and lower placebo responses, which were negatively correlated with baseline μ-opioid receptor availability in the aINS and subgenual anterior cingulate cortex (sgACC). Our results demonstrate that the A118G OPRM1 polymorphism contributes to interindividual variations in the function of neurotransmitters responsive to pain (endogenous opioid and dopamine), as well as their regulation through cognitive-emotional influences in the context of therapeutic expectations, the so-called placebo effect. These effects are relevant to human vulnerability to disease processes where these neurotransmitters play a role, such as persistent pain, mood and substance use disorders, and responses to their treatments.Neuropsychopharmacology accepted article preview online, 13 October 2014. doi:10.1038/npp.2014.272.
- Animal models for opioid addiction drug discovery. [JOURNAL ARTICLE]
- Expert Opin Drug Discov 2014 Oct 13.:1-10.
Introduction: Since ancient times, the opium poppy has been used in a variety of settings, including pain management. Natural and synthetic derivatives of opium are commonly used in medicine today and include drugs, such as morphine, codeine, hydromorphone and oxycodone. Although excellent at inhibiting pain, these narcotics often produce a state of euphoria leading to misuse and abuse by the general population, particularly in young adults. The misuse of prescription opiates has continually increased over the past 10 years despite associated negative outcomes, resulting in opiate psychological dependence, withdrawal and relapse. Areas covered: This paper briefly refers to the history of opiate use and the modern challenges associated with chronic exposure. The authors present the prevalence of addiction and misuse of prescription opiates and discuss some of the opiate-associated effects. This includes activation of reward circuitry and compensatory receptor mechanisms. Finally, the authors provide a review on neuroadaptive changes that manifest during opiate dependence, withdrawal and relapse in animal models. Expert opinion: In spite of the various methods available to treat opiate addiction, there is still a huge unmet need for its management, including the creative design of novel, non-addictive pain medications. The authors believe that multifunctional compounds or combinations of compounds that inhibit pain pathways, whereas not activating the reward pathways, will begin to subdue the opiate addiction endemic.