Shifting blame: Buprenorphine prescribers, addiction treatment, and prescription monitoring in middle-class America

PubMed Central

Mendoza, Sonia; Rivera-Cabrero, Allyssa S.; Hansen, Helena

2016-01-01

Growing nonmedical prescription opioid analgesic use among suburban and rural Whites has changed the public’s perception of the nature of opioid addiction, and of appropriate interventions. Opioid addiction has been recast as a biological disorder in which patients are victims of their neurotransmitters and opioid prescribers are irresponsible purveyors of dangerous substances requiring controls. This framing has led to a different set of policy responses than the “War on Drugs” that has focused on heroin trade in poor urban communities; in response to prescription opioid addiction, prescription drug monitoring programs and tamper-resistant opioid formulations have arisen as primary interventions in place of law enforcement. Through the analysis of preliminary findings from interviews with physicians who are certified to manage opioid addiction with the opioid pharmaceutical buprenorphine, we argue that an increase in prescriber monitoring has shifted the focus from addicted people to prescribers as a threat, paradoxically driving users to illicit markets and constricting their access to pharmaceutical treatment for opioid addiction. Prescriber monitoring is also altering clinical cultures of care, as general physicians respond to heightened surveillance and the psychosocial complexities of treating addiction with either rejection of opioid dependent patients, or with resourceful attempts to create support systems for their treatment where none exists. PMID:27488225

Shifting blame: Buprenorphine prescribers, addiction treatment, and prescription monitoring in middle-class America.

PubMed

Mendoza, Sonia; Rivera-Cabrero, Allyssa S; Hansen, Helena

2016-08-01

Growing nonmedical prescription opioid analgesic use among suburban and rural Whites has changed the public's perception of the nature of opioid addiction, and of appropriate interventions. Opioid addiction has been recast as a biological disorder in which patients are victims of their neurotransmitters and opioid prescribers are irresponsible purveyors of dangerous substances requiring controls. This framing has led to a different set of policy responses than the "War on Drugs" that has focused on heroin trade in poor urban communities; in response to prescription opioid addiction, prescription drug monitoring programs and tamper-resistant opioid formulations have arisen as primary interventions in place of law enforcement. Through the analysis of preliminary findings from interviews with physicians who are certified to manage opioid addiction with the opioid pharmaceutical buprenorphine, we argue that an increase in prescriber monitoring has shifted the focus from addicted people to prescribers as a threat, paradoxically driving users to illicit markets and constricting their access to pharmaceutical treatment for opioid addiction. Prescriber monitoring is also altering clinical cultures of care, as general physicians respond to heightened surveillance and the psychosocial complexities of treating addiction with either rejection of opioid dependent patients, or with resourceful attempts to create support systems for their treatment where none exists. © The Author(s) 2016.

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

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo

2014-01-01

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

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

PubMed

Wachholtz, Amy; Gonzalez, Gerardo

2014-12-01

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. 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. 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). 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pain Relievers - Multiple Languages

MedlinePlus

... español (Spanish) Bilingual PDF Health Information Translations Fentanyl - Opioid addiction, part 6 - English PDF Fentanyl - Opioid addiction, part 6 - español (Spanish) PDF Fentanyl - Opioid addiction, ...

Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments.

PubMed

Kreek, Mary Jeanne; Bart, Gavin; Lilly, Charles; LaForge, K Steven; Nielsen, David A

2005-03-01

Opiate and cocaine addictions are major social and medical problems that impose a significant burden on society. Despite the size and scope of these problems, there are few effective treatments for these addictions. Methadone maintenance is an effective and most widely used treatment for opiate addiction, allowing normalization of many physiological abnormalities caused by chronic use of short-acting opiates. There are no pharmacological treatments for cocaine addiction. Epidemiological, linkage, and association studies have demonstrated a significant contribution of genetic factors to the addictive diseases. This article reviews the molecular genetics and pharmacogenetics of opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems that have been associated with or have evidence for linkage to opiate or cocaine addiction. This evidence has been marshalled either through identification of variant alleles that lead to functional alterations of gene products, altered gene expression, or findings of linkage or association studies. Studies of polymorphisms in the mu opioid receptor gene, which encodes the receptor target of some endogenous opioids, heroin, morphine, and synthetic opioids, have contributed substantially to knowledge of genetic influences on opiate and cocaine addiction. Other genes of the endogenous opioid and monoaminergic systems, particularly genes encoding dopamine beta-hydroxylase, and the dopamine, serotonin, and norepinephrine transporters have also been implicated. Variants in genes encoding proteins involved in metabolism or biotransformation of drugs of abuse and also of treatment agents are reviewed.

Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?

PubMed Central

Kissin, Igor

2013-01-01

Background For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1) there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2) the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods Scientometric analysis of the articles representing clinical research in this area was performed to assess (1) the quality of presented evidence (type of study); and (2) the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1) editorials; (2) articles in the top specialty journals; and (3) articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles). Results Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16) were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present. PMID:23874119

Emergency Department Patient Perspectives on the Risk of Addiction to Prescription Opioids.

PubMed

Conrardy, Michael; Lank, Patrick; Cameron, Kenzie A; McConnell, Ryan; Chevrier, Alison; Sears, Jill; Ahlstrom, Eric; Wolf, Michael S; Courtney, D Mark; McCarthy, Danielle M

2016-01-01

To characterize emergency department (ED) patients' knowledge and beliefs about the addictive potential of opioids. Mixed methods analysis of data from a randomized controlled trial. Urban academic ED (>88,000 visits). One hundred and seventy four discharged ED patients prescribed hydrocodone-acetaminophen for acute pain. The study analyzed data collected from a randomized controlled trial investigating patients' knowledge of opioids. ED patients discharged with hydrocodone-acetaminophen completed an audio-recorded phone interview 4–7 days later. This analysis focuses on responses about addiction. Responses were categorized using content analysis; thematic analysis identified broad themes common across different categories. Participants' mean age was 45.5 years (SD, 14.8), 58.6% female, 50.6% white, and the majority had an orthopedic diagnosis (24.1% back pain, 52.3% other injuries). Responses were categorized first based on whether the patient believed that opioids could be addictive (categorized as: yes, 58.7%; no, 19.5%; depends, 17.2%; or do not know, 4.6%), and second based on whether or not the patient discussed his/her own experience with the medication (categorized as: personalized, 35.6%; or not personalized, 64.4%). Cohen's Kappa was 0.84 for all categories. Three themes emerged in the thematic analysis: theme 1) patients expect to “feel” addicted if they are addicted, theme 2) patients fear addiction, and theme 3) side effects affected patient views of addiction. In this sample, patients had misconceptions about opioid addiction. Some patients did not know opioids could be addictive, others underestimated their personal risk of addiction, and others overtly feared addiction and, therefore, risked inadequate pain management. Despite limited data, we recommend providers discuss opioid addiction with their patients. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government employees and is in the public domain in the US.

Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors

PubMed Central

2013-01-01

Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the opioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet, the molecular mechanism underlying the differences between males and females is still unclear. Here, we reviewed the literature describing the sex differences in analgesic responses and addiction liabilities to clinically relevant opioids. The reported interactions among opioids, estrogens, opioid receptors, and estrogen receptors are also evaluated. We postulate that the sex differences partly originated from the crosstalk among the estrogen and opioid receptors when stimulated by the exogenous opioids, possibly through common secondary messengers and the downstream gene transcriptional regulators. PMID:24010861

Usefulness of the Brief Pain Inventory in Patients with Opioid Addiction Receiving Methadone Maintenance Treatment.

PubMed

Dennis, Brittany B; Roshanov, Pavel S; Bawor, Monica; Paul, James; Varenbut, Michael; Daiter, Jeff; Plater, Carolyn; Pare, Guillame; Marsh, David C; Worster, Andrew; Desai, Dipika; Thabane, Lehana; Samaan, Zainab

2016-01-01

Chronic pain is implicated as a risk factor for illicit opioid use among patients with opioid addiction treated with methadone. However, there exists conflicting evidence that supports and refutes this claim. These discrepancies may stem from the large variability in pain measurement reported across studies. We aim to determine the clinical and demographic characteristics of patients reporting pain and evaluate the prognostic value of different pain classification measures in a sample of opioid addiction patients. Multi-center prospective cohort study. Methadone maintenance treatment facilities for managing patients with opioid addiction. This study includes participants from the Genetics of Opioid Addiction (GENOA) prospective cohort study. We assessed the prognostic value of different pain measures for predicting opioid relapse. Pain measures include the Brief Pain Inventory (BPI) and patients' response to a direct pain question all study participants were asked from the GENOA case report form (CRF) "are you currently experiencing or have been diagnosed with chronic pain?" Performance characteristics of the GENOA CRF pain measure was estimated with sensitivity and specificity using the BPI as the gold standard reference. Prognostic value was assessed using pain classification as the primary independent variable in an adjusted analysis using 1) the percentage of positive opioid urine screens and 2) high-risk opioid use (= 50% positive opioid urine screens) as the dependent variables in a linear and logistic regression analyses, respectively. Among participants eligible for inclusion (n = 444) the BPI was found to be highly sensitive, classifying a large number of GENOA participants with pain (n = 281 of the 297 classified with pain, 94.6%) in comparison to the GENOA CRF (n = 154 of 297 classified with pain, 51.8%). Participants concordantly classified as having pain according to the GENOA CRF and BPI were found to have an estimated 7.79% increase in positive opioid urine screens (estimated coefficient: 7.79; 95% CI 0.74, 14.85: P = 0.031) and a 4 times greater odds (odds ratio [OR]: 4.10 P = 0.008; 95% CI: 1.44, 11.63) of engaging in a "high risk" level of illicit opioids use. The prognostic relevance of pain classification was not maintained for the additional participants classified by the BPI (n = 143 discordant). These results suggest that while the BPI may be more sensitive in capturing pain among patients with opioid addiction, this tool is of less value for predicting the impact of pain on illicit opioid use for opioid addiction patients on methadone maintenance treatment. The GENOA CRF showed high predictive ability, whereby patients classified according to the GENOA CRF are at serious risk for opioid relapse. Using the appropriate tool to assess pain in opioid addiction may serve to improve the current detection and management of comorbid pain. We caution the interpretation of these result since they are still reflective of participants already maintained on an opioid substitution therapy (OST), which can largely differ from patients who drop out of methadone maintenance treatment (MMT) or never seek treatment altogether.

Injectable and implantable sustained release naltrexone in the treatment of opioid addiction

PubMed Central

Kunøe, Nikolaj; Lobmaier, Philipp; Ngo, Hanh; Hulse, Gary

2014-01-01

Sustained release technologies for administering the opioid antagonist naltrexone (SRX) have the potential to assist opioid-addicted patients in their efforts to maintain abstinence from heroin and other opioid agonists. Recently, reliable SRX formulations in intramuscular or implantable polymers that release naltrexone for 1–7 months have become available for clinical use and research. This qualitative review of the literature provides an overview of the technologies currently available for SRX and their effectiveness in reducing opioid use and other relevant outcomes. The majority of studies indicate that SRX is effective in reducing heroin use, and the most frequently studied SRX formulations have acceptable adverse events profiles. Registry data indicate a protective effect of SRX on mortality and morbidity. In some studies, SRX also seems to affect other outcomes, such as concomitant substance use, vocational training attendance, needle use, and risk behaviour for blood-borne diseases such as hepatitis or human immunodeficiency virus. There is a general need for more controlled studies, in particular to compare SRX with agonist maintenance treatment, to study combinations of SRX with behavioural interventions, and to study at-risk groups such as prison inmates or opioid-addicted pregnant patients. The literature suggests that sustained release naltrexone is a feasible, safe and effective option for assisting abstinence efforts in opioid addiction. PMID:23088328

Spiritual Well-Being and Associated Factors with Relapse in Opioid Addicts.

PubMed

Noormohammadi, Mohammad-Reza; Nikfarjam, Masoud; Deris, Fatemeh; Parvin, Neda

2017-03-01

Opioid dependence relapse is a complex and multidimensional problem, and lack of spiritual well-being is a major concern in opioid addicts. This study was conducted to determine spiritual well-being and factors associated with relapse among opioid addicts. This cross-sectional study was conducted from April 2015 to September 2015. According to purposive sampling, 312 eligible addicted patients were enrolled in the study. The patients had at least an attempt of detoxification in the past six months and referred to an outpatient detoxification clinic in Shahrekord (Southwest, Iran). They completed Paloutzian and Ellison's Spiritual Well-being Scale. A researcher-developed questionnaire consisting of demographic characteristics and 20 questions about associated factors with relapse was administered. Data were analysed by version 16.0 (SPSS Inc.,Chicago, IL) using one-way ANOVA, Pearson's correlation test, chi-square, Friedman test, and student's t-test. The most important factors associated with opioid dependence relapse consist of relation with an addict friend, unemployment, living expenses, family conflicts, and somatic pain. In the present study, 157 patients had never experienced relapse while the mean of relapse in the rest participants was (3.25±1.53) times. Furthermore, the addicted patients with relapse had significantly lower scores of spiritual well-being and its subscales compared with non-relapse patients (p<0.001). The findings of the present study indicate the necessity of paying attention to spiritual well-being, family and economical, personal, and occupational factors as crucial factors in opiate addiction relapse.

Abuse liability in opioid therapy for pain treatment in patients with an addiction history.

PubMed

Weaver, Michael; Schnoll, Sidney

2002-01-01

Patients may present to physicians with complaints of acute or chronic pain. Some of these patients will have a history of addiction to drugs or alcohol, and a few will have active addiction. Controlled-substance prescriptions, especially opioid pain medications, can be very beneficial for treatment of pain in patients. There are clear differences between physical dependence on medication, active addiction, addiction in remission, and pseudoaddiction. A search of the medical literature revealed different rates of addiction in patients with chronic pain because different criteria were used to define addiction and the types of chronic pain. It appears that rates of addiction in patient populations with chronic pain are no different than rates of addiction in the general population, according to some recent studies. "Drug-seeking behavior" may be seen with either active addiction or pseudoaddiction. A way to distinguish between these conditions is by giving the patient more pain medication and observing the patient's pattern of behavior. Some patients may be at higher risk to abuse prescription opioids, and some types of drug-seeking behavior may be more predictive of active addiction than pseudoaddiction. General guidelines can improve physicians' comfort level in prescribing opioids for patients with chronic pain, even those with a history of addiction. These include using a medication agreement or contract, setting appropriate goals with the patient, giving appropriate amounts of pain medication, monitoring with drug screens and pill counts, and documenting the case carefully. Even patients with a history of addiction can benefit from opioid pain medications if the patients are monitored appropriately.

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

PubMed Central

Morgan, Michael M; Christie, MacDonald J

2011-01-01

Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21434879

Buprenorphine-naloxone therapy in pain management.

PubMed

Chen, Kelly Yan; Chen, Lucy; Mao, Jianren

2014-05-01

Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management.

Injectable and implantable sustained release naltrexone in the treatment of opioid addiction.

PubMed

Kunøe, Nikolaj; Lobmaier, Philipp; Ngo, Hanh; Hulse, Gary

2014-02-01

Sustained release technologies for administering the opioid antagonist naltrexone (SRX) have the potential to assist opioid-addicted patients in their efforts to maintain abstinence from heroin and other opioid agonists. Recently, reliable SRX formulations in intramuscular or implantable polymers that release naltrexone for 1-7 months have become available for clinical use and research. This qualitative review of the literature provides an overview of the technologies currently available for SRX and their effectiveness in reducing opioid use and other relevant outcomes. The majority of studies indicate that SRX is effective in reducing heroin use, and the most frequently studied SRX formulations have acceptable adverse events profiles. Registry data indicate a protective effect of SRX on mortality and morbidity. In some studies, SRX also seems to affect other outcomes, such as concomitant substance use, vocational training attendance, needle use, and risk behaviour for blood-borne diseases such as hepatitis or human immunodeficiency virus. There is a general need for more controlled studies, in particular to compare SRX with agonist maintenance treatment, to study combinations of SRX with behavioural interventions, and to study at-risk groups such as prison inmates or opioid-addicted pregnant patients. The literature suggests that sustained release naltrexone is a feasible, safe and effective option for assisting abstinence efforts in opioid addiction. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

The Downward Spiral of Chronic Pain, Prescription Opioid Misuse, and Addiction: Cognitive, Affective, and Neuropsychopharmacologic Pathways

PubMed Central

Garland, Eric L.; Froeliger, Brett; Zeidan, Fadel; Partin, Kaitlyn; Howard, Matthew O.

2013-01-01

Prescription opioid misuse and addiction among chronic pain patients are emerging public health concerns of considerable significance. Estimates suggest that more than 10% of chronic pain patients misuse opioid analgesics, and the number of fatalities related to nonmedical or inappropriate use of prescription opioids is climbing. Because the prevalence and adverse consequences of this threat are increasing, there is a pressing need for research that identifies the biobehavioral risk chain linking chronic pain, opioid analgesia, and addictive behaviors. To that end, the current manuscript draws upon current neuropsychopharmacologic research to provide a conceptual framework of the downward spiral leading to prescription opioid misuse and addiction among chronic pain patients receiving opioid analgesic pharmacotherapy. Addictive use of opioids is described as the outcome of a cycle initiated by chronic pain and negative affect and reinforced by opioidergic-dopamingeric interactions, leading to attentional hypervigilance for pain and drug cues, dysfunctional connectivity between self-referential and cognitive control networks in the brain, and allostatic dysregulation of stress and reward circuitry. Implications for clinical practice are discussed; multimodal, mindfulness-oriented treatment is introduced as a potentially effective approach to disrupting the downward spiral and facilitating recovery from chronic pain and opioid addiction. PMID:23988582

The downward spiral of chronic pain, prescription opioid misuse, and addiction: cognitive, affective, and neuropsychopharmacologic pathways.

PubMed

Garland, Eric L; Froeliger, Brett; Zeidan, Fadel; Partin, Kaitlyn; Howard, Matthew O

2013-12-01

Prescription opioid misuse and addiction among chronic pain patients are emerging public health concerns of considerable significance. Estimates suggest that more than 10% of chronic pain patients misuse opioid analgesics, and the number of fatalities related to nonmedical or inappropriate use of prescription opioids is climbing. Because the prevalence and adverse consequences of this threat are increasing, there is a pressing need for research that identifies the biobehavioral risk chain linking chronic pain, opioid analgesia, and addictive behaviors. To that end, the current manuscript draws upon current neuropsychopharmacologic research to provide a conceptual framework of the downward spiral leading to prescription opioid misuse and addiction among chronic pain patients receiving opioid analgesic pharmacotherapy. Addictive use of opioids is described as the outcome of a cycle initiated by chronic pain and negative affect and reinforced by opioidergic-dopamingeric interactions, leading to attentional hypervigilance for pain and drug cues, dysfunctional connectivity between self-referential and cognitive control networks in the brain, and allostatic dysregulation of stress and reward circuitry. Implications for clinical practice are discussed; multimodal, mindfulness-oriented treatment is introduced as a potentially effective approach to disrupting the downward spiral and facilitating recovery from chronic pain and opioid addiction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Buprenorphine and addiction: challenges for the pharmacist.

PubMed

Boatwright, Deborah E

2002-01-01

To present an analysis of the Drug Addiction Treatment Act of 2000 (DATA) and its impact on the practice of pharmacy. Statutes, codes, regulations, newspaper articles, journal articles; search of articles posted on MEDLINE identified using the search terms methadone, buprenorphine, treatment, opioid abuse, and opioid addiction. Not applicable. Not applicable. DATA and Food and Drug Administration approval of sublingual tablets of buprenorphine and buprenorphine with naloxone (Reckitt and Benckiser) will dramatically expand opioid addicts' access to treatment and increase the number of opioid addicts receiving prescriptions for buprenorphine and buprenorphine with naloxone. The availability of buprenorphine will pose unique challenges to pharmacists and suggests the need for education on addiction and greater awareness of the unique needs of patients recovering from addiction. The stage is being set to expand access to treatment and reach more untreated opioid addicts in the United States. Professional organizations such as the American Pharmaceutical Association should work with the U.S. Department of Health and Human Services and its Substance Abuse and Mental Health Services Administration to develop training materials, curricula, and guidelines for pharmacists on substance abuse with a special focus on outpatient opioid treatment. Such materials could be used in continuing education programs and materials and in pharmacy schools.

Heroin - Multiple Languages

MedlinePlus

... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... Spanish) PDF Heroin - Opioid addiction, part 7 - English MP3 Heroin - Opioid addiction, part 7 - español (Spanish) MP3 ...

Opioid Addiction and Abuse in Primary Care Practice: A Comparison of Methadone and Buprenorphine as Treatment Options

PubMed Central

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

2014-01-01

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, 200 000 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. PMID:23092049

Contingency management for tobacco smoking during opioid addiction treatment: a randomised pilot study.

PubMed

Ainscough, Tom Stephen; Brose, Leonie S; Strang, John; McNeill, Ann

2017-09-01

Smoking rates among individuals in treatment for opioid addiction are close to five times that of the general public. Moreover, drug-addicted smokers have a premature mortality rate four times greater than drug-addicted non-smokers. The aim of this pilot study was to investigate whether contingency management (CM) can be successfully added to evidence-based stop smoking treatment in individuals undergoing treatment for opioid addiction and assess preliminary evidence for its impact. Forty tobacco smokers currently undergoing treatment for opioid addiction. Escalating with reset CM as an adjunct to standard smoking cessation treatment. Financial incentives will be administered over a 5-week period for either biochemically verified abstinence from smoking or attendance at the clinic. Participants will be randomised to conditions stratified on current levels of smoking (high or low). To assess whether a CM intervention can be successfully added to standard stop smoking services treatment, in patients undergoing outpatient treatment for opioid addiction. This will be measured as the number of people completing the 5 weeks of the intervention. Ethics approval for the study was granted on the 16 June 2016 by the London-city and east (reference 16/LO/0990) ethics committee. The pilot study was retrospectively registered on clincaltrials.gov in January 2017 (ID: NCT03015597). A SPIRIT checklist and figure are available for this protocol. It is planned that the results of this study will be published in an academic journal. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder.

PubMed

Brenton, Ashley; Richeimer, Steven; Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Blanchard, John; Meshkin, Brian

2017-01-01

Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes.

Prescription opioid abuse, pain and addiction: clinical issues and implications.

PubMed

Ling, Walter; Mooney, Larissa; Hillhouse, Maureen

2011-05-01

Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. © 2011 Australasian Professional Society on Alcohol and other Drugs.

Prescription opioid abuse, pain and addiction: Clinical issues and implications

PubMed Central

LING, WALTER; MOONEY, LARISSA; HILLHOUSE, MAUREEN

2014-01-01

Issues Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. Approach This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial μ agonist buprenorphine in the management of concurrent pain and opioid addiction. Implications Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. Conclusions The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. PMID:21545561

Time-dependent regional brain distribution of methadone and naltrexone in the treatment of opioid addiction.

PubMed

Teklezgi, Belin G; Pamreddy, Annapurna; Baijnath, Sooraj; Kruger, Hendrik G; Naicker, Tricia; Gopal, Nirmala D; Govender, Thavendran

2018-02-14

Opioid addiction is a serious public health concern with severe health and social implications; therefore, extensive therapeutic efforts are required to keep users drug free. The two main pharmacological interventions, in the treatment of addiction, involve management with methadone an mu (μ)-opioid agonist and treatment with naltrexone, μ-opioid, kappa (κ)-opioid and delta (δ)-opioid antagonist. MET and NAL are believed to help individuals to derive maximum benefit from treatment and undergo a full recovery. The aim of this study was to determine the localization and distribution of MET and NAL, over a 24-hour period in rodent brain, in order to investigate the differences in their respective regional brain distributions. This would provide a better understanding of the role of each individual drug in the treatment of addiction, especially NAL, whose efficacy is controversial. Tissue distribution was determined by using mass spectrometric imaging (MSI), in combination with quantification via liquid chromatography tandem mass spectrometry. MSI image analysis showed that MET was highly localized in the striatal and hippocampal regions, including the nucleus caudate, putamen and the upper cortex. NAL was distributed with high intensities in the mesocorticolimbic system including areas of the cortex, caudate putamen and ventral pallidum regions. Our results demonstrate that MET and NAL are highly localized in the brain regions with a high density of μ-receptors, the primary sites of heroin binding. These areas are strongly implicated in the development of addiction and are the major pathways that mediate brain stimulation during reward. © 2018 Society for the Study of Addiction.

Treating opioid dependence. Growing implications for primary care.

PubMed

Krantz, Mori J; Mehler, Philip S

2004-02-09

Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

Evaluation of CART peptide level in rat plasma and CSF: Possible role as a biomarker in opioid addiction.

PubMed

Bakhtazad, Atefeh; Vousooghi, Nasim; Garmabi, Behzad; Zarrindast, Mohammad Reza

2016-10-01

It has been shown previously that cocaine- and amphetamine-regulated transcript (CART) peptide has a modulatory role and homeostatic regulatory effect in motivation to and reward of the drugs of abuse specially psychostimulants. Recent data also showed that in addition to psychostimulants, CART is critically involved in the different stages of opioid addiction. Here we have evaluated the fluctuations in the level of CART peptide in plasma and CSF in different phases of opioid addiction to find out whether CART can serve as a suitable marker in opioid addiction studies. Male rats were randomly distributed in groups of control, acute low-dose (10mg/kg) morphine, acute high-dose morphine (80mg/kg), chronic escalating doses of morphine, withdrawal syndrome precipitated by administration of naloxone (1mg/kg), and abstinent after long-term drug-free maintenance of addicted animals. The level of CART peptide in CSF and plasma samples was measured by enzyme immunoassay. CART peptide concentration in the CSF and plasma was significantly elevated in acute high-dose morphine and withdrawal state animals and down-regulated in addicted rats. In abstinent group, CART peptide level was up-regulated in plasma but not in CSF samples. As the observed results are in agreement with data regarding the CART mRNA and protein expression in the brain reward pathway in opioid addiction phases, it may be suggested that evaluation of CART peptide level in CSF or plasma could be a suitable marker which reflects the rises and falls of the peptide concentration in brain in the development of opioid addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis.

PubMed

Vowles, Kevin E; McEntee, Mindy L; Julnes, Peter Siyahhan; Frohe, Tessa; Ney, John P; van der Goes, David N

2015-04-01

Opioid use in chronic pain treatment is complex, as patients may derive both benefit and harm. Identification of individuals currently using opioids in a problematic way is important given the substantial recent increases in prescription rates and consequent increases in morbidity and mortality. The present review provides updated and expanded information regarding rates of problematic opioid use in chronic pain. Because previous reviews have indicated substantial variability in this literature, several steps were taken to enhance precision and utility. First, problematic use was coded using explicitly defined terms, referring to different patterns of use (ie, misuse, abuse, and addiction). Second, average prevalence rates were calculated and weighted by sample size and study quality. Third, the influence of differences in study methodology was examined. In total, data from 38 studies were included. Rates of problematic use were quite broad, ranging from <1% to 81% across studies. Across most calculations, rates of misuse averaged between 21% and 29% (range, 95% confidence interval [CI]: 13%-38%). Rates of addiction averaged between 8% and 12% (range, 95% CI: 3%-17%). Abuse was reported in only a single study. Only 1 difference emerged when study methods were examined, where rates of addiction were lower in studies that identified prevalence assessment as a primary, rather than secondary, objective. Although significant variability remains in this literature, this review provides guidance regarding possible average rates of opioid misuse and addiction and also highlights areas in need of further clarification.

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.

PubMed

Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M; Kreek, Mary Jeanne

2016-11-01

Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; p corrected =0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; p corrected =0.041) (HC vs. NOD). This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The endogenous opioid system in cocaine addiction: what lessons have opioid peptide and receptor knockout mice taught us?

PubMed Central

Yoo, Ji Hoon; Kitchen, Ian; Bailey, Alexis

2012-01-01

Cocaine addiction has become a major concern in the UK as Britain tops the European ‘league table’ for cocaine abuse. Despite its devastating health and socio-economic consequences, no effective pharmacotherapy for treating cocaine addiction is available. Identifying neurochemical changes induced by repeated drug exposure is critical not only for understanding the transition from recreational drug use towards compulsive drug abuse but also for the development of novel targets for the treatment of the disease and especially for relapse prevention. This article focuses on the effects of chronic cocaine exposure and withdrawal on each of the endogenous opioid peptides and receptors in rodent models. In addition, we review the studies that utilized opioid peptide or receptor knockout mice in order to identify and/or clarify the role of different components of the opioid system in cocaine-addictive behaviours and in cocaine-induced alterations of brain neurochemistry. The review of these studies indicates a region-specific activation of the µ-opioid receptor system following chronic cocaine exposure, which may contribute towards the rewarding effect of the drug and possibly towards cocaine craving during withdrawal followed by relapse. Cocaine also causes a region-specific activation of the κ-opioid receptor/dynorphin system, which may antagonize the rewarding effect of the drug, and at the same time, contribute to the stress-inducing properties of the drug and the triggering of relapse. These conclusions have important implications for the development of effective pharmacotherapy for the treatment of cocaine addiction and the prevention of relapse. PMID:22428846

The endogenous opioid system: a common substrate in drug addiction.

PubMed

Trigo, José Manuel; Martin-García, Elena; Berrendero, Fernando; Robledo, Patricia; Maldonado, Rafael

2010-05-01

Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits that involve several neurotransmitters. One of the neurochemical systems that plays a pivotal role in different aspects of addiction is the endogenous opioid system (EOS). Opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within these reward circuits. Chronic exposure to the different prototypical drugs of abuse, including opioids, alcohol, nicotine, psychostimulants and cannabinoids has been reported to produce significant alterations within the EOS, which seem to play an important role in the development of the addictive process. In this review, we will describe the adaptive changes produced by different drugs of abuse on the EOS, and the current knowledge about the contribution of each component of this neurobiological system to their addictive properties.

Low-dose memantine attenuated morphine addictive behavior through its anti-inflammation and neurotrophic effects in rats.

PubMed

Chen, Shiou-Lan; Tao, Pao-Luh; Chu, Chun-Hsien; Chen, Shih-Heng; Wu, Hsiang-En; Tseng, Leon F; Hong, Jau-Shyong; Lu, Ru-Band

2012-06-01

Opioid abuse and dependency are international problems. Studies have shown that neuronal inflammation and degeneration might be related to the development of opioid addiction. Thus, using neuroprotective agents might be beneficial for treating opioid addiction. Memantine, an Alzheimer's disease medication, has neuroprotective effects in vitro and in vivo. In this study, we evaluated whether a low dose of memantine prevents opioid-induced drug-seeking behavior in rats and analyzed its mechanism. A conditioned-place-preference test was used to investigate the morphine-induced drug-seeking behaviors in rats. We found that a low-dose (0.2-1 mg/kg) of subcutaneous memantine significantly attenuated the chronic morphine-induced place-preference in rats. To clarify the effects of chronic morphine and low-dose memantine, serum and brain levels of cytokines and brain-derived neurotrophic factor (BDNF) were measured. After 6 days of morphine treatment, cytokine (IL-1β, IL-6) levels had significantly increased in serum; IL-1β and IL-6 mRNA levels had significantly increased in the nucleus accumbens and medial prefrontal cortex, both addiction-related brain areas; and BDNF levels had significantly decreased, both in serum and in addiction-related brain areas. Pretreatment with low-dose memantine significantly attenuated chronic morphine-induced increases in serum and brain cytokines. Low-dose memantine also significantly potentiated serum and brain BDNF levels. We hypothesize that neuronal inflammation and BDNF downregulation are related to the progression of opioid addiction. We hypothesize that the mechanism low-dose memantine uses to attenuate morphine-induced addiction behavior is its anti-inflammatory and neurotrophic effects.

Psychophysiology of pain and opioid use: implications for managing pain in patients with an opioid use disorder.

PubMed

Wachholtz, Amy; Foster, Simmie; Cheatle, Martin

2015-01-01

Opioid therapy is one component of an effective pain management regimen for patients with chronic pain and the majority of these patients use their medications responsibly. However, there are a growing number of these patients who develop an opioid use disorder and in some cases require opioid replacement therapy. Managing these patients is complex and the underlying mechanisms of pain and addiction are not well understood. Developing an effective interdisciplinary treatment program for the individual with pain and an opioid use disorder will depend on enhancing our knowledge of the psychophysiology of pain and addiction. Authors gathered key empirical and theoretical papers examining the psychophysiology of comorbid pain and opioid misuse disorders. This article reviews the current theory of the effect of pain on patients with pain and concomitant addiction, the psychophysiology of pain, opioid use and addiction, and future research in this area. Individuals with a history of opioid misuse have greater levels of hyperalgesia which may be due to alterations in psychophysiological pathways. More research is needed into the psychophysiological biomarkers among individuals with comorbid pain and addiction in order to develop better treatment approaches and improve outcomes among this difficult to treat population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neuroscience of opiates for addiction medicine: From stress-responsive systems to behavior.

PubMed

Zhou, Yan; Leri, Francesco

2016-01-01

Opiate addiction, similarly to addiction to other psychoactive drugs, is chronic relapsing brain disease caused by drug-induced short-term and long-term neuroadaptations at the molecular, cellular, and behavioral levels. Preclinical research in laboratory animals has found important interactions between opiate exposure and stress-responsive systems. In this review, we will discuss the dysregulation of several stress-responsive systems in opiate addiction: vasopressin and its receptor system, endogenous opioid systems (including proopiomelanocortin/mu opioid receptor and dynorphin/kappa opioid receptor), orexin and its receptor system, and the hypothalamic-pituitary-adrenal axis. A more complete understanding of how opiates alter these stress systems, through further laboratory-based studies, is required to identify novel and effective pharmacological targets for the long-term treatment of heroin addiction. © 2016 Elsevier B.V. All rights reserved.

A psycho-genetic study of hedonic responsiveness in relation to "food addiction".

PubMed

Davis, Caroline; Loxton, Natalie J

2014-10-16

While food addiction has no formally-recognized definition, it is typically operationalized according to the diagnostic principles established by the Yale Food Addiction Scale-an inventory based on the symptom criteria for substance dependence in the DSM-IV. Currently, there is little biologically-based research investigating the risk factors for food addiction. What does exist has focused almost exclusively on dopaminergic reward pathways in the brain. While brain opioid signaling has also been strongly implicated in the control of food intake, there is no research examining this neural circuitry in the association with food addiction. The purpose of the study was therefore to test a model predicting that a stronger activation potential of opioid circuitry-as indicated by the functional A118G marker of the mu-opioid receptor gene-would serve as an indirect risk factor for food addiction via a heightened hedonic responsiveness to palatable food. Results confirmed these relationships. In addition, our findings that the food-addiction group had significantly higher levels of hedonic responsiveness to food suggests that this bio-behavioral trait may foster a proneness to overeating, to episodes of binge eating, and ultimately to a compulsive and addictive pattern of food intake.

Volatility and change in chronic pain severity predict outcomes of treatment for prescription opioid addiction.

PubMed

Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

2017-07-01

Buprenorphine-naloxone (BUP-NLX) can be used to manage prescription opioid addiction among persons with chronic pain, but post-treatment relapse is common and difficult to predict. This study estimated whether changes in pain over time and pain volatility during BUP-NLX maintenance would predict opioid use during the taper BUP-NLX taper. Secondary analysis of a multi-site clinical trial for prescription opioid addiction, using data obtained during a 12-week BUP-NLX stabilization and 4-week BUP-NLX taper. Community clinics affiliated with a national clinical trials network in 10 US cities. Subjects with chronic pain who entered the BUP-NLX taper phase (n = 125) with enrollment occurring from June 2006 to July 2009 (52% male, 88% Caucasian, 31% married). Outcomes were weekly biologically verified and self-reported opioid use from the 4-week taper phase. Predictors were estimates of baseline severity, rate of change and volatility in pain from weekly self-reports during the 12-week maintenance phase. Controlling for baseline pain and treatment condition, increased pain [odds ratio (OR) = 2.38, P = 0.02] and greater pain volatility (OR = 2.43, P = 0.04) predicted greater odds of positive opioid urine screen during BUP-NLX taper. Increased pain (IRR = 1.40, P = 0.04) and greater pain volatility [incidence-rate ratio (IRR) = 1.66, P = 0.009] also predicted greater frequency of self-reported opioid use. Adults with chronic pain receiving out-patient treatment with buprenorphine-naloxone (BUP-NLX) for prescription opioid addiction have an elevated risk for opioid use when tapering off maintenance treatment. Those with relative persistence in pain over time and greater volatility in pain during treatment are less likely to sustain abstinence during BUP-NLX taper. © 2017 Society for the Study of Addiction.

Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder

PubMed Central

Brenton, Ashley; Richeimer, Steven; Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Blanchard, John; Meshkin, Brian

2017-01-01

Background Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Purpose This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). Patients and methods The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. Conclusion The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes. PMID:28572737

Medicaid Coverage for Methadone Maintenance and Use of Opioid Agonist Therapy in Specialty Addiction Treatment.

PubMed

Saloner, Brendan; Stoller, Kenneth B; Barry, Colleen L

2016-06-01

This study examined differences in opioid agonist therapy (OAT) utilization among Medicaid-enrolled adults receiving public-sector opioid use disorder treatment in states with Medicaid coverage of methadone maintenance, states with block grant funding only, and states without public coverage of methadone. Person-level treatment admission data, which included information on reason for treatment and use of OAT from 36 states were linked to state-level Medicaid policies collected in a 50-state survey. Probabilities of OAT use among Medicaid enrollees in opioid addiction treatment were calculated, with adjustment for demographic characteristics and patterns of substance use. In adjusted analysis, 45.0% of Medicaid-enrolled individuals in opioid addiction treatment in states with Medicaid coverage for methadone maintenance used OAT, compared with 30.1% in states with block grant coverage only and 17.0% in states with no coverage. Differences were widest in nonintensive outpatient settings. Medicaid methadone maintenance coverage is critical for encouraging OAT among individuals with opioid use disorders.

Informed consent to opioid agonist maintenance treatment: recommended ethical guidelines.

PubMed

Carter, Adrian; Hall, Wayne

2008-02-01

Some bioethicists have questioned whether opioid addicted individuals are able to provide free and informed consent to opioid agonist maintenance treatment. Conflicting motives for providing such treatment (e.g. improving the personal health of addicts and protecting public health and order) can also influence what individuals are required to consent to, and how that consent is obtained. We discuss both issues and attempt to specify the conditions for obtaining informed consent to agonist maintenance treatment for opioid addiction. We briefly review the neuroscientific literature on the effects of addiction on the autonomy and decision-making capacity of opioid dependent individuals, and ascertain how informed consent to the treatment of opioid addiction should be obtained. We also provide an ethical analysis of the competing social and medical forces that influence the consent process and make some recommendations on how to ensure that individuals enter maintenance treatment that is provided in an effective and ethical way. Our analysis shows that whilst the autonomy of opioid dependent individuals is impaired by their addiction, they do retain the ability to consent to treatment provided they are not in acute withdrawal or intoxication. These symptoms should have abated, either by supervised withdrawal or stabilisation on agonist maintenance, before they are asked to consent to a detailed treatment contract. Once stabilised, individuals should be provided with detailed information about the risks and benefits of all treatments, and restrictions and regulations under which they are provided. Informed consent is an important part of the treatment process that should be obtained in ways that increase the autonomy and decision-making capacity in opioid addicts.

Investigating expectation and reward in human opioid addiction with [(11) C]raclopride PET.

PubMed

Watson, Ben J; Taylor, Lindsay G; Reid, Alastair G; Wilson, Sue J; Stokes, Paul R; Brooks, David J; Myers, James F; Turkheimer, Federico E; Nutt, David J; Lingford-Hughes, Anne R

2014-11-01

The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [(11) C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals. © 2013 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Novel pharmacotherapeutic strategies for treatment of opioid-induced neonatal abstinence syndrome

PubMed Central

McLemore, Gabrielle L.; Lewis, Tamorah; Jones, Catherine H.; Gauda, Estelle B.

2014-01-01

Summary The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care in maternal and fetal/neonatal (M-F/N) medicine. The standard of care for illicit or prescription opioid dependence during pregnancy is opioid agonist (methadone or buprenorphine) substitution therapy, which are also frequently abused. The next generation of pharmacotherapies for the treatment of illicit or prescription opioid addiction in the M-F/N interactional dyad must take into consideration the interplay between genetic, epigenetic, and environmental factors. Addiction to illicit drugs during pregnancy presents unique challenges to effectively treat the mother, and the developing fetus and infant after delivery. New pharmacotherapies should be safe to the developing fetus, effective in treating the physical and psychological consequences of addiction in the mother, and reduce the incidence and severity of NAS in the infant after birth. More pharmacotherapeutic options should be available to the physician such that a more individualized rather than a one-drug/strategy-fits-all approach can be used. A myriad of new and exciting pharmacotherapeutic strategies for the treatment of opioid dependence and addiction are on the horizon. This review focuses on such three strategies: (i) pharmacotherapeutic targeting of the serotoninergic system; (ii) mixed opioid immunotherapeutics (vaccines); (iii) pharmacogenomics as a therapeutic strategy to insure personalized care. We review and discuss how these strategies may offer additional treatment modalities for the treatment of M-F/N during pregnancy and the treatment of the infant after birth. PMID:23059064

Cancer pain in the opioid-addicted patient: can we treat it right?

PubMed

Modesto-Lowe, Vania; Girard, Lisa; Chaplin, Margaret

2012-01-01

Although cancer elicits an array of physical and emotional symptoms, pain is often identified as the most distressing. Cancer pain may result from the primary tumor, metastasis, surgery, radiation, chemotherapy, or medical comorbidities. Although treatment with opioid analgesics is accepted as appropriate therapy for cancer-related pain, under treatment may persist among certain patients. Opioid-addicted individuals represent a challenging and heterogeneous population to treat. Addiction is linked to psychopathology and antisocial behaviors (eg, lying) which often complicate evaluation. Chronic exposure to opioids may lead to physiologic dependence and its correlates, tolerance and hyperalgesia. Given the variability and subjectivity of the cancer pain experience, there are no objective measures which capture the adequacy of pain control. Thus, when faced with complaints of uncontrolled pain, clinicians must consider a differential diagnosis of tolerance, disease progression, addiction, pseudoaddiction, chemical coping, or even criminal behavior. This article explores the cognitive, behavioral, and physiological correlates of opioid addiction that may impact cancer pain management. It also discusses risk reduction strategies for opioid misuse and research directions that may lead to improved clinical outcomes in these patients.

Disciplining virtue: investigating the discourses of opioid addiction in nursing.

PubMed

Kunyk, Diane; Milner, Margaret; Overend, Alissa

2016-12-01

Two nurses diagnosed with opioid addiction launched legal action after being found guilty of unprofessional conduct due to addiction-related behaviors. When covered by the media, their cases sparked both public and legal controversies. We are curious about the broader discursive framings that led to these strong reactions, and analyze the underlying structures of knowledge and power that shape the issue of opioid addiction in the profession of nursing through a critical discourse analysis of popular media, legal blogs and hearing tribunals. We argue that addiction in nursing is framed as personal choice, as a failure in the moral character of the nurses, as decontextualized from addiction as disease arguments, and as an individualized issue devoid of contextual factors leading to addiction. Our investigation offers a critical case study of a nursing regulatory body that upheld popular assumptions of addiction as an autonomous, rational choice replete with individual-based consequences - a framing that is inconsistent with evidence-based practice in health-care. We put forth this critical interrogation to open up possibilities for counterdiscourses that may promote more nuanced and effective responses to the issue of addiction in nursing. © 2016 John Wiley & Sons Ltd.

A Psycho-Genetic Study of Hedonic Responsiveness in Relation to “Food Addiction”

PubMed Central

Davis, Caroline; Loxton, Natalie J.

2014-01-01

While food addiction has no formally-recognized definition, it is typically operationalized according to the diagnostic principles established by the Yale Food Addiction Scale—an inventory based on the symptom criteria for substance dependence in the DSM-IV. Currently, there is little biologically-based research investigating the risk factors for food addiction. What does exist has focused almost exclusively on dopaminergic reward pathways in the brain. While brain opioid signaling has also been strongly implicated in the control of food intake, there is no research examining this neural circuitry in the association with food addiction. The purpose of the study was therefore to test a model predicting that a stronger activation potential of opioid circuitry-as indicated by the functional A118G marker of the mu-opioid receptor gene-would serve as an indirect risk factor for food addiction via a heightened hedonic responsiveness to palatable food. Results confirmed these relationships. In addition, our findings that the food-addiction group had significantly higher levels of hedonic responsiveness to food suggests that this bio-behavioral trait may foster a proneness to overeating, to episodes of binge eating, and ultimately to a compulsive and addictive pattern of food intake. PMID:25325253

Management of opioid addiction with buprenorphine: French history and current management.

PubMed

Poloméni, Pierre; Schwan, Raymund

2014-01-01

The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000-360,000 "problem drug users" being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the pathophysiologic mechanisms of the disease, better knowledge of the pharmacology of opioid substitution treatments, and clear definition of short-, medium- and long-term treatment objectives. Data related to the management of opioid addiction by general practitioners in France have been published in 2005. Since then, the context has changed, other drugs were launched on the market such as generics of buprenorphine, methadone capsule, and Suboxone. Thus, an update seems necessary. This paper provides a description of opioid addiction management objectives and treatment modalities for general practitioners, based on currently available knowledge.

Medication-Assisted Treatment For Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43

ERIC Educational Resources Information Center

Tinkler, Emily; Vallejos Bartlett, Catalina; Brooks, Margaret; Gilbert, Johnatnan Max; Henderson, Randi; Shuman, Deborah, J.

2005-01-01

TIP 43 provides best-practice guidelines for medication-assisted treatment of opioid addiction in opioid treatment programs (OTPs). The primary intended audience for this volume is substance abuse treatment providers and administrators who work in OTPs. Recommendations in the TIP are based on both an analysis of current research and determinations…

Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors

DTIC Science & Technology

2016-07-01

treat, and current opioids (i.e. mu opioid receptor agonists such as morphine) cause unacceptable side effects including addiction . Injuries suffered...treat, and current opioids that act on mu opioid receptors such as morphine generate significant side effects including addiction . War-related...slides. Slides were then processed for fluorescent in situ hybridization with RNAscope technology (ACD Biosystems) to detect Oprd1 mRNA, as described

Herbal medicines for the management of opioid addiction: safe and effective alternatives to conventional pharmacotherapy?

PubMed

Ward, Jeanine; Rosenbaum, Christopher; Hernon, Christina; McCurdy, Christopher R; Boyer, Edward W

2011-12-01

Striking increases in the abuse of opioids have expanded the need for pharmacotherapeutic interventions. The obstacles that confront effective treatment of opioid addiction - shortage of treatment professionals, stigma associated with treatment and the ability to maintain abstinence - have led to increased interest in alternative treatment strategies among both treatment providers and patients alike. Herbal products for opioid addiction and withdrawal, such as kratom and specific Chinese herbal medications such as WeiniCom, can complement existing treatments. Unfortunately, herbal treatments, while offering some advantages over existing evidence-based pharmacotherapies, have poorly described pharmacokinetics, a lack of supportive data derived from well controlled clinical trials, and severe toxicity, the cause for which remains poorly defined. Herbal products, therefore, require greater additional testing in rigorous clinical trials before they can expect widespread acceptance in the management of opioid addiction.

Discovery of a novel site of opioid action at the innate immune pattern-recognition receptor TLR4 and its role in addiction.

PubMed

Jacobsen, Jonathan Henry W; Watkins, Linda R; Hutchinson, Mark R

2014-01-01

Opioids have historically, and continue to be, an integral component of pain management. However, despite pharmacokinetic and dynamic optimization over the past 100 years, opioids continue to produce many undesirable side effects such as tolerance, reward, and dependence. As such, opioids are liable for addiction. Traditionally, opioid addiction was viewed as a solely neuronal process, and while substantial headway has been made into understanding the molecular and cellular mechanisms mediating this process, research has however, been relatively ambivalent to how the rest of the central nervous system (CNS) responds to opioids. Evidence over the past 20 years has clearly demonstrated the importance of the immunocompetent cells of the CNS (glia) in many aspects of opioid pharmacology. Particular focus has been placed on microglia and astrocytes, who in response to opioids, become activated and release inflammatory mediators. Importantly, the mechanism underlying immune activation is beginning to be elucidated. Evidence suggests an innate immune pattern-recognition receptor (toll-like receptor 4) as an integral component underlying opioid-induced glial activation. The subsequent proinflammatory response may be viewed akin to neurotransmission creating a process termed central immune signaling. Translationally, we are beginning to appreciate the importance of central immune signaling as it contributes to many behavioral actions of addiction including reward, withdrawal, and craving. As such, the aim of this chapter is to review and integrate the neuronal and central immune signaling perspective of addiction. © 2014 Elsevier Inc. All rights reserved.

Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals.

PubMed

Turton, Samuel; Myers, James Fm; Mick, Inge; Colasanti, Alessandro; Venkataraman, Ashwin; Durant, Claire; Waldman, Adam; Brailsford, Alan; Parkin, Mark C; Dawe, Gemma; Rabiner, Eugenii A; Gunn, Roger N; Lightman, Stafford L; Nutt, David J; Lingford-Hughes, Anne

2018-06-25

Addiction has been proposed as a 'reward deficient' state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [ 11 C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [ 11 C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.

Promising roles for pharmacists in addressing the U.S. opioid crisis.

PubMed

Compton, Wilson M; Jones, Christopher M; Stein, Jack B; Wargo, Eric M

2017-12-31

Overdoses of prescription or illicit opioids claimed the lives of 116 Americans each day in 2016, and the crisis continues to escalate. As healthcare systems evolve to address the crisis, the potential of pharmacists to make a positive difference is significant. In addition to utilizing available prescription drug monitoring programs to help prevent diversion of opioids, practicing pharmacists can be alert for signs of opioid misuse by patients (e.g., multiple prescriptions from different physicians) as well as inappropriate prescribing or hazardous drug combinations that physicians may not be aware of (e.g., opioid analgesics combined with benzodiazepines). They can also supply patients with information on risks of opioids, proper storage and disposal of medications, and the harms (and illegality) of sharing medications with other people. Increasingly, pharmacies are sites of distribution of the opioid antagonist naloxone, which has been shown to save lives when made available to opioid users and their families or other potential bystanders to an overdose; and pharmacists can provide guidance about its use and even legal protections for bystanders to an overdose that customers may not be aware of. Pharmacists can also recommend addiction treatment to patients and be a resource for information on addiction treatment options in the community. As addiction treatment becomes more integrated with general healthcare, pharmacies are also increasingly dispensing medications like buprenorphine and, in the future, possibly methadone. Pharmacists in private research labs and at universities are helping to develop the next generation of addiction treatments and safer, non-addictive pain medications; they can also play a role in implementation research to enhance the delivery of addiction interventions and medications in pharmacy settings. Meanwhile, pharmacists in educational settings can promote improved education about the neurobiology and management of pain and its links to opioid misuse and addiction. Published by Elsevier Inc.

Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers

PubMed Central

Mick, Inge; Myers, Jim; Ramos, Anna C; Stokes, Paul R A; Erritzoe, David; Colasanti, Alessandro; Gunn, Roger N; Rabiner, Eugenii A; Searle, Graham E; Waldman, Adam D; Parkin, Mark C; Brailsford, Alan D; Galduróz, José C F; Bowden-Jones, Henrietta; Clark, Luke; Nutt, David J; Lingford-Hughes, Anne R

2016-01-01

Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [11C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [11C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [11C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [11C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions. PMID:26552847

Women and the opioid crisis: historical context and public health solutions.

PubMed

Terplan, Mishka

2017-08-01

Driven by a legitimate but overly opioid-focused response to pain, the United States is currently experiencing an opioid crisis, a crisis with parallels to the first opioid epidemic at the turn of the 20th century. Women, particularly white reproductive-age women, are increasingly the face of the opioid crisis. Given the penetration of opioid misuse and addiction across all income and insurance strata, any provider who cares for women needs to be prepared to assess and evaluate opioid use, misuse, and addiction. Although responsible opioid prescribing is essential, treatment capacity must be expanded and be inclusive of the unique needs of women. However, the public and public health response to the opioid crisis must include rolling back the war on drugs. The continued criminalization of the public health issue of drug use and the medical condition of addiction is unethical, ineffective, and inhumane. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Probabilistic reward- and punishment-based learning in opioid addiction: Experimental and computational data.

PubMed

Myers, Catherine E; Sheynin, Jony; Balsdon, Tarryn; Luzardo, Andre; Beck, Kevin D; Hogarth, Lee; Haber, Paul; Moustafa, Ahmed A

2016-01-01

Addiction is the continuation of a habit in spite of negative consequences. A vast literature gives evidence that this poor decision-making behavior in individuals addicted to drugs also generalizes to laboratory decision making tasks, suggesting that the impairment in decision-making is not limited to decisions about taking drugs. In the current experiment, opioid-addicted individuals and matched controls with no history of illicit drug use were administered a probabilistic classification task that embeds both reward-based and punishment-based learning trials, and a computational model of decision making was applied to understand the mechanisms describing individuals' performance on the task. Although behavioral results showed that opioid-addicted individuals performed as well as controls on both reward- and punishment-based learning, the modeling results suggested subtle differences in how decisions were made between the two groups. Specifically, the opioid-addicted group showed decreased tendency to repeat prior responses, meaning that they were more likely to "chase reward" when expectancies were violated, whereas controls were more likely to stick with a previously-successful response rule, despite occasional expectancy violations. This tendency to chase short-term reward, potentially at the expense of developing rules that maximize reward over the long term, may be a contributing factor to opioid addiction. Further work is indicated to better understand whether this tendency arises as a result of brain changes in the wake of continued opioid use/abuse, or might be a pre-existing factor that may contribute to risk for addiction. Copyright © 2015 Elsevier B.V. All rights reserved.

Pain Volatility and Prescription Opioid Addiction Treatment Outcomes in Patients with Chronic Pain

PubMed Central

Worley, Matthew J.; Heinzerling, Keith G.; Shoptaw, Steven; Ling, Walter

2015-01-01

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (N = 149) who received buprenorphine-naloxone (BUP-NLX) and counseling for 12 weeks in an outpatient, multi-site clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least two of the previous three weeks. Pain severity significantly declined over time during treatment (b = − 0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (OR = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A one standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP-NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk for returning to opioid use by the conclusion of an intensive treatment with BUP-NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. PMID:26302337

Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

PubMed

Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

2015-12-01

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Re-racialization of Addiction and the Redistribution of Blame in the White Opioid Epidemic.

PubMed

Mendoza, Sonia; Rivera, Allyssa Stephanie; Hansen, Helena Bjerring

2018-04-27

New York City has the largest number of opioid dependent people of U.S. cities, and within New York, Whites have the highest rate of prescription opioid and heroin overdose deaths. The rise of opioid abuse among Whites has resulted in popular narratives of victimization by prescribers, framing of addiction as a biological disease, and the promise of pharmaceutical treatments that differ from the criminalizing narratives that have historically described urban Latino and black narcotic use. Through an analysis of popular media press and interviews with opioid prescribers and community pharmacists in Staten Island-the epicenter of opioid overdose in New York City and the most suburban and white of its boroughs-we found that narratives of white opioid users disrupted notions of the addict as "other," producing alternative logics of blame that focus on prescribers and the encroachment of dealers from outside of white neighborhoods. © 2018 by the American Anthropological Association.

The Neurobiology of Opioid Dependence: Implications for Treatment

PubMed Central

Kosten, Thomas R.; George, Tony P.

2002-01-01

Opioid tolerance, dependence, and addiction are all manifestations of brain changes resulting from chronic opioid abuse. The opioid abuser’s struggle for recovery is in great part a struggle to overcome the effects of these changes. Medications such as methadone, LAAM, buprenorphine, and naltrexone act on the same brain structures and processes as addictive opioids, but with protective or normalizing effects. Despite the effectiveness of medications, they must be used in conjunction with appropriate psychosocial treatments. PMID:18567959

Dual Diagnosis - Multiple Languages

MedlinePlus

... National Library of Medicine Comorbidity or dual diagnosis - Opioid addiction, part 9 - English PDF Comorbidity or dual diagnosis - Opioid addiction, part 9 - español (Spanish) PDF Comorbidity or dual ...

Prescription opioid use and misuse: piloting an educational strategy for rural primary care physicians.

PubMed

Srivastava, Anita; Kahan, Meldon; Jiwa, Ashifa

2012-04-01

To evaluate the feasibility and effectiveness of a multifaceted educational intervention to improve the opioid prescribing practices of rural family physicians in a remote First Nations community. Prospective cohort study. Sioux Lookout, Ont. Family physicians. Eighteen family physicians participated in a 1-year study of a series of educational interventions on safe opioid prescribing. Interventions included a main workshop with a lecture and interactive case discussions, an online chat room, video case conferencing, and consultant support. Responses to questionnaires at baseline and after 1 year on knowledge, attitudes, and practices related to opioid prescribing. The main workshop was feasible and was well received by primary care physicians in remote communities. At 1 year, physicians were less concerned about getting patients addicted to opioids and more comfortable with opioid dosing. Multifaceted education and consultant support might play an important role in improving family physician comfort with opioid prescribing, and could improve the treatment of chronic pain while minimizing the risk of addiction.

Traditional Chinese and Indian medicine in the treatment of opioid-dependence: a review.

PubMed

Doosti, Fatemeh; Dashti, Saeedeh; Tabatabai, Seyed Meghdad; Hosseinzadeh, Hossein

2013-01-01

In this study, the current literatures on the use of herbs and herbal preparations of Traditional Chinese and Indian Medicine for the treatment of opioid addiction were reviewed. Matherials and Methods: Search was done in databases such as Pub Med, Science Direct, Scopus, Springer Link, and Google Scholar. Among 18 retrieved studies, 3 studies were about asafetida extract, an approved preparation for ameliorating drug abstinence in China. Chinese preparations including Composite Dong Yuan Gao, Qingjunyin and TJ-97 (a water extract of dai-bofu-to) as well as Indian ones, Mentate and Shilajit, were reported to have positive effects against opioid withdrawal, dependence, and tolerance. Moreover, Levo-tetrahydropalmatine and L-Stepholidine, in addition to extracts of Caulis Sinomenii and Sinomenium acutum showed similar effects. Banxia Houpu Decoction, Fu-Yuan pellet, Jinniu capsules, Qingjunyin, Tai-Kang-Ning capsule, and Xuan Xia Qudu Jiaonang (WeiniCom) from Chinese preparations, showed anti-addiction effects in randomized, double-blind and, in some studies, multicenter clinical trials. Conclusion : Traditional herbal preparations of China and India have anti-addiction effects with less adverse effects than alpha2-adrenergic or opioid agonists.

Learning and generalization from reward and punishment in opioid addiction

PubMed Central

Myers, Catherine E.; Rego, Janice; Haber, Paul; Morley, Kirsten; Beck, Kevin D.; Hogarth, Lee; Moustafa, Ahmed A.

2016-01-01

This study adapts a widely-used acquired equivalence paradigm to investigate how opioid-addicted individuals learn from positive and negative feedback, and how they generalize this learning. The opioid-addicted group consisted of 33 participants with a history of heroin dependency currently in a methadone maintenance program; the control group consisted of 32 healthy participants without a history of drug addiction. All participants performed a novel variant of the acquired equivalence task, where they learned to map some stimuli to correct outcomes in order to obtain reward, and to map other stimuli to correct outcomes in order to avoid punishment; some stimuli were implicitly “equivalent” in the sense of being paired with the same outcome. On the initial training phase, both groups performed similarly on learning to obtain reward, but as memory load grew, the control group outperformed the addicted group on learning to avoid punishment. On a subsequent testing phase, the addicted and control groups performed similarly on retention trials involving previously-trained stimulus-outcome pairs, as well as on generalization trials to assess acquired equivalence. Since prior work with acquired equivalence tasks has associated stimulus-outcome learning with the nigrostriatal dopamine system, and generalization with the hippocampal region, the current results are consistent with basal ganglia dysfunction in the opioid-addicted patients. Further, a selective deficit in learning from punishment could contribute to processes by which addicted individuals continue to pursue drug use even at the cost of negative consequences such as loss of income and the opportunity to engage in other life activities. PMID:27641323

Learning and generalization from reward and punishment in opioid addiction.

PubMed

Myers, Catherine E; Rego, Janice; Haber, Paul; Morley, Kirsten; Beck, Kevin D; Hogarth, Lee; Moustafa, Ahmed A

2017-01-15

This study adapts a widely-used acquired equivalence paradigm to investigate how opioid-addicted individuals learn from positive and negative feedback, and how they generalize this learning. The opioid-addicted group consisted of 33 participants with a history of heroin dependency currently in a methadone maintenance program; the control group consisted of 32 healthy participants without a history of drug addiction. All participants performed a novel variant of the acquired equivalence task, where they learned to map some stimuli to correct outcomes in order to obtain reward, and to map other stimuli to correct outcomes in order to avoid punishment; some stimuli were implicitly "equivalent" in the sense of being paired with the same outcome. On the initial training phase, both groups performed similarly on learning to obtain reward, but as memory load grew, the control group outperformed the addicted group on learning to avoid punishment. On a subsequent testing phase, the addicted and control groups performed similarly on retention trials involving previously-trained stimulus-outcome pairs, as well as on generalization trials to assess acquired equivalence. Since prior work with acquired equivalence tasks has associated stimulus-outcome learning with the nigrostriatal dopamine system, and generalization with the hippocampal region, the current results are consistent with basal ganglia dysfunction in the opioid-addicted patients. Further, a selective deficit in learning from punishment could contribute to processes by which addicted individuals continue to pursue drug use even at the cost of negative consequences such as loss of income and the opportunity to engage in other life activities. Published by Elsevier B.V.

A Comparison of Opioid and Nonopioid Substance Users in Residential Treatment for Co-Occurring Substance Use and Mental Disorders.

PubMed

Bride, Brian E; Macmaster, Samuel A; Morse, Siobhan A; Watson, Cayce M; Choi, Sam; Seiters, John

2016-01-01

The past decade has seen a marked increase in the illicit use of opioids, as well as a doubling of the percentage of individuals seeking treatment for opioid use disorders. However, little is known about the differences between opioid users and nonopioid users in residential treatment. Further, no studies have been published that compare opioid users and nonopioid users in treatment for co-occurring substance use and mental disorders. To address this gap, this study examined differences between opioid and nonopioid substance users in residential treatment for co-occurring disorders. Data was drawn from 1,972 individuals treated between 2009 and 2011 at one of three private residential treatment centers that provide integrated treatment for co-occurring substance use and mental disorders. Data was collected at program intake, and 1- and 6-month postdischarge using the Addiction Severity Index and the University of Rhode Island Change Assessment. To examine within-group changes in substance use, addiction severity, and mental health across time, linear mixed-model analyses were conducted with facility, year, age, gender, and race included as covariates. The authors found more similarities than differences between the two groups on baseline characteristics, treatment motivation, length of stay, and outcomes on measures of substance use, addiction severity, and mental health. The results demonstrate that though opioid users entered treatment with higher levels of substance use-related impairment, they were just as successful in treatment outcomes as their non-opioid-using peers.

Probabilistic Reward- and Punishment-based Learning in Opioid Addiction: Experimental and Computational Data

PubMed Central

Myers, Catherine E.; Sheynin, Jony; Baldson, Tarryn; Luzardo, Andre; Beck, Kevin D.; Hogarth, Lee; Haber, Paul; Moustafa, Ahmed A.

2016-01-01

Addiction is the continuation of a habit in spite of negative consequences. A vast literature gives evidence that this poor decision-making behavior in individuals addicted to drugs also generalizes to laboratory decision making tasks, suggesting that the impairment in decision-making is not limited to decisions about taking drugs. In the current experiment, opioid-addicted individuals and matched controls with no history of illicit drug use were administered a probabilistic classification task that embeds both reward-based and punishment-based learning trials, and a computational model of decision making was applied to understand the mechanisms describing individuals’ performance on the task. Although behavioral results showed thatopioid-addicted individuals performed as well as controls on both reward- and punishment-based learning, the modeling results suggested subtle differences in how decisions were made between the two groups. Specifically, the opioid-addicted group showed decreased tendency to repeat prior responses, meaning that they were more likely to “chase reward” when expectancies were violated, whereas controls were more likely to stick with a previously-successful response rule, despite occasional expectancy violations. This tendency to chase short-term reward, potentially at the expense of developing rules that maximize reward over the long term, may be a contributing factor to opioid addiction. Further work is indicated to better understand whether this tendency arises as a result of brain changes in the wake of continued opioid use/abuse, or might be a pre-existing factor that may contribute to risk for addiction. PMID:26381438

Challenges and Opportunities for the Use of Medications to Treat Opioid Addiction in the United States and Other Nations of the World.

PubMed

Parrino, Mark W; Maremmani, Angelo Giovanni Icro; Samuels, Paul N; Maremmani, Icro

2015-01-01

There has been a well documented increase in the use and abuse of prescription opioids and heroin in the United States and other parts of the world. There has also been an increasing focus to increase access to the use of medications (methadone, buprenorphine, Naltrexone/Vivitrol) for opioid addicted individuals under legal supervision. As policymakers engage in strategic initiatives to better prevent and effectively treat chronic opioid addiction, both in the United States and other countries, there are a number of unintended consequences, complicating how best to increase access to effective treatment.

Something for pain: Responsible opioid use in emergency medicine.

PubMed

Strayer, Reuben J; Motov, Sergey M; Nelson, Lewis S

2017-02-01

The United States is currently experiencing a public health crisis of opioid addiction, which has its genesis in an industry marketing effort that successfully encouraged clinicians to prescribe opioids liberally, and asserted the safety of prescribing opioids for chronic non-cancer pain, despite a preponderance of evidence demonstrating the risks of dependence and misuse. The resulting rise in opioid use has pushed drug overdose deaths in front of motor vehicle collisions to become the leading cause of accidental death in the country. Emergency providers frequently treat patients for complications of opioid abuse, and also manage patients with acute and chronic pain, for which opioids are routinely prescribed. Emergency providers are therefore well positioned to both prevent new cases of opioid misuse and initiate appropriate treatment of existing opioid addicts. In opioid-naive patients, this is accomplished by a careful consideration of the likelihood of benefit and harm of an opioid prescription for acute pain. If opioids are prescribed, the chance of harm is reduced by matching the number of pills prescribed to the expected duration of pain and selecting an opioid preparation with low abuse liability. Patients who present to acute care with exacerbations of chronic pain or painful conditions associated with opioid misuse are best managed by treating symptoms with opioid alternatives and encouraging treatment for opioid addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

GLOBAL OPIOID EPIDEMIC: DOOMED TO FAIL WITHOUT GENETICALLY BASED PRECISION ADDICTION MEDICINE (PAM™): LESSONS LEARNED FROM AMERICA.

PubMed

Blum, Kenneth; Modestino, Edward J; Gondré-Lewis, Marjorie C; Neary, Jennifer; Siwicki, David; Hauser, Mary; Barh, Debmalya; Steinberg, Bruce; Badgaiyan, Rajendra D

2017-01-01

It is a reality that globally opioid deaths have soared for men and women of all social, economic status and age from heroin and fentanyl overdoses. Specifically, in the United States, deaths from narcotic overdoses have reached alarming metrics since 2010. In fact, the Fentanyl rise is driven by drug dealers who sell it as heroin or who use it to lace cocaine or to make illegal counterfeit prescription opioids. The President's Commission on the crisis has linked the death toll as equivalent to "September 11th every three weeks." In fact, The U.S. Centre for Disease Control (CDC) released data showing that opioid-related overdoses were up 15% in the first three quarters of 2016 compared to 2015. Various governmental organizations including NIDA, are actively seeking solutions. However, we argue that unless the scientific community embraces genetic addiction risk coupled with potential precision or personalized medicine to induce "dopamine homeostasis" it will fail. We now have evidence that a ten-gene and eleven single nucleotide polymorphism (SNP) panel predicts Addiction Severity Index (ASI) for both alcohol and drugs of abuse (e.g., Opioids). In a large multi-addiction centre study involving seven diverse treatment programs, the genetic addiction risk score (GARS ™ ) was shown to have a predictive relationship with ASI-MV derived alcohol (≥ seven alleles), and other drugs (≥ 4 alleles) severity risk scores. In a number of neuroimaging studies, we also display that in both animal (bench) and abstinent Chinese severe heroin-dependent patients (bedside), BOLD dopamine activation across the brain reward circuitry revealed increases in resting state functional connectivity as well volume connectivity. It is also known that published nutrigenomic (coupling gene polymorphisms with altered KB220z) studies reveal improved clinical outcomes related to obesity.

Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine.

PubMed

Malcolm, Benjamin J; Polanco, Martin; Barsuglia, Joseph P

2018-04-02

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants' OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.

The role of δ-opioid receptors in learning and memory underlying the development of addiction.

PubMed

Klenowski, Paul; Morgan, Michael; Bartlett, Selena E

2015-01-01

Opioids are important endogenous ligands that exist in both invertebrates and vertebrates and signal by activation of opioid receptors to produce analgesia and reward or pleasure. The μ-opioid receptor is the best known of the opioid receptors and mediates the acute analgesic effects of opiates, while the δ-opioid receptor (DOR) has been less well studied and has been linked to effects that follow from chronic use of opiates such as stress, inflammation and anxiety. Recently, DORs have been shown to play an essential role in emotions and increasing evidence points to a role in learning actions and outcomes. The process of learning and memory in addiction has been proposed to involve strengthening of specific brain circuits when a drug is paired with a context or environment. The DOR is highly expressed in the hippocampus, amygdala, striatum and other basal ganglia structures known to participate in learning and memory. In this review, we will focus on the role of the DOR and its potential role in learning and memory underlying the development of addiction. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British Pharmacological Society.

Insurance Companies Fighting the Peer Review Empire without any Validity: the Case for Addiction and Pain Modalities in the face of an American Drug Epidemic.

PubMed

Blum, K; Jacobs, W; Modestino, E J; DiNubile, N; Baron, D; McLaughlin, T; Siwicki, D; Elman, I; Moran, M; Braverman, E R; Thanos, P K; Badgaiyan, R D

2018-10-04

The United States are amid an opioid overdose epidemic; we are challenged to provide non-addicting/non-pharmacological alternatives to assist in pain attenuation. There are proven strategies available to manage chronic pain effectively without opioids. Utilization review providers for insurance companies often ignore medicine based scientific peer-reviewed studies that warn against the chronic use of opioid medications, as well as the lack of evidence to support long-term use of opioids for pain. This paradigm must change if we are to indeed change the drug-embracing culture in American chronic pain management. A barrier to treatment is pushback on the part of insurance companies especially as it relates to fighting against pain relief alternatives compared to classical analgesic agents. Pain specialists in the U.S., are compelled to find alternative solutions to help pain victims without promoting unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain." It is noteworthy that reward center of the brain plays a crucial role in the modulation of nociception, and that adaptations in dopaminergic circuitry may affect several sensory and affective components of chronic pain syndromes. Possibly knowing a patient's genetic addiction risk score (GARS™) could eliminate guessing as it relates to becoming addicted.

Effects of Competing Narratives on Public Perceptions of Opioid Pain Reliever Addiction during Pregnancy.

PubMed

Kennedy-Hendricks, Alene; McGinty, Emma E; Barry, Colleen L

2016-10-01

Opioid pain reliever addiction has increased among women of reproductive age over the last fifteen years. News media and public attention have focused on the implications of this trend for infants exposed to opioids prenatally, with state policy responses varying in the extent to which they are punitive or public health oriented. We fielded a six-group randomized experiment among a nationally representative sample of US adults to test the effects of narratives portraying a woman with opioid pain reliever addiction during pregnancy on beliefs about people addicted to opioid pain relievers, perceptions of treatment effectiveness, policy attitudes, and emotional responses. Portraying a high socioeconomic status (SES) woman in the narrative lowered perceptions of individual blame for addiction and reduced public support for punitive policies. Depicting the barriers to treatment faced by a low SES woman lowered support for punitive policies and increased support for expanded insurance coverage for treatment. The extent to which narratives portraying successfully treated addiction affected public attitudes depended on the SES of the woman portrayed. These findings can inform the development of communication strategies to reduce stigma toward this population, reduce support for punitive policies, and increase support for more public health-oriented approaches to addressing this problem. Copyright © 2016 by Duke University Press.

Managing Opioid Addiction Risk in Plastic Surgery during the Perioperative Period.

PubMed

Demsey, Daniel; Carr, Nicholas J; Clarke, Hance; Vipler, Sharon

2017-10-01

Opioid addiction is a public health crisis that affects all areas of medicine. Large numbers of the population across all racial and economic demographics misuse prescription opioids and use illicit opioids. The current understanding is that opioid misuse is a disease that requires treatment, and is not an issue of choice or character. Use of opioid medication is a necessary part of postoperative analgesia, but many physicians are unsure of how to do this safely given the risk of patients developing an opioid misuse disorder. This review gives an update of the current state of the opioid crisis, explains how current surgeons' prescribing practices are contributing to it, and gives recommendations on how to use opioid medication safely in the perioperative period.

Addressing the growing opioid and heroin abuse epidemic: a call for medical school curricula.

PubMed

Ratycz, Madison C; Papadimos, Thomas J; Vanderbilt, Allison A

2018-12-01

Substance abuse is a growing public health concern in the USA (US), especially now that the US faces a national drug overdose epidemic. Over the past decade, the number of drug overdose deaths has rapidly grown, largely driven by increases in prescription opioid-related overdoses. In recent years, increased heroin and illicitly manufactured fentanyl overdoses have substantially contributed to the rise of overdose deaths. Given the role of physicians in interacting with patients who are at risk for or currently abusing opioids and heroin, it is essential that physicians are aware of this issue and know how to respond. Unfortunately, medical school curricula do not devote substantial time to addiction education and many physicians lack knowledge regarding assessment and management of opioid addiction. While some schools have modified curricula to include content related to opioid prescription techniques and pain management, an added emphasis about the growing role of heroin and fentanyl is needed to adequately address the epidemic. By adapting curricula to address the rising opioid and heroin epidemic, medical schools have the potential to ensure that our future physicians can effectively recognize the signs, symptoms, and risks of opioid/heroin abuse and improve patient outcomes. This article proposes ways to include heroin and fentanyl education into medical school curricula and highlights the potential of simulation-based medical education to enable students to develop the skillset and emotional intelligence necessary to work with patients struggling with opioid and heroin addiction. This will result in future doctors who are better prepared to both prevent and recognize opioid and heroin addiction in patients, an important step in helping reduce the number of addicted patients and address the drug overdose epidemic.

Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

PubMed Central

Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

2010-01-01

Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies.

PubMed

Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R

2014-10-01

Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA. This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion. Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need.

Risk Factors for Opioid-Use Disorder and Overdose.

PubMed

Webster, Lynn R

2017-11-01

Opioid analgesics are recognized as a legitimate medical therapy for selected patients with severe chronic pain that does not respond to other therapies. However, opioids are associated with risks for patients and society that include misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success depends on proper candidate selection, assessment before administering opioid therapy, and close monitoring throughout the course of treatment. Risk assessment and prevention include knowledge of patient factors that may contribute to misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse. Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities. Suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths. Greater understanding and better assessment are needed of the risk associated with suicide risk in patients with pain. Clinical tools and an evolving evidence base are available to assist clinicians with identifying patients whose risk factors put them at risk for adverse outcomes with opioids.

Opioid pharmaceuticals and addiction: the issues, and research directions seeking solutions.

PubMed

Walwyn, Wendy M; Miotto, Karen A; Evans, Christopher J

2010-05-01

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies.

Opioid pharmaceuticals and addiction: The issues, and research directions seeking solutions

PubMed Central

Walwyn, Wendy M.; Miotto, Karen A.; Evans, Christopher J.

2011-01-01

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies. PMID:20188495

Ten Years of Abstinence in Former Opiate Addicts: Medication-Free Non-Patients Compared to Methadone Maintenance Patients.

PubMed

Peles, Einat; Sason, Anat; Tene, Oren; Domany, Yoav; Schreiber, Shaul; Adelson, Miriam

2015-01-01

Fifty-five former opioid addicts who have been methadone maintained patients for 10 or more years and whose urine has tested negative for drugs for 2 or more years were compared to 99 former opioid addicts who have been medication-free for 10 or more years. Groups were comparable in age and education, but the medication-free subjects were younger when having started opioids with more severe addiction scores. Methadone maintained patients presented with a higher proportion of psychiatric comorbidity and chronic pain. Their scores of perceived sleep quality and cognitive state were poorer than the medication-free individuals. Possible explanations of the differences are discussed in this article.

Opioid Addiction and Implications for Employers.

PubMed

Kuhn, Sandra

2017-01-01

Although the prevalence and destruction of opioid addiction have touched individuals and families across all social groups and geographies, until recently, federal and state-level efforts to confront this growing problem have lacked focus and rigor. With several legislative actions already underway and the recent enactment of the Comprehensive Addiction and Recovery Act (CARA), we will continue to see a focus on program development and treatment strategies. Employers can contribute toward curbing the opioid addiction epidemic in a number of ways and should play an instrumental role in facilitating increased awareness of and access to needed programming. These efforts will improve quality of life for employees and their dependents, as well as have a positive impact on productivity (including reduced absenteeism and decreased presenteeism). This article will explore the size and prevalence of the opioid epidemic, reflect on its implications for employers-including public policy initiatives-and suggest specific strategies for employer interventions.

Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction.

PubMed

Bond, C; LaForge, K S; Tian, M; Melia, D; Zhang, S; Borg, L; Gong, J; Schluger, J; Strong, J A; Leal, S M; Tischfield, J A; Kreek, M J; Yu, L

1998-08-04

Opioid drugs play important roles in the clinical management of pain, as well as in the development and treatment of drug abuse. The mu opioid receptor is the primary site of action for the most commonly used opioids, including morphine, heroin, fentanyl, and methadone. By sequencing DNA from 113 former heroin addicts in methadone maintenance and 39 individuals with no history of drug or alcohol abuse or dependence, we have identified five different single-nucleotide polymorphisms (SNPs) in the coding region of the mu opioid receptor gene. The most prevalent SNP is a nucleotide substitution at position 118 (A118G), predicting an amino acid change at a putative N-glycosylation site. This SNP displays an allelic frequency of approximately 10% in our study population. Significant differences in allele distribution were observed among ethnic groups studied. The variant receptor resulting from the A118G SNP did not show altered binding affinities for most opioid peptides and alkaloids tested. However, the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor. Furthermore, beta-endorphin is approximately three times more potent at the A118G variant receptor than at the most common allelic form in agonist-induced activation of G protein-coupled potassium channels. These results show that SNPs in the mu opioid receptor gene can alter binding and signal transduction in the resulting receptor and may have implications for normal physiology, therapeutics, and vulnerability to develop or protection from diverse diseases including the addictive diseases.

Traditional Chinese and Indian medicine in the treatment of opioid-dependence: a review

PubMed Central

Doosti, Fatemeh; Dashti, Saeedeh; Tabatabai, Seyed Meghdad; Hosseinzadeh, Hossein

2013-01-01

Objective: In this study, the current literatures on the use of herbs and herbal preparations of Traditional Chinese and Indian Medicine for the treatment of opioid addiction were reviewed. Matherials and Methods: Search was done in databases such as Pub Med, Science Direct, Scopus, Springer Link, and Google Scholar. Results: Among 18 retrieved studies, 3 studies were about asafetida extract, an approved preparation for ameliorating drug abstinence in China. Chinese preparations including Composite Dong Yuan Gao, Qingjunyin and TJ-97 (a water extract of dai-bofu-to) as well as Indian ones, Mentate and Shilajit, were reported to have positive effects against opioid withdrawal, dependence, and tolerance. Moreover, Levo-tetrahydropalmatine and L-Stepholidine, in addition to extracts of Caulis Sinomenii and Sinomenium acutum showed similar effects. Banxia Houpu Decoction, Fu-Yuan pellet, Jinniu capsules, Qingjunyin, Tai-Kang-Ning capsule, and Xuan Xia Qudu Jiaonang (WeiniCom) from Chinese preparations, showed anti-addiction effects in randomized, double-blind and, in some studies, multicenter clinical trials. Conclusion : Traditional herbal preparations of China and India have anti-addiction effects with less adverse effects than alpha2-adrenergic or opioid agonists. PMID:25050276

15 years of genetic approaches in vivo for addiction research: Opioid receptor and peptide gene knockout in mouse models of drug abuse.

PubMed

Charbogne, Pauline; Kieffer, Brigitte L; Befort, Katia

2014-01-01

The endogenous opioid system is expressed throughout the brain reinforcement circuitry, and plays a major role in reward processing, mood control and the development of addiction. This neuromodulator system is composed of three receptors, mu, delta and kappa, interacting with a family of opioid peptides derived from POMC (β-endorphin), preproenkephalin (pEnk) and preprodynorphin (pDyn) precursors. Knockout mice targeting each gene of the opioid system have been created almost two decades ago. Extending classical pharmacology, these mutant mice represent unique tools to tease apart the specific role of each opioid receptor and peptide in vivo, and a powerful approach to understand how the opioid system modulates behavioral effects of drugs of abuse. The present review summarizes these studies, with a focus on major drugs of abuse including morphine/heroin, cannabinoids, psychostimulants, nicotine or alcohol. Genetic data, altogether, set the mu receptor as the primary target for morphine and heroin. In addition, this receptor is essential to mediate rewarding properties of non-opioid drugs of abuse, with a demonstrated implication of β-endorphin for cocaine and nicotine. Delta receptor activity reduces levels of anxiety and depressive-like behaviors, and facilitates morphine-context association. pEnk is involved in these processes and delta/pEnk signaling likely regulates alcohol intake. The kappa receptor mainly interacts with pDyn peptides to limit drug reward, and mediate dysphoric effects of cannabinoids and nicotine. Kappa/dynorphin activity also increases sensitivity to cocaine reward under stressful conditions. The opioid system remains a prime candidate to develop successful therapies in addicted individuals, and understanding opioid-mediated processes at systems level, through emerging genetic and imaging technologies, represents the next challenging goal and a promising avenue in addiction research. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Interactions between opioids and anabolic androgenic steroids: implications for the development of addictive behavior.

PubMed

Nyberg, Fred; Hallberg, Mathias

2012-01-01

Over the past decades, research on doping agents, such as anabolic androgenic steroids (AAS), has revealed that these compounds are often used in combination with other drugs of abuse. It seems that misuse of AAS probably involves more than a desire to enhance appearance or sports performance and studies have revealed that steroids are commonly connected with alcohol, opioids, tobacco, and psychotropic drugs. We have observed that AAS may interact with the endogenous opioids, excitatory amino acids, and dopaminergic pathways involved in the brain reward system. Furthermore, our studies provide evidence that AAS may induce an imbalance in these signal systems leading to an increased sensitivity toward opioid narcotics and central stimulants. In fact, studies performed in various clinics have shown that individuals taking AAS are likely to get addicted to opioids like heroin. This chapter reviews current knowledge on interactions between AAS and endogenous as well as exogenous opioids based not only on research in our laboratory but also on research carried out by several other clinical and preclinical investigators. Copyright © 2012 Elsevier Inc. All rights reserved.

Feasibility of applying the life history calendar in a population of chronic opioid users to identify patterns of drug use and addiction treatment.

PubMed

Fikowski, Jill; Marchand, Kirsten; Palis, Heather; Oviedo-Joekes, Eugenia

2014-01-01

Uncovering patterns of drug use and treatment access is essential to improving treatment for opioid dependence. The life history calendar (LHC) could be a valuable instrument for capturing time-sensitive data on lifetime patterns of drug use and addiction treatment. This study describes the methodology applied when collecting data using the LHC in a sample of individuals with long-term opioid dependence and aims to identify specific factors that impact the feasibility of administering the LHC interview. In this study, the LHC allowed important events such as births, intimate relationships, housing, or incarcerations to become reference points for recalling details surrounding drug use and treatment access. The paper concludes that the administration of the LHC was a resource-intensive process and required special attention to interviewer training and experience with the study population. These factors should be considered and integrated into study plans by researchers using the LHC in addiction research.

Intolerance of uncertainty in opioid dependency - Relationship with trait anxiety and impulsivity.

PubMed

Garami, Julia; Haber, Paul; Myers, Catherine E; Allen, Michael T; Misiak, Blazej; Frydecka, Dorota; Moustafa, Ahmed A

2017-01-01

Intolerance of uncertainty (IU) is the tendency to interpret ambiguous situations as threatening and having negative consequences, resulting in feelings of distress and anxiety. IU has been linked to a number of anxiety disorders, and anxiety felt in the face of uncertainty may result in maladaptive behaviors such as impulsive decision making. Although there is strong evidence that anxiety and impulsivity are risk factors for addiction, there is a paucity of research examining the role of IU in this disorder. The rate of opioid addiction, in particular, has been rising steadily in recent years, which necessitates deeper understanding of risk factors in order to develop effective prevention and treatment methods. The current study tested for the first time whether opioid-dependent adults are less tolerant of uncertainty compared to a healthy comparison group. Opioid dependent patients undergoing methadone maintenance therapy (n = 114) and healthy comparisons (n = 69) completed the following scales: Intolerance of Uncertainty Scale, the Barrett Impulsivity Scale, and the State Trait Anxiety Inventory. Analysis revealed that these measures were positively correlated with each other and that opioid-dependent patients had significantly higher IU scores. Regression analysis revealed that anxiety mediated the relationship between IU and impulsivity. Hierarchical moderation regression found an interaction between addiction status and impulsivity on IU scores in that the relationship between these variables was only observed in the patient group. Findings suggest that IU is a feature of addiction but does not necessarily play a unique role. Further research is needed to explore the complex relationship between traits and how they may contribute to the development and maintenance of addiction.

Addiction research centres and the nurturing of creativity The Norwegian Centre for Addiction Research (SERAF).

PubMed

Bramness, Jørgen G; Clausen, Thomas; Duckert, Fanny; Ravndal, Edle; Waal, Helge

2011-08-01

The Norwegian Centre for Addiction Research (SERAF) at the University of Oslo is a newly established, clinical addiction research centre. It is located at the Oslo University Hospital and has a major focus on opioid dependency, investigating Norwegian opioid maintenance treatment (OMT), with special interest in OMT during pregnancy, mortality, morbidity and criminality before, during and after OMT and alternatives to OMT, such as the use of naltrexone implants. The well-developed health registries of Norway are core assets that also allow the opportunity for other types of substance abuse research. This research includes health services, abuse of prescription drugs and drugs of abuse in connection with traffic. The centre also focuses upon comorbidity, investigating the usefulness and limitations of psychometric instruments, drug abuse in different psychiatric treatment settings and internet-based interventions for hazardous alcohol consumption. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Physicians' attitude and practices in sickle cell disease pain management.

PubMed

Labbé, Elise; Herbert, Donald; Haynes, Johnson

2005-01-01

Many physicians believe that patients with sickle cell disease (SCD) are more likely to become addicted to pain medication than are other patient populations. This study hypothesizes that physicians' attitudes towards addiction in patients with SCD affects pain management practices. The Physician Attitudes Survey was sent to 286 physicians at seven National Institutes of Health-funded university-based comprehensive sickle cell centres. The survey assessed demographic information; and physician's attitudes toward and knowledge of pain, pain treatment, and drug addiction and abuse. Significant Pearson product-moment correlations were found between attitudes towards pain and beliefs regarding addiction to prescribed opioids. Physicians reported varied pain management strategies, however, many believe that attitudes toward addiction and to patients in pain crises may result in undertreatment of pain. These results indicate that physicians might benefit from additional education regarding sickle cell disease, addiction to pain medication, the pharmacology of opioids, and the assessment and treatment of pain.

Chronic Pain, Chronic Opioid Addiction: a Complex Nexus.

PubMed

Salsitz, Edwin A

2016-03-01

Over the past two decades, there has been a significant increase in the prescribing of opioids, with associated increases in opioid addiction and overdose deaths. This article reviews the evidence for the effectiveness and risk of developing an opioid use disorder (OUD) in those patients treated with chronic opioid therapy (COT) for chronic non-cancer pain (CNCP). Rates of development of OUD range from 0-50 %, and aberrant drug related behaviors (ADRBs) are reported to be 20 %. Health care providers must properly assess, screen, and carefully monitor patients on COT utilizing evidence-based tools.

Opioids, Chronic Pain, and Addiction in Primary Care

PubMed Central

Barry, Declan T.; Irwin, Kevin S.; Jones, Emlyn S.; Becker, William C.; Tetrault, Jeanette M.; Sullivan, Lynn E.; Hansen, Helena; O’Connor, Patrick G.; Schottenfeld, Richard S.; Fiellin, David A.

2010-01-01

Research has largely ignored the systematic examination of physicians’ attitudes towards providing care for patients with chronic non-cancer pain. The objective of this study was to identify barriers and facilitators to opioid treatment of chronic non-cancer pain patients by office-based medical providers. We used a qualitative study design using individual and group interviews. Participants were twenty-three office-based physicians in New England. Interviews were audiotaped, transcribed, and systematically coded by a multidisciplinary team using the constant comparative method. Physician barriers included lack of expertise in the treatment of chronic pain and co-existing disorders, including addiction; lack of interest in pain management; patients’ aberrant behaviors; and physicians’ attitudes toward prescribing opioid analgesics. Physician facilitators included promoting continuity of patient care and the use of opioid agreements. Physicians’ perceptions of patient-related barriers included lack of physician responsiveness to patients’ pain reports, negative attitudes toward opioid analgesics, concerns about cost, and patients’ low motivation for pain treatment. Perceived logistical barriers included lack of appropriate pain management and addiction referral options, limited information regarding diagnostic workup, limited insurance coverage for pain management services, limited ancillary support for physicians, and insufficient time. Addressing these barriers to pain treatment will be crucial to improving pain management service delivery. PMID:20627817

Development of dependence following treatment with opioid analgesics for pain relief: a systematic review.

PubMed

Minozzi, Silvia; Amato, Laura; Davoli, Marina

2013-04-01

To assess the incidence or prevalence of opioid dependence syndrome in adults (with and without previous history of substance abuse) following treatment with opioid analgesics for pain relief. Medline, Embase, CINHAL and the Cochrane Library were searched up to January 2011. Systematic reviews and primary studies were included if they reported data about incidence or prevalence of opioid dependence syndrome (as defined by DSM-IV or ICD-10) in patients receiving strong opioids (or opioid-type analgesics) for treatment of acute or chronic pain due to any physical condition. The data were abstracted, and the methodological quality was assessed using validated checklists. Data were extracted from 17 studies involving a total of 88 235 participants. The studies included three systematic reviews, one randomized controlled trial, eight cross-sectional studies and four uncontrolled case series. Most studies included adult patients with chronic non-malignant pain; two also included patients with cancer pain; only one included patients with a previous history of dependence. Incidence ranged from 0 to 24% (median 0.5%); prevalence ranged from 0 to 31% (median 4.5%). The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Long-term outcomes from the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study.

PubMed

Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; Provost, Scott E; Fitzmaurice, Garrett M; McDermott, Katherine A; Srisarajivakul, Emily N; Dodd, Dorian R; Dreifuss, Jessica A; McHugh, R Kathryn; Carroll, Kathleen M

2015-05-01

Despite the growing prevalence of prescription opioid dependence, longitudinal studies have not examined long-term treatment response. The current study examined outcomes over 42 months in the Prescription Opioid Addiction Treatment Study (POATS). POATS was a multi-site clinical trial lasting up to 9 months, examining different durations of buprenorphine-naloxone plus standard medical management for prescription opioid dependence, with participants randomized to receive or not receive additional opioid drug counseling. A subset of participants (N=375 of 653) enrolled in a follow-up study. Telephone interviews were administered approximately 18, 30, and 42 months after main-trial enrollment. Comparison of baseline characteristics by follow-up participation suggested few differences. At Month 42, much improvement was seen: 31.7% were abstinent from opioids and not on agonist therapy; 29.4% were receiving opioid agonist therapy, but met no symptom criteria for current opioid dependence; 7.5% were using illicit opioids while on agonist therapy; and the remaining 31.4% were using opioids without agonist therapy. Participants reporting a lifetime history of heroin use at baseline were more likely to meet DSM-IV criteria for opioid dependence at Month 42 (OR=4.56, 95% CI=1.29-16.04, p<.05). Engagement in agonist therapy was associated with a greater likelihood of illicit-opioid abstinence. Eight percent (n=27/338) used heroin for the first time during follow-up; 10.1% reported first-time injection heroin use. Long-term outcomes for those dependent on prescription opioids demonstrated clear improvement from baseline. However, a subset exhibited a worsening course, by initiating heroin use and/or injection opioid use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Introduction of low dose transdermal buprenorphine -- did it influence use of potentially addictive drugs in chronic non-malignant pain patients?

PubMed

Skurtveit, Svetlana; Furu, Kari; Kaasa, Stein; Borchgrevink, Petter C

2009-10-01

The aim was to study the introduction of the new low dose transdermal buprenorphine (LD-TD-BUP) in Norway, particularly with regard to former use and co-medication with other potentially addictive drugs. The nationwide Norwegian Prescription Database contains information on all prescription drugs dispensed to individual non-institutionalised patients, and we may follow all individuals who received LD-TD-BUP (Norspan) after marketing on the Norwegian market on 15/11/05. We studied all prescriptions of opioids and other potentially addictive drugs to patients receiving at least two LD-TD-BUP prescriptions during 2004-2006. Poisson regressions were run with concomitant use of addictive drugs (yes, no) as the endpoint. Overall, 1884, non cancer individuals received at least two prescription of LD-TD-BUP. Of these 91.7% received prescriptions of other opioids and 58.6% of them had also been prescribed benzodiazepines/carisoprodol before the prescription of LD-TD-BUP. Of the LD-TD-BUP users who received more than one prescription, 60% co-medicated with at least one other potentially addictive drug, and 24% with at least two. In the multivariate analysis, the variables associated with a higher likelihood of using co-medicated drugs were: previous use of benzodiazepines/carisoprodol relative risk RR=16.7 (95% CI 10.4-26.9), previous use of opioids RR=4.0 (1.9-8.7) and younger age 20-40 years RR=1.9 (1.6-2.3). So far, it is questionable whether the introduction of LD-TD-BUP actually has stabilised opioids consumption or whether it has complicated and increased the consumption of potentially addictive drugs.

Strategies to Prevent Opioid Misuse, Abuse, and Diversion That May Also Reduce the Associated Costs

PubMed Central

Hahn, Kathryn L.

2011-01-01

Background The use of prescription opioid drugs has the potential to lead to patient abuse of these medications, addiction, and diversion. Such an abuse is associated with increased costs because of excessive healthcare utilization. Finding ways to minimize the risk for abuse and addiction can enhance patient outcomes and reduce costs to patients and to payers. Objective To review current strategies that may reduce the risk for misuse and abuse of opioid medications, which in turn can enhance patient outcomes and lower costs to health insurers and patients. Discussion Implementing approaches that will encourage the use of safe practices (universal precautions) in pain management by providers can reduce the risk for abuse and misuse associated with chronic pain medications, especially opioids. These approaches include, but are not limited to, extensive physician and patient education regarding these medications and their associated risks for abuse; the development of prescription monitoring programs to detect physician or pharmacy shopping; the detection of inappropriate prescribing and medical errors; the use of physician-patient contracts concerning opioid treatment; the requirement of presenting a photo identification to pick up an opioid prescription at the pharmacy; urine drug toxicology screening; provisions for safe disposal of unused opioids; referrals to pain and addiction specialists; and potentially encouraging the use of opioid formulations aimed at reducing abuse. Conclusion Supporting such approaches by health insurers and educating providers and patients on the risks associated with chronic pain medications can help minimize the risk of prescription opioid abuse, addiction, and diversion; reduce health services utilization associated with opioid abuse; improve patient outcomes; and reduce overall costs. PMID:25126342

Opioid Abuse and Addiction

MedlinePlus

Opioids, sometimes called narcotics, are a type of drug. They include strong prescription pain relievers, such as ... tramadol. The illegal drug heroin is also an opioid. Some opioids are made from the opium plant, ...

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.…

Drug-Abuse Nanotechnology: Opportunities and Challenges.

PubMed

Mahmoudi, Morteza; Pakpour, Sepideh; Perry, George

2018-05-31

Opioid drug abuse and dependence/addiction are complex disorders regulated by a wide range of interacting networks of genes and pathways that control a variety of phenotypes. Although the field has been extensively progressed since the birth of the National Institute on Drug Abuse in 1974, the fundamental knowledge and involved mechanisms that lead to drug dependence/addiction are poorly understood, and thus, there has been limited success in the prevention of drug addiction and development of therapeutics for definitive treatment and cure of addiction disease. The lack of success in both identification of addiction in at-risk populations and the development of efficient drugs has resulted in a serious social and economic burden from opioid drug abuse with global increasing rate of mortality from drug overdoses. This perspective aims to draw the attention of scientists to the potential role of nanotechnologies, which might pave the way for the development of more practical platforms for either drug development or identification and screening of patients who may be vulnerable to addiction after using opioid drugs.

First Dutch national guidelines--pharmacological care for detained opioid addicts.

PubMed

Arends, M T; De Haan, H A; Van 't Hoff, G I C M

2009-01-01

Heterogenic care of addicted detainees in the various prisons in The Netherlands triggered the National Agency of Correctional Institutions of the Ministry of Justice, to order the Dutch Institute for Health Care Improvement (CBO) to formulate the first national guideline titled 'Pharmacological care for detained addicts'. This article presents the content of this guideline, which mainly focuses on opioid-dependent addicts. In The Netherlands, approximately 50% of the detainees are problematic substance abusers, while again half of this group suffers from psychiatric co-morbidity. In addition, somatic co-morbidity, especially infectious diseases, is also common. Due to the moderate outcome seen with voluntary drug counselling regimes in prison, there is a policy shift to extent utilization of legally enforced approaches. Continuity of care is of great importance. In case of opioid addicts this, in general, means continuation of methadone maintenance treatment. Aftercare immediately after detention and optimalization of medical information transfer is crucial. This guideline aims to realize optimal and uniform management of addiction disorders in the Dutch prison system.

Opioid tolerance and dependence -- do they matter?

PubMed

Jage, Jürgen

2005-04-01

The use of opioids has long been accepted as the standard of care in patients with cancer and acute pain. Opioids can further be used effectively in specific subgroups of patients with chronic nonmalignant pain states. While the development of tolerance and physical dependence are known effects of opioids in cancer and noncancer pain populations, these patients can not be regarded as addicted. However, long-term therapy with short-acting opioids predisposes to tolerance and addiction. Recent research has confirmed the important role of psychopathologic and psychosocial conditions as predictors of failed opioid effectiveness in a significant number of noncancer pain subgroups. The clinical picture of failed therapy may be complicated by noncompliance, concealed consumption of psychotropic substances, and diversion of prescribed opioids for various purposes as, e.g., selling for profit, or sharing excess opioids with others. This article discusses the effects of opioid therapy, including tolerance, physical dependence, drug-aberrant behavior, drug history, psychopathology, and somatization.

The challenge of perioperative pain management in opioid-tolerant patients

PubMed Central

Coluzzi, Flaminia; Bifulco, Francesca; Cuomo, Arturo; Dauri, Mario; Leonardi, Claudio; Melotti, Rita Maria; Natoli, Silvia; Romualdi, Patrizia; Savoia, Gennaro; Corcione, Antonio

2017-01-01

The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone. PMID:28919771

Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial.

PubMed

Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S; Swartz, Marvin S; Woody, George E

2014-05-01

The approval of extended release injectable naltrexone (XR-NTX; Vivitrol(®)) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine. Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month. Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded. Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Medication assisted treatment in US drug courts: results from a nationwide survey of availability, barriers and attitudes.

PubMed

Matusow, Harlan; Dickman, Samuel L; Rich, Josiah D; Fong, Chunki; Dumont, Dora M; Hardin, Carolyn; Marlowe, Douglas; Rosenblum, Andrew

2013-01-01

Drug treatment courts are an increasingly important tool in reducing the census of those incarcerated for non-violent drug offenses; medication assisted treatment (MAT) is proven to be an effective treatment for opioid addiction. However, little is known about the availability of and barriers to MAT provision for opioid-addicted people under drug court jurisdiction. Using an online survey, we assessed availability, barriers, and need for MAT (especially agonist medication) for opioid addiction in drug courts. Ninety-eight percent reported opioid-addicted participants, and 47% offered agonist medication (56% for all MAT including naltrexone). Barriers included cost and court policy. Responses revealed significant uncertainty, especially among non-MAT providing courts. Political, judicial and administrative opposition appear to affect MAT's inconsistent use and availability in drug court settings. These data suggest that a substantial, targeted educational initiative is needed to increase awareness of the treatment and criminal justice benefits of MAT in the drug courts. Copyright © 2013 Elsevier Inc. All rights reserved.

Intolerance of uncertainty in opioid dependency – Relationship with trait anxiety and impulsivity

PubMed Central

Haber, Paul; Myers, Catherine E.; Allen, Michael T.; Misiak, Blazej; Frydecka, Dorota; Moustafa, Ahmed A.

2017-01-01

Intolerance of uncertainty (IU) is the tendency to interpret ambiguous situations as threatening and having negative consequences, resulting in feelings of distress and anxiety. IU has been linked to a number of anxiety disorders, and anxiety felt in the face of uncertainty may result in maladaptive behaviors such as impulsive decision making. Although there is strong evidence that anxiety and impulsivity are risk factors for addiction, there is a paucity of research examining the role of IU in this disorder. The rate of opioid addiction, in particular, has been rising steadily in recent years, which necessitates deeper understanding of risk factors in order to develop effective prevention and treatment methods. The current study tested for the first time whether opioid-dependent adults are less tolerant of uncertainty compared to a healthy comparison group. Opioid dependent patients undergoing methadone maintenance therapy (n = 114) and healthy comparisons (n = 69) completed the following scales: Intolerance of Uncertainty Scale, the Barrett Impulsivity Scale, and the State Trait Anxiety Inventory. Analysis revealed that these measures were positively correlated with each other and that opioid-dependent patients had significantly higher IU scores. Regression analysis revealed that anxiety mediated the relationship between IU and impulsivity. Hierarchical moderation regression found an interaction between addiction status and impulsivity on IU scores in that the relationship between these variables was only observed in the patient group. Findings suggest that IU is a feature of addiction but does not necessarily play a unique role. Further research is needed to explore the complex relationship between traits and how they may contribute to the development and maintenance of addiction. PMID:28759635

The prescription of addiction medications after implementation of chronic care management for substance dependence in primary care

PubMed Central

Park, Tae Woo; Samet, Jeffrey H.; Cheng, Debbie M.; Winter, Michael R.; Kim, Theresa W.; Fitzgerald, Anna; Saitz, Richard

2014-01-01

People with addictive disorders commonly do not receive efficacious medications. Chronic care management (CCM) is designed to facilitate delivery of effective therapies. Using data from the CCM group in a trial testing its effectiveness for addiction (n=282), we examined factors associated with the prescription of addiction medications. Among participants with alcohol dependence, 17% (95%CI 12.0–22.1%) were prescribed alcohol dependence medications. Among those with drug dependence, 9% (95%CI 5.5–12.6%) were prescribed drug dependence medications. Among those with opioids as a substance of choice, 15% (95%CI 9.3–20.9%) were prescribed opioid agonist therapy. In contrast, psychiatric medications were prescribed to 64% (95%CI 58.2–69.4%). Absence of co-morbid drug dependence was associated with prescription of alcohol dependence medications. Lower alcohol addiction severity and recent opioid use were associated with prescription of drug dependence medications. Better understanding of infrequent prescription of addiction medications, despite a supportive clinical setting, might inform optimal approaches to delivering addiction medications. PMID:25524751

Nonopioid substance use disorders and opioid dose predict therapeutic opioid addiction.

PubMed

Huffman, Kelly L; Shella, Elizabeth R; Sweis, Giries; Griffith, Sandra D; Scheman, Judith; Covington, Edward C

2015-02-01

Limited research examines the risk of therapeutic opioid addiction (TOA) in patients with chronic noncancer pain. This study examined TOA among 199 patients undergoing long-term opioid therapy at the time of admission to a pain rehabilitation program. It was hypothesized that nonopioid substance use disorders and opioid dosage would predict TOA. Daily mean opioid dose was 132.85 mg ± 175.39. Patients with nonopioid substance use disorders had 28 times the odds (odds ratio [OR] = 28.58; 95% confidence interval [CI] = 10.86, 75.27) of having TOA. Each 50-mg increase in opioid dose nearly doubled the odds of TOA (OR = 1.73; 95% CI = 1.29, 2.32). A 100-mg increase was associated with a 3-fold increase in odds (OR = 3.00; 95% CI = 1.67, 5.41). Receiver operating characteristic analysis revealed that opioid dose was a moderately accurate predictor (area under the curve = .75; 95% CI = .68, .82) of TOA. The sensitivity (.70) and specificity (.68) of opioid dose in predicting TOA was maximized at 76.10 mg; in addition, 46.00 mg yielded 80% sensitivity in identifying TOA. These results underscore the importance of obtaining a substance use history prior to prescribing and suggest a low screening threshold for TOA in patients who use opioids in the absence of improvement in pain or functional impairment. This article examines TOA in patients with chronic noncancer pain undergoing long-term opioid therapy. Results suggest that patients should be screened for nonopioid substance use disorders prior to prescribing. In the absence of improvement in pain or function, there is a low threshold (∼50 mg daily opioid dose) for addiction screening. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Hepatitis Infection in the Treatment of Opioid Dependence and Abuse

PubMed Central

Kresina, Thomas F; Sylvestre, Diana; Seeff, Leonard; Litwin, Alain H; Hoffman, Kenneth; Lubran, Robert; Clark, H Westley

2008-01-01

Many new and existing cases of viral hepatitis infections are related to injection drug use. Transmission of these infections can result directly from the use of injection equipment that is contaminated with blood containing the hepatitis B or C virus or through sexual contact with an infected individual. In the latter case, drug use can indirectly contribute to hepatitis transmission through the dis-inhibited at-risk behavior, that is, unprotected sex with an infected partner. Individuals who inject drugs are at-risk for infection from different hepatitis viruses, hepatitis A, B, or C. Those with chronic hepatitis B virus infection also face additional risk should they become co-infected with hepatitis D virus. Protection from the transmission of hepatitis viruses A and B is best achieved by vaccination. For those with a history of or who currently inject drugs, the medical management of viral hepatitis infection comprising screening, testing, counseling and providing care and treatment is evolving. Components of the medical management of hepatitis infection, for persons considering, initiating, or receiving pharmacologic therapy for opioid addiction include: testing for hepatitis B and C infections; education and counseling regarding at-risk behavior and hepatitis transmission, acute and chronic hepatitis infection, liver disease and its care and treatment; vaccination against hepatitis A and B infection; and integrative primary care as part of the comprehensive treatment approach for recovery from opioid abuse and dependence. In addition, participation in a peer support group as part of integrated medical care enhances treatment outcomes. Liver disease is highly prevalent in patient populations seeking recovery from opioid addiction or who are currently receiving pharmacotherapy for opioid addiction. Pharmacotherapy for opioid addiction is not a contraindication to evaluation, care, or treatment of liver disease due to hepatitis virus infection. Successful pharmacotherapy for opioid addiction stabilizes patients and improves patient compliance to care and treatment regimens as well as promotes good patient outcomes. Implementation and integration of effective hepatitis prevention programs, care programs, and treatment regimens in concert with the pharmacological therapy of opioid addiction can reduce the public health burdens of hepatitis and injection drug use. PMID:25977607

Sex differences in opioid use and medical issues during buprenorphine/naloxone treatment.

PubMed

Barbosa-Leiker, Celestina; McPherson, Sterling; Layton, Matthew E; Burduli, Ekaterina; Roll, John M; Ling, Walter

2018-01-01

There are sex differences in buprenorphine/naloxone clinical trials for opioid use. While women have fewer opioid-positive urine samples, relative to men, a significant decrease in opioid-positive samples was found during treatment for men, but not women. In order to inform sex-based approaches to improve treatment outcomes, research is needed to determine if opioid use, and predictors of opioid use, differs between men and women during treatment. To test for sex differences in opioid use during a buprenorphine/naloxone clinical trial and determine if sex differences exist in the associations between addiction-related problem areas and opioid use over the course of the trial. This secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003 examined sex differences (men = 347, women = 169) in opioid-positive samples in a randomized clinical trial comparing 7-day vs. 28-day buprenorphine/naloxone tapering strategies. Addiction-related problem areas were defined by Addiction Severity-Lite (ASI-L) domain composite scores. Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial (B = .33, p = .01) and medical issues were positively related to submitting an opioid-positive sample during treatment for women (B = 1.67, p = .01). No ASI-L domain composite score was associated with opioid-positive samples during treatment for men. Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial, and medical issues predicted opioid use during treatment for women but not men. Complementary treatment for medical problems during opioid replacement therapy may benefit women.

Opioid Use Disorders

PubMed Central

Sharma, Bikash; Bruner, Ann; Barnett, Gabrielle; Fishman, Marc

2016-01-01

Opioid use and addiction in adolescents and young adults, including heroin and non-medical use of prescription opioids, is a serious and growing health problem of epidemic proportions. Opioid use has devastating consequences for youth and their families, including: progression to full addiction, severe psychosocial impairment, HCV and HIV transmission with injection use, exacerbation of co-occurring psychiatric disorders, overdose, and death. This chapter will provide an overview of opioid use disorders (OUDs) in youth, including: etiologic factors, epidemiology, consequences, clinical presentation and course, assessment and diagnosis, overdose, detoxification, and treatment. Opioid overdose is a life-threatening emergency. Respiratory depression should be treated with naloxone, and respiratory support if necessary. Overdose should always be utilized as an opportunity to initiate addiction treatment. Opioid withdrawal management (detoxification) is often a necessary, but never sufficient, component of treatment for OUDs. Medications used in the treatment of withdrawal may include buprenorphine, clonidine and others for relief of symptoms. Treatment for OUDs is effective but treatment capacity is alarmingly limited and under-developed. Although there is a limited evidence base for youth specific treatment, emerging consensus supports the incorporation of relapse prevention medications such as buprenorphine and extended release naltrexone into comprehensive psychosocial treatment including counseling and family involvement. PMID:27338968

Special indications for Opioid Free Anaesthesia and Analgesia, patient and procedure related: Including obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, opioid addiction and cancer surgery.

PubMed

Sultana, Adrian; Torres, David; Schumann, Roman

2017-12-01

Opioid-free anaesthesia (OFA) is a technique where no intraoperative systemic, neuraxial or intracavitary opioid is administered with the anaesthetic. Opioid-free analgesia similarly avoids opioids in the perioperative period. There are many compelling reasons to avoid opioids in the surgical population. A number of case reports and, increasingly, prospective studies from all over the world support its benefits, especially in the morbidly obese population with or without sleep apnoea. A derivative technique is opioid sparing, where the same techniques are used but some opioid use is allowed. This chapter is a review of the current knowledge regarding opioid-free or low-dose opioid anaesthetic and analgesic techniques for the following special populations: obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, acute/chronic opioid addiction and cancer surgery. Practical aspects include sympatholysis, analgesia and Minimum Alveolar Concentration (MAC) reduction with dexmedetomidine; analgesia with low-dose ketamine and co-anaesthesia; and sympatholysis with intravenous lignocaine. Non-opioid adjuvants such as NSAIDS, paracetamol, magnesium, local anaesthetic infiltration and high-dose steroids are added in the perioperative period to further achieve co-analgesia. Loco-regional anaesthesia and analgesia are also maximised. It remains to be seen whether OFA and early postoperative analgesia, which similarly avoids opioids, can prevent the development of hyperalgesia and persistent postoperative pain syndromes. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Addictions].

PubMed

Besson, Jacques; Grivel, Jeremy; Tomei, Alexander; Zullino, Daniele; Thorens, Gabriel; Castro, Erika; Hachaichi, Mohamed; Devaud Cornaz, Corinne; Dudzus, Mathias; Gothuey, Isabelle

2017-01-11

In 2016, the actuality for addictions in this edition addresses four points. Social neurosciences of addiction are of great importance regarding the vulnerabilities for addiction and for the recovery. Deep brain stimulation is emerging in the therapeutic panel coming from the clinical neurosciences for the addictions. Novelties in opioid agonists for the treatment of opiates dependence, with the apparition in the Swiss market of release morphine and of levomethadone. Cannabis and prison, a pilot study for the maintenance of abstinence in prison.

Hypothalamic opioid-melanocortin appetitive balance and addictive craving.

PubMed

Reece, Albert Stuart

2011-01-01

Whilst the parallels between drug and food craving are receiving increasing attention, the recently elucidated complex physiology of the hypothalamic appetite regulatory centres has been largely overlooked in the efforts to understand drug craving which is one of the most refractory and problematic aspects of drug and behavioural addictions. Important conceptual gains could be made by researchers from both appetite and addiction neuroscience if they were to have an improved understanding of each others' disciplines. It is well known in addiction medicine that the use of many substances is elevated in opiate dependency. There is voluminous evidence of very high rates of drug use in opiate agonist maintained patients, and the real possibility exists that opiate agonist therapy therefore increases drug craving. Conversely, opiate antagonist therapy with naloxone or naltrexone has been shown to reduce most chemical and behavioural addictions, and naltrexone is now being developed together with bupropion as the anti-obesity drug "Contrave". Hypothalamic melanocortins, particularly α-MSH, are known to constitute the main brake to consumptive behaviour of food. There is a well described antagonism between melanocortins and opioids at many loci including the hypothalamus. Administration of exogenous opiates is known to both suppress α-MSH and to stimulate hedonic food consumption. Opiate maintenance programs are associated with weight gain. As monoamines, opioids and cannabinoids are known to be involved in appetite regulation, and as endorphin opioids are known to be perturbed in other addictions, further exploration of the hypothalamic appetite regulatory centre would appear to be an obvious, albeit presently largely overlooked, locus in which to study drug and other craving mechanisms. Copyright © 2010 Elsevier Ltd. All rights reserved.

42 CFR 8.11 - Opioid treatment program certification.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

42 CFR 8.11 - Opioid treatment program certification.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

42 CFR 8.11 - Opioid treatment program certification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

42 CFR 8.11 - Opioid treatment program certification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

42 CFR 8.11 - Opioid treatment program certification.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

Effectiveness of social work intervention with a systematic approach to improve general health in opioid addicts in addiction treatment centers.

PubMed

Raheb, Ghoncheh; Khaleghi, Esmat; Moghanibashi-Mansourieh, Amir; Farhoudian, Ali; Teymouri, Robab

2016-01-01

This study takes a systematic approach to investigate the effect of social work intervention aimed at increasing general health among opioid addicts in addiction treatment centers. This is an experimental plan (pretest to posttest with a control group); the study sample included 60 patients with drug dependencies undergoing treatment in addiction treatment centers. These patients were randomly assigned as case (30) and control (30) groups. The case group was subjected to intervention over ten sessions, whereas the control group received no intervention. Both groups then passed through a posttest, while a follow-up was conducted after 4 months. Data were obtained via a General Health Questionnaire. A covariance analysis test and independent and dependent t -test results indicated that a social work intervention adopting systematic approach was effective in increasing the general health of drug-addicted patients under treatment. Thus, the nature of the presence of social workers in addiction treatment centers has been effective and can have a significant influence by reducing anxiety and insomnia and somatic symptoms, improving patients' self-understanding and self-recognition, and enhancing social functioning.

Effectiveness of social work intervention with a systematic approach to improve general health in opioid addicts in addiction treatment centers

PubMed Central

Raheb, Ghoncheh; Khaleghi, Esmat; Moghanibashi-Mansourieh, Amir; Farhoudian, Ali; Teymouri, Robab

2016-01-01

Purpose This study takes a systematic approach to investigate the effect of social work intervention aimed at increasing general health among opioid addicts in addiction treatment centers. Patients and methods This is an experimental plan (pretest to posttest with a control group); the study sample included 60 patients with drug dependencies undergoing treatment in addiction treatment centers. These patients were randomly assigned as case (30) and control (30) groups. The case group was subjected to intervention over ten sessions, whereas the control group received no intervention. Both groups then passed through a posttest, while a follow-up was conducted after 4 months. Data were obtained via a General Health Questionnaire. Results A covariance analysis test and independent and dependent t-test results indicated that a social work intervention adopting systematic approach was effective in increasing the general health of drug-addicted patients under treatment. Conclusion Thus, the nature of the presence of social workers in addiction treatment centers has been effective and can have a significant influence by reducing anxiety and insomnia and somatic symptoms, improving patients’ self-understanding and self-recognition, and enhancing social functioning. PMID:27895520

Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system.

PubMed

Boscarino, Joseph A; Rukstalis, Margaret; Hoffman, Stuart N; Han, John J; Erlich, Porat M; Gerhard, Glenn S; Stewart, Walter F

2010-10-01

Our study sought to assess the prevalence of and risk factors for opioid drug dependence among out-patients on long-term opioid therapy in a large health-care system. Using electronic health records, we identified out-patients receiving 4+ physician orders for opioid therapy in the past 12 months for non-cancer pain within a large US health-care system. We completed diagnostic interviews with 705 of these patients to identify opioid use disorders and assess risk factors. Preliminary analyses suggested that current opioid dependence might be as high as 26% [95% confidence interval (CI) = 22.0-29.9] among the patients studied. Logistic regressions indicated that current dependence was associated with variables often in the medical record, including age <65 [odds ratio (OR) = 2.33, P = 0.001], opioid abuse history (OR = 3.81, P < 0.001), high dependence severity (OR = 1.85, P = 0.001), major depression (OR = 1.29, P = 0.022) and psychotropic medication use (OR = 1.73, P = 0.006). Four variables combined (age, depression, psychotropic medications and pain impairment) predicted increased risk for current dependence, compared to those without these factors (OR = 8.01, P < 0.001). Knowing that the patient also had a history of severe dependence and opioid abuse increased this risk substantially (OR = 56.36, P < 0.001). Opioid misuse and dependence among prescription opioid patients in the United States may be higher than expected. A small number of factors, many documented in the medical record, predicted opioid dependence among the out-patients studied. These preliminary findings should be useful in future research efforts. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

The development and feasibility of a pharmacy-delivered opioid intervention in the emergency department

PubMed Central

Winstanley, Erin L.; Mashni, Rebecca; Schnee, Sydney; Miller, Nate; Mashni, Susan M.

2017-01-01

Objectives To develop a brief intervention and to assess the feasibility of pharmacy-delivered education on opioid safety and overdose prevention in the emergency department. Methods A convenience sample of patients (n = 102) approached between May and June 2016 at a single community-based suburban emergency department located in the Midwest. Results The intervention included scripted counseling to be delivered in person and 2 educational brochures. The counseling took approximately 5 minutes, and only 2 patients refused the counseling. All the patients were satisfied with the intervention, and 97.4% of them reported that the counseling improved their knowledge of opioid side effects. The majority of patients thought that their own risk of addiction was significantly less than the general public’s risk of addiction when taking opioids. Conclusion This study provides preliminary evidence that student pharmacists or pharmacists are able to deliver opioid safety and overdose education in the emergency department. PMID:28292506

Mortality and employment after in-patient opiate detoxification.

PubMed

Naderi-Heiden, A; Gleiss, A; Bäcker, C; Bieber, D; Nassan-Agha, H; Kasper, S; Frey, R

2012-05-01

We considered that completed opiate detoxification resulted in increased life expectancy and earning capacity as compared to non-completed detoxification. The cohort study sample included pure opioid or poly-substance addicts admitted for voluntary in-patient detoxification between 1997 and 2004. Of 404 patients, 58.7% completed the detoxification program and 41.3% did not. The Austrian Social Security Institution supplied data on survival and employment records for every single day in the individual observation period between discharge and December 2007. Statistical analyses included the calculation of standardized mortality rates for the follow-up period of up to 11 years. The standardized mortality ratios (SMRs) were between 13.5 and 17.9 during the first five years after discharge, thereafter they fell clearly with time. Mortality did not differ statistically significantly between completers and non-completers. The median employment rate was insignificantly higher in completers (12.0%) than in non-completers (5.5%). The odds for being employed were higher in pure opioid addicts than in poly-substance addicts (p=0.003). The assumption that completers of detoxification treatment have a better outcome than non-completers has not been confirmed. The decrease in mortality with time elapsed since detoxification is interesting. Pure opioid addicts had better employment prospects than poly-substance addicts. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

PubMed Central

2011-01-01

Background The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. Methods Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. Results No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. Conclusions Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too. PMID:21569624

Opioid neuroscience for addiction medicine: From animal models to FDA approval for alcohol addiction.

PubMed

Berrettini, Wade

2016-01-01

Alcohol addiction is one of the most common and devastating diseases in the world. Given the tremendous heterogeneity of alcohol-addicted individuals, it is unlikely that one medication will help nearly all patients. Thus, there is a clear need to develop predictors of response to existing medications. Naltrexone is a mu opioid receptor antagonist which has been approved in the United States for treatment of alcohol addiction since 1994. It has limited efficacy, in part due to noncompliance, but many patients do not respond despite high levels of compliance. There are reports that a mis-sense single-nucleotide polymorphism (rs179919 or A118G) in the mu opioid receptor gene predicts a favorable response to naltrexone if an individual carries a "G" allele. This chapter will review the evidence for this hypothesis. The data suggest that the "G" allele has a complex role in alcohol addiction, increasing the rewarding valence of alcohol. Whether the G allele increases risk for alcoholism and whether it predisposes to a beneficial naltrexone response among alcohol-addicted persons must await additional research with large sample sizes of multiple ethnicities in prospective clinical trials. © 2016 Elsevier B.V. All rights reserved.

Conducting Clinical Research with Prescription Opioid Dependence: Defining the Population

PubMed Central

Weiss, Roger D.; Potter, Jennifer S.; Copersino, Marc L.; Prather, Kristi; Jacobs, Petra; Provost, Scott; Chim, David; Selzer, Jeffrey; Ling, Walter

2010-01-01

Most treatment studies of opioid-dependent populations have focused predominantly on heroin users, despite a recent increase in those dependent upon prescription opioids. A key methodological challenge involved in studying the latter group involves defining the population. Specifically, researchers must decide whether to include 1) concurrent heroin users and 2) individuals with pain. The multi-site Prescription Opioid Addiction Treatment Study is examining treatments for this population. This paper describes various inclusion criteria considered by the study team related to heroin use and pain. The goal was to recruit a distinct but generalizable population of individuals dependent upon prescription opioids. PMID:20163386

Improving recruitment to pharmacological trials for illicit opioid use: findings from a qualitative focus group study.

PubMed

Neale, Joanne; Tompkins, Charlotte N E; McDonald, Rebecca; Strang, John

2018-06-01

To explore potential study participants' views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies. Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)]. Drug and alcohol services and a peer support recovery service (London, UK). Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33-66 years). Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio-recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization. Participants' willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers' explanations. Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Effectiveness, safety and feasibility of extended-release naltrexone for opioid dependence: a 9-month follow-up to a 3-month randomized trial.

PubMed

Solli, Kristin Klemmetsby; Latif, Zill-E-Huma; Opheim, Arild; Krajci, Peter; Sharma-Haase, Kamni; Benth, Jūratė Šaltytė; Tanum, Lars; Kunoe, Nikolaj

2018-05-28

This is a follow-up study of a previously published randomized clinical trial conducted in Norway that compared extended-release naltrexone (XR-NTX) to buprenorphine-naloxone (BP-NLX) over 3 months. At the conclusion of the trial, participants were offered their choice of study medication for an additional 9 months. While BP-NLX was available at no cost through opioid maintenance treatment programmes, XR-NTX was available only through study participation, accounting for why almost all participants chose XR-NTX in the follow-up. The aim of this follow-up study was to compare differences in outcome between adults with opioid dependence continuing XR-NTX and those inducted on XR-NTX for a 9-month period, on measures of effectiveness, safety and feasibility. In this prospective cohort study, participants were either continuing XR-NTX, changed from BP-NLX to XR-NTX or re-included into the study and inducted on XR-NTX treatment. Five urban, out-patient addiction clinics in Norway. Opioid-dependent adults continuing (n = 54) or inducted on (n = 63) XR-NTX. XR-NTX administrated as intramuscular injections (380 mg) every fourth week. Data on retention, use of heroin and other illicit substances, opioid craving, treatment satisfaction, addiction-related problems and adverse events were reported every fourth week. Nine-month follow-up completion rates were 51.9% among participants continuing XR-NTX in the follow-up and 47.6% among those inducted on XR-NTX. Opioid abstinence rates were, respectively, 53.7 and 44.4%. No significant group differences were found in use of heroin and other opioids. Opioid-dependent individuals who elect to switch from buprenorphine-naltrexone treatment after 3 months to extended-release naltrexone treatment for 9 months appear to experience similar treatment completion and abstinence rates and similar adverse event profiles to individuals who had been on extended-release naltrexone from the start of treatment. © 2018 Society for the Study of Addiction.

Evaluation of Abuse-Deterrent or Tamper-Resistant Opioid Formulations on Overall Health Care Expenditures in a State Medicaid Program.

PubMed

Keast, Shellie L; Owora, Arthur; Nesser, Nancy; Farmer, Kevin

2016-04-01

The development of abuse-deterrent opioid prescription medications is a priority at the national level. Pharmaceutical manufacturers have begun marketing new formulations of currently available opioids that meet higher abuse resistance standards. Little information is available regarding the impact of these formulations on overall health care expenditures. To (a) examine the relationship between health care expenditures and use of brand abuse-deterrent or tamper-resistant (ADTR) extended-release opioids versus standard dosage form (SDF) extended-release opioids in a state Medicaid population, and (b) determine whether this relationship was influenced by member-specific characteristics. The study is a cross-sectional review of Oklahoma Medicaid members (aged ≥ 21 years) with at least 1 paid pharmacy claim for long-acting opioids between September 2013 and August 2014. Members who were adherent to extended-release opioid products were classified into ADTR and SDF opioid groups. The relationship between health care expenditures (prescription, medical, and overall) and opioid groups was examined using multiple linear regression models. The impact of member-specific characteristics (age, sex, race, urban classifications, and various comorbidities) on this relationship was examined. Prescription spending ($9,265,554) accounted for 35% of overall health care expenditures ($26,304,693) among 938 members during the 12-month reference period. Total prescription expenditures were higher among ADTR than SDF user groups, and the difference in median expenditures between these 2 groups was larger among members with more comorbidities, as measured by the Charlson Comorbidity Index score. Overall, ADTR users had higher median total health care and medical expenditures, and the difference in median expenditures was dependent on whether a member had comorbidities of addiction or not (higher expenditures were observed among members with comorbidities of addiction). The abuse and misuse of medically prescribed opioid products is a growing health epidemic. A variety of attempts have been made to reduce the potential of abuse and misuse of these products, including changes to product formulations. The results of this study indicate that both prescription spending and physician and pharmacy spending combined may be increased with the use of these new products because of higher pricing. Study findings also suggest that the use of ADTR opioids among members with comorbidities of addiction may be related to slightly lower overall health care and medical expenditures than those among members without comorbidities of addiction. Further research is required to answer questions regarding the comparative effectiveness of existing opioid prescription formulations. No outside funding supported this research. Nesser is employed by the Oklahoma Health Care Authority, and Keast is a contractual employee for the Oklahoma Health Care Authority. The authors declare no other conflicts of interest. Study design was primarily contributed by Keast, along with Nesser and Farmer. Keast took the lead in data collection, while data interpretation was primarily performed by Owora, along with Keast and assisted by Nesser and Farmer. The manuscript was written and revised by all authors equally.

Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction

PubMed Central

Zanos, Panos; Georgiou, Polymnia; Gonzalez, Loreto Rojo; Hourani, Susanna; Chen, Ying; Kitchen, Ian; Kieffer, Brigitte L; Winsky-Sommerer, Raphaelle

2016-01-01

Background: A difficult problem in treating opioid addicts is the maintenance of a drug-free state because of the negative emotional symptoms associated with withdrawal, which may trigger relapse. Several lines of evidence suggest a role for the metabotropic glutamate receptor 5 in opioid addiction; however, its involvement during opioid withdrawal is not clear. Methods: Mice were treated with a 7-day escalating-dose morphine administration paradigm. Following withdrawal, the development of affective behaviors was assessed using the 3-chambered box, open-field, elevated plus-maze and forced-swim tests. Metabotropic glutamate receptor 5 autoradiographic binding was performed in mouse brains undergoing chronic morphine treatment and 7 days withdrawal. Moreover, since there is evidence showing direct effects of opioid drugs on the metabotropic glutamate receptor 5 system, the presence of an metabotropic glutamate receptor 5/μ-opioid receptor interaction was assessed by performing metabotropic glutamate receptor 5 autoradiographic binding in brains of mice lacking the μ-opioid receptor gene. Results: Withdrawal from chronic morphine administration induced anxiety-like, depressive-like, and impaired sociability behaviors concomitant with a marked upregulation of metabotropic glutamate receptor 5 binding. Administration of the metabotropic glutamate receptor 5 antagonist, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine, reversed morphine abstinence-induced depressive-like behaviors. A brain region-specific increase in metabotropic glutamate receptor 5 binding was observed in the nucleus accumbens shell, thalamus, hypothalamus, and amygdala of μ-opioid receptor knockout mice compared with controls. Conclusions: These results suggest an association between metabotropic glutamate receptor 5 alterations and the emergence of opioid withdrawal-related affective behaviors. This study supports metabotropic glutamate receptor 5 system as a target for the development of pharmacotherapies for the treatment of opioid addiction. Moreover, our data show direct effects of μ-opioid receptor system manipulation on metabotropic glutamate receptor 5 binding in the brain. PMID:26861145

Hypothesizing that a Pro-Dopaminergic Regulator (KB220z™ Liquid Variant) can Induce “Dopamine Homeostasis” and Provide Adjunctive Detoxification Benefits in Opiate/Opioid Dependence

PubMed Central

Blum, Kenneth; Whitney, Debra; Fried, Lye; Febo, Marcelo; Waite, Roger L; Braverman, Eric R; Dushaj, Kristina; Li, Mona; Giordano, John; Demetrovics, Zsolt; Badgaiyan, Rajendra D

2017-01-01

In order to explore the initiation of detoxification of addictive patients to opiates/opioids (along with some other anti-withdrawal agents), we developed a protocol to be utilized in treatment centers particularly with heavily dependent opiate/opioid subjects. Out of 17 subjects, only three received Buprenorphine/Naloxone (Bup/nx) along with KB220Z. In this pilot, we first used a dose of KB220Z of 2 oz twice daily before meals along with clonidine and benzodiazepines and other anti-nausea and sleep aids including Gabapentin. The dose of KB220Z was maintained for 6 days in five individuals. In a second scenario, we utilized a higher dose of 4 oz every 6 hours, over a 6-day period. The higher dose was employed in another 12 patients. It is noteworthy that only 3 people have relapsed utilizing these two protocols during the first two weeks of the study, allowing for the remaining 82% to be maintained on KB220Z. The patients have been maintained without any additional Bup/nx for a minimum of 120 days and in one subject, 214 days. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates utilizing data from the Clinical opiate Withdrawal Scale (COWS) pre and post KB220Z. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates. While this does not constitute an acceptable controlled experiment, it does provide some preliminary evidence that agrees with an earlier study. Moreover, because of the utilization of standard detoxifying agents in this detoxification protocol, we cannot make any inference to KB220Z’s effects. However, out of 17 subjects, only three required Bup/nx suggesting an interesting finding. If further confirmed in larger studies, the utilization for opiate/opioid detoxification may provide a novel way to eliminate the need for addictive opioids during withdrawal and detoxification. This paradigm shift may translate to a reduction in utilizing powerful and addictive opioids like buprenorphine and methadone (especially in these patients at high genetic risk for addiction) as not only detoxifying agents, but also maintenance drugs. While extensive research is required, this pilot paves the way for future investigations that could assist in the reduction of addictive opiate/opioid use and mortalities amongst both the young and old in America. PMID:29034323

Risk Management for Opioid Prescribing in the Treatment of Patients With Pain From Cancer or Terminal Illness: Inadvertent Oversight or Taboo?

PubMed

Copenhaver, David J; Karvelas, Nicolas B; Fishman, Scott M

2017-11-01

As the United States experiences an epidemic of prescription drug abuse, and guidelines on safe practices in prescribing opioids in chronic pain have subsequently emerged from professional organizations and governmental agencies, limited guidance exists for prescribers of opioids to treat pain in patients with cancer or terminal illness. Patients with active cancer or terminal illness often have pain and are frequently prescribed opioids and other controlled substances. Current studies suggest that patients with cancer have similar rates of risk for misuse, abuse, and addiction as the general public. Moreover, palliative care and hospice programs appear poorly prepared for assessing or managing patients with aberrant behaviors or evidence of drug abuse. Further research and professional consensus are needed to help address the challenges associated with misuse, abuse, and addiction in patients with cancer and terminal illness.

From morphine clinics to buprenorphine: regulating opioid agonist treatment of addiction in the United States.

PubMed

Jaffe, Jerome H; O'Keeffe, Charles

2003-05-21

The practice of prescribing opioid drugs for opioid dependent patients in the U.S. has been subjected to special government scrutiny for almost 100 years. From 1920 until 1964, doctors who used opioids to treat addicts risked federal and/or state criminal prosecution. Although that period ended when oral methadone maintenance was established as legitimate medical practice, public concern about methadone diversion and accidental overdose fatalities, combined with political pressure from both hostile bureaucracies and groups committed to drug-free treatments, led to the development of unprecedented and detailed Food and Drug Administration (FDA) regulations that specified the manner in which methadone (and later, levo-alpha-acetyl methadol, or levomethadyl acetate, (LAAM)) could be provided. In 1974, Congress gave the Drug Enforcement Administration (DEA) additional oversight of methadone treatment programs. Efforts to liberalize the FDA regulations over the past 30 years have been resisted by both the DEA and existing treatment providers. Additional flexibility for clinicians may evolve from the most recent effort to create an accreditation system to replace some of the FDA regulations. The development of buprenorphine, a partial opioid agonist, as an effective treatment for opioid addiction reopened the possibility for having a less burdensome oversight process, especially because of its reduced toxicity if ingested by non-tolerant individuals. New legislation, the Drug Addiction Treatment Act (DATA) of 2000, created an opportunity for clinicians with special training to be exempted from both federal methadone regulations and the requirement to obtain a special DEA license when using buprenorphine to treat addicts. Some details of how the DATA was developed, moved through Congress, and signed into law are described.

[Differences in depression severity and frequency of relapses in opiate addicts treated with methadone or opiate blocker after detoxification].

PubMed

Jovanović, Tatjana; Lazarević, Dusan; Nikolić, Gordana

2012-04-01

Relapse of opiate dependence is a common occurrence after detoxification and introduction of opiate addicts in abstinence from opiates. Clinical evaluation showed that over 90% of opiate addicts exhibit depressive manifestations during detoxification, or develop post-detoxification depression. The aim of this study was to determine differences in the frequency of relapses, severity and course of depression during a of 6-month period, and previous patterns of use of opioids in the two groups of opiate addicts treated by two different therapeutic modalities. The results of the two groups of opiate addicts were compared: the patients on substitution methadone treatment (M) and the patients treated with opiate blocker naltrexone (B). In all the patients, clinical and instrumental evaluations confirmed depressive syndrome. Opioid relapses were diagnosed by the panel test for rapid detection of metabolites of opiates in urine. Then they were brought in connection with scores of depression and addiction variables. The Hamilton Depression Scale (HAMD) and Zunge Depression Scale were the applied instruments for measuring the level of depression. All the subjects completed a questionnaire Pompidou (short version). Psychological measurements were carried out during a 6-month follow-up on three occasions. The presence of opiate metabolites in urine was controlled every two weeks. Both groups of patients (M and B) had high scores on HAMD during the study. The group on methadone had a strong depression in all three measurements. There was a drop in the level of depression in both experimental groups over time, which was accompanied by a decrease in the incidence of recurrence. In both tested groups the frequency of relapses was positively correlated with earlier addiction variables - intravenous application of opioids, the experience of overdose, the absence of immunization against hepatitis C and hepatitis C virus carriers. The opioid relapse behavior is associated with a marked depression in post-detoxification period. The tested group M had a more expressed depression which is consistent with the literature data. In both tested groups the frequency of relapses was positively correlated with individual addiction variables associated with latent suicidal behavior. Diagnosing and monitoring depression of opiate addicts as well as timely remediation of post-detoxification depression symtoms, could help in prevention of opiate relapse.

Compulsive-like responding for opioid analgesics in rats with extended access.

PubMed

Wade, Carrie L; Vendruscolo, Leandro F; Schlosburg, Joel E; Hernandez, Daniel O; Koob, George F

2015-01-01

The abuse of prescription opioids that are used for the treatment of chronic pain is a major public health concern, costing ∼$53.4 billion annually in lost wages, health-care costs, and criminal costs. Although opioids remain a first-line therapy for the treatment of severe chronic pain, practitioners remain cautious because of the potential for abuse and addiction. Opioids such as heroin are considered very rewarding and reinforcing, but direct and systematic comparisons of compulsive intake between commonly prescribed opioids and heroin in animal models have not yet been performed. In the present study, we evaluated the potential for compulsive-like drug seeking and taking, using intravenous self-administration of oxycodone, fentanyl, and buprenorphine in rats allowed long access sessions (12 h). We measured compulsive-like intake using an established escalation model and responding on a progressive ratio schedule of reinforcement. We compared the potential for compulsive-like self-administration of these prescription opioids and heroin, which has been previously established to induce increasing intake that models the transition to addiction in humans. We found that animals that self-administered oxycodone, fentanyl, or heroin, but not buprenorphine had similar profiles of escalation and increases in breakpoints. The use of extended access models of prescription opioid intake will help better understand the biological factors that underlie opioid dependence.

National Institute on Drug Abuse International Program: improving opioid use disorder treatment through international research training.

PubMed

Gust, Steven W; McCormally, Judy

2018-07-01

For more than 25 years, the National Institute on Drug Abuse (NIDA) has supported research-training programs, establishing a global research network and expanding the knowledge base on substance use disorders. International research to inform approaches to opioid addiction is particularly important and relevant to the United States, where opioid misuse, addiction, and overdose constitute an emerging public health crisis. This article summarizes the NIDA International Program and illustrates its impact by reviewing recent articles about treatment approaches for opioid use disorders (OUD). Studies in several countries have demonstrated the effectiveness of physician office-based opioid substitution therapies. Other research has demonstrated the effectiveness of different formulations and doses of the opioid antagonist naltrexone, as well as different approaches to providing naloxone to treat opioid overdose. Continuing research into implementation of evidence-based treatment in international settings with limited resources is applicable to US regions that face similar structural, legal, and fiscal constraints. The current review describes international research on OUD treatment and opioid overdose, most coauthored by former NIDA fellows. The findings from outside the United States have important implications for best practices domestically and in other countries that are experiencing increases in OUD prevalence and related overdose deaths.

The impact of chronic pain on opioid addiction treatment: a systematic review protocol.

PubMed

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

2015-04-16

The consequences of opioid relapse among patients being treated with opioid substitution treatment (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Chronic pain is a major risk factor for opioid relapse within the addiction treatment setting. There exist a number of opioid maintenance therapies including methadone, buprenorphine, naltrexone, and levomethadyl acetate (LAAM), of which the mediating effects of pain on treatment attrition, substance use behavior, and social functioning may differ across therapies. We aim to 1) evaluate the impact of pain on the treatment outcomes of addiction patients being managed with OST and 2) identify the most recently published opioid maintenance treatment guidelines from the United States, Canada, and the UK to determine how the evidence is being translated into clinical practice. The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. We will search www. gov and the National Institute for Care and Excellence (NICE) databases to identify the most recently published OST guidelines. All screening and data extraction will be completed in duplicate. Provided the data are suitable, we will perform a multiple treatment comparison using Bayesian meta-analytic methods to produce summary statistics estimating the effect of chronic pain on all OSTs. Our primary outcome is substance use behavior, which includes opioid and non-opioid substance use. We will also evaluate secondary endpoints such as treatment retention, general physical health, intervention adherence, personal and social functioning, as well as psychiatric symptoms. This review will capture the experience of treatment outcomes for a sub-population of opioid addiction patients and provide an opportunity to distinguish the best quality guidelines for OST. If chronic pain truly does result in negative consequences for opioid addiction patients, it is important we identify which OSTs are most appropriate for chronic pain patients as well as ensure the treatment guidelines incorporate this information. PROSPERO CRD42014014015 http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014014015#.VS1Qw1wkKGM.

Medication-assisted recovery from opioid addiction: historical and contemporary perspectives.

PubMed

White, William L

2012-01-01

Recovery is being used as a conceptual fulcrum for the redesign of addiction treatment and related support services in the United States. Efforts by policy, research, and clinical leaders to define recovery and calls for assertive models of long-term recovery management raise critical questions about how transformation efforts of recovery-focused systems will affect the pharmacotherapeutic treatment of opioid addiction and the status of patients participating in such treatment. This article highlights recent work advocating a recovery-oriented approach to medication-assisted treatment.

The Effect of Oral Feeding of Tribulus terrestris L. on Sex Hormone and Gonadotropin Levels in Addicted Male Rats

PubMed Central

Ghosian Moghaddam, Mohammad Hassan; Khalili, Mohsen; Maleki, Maryam; Ahmad Abadi, Mohammad Esmail

2013-01-01

Background: Opioids can exert adverse effects on the body. Morphine, an opioid drug, reduces hormone levels and fertility, and causes sexual activity disorders. Tribulus terrestris (TT) is a traditional herbal medicine used to enhance sexual activities. This study investigates the possible role of TT on sex hormones and gonadotropins with the intent to show its usefulness in treating fertility disorders in opioid users. Materials and Methods: In this experimental study, we randomly divided 48 rats into four groups: i. control, ii. TT-treated, iii. addicted and iv. TT-treated addicted. Watersoluble morphine was administrated orally for 21 days to induce addiction, after which the treated groups 2 and 4 received plant-mixed pelleted food (6.25%) orally for four weeks. At the end of the treatment period, the sex hormone and gonadotropin levels of all rats’ sera were determined by radioimmunoassay and Elisa kits. The data obtained were statistically analyzed using the one-way analysis of variance, followed by post-hoc Tukey test. P<0.05 was considered significant. Results: The addicted group had a significantly lower luteinizing hormone (LH) level than the control group (p<0.027). LH levels increased significantly in the TT-treated addicted group (p<0.031). The testosterone level in the treated addicted group was lower than the treated control group. The addicted group had a significantly low testosterone level (p<0.001). The estrogen level was significantly (p<0.002) lower in the addicted group than in the control group. In addition, there was a significant difference between the treated addicted group and the treated control group (p<0.048). The treated control group had a significant increase in its progesterone level (p<0.002). Overall, except for follicle-stimulating hormone (FSH), morphine reduced most of the gonadotropins and sexual hormones. Whereas TT caused a considerable increase (p<0.05) in the hormones in the treated addicted group, there was only a slight increase in the treated control group. Conclusion: Oral consumption of TT could markedly antagonize the reduction of sex hormones and gonadotropins (except for FSH) due to morphine addiction. PMID:24520465

Endogenous opioid system: a promising target for future smoking cessation medications.

PubMed

Norman, Haval; D'Souza, Manoranjan S

2017-05-01

Nicotine addiction continues to be a health challenge across the world. Despite several approved medications, smokers continue to relapse. Several human and animal studies have evaluated the role of the endogenous opioid system as a potential target for smoking cessation medications. In this review, studies that have elucidated the role of the mu (MORs), delta (DORs), and kappa (KORs) opioid receptors in nicotine reward, nicotine withdrawal, and reinstatement of nicotine seeking will be discussed. Additionally, the review will discuss discrepancies in the literature and therapeutic potential of the endogenous opioid system, and suggest studies to address gaps in knowledge with respect to the role of the opioid receptors in nicotine dependence. Data available till date suggest that blockade of the MORs and DORs decreased the rewarding effects of nicotine, while activation of the MORs and DORs decreased nicotine withdrawal-induced aversive effects. In contrast, activation of the KORs decreased the rewarding effects of nicotine, while blockade of the KORs decreased nicotine withdrawal-induced aversive effects. Interestingly, blockade of the MORs and KORs attenuated reinstatement of nicotine seeking. In humans, MOR antagonists have shown benefits in select subpopulations of smokers and further investigation is required to realize their full therapeutic potential. Future work must assess the influence of polymorphisms in opioid receptor-linked genes in nicotine dependence, which will help in both identifying individuals vulnerable to nicotine addiction and the development of opioid-based smoking cessation medications. Overall, the endogenous opioid system continues to be a promising target for future smoking cessation medications.

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse

PubMed Central

Peterson, S. J.; Laudenbach, M.; Baruffaldi, F.; Carroll, F. I.; Comer, S. D.; Navarro, H. A.; Langston, T. L.; Runyon, S. P.; Winston, S.; Pravetoni, M.; Pentel, P. R.

2017-01-01

Among vaccines aimed at treating substance use disorders, those targeting opioids present several unique medication development challenges. 1) Opioid overdose is a common complication of abuse, so it is desirable for an opioid vaccine to block the toxic as well as the addictive effects of opioids. 2) It is important that an opioid vaccine not interfere with the action of opioid antagonists used to reverse opioid overdose or treat addiction. 3) Some opioids are immunosuppressive and chronic ongoing opioid use could interfere with vaccine immunogenicity. 4) Although antibody-bound oxycodone is unable to enter the brain because of its size, it might still be able to activate peripheral opioid receptors. To assess vaccine impact on opioid toxicity, rats vaccinated with oxycodone conjugated to keyhole limpet hemocyanin subunit dimer (OXY-dKLH) adsorbed to alum or controls vaccinated with dKLH were compared with regard to oxycodone-induced hotplate analgesia and oxycodone-induced respiratory depression and bradycardia. Vaccination shifted the dose-response curves to the right, representing protection, for each of these endpoints. Naloxone was equally effective in both OXY-dKLH and control groups, providing complete and rapid reversal of respiratory depression. The administration of a long-acting naltrexone formulation during vaccination did not impair vaccine immunogenicity in mice. Similarly, serum anti-oxycodone antibody titers were not altered by continuous morphine infusion during vaccination compared to opioid-naïve controls. Competitive ELISA assay showed negligible or low affinity of immune antiserum for endogenous opioids or opioid antagonists. In vitro receptor binding assays showed that antibody-bound oxycodone does not activate mu opioid receptors. These data support further study of OXY-dKLH as a potential treatment for oxycodone abuse and suggest that vaccination might also reduce the severity of oxycodone overdose. PMID:29194445

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant

PubMed Central

Itzoe, MariaLisa; Guarnieri, Michael

2017-01-01

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine®, which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed. PMID:28546740

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant.

PubMed

Itzoe, MariaLisa; Guarnieri, Michael

2017-01-01

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine ® , which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed.

Screening for Addictive Disorders Within a Workers’ Compensation Clinic: An Exploratory Study

PubMed Central

Parhami, Iman; Hyman, Mark; Siani, Aaron; Lin, Stephanie; Collard, Michael; Garcia, Johnny; Casaus, Laurie; Tsuang, John; Fong, Timothy W.

2012-01-01

We conducted a cross-sectional study investigating the extent of addictive disorders within a workers’ compensation (WC) clinic. We also examined the feasibility of substance abuse screening within the same clinic. In 2009, 100 patients were asked to complete the World Health Organization’s Alcohol, Smoking, Substance Involvement Screening Test (WHO-ASSIST) and the Current Opioid Misuse Measure (COMM). According to the WHO-ASSIST, we found that 46% of WC patients required intervention for at least one substance-related disorder (25% tobacco, 23% sedatives, 8% opioids), and according to the COMM, 46% screened positive for prescription opioid misuse. Importantly, the addition of this screening was brief, economical, and well accepted by patients. Further research should analyze the costs and benefits of detection and intervention of substance-related disorders in this setting. PMID:22066751

Women who abuse prescription opioids: findings from the Addiction Severity Index-Multimedia Version Connect prescription opioid database.

PubMed

Green, Traci C; Grimes Serrano, Jill M; Licari, Andrea; Budman, Simon H; Butler, Stephen F

2009-07-01

Evidence suggests gender differences in abuse of prescription opioids. This study aimed to describe characteristics of women who abuse prescription opioids in a treatment-seeking sample and to contrast gender differences among prescription opioid abusers. Data collected November 2005 to April 2008 derived from the Addiction Severity Index Multimedia Version Connect (ASI-MV Connect) database. Bivariate and multivariable logistic regression examined correlates of prescription opioid abuse stratified by gender. 29,906 assessments from 220 treatment centers were included, of which 12.8% (N=3821) reported past month prescription opioid abuse. Women were more likely than men to report use of any prescription opioid (29.8% females vs. 21.1% males, p<0.001) and abuse of any prescription opioid (15.4% females vs. 11.1% males, p<0.001) in the past month. Route of administration and source of prescription opioids displayed gender-specific tendencies. Women-specific correlates of recent prescription opioid abuse were problem drinking, age <54, inhalant use, residence outside of West US Census region, and history of drug overdose. Men-specific correlates were age <34, currently living with their children, residence in the South and Midwest, hallucinogen use, and recent depression. Women prescription opioid abusers were less likely to report a pain problem although they were more likely to report medical problems than women who abused other drugs. Gender-specific factors should be taken into account in efforts to screen and identify those at highest risk of prescription opioid abuse. Prevention and intervention efforts with a gender-specific approach are warranted.

Disrupting the downward spiral of chronic pain and opioid addiction with mindfulness-oriented recovery enhancement: a review of clinical outcomes and neurocognitive targets.

PubMed

Garland, Eric L

2014-06-01

Prescription opioid misuse and addiction among chronic pain patients are problems of growing medical and social significance. Chronic pain patients often require intervention to improve their well-being and functioning, and yet, the most commonly available form of pharmacotherapy for chronic pain is centered on opioid analgesics--drugs that have high abuse liability. Consequently, health care and legal systems are often stymied in their attempts to intervene with individuals who suffer from both pain and addiction. As such, novel, nonpharmacologic interventions are needed to complement pharmacotherapy and interrupt the cycle of behavioral escalation. The purpose of this paper is to describe how the downward spiral of chronic pain and prescription opioid misuse may be targeted by one such intervention, Mindfulness-Oriented Recovery Enhancement (MORE), a new behavioral treatment that integrates elements from mindfulness training, cognitive-behavioral therapy, and positive psychology. The clinical outcomes and neurocognitive mechanisms of this intervention are reviewed with respect to their effects on the risk chain linking chronic pain and prescription opioid misuse. Future directions for clinical and pharmacologic research are discussed.

Opioids and Chronic Pain | NIH MedlinePlus the Magazine

MedlinePlus

... term daily use of opioids leads to physical dependence, which is not to be confused with addiction ... screened and closely monitored. When people have physical dependence and the opioid use is stopped, withdrawal symptoms ...

The Comprehensive Addiction and Recovery Act: Opioid Use Disorder and Midwifery Practice.

PubMed

Murphy, Jeanne; Goodman, Daisy; Johnson, M Christina; Terplan, Mishka

2018-03-01

The federal response to the opioid use disorder crisis has included a mobilization of resources to encourage office-based pharmacotherapy with buprenorphine, an effort culminating in the 2016 Comprehensive Addiction and Recovery Act, signed into law as Public Law 114-198. The Comprehensive Addiction and Recovery Act was designed to increase access to treatment with special emphasis on services for pregnant women and follow-up for infants affected by prenatal substance exposure. In this effort, the Comprehensive Addiction and Recovery Act laudably expands eligibility for obtaining a waiver to prescribe buprenorphine to nurse practitioners and physician assistants. However, certified nurse-midwives and certified midwives, who care for a significant proportion of pregnant and postpartum women and attend a significant proportion of births in the United States, were not included in the Comprehensive Addiction and Recovery Act legislation. In this commentary, we argue that an "all-hands" approach to providing office-based medication-assisted treatment for opioid use disorder is essential to improving access to treatment. Introduced in the House of Representatives in September 2017, the Addiction Treatment Access Improvement Act (H.R. 3692) would allow midwives to apply for the federal waiver to prescribe buprenorphine and is supported by the American College of Obstetricians and Gynecologists and the American College of Nurse-Midwives. We support this change and encourage the U.S. Congress to act quickly to allow midwives to prescribe medication-assisted treatment for pregnant women with opioid use disorder.

Assessment of Tapentadol API Abuse Liability With the Researched Abuse, Diversion and Addiction-Related Surveillance System.

PubMed

Vosburg, Suzanne K; Severtson, S Geoffrey; Dart, Richard C; Cicero, Theodore J; Kurtz, Steven P; Parrino, Mark W; Green, Jody L

2018-04-01

Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted. This article presents the results from an examination of tapentadol API across the Researched Abuse, Diversion and Addiction-Related Surveillance System: a broad and carefully designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion, and Treatment Centers combined suggest a low, but present public health burden related to tapentadol. Copyright © 2018. Published by Elsevier Inc.

Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40

ERIC Educational Resources Information Center

Boone, Margaret; Brown, Nancy J.; Moon, Mary A.; Schuman, Deborah J.; Thomas, Josephine; Wright, Denise L.

2004-01-01

This Treatment Improvement Protocol (TIP) addresses the clinical use of buprenorphine in the treatment of opioid addiction. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts…

Identifying novel members of the Wntless interactome through genetic and candidate gene approaches.

PubMed

Petko, Jessica; Tranchina, Trevor; Patel, Goral; Levenson, Robert; Justice-Bitner, Stephanie

2018-04-01

Wnt signaling is an important pathway that regulates several aspects of embryogenesis, stem cell maintenance, and neural connectivity. We have recently determined that opioids decrease Wnt secretion, presumably by inhibiting the recycling of the Wnt trafficking protein Wntless (Wls). This effect appears to be mediated by protein-protein interaction between Wls and the mu-opioid receptor (MOR), the primary cellular target of opioid drugs. The goal of this study was to identify novel protein interactors of Wls that are expressed in the brain and may also play a role in reward or addiction. Using genetic and candidate gene approaches, we show that among a variety of protein, Wls interacts with the dopamine transporter (target of cocaine), cannabinoid receptors (target of THC), Adenosine A2A receptor (target of caffeine), and SGIP1 (endocytic regulator of cannabinoid receptors). Our study shows that aside from opioid receptors, Wntless interacts with additional proteins involved in reward and/or addiction. Future studies will determine whether Wntless and WNT signaling play a more universal role in these processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacotherapy of Opioid Addiction: "Putting a Real Face on a False Demon".

PubMed

Salsitz, E; Wiegand, T

2016-03-01

Methadone maintenance therapy (MMT), a pharmacological treatment for opioid use disorder for the past 50 years, continues to remain controversial. Despite consistent and overwhelming evidence confirming the effectiveness and safety of MMT, misconceptions and myths persist regarding its legitimacy as a treatment for opioid addiction. This often results in the underutilization and limited availability of this treatment modality. Despite successful outcomes, the controversial nature of MMT, and the stigma experienced by the patients on methadone, has been a particularly difficult obstacle to overcome. We present the history of MMT, review the evidence for its efficacy in the treatment of opioid dependence, and explore the origins of the stigma and misconceptions related to MMT.

Understanding Americans' views on opioid pain reliever abuse.

PubMed

Barry, Colleen L; Kennedy-Hendricks, Alene; Gollust, Sarah E; Niederdeppe, Jeff; Bachhuber, Marcus A; Webster, Daniel W; McGinty, Emma E

2016-01-01

Opioid pain reliever abuse rates have increased sharply in the United States. This study examines Americans' personal experience with opioid pain reliever use and abuse, and views about the seriousness of the problem, factors causing it, responsibility for addressing it and support for policies to resolve it. Public opinion survey. A nationally representative US adult sample (n = 1111). Experiences with opioid pain relievers and views about the seriousness, causes of and responsibility for addressing the problem, and support for policies to reduce opioid pain reliever abuse. 28.2 per cent of Americans reported using opioid pain relievers in the last 12 months, 69.5% have used them in their life-time and 17.3% reported using these medications when not prescribed to them. Fifty-eight per cent ranked the problem as serious, on a par with other major health concerns. Individual-orientated factors, including a lack of understanding about how easy it is to become addicted (80.0%) and improper storage (65.1%) and disposal (64.1%), ranked highest as causes, and those abusing opioid pain relievers (83.8%) and their physicians (78.0%) were viewed as most responsible for solving the problem. Of the policies recommended to curb the epidemic, 14 of 16 were supported by a majority of Americans. Americans view the problem of opioid pain reliever abuse as serious, and support nearly all the policies recommended by medical, law enforcement, disease control and public health experts to curb the epidemic. © 2015 Society for the Study of Addiction.

Neurophysiological mechanisms in acceptance and commitment therapy in opioid-addicted patients with chronic pain.

PubMed

Smallwood, Rachel F; Potter, Jennifer S; Robin, Donald A

2016-04-30

Acceptance and Commitment Therapy (ACT) has been effectively utilized to treat both chronic pain and substance use disorder independently. Given these results and the vital need to treat the comorbidity of the two disorders, a pilot ACT treatment was implemented in individuals with comorbid chronic pain and opioid addiction. This pilot study supported using neurophysiology to characterize treatment effects and revealed that, following ACT, participants with this comorbidity exhibited reductions in brain activation due to painful stimulus and in connectivity at rest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Use of Pharmacotherapies in the Treatment of Alcohol Use Disorders and Opioid Dependence in Primary Care

PubMed Central

Lee, Jinhee; Kresina, Thomas F.; Campopiano, Melinda; Lubran, Robert; Clark, H. Westley

2015-01-01

Substance-related and addictive disorders are chronic relapsing conditions that substantially impact public health. Effective treatments for these disorders require addressing substance use/dependence comprehensively as well as other associated comorbidities. Comprehensive addressing of substance use in a medical setting involves screening for substance use, addressing substance use directly with the patient, and formulating an appropriate intervention. For alcohol dependence and opioid dependence, pharmacotherapies are available that are safe and effective when utilized in a comprehensive treatment paradigm, such as medication assisted treatment. In primary care, substance use disorders involving alcohol, illicit opioids, and prescription opioid abuse are common among patients who seek primary care services. Primary care providers report low levels of preparedness and confidence in identifying substance-related and addictive disorders and providing appropriate care and treatment. However, new models of service delivery in primary care for individuals with substance-related and addictive disorders are being developed to promote screening, care and treatment, and relapse prevention. The education and training of primary care providers utilizing approved medications for the treatment of alcohol use disorders and opioid dependence in a primary care setting would have important public health impact and reduce the burden of alcohol abuse and opioid dependence. PMID:25629034

Low expression of D2R and Wntless correlates with high motivation for heroin.

PubMed

Tacelosky, Diana M; Alexander, Danielle N; Morse, Megan; Hajnal, Andras; Berg, Arthur; Levenson, Robert; Grigson, Patricia S

2015-12-01

Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se. (c) 2015 APA, all rights reserved).

Opioids for neuropathic pain.

PubMed

Katz, Nathaniel; Benoit, Christine

2005-06-01

Whether opioids are effective for neuropathic pain has been a matter of controversy for decades. Within limits, it is clear that opioids in general are effective for neuropathic pain. Furthermore, there is no evidence that opioids are any less effective for neuropathic pain than for non-neuropathic pain, no evidence that opioids are less effective for neuropathic pain than are other medications, and no evidence that one opioid is any more effective than another for neuropathic pain. It remains uncertain whether opioids are effective for central pain, although they may have a role. Although some patients appear to enjoy long-term benefits, most studies have been short-term. Opioids have an important role in the treatment of neuropathic pain; however, skillful opioid use balances the benefits with management of side effects and prevention and treatment of abuse and addiction.

Opioid receptors: from binding sites to visible molecules in vivo

PubMed Central

Kieffer, Brigitte L.; Evans, Christopher J.

2010-01-01

Opioid drugs such as heroin interact directly with opioid receptors whilst other addictive drugs, including marijuana, alcohol and nicotine indirectly activate endogenous opioid systems to contribute to their rewarding properties. The opioid system therefore plays a key role in addiction neurobiology and continues to be a primary focus for NIDA-supported research. Opioid receptors and their peptide ligands, the endorphins and enkephalins, form an extensive heterogeneous network throughout the central and peripheral nervous system. In addition to reward, opioid drugs regulate many functions such that opioid receptors are targets of choice in several physiological, neurological and psychiatric disorders. Because of the multiplicity and diversity of ligands and receptors, opioid receptors have served as an optimal model for G protein coupled receptor (GPCR) research. The isolation of opioid receptor genes opened the way to molecular manipulations of the receptors, both in artificial systems and in vivo, contributing to our current understanding of the diversity of opioid receptor biology at the behavioral, cellular and molecular levels. This review will briefly summarize some aspects of current knowledge that has accumulated since the very early characterization of opioid receptor genes. Importantly, we will identify a number of research directions that are likely to develop during the next decade. PMID:18718480

[Psychophysiology of sports addiction (exercises addiction)].

PubMed

Krivoshchekov, S G; Lushnikov, O N

2011-01-01

Addiction is a prevalent and growing concern in all aspects of our modern society. There are considerable concerns for the growing frequency of addictions to drugs, alcohol, gambling, eating, and even sex. Though exercise is generally accepted as a positive behaviour that has many benefits associated with enhanced physical and psychological wellbeing, there is an increasing awareness that exercise addiction is becoming a common phenomenon. Theories regarding how exercise can become addictive, and studies of withdrawal from exercise are reviewed. Several physiological mechanisms, including endogenous opioids, catecholamines, functional asymmetry of brain activity and thermoregulation have been implicated in exercise dependence.

Deficiency in the Opioid Hypotheses of Self-Injurious Behavior.

ERIC Educational Resources Information Center

King, Bryan H.; And Others

1991-01-01

This commentary critiques two papers by Curt Sandman, pointing out interpretive problems in models explaining self-injurious behavior in terms of opioids. Withdrawal effects are emphasized as an alternative to hypotheses asserting congenital opioid excess as a cause of sensory depression or an addiction to a relative excess of opioid activity in…

Role of olfactory reactions, nociception, and immunoendocrine shifts in addictive disorders.

PubMed

Masterova, Elena; Nevidimova, Tatiana; Savochkina, Dariya; Nikitina, Valentina; Lobacheva, Olga; Vetlugina, Tamara; Bokhan, Nikolay

2017-09-01

Addictive pathology is associated with nervous, immune, and endocrine shifts. Meanwhile, the nature of intersystemic relationship lying beneath addictive disorders remains unclear. The purpose of the study was to identify neuroimmunoendocrine markers of addictive disorders in male subjects defining the nature of their interaction. The study enrolled 69 subjects aged 18-43 years: 59 males and 10 females divided into those with addictive disorders (n = 39) and conditionally healthy subjects (n = 30). EEG testing with olfactory stimulation, olfactometric, and pressure algometric examinations was carried out. Multiplex technique was applied to determine mitogen-induced production of cytokines IL-10, IL-1, IL-1RA, IL-2, IFN-gamma, TNF-alpha. ELISA method was applied to measure serum cortisol and testosterone levels. Olfactory responses to isopropanol with open eyes in addicted patients manifested as increase in alpha-rhythm and beta1-rhythm, with closed eyes presentation of this odorant was accompanied by increase of theta-rhythm in opioid-addicted patients. Male subjects with addictive disorders showed reduced alpha-rhythm in terms of olfactory stimulation with modified emotional evaluation of the odorant, deficient mitogen-induced production of IFN-gamma, and reduced pain sensitivity. Male subjects with opioid addiction had reduced beta1-rhythm in terms of olfactory stimulation, mitogen-induced production of IFN-gamma, and elevated testosterone level. The findings obtained verify potential involvement of nociception, olfaction, and cytokine production in addiction pathogenesis evidencing their various roles depending on the range of psychoactive substances (PAS) and pathology progression. The data obtained may provide background for unification of reward circuit and inhibitory control concepts in regulation of addictive behavior. (Am J Addict 2017;26:640-648). © 2017 American Academy of Addiction Psychiatry.

Backstories on the US Opioid Epidemic. Good Intentions Gone Bad, an Industry Gone Rogue, and Watch Dogs Gone to Sleep.

PubMed

deShazo, Richard D; Johnson, McKenzie; Eriator, Ike; Rodenmeyer, Kathryn

2018-06-01

Epidemics of opioid use are old news in the United States, but an epidemic that kills over 200,000 Americans is not. A multiplicity of intertwined factors have brought us to this place. From 30,000 feet, it is the story of good intentions gone bad, a drug industry gone rogue, and government watch dog agencies gone to sleep. At ground level, it is the story of physicians unfamiliar with addictive drugs and drug addiction, new long-acting opioids deceptively marketed, cheap black tar heroin, encouragement to use opioids for chronic noncancer pain by professional organizations with conflicts of interest and without science, a culture intolerant to pain and tolerant to drug use, and the greedy response of the pharmaceutical industry and drug cartels to an expanding market opportunity. These factors are among those that have joined to form a tsunami of addiction and deaths that keeps on coming. A better understanding of them could speed the end of the present cycle of opioid abuse, perhaps prevent others, and inform future decisions about pain management. Copyright © 2018 Elsevier Inc. All rights reserved.

Post opioid overdose outreach by public health and public safety agencies: Exploration of emerging programs in Massachusetts.

PubMed

Formica, Scott W; Apsler, Robert; Wilkins, Lindsay; Ruiz, Sarah; Reilly, Brittni; Walley, Alexander Y

2018-04-01

Opioid overdose is a significant public health problem. Collaborative programs between local public health and public safety agencies have emerged to connect overdose survivors and their personal networks with harm reduction and addiction treatment services following a non-fatal overdose event. This study explored the prevalence of these programs in Massachusetts and the different ways they have been structured and function. We sent an online screening questionnaire to police and fire departments in all 351 communities in Massachusetts to find instances in which they collaborated with a community-based public health agency to implement a post-overdose outreach and support program. We conducted telephone interviews with communities that implemented this type of program and categorized programs based on their structure, outreach approach, and other key characteristics. Police and fire personnel from 110 of the 351 communities in Massachusetts (31% response rate) completed the screening survey. Among respondents, 21% (23/110) had implemented a collaborative, community-based, post-overdose program with a well-defined process to connect overdose survivors and their personal networks with support services or addiction treatment services. Using data from the interviews, we identified four types of programs: (1) Multi-Disciplinary Team Visit, (2) Police Visit with Referrals, (3) Clinician Outreach, and (4) Location-Based Outreach. This study represents the first attempt to systematically document an emerging approach intended to connect opioid overdose survivors and their personal networks with harm reduction and addiction treatment services soon after a non-fatal overdose event. These programs have the potential to increase engagement with the social service and addiction treatment systems by those who are at elevated risk for experiencing a fatal opioid overdose. Copyright © 2018 Elsevier B.V. All rights reserved.

Preference for brand-name buprenorphine is related to severity of addiction among outpatients in opioid maintenance treatment.

PubMed

Binder, Philippe; Messaadi, Nassir; Perault-Pochat, Marie-Christine; Gagey, Stéphanie; Brabant, Yann; Ingrand, Pierre

2016-01-01

As a form of opioid maintenance treatment, high-dose buprenorphine is increasingly being used in the United States. On the French market since 1996, it is the most commonly prescribed and frequently employed opioid maintenance treatment. For unknown reasons, the brand-name form is used far more often than the generic form (76-24%). The objective was to show that the patients' levels of addiction were differentiated according to the form of buprenorphine currently being used and to their previous experience of a different form. An observational study in 9 sites throughout France used self-assessment questionnaires filled out in retail pharmacies by all patients to whom their prescribed buprenorphine treatment was being delivered. The 151 canvassed pharmacies solicited 879 patients, of whom 724 completed the questionnaires. Participants were statistically similar to non-participants. The patients using the brand-name form subsequent to experience with the generic form exhibited a more elevated addiction severity index and a higher dosage than brand-name form users with no experience of a different form. Compared to generic users, their doses were higher, their was addiction more severe, and their alcohol consumption was more excessive; they were also more likely to make daily use of psychotropic substances. However, the level of misuse or illicit consumption was similar between these groups. Preferring the brand-name buprenorphine form to the generic form is associated with a higher level of severe addiction, a more frequent need for daily psychotropics, and excessive drinking; but the study was unable to show a causal link.

Comparative Trial to Study the Effectiveness of Clonidine Hydrochloride and Buprenorphine-Naloxone in Opioid Withdrawal – A Hospital Based Study

PubMed Central

Farhat, Samina; Rather, Yasir Hassan; Abbas, Zaffar

2015-01-01

Objectives: Prevalence of opioid addiction has alarmingly increased over the recent years. In South Asian region alone there are more than 10 million opioid abusers amounting to 2% of world population. Detoxification remains to be the first step for the successful treatment of opioid addiction. The present study was carried out to compare the relative efficacy and safety of buprenorphine –naloxone and clonidine hydrochloride in the detoxification of opioid-dependents. Materials and Methods: Present trial was conducted at De- addiction centre of Institute of Mental and Neurosciences (IMNS), GMC Srinagar. Fifty four (54) treatment seeking subjects, 15-50 years of age, fulfilling DSM-1V TR (American Psychiatric association`s Mental Disorders-1V text revision) criteria for opioid dependence were included and randomized into two groups. The groups received either clonidine hydrochloride (Group A) or buprenorphine- naloxone (Bup-Nax) (Group B) for the duration of 10 days. The efficacy of the two drugs in controlling the opioid withdrawal was evaluated by Clinical Opioid Withdrawal Scale (COWS) and their effect on the desire for the abused substance was measured by Visual Analogue Scale (VAS). The safety of the two drugs was measured by taking the side effect profile of the two compared drugs into consideration. Results: There was significant difference of COWS-score between the two groups which was evident from day 3 (14.85 ± 3.43 vs. 11.67 ± 2.40, p<0.005) and continued till day 6 (2.56 ± 1.40 vs. 0.30 ± 0.61, p<0.005), for Group A and group B respectively. The effect of two drugs in controlling the craving for the abused substance also showed significant difference from day 2 (66.30 ± 10.80 vs. 47.40 ± 12.90, p<0.005) till day 5 (7.78 ± 6.41 vs. 1.85 ± 6.22, p<0.005), for Group A and Group B respectively. Conclusion: Administration of buprenorphine-naloxone was more efficient in reducing the signs and symptoms of opioid withdrawal and in controlling the craving for the abused substance during the first few days of detoxification. PMID:25738001

Similarities and Differences in Neurobiology.

PubMed

Chen, Manli; Sun, Yan; Lu, Lin; Shi, Jie

2017-01-01

Substance addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite harmful consequences. Non-substance addiction is defined recently that people may compulsively engage in an activity despite any negative consequences to their lives. Despite differences with respect to their addictive object, substance addiction and non-substance addiction may share similarities with respect to biological, epidemiological, clinical, genetic and other features. Here we review the similarities and differences in neurobiology between these two addictions with a focus on dopamine, serotonin, opioid, glutamate and norepinephrine systems. Studies suggest the involvement of all these systems in both substance addiction and non-substance addiction while differences may exist with respect to their contributions.

Genetics of Opioid Dependence: A Review of the Genetic Contribution to Opioid Dependence

PubMed Central

Mistry, Chetna J; Bawor, Monica; Desai, Dipika; Marsh, David C; Samaan, Zainab

2014-01-01

This narrative review aims to provide an overview of the impact of opioid dependence and the contribution of genetics to opioid dependence. Epidemiological data demonstrate that opioid dependence is a global trend with far-reaching effects on the social, economic, and health care systems. A review of classical genetic studies of opioid use suggests significant heritability of drug use behavior, however the evidence from molecular genetic studies is inconclusive. Nonetheless, certain genetic variants are important to consider given their role in the pathophysiology of addictive behavior. We undertook a literature review to identify the current state of knowledge regarding the role of genes in opioid dependence. Determining the association of genetic markers could change the current understanding of the various factors contributing to opioid dependence and therefore may improve recognition of individuals at risk for the disorder and prevention and treatment strategies. PMID:25242908

Global Scientific Production on Illicit Drug Addiction: A Two-Decade Analysis.

PubMed

Khalili, Malahat; Rahimi-Movaghar, Afarin; Shadloo, Behrang; Mojtabai, Ramin; Mann, Karl; Amin-Esmaeili, Masoumeh

2018-04-06

Addiction science has made great progress in the past decades. We conducted a scientometric study in order to quantify the number of publications and the growth rate globally, regionally, and at country levels. In October 2015, we searched the Scopus database using the general keywords of addiction or drug-use disorders combined with specific terms regarding 4 groups of illicit drugs - cannabis, opioids, cocaine, and other stimulants or hallucinogens. All documents published during the 20-year period from 1995 to 2014 were included. A total of 95,398 documents were retrieved. The highest number of documents were on opioids, both globally (60.1%) and in each of 5 continents. However, studies on cannabis showed a higher growth rate in the last 5-year period of the study (2010-2014). The United States, the United Kingdom, Germany, Canada, Australia, France, Spain, Italy, China, and Japan - almost all studies were from high-income countries - occupied the top 10 positions and produced 81.4% of the global science on drug addiction. As there are important socio-cultural differences in the epidemiology and optimal clinical care of addictive disorders, it is suggested that low- and more affected middle-income countries increase their capacity to conduct research and disseminate the knowledge in this field. © 2018 S. Karger AG, Basel.

42 CFR 8.1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CERTIFICATION OF OPIOID TREATMENT... under section 303(g) of the Controlled Substances Act (21 U.S.C. 823(g)) to dispense opioid drugs in the treatment of opioid addiction. These regulations also establish the Secretary's standards regarding the...

42 CFR 8.1 - Scope.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CERTIFICATION OF OPIOID TREATMENT... under section 303(g) of the Controlled Substances Act (21 U.S.C. 823(g)) to dispense opioid drugs in the treatment of opioid addiction. These regulations also establish the Secretary's standards regarding the...

42 CFR 8.1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CERTIFICATION OF OPIOID TREATMENT... under section 303(g) of the Controlled Substances Act (21 U.S.C. 823(g)) to dispense opioid drugs in the treatment of opioid addiction. These regulations also establish the Secretary's standards regarding the...

42 CFR 8.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CERTIFICATION OF OPIOID TREATMENT... under section 303(g) of the Controlled Substances Act (21 U.S.C. 823(g)) to dispense opioid drugs in the treatment of opioid addiction. These regulations also establish the Secretary's standards regarding the...

The risk of disciplinary action by state medical boards against physicians prescribing opioids.

PubMed

Richard, Jack; Reidenberg, Marcus M

2005-02-01

Concern of physicians about being disciplined for prescribing opioids for patients in pain is one cause for undertreatment of pain. This study was done to assess the actual risk of being disciplined by state medical boards. A review of records of actions by the New York State Board for Professional Medical Misconduct for 3 years and of all medical boards in the United States for 9 months was done to determine this risk. New York State, with 7.8% of U.S. physicians, had 10 physicians disciplined annually related to overprescribing opioids, while the total for the entire U.S. was 120 physicians annually. Most physicians disciplined had multiple violations in addition to overprescribing controlled substances. In the national sample, 43% were prescribing for themselves or for nonpatients, 12% prescribed for addicts without addressing the patients' problems of addiction, 42% had inadequate records, 19% prescribed without indication for opioids, 13% were incompetent in additional ways, and 8% were having sexual activity with patients. Not a single physician, for whom information was available, was disciplined solely for overprescribing opioids. The actual risk of an American physician being disciplined by a state medical board for treating a real patient with opioids for a painful medical condition is virtually nonexistent.

Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes.

PubMed

Brown, Thomas Kingsley; Alper, Kenneth

2018-01-01

Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine. To study outcomes following opioid detoxification with ibogaine. In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl. Subjects used oxycodone (n = 21; 70%) and/or heroin (n = 18; 60%) in respective amounts of 250 ± 180 mg/day and 1.3 ± 0.94 g/day, and averaged 3.1 ± 2.6 previous episodes of treatment for opioid dependence. Detoxification and follow-up outcomes at 1, 3, 6, 9, and 12 months were evaluated utilizing the Subjective Opioid Withdrawal Scale (SOWS) and Addiction Severity Index Composite (ASIC) scores, respectively. SOWS scores decreased from 31.0 ± 11.6 pretreatment to 14.0 ± 9.8 at 76.5 ± 30 hours posttreatment (t = 7.07, df = 26, p < 0.001). At 1-month posttreatment follow-up, 15 subjects (50%) reported no opioid use during the previous 30 days. ASIC Drug Use and Legal and Family/Social Status scores were improved relative to pretreatment baseline at all posttreatment time points (p < .001). Improvement in Drug Use scores was maximal at 1 month, and subsequently sustained from 3 to 12 months at levels that did not reach equivalence to the effect at 1 month. Ibogaine was associated with substantive effects on opioid withdrawal symptoms and drug use in subjects for whom other treatments had been unsuccessful, and may provide a useful prototype for discovery and development of innovative pharmacotherapy of addiction.

Controlling pain and reducing misuse of opioids

PubMed Central

Kotalik, Jaro

2012-01-01

Abstract Objective To help family physicians achieve an ethical balance in their opioid prescribing practices. Quality of evidence MEDLINE was searched for English-language articles published between 1985 and 2011. Most available evidence was level III. Main message It is essential to follow practice guidelines when prescribing opioids, except when another course of action is demonstrably justified. In addition, when considering the appropriateness of an opioid prescription, with its many ethical implications, the decision can be usefully guided by the application of the ethical principles of beneficence, nonmaleficence, respect for autonomy, and justice. As well, it is essential to keep current about legal and regulatory changes and provincial electronic registries of opioid prescriptions. Conclusion Physicians need to ensure that their patients’ pain is properly assessed and managed. Reaching optimal pain control might necessitate prescribing opioids. But the obligation to provide pain relief needs to be balanced with an equally important responsibility not to expose patients to risk of addiction and not to create opportunities for drug diversion, trafficking, and the addiction of others. Basic ethical principles can provide a framework to help physicians make ethically appropriate decisions about opioid prescribing. PMID:22611604

Long Term Suboxone™ Emotional Reactivity As Measured by Automatic Detection in Speech

PubMed Central

Hill, Edward; Han, David; Dumouchel, Pierre; Dehak, Najim; Quatieri, Thomas; Moehs, Charles; Oscar-Berman, Marlene; Giordano, John; Simpatico, Thomas; Blum, Kenneth

2013-01-01

Addictions to illicit drugs are among the nation’s most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX) as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states (“true ground emotionality”) in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of “true” emotionality in 36 SUBX patients compared to 44 individuals from the general population (GP) and 33 members of Alcoholics Anonymous (AA). Other less objective studies have investigated emotional reactivity of heroin, methadone and opioid abstinent patients. These studies indicate that current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. However, this is the first study to our knowledge to evaluate “true ground” emotionality in long-term buprenorphine/naloxone combination (Suboxone™). We found in long-term SUBX patients a significantly flat affect (p<0.01), and they had less self-awareness of being happy, sad, and anxious compared to both the GP and AA groups. We caution definitive interpretation of these seemingly important results until we compare the emotional reactivity of an opioid abstinent control using automatic detection in speech. These findings encourage continued research strategies in SUBX patients to target the specific brain regions responsible for relapse prevention of opioid addiction. PMID:23874860

Help, Resources and Information: National Opioids Crisis

MedlinePlus

... HHS 5-POINT STRATEGY TO COMBAT THE OPIOIDS CRISIS BETTER ADDICTION PREVENTION, TREATMENT, AND RECOVERY SERVICES BETTER DATA BETTER PAIN MANAGEMENT BETTER TARGETING OF OVERDOSE REVERSING DRUGS BETTER RESEARCH ...

Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review.

PubMed

McCance-Katz, Elinore F; Sullivan, Lynn E; Nallani, Srikanth

2010-01-01

Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area.

Drug Interactions of Clinical Importance among the Opioids, Methadone and Buprenorphine, and other Frequently Prescribed Medications: A Review

PubMed Central

McCance-Katz, Elinore F.; Sullivan, Lynn; Nallani, Srikanth

2012-01-01

Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area. PMID:20132117

Multiple mechanisms underlying the long duration of action of thienorphine, a novel partial opioid agonist for the treatment of addiction.

PubMed

Yu, Gang; Li, Shu-Hui; Cui, Meng-Xun; Yan, Ling-Di; Yong, Zheng; Zhou, Pei-Lan; Su, Rui-Bin; Gong, Ze-Hui

2014-03-01

It is considered that a long-acting therapy would be advantageous in the treatment of addiction. In a search for novel buprenorphine analogues, thienorphine was demonstrated to be an extremely long-acting orally active partial opioid agonist. This study explored the mechanisms underlying the long-lasting effects of thienorphine. The binding kinetics of [(3) H]thienorphine were measured in membrane preparations expressing cloned rat opioid receptors. Flow cytometric analysis was used to determine the effect of thienorphine on the surface opioid receptor number. The long-lasting effects of thienorphine were also confirmed at the tissue level and in vivo. At 37°C, [(3) H]thienorphine showed rapid association with μ- and κ-opioid receptors, while its dissociation was sluggish and biphasic (K-1 = 0.21 min(-1) , K-2 = 0.0078 min(-1) for the μ-receptor; K-1 = 0.17 min(-1) , K-2 = 0.0042 min(-1) for the κ-receptor). Treatment with thienorphine for 24, 48, and 72 h downregulated surface μ-receptor in a dose- and time-dependent manner. The inhibitory effect of thienorphine on guinea pig ileum persisted for more than 120 min after prolonged washing. In vivo, thienorphine exhibited significant antagonism of morphine-induced antinociception for more than 7 days. These results indicate that multiple factors, including persistent receptor occupation and enhanced receptor downregulation, may contribute to the long-lasting effects of thienorphine that would be beneficial for its application in addiction treatment. © 2013 John Wiley & Sons Ltd.

Dopamine and Opioid Neurotransmission in Behavioral Addictions: A Comparative PET Study in Pathological Gambling and Binge Eating.

PubMed

Majuri, Joonas; Joutsa, Juho; Johansson, Jarkko; Voon, Valerie; Alakurtti, Kati; Parkkola, Riitta; Lahti, Tuuli; Alho, Hannu; Hirvonen, Jussi; Arponen, Eveliina; Forsback, Sarita; Kaasinen, Valtteri

2017-04-01

Although behavioral addictions share many clinical features with drug addictions, they show strikingly large variation in their behavioral phenotypes (such as in uncontrollable gambling or eating). Neurotransmitter function in behavioral addictions is poorly understood, but has important implications in understanding its relationship with substance use disorders and underlying mechanisms of therapeutic efficacy. Here, we compare opioid and dopamine function between two behavioral addiction phenotypes: pathological gambling (PG) and binge eating disorder (BED). Thirty-nine participants (15 PG, 7 BED, and 17 controls) were scanned with [ 11 C]carfentanil and [ 18 F]fluorodopa positron emission tomography using a high-resolution scanner. Binding potentials relative to non-displaceable binding (BP ND ) for [ 11 C]carfentanil and influx rate constant (K i ) values for [ 18 F]fluorodopa were analyzed with region-of-interest and whole-brain voxel-by-voxel analyses. BED subjects showed widespread reductions in [ 11 C]carfentanil BP ND in multiple subcortical and cortical brain regions and in striatal [ 18 F]fluorodopa K i compared with controls. In PG patients, [ 11 C]carfentanil BP ND was reduced in the anterior cingulate with no differences in [ 18 F]fluorodopa K i compared with controls. In the nucleus accumbens, a key region involved in reward processing, [ 11 C]Carfentanil BP ND was 30-34% lower and [ 18 F]fluorodopa K i was 20% lower in BED compared with PG and controls (p<0.002). BED and PG are thus dissociable as a function of dopaminergic and opioidergic neurotransmission. Compared with PG, BED patients show widespread losses of mu-opioid receptor availability together with presynaptic dopaminergic defects. These findings highlight the heterogeneity underlying the subtypes of addiction and indicate differential mechanisms in the expression of pathological behaviors and responses to treatment.

Patterns of co-occurring addictions, posttraumatic stress disorder, and major depressive disorder in detoxification treatment seekers: Implications for improving detoxification treatment outcomes.

PubMed

Anderson, RaeAnn E; Hruska, Bryce; Boros, Alec P; Richardson, Christopher J; Delahanty, Douglas L

2018-03-01

Poly-substance use and psychiatric comorbidity are common among individuals receiving substance detoxification services. Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are the most common co-occurring psychiatric disorders with substance use disorder (SUD). Current treatment favors a one-size-fits-all approach to treating addiction focusing on one substance or one comorbidity. Research examining patterns of substance use and comorbidities can inform efforts to effectively identify and differentially treat individuals with co-occurring conditions. Using latent class analysis, the current study identified four patterns of PTSD, MDD, and substance use among 375 addiction treatment seekers receiving medically supervised detoxification. The four identified classes were: 1) a PTSD-MDD-Poly SUD class characterized by PTSD and MDD occurring in the context of opioid, cannabis, and tobacco use disorders; 2) an MDD-Poly SUD class characterized by MDD and alcohol, opioid, tobacco, and cannabis use disorders; 3) an alcohol-tobacco class characterized by alcohol and tobacco use disorders; and 4) an opioid-tobacco use disorder class characterized by opioid and tobacco use disorders. The observed classes differed on gender and clinical characteristics including addiction severity, trauma history, and PTSD/MDD symptom severity. The observed classes likely require differing treatment approaches. For example, people in the PTSD-MDD-Poly SUD class would likely benefit from treatment approaches targeting anxiety sensitivity and distress tolerance, while the opioid-tobacco class would benefit from treatments that incorporate motivational interviewing. Appropriate matching of treatment to class could optimize treatment outcomes for polysubstance and comorbid psychiatric treatment seekers. These findings also underscore the importance of well-developed referral networks to optimize outpatient psychotherapy for detoxification treatment-seekers to enhance long-term recovery, particularly those that include transdiagnostic treatment components. Copyright © 2017. Published by Elsevier Inc.

Use and abuse of opioid analgesics in chronic pain.

PubMed Central

Goldman, B.

1993-01-01

Primary care physicians are frequently required to treat patients with chronic debilitating pain. Opioid analgesics can successfully manage chronic pain. To prescribe opioid analgesics effectively, physicians must identify appropriate patients. Several methods can be used to identify and distinguish appropriate patients, addicted patients, and for-profit drug seekers. PMID:8097128

Suicide by means of opioid overdose in patients with chronic pain.

PubMed

Madadi, Parvaz; Persaud, Nav

2014-11-01

Deaths from prescription opioid use continue to rise in North America. The main focus to date has been developing strategies to prevent nonintentional (accidental) fatalities, which constitute the majority of opioid deaths across all jurisdictions. Often overlooked is the complex group of individuals whose cause of death was suicide by opioid overdose. Although most opioid prescribing tools focus on identifying risk factors for potential abuse, diversion, and propensity for opioid addiction, physicians who consider prescribing opioids should also screen and optimize chronic pain treatment for patients at risk for suicide.

Buprenorphine Injection

MedlinePlus

Buprenorphine extended-release injection is used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic painkillers) ... sublingual buprenorphine for at least 7 days. Buprenorphine extended-release injection is in a class of medications ...

Sex Differences in Kappa Opioid Receptor Function and Their Potential Impact on Addiction

PubMed Central

Chartoff, Elena H.; Mavrikaki, Maria

2015-01-01

Behavioral, biological, and social sequelae that lead to drug addiction differ between men and women. Our efforts to understand addiction on a mechanistic level must include studies in both males and females. Stress, anxiety, and depression are tightly linked to addiction, and whether they precede or result from compulsive drug use depends on many factors, including biological sex. The neuropeptide dynorphin (DYN), an endogenous ligand at kappa opioid receptors (KORs), is necessary for stress-induced aversive states and is upregulated in the brain after chronic exposure to drugs of abuse. KOR agonists produce signs of anxiety, fear, and depression in laboratory animals and humans, findings that have led to the hypothesis that drug withdrawal-induced DYN release is instrumental in negative reinforcement processes that drive addiction. However, these studies were almost exclusively conducted in males. Only recently is evidence available that there are sex differences in the effects of KOR activation on affective state. This review focuses on sex differences in DYN and KOR systems and how these might contribute to sex differences in addictive behavior. Much of what is known about how biological sex influences KOR systems is from research on pain systems. The basic molecular and genetic mechanisms that have been discovered to underlie sex differences in KOR function in pain systems may apply to sex differences in KOR function in reward systems. Our goals are to discuss the current state of knowledge on how biological sex contributes to KOR function in the context of pain, mood, and addiction and to explore potential mechanisms for sex differences in KOR function. We will highlight evidence that the function of DYN-KOR systems is influenced in a sex-dependent manner by: polymorphisms in the prodynorphin (pDYN) gene, genetic linkage with the melanocortin-1 receptor (MC1R), heterodimerization of KORs and mu opioid receptors (MORs), and gonadal hormones. Finally, we identify several gaps in our understanding of “if” and “how” DYN and KORs modulate addictive behavior in a sex-dependent manner. Future work may address these gaps by building on the mechanistic studies outlined in this review. Ultimately this will enable the development of novel and effective addiction treatments tailored to either males or females. PMID:26733781

Opioid dependence - management in general practice.

PubMed

Frei, Matthew

2010-08-01

Addiction to opioids, or opioid dependence, encompasses the biopsychosocial dysfunction seen in illicit heroin injectors, as well as aberrant behaviours in patients prescribed opioids for chronic nonmalignant pain. To outline the management of opioid dependence using opioid pharmacotherapy as part of a comprehensive chronic illness management strategy. The same principles and skills general practitioners employ in chronic illness management underpin the care of patients with opioid dependence. Opioid pharmacotherapy, with the substitution medications methadone and buprenorphine, is an effective management of opioid dependence. Training and regulatory requirements for prescribing opioid pharmacotherapies vary between jurisdictions, but this treatment should be within the scope of most Australian GPs.

Family burden in opioid dependence syndrome in tertiary care centre.

PubMed

Shyangwa, P M; Tripathi, B M; Lal, R

2008-01-01

This is a cross-sectional, hospital based study conducted in De-Addiction centre under department of psychiatry, AIIMS, New Delhi, India. Patients and their spouses fulfilling inclusion criteria were enrolled in the study after taking informed consent. A diagnosis of Opioid Dependence Syndrome (ODS) was made based on ICD-10 criteria and the assessment of severity of ODS was determined by Addiction Severity Index (Hindi version). Subsequently the family burden, perceived by spouses was assessed using Family Burden Interview Schedule (FBIS). Most of the subjects were from urban or semi-urban areas, mostly from around the service facility. The maximum number of subjects was of age group 31-40 years with majority of having below high school level education. Both subjective and objective family burden was perceived as "severe" by subjects' spouses. The relationship between spouses' perceived burden and socio-demographic variables including duration of substance abuse were not correlated. Hence it was found that opioid dependent subjects cause considerable amount of distress to their care providers.

Genetics Home Reference: opioid addiction

MedlinePlus

... disease that can cause major health, social, and economic problems. Opioids are a class of drugs that ... is likely that a combination of health, social, economic, and lifestyle factors interact with genetic factors to ...

Opioid Addiction

MedlinePlus

... breathing rate nausea, vomiting constipation physical agitation poor decision making abandoning responsibilities slurred speech sleeping more or less than normal mood swings euphoria (feeling high) irritability depression lowered motivation anxiety attacks. Symptoms of opioid overdose An overdose ...

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

The Prescription Opioid Addiction Treatment Study: What have we learned.

PubMed

Weiss, Roger D; Rao, Vinod

2017-04-01

The multi-site Prescription Opioid Addiction Treatment Study (POATS), conducted by the National Drug Abuse Treatment Clinical Trials Network, was the largest clinical trial yet conducted with patients dependent upon prescription opioids (N=653). In addition to main trial results, the study yielded numerous secondary analyses, and included a 3.5-year follow-up study, the first of its kind with this population. This paper reviews key findings from POATS and its follow-up study. The paper summarizes the POATS design, main outcomes, predictors of outcome, subgroup analyses, the predictive power of early treatment response, and the long-term follow-up study. POATS examined combinations of buprenorphine-naloxone of varying duration and counseling of varying intensity. The primary outcome analysis showed no overall benefit to adding drug counseling to buprenorphine-naloxone and weekly medical management. Only 7% of patients achieved a successful outcome (abstinence or near-abstinence from opioids) during a 4-week taper and 8-week follow-up; by comparison, 49% of patients achieved success while subsequently stabilized on buprenorphine-naloxone. Long-term follow-up results were more encouraging, with higher abstinence rates than in the main trial. Patients receiving opioid agonist treatment at the time of follow-up were more likely to have better outcomes, though a sizeable number of patients succeeded without agonist treatment. Some patients initiated risky use patterns, including heroin use and drug injection. A limitation of the long-term follow-up study was the low follow-up rate. POATS was the first large-scale study of the treatment of prescription opioid dependence; its findings can influence both treatment guidelines and future studies. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Continuous opioid treatment for chronic noncancer pain: a time for moderation in prescribing.

PubMed

Colameco, Stephen; Coren, Joshua S; Ciervo, Carman A

2009-07-01

Physicians have embraced the concept of long-term opioid treatment for chronic noncancer pain (CNCP), as evidenced by increased prescribing. Many patients have benefited from more liberal opioid prescribing, but many have not, and prescription opioid abuse has risen significantly coincident with increased prescribing. Because of the potentially serious adverse effects of opioids, physicians must balance potential benefits against risks, especially in individuals at risk for opioid misuse, abuse, or dependence. This article reviews long-term, continuous opioid treatment of CNCP, current treatment guidelines, addiction risk stratification, opioid-induced hyperalgesia, and endocrine dysfunction.

Maintenance Medication for Opiate Addiction: The Foundation of Recovery

PubMed Central

Bart, Gavin

2012-01-01

Illicit use of opiates is the fastest growing substance use problem in the United States and the main reason for seeking addiction treatment services for illicit drug use throughout the world. It is associated with significant morbidity and mortality related to HIV, hepatitis C, and overdose. Treatment for opiate addiction requires long-term management. Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use. Similarly poor results are seen with medication assisted detoxification. This article provides a topical review of the three medications approved by the FDA for long-term treatment of opiate dependence: the opioid agonist methadone, the opioid partial agonist buprenorphine, and the opioid antagonist naltrexone. Basic mechanisms of action and treatment outcomes are described for each medication. Results indicate that maintenance medication provides the best opportunity for patients to achieve recovery from opiate addiction. Extensive literature and systematic reviews show that maintenance treatment with either methadone or buprenorphine is associated with retention in treatment, reduction in illicit opiate use, decreased craving, and improved social function. Oral naltrexone is ineffective in treating opiate addiction but recent studies using extended release naltrexone injections have shown promise. While no direct comparisons between extended release naltrexone injections and either methadone or buprenorphine exist, indirect comparison of retention shows inferior outcome compared to methadone and buprenorphine. Further work is needed to compare directly each medication and determine individual factors that can assist in medication selection. Until such time, selection of medication should be based on informed choice following a discussion of outcomes, risks, and benefits of each medication. PMID:22873183

Hydromorphone Injection

MedlinePlus

... guidance if you think that you have an opioid addiction or call the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at ... if you are opioid tolerant (have been treated with certain doses of ...

Risk Evaluation and Mitigation Strategies (REMS) for extended-release and long-acting opioid analgesics: considerations for palliative care practice.

PubMed

Gudin, Jeffrey

2012-06-01

Prescription opioid analgesics are an essential treatment option for patients with moderate to severe pain. Over the last decade the increased medical use of these agents has contributed to a public health epidemic of abuse, addiction, and overdose-related deaths. These medications remain mainstays in both primary care and pain management practices. As palliative services are incorporated at earlier stages of the disease process and the number of individuals with chronic illness increases, palliative care specialists may encounter an increasing number of patients with opioid abuse and addiction problems. Extended-release (ER) and long-acting (LA) opioid formulations are administered to patients with moderate to severe chronic pain requiring around-the-clock analgesia. Given the large quantity of active ingredient contained within some dosage strengths, this medication class is associated with serious risks when taken improperly. In response to growing reports of abuse and overdose deaths, the US Food and Drug Administration (FDA) announced the need for a risk mitigation strategy for the entire class of medication. The class-wide Risk Evaluation and Mitigation Strategy (REMS) for ER/LA opioids will emphasize prescriber training and patient education to ensure that the therapeutic benefits outweigh the risks of addiction, unintentional overdose, and death. As primary care, pain management, and palliative care clinicians often encounter patients who require ER/LA opioids, an understanding of the suggested requirements and potential impact of this regulation is essential.

ER/LA Opioid Analgesics REMS: Overview of Ongoing Assessments of Its Progress and Its Impact on Health Outcomes.

PubMed

Cepeda, M Soledad; Coplan, Paul M; Kopper, Nathan W; Maziere, Jean-Yves; Wedin, Gregory P; Wallace, Laura E

2017-01-01

Opioid abuse is a serious public health concern. In response, the Food and Drug Administration (FDA) determined that a risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids was necessary to ensure that the benefits of these analgesics continue to outweigh the risks. Key components of the REMS are training for prescribers through accredited continuing education (CE), and providing patient educational materials. The impact of this REMS has been assessed using diverse metrics including evaluation of prescriber and patient understanding of the risks associated with opioids; patient receipt and comprehension of the medication guide and patient counseling document; patient satisfaction with access to opioids; drug utilization and changes in prescribing patterns; and surveillance of ER/LA opioid misuse, abuse, overdose, addiction, and death. The results of these assessments indicate that the increasing rates of opioid abuse, addiction, overdose, and death observed prior to implementation of the REMS have since leveled off or started to decline. However, these benefits cannot be attributed solely to the ER/LA opioid analgesics REMS since many other initiatives to prevent abuse occurred contemporaneously. These improvements occurred while preserving patient access to opioids as a large majority of patients surveyed expressed satisfaction with their access to opioids. © 2016 American Academy of Pain Medicine.

ER/LA Opioid Analgesics REMS: Overview of Ongoing Assessments of Its Progress and Its Impact on Health Outcomes

PubMed Central

Cepeda, M. Soledad; Kopper, Nathan W.; Maziere, Jean-Yves; Wedin, Gregory P.; Wallace, Laura E.

2017-01-01

Objective. Opioid abuse is a serious public health concern. In response, the Food and Drug Administration (FDA) determined that a risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids was necessary to ensure that the benefits of these analgesics continue to outweigh the risks. Key components of the REMS are training for prescribers through accredited continuing education (CE), and providing patient educational materials. Methods. The impact of this REMS has been assessed using diverse metrics including evaluation of prescriber and patient understanding of the risks associated with opioids; patient receipt and comprehension of the medication guide and patient counseling document; patient satisfaction with access to opioids; drug utilization and changes in prescribing patterns; and surveillance of ER/LA opioid misuse, abuse, overdose, addiction, and death. Results and Conclusions. The results of these assessments indicate that the increasing rates of opioid abuse, addiction, overdose, and death observed prior to implementation of the REMS have since leveled off or started to decline. However, these benefits cannot be attributed solely to the ER/LA opioid analgesics REMS since many other initiatives to prevent abuse occurred contemporaneously. These improvements occurred while preserving patient access to opioids as a large majority of patients surveyed expressed satisfaction with their access to opioids. PMID:27373304

Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study.

PubMed

Noller, Geoffrey E; Frampton, Chris M; Yazar-Klosinski, Berra

2018-01-01

The psychoactive indole alkaloid ibogaine has been associated with encouraging treatment outcomes for opioid dependence. The legal status of ibogaine in New Zealand provides a unique opportunity to evaluate durability of treatment outcomes. To examine longitudinal treatment effects over a 12-month period among individuals receiving legal ibogaine treatment for opioid dependence. This observational study measured addiction severity as the primary outcome in 14 participants (50% female) over 12 months post-treatment using the Addiction Severity Index-Lite (ASI-Lite) following a single ibogaine treatment by either of two treatment providers. Secondary effects on depression were assessed via the Beck Depression Inventory-II (BDI-II). The Subjective Opioid Withdrawal Scale (SOWS) was collected before and immediately after treatment to measure opioid withdrawal symptoms. Nonparametric comparisons via Friedman Test between baseline and 12-month follow-up for participants completing all interviews (n = 8) showed a significant reduction for the ASI-Lite drug use (p = 0.002) composite score. Reductions in BDI-II scores from baseline to 12-month follow-up were also significant (p < 0.001). Significant reductions in SOWS scores for all participants (n = 14) were also observed acutely after treatment (p = 0.015). Patients with partial data (n = 4) also showed reductions in ASI-Lite drug use scores and family/social status problems. One patient enrolled in the study died during treatment. A single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals as measured over 12 months. Ibogaine's legal availability in New Zealand may offer improved outcomes where legislation supports treatment providers to work closely with other health professionals.

Models of the Opiate System in Self-Injurious Behavior: A Reply.

ERIC Educational Resources Information Center

Demet, Edward M.; Sandman, Curt A.

1991-01-01

This paper answers criticism (EC 601 030) of the authors' work regarding opioid explanations of self-injurious behavior. Possible withdrawal effects are ruled out as an explanation, in favor of opioid excess leading to sensory depression and addiction to relative excesses of opioid activity in the brain. Alternative models of consequences of…

Pain Therapy Guided by Purpose and Perspective in Light of the Opioid Epidemic

PubMed Central

Severino, Amie L.; Shadfar, Arash; Hakimian, Joshua K.; Crane, Oliver; Singh, Ganeev; Heinzerling, Keith; Walwyn, Wendy M.

2018-01-01

Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses. Understanding the history of opioid drug development, the widespread marketing campaign for opioids, the immense financial incentive behind the treatment of pain, and vulnerable socioeconomic and physical demographics for opioid misuse give perspective on the current epidemic as an American-born problem that has expanded to global significance. In light of the current worldwide opioid epidemic, it is imperative that novel opioids are developed to treat pain without inducing the euphoria that fosters physical dependence and addiction. We describe insights from preclinical findings on the properties of opioid drugs that offer insights into improving abuse-deterrent formulations. One finding is that the ability of some agonists to activate one pathway over another, or agonist bias, can predict whether several novel opioid compounds bear promise in treating pain without causing reward among other off-target effects. In addition, we outline how the pharmacokinetic profile of each opioid contributes to their potential for misuse and discuss the emergence of mixed agonists as a promising pipeline of opioid-based analgesics. These insights from preclinical findings can be used to more effectively identify opioids that treat pain without causing physical dependence and subsequent opioid abuse. PMID:29740351

Opioid addiction and misuse in adult and adolescent patients with cancer.

PubMed

Pinkerton, Ross; Hardy, Janet R

2017-06-01

In the context of a therapeutic opioid epidemic, particularly in the USA, where increasingly stringent screening for 'at risk' individuals and close monitoring of opioid prescription and use is strongly recommended, the issue of misuse within the cancer population must be addressed. Most patients with advanced cancer will have pain requiring opioid therapy at some stage during their disease course. In the majority, this will provide good pain relief with no short- or longer-term adverse sequelae. A subset will present with substance misuse issues that will influence management and prescribing practice. The potential ethical issues of limiting effective analgesia on the basis of addiction risk or history must be acknowledged. Both a judgemental or 'relaxed' approach to such patients is problematic. Ignoring the situation will not be in the patient's best interest, but an undue focus on this aspect may damage therapeutic relationships with clinicians and adversely affect a holistic approach to care. Clinical practitioners must be aware of the risk factors for opioid misuse and in patients who are not under palliative care consider screening prior to commencing opioids. Clinicians must be able to manage and monitor those identified as having an opioid misuse problem. © 2017 Royal Australasian College of Physicians.

Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics.

PubMed

Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry; Luo, Yu

2016-08-01

The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC-derived human DA neurons are also examined. We present the first evidence suggesting that the 3' VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC-derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid-dependent iPSC cell lines. Our data suggest that human iPSC-derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

Substance Abuse and Addiction: Implications for Early Relationships and Interventions

ERIC Educational Resources Information Center

Suchman, Nancy E.; DeCoste, Cindy L.

2018-01-01

New developments in the treatment of mothers and infants affected by opioid addiction point to the promising effects of interventions that adopt a developmental perspective, occur concurrently with addiction treatment, and target the parent-infant relationship as early as possible. In this article, the authors provide general guidelines for…

Effectiveness of opioids in the treatment of chronic non-cancer pain.

PubMed

Trescot, Andrea M; Glaser, Scott E; Hansen, Hans; Benyamin, Ramsin; Patel, Samir; Manchikanti, Laxmaiah

2008-03-01

For thousands of years, opioids have been used to treat pain, and they continue to be one of the most commonly prescribed medications for pain. It is estimated that 90% of patients presenting to pain centers and receiving treatment in such facilities are on opioids. Opioids can be considered broad-spectrum analgesics that act at multiple points along the pain pathway. Unfortunately, opioids also have the potential for great harm, with multiple side effects and potential complications, some of which are lethal. They are also uniquely addictive, which can lead to misuse and diversion. We reviewed the relevant English literature and did thorough manual searches of the bibliographies of known primary and review articles. We utilized pain relief as the primary outcome measure. Other outcome measures were functional improvement, improvement of psychological status, improvement in work status, and evidence of addiction. Short-term use and improvement was defined as less than 6 months and long-term relief was defined as 6 months or longer. The 3 systematic reviews evaluating long-term effectiveness of opioids for chronic non-cancer pain provided unclear and weak evidence. The results of this review showed that many patients in the included studies were dissatisfied with adverse events or insufficient pain relief from opioids and withdrew from the studies. For patients able to continue on opioids, evidence was weak suggesting that their pain scores were lower than before therapy and that this relief could be maintained long-term (> 6 months). There was also weak evidence that long-term opioid therapy with morphine and transdermal fentanyl not only decreases pain but also improves functioning. Limited evidence was available for the most commonly used opioids, oxycodone and hydrocodone. Evidence for the ability to drive on chronic opioid therapy was moderate without major side effects or complications. It is concluded that, for long-term opioid therapy of 6 months or longer in managing chronic non-cancer pain, with improvement in function and reduction in pain, there is weak evidence for morphine and transdermal fentanyl. However, there is limited or lack of evidence for all other controlled substances, including the most commonly used drugs, oxycodone and hydrocodone.

Surgeon General Outlines Opioid Plan | NIH MedlinePlus the Magazine

MedlinePlus

... staff, Dr. Adams said the opioid epidemic is cutting too many American lives short. “Ninety-one Americans ... public health data and reporting Providing support for cutting-edge research on pain and addiction Advancing the ...

Faculty Development in Small-Group Teaching Skills Associated with a Training Course on Office-Based Treatment of Opioid Dependence

ERIC Educational Resources Information Center

Wong, Jeffrey G.; Holmboe, Eric S.; Becker, William C.; Fiellin, David A.; Jara, Gail B.; Martin, Judith

2005-01-01

The Drug Addiction Treatment Act of 2000 (DATA-2000) allows qualified physicians to treat opioid-dependent patients with schedule III-V medications, such as buprenorphine, in practices separate from licensed, accredited opioid treatment programs. Physicians may attain this qualification by completing 8-hours of training in treating opioid…

Skin β-endorphin mediates addiction to UV light.

PubMed

Fell, Gillian L; Robinson, Kathleen C; Mao, Jianren; Woolf, Clifford J; Fisher, David E

2014-06-19

UV light is an established carcinogen, yet evidence suggests that UV-seeking behavior has addictive features. Following UV exposure, epidermal keratinocytes synthesize proopiomelanocortin (POMC) that is processed to melanocyte-stimulating hormone, inducing tanning. We show that, in rodents, another POMC-derived peptide, β-endorphin, is coordinately synthesized in skin, elevating plasma levels after low-dose UV. Increases in pain-related thresholds are observed and reversed by pharmacologic opioid antagonism. Opioid blockade also elicits withdrawal signs after chronic UV exposure. This effect was sufficient to guide operant behavioral choices to avoidance of opioid withdrawal (conditioned place aversion). These UV-induced nociceptive and behavioral effects were absent in β-endorphin knockout mice and in mice lacking p53-mediated POMC induction in epidermal keratinocytes. Although primordial UV addiction, mediated by the hedonic action of β-endorphin and anhedonic effects of withdrawal, may theoretically have enhanced evolutionary vitamin D biosynthesis, it now may contribute to the relentless rise in skin cancer incidence in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Skin β-endorphin mediates addiction to ultraviolet light

PubMed Central

Fell, Gillian L.; Robinson, Kathleen C.; Mao, Jianren; Woolf, Clifford J.; Fisher, David E.

2014-01-01

SUMMARY Ultraviolet light is an established carcinogen yet evidence suggests that UV-seeking behavior has addictive features. Following UV exposure, epidermal keratinocytes synthesize Proopiomelanocortin that is processed to Melanocyte Stimulating Hormone, inducing tanning. We show that in rodents another POMC-derived peptide, β-endorphin, is coordinately synthesized in skin, elevating plasma levels after low-dose UV. Increases in pain-related thresholds are observed, and reversed by pharmacologic opioid antagonism. Opioid blockade also elicits withdrawal signs after chronic UV exposure. This effect was sufficient to guide operant behavioral choices to avoidance of opioid withdrawal (conditioned place aversion). These UV-induced nociceptive and behavioral effects were absent in β-endorphin knockout mice and in mice lacking p53-mediated POMC induction in epidermal keratinocytes. While primordial UV addiction, mediated by the hedonic action of β-endorphin and anhedonic effects of withdrawal, may theoretically have enhanced evolutionary vitamin D biosynthesis, it now may contribute to the relentless rise in skin cancer incidence in man. PMID:24949966

Physician Introduction to Opioids for Pain Among Patients with Opioid Dependence and Depressive Symptoms

PubMed Central

Tsui, Judith I.; Herman, Debra S.; Kettavong, Malyna; Alford, Daniel; Anderson, Bradley J.; Stein, Michael D.

2011-01-01

This study determined the frequency of reporting being introduced to opioids by a physician among opioid dependent patients. Cross-sectional analyses were performed using baseline data from a cohort of opioid addicts seeking treatment with buprenorphine. The primary outcome was response to the question: “Who introduced you to opiates?” Covariates included sociodemographics, depression, pain, current and prior substance use. Of 140 participants, 29% reported that they had been introduced to opioids by a physician. Of those who were introduced to opioids by a physician, all indicated that they had initially used opioids for pain, versus only 11% of those who did not report being introduced to opioids by a physician (p<0.01). There was no difference in current pain (78% vs. 85%, p=0.29), however participants who were introduced to opioids by a physician were more likely to have chronic pain (63% vs. 43%, p=0.04). A substantial proportion of individuals with opioid dependence seeking treatment may have been introduced to opioids by a physician. PMID:20727704

Long-Term Opioid Therapy Reconsidered

PubMed Central

Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A.; Chou, Roger

2012-01-01

In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment. PMID:21893626

Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain

PubMed Central

Olson, Keith M.; Lei, Wei; Keresztes, Attila; LaVigne, Justin; Streicher, John M.

2017-01-01

Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients. PMID:28356897

The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol

PubMed Central

2014-01-01

Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507. PMID:25239213

Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats.

PubMed

Wang, Xiao-Fei; Zhao, Tai-Yun; Su, Rui-Bin; Wu, Ning; Li, Jin

2016-12-01

Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

Genome-wide association study of therapeutic opioid dosing identifies a novel locus upstream of OPRM1

PubMed Central

Smith, Andrew H.; Jensen, Kevin P.; Li, Jin; Nunez, Yaira; Farrer, Lindsay A.; Hakonarson, Hakon; Cook-Sather, Scott D.; Kranzler, Henry R.; Gelernter, Joel

2017-01-01

Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the μ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time-consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study (GWAS) of usual daily methadone dose. In African-American (AA) OD subjects (n = 383), we identified a genome-wide significant association between therapeutic methadone dose (mean = 68.0 mg, standard deviation (SD) = 30.1 mg) and rs73568641 (P = 2.8 × 10−8), the nearest gene (306 kilobases) being OPRM1. Each minor (C) allele corresponded to an additional ~20 mg/day of oral methadone, an effect specific to AAs. In European-Americans (EAs) (n = 1,027), no genome-wide significant associations with methadone dose (mean = 77.8 mg, SD = 33.9 mg) were observed. In an independent set of opioid-naïve AA children being treated for surgical pain, rs73568641-C was associated with a higher required dose of morphine (n = 241, P = 3.9 × 10−2). Similarly, independent genomic loci previously shown to associate with higher opioid analgesic dose were associated with higher methadone dose in the OD sample (AA and EA: n = 1,410, genetic score P = 1.3 × 10−3). The present results in AAs indicate that genetic variants influencing opioid sensitivity across different clinical settings could contribute to precision pharmacotherapy for pain and addiction. PMID:28115739

Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone.

PubMed

Rosenthal, Richard N; Ling, Walter; Casadonte, Paul; Vocci, Frank; Bailey, Genie L; Kampman, Kyle; Patkar, Ashwin; Chavoustie, Steven; Blasey, Christine; Sigmon, Stacey; Beebe, Katherine L

2013-12-01

To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119). Twenty addiction treatment centers. Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence. The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)]. Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets. © 2013 Society for the Study of Addiction.

Opioid overdose and naloxone education in a substance use disorder treatment program.

PubMed

Lott, David C; Rhodes, Jonathan

2016-04-01

Opioid users in treatment are at high risk of relapse and overdose, making them an important target for efforts to reduce opioid overdose mortality. Overdose Education (OE) is one such intervention, and this study tests the effectiveness of OE in a community substance use disorder treatment program. Opioid users were recruited from a community treatment center for the study. The Opioid Overdose Knowledge Scale (OOKS) was administered before and after an educational intervention (small group lecture, slideshow, and handout based on previously published content) to assess knowledge of the risks, signs, and actions associated with opioid overdose, including use of naloxone. Additional survey questions assessed naloxone access, naloxone education, and overdose experiences at treatment and 3-month follow-up. Subjects (n = 43) were 28% female and had a mean age of 31 years. OOKS scores were compared at pre-intervention, post-intervention, and follow-up, and results were also compared with a historical non-intervention control group (n = 14). Total score on the OOKS increased significantly from pre- to post-education, and improvement was maintained at follow-up (p < .0001). OOKS subdomains of actions and naloxone use also had significant increases (p < .0001). Four subjects reported possessing naloxone in the past, and only one subject who did not already have naloxone at the time of treatment had obtained it at follow-up. Education about opioid overdose and naloxone use in a community treatment program increases overdose knowledge, providing support for the idea of making OE a routine part of substance use disorder treatment. However, the rate of follow through on accessing naloxone was low with this education-only intervention. © 2016 The Authors. The American Journal on Addictions Published by American Academy of Addiction Psychiatry.

A Combination of Buprenorphine and Naltrexone Blocks Compulsive Cocaine Intake in Rodents Without Producing Dependence

PubMed Central

Wee, Sunmee; Vendruscolo, Leandro F.; Misra, Kaushik K.; Schlosburg, Joel E.; Koob, George F.

2012-01-01

Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non–opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block κ agonist–induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction. PMID:22875830

A combination of buprenorphine and naltrexone blocks compulsive cocaine intake in rodents without producing dependence.

PubMed

Wee, Sunmee; Vendruscolo, Leandro F; Misra, Kaushik K; Schlosburg, Joel E; Koob, George F

2012-08-08

Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block κ agonist-induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction.

Which Classes of Prescription Drugs Are Commonly Misused?

MedlinePlus

... a part of addiction, but they are not equivalent. Addiction involves other changes to brain circuitry and ... physicians should assess pain and functioning, consider if non-opioid treatment options are appropriate, discuss a treatment ...

Impact of treatment for opioid dependence on fatal drug-related poisoning: a national cohort study in England.

PubMed

Pierce, Matthias; Bird, Sheila M; Hickman, Matthew; Marsden, John; Dunn, Graham; Jones, Andrew; Millar, Tim

2016-02-01

To compare the change in illicit opioid users' risk of fatal drug-related poisoning (DRP) associated with opioid agonist pharmacotherapy (OAP) and psychological support, and investigate the modifying effect of patient characteristics, criminal justice system (CJS) referral and treatment completion. National data linkage cohort study of the English National Drug Treatment Monitoring System and the Office for National Statistics national mortality database. Data were analysed using survival methods. All services in England that provide publicly funded, structured treatment for illicit opioid users. Adults treated for opioid dependence during April 2005 to March 2009: 151,983 individuals; 69% male; median age 32.6 with 442,950 person-years of observation. The outcome was fatal DRP occurring during periods in or out of treatment, with adjustment for age, gender, substances used, injecting status and CJS referral. There were 1499 DRP deaths [3.4 per 1000 person-years, 95% confidence interval (CI) = 3.2-3.6]. DRP risk increased while patients were not enrolled in any treatment [adjusted hazard ratio (aHR) = 1.73, 95% CI = 1.55-1.92]. Risk when enrolled only in a psychological intervention was double that during OAP (aHR = 2.07, 95% CI = 1.75-2.46). The increased risk when out of treatment was greater for men (aHR = 1.88, 95% CI = 1.67-2.12), illicit drug injectors (aHR = 2.27, 95% CI = 1.97-2.62) and those reporting problematic alcohol use (aHR = 2.37, 95% CI = 1.90-2.98). Patients who received only psychological support for opioid dependence in England appear to be at greater risk of fatal opioid poisoning than those who received opioid agonist pharmacotherapy. © 2015 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

What is addiction?

PubMed

Kranzler, Henry R; Li, Ting-Kai

2008-01-01

This issue of Alcohol Research & Health examines addiction to multiple substances--that is, combined dependence on alcohol and other drugs (AODs), including marijuana, cocaine, and opioids. It seems fitting, then, to begin the issue with a look at what constitutes "addiction." The Oxford English Dictionary (pp. 24-25) traces the term addiction to Roman law, under which addiction was a "formal giving over by sentence of court; hence, a dedication of person to a master." This notion of relinquishment of control by the addicted person is the central feature of many lay and professional definitions of the term. The study of addictive behavior crosses several disciplines, including, among others, behavioral neuroscience, epidemiology, genetics, molecular biology, pharmacology, psychology, psychiatry, and sociology. Articles in this issue examine aspects of AOD use disorders from the perspective of some of these varied disciplines.

Psychotropic drugs in opioid addicts on methadone treatment.

PubMed

Ferris, G N

1976-07-01

Psychotropic drug treatment of persons on methadone maintenance is discussed. Patients with clear target symptoms, such as anxiety, depression, or psychosis responded just as non-opioid addicts would to the major psychotropic agents. The minor tranquilizers are felt to be of doubtful value, and subject to abuse. Sleep disturbances cannot be treated by the usual means, as the drugs needed again are abused. However, chlorpromazine shows some promise here. Methods of drug delivery and goals of treatment must be adapted to the realities of this patient-group's characteristics, particularly anti-social traits, poor motivation and unreliability. Psychotropic drugs are unlikely to be of aid in multiple drug abusers, personality and character disorders, and opioid withdrawal. Four case histories are presented.

An update on the role of opioids in the management of chronic pain of nonmalignant origin.

PubMed

Højsted, Jette; Sjøgren, Per

2007-10-01

To summarize and reflect over primarily recent epidemiological and randomized controlled trials in opioid-treated chronic nonmalignant pain patients, focusing on effects, side effects, risks and long-term consequences of the treatment. In the western world opioids are increasingly being used for long-term treatment of chronic nonmalignant pain. While the long-term benefits of opioids regarding pain relief, functional capacity and health-related quality of life still remain to be proven, studies are emerging that describe serious long-term consequences such as addiction, opioid-induced hyperalgesia, cognitive disorders, and suppression of the immune and reproductive systems. Much more research is needed concerning long-time effects and consequences of opioid therapy in chronic nonmalignant pain patients; however, some clear warning signals have been sent out within recent years.

Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake

PubMed Central

Avena, Nicole M.; Rada, Pedro; Hoebel, Bartley G.

2008-01-01

The experimental question is whether or not sugar can be a substance of abuse and lead to a natural form of addiction. “Food addiction” seems plausible because brain pathways that evolved to respond to natural rewards are also activated by addictive drugs. Sugar is noteworthy as a substance that releases opioids and dopamine and thus might be expected to have addictive potential. This review summarizes evidence of sugar dependence in an animal model. Four components of addiction are analyzed. “Bingeing”, “withdrawal”, “craving” and cross-sensitization are each given operational definitions and demonstrated behaviorally with sugar bingeing as the reinforcer. These behaviors are then related to neurochemical changes in the brain that also occur with addictive drugs. Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin mRNA expression and dopamine and acetylcholine release in the nucleus accumbens. The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent. This may translate to some human conditions as suggested by the literature on eating disorders and obesity. PMID:17617461

Pharmacogenetic approaches to the treatment of alcohol addiction

PubMed Central

Heilig, Markus; Goldman, David; Berrettini, Wade; O’Brien, Charles P.

2012-01-01

Addictive disorders are partly heritable, chronic, relapsing conditions that account for a tremendous disease burden. Currently available addiction pharmacotherapies are only moderately successful, continue to be viewed with considerable scepticism outside the scientific community and have not become widely adopted as treatments. More effective medical treatments are needed to transform addiction treatment and address currently unmet medical needs. Emerging evidence from alcoholism research suggests that no single advance can be expected to fundamentally change treatment outcomes. Rather, studies of opioid, corticotropin-releasing factor, GABA and serotonin systems suggest that incremental advances in treatment outcomes will result from an improved understanding of the genetic heterogeneity among patients with alcohol addiction, and the development of personalized treatments. PMID:22011682

Prescription opioid misusing chronic pain patients exhibit dysregulated context-dependent associations: Investigating associative learning in addiction with the cue-primed reactivity task.

PubMed

Garland, Eric L; Bryan, Craig J; Kreighbaum, Lydia; Nakamura, Yoshio; Howard, Matthew O; Froeliger, Brett

2018-06-01

Associative learning undergirds the development of addiction, such that drug-related cues serve as conditioned stimuli to elicit drug-seeking responses. Plausibly, among opioid misusing chronic pain patients, pain-related information may serve as a conditioned stimulus to magnify opioid cue-elicited autonomic and craving responses through a process of second-order conditioning. We utilized a novel psychophysiological probe of pain-opioid conditioned associations, the Cue-Primed Reactivity (CPR) task. In this task, participants were presented with images as primes (200 ms) and cues (6000 ms) in pairs organized in four task blocks: "control-opioid," "pain-opioid," "control-pain," and "opioid-pain." Opioid-treated chronic pain patients (N = 30) recruited from an Army base in the Western United States were classified as opioid misusers (n = 17) or non-misusers (n = 13) via a validated cutpoint on the Prescription Drug Use Questionnaire (PDUQ; Compton et al., 2008). Opioid misuse status was examined as a predictor of HRV, craving, and mood responses on the CPR task. HRV increased to a greater extent during the pain-opioid block compared to the control-opioid block for non-misusers compared to misusers (p = .003, η 2 partial  = 0.27). In contrast, craving increased to a greater extent from baseline to the pain-opioid block for misusers than for non-misusers (p = .03, η 2 partial  = .16). Findings suggest that opioid-treated chronic pain patients exhibit Pavlovian conditioned responses to opioid cues strengthened by an associative learning process of second-order conditioning when primed by pain-related images. This pain-opioid contingency appears to become disrupted among individuals who engage in opioid misuse, such that opioid-related stimuli elicit motivational responses irrespective of pain-related contextual stimuli. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of drugs of abuse on the central neuropeptide Y system.

PubMed

Gonçalves, Joana; Martins, João; Baptista, Sofia; Ambrósio, António Francisco; Silva, Ana Paula

2016-07-01

Neuropeptide Y (NPY), which is widely expressed in the central nervous system is involved in several neuropathologies including addiction. Here we comprehensively and systematically review alterations on the central NPY system induced by several drugs. We report on the effects of psychostimulants [cocaine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and nicotine], ethanol, and opioids on NPY protein levels and expression of different NPY receptors. Overall, expression and function of NPY and its receptors are changed under conditions of drug exposure, thus affecting several physiologic behaviors, such as feeding, stress and anxiety. Drugs of abuse differentially affect the components of the NPY system. For example methamphetamine and nicotine lead to a consistent increase in NPY mRNA and protein levels in different brain sites whereas ethanol and opioids decrease NPY mRNA and protein expression. Drug-induced alterations on the different NPY receptors show more complex regulation pattern. Manipulation of the NPY system can have opposing effects on reinforcing and addictive properties of drugs of abuse. NPY can produce pro-addictive effects (nicotine and heroin), but can also exert inhibitory effects on addictive behavior (AMPH, ethanol). Furthermore, NPY can act as a neuroprotective agent in chronically methamphetamine and MDMA-treated rodents. In conclusion, manipulation of the NPY system seems to be a potential target to counteract neural alterations, addiction-related behaviors and cognitive deficits induced by these drugs. © 2015 Society for the Study of Addiction.

Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain.

PubMed

Shurman, Joseph; Koob, George F; Gutstein, Howard B

2010-07-01

Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek "katifeia" for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). Repeated engagement of opponent processes without time for the brain's emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

Effectiveness of Mindfulness-Based Group Therapy Compared to the Usual Opioid Dependence Treatment.

PubMed

Imani, Saeed; Atef Vahid, Mohammad Kazem; Gharraee, Banafsheh; Noroozi, Alireza; Habibi, Mojtaba; Bowen, Sarah

2015-06-01

This study investigated the effectiveness of mindfulness-based group therapy (MBGT) compared to the usual opioid dependence treatment (TAU).Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS) were randomly assigned into experimental (Mindfulness-Based Group Therapy) and control groups (the Usual Treatment).The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program. The Five Factor Mindfulness Questionnaire (FFMQ) and the Addiction Sevier Index (ASI) were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders.

Effectiveness of Mindfulness-Based Group Therapy Compared to the Usual Opioid Dependence Treatment

PubMed Central

Imani, Saeed; Atef Vahid, Mohammad Kazem; Gharraee, Banafsheh; Noroozi, Alireza; Habibi, Mojtaba; Bowen, Sarah

2015-01-01

Objective: This study investigated the effectiveness of mindfulness-based group therapy (MBGT) compared to the usual opioid dependence treatment (TAU).Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS) were randomly assigned into experimental (Mindfulness-Based Group Therapy) and control groups (the Usual Treatment).The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program. Methods: The Five Factor Mindfulness Questionnaire (FFMQ) and the Addiction Sevier Index (ASI) were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. Results: The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. Conclusion: The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders. PMID:26877751

Challenges in using opioids to treat pain in persons with substance use disorders.

PubMed

Savage, Seddon R; Kirsh, Kenneth L; Passik, Steven D

2008-06-01

Pain and substance abuse co-occur frequently, and each can make the other more difficult to treat. A knowledge of pain and its interrelationships with addiction enhances the addiction specialist's efficacy with many patients, both in the substance abuse setting and in collaboration with pain specialists. This article discusses the neurobiology and clinical presentation of pain and its synergies with substance use disorders, presents methodical approaches to the evaluation and treatment of pain that co-occurs with substance use disorders, and provides practical guidelines for the use of opioids to treat pain in individuals with histories of addiction. The authors consider that every pain complaint deserves careful investigation and every patient in pain has a right to effective treatment.

Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 versus D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

PubMed

Jing Li, Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

2018-05-09

Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward- or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally subthreshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II or extracellular signal-related kinase 1-2, following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. SIGNIFICANCE STATEMENT Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex (PFC), may differentially control acquisition or recall of fear memories and how these mechanisms might regulate sensitivity to the rewarding effects of opioids. We demonstrate that PFC D4 activation not only controls the salience of fear memory acquisition, but potentiates the rewarding effects of opioids. In contrast, PFC D1 receptor activation blocks recall of fear memories and prevents potentiation of opioid reward effects. Together, these findings demonstrate novel PFC mechanisms that may account for how emotional memory disturbances might increase the addictive liability of opioid-class drugs. Copyright © 2018 the authors 0270-6474/18/384543-13$15.00/0.

Financial factors and the implementation of medications for treating opioid use disorders.

PubMed

Knudsen, Hannah K; Roman, Paul M

2012-12-01

Despite the established effectiveness of pharmacotherapies for treating opioid use disorders, implementation of medications for addiction treatment (MAT) by specialty treatment programs is limited. This research examined relationships between organizational factors and the program-level implementation of MAT, with attention paid to specific sources of funding, organizational structure, and workforce resources. Face-to-face structured interviews were conducted in 2008 to 2009 with administrators of 154 community-based treatment programs affiliated with the National Institute on Drug Abuse's Clinical Trials Network; none of these programs exclusively dispensed methadone without offering other levels of care. Implementation of MAT was measured by summing the percentages of opioid patients receiving buprenorphine maintenance, methadone maintenance, and tablet naltrexone. Financial factors included the percentages of revenues received from Medicaid, private insurance, criminal justice, the Federal block grant, state government, and county government. Organizational structure and workforce characteristics were also measured. Implementation of MAT for opioid use disorders was low. Greater reliance on Medicaid was positively associated with implementation after controlling for organizational structure and workforce measures, whereas the association for reliance on criminal justice revenues was negative. The implementation of MAT for opioid use disorders by specialty addiction treatment programs may be facilitated by Medicaid but may be impeded by reliance on funding from the criminal justice system. These findings point to the need for additional research that considers the impact of organizational dependence on different types of funding on patterns of addiction treatment practice.

Zohydro approval by food and drug administration: controversial or frightening?

PubMed

Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

2014-01-01

The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health consequences, despite numerous regulations enforced by multiple organizations. The approval of Zohydro and its defense from the FDA were based on a misunderstanding of the prevalence of chronic severe disabling pain. Based on inaccurate data from the Institute of Medicine, in part caused by conflicts of interest, 100 million persons have been described to suffer from severe pain - the correct number is 22.6 million. This manuscript analyzes 3 important principles of drug approval and utilization based on safety, efficacy, and medical necessity. Based on the limited literature that the authors were able to review including that which was submitted to the FDA by the manufacturers, it appears the safety, efficacy, and medical necessity were not demonstrated. In fact, the study submitted to the FDA showed a 50% pain improvement in only 48% of the patients in the treatment group and 21% of the patients in the placebo group at 85 day follow-up. This is a statistically significant result but its clinical relevance is unknown. The FDA approval decision occurring against the backdrop of the advisory panel recommendation is concerning and may result in serious consequences in the future.

Opioid Dependence Treatment: Options In Pharmacotherapy

PubMed Central

Stotts, Angela L.; Dodrill, Carrie L.; Kosten, Thomas R.

2010-01-01

The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long term efficacy and patient discomfort remains a significant therapy challenge. Buprenorphine’s effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the US is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence, however, randomized clinical trials are needed. PMID:19538000

Opioid Attentional Bias and Cue-Elicited Craving Predict Future Risk of Prescription Opioid Misuse Among Chronic Pain Patients*

PubMed Central

Garland, Eric L.; Howard, Matthew O.

2014-01-01

Background Some chronic pain patients receiving long-term opioid analgesic pharmacotherapy are at risk for misusing opioids. Like other addictive behaviors, risk of opioid misuse may be signaled by an attentional bias (AB) towards drug-related cues. The purpose of this study was to examine opioid AB as a potential predictor of opioid misuse among chronic pain patients following behavioral treatment. Methods Chronic pain patients taking long-term opioid analgesics (N = 47) completed a dot probe task designed to assess opioid AB, as well as self-report measures of opioid misuse and pain severity, and then participated in behavioral treatment. Regression analyses examined opioid AB and cue-elicited craving as predictors of opioid misuse at 3-months posttreatment follow-up. Results Patients who scored high on a measure of opioid misuse risk following treatment exhibited significantly greater opioid AB scores than patients at low risk for opioid misuse. Opioid AB for 200 ms cues and cue-elicited craving significantly predicted opioid misuse risk 20 weeks later, even after controlling for pre-treatment opioid dependence diagnosis, opioid misuse, and pain severity (Model R2 = .50). Conclusion Biased initial attentional orienting to prescription opioid cues and cue-elicited craving may reliably signal future opioid misuse risk following treatment. These measures may therefore provide potential prognostic indicators of treatment outcome. PMID:25282309

Why is neuroimmunopharmacology crucial for the future of addiction research?

PubMed

Hutchinson, Mark R; Watkins, Linda R

2014-01-01

A major development in drug addiction research in recent years has been the discovery that immune signaling within the central nervous system contributes significantly to mesolimbic dopamine reward signaling induced by drugs of abuse, and hence is involved in the presentation of reward behaviors. Additionally, in the case of opioids, these hypotheses have advanced through to the discovery of the novel site of opioid action at the innate immune pattern recognition receptor Toll-like receptor 4 as the necessary triggering event that engages this reward facilitating central immune signaling. Thus, the hypothesis of major proinflammatory contributions to drug abuse was born. This review will examine these key discoveries, but also address several key lingering questions of how central immune signaling is able to contribute in this fashion to the pharmacodynamics of drugs of abuse. It is hoped that by combining the collective wisdom of neuroscience, immunology and pharmacology, into Neuroimmunopharmacology, we may more fully understanding the neuronal and immune complexities of how drugs of abuse, such as opioids, create their rewarding and addiction states. Such discoveries will point us in the direction such that one day soon we might successfully intervene to successfully treat drug addiction. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Opioid Epidemic: 7 Things Educators Need to Know

ERIC Educational Resources Information Center

Welsh, Justine W.; Rappaport, Nancy; Tretyak, Valeria

2018-01-01

Opioid abuse has become an epidemic in America and exposure to the drugs often begins in high school. This article shares some facts about opioid use and some signs and symptoms to look for in students who may be addicted to the drug. The authors also offer tips for educators on how to deal with the legal issues involved in assessing, reporting,…

"I'm not abusing or anything": patient-physician communication about opioid treatment in chronic pain.

PubMed

Matthias, Marianne S; Krebs, Erin E; Collins, Linda A; Bergman, Alicia A; Coffing, Jessica; Bair, Matthew J

2013-11-01

To characterize clinical communication about opioids through direct analysis of clinic visits and in-depth interviews with patients. This was a pilot study of 30 patients with chronic pain, who were audio-recorded in their primary care visits and interviewed after the visit about their pain care and relationship with their physicians. Emergent thematic analysis guided data interpretation. Uncertainties about opioid treatment for chronic pain, particularly addiction and misuse, play an important role in communicating about pain treatment. Three patterns of responding to uncertainty emerged in conversations between patients and physicians: reassurance, avoiding opioids, and gathering additional information. Results are interpreted within the framework of Problematic Integration theory. Although it is well-established that opioid treatment for chronic pain poses numerous uncertainties, little is known about how patients and their physicians navigate these uncertainties. This study illuminates ways in which patients and physicians face uncertainty communicatively and collaboratively. Acknowledging and confronting the uncertainties inherent in chronic opioid treatment are critical communication skills for patients taking opioids and their physicians. Many of the communication behaviors documented in this study may serve as a model for training patients and physicians to communicate effectively about opioids. Published by Elsevier Ireland Ltd.

A Heroin Addiction Severity-Associated Intronic Single Nucleotide Polymorphism Modulates Alternative Pre-mRNA Splicing of the μ Opioid Receptor Gene OPRM1 via hnRNPH Interactions

PubMed Central

Xu, Jin; Lu, Zhigang; Xu, Mingming; Pan, Ling; Deng, Yi; Xie, Xiaohu; Liu, Huifen; Ding, Shixiong; Hurd, Yasmin L.; Pasternak, Gavril W.; Klein, Robert J.; Cartegni, Luca

2014-01-01

Single nucleotide polymorphisms (SNPs) in the OPRM1 gene have been associated with vulnerability to opioid dependence. The current study identifies an association of an intronic SNP (rs9479757) with the severity of heroin addiction among Han-Chinese male heroin addicts. Individual SNP analysis and haplotype-based analysis with additional SNPs in the OPRM1 locus showed that mild heroin addiction was associated with the AG genotype, whereas severe heroin addiction was associated with the GG genotype. In vitro studies such as electrophoretic mobility shift assay, minigene, siRNA, and antisense morpholino oligonucleotide studies have identified heterogeneous nuclear ribonucleoprotein H (hnRNPH) as the major binding partner for the G-containing SNP site. The G-to-A transition weakens hnRNPH binding and facilitates exon 2 skipping, leading to altered expressions of OPRM1 splice-variant mRNAs and hMOR-1 proteins. Similar changes in splicing and hMOR-1 proteins were observed in human postmortem prefrontal cortex with the AG genotype of this SNP when compared with the GG genotype. Interestingly, the altered splicing led to an increase in hMOR-1 protein levels despite decreased hMOR-1 mRNA levels, which is likely contributed by a concurrent increase in single transmembrane domain variants that have a chaperone-like function on MOR-1 protein stability. Our studies delineate the role of this SNP as a modifier of OPRM1 alternative splicing via hnRNPH interactions, and suggest a functional link between an SNP-containing splicing modifier and the severity of heroin addiction. PMID:25122903

Opioid Receptors: Toward Separation of Analgesic from Undesirable Effects

PubMed Central

Law, P.Y.; Reggio, Patricia H.; Loh, H.H.

2013-01-01

The use of opioid analgesics for pain has always been hampered by their many side effects; in particular, the addictive liability associated with chronic use. Recently, attempts to develop analgesic agents with reduced side effects have targeted either the putative opioid receptor splice variants or the receptor heterooligomers. This review discusses the potential for receptor splice variant- and the hetero-oligomer-based discovery of new opioid analgesics. We also examine an alternative approach of using receptor mutants for pain management. Finally, we discuss the role of the biased agonism observed and the recently reported opioid receptor crystal structures in guiding the future development of opioid analgesics PMID:23598157

Long-term Use of Opioids for Complex Chronic Pain

PubMed Central

Von Korff, Michael R.

2014-01-01

Increased opioid prescribing for back pain and other chronic musculoskeletal pain conditions has been accompanied by dramatic increases in prescription opioid addiction and fatal overdose. Opioid-related risks appear to increase with dose. While short-term randomized trials of opioids for chronic pain have found modest analgesic benefits (a one-third reduction in pain intensity on average), the long-term safety and effectiveness of opioids for chronic musculoskeletal pain is unknown. Given the lack of large, long-term randomized trials, recent epidemiologic data suggests the need for caution when considering long-term use of opioids to manage chronic musculoskeletal pain, particularly at higher dosage levels. Principles for achieving more selective and cautious use of opioids for chronic musculoskeletal pain are proposed. PMID:24315147

Breaking the Silence and Other Prevention Lessons From the Opioid Epidemic.

PubMed

Terry, Paul E

2018-05-01

The goal of this editorial is to equip readers with opioid education resources that enable you to role model what it looks like to speak out about addiction. How are we doing as a profession speaking up about addiction? Stigma is commanded by a deep irony: where peer pressure is what likely keeps us quiet, peer support is what enables us to speak up. The "#MeToo" movement is an extraordinary example of the inertia needed to break open a taboo topic. From Hollywood celebrities to US women's gymnastics stars, it was clear that as more women spoke up about sexual harassment, well, the more women spoke out. As unnatural as it felt to talk about being harassed or abused, many simply acknowledged that it was the courage of their peers that helped them find their courage. Workplace supervisors have a front row seat for watching the epidemic and our role relates to what I consider the most straightforward definition of addiction: It is when "it" (i.e., alcohol, opioids, gambling) begins to cause problems.

The Opioid Epidemic: What Does it Mean for Nurses?

PubMed

Leahy, Laura G

2017-01-01

The United States is facing a major crisis with the current opioid epidemic. Tens of thousands of individuals are dying each year due to abuse and misuse of heroin and prescription opiate drugs. Nurses play an integral role in these aspects of health care and offer solutions by providing education; preventive measures; treatments, including medication-assisted treatments (MATs); and ongoing recovery options for individuals with opioid use disorders. Nurses provide education, issue prescriptions and dispense medications, and provide overall physical and mental health care to patients struggling with this "disease of the brain," and with the signing of the Comprehensive Addiction and Recovery Act, advanced practice RNs will soon be able to include MATs related to buprenorphine as part of their treatment plan. The current article explores the anatomy, physiology, and genetics of addiction and how they relate to the pharmacological MATs used to treat opioid use disorders. [Journal of Psychosocial Nursing and Mental Health Services, 55(1), 18-23.]. Copyright 2017, SLACK Incorporated.

Prescription opioid abuse, chronic pain, and primary care: a Co-occurring Disorders Clinic in the chronic disease model.

PubMed

Pade, Patricia A; Cardon, Karen E; Hoffman, Richard M; Geppert, Cynthia M A

2012-12-01

Abuse of opioids has become a public health crisis. The historic separation between the addiction and pain communities and a lack of training in medical education have made treatment difficult to provide, especially in primary care. The Co-occurring Disorders Clinic (COD) was established to treat patients with co-morbid chronic pain and addiction. This retrospective chart review reports results of a quality improvement project using buprenorphine/naloxone to treat co-occurring chronic non-cancer pain (CNCP) and opioid dependence in a primary care setting. Data were collected for 143 patients who were induced with buprenorphine/naloxone (BUP/NLX) between June 2009 and November 2011. Ninety-three patients (65%) continued to be maintained on the medication and seven completed treatment and were no longer taking any opioid (5%). Pain scores showed a modest, but statistically significant improvement on BUP/NLX, which was contrary to our expectations and may be an important factor in treatment retention for this challenging population. Published by Elsevier Inc.

American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use.

PubMed

Kampman, Kyle; Jarvis, Margaret

2015-01-01

The Centers for Disease Control have recently described opioid use and resultant deaths as an epidemic. At this point in time, treating this disease well with medication requires skill and time that are not generally available to primary care doctors in most practice models. Suboptimal treatment has likely contributed to expansion of the epidemic and concerns for unethical practices. At the same time, access to competent treatment is profoundly restricted because few physicians are willing and able to provide it. This "Practice Guideline" was developed to assist in the evaluation and treatment of opioid use disorder, and in the hope that, using this tool, more physicians will be able to provide effective treatment. Although there are existing guidelines for the treatment of opioid use disorder, none have included all of the medications used at present for its treatment. Moreover, few of the existing guidelines address the needs of special populations such as pregnant women, individuals with co-occurring psychiatric disorders, individuals with pain, adolescents, or individuals involved in the criminal justice system. This Practice Guideline was developed using the RAND Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Method (RAM) - a process that combines scientific evidence and clinical knowledge to determine the appropriateness of a set of clinical procedures. The RAM is a deliberate approach encompassing review of existing guidelines, literature reviews, appropriateness ratings, necessity reviews, and document development. For this project, American Society of Addiction Medicine selected an independent committee to oversee guideline development and to assist in writing. American Society of Addiction Medicine's Quality Improvement Council oversaw the selection process for the independent development committee. Recommendations included in the guideline encompass a broad range of topics, starting with the initial evaluation of the patient, the selection of medications, the use of all the approved medications for opioid use disorder, combining psychosocial treatment with medications, the treatment of special populations, and the use of naloxone for the treatment of opioid overdose. Topics needing further research were noted.

The effectiveness of opioid maintenance treatment in prison settings: a systematic review.

PubMed

Hedrich, Dagmar; Alves, Paula; Farrell, Michael; Stöver, Heino; Møller, Lars; Mayet, Soraya

2012-03-01

To review evidence on the effectiveness of opioid maintenance treatment (OMT) in prison and post-release. Systematic review of experimental and observational studies of prisoners receiving OMT regarding treatment retention, opioid use, risk behaviours, human immunodeficiency virus (HIV)/hepatitis C virus (HCV) incidence, criminality, re-incarceration and mortality. We searched electronic research databases, specialist journals and the EMCDDA library for relevant studies until January 2011. Review conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-one studies were identified: six experimental and 15 observational. OMT was associated significantly with reduced heroin use, injecting and syringe-sharing in prison if doses were adequate. Pre-release OMT was associated significantly with increased treatment entry and retention after release if arrangements existed to continue treatment. For other outcomes, associations with pre-release OMT were weaker. Four of five studies found post-release reductions in heroin use. Evidence regarding crime and re-incarceration was equivocal. There was insufficient evidence concerning HIV/HCV incidence. There was limited evidence that pre-release OMT reduces post-release mortality. Disruption of OMT continuity, especially due to brief periods of imprisonment, was associated with very significant increases in HCV incidence. Benefits of prison OMT are similar to those in community settings. OMT presents an opportunity to recruit problem opioid users into treatment, to reduce illicit opioid use and risk behaviours in prison and potentially minimize overdose risks on release. If liaison with community-based programmes exists, prison OMT facilitates continuity of treatment and longer-term benefits can be achieved. For prisoners in OMT before imprisonment, prison OMT provides treatment continuity. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Role of opioid receptors in the reinstatement of opioid-seeking behavior: an overview.

PubMed

Fattore, Liana; Fadda, Paola; Antinori, Silvia; Fratta, Walter

2015-01-01

Opioid abuse in humans is characterized by discontinuous periods of drug use and abstinence. With time, the probability of falling into renewed drug consumption becomes particularly high and constitutes a considerable problem in the management of heroin addicts. The major problem in the treatment of opioid dependence still remains the occurrence of relapse, to which stressful life events, renewed use of heroin, and exposure to drug-associated environmental cues are all positively correlated. To study the neurobiology of relapse, many research groups currently use the reinstatement animal model, which greatly contributed to disentangle the mechanisms underlying relapse to drug-seeking in laboratory animals. The use of this model is becoming increasingly popular worldwide, and new versions have been recently developed to better appreciate the differential contribution of each opioid receptor subtype to the relapse phenomenon. In this chapter we review the state of the art of our knowledge on the specific role of the opioid receptors as unrevealed by the reinstatement animal model of opioid-seeking behavior.

Chinese Herbal Medicine for the Treatment of Drug Addiction.

PubMed

Zhu, Weili; Zhang, Yinan; Huang, Yingjie; Lu, Lin

2017-01-01

This chapter summarizes recent developments in preclinical and clinical research on Chinese herbal medicines and their neurochemical mechanism of action for the treatment of drug addiction. We searched Chinese and English scientific literature and selected several kinds of Chinese herbal medicines that have beneficial effects on drug addiction. Ginseng (Renshen) may be clinically useful for the prevention of opioid abuse and dependence. Rhizoma Corydalis (Yanhusuo) may be used to prevent relapse to chronic drug dependence. Alkaloids of Uncaria rhynchophylla (Gouteng) appear to have positive effects on methamphetamine and ketamine addiction. Both Salvia miltiorrhiza (Danshen) and Radix Pueraiae (Gegen) have beneficial inhibitory effects on alcohol intake. Sinomenine has been shown to have preventive and curative effects on opioid dependence. l-Stepholidine, an alkaloid extract of the Chinese herb Stephania intermedia (Rulan), attenuated the acquisition, maintenance, and reacquisition of morphine-induced conditioned place preference and antagonized the heroin-induced reinstatement of heroin seeking. Traditional Chinese herbal medicines may be used to complement current treatments for drug addiction, including withdrawal and relapse. As the molecular mechanisms of action of traditional Chinese herbal medicines are elucidated, further advances in their use for the treatment of drug addiction are promising. © 2017 Elsevier Inc. All rights reserved.

Pain Control in the Presence of Drug Addiction.

PubMed

Vadivelu, Nalini; Lumermann, Leandro; Zhu, Richard; Kodumudi, Gopal; Elhassan, Amir O; Kaye, Alan David

2016-05-01

Drug addiction is present in a significant proportion of the population in the USA and worldwide. Drug addiction can occur with the abuse of many types of substances including cocaine, marijuana, stimulants, alcohol, opioids, and tranquilizers. There is a high likelihood that clinicians will encounter patients with substance abuse disorders on a regular basis with the prevalence of the use of illicit substances and the high rate of abuse of prescription drugs. The use of abuse deterrent formulations of prescription opioid agents, pill counts, and urine drug abuse screenings are all useful strategies. Optimum pain management of patients with addiction in the outpatient and inpatient setting is essential to minimize pain states. Careful selection of medications and appropriate oversight, including drug agreements, can reduce drug-induced impairments, including sleep deficits and diminished physical, social, and sexual functioning. This review, therefore, discusses the prevalence of illicit and prescription drug addiction, the challenges of achieving optimum pain control, and the therapeutic approaches to be considered in this challenging population. More research is warranted to develop improved therapies and routes of treatments for optimum pain relief and to prevent the development of central sensitization, chronic pain, and impaired physical and social functioning in patients with drug addiction.

Attentional bias for prescription opioid cues among opioid dependent chronic pain patients.

PubMed

Garland, Eric L; Froeliger, Brett E; Passik, Steven D; Howard, Matthew O

2013-12-01

Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioid-related cues. Opioid-dependent chronic pain patients (n = 32) and a comparison group of non-dependent opioid users with chronic pain (n = 33) completed a dot probe task designed to measure opioid AB. Participants also rated their opioid craving and self-reported arousal associated with opioid-related and neutral images, pain severity, and relief from pain treatments. Repeated-measures ANOVA revealed a significant group (opioid-dependent vs. non-dependent opioid user) × presentation duration (200. vs. 2,000 ms.) interaction, such that opioid-dependent individuals evidenced a significant AB towards opioid cues presented for 200 ms but not for cues presented for 2,000 ms, whereas non-dependent opioid users did not exhibit a significant mean AB at either stimulus duration. Among opioid-dependent individuals, 200 ms opioid AB was significantly associated with opioid craving, while among non-dependent opioid users, 200 ms opioid AB was significantly associated with relief from pain treatments. Furthermore, dependent and non-dependent opioid users experienced opioid cues as significantly more arousing than neutral cues. Opioid dependence among chronic pain patients appears to involve an automatic AB towards opioid-related cues. When coupled with chronic pain, attentional fixation on opioid cues may promote compulsive drug use and addictive behavior.

Sociodemographic profile and pattern of opioid abuse among patients presenting to a de-addiction centre in tertiary care Hospital of Kashmir

PubMed Central

Farhat, Samina; Hussain, Syed Sajad; Rather, Yasir Hassan; Hussain, Syed Karrar

2015-01-01

Background: The substances abuse has become one of the major public health problems of present society. Recently there has been an increase in the incidence of substance abuse including that of opioids throughout the world. The proper assessment of the current trends and pattern of opioid abuse can be helpful in more effective intervention of this menace. Materials and Methods: To find out various socio-demographic variables and pattern of opioid abuse, a predevised questionnaire was administered to 200 opioid patients who presented to de-addiction center for treatment. Results: Majority of the participants (75%) were of young age group (20–30 years) and the mean age of subjects was 27.6 years. More than half of participants (55%) were abusing the opioid substances for < 3 years followed by 30% of the abusers who were using the opioids for 4–6 years. Oral route was the most common route(35%)of substance administration followed by chasing(13%) and intravenous(11%) routes. Diverted pharmaceuticals emerged as one of the common substances of abuse, and peer pressure was found to be the main reason to start substance abuse. Conclusion: A comprehensive preventive program targeting young adults needs to be formulated and strict laws against sales of diverted pharmaceuticals to be implemented. PMID:26229346

The War on Drugs That Wasn't: Wasted Whiteness, “Dirty Doctors,” and Race in Media Coverage of Prescription Opioid Misuse

PubMed Central

Netherland, Julie; Hansen, Helena B.

2016-01-01

The past decade in the U.S. has been marked by a media fascination with the white prescription opioid cum heroin user. In this paper, we contrast media coverage of white non-medical opioid users with that of black and brown heroin users to show how divergent representations lead to different public and policy responses. A content analysis of 100 popular press articles from 2001 and 2011 in which half describe heroin users and half describe prescription opioid users revealed a consistent contrast between criminalized urban black and Latino heroin injectors with sympathetic portrayals of suburban white prescription opioid users. Media coverage of the suburban and rural opioid “epidemic” of the 2000s helped draw a symbolic, and then legal, distinction between (urban) heroin addiction and (suburban and rural) prescription opioid addiction that is reminiscent of the legal distinction between crack cocaine and powder cocaine of the 1980s and 90s. This distinction reinforces the racialized deployment of the War on Drugs and is sustained by the lack of explicit discussion of race in the service of “color blind ideology.” We suggest potential correctives to these racially divergent patterns, in the form of socially responsible media practices and of clinical engagement with public policy. PMID:27272904

DOE Office of Scientific and Technical Information (OSTI.GOV)

Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.

Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-inducedmore » increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.« less

Fatal poisoning in drug addicts in the Nordic countries in 2012.

PubMed

Simonsen, K Wiese; Edvardsen, H M E; Thelander, G; Ojanperä, I; Thordardottir, S; Andersen, L V; Kriikku, P; Vindenes, V; Christoffersen, D; Delaveris, G J M; Frost, J

2015-03-01

This report is a follow-up to a study on fatal poisoning in drug addicts conducted in 2012 by a Nordic working group. Here we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on sex, number of deaths, places of death, age, main intoxicants and other drugs detected in the blood were recorded. National data are presented and compared between the Nordic countries and with data from similar studies conducted in 1991, 1997, 2002 and 2007. The death rates (number of deaths per 100,000 inhabitants) increased in drug addicts in Finland, Iceland and Sweden but decreased in Norway compared to the rates in earlier studies. The death rate was stable in Denmark from 1991 to 2012. The death rate remained highest in Norway (5.79) followed by Denmark (5.19) and Iceland (5.16). The differences between the countries diminished compared to earlier studies, with death rates in Finland (4.61) and Sweden (4.17) approaching the levels in the other countries. Women accounted for 15-27% of the fatal poisonings. The median age of the deceased drug addicts was still highest in Denmark, and deaths of addicts >45 years old increased in all countries. Opioids remained the main cause of death, but medicinal opioids like methadone, buprenorphine, fentanyl and tramadol mainly replaced heroin. Methadone was the main intoxicant in Denmark and Sweden, whereas heroin/morphine caused the most deaths in Norway. Finland differed from the other Nordic countries in that buprenorphine was the main intoxicant with only a few heroin/morphine and methadone deaths. Deaths from methadone, buprenorphine and fentanyl increased immensely in Sweden compared to 2007. Poly-drug use was widespread in all countries. The median number of drugs per case varied from 4 to 5. Heroin/morphine, medicinal opioids, cocaine, amphetamines, benzodiazepines and alcohol were the main abused drugs. However, less widely used drugs, like gamma-hydroxybutyric acid (GHB), methylphenidate, fentanyl and pregabalin, appeared in all countries. New psychotropic substances emerged in all countries, with the largest selection, including MDPV, alpha-PVP and 5-IT, seen in Finland and Sweden. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Addiction and dependence in DSM-V.

PubMed

O'Brien, Charles

2011-05-01

As preparations for the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM) are under way, this paper focuses upon changes proposed for the substance use disorders section. It briefly outlines the history behind the current nomenclature, and the selection of the term 'dependence' over 'addiction' in earlier versions of the DSM. The term 'dependence', while used in past decades to refer to uncontrolled drug-seeking behavior, has an alternative meaning--the physiological adaptation that occurs when medications acting on the central nervous system are ingested with rebound when the medication is abruptly discontinued. These dual meanings have led to confusion and may have propagated current clinical practices related to under-treatment of pain, as physicians fear creating an 'addiction' by prescribing opioids. In part to address this problem, a change proposed for DSM-V is to alter the chapter name to 'Addiction and Related Disorders', which will include disordered gambling. The specific substance use disorders may be referred to as 'alcohol use' or 'opioid use' disorders. The criteria for the disorders are likely to remain similar, with the exception of removal of the 'committing illegal acts' criterion and addition of a 'craving' criterion. The other major change relates to the elimination of the abuse/dependence dichotomy, given the lack of data supporting an intermediate stage. These changes are anticipated to improve clarification and diagnosis and treatment of substance use and related disorders. © 2010 The Author, Addiction © 2010 Society for the Study of Addiction.

Attentional Bias For Prescription Opioid Cues Among Opioid Dependent Chronic Pain Patients

PubMed Central

Garland, Eric L.; Froeliger, Brett; Passik, Steven D.; Howard, Matthew O.

2012-01-01

Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioidrelated cues. Opioid-dependent chronic pain patients (n = 32) and a comparison group of non-dependent opioid users with chronic pain (n = 33) completed a dot probe task designed to measure opioid AB. Participants also rated their opioid craving and self-reported arousal associated with opioid-related and neutral images, pain severity, and relief from pain treatments. Repeated-measures ANOVA revealed a significant group (opioid-dependent vs. non-dependent opioid user) × presentation duration (200 ms. vs. 2000 ms.) interaction, such that opioid-dependent individuals evidenced a significant AB towards opioid cues presented for 200 ms but not for cues presented for 2000 ms, whereas non-dependent opioid users did not exhibit a significant mean AB at either stimulus duration. Among opioid-dependent individuals, 200 ms opioid AB was significantly associated with opioid craving, while among non-dependent opioid users, 200 ms opioid AB was significantly associated with relief from pain treatments. Furthermore, dependent and non-dependent opioid users experienced opioid cues as significantly more arousing than neutral cues. Opioid dependence among chronic pain patients appears to involve an automatic AB towards opioid-related cues. When coupled with chronic pain, attentional fixation on opioid cues may promote compulsive drug use and addictive behavior. PMID:22968666

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery.

PubMed

Savulich, G; Riccelli, R; Passamonti, L; Correia, M; Deakin, J F W; Elliott, R; Flechais, R S A; Lingford-Hughes, A R; McGonigle, J; Murphy, A; Nutt, D J; Orban, C; Paterson, L M; Reed, L J; Smith, D G; Suckling, J; Tait, R; Taylor, E M; Sahakian, B J; Robbins, T W; Ersche, K D

2017-03-07

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

PubMed Central

Savulich, G; Riccelli, R; Passamonti, L; Correia, M; Deakin, J F W; Elliott, R; Flechais, R S A; Lingford-Hughes, A R; McGonigle, J; Murphy, A; Nutt, D J; Orban, C; Paterson, L M; Reed, L J; Smith, D G; Suckling, J; Tait, R; Taylor, E M; Sahakian, B J; Robbins, T W; Ersche, K D

2017-01-01

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone. PMID:28267152

Extended vs Short-term Buprenorphine-Naloxone for Treatment of Opioid-Addicted Youth

PubMed Central

Woody, George E.; Poole, Sabrina A.; Subramaniam, Geetha; Dugosh, Karen; Bogenschutz, Michael; Abbott, Patrick; Patkar, Ashwin; Publicker, Mark; McCain, Karen; Potter, Jennifer Sharpe; Forman, Robert; Vetter, Victoria; McNicholas, Laura; Blaine, Jack; Lynch, Kevin G.; Fudala, Paul

2008-01-01

Context The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful. Objective To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth. Design, Setting, and Patients Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox). Interventions Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Main Outcome Measure Opioid-positive urine test result at weeks 4, 8, and 12. Results The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 ( χ22 = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; χ12 = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use ( χ12 = 18.45, P < .001), less injecting ( χ12 = 6.00, P = .01), and less nonstudy addiction treatment ( χ12 = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12. Conclusions Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence. PMID:18984887

Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial.

PubMed

Woody, George E; Poole, Sabrina A; Subramaniam, Geetha; Dugosh, Karen; Bogenschutz, Michael; Abbott, Patrick; Patkar, Ashwin; Publicker, Mark; McCain, Karen; Potter, Jennifer Sharpe; Forman, Robert; Vetter, Victoria; McNicholas, Laura; Blaine, Jack; Lynch, Kevin G; Fudala, Paul

2008-11-05

The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful. To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth. Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox). Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Opioid-positive urine test result at weeks 4, 8, and 12. The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; chi(2)(1) = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use (chi(2)(1) = 18.45, P < .001), less injecting (chi(2)(1) = 6.00, P = .01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12. Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence. clinicaltrials.gov Identifier: NCT00078130.

Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

PubMed

Hermann, Derik; Klages, Eckard; Welzel, Helga; Mann, Karl; Croissant, Bernhard

2005-06-01

Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

Characterizing Durations of Heroin Abstinence in the California Civil Addict Program: Results From a 33-Year Observational Cohort Study

PubMed Central

Nosyk, Bohdan; Anglin, M. Douglas; Brecht, Mary-Lynn; Lima, Viviane Dias; Hser, Yih-Ing

2013-01-01

In accordance with the chronic disease model of opioid dependence, cessation is often observed as a longitudinal process rather than a discrete endpoint. We aimed to characterize and identify predictors of periods of heroin abstinence in the natural history of recovery from opioid dependence. Data were collected on participants from California who were enrolled in the Civil Addict Program from 1962 onward by use of a natural history interview. Multivariate regression using proportional hazards frailty models was applied to identify independent predictors and correlates of repeated abstinence episode durations. Among 471 heroin-dependent males, 387 (82.2%) reported 932 abstinence episodes, 60.3% of which lasted at least 1 year. Multivariate analysis revealed several important findings. First, demographic factors such as age and ethnicity did not explain variation in durations of abstinence episodes. However, employment and lower drug use severity predicted longer episodes. Second, abstinence durations were longer following sustained treatment versus incarceration. Third, individuals with multiple abstinence episodes remained abstinent for longer durations in successive episodes. Finally, abstinence episodes initiated >10 and ≤20 years after first use lasted longer than others. Public policy facilitating engagement of opioid-dependent individuals in maintenance-oriented drug treatment and employment is recommended to achieve and sustain opioid abstinence. PMID:23445901

Opioid Addiction: Social Problems Associated and Implications of Both Current and Possible Future Treatments, including Polymeric Therapeutics for Giving Up the Habit of Opioid Consumption.

PubMed

Benéitez, M Cristina; Gil-Alegre, M Esther

2017-01-01

Detoxification programmes seek to implement the most secure and compassionate ways of withdrawing from opiates so that the inevitable withdrawal symptoms and other complications are minimized. Once detoxification has been achieved, the next stage is to enable the patient to overcome his or her drug addiction by ensuring consumption is permanently and completely abandoned, only after which can the subject be regarded as fully recovered. A systematic search on the common databases of relevant papers published until 2016 inclusive. Our study of the available oral treatments for opioid dependence has revealed that no current treatment can actually claim to be fully effective. These treatments require daily oral administration and, consequently, regular visits to dispensaries, which in most cases results in a lack of patient compliance, which causes fluctuations in drug plasma levels. We then reviewed alternative treatments in the available scientific literature on polymeric sustained release formulations. Research has been done not only on release systems for detoxification but also on release systems for giving up the habit of taking opioids. These efforts have obtained the recent authorization of polymeric systems for use in patients that could help them to reduce their craving for drugs.

A Multi-site, Two-Phase, Prescription Opioid Addiction Treatment Study (POATS): Rationale, Design, and Methodology

PubMed Central

Weiss, Roger D.; Potter, Jennifer Sharpe; Provost, Scott E.; Huang, Zhen; Jacobs, Petra; Hasson, Albert; Lindblad, Robert; Connery, Hilary Smith; Prather, Kristi; Ling, Walter

2010-01-01

The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age ≥18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study. PMID:20116457

A multi-site, two-phase, Prescription Opioid Addiction Treatment Study (POATS): rationale, design, and methodology.

PubMed

Weiss, Roger D; Potter, Jennifer Sharpe; Provost, Scott E; Huang, Zhen; Jacobs, Petra; Hasson, Albert; Lindblad, Robert; Connery, Hilary Smith; Prather, Kristi; Ling, Walter

2010-03-01

The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age > or =18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study. Copyright 2010 Elsevier Inc. All rights reserved.

Addiction as a Stress Surfeit Disorder

PubMed Central

Koob, George F.; Buck, Cara L.; Cohen, Ami; Edwards, Scott; Park, Paula E.; Schlosburg, Joel E.; Schmeichel, Brooke; Vendruscolo, Leandro F.; Wade, Carrie L.; Whitfield, Timothy W.; George, Olivier

2013-01-01

Drug addiction has been conceptualized as a chronically relapsing disorder of compulsive drug seeking and taking that progresses through three stages: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from positive reinforcement (binge/intoxication stage) to negative reinforcement (withdrawal/negative affect stage). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. Our hypothesis is that the negative emotional state that drives such negative reinforcement is derived from dysregulation of key neurochemical elements involved in the brain stress systems within the frontal cortex, ventral striatum, and extended amygdala. Specific neurochemical elements in these structures include not only recruitment of the classic stress axis mediated by corticotropin-releasing factor (CRF) in the extended amygdala as previously hypothesized but also recruitment of dynorphin-κ opioid aversive systems in the ventral striatum and extended amygdala. Additionally, we hypothesized that these brain stress systems may be engaged in the frontal cortex early in the addiction process. Excessive drug taking engages activation of CRF not only in the extended amygdala, accompanied by anxiety-like states, but also in the medial prefrontal cortex, accompanied by deficits in executive function that may facilitate the transition to compulsive-like responding. Excessive activation of the nucleus accumbens via the release of mesocorticolimbic dopamine or activation of opioid receptors has long been hypothesized to subsequently activate the dynorphin-κ opioid system, which in turn can decrease dopaminergic activity in the mesocorticolimbic dopamine system. Blockade of the κ opioid system can also block anxiety-like and reward deficits associated with withdrawal from drugs of abuse and block the development of compulsive-like responding during extended access to drugs of abuse, suggesting another powerful brain stress/anti-reward system that contributes to compulsive drug seeking. Thus, brain stress response systems are hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the development and persistence of addiction. The recruitment of anti-reward systems provides a powerful neurochemical basis for the negative emotional states that are responsible for the dark side of addiction. PMID:23747571

Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study.

PubMed

Uyei, Jennifer; Fiellin, David A; Buchelli, Marianne; Rodriguez-Santana, Ramon; Braithwaite, R Scott

2017-03-01

In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a willingness-to-pay threshold of $100 000. In probabilistic sensitivity analysis, the combination of naloxone distribution, PrEP, and linkage to addiction treatment was the optimal strategy in 37% of iterations and the combination of naloxone distribution and linkage to addiction treatment was the optimal strategy in 34% of iterations. Naloxone distribution through syringe service programmes is cost-effective compared with syringe distribution alone, but when combined with linkage to addiction treatment is cost saving compared with no additional services. A strategy that combines naloxone distribution, PrEP, and linkage to addiction treatment results in greater health benefits in people who inject drugs and is also cost-effective. State of Connecticut Department of Public Health and the National Institute of Mental Health. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Combined Interactions with I1-, I2-Imidazoline Binding Sites and α2-Adrenoceptors To Manage Opioid Addiction

PubMed Central

2016-01-01

Tolerance and dependence associated with chronic opioid exposure result from molecular, cellular, and neural network adaptations. Such adaptations concern opioid and nonopioid systems, including α2-adrenoceptors (α2-ARs) and I1- and I2-imidazoline binding sites (IBS). Agmatine, one of the hypothesized endogenous ligands of IBS, targeting several systems including α2-ARs and IBS, proved to be able to regulate opioid-induced analgesia and to attenuate the development of tolerance and dependence. Interested in the complex pharmacological profile of agmatine and considering the nature of its targets, we evaluated two series of imidazolines, rationally designed to simultaneously interact with I1-/I2-IBS or I1-/I2-IBS/α2-ARs. The compounds showing the highest affinities for I1-/I2-IBS or I1-/I2-IBS/α2-ARs have been selected for their in vivo evaluation on opiate withdrawal syndrome. Interestingly, 9, displaying I1-/I2-IBS/α2-ARs interaction profile, appears more effective in reducing expression and acquisition of morphine dependence and, therefore, might be considered a promising tool in managing opioid addiction. PMID:27774136

Vermont responds to its opioid crisis.

PubMed

Simpatico, Thomas A

2015-11-01

Vermont is one of the more forward-thinking states in the nation with a history of taking groundbreaking approaches to complex social issues. In his Jan 8, 2014 State of the State Address, Vermont Governor Peter Shumlin announced that Vermont was in the midst of an opioid addiction epidemic. Though Vermont had called attention to its opioid crisis, it soon became clear that many other states shared this problem. Economic modeling of expanded access to maintenance therapy with either methadone or buprenorphine is felt to have "high value" because the added health care costs of treatment are offset by reductions in other health care costs that occur when individuals with opioid dependence begin treatment. Moreover, when broader societal costs such as criminal activity and work productivity are included, maintenance treatment is estimated to produce substantial overall savings. Coordinated efforts between the Vermont Department of Health's Division of Alcohol and Drug Abuse Programs (ADAP) and the Department of Vermont Health Access (DVHA-Vermont Medicaid Authority) have resulted in the creation of the Care Alliance for Opioid Addiction (or Hub & Spoke model). Vermont intends to develop a reproducible and exportable model based on cost effective, outcomes driven public policy. Copyright © 2015 Elsevier Inc. All rights reserved.

A systematic review of opioid use after extremity trauma in orthopedic surgery.

PubMed

Koehler, Rikki M; Okoroafor, Ugochi C; Cannada, Lisa K

2018-06-01

The United States is in a prescription opioid crisis. Orthopedic surgeons prescribe more opioid narcotics than any other surgical specialty. The purpose of this study was to evaluate the state of opioid use after extremity trauma in orthopedic surgery. A computerized literature search of PubMed/MEDLINE was conducted to evaluate the status of opioids after extremity fractures. Six articles were identified and included in the review. Patients who consume more opioids communicate greater pain intensity and less satisfaction with pain control. Intraoperative multimodal drug injection and nerve blockade are viable alternatives for postoperative pain control and can help decrease systemic opioid use. Orthopedic surgeons are overprescribing opioids. Compared to other countries, the United States consumes more opioids with no better satisfaction with pain control. Orthopedic trauma surgeons should tailor their postoperative opioid prescriptions to the individual patient and utilize alternative options in order to control postoperative pain. Patients should be counseled regarding narcotic addiction and dependence. Patients unable to manage pain postoperatively should be followed closely and receive the proper chronic pain management, mental and social health services referrals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Personality Disorders Classification and Symptoms in Cocaine and Opioid Addicts.

ERIC Educational Resources Information Center

Malow, Robert M.; And Others

1989-01-01

Examined extent to which personality disorders and associated symptom criteria were found among 117 cocaine- and opioid-dependent men in drug dependence treatment unit. Drug groups were distinguished by higher rates of antisocial and borderline symptomatology rather than by features associated with other personality disorders. Different…

The Crisis in Our Neighborhood.

PubMed

Bitterman, Jason

2018-02-01

This comic represents various clinical and ethical dimensions of the skyrocketing incidence of opioid overdose. The comic also seeks to represent the humanity of patients struggling with addiction and to highlight the importance of clinicians' roles in helping mitigate the harms of opioid dependence. © 2018 American Medical Association. All Rights Reserved.

Attitudes of Medical Students Regarding Cancer Pain Management: Comparison Between Pre- and Post-Lecture Test Findings.

PubMed

Nimmaanrat, Sasikaan; Oofuvong, Maliwan

2015-01-01

Medical practitioners' attitudes have a significant impact on quality of care for cancer pain patients. This study was conducted to determine if being given a lecture concerning cancer pain and its management could improve the attitudes of medical students. A comparative study was conducted in 126 fifth-year medical students. Each student completed a pretest consisting of 3 questions about attitudes toward the optimal use of analgesics and 5 questions about attitudes toward prescribing opioids. Then they were given a 1.5-hour lecture, immediately following which they completed a post-test with the same questions. Analysis with either comparison between groups or by matching, the post-test showed significantly more positive attitudes (p<0.05) of the medical students in all 3 questions about optimal use of analgesics and 4 out of 5 questions about prescription of opioids. The post-test results showed significantly more negative attitudes concerning the most appropriate stage for patients with severe pain to receive maximal doses of analgesics. Conservative attitudes, especially concerns about addiction, have been associated with a reluctance in many physicians to prescribe opioids. This study found that cancer pain education can help to improve medical student attitudes. However, fear of addiction and tolerance was still evident so emphasis of this particular issue during a lecture is essential. Providing appropriate information by means of a lecture can improve the attitudes of medical students regarding cancer pain management. However, more information should be given to lessen fear of addiction and tolerance.

The North American Opiate Medication Initiative (NAOMI): Profile of Participants in North America’s First Trial of Heroin-Assisted Treatment

PubMed Central

Nosyk, Bohdan; Brissette, Suzanne; Chettiar, Jill; Schneeberger, Pascal; Marsh, David C.; Krausz, Michael; Anis, Aslam; Schechter, Martin T.

2008-01-01

The North American Opiate Medication Initiative (NAOMI) is a randomized controlled trial evaluating the feasibility and effectiveness of heroin-assisted treatment (HAT) in the Canadian context. Our objective is to analyze the profile of the NAOMI participant cohort in the context of illicit opioid use in Canada and to evaluate its comparability with patient profiles of European HAT studies. Recruitment began in February 2005 and ended in March 2007. Inclusion criteria included opioid dependence, 5 or more years of opioid use, regular opioid injection, and at least two previous opiate addiction treatment attempts. Standardized assessment instruments such as the European Addiction Severity Index and the Maudsley Addiction Profile were employed. A total of 251 individuals were randomized from Vancouver, BC (192, 76.5%), and Montreal, Quebec (59, 23.5%); 38.5% were female, the mean age was 39.7 years (SD:8.6), and participants had injected drugs for 16.5 years (SD:9.9), on average. In the prior month, heroin was used a mean of 26.5 days (SD:7.4) and cocaine 16 days (SD;12.6). Vancouver had significantly more patients residing in unstable housing (88.5 vs. 22%; p < 0.001) and higher use of smoked crack cocaine (16.9 days vs. 2.3 days in the prior month; p < 0.001), while a significantly higher proportion of Montreal participants reported needle sharing in the prior 6 months (25% vs. 3.7%; p < 0.001). In many respects, the patient cohort was similar to the European trials; however, NAOMI had a higher proportion of female participants and participants residing in unstable housing. This study suggests that the NAOMI study successfully recruited participants with a profile indicated for HAT. It also raises concern about the high levels of crack cocaine use and social marginalization. PMID:18758964

An inevitable wave of prescription drug monitoring programs in the context of prescription opioids: pros, cons and tensions.

PubMed

Islam, M Mofizul; McRae, Ian S

2014-08-16

In an effort to control non-medical use and/or medical abuse of prescription drugs, particularly prescription opioids, electronic prescription drug monitoring programs (PDMP) have been introduced in North-American countries, Australia and some parts of Europe. Paradoxically, there are simultaneous pressures to increase opioid prescribing for the benefit of individual patients and to reduce it for the sake of public health, and this pressure warrants a delicate balance of appropriate therapeutic uses of these drugs with the risk of developing dependence. This article discusses pros and cons of PDMP in reducing diversion of prescription opioids, without hampering access to those medications for those with genuine needs, and highlights tensions around PDMP implementation. PDMPs may help alleviate diversion, over-prescription and fraudulent prescribing/dispensing; prompt drug treatment referrals; avoid awkward drug urine test; and inform spatial changes in prescribing practices and help designing tailored interventions. Fear of legal retribution, privacy and data security, potential confusion about addiction and pseudo-addiction, and potential undue pressure of detecting misuse/diversion - are the major problems. There are tensions about unintended consequence of excessive regulatory enforcements, corresponding collateral damages particularly about inadequate prescribing for patients with genuine needs, and mandatory consultation requirements of PDMP. In this era of information technology PDMP is likely to flourish and remain with us for a long time. A clear standard of practice against which physicians' care will be judged may expedite the utilisation of PDMP. In addition, adequate training on addiction and pain management along with public awareness, point-of-supply data entry from pharmacy, point-of-care real-time access to data, increasing access to addiction treatment and appropriate regulatory enforcement preferably through healthcare administration, together, may help remove barriers to PDMP use.

An inevitable wave of prescription drug monitoring programs in the context of prescription opioids: pros, cons and tensions

PubMed Central

2014-01-01

Background In an effort to control non-medical use and/or medical abuse of prescription drugs, particularly prescription opioids, electronic prescription drug monitoring programs (PDMP) have been introduced in North-American countries, Australia and some parts of Europe. Paradoxically, there are simultaneous pressures to increase opioid prescribing for the benefit of individual patients and to reduce it for the sake of public health, and this pressure warrants a delicate balance of appropriate therapeutic uses of these drugs with the risk of developing dependence. This article discusses pros and cons of PDMP in reducing diversion of prescription opioids, without hampering access to those medications for those with genuine needs, and highlights tensions around PDMP implementation. Discussion PDMPs may help alleviate diversion, over-prescription and fraudulent prescribing/dispensing; prompt drug treatment referrals; avoid awkward drug urine test; and inform spatial changes in prescribing practices and help designing tailored interventions. Fear of legal retribution, privacy and data security, potential confusion about addiction and pseudo-addiction, and potential undue pressure of detecting misuse/diversion - are the major problems. There are tensions about unintended consequence of excessive regulatory enforcements, corresponding collateral damages particularly about inadequate prescribing for patients with genuine needs, and mandatory consultation requirements of PDMP. Summary In this era of information technology PDMP is likely to flourish and remain with us for a long time. A clear standard of practice against which physicians’ care will be judged may expedite the utilisation of PDMP. In addition, adequate training on addiction and pain management along with public awareness, point-of-supply data entry from pharmacy, point-of-care real-time access to data, increasing access to addiction treatment and appropriate regulatory enforcement preferably through healthcare administration, together, may help remove barriers to PDMP use. PMID:25127880

Temporal effect of manipulating NeuroD1 expression with the synthetic small molecule KHS101 on morphine contextual memory.

PubMed

Zhang, Yue; Kibaly, Cherkaouia; Xu, Chi; Loh, Horace H; Law, Ping-Yee

2017-11-01

The treatment of opioid addiction is challenging because addicts are highly prone to relapse when the memory of the former drug experience is triggered by emotional or environmental cues. An emerging and promising concept in addiction biology is that by manipulating adult hippocampal neurogenesis, a phenomenon involved in learning and memory, drug reward-like behaviors and relapse can be attenuated. We tested a new synthetic compound, KHS101, in an animal model of drug-associated contextual memory. KHS101 has been reported to increase the expression of neurogenic differentiation 1 (NeuroD1), a transcription factor involved in adult neurogenesis, and to specifically induce neuronal differentiation both in vitro and in vivo. Our results indicated that the subcutaneous injection of 3 mg/kg KHS101 for 7 days before conditioned place preference (CPP) training prolonged CPP extinction, while the same treatment after training accelerated extinction. This effect paralleled that observed following temporally controlled, tetracycline-induced NeuroD1 overexpression. Furthermore, the effect of KHS101 may occur via its induction of NeuroD1 expression as demonstrated by the abolition of the KHS101-mediated modulation of morphine-induced CPP extinction after the stereotaxic injection of lentiviral NeuroD1 small interfering RNA into the dentate gyrus (DG) of the hippocampus. These results suggest that the KHS101-mediated modulation of neurogenesis at a critical stage of the conditioning or the extinction of an opioid-associated experience may disrupt the memory trace of the existing opioid-associated experience to facilitate the extinction of drug-associated contextual memory. This implies that KHS101 has therapeutic potential for the treatment of opioid addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Commonly Carried Genetic Variant in the Delta Opioid Receptor Gene, OPRD1, is Associated with Smaller Regional Brain Volumes: Replication in Elderly and Young Populations

PubMed Central

Roussotte, Florence F.; Jahanshad, Neda; Hibar, Derrek P.; Sowell, Elizabeth R.; Kohannim, Omid; Barysheva, Marina; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Montgomery, Grant W.; Martin, Nicholas G.; Wright, Margaret J.; Toga, Arthur W.; Jack, Clifford R.; Weiner, Michael W.; Thompson, Paul M.

2014-01-01

Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer’s Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single-nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders. PMID:23427138

Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy.

PubMed

Sehgal, Nalini; Colson, James; Smith, Howard S

2013-11-01

Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

Mindfulness meditation-based pain relief: a mechanistic account.

PubMed

Zeidan, Fadel; Vago, David R

2016-06-01

Pain is a multidimensional experience that involves interacting sensory, cognitive, and affective factors, rendering the treatment of chronic pain challenging and financially burdensome. Further, the widespread use of opioids to treat chronic pain has led to an opioid epidemic characterized by exponential growth in opioid misuse and addiction. The staggering statistics related to opioid use highlight the importance of developing, testing, and validating fast-acting nonpharmacological approaches to treat pain. Mindfulness meditation is a technique that has been found to significantly reduce pain in experimental and clinical settings. The present review delineates findings from recent studies demonstrating that mindfulness meditation significantly attenuates pain through multiple, unique mechanisms-an important consideration for the millions of chronic pain patients seeking narcotic-free, self-facilitated pain therapy. © 2016 New York Academy of Sciences.

Mindfulness meditation–based pain relief: a mechanistic account

PubMed Central

Zeidan, Fadel; Vago, David

2016-01-01

Pain is a multidimensional experience that involves sensory, cognitive, and affective factors. The constellation of interactions between these factors renders the treatment of chronic pain challenging and financially burdensome. Further, the widespread use of opioids to treat chronic pain has led to an opioid epidemic characterized by exponential growth in opioid misuse and addiction. The staggering statistics related to opioid use highlight the importance of developing, testing, and validating fast-acting nonpharmacological approaches to treat pain. Mindfulness meditation is a technique that has been found to significantly reduce pain in experimental and clinical settings. The present review delineates findings from recent studies demonstrating that mindfulness meditation significantly attenuates pain through multiple, unique mechanisms—an important consideration for the millions of chronic pain patients seeking narcotic-free, self-facilitated pain therapy. PMID:27398643

[Pain and opioid dependency as multilevel network phenomenon : Theoretical and metatheoretical aspects].

PubMed

Tretter, F

2016-08-01

Methodological reflections on pain research and pain therapy focussing on addiction risks are addressed in this article. Starting from the incompleteness of objectification of the purely subjectively fully understandable phenomena of pain and addiction, the relevance of a comprehensive general psychology is underlined. It is shown that that reduction of pain and addiction to a mainly focally arguing neurobiology is only possible if both disciplines have a systemic concept of pain and addiction. With this aim, parallelized conceptual network models are presented.

Opioid addiction, diversion, and abuse in chronic and cancer pain.

PubMed

Kata, Vijay; Novitch, Matthew B; Jones, Mark R; Anyama, Best O; Helander, Erik M; Kaye, Alan D

2018-06-01

The primary cause of overdose death in the United States is related to pharmaceutical opioids. A few particular populations that struggle with adverse outcomes related to opioid abuse are those in palliative care, those with chronic pain, and those receiving pain treatments secondary to cancer or chemotherapy. There have been massive efforts to decrease the use of opioid abuse in patient care in a gestalt manner, but palliative care provides unique challenges in applying these reduction tactics used by other specialties. We explore behavioral interventions, provider education, alternative pain management techniques, postmarketing surveillance, and abuse-deterrent formulas as emerging methods to counteract opioid abuse in these populations.

The effect of state laws designed to prevent nonmedical prescription opioid use on overdose deaths and treatment.

PubMed

Popovici, Ioana; Maclean, Johanna Catherine; Hijazi, Bushra; Radakrishnan, Sharmini

2018-02-01

Nonmedical use of prescription opioids has reached epidemic levels in the United States and globally. In response, federal, state, and local governments are taking actions to address substantial increases in prescription opioid addiction and its associated harms. This study examines the effect of two state laws specifically designed to curtail access to prescription opioids to nonmedical users: pain management clinic and doctor shopping laws. We use administrative data on overdose deaths and admissions to specialty substance use disorder treatment coupled with a differences-in-differences design. Our findings suggest that both pain management clinic and doctor shopping laws have the potential to reduce prescription opioid overdose deaths. Moreover, doctor shopping laws appear to reduce prescription opioid treatment admissions. As many states have adopted these laws in recent years, the full effects of the laws may not yet be realized. Future research using more postlaw passage data should reevaluate the effectiveness of these laws. Copyright © 2017 John Wiley & Sons, Ltd.

Attitudes and Beliefs of Working and Work-Disabled People with Chronic Pain Prescribed Long-Term Opioids.

PubMed

Robinson, James P; Dansie, Elizabeth J; Wilson, Hilary D; Rapp, Suzanne; Turk, Dennis C

2015-07-01

This study was designed to gain insight into the apparent contradiction between the perspectives of researchers and policy makers, who have questioned the efficacy and safety of chronic opioid therapy for non-cancer pain patients, and the patients themselves, who often indicate that the therapy has value. A convenience sample of 54 patients on chronic opioid therapy was studied. Participants completed a questionnaire specifically designed for the study, and also several standard instruments that addressed functional interference, emotional functioning, and possible misuse of opioids. Their treating physicians rated the participants on the severity of their disability and the success of their opioid therapy. Although participants reported significant ongoing pain, they gave positive global ratings to their opioid therapy, and reported little concern about addiction or side effects of opioids. They strongly endorsed the beliefs that opioids helped them control their pain and allowed them to participate in important activities such as work. They expressed the belief that their pain would be severe if they did not have access to opioids, and reported negative experiences with tapering or discontinuing opioids in the past. Work-disabled participants reported higher levels of affective distress, catastrophizing, and functional interference than working participants, and were judged by their physicians to be relatively less successful in managing their pain. The results of this study suggest several tentative hypotheses about why patients on chronic opioid therapy value opioids, and identified several areas for systematic investigation in the future. © 2015 American Academy of Pain Medicine.

Ethical Issues in Research Involving Participants With Opioid Use Disorder.

PubMed

Anderson, Emily; McNair, Lindsay

2018-05-01

In the current epidemic of opioid use disorders, there is both a scientific and ethical imperative to develop effective medical and behavioral treatments for opioid addiction. Research in subject populations with active and ongoing drug addictions bring unique ethical considerations and challenges. Sponsors, researchers, and institutional review board (IRB) members should be familiar with these unique ethical and medical issues as they design, review, and conduct research planned for this population. Issues include those of informed consent and decision-making capacity of research participants, compensation for participation and concerns about undue inducement, forces that threaten the voluntary nature of research participation including the scarcity of available drug treatment programs, and ensuring that participants are aware of and understand risks that may continue after research participation such as increased risk of overdose after research-mandated drug abstinence. This manuscript discusses the current thinking on these issues.

Stress psychobiology in the context of addiction medicine: from drugs of abuse to behavioral addictions.

PubMed

Lemieux, Andrine; al'Absi, Mustafa

2016-01-01

In this chapter, we briefly review the basic biology of psychological stress and the stress response. We propose that psychological stress and the neurobiology of the stress response play in substance use initiation, maintenance, and relapse. The proposed mechanisms for this include, on the one hand, the complex interactions between biological mediators of the stress response and the dopaminergic reward system and, on the other hand, mediators of the stress response and other systems crucial in moderating key addiction-related behaviors such as endogenous opioids, the sympathetic-adrenal-medullary system, and endocannabinoids. Exciting new avenues of study including genomics, sex as a moderator of the stress response, and behavioral addictions (gambling, hypersexuality, dysfunctional internet use, and food as an addictive substance) are also briefly presented within the context of stress as a moderator of the addictive process. © 2016 Elsevier B.V. All rights reserved.

The oxytocin analogue carbetocin prevents emotional impairment and stress-induced reinstatement of opioid-seeking in morphine-abstinent mice.

PubMed

Zanos, Panos; Georgiou, Polymnia; Wright, Sherie R; Hourani, Susanna M; Kitchen, Ian; Winsky-Sommerer, Raphaëlle; Bailey, Alexis

2014-03-01

The main challenge in treating opioid addicts is to maintain abstinence due to the affective consequences associated with withdrawal which may trigger relapse. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT) in the modulation of mood disorders as well as drug addiction. However, its involvement in the emotional consequences of drug abstinence remains unclear. We investigated the effect of 7-day opioid abstinence on the oxytocinergic system and assessed the effect of the OT analogue carbetocin (CBT) on the emotional consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.). Seven days withdrawal from this administration paradigm induced a decrease of hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR) binding in the lateral septum and amygdala. Although no physical withdrawal symptoms or alterations in the plasma corticosterone levels were observed after 7 days of abstinence, mice exhibited increased anxiety-like and depressive-like behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed negative emotional consequences of opioid withdrawal. Furthermore, in the conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to morphine-seeking following extinction. Overall, our results suggest that alterations of the oxytocinergic system contribute to the mechanisms underlying anxiety, depression, and social deficits observed during opioid abstinence. This study also highlights the oxytocinergic system as a target for developing pharmacotherapy for the treatment of emotional impairment associated with abstinence and thereby prevention of relapse.

Opioid contracts and random drug testing for people with chronic pain - think twice.

PubMed

Collen, Mark

2009-01-01

The use of opioid contracts, which often require patients to submit to random drug screens, have become widespread amongst physicians using opioids to treat chronic pain. The main purpose of the contract is to improve care through better adherence to opioid therapy but there is little evidence as to its efficacy. The author suggests the use of opioid contracts and random drug testing destroys patients' trust which impacts health outcomes, and that physicians' motivation for their use are concerns about prosecution, medication abuse and misuse, and addiction. Statistics are provided to counter fears, and evidence is offered suggesting opioid contracts are unenforceable and lack efficacy; random drug testing is often inconclusive, and a patient's trust improves adherence to treatment.

Effects of heroin on rat prosocial behavior.

PubMed

Tomek, Seven E; Stegmann, Gabriela M; Olive, M Foster

2018-05-04

Opioid use disorders are characterized in part by impairments in social functioning. Previous research indicates that laboratory rats, which are frequently used as animal models of addiction-related behaviors, are capable of prosocial behavior. For example, under normal conditions, when a 'free' rat is placed in the vicinity of rat trapped in a plastic restrainer, the rat will release or 'rescue' the other rat from confinement. The present study was conducted to determine the effects of heroin on prosocial behavior in rats. For 2 weeks, rats were given the opportunity to rescue their cagemate from confinement, and the occurrence of and latency to free the confined rat was recorded. After baseline rescuing behavior was established, rats were randomly selected to self-administer heroin (0.06 mg/kg/infusion i.v.) or sucrose pellets (orally) for 14 days. Next, rats were retested for rescuing behavior once daily for 3 days, during which they were provided with a choice between freeing the trapped cagemate and continuing to self-administer their respective reinforcer. Our results indicate that rats self-administering sucrose continued to rescue their cagemate, whereas heroin rats chose to self-administer heroin and not rescue their cagemate. These findings suggest that rats with a history of heroin self-administration show deficits in prosocial behavior, consistent with specific diagnostic criteria for opioid use disorder. Behavioral paradigms providing a choice between engaging in prosocial behavior and continuing drug use may be useful in modeling and investigating the neural basis of social functioning deficits in opioid addiction. © 2018 Society for the Study of Addiction.

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

PubMed

Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M; Culverhouse, Robert C; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N; Maher, Brion S; Melroy, Whitney E; Nelson, Elliot C; Reid, Mark W; Robinson, Jason D; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A; Cannon, Dale S; Cichon, Sven; Corley, Robin P; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J; Grucza, Richard A; Hardin, Jill; Hartmann, Annette M; Heath, Andrew C; Herms, Stefan; Hodgkinson, Colin A; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O; Johnstone, Elaine; Kaneva, Radka P; Kendler, Kenneth S; Kiefer, Falk; Kranzler, Henry R; Krauter, Ken S; Levran, Orna; Lucae, Susanne; Lynskey, Michael T; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G; Mattheisen, Manuel; Montgomery, Grant W; Müller-Myhsok, Bertram; Murphy, Michael F; Neale, Michael C; Nikolov, Momchil A; Nishita, Denise; Nöthen, Markus M; Nurnberger, John; Partonen, Timo; Pergadia, Michele L; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wall, Tamara L; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W; Chen, Jingchun; Cinciripini, Paul M; Edenberg, Howard J; Ehringer, Marissa A; Ferrell, Robert E; Gelernter, Joel; Goldman, David; Hewitt, John K; Hopfer, Christian J; Iacono, William G; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M; Madden, Pamela A F; McGue, Matt; Munafò, Marcus R; Philibert, Robert A; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T; Swan, Gary E; Todorov, Alexandre A; Vanyukov, Michael M; Weiss, Robert B; Bierut, Laura J; Saccone, Nancy L

2016-03-01

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.

Association of the OPRM1 variant rs1799971 (A118G) with non-specific liability to substance dependence in a collaborative de novo meta-analysis of European-ancestry cohorts

PubMed Central

Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M.; Culverhouse, Robert C.; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M.; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N.; Maher, Brion S.; Melroy, Whitney E.; Nelson, Elliot C.; Reid, Mark W.; Robinson, Jason D.; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A.; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A.; Cannon, Dale S.; Cichon, Sven; Corley, Robin P.; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J.; Grucza, Richard A.; Hardin, Jill; Hartmann, Annette M.; Heath, Andrew C.; Herms, Stefan; Hodgkinson, Colin A.; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O.; Johnstone, Elaine; Kaneva, Radka P.; Kendler, Kenneth S.; Kiefer, Falk; Kranzler, Henry R.; Krauter, Ken S.; Levran, Orna; Lucae, Susanne; Lynskey, Michael T.; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G.; Mattheisen, Manuel; Montgomery, Grant W.; Müller-Myhsok, Bertram; Murphy, Michael F.; Neale, Michael C.; Nikolov, Momchil A.; Nishita, Denise; Nöthen, Markus M; Nurnberger, John; Partonen, Timo; Pergadia, Michele L.; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J.; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C.; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wall, Tamara L.; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W.; Chen, Jingchun; Cinciripini, Paul M.; Edenberg, Howard J; Ehringer, Marissa A.; Ferrell, Robert E.; Gelernter, Joel; Goldman, David; Hewitt, John K.; Hopfer, Christian J.; Iacono, William G.; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M.; Madden, Pamela A.F.; McGue, Matt; Munafò, Marcus R.; Philibert, Robert A.; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T.; Swan, Gary E.; Todorov, Alexandre A.; Vanyukov, Michael M.; Weiss, Robert B.; Bierut, Laura J.; Saccone, Nancy L.

2015-01-01

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for “general” substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day > 20 versus ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83–0.97], p-value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses. PMID:26392368

The SALOME study: recruitment experiences in a clinical trial offering injectable diacetylmorphine and hydromorphone for opioid dependency.

PubMed

Oviedo-Joekes, Eugenia; Marchand, Kirsten; Lock, Kurt; MacDonald, Scott; Guh, Daphne; Schechter, Martin T

2015-01-26

The Study to Assess Long-term Opioid Medication Effectiveness (SALOME) is a two-stage phase III, single site (Vancouver, Canada), randomized, double blind controlled trial designed to test if hydromorphone is as effective as diacetylmorphine for the treatment of long-term illicit opioid injection. Recruiting participants for clinical trials continues to be a challenge in medical and addiction research, with many studies not being able to reach the planned sample size in a timely manner. The aim of this study is to describe the recruitment strategies in SALOME, which offered appealing treatments but had limited clinic capacity and no guaranteed post-trial continuation of the treatments. SALOME included chronic opioid-dependent, current illicit injection opioid users who had at least one previous episode of opioid maintenance treatment. Regulatory approvals were received in June 2011 and recruitment strategies were implemented over the next 5 months. Recruitment strategies included ongoing open communication with the community, a consistent and accessible team and participant-centered screening. All applicants completed a pre-screening checklist to assess prerequisites. Applicants meeting these prerequisites were later contacted to commence the screening process. A total of 598 applications were received over the two-year recruitment period; 130 were received on the first day of recruitment. Of these applicants, 485 met prerequisites; however, many could not be found or were not reached before recruitment ended. For the 253 candidates who initiated the screening process, the average time lapse between application and screening date was 8.3 months (standard deviation [SD] = 4.44) and for the 202 randomized to the study, the average processing time from initial screen to randomization was 25.9 days (SD = 37.48; Median = 15.0). As in prior trials offering injectable diacetylmorphine within a supervised model, recruiting participants for this study took longer than planned. The recruitment challenges overcome in SALOME were due to the high number of applicants compared with the limited number that could be randomized and treated. Our study emphasizes the value of integrating these strategies into clinical addiction research to overcome study-specific barriers. ClinicalTrials.gov: NCT01447212.

Risk factors for opioid overdose and awareness of overdose risk among veterans prescribed chronic opioids for addiction or pain.

PubMed

Wilder, Christine M; Miller, Shannon C; Tiffany, Elizabeth; Winhusen, Theresa; Winstanley, Erin L; Stein, Michael D

2016-01-01

Rising overdose fatalities among U.S. veterans suggest veterans taking prescription opioids may be at risk for overdose. However, it is unclear whether veterans prescribed chronic opioids are aware of this risk. The objective of this study was to identify risk factors and determine awareness of risk for opioid overdose in veterans treated with opioids for chronic pain, using veterans treated with methadone or buprenorphine for opioid use disorder as a high-risk comparator group. In the current study, 90 veterans on chronic opioid medication, for either opioid use disorder or pain management, completed a questionnaire assessing risk factors, knowledge, and self-estimate of risk for overdose. Nearly all veterans in both groups had multiple overdose risk factors, although individuals in the pain management group had on average a significantly lower total number of risk factors than did individuals in the opioid use disorder group (5.9 versus 8.5, p < .0001). On average, participants treated for pain management scored slightly but significantly lower on knowledge of opioid overdose risk factors (12.1 versus 13.5, p < .01). About 70% of participants, regardless of group, believed their overdose risk was below that of the average American adult. There was no significant relationship between self-estimate of overdose risk and either number or knowledge of opioid overdose risk factors. Our results suggest that veterans in both groups underestimated their risk for opioid overdose. Expansion of overdose education to include individuals on chronic opioids for pain management and a shift in educational approaches to overdose prevention may be indicated.

Sublingual Buprenorphine/Naloxone for Chronic Pain in At-Risk Patients: Development and Pilot Test of a Clinical Protocol

PubMed Central

Rosenblum, Andrew; Cruciani, Ricardo A.; Strain, Eric C; Cleland, Charles M.; Joseph, Herman; Magura, Stephen; Marsch, Lisa A; McNicholas, Laura F; Savage, Seddon R; Sundaram, Arun; Portenoy, Russell K.

2013-01-01

Objective Sublingual buprenorphine/naloxone (Bup/Nx) is approved for addiction treatment and may be useful for pain management, particularly in opioid-treated pain patients with nonadherence behaviors. The transition of opioid-treated pain patients to buprenorphine carries the risk of precipitated withdrawal and increased pain. This study convened pain and addiction specialists to develop and pilot a clinical protocol for safe transitioning to Bup/Nx. Design The protocol was revised three times based on outside expert review and pilot study observations. The pilot was conducted with a prospective cohort of 12 patients with moderate to severe chronic pain, who were receiving long-term opioid therapy with any full μ-agonist drug, and had exhibited one or more aberrant drug-related behaviors. Patients were followed up for 3 to 6 months with the expectation that they would experience few adverse events and report lower pain severity. Results The three patients on the highest baseline opioid dose (equivalent to 303–450 mg of oral morphine) and the three on the lowest doses (≤20 mg) had early adverse events (AEs) when switched to Bup/Nx and did not complete the trial. Of the remaining six, one withdrew due to AEs; one responded well, then withdrew; and four completed a three-month trial. A mixed effects model controlling for dropouts found that average and worst pain significantly decreased after the switch to Bup/Nx (both p < .01). Conclusion Based on this experience, the protocol recommends Bup/Nx for pain only when baseline opioid doses are within bounds that reduce AEs at transition and incorporates dose flexibility to further reduce risks. This protocol warrants further testing. PMID:23264315

A cell biologist's perspective on physiological adaptation to opiate drugs.

PubMed

von Zastrow, Mark

2004-01-01

Opiate drugs such as morphine and heroin are among the most effective analgesics known but are also highly addictive. The clinical utility of opiates is limited by adaptive changes in the nervous system occurring after prolonged or repeated drug administration. These adaptations are believed to play an important role in the development of physiological tolerance and dependence to opiates, and to contribute to additional changes underlying the complex neurobehavioral syndrome of drug addiction. All of these adaptive changes are initiated by the binding of opiate drugs to a subfamily of G protein-coupled receptors that are also activated by endogenously produced opioid neuropeptides. It is increasingly evident that opiate-induced adaptations occur at multiple levels in the nervous system, beginning with regulation of opioid receptors themselves and extending to a complex network of direct and indirect modifications of "downstream" signaling machinery. Efforts in my laboratory are directed at understanding the biochemical and cell biological basis of opiate adaptations. So far, we have focused primarily on adaptations occurring at the level of opioid receptors themselves. These studies have contributed to defining a set of membrane trafficking mechanisms by which the number and functional activity of opioid receptors are controlled. The role of these mechanisms in affecting adaptation of "downstream" neurobiological substrates, and in mediating opiate-induced changes in whole-animal physiology and behavior, are exciting questions that are only beginning to be explored.

Adherence Monitoring with Chronic Opioid Therapy for Persistent Pain: A Biopsychosocial-spiritual Approach to Mitigate Risk

PubMed Central

Matteliano, Deborah; St. Marie, Barbara J.; Oliver, June

2013-01-01

Opioids represent a mainstay in the pharmacological management of persistent pain. While these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a past history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing (ASPMN) Position Statement on Pain Management in Patients with Substance Use Disorders (2012) focuses on the intersection of persistent pain, SUD, and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to now include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care. PMID:24602442

BUPRENORPHINE ABUSE IN INDIA : AN UPDATE

PubMed Central

Sharma, Yogesh; Mattoo, S.K.

1999-01-01

This study reviews the available Indian literature on buprenorphine abuse. Buprenorphine was introduced in 1986; the abuse, first noticed in 1987, increased rapidly till 1994, and then decreased gradually. Initiated through other addicts and medical practitioners, the abuse was mostly as a cheap, easily and legally available substitute for opioids. The typical young adult male abuser used an intravenous cocktail with diazepam, pheneramine or promethazine for a better kick. The withdrawal syndrome was typical of the opioids and without an expected delayed onset. Complications of pseudoaneurysm and recurrent koro in repeated withdrawal were reported. Buprenorphine as a detoxifying agent for opioids reportedly gave better symptom control in the first week but high rates of dependence induction were reported. The Indian data tends to caution against the Western enthusiasm to use buprenorphine for detoxification or maintenance of opioid abusers. PMID:21455379

Development and validation of the Current Opioid Misuse Measure.

PubMed

Butler, Stephen F; Budman, Simon H; Fernandez, Kathrine C; Houle, Brian; Benoit, Christine; Katz, Nathaniel; Jamison, Robert N

2007-07-01

Clinicians recognize the importance of monitoring aberrant medication-related behaviors of chronic pain patients while being prescribed opioid therapy. The purpose of this study was to develop and validate the Current Opioid Misuse Measure (COMM) for those pain patients already on long-term opioid therapy. An initial pool of 177 items was developed with input from 26 pain management and addiction specialists. Concept mapping identified six primary concepts underlying medication misuse, which were used to develop an initial item pool. Twenty-two pain and addiction specialists rated the items on importance and relevance, resulting in selection of a 40-item alpha COMM. Final item selection was based on empirical evaluation of items with patients taking opioids for chronic, noncancer pain (N=227). One-week test-retest reliability was examined with 55 participants. All participants were administered the alpha version of the COMM, the Prescription Drug Use Questionnaire (PDUQ) interview, and submitted a urine sample for toxicology screening. Physician ratings of patient aberrant behaviors were also obtained. Of the 40 items, 17 items appeared to adequately measure aberrant behavior, demonstrating excellent internal consistency and test-retest reliability. Cutoff scores were examined using ROC curve analysis and reasonable sensitivity and specificity were established. To evaluate the COMM's ability to capture change in patient status, it was tested on a subset of patients (N=86) that were followed and reassessed three months later. The COMM was found to have promise as a brief, self-report measure of current aberrant drug-related behavior. Further cross-validation and replication of these preliminary results is pending.

Exaggerated acquisition and resistance to extinction of avoidance behavior in treated heroin-dependent males

PubMed Central

Sheynin, Jony; Moustafa, Ahmed A.; Beck, Kevin D.; Servatius, Richard J.; Casbolt, Peter A.; Haber, Paul; Elsayed, Mahmoud; Hogarth, Lee; Myers, Catherine E.

2015-01-01

Objective Addiction is often conceptualized as a behavioral strategy for avoiding negative experiences. In rodents, opioid intake has been associated with abnormal acquisition and extinction of avoidance behavior. Here, we tested the hypothesis that these findings would generalize to human opioid-dependent subjects. Method Adults meeting DSM-IV criteria for heroin-dependence and treated with opioid medication (n=27), and healthy controls (n=26), were recruited between March–October 2013 and given a computer-based task to assess avoidance behavior. On this task, subjects controlled a spaceship and could either gain points by shooting an enemy spaceship, or hide in safe areas to avoid on-screen aversive events. Results While groups did not differ on escape responding (hiding) during the aversive event, heroin-dependent males (but not females) made more avoidance responses during a warning signal that predicted the aversive event (ANOVA, sex × group interaction, p=0.007). This group was also slower to extinguish the avoidance response when the aversive event no longer followed the warning signal (p=0.011). This behavioral pattern resulted in reduced opportunity to obtain reward without reducing risk of punishment. Results suggest that differences in avoidance behavior cannot be easily explained by impaired task performance or by exaggerated motor activity in male patients. Conclusion This study provides evidence for abnormal acquisition and extinction of avoidance behavior in opioid-dependent patients. Interestingly, data suggest abnormal avoidance is demonstrated only by male patients. Findings shed light on cognitive and behavioral manifestations of opioid addiction, and may facilitate development of therapeutic approaches to help affected individuals. PMID:27046310

Developing a Competence-Based Addiction Medicine Curriculum in Indonesia: The Training Needs Assessment

ERIC Educational Resources Information Center

Pinxten, W. J. L.; De Jong, C.; Hidayat, T.; Istiqomah, A. N.; Achmad, Y. M.; Raya, R. P.; Norviatin, D.; Siregar, I. M. P.

2011-01-01

Indonesia has one of the fastest growing, injecting drugs user-driven, human immunodeficiency virus (HIV) epidemics in Asia. Coverage of needle and syringe programs (NSPs), opioid substitution therapy (OST), and antiretroviral treatment (ART) is increasing, but is still low, whereas professional training in addiction medicine is not yet…

The gut-brain interaction in opioid tolerance.

PubMed

Akbarali, Hamid I; Dewey, William L

2017-12-01

The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function. Copyright © 2017 Elsevier Ltd. All rights reserved.

The opioid receptor triple agonist DPI-125 produces analgesia with less respiratory depression and reduced abuse liability.

PubMed

Yi, Shou-Pu; Kong, Qing-Hong; Li, Yu-Lei; Pan, Chen-Ling; Yu, Jie; Cui, Ben-Qiang; Wang, Ying-Fei; Wang, Guan-Lin; Zhou, Pei-Lan; Wang, Li-Li; Gong, Ze-Hui; Su, Rui-Bin; Shen, Yue-Hai; Yu, Gang; Chang, Kwen-Jen

2017-07-01

Opioid analgesics remain the first choice for the treatment of moderate to severe pain, but they are also notorious for their respiratory depression and addictive effects. This study focused on the pharmacology of a novel opioid receptor mixed agonist DPI-125 and attempted to elucidate the relationship between the δ-, μ- and κ-receptor potency ratio and respiratory depression and abuse liability. Five diarylmethylpiperazine compounds (DPI-125, DPI-3290, DPI-130, KUST202 and KUST13T02) were selected for this study. PKA fluorescence redistribution assays in CHO cells individually expressing δ-, μ- or κ-receptors were used to measure the agonist potency. The respiratory safety profiles were estimated in rats by the ratio of ED 50 (pCO 2 increase)/ED 50 (antinociception). The abuse liability of DPI-125 was evaluated with a self-administration model in rhesus monkeys. The observed agonist potencies of DPI-125 for δ-, μ- and κ-opioid receptors were 4.29±0.36, 11.10±3.04, and 16.57±4.14 nmol/L, respectively. The other four compounds were also mixed agonists with varying potencies. DPI-125 exhibited a high respiratory safety profile, clearly related to its high δ-receptor potency. The ratio of the EC 50 potencies for the μ- and δ-receptors was found to be positively correlated with the respiratory safety ratio. DPI-125 has similar potencies for μ- and κ-receptors, which is likely the reason for its reduced abuse potential. Our results demonstrate that the opioid receptor mixed agonist DPI-125 is safer and less addictive than traditional μ-agonist analgesics. These findings suggest that the development of δ>μ∼κ opioid receptor mixed agonists is feasible, and such compounds could represent a promising class of potent analgesics with wider therapeutic windows.

Frontline Science: Buprenorphine decreases CCL2-mediated migration of CD14+ CD16+ monocytes.

PubMed

Jaureguiberry-Bravo, Matias; Lopez, Lillie; Berman, Joan W

2018-05-23

HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB). CD14 + CD16 + monocytes are a mature subpopulation that is increased in number in the peripheral blood of HIV-infected people. Mature monocytes can be productively infected with HIV, and they transmigrate preferentially across the BBB in response to CCL2, a chemokine elevated in the CNS and CSF of HIV-infected people even with ART. Buprenorphine, an opioid derivate, is an opioid replacement therapy for heroin addiction. It is a partial agonist of μ-opioid receptor and full antagonist of κ-opioid receptor. The effects of buprenorphine on CCL2-mediated CD14 + CD16 + monocytes transmigration across the BBB, a critical mechanism that promotes neuroinflammation and HAND, have not been characterized. We showed for the first time that buprenorphine decreases several steps of CCL2-mediated human mature monocyte transmigration. We propose that buprenorphine treatment in the context of HIV infection could serve a dual purpose, to treat opioid addiction and also to reduce neuroinflammation. Additionally, buprenorphine may be used as a treatment for HAND not only in the context of opioid abuse. ©2018 Society for Leukocyte Biology.

The impact of opioids on the endocrine system.

PubMed

Katz, Nathaniel; Mazer, Norman A

2009-02-01

Opioids have been used for medicinal and analgesic purposes for centuries. However, their negative effects on the endocrine system, which have been known for some times, are barely discussed in modern medicine. Therefore, we conducted a systematic review of the impact of opioids on the endocrine system. A review of the English language literature on preclinical and clinical studies of any type on the influence of opioids on the endocrine system was conducted. Preliminary recommendations for monitoring and managing these problems were provided. Long-term opioid therapy for either addiction or chronic pain often induces hypogonadism owing to central suppression of hypothalamic secretion of gonadotropin-releasing hormone. Symptoms of opioid-induced hypogonadism include loss of libido, infertility, fatigue, depression, anxiety, loss of muscle strength and mass, osteoporosis, and compression fractures in both men and women; impotence in men; and menstrual irregularities and galactorrhea in women. In view of the increased use of opioids for chronic pain, it has become increasingly important to monitor patients taking opioids and manage endocrine complications. Therefore, patients on opioid therapy should be routinely screened for such symptoms and for laboratory abnormalities in sex hormones. Opioid-induced hypogonadism seems to be a common complication of therapeutic or illicit opioid use. Patients on long-term opioid therapy should be prospectively monitored, and in cases of opioid-induced hypogonadism, we recommend nonopioid pain management, opioid rotation, or sex hormone supplementation after careful consideration of the risks and benefits.

Attention-Deficit Hyperactivity Disorder (ADHD)

MedlinePlus

... Tube DysfunctionStrep ThroatAnemiaHyperthyroidismOpioid AddictionDiabetesCroup Home Diseases and Conditions Attention-Deficit Hyperactivity Disorder (ADHD) Condition Attention-Deficit Hyperactivity ...

Pain and Opioid Addiction: A Systematic Review and Evaluation of Pain Measurement in Patients with Opioid Dependence on Methadone Maintenance Treatment.

PubMed

Dennis, B B; Bawor, M; Paul, J; Plater, C; Pare, G; Worster, A; Varenbut, M; Daiter, J; Marsh, D C; Desai, D; Thabane, L; Samaan, Z

2016-01-01

While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These discrepancies may be a direct result of variations in the measurement of chronic pain or definitions of response to methadone treatment. The goal of this study is to evaluate the association between pain and substance use behaviour to determine the real impact of comorbid pain in the methadone population. We also aim to examine sources of variation across the literature with a specific focus on the measurement of pain. We performed a systematic review using an electronic search strategy across CINAHL, MEDLINE, Web of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane Reviews and the Cochrane Central Register of Controlled Trials databases. Title, abstract, as well as full text screening and extraction were performed in duplicate. Studies evaluating the association between chronic pain and methadone maintenance treatment response were eligible for inclusion in this review. Using a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA) research collaborative, we assessed the reliability of patient self-reported pain and the validated Brief Pain Inventory (BPI) assessment tool. After screening 826 articles we identified five studies eligible for full text extraction, of which three showed a significant relationship between the presence of pain and the increase in substance abuse among patients on methadone for the treatment of opioid dependence. Studies varied largely in the definitions and measurement of both pain and response to treatment. Results from our validation of pain measurement in the GENOA sample (n=297) showed the use of a simple self-reported pain question is highly correlated to the use of the BPI. Simply asking patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity, 84.4% PPV and 53.6% NPV to the BPI. The area under the ROC curve was 0.67 and the Pearson χ(2) was 37.3; (p<0.0001). The field of addiction medicine is at a lack of consensus as to the real effect of chronic pain on treatment response among opioid dependent patients. Whether it be the lack of a single "gold standard" measurement of response, or a lack of consistent measurement of pain, it is difficult to summarize and compare the results of these relatively small investigations. In comparison to the BPI, use of the simple self-reported pain has lower sensitivity for identifying patients with pain, suggesting the inconsistencies in these studies may result from differences in pain measurement. Future validation studies of pain measurement are required to address the predictive value of self-reported pain.

Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence

PubMed Central

Wang, A-L; Elman, I; Lowen, S B; Blady, S J; Lynch, K G; Hyatt, J M; O'Brien, C P; Langleben, D D

2015-01-01

Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its utility could be hampered by poor adherence. To gain a better insight into this phenomenon, we utilized blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) in conjunction with a validated cue-induced craving procedure to examine neural correlates of XRNTX adherence. We operationalized treatment adherence as the number of monthly XRNTX injections (range: 0–3) administered to a group of fully detoxified heroin-dependent subjects (n=32). Additional outcomes included urine toxicology screening and self-reported tobacco use. The presented heroin-related visual cues reliably elicited heroin craving in all tested subjects. Nine, five, three and 15 of the participants, respectively, received zero, one, two and three XRNTX injections, predicted by the individual baseline fMRI signal change in response to the cues in the medial prefrontal cortex, a brain region involved in inhibitory self-control and emotional appraisal. The incidence of opioid-positive urines during the XRNTX therapy was low and remained about half the pre-treatment rate after the XRNTX ended. During the treatment, cigarette smoking behaviors followed patterns of opioid use, while cocaine consumption was increased with reductions in opioid use. The present data support the hypothesis that medial prefrontal cortex functions are involved in adherence to opioid antagonist therapy. A potential role of concurrent non-opioid addictive substances consumption during the XRNTX pharmacotherapy warrants further investigation. Our findings set the stage for further bio-behavioral investigations of the mechanisms of relapse prevention in opioid dependence. PMID:25781230

A critical analysis of user satisfaction surveys in addiction services: opioid maintenance treatment as a representative case study.

PubMed

Trujols, Joan; Iraurgi, Ioseba; Oviedo-Joekes, Eugenia; Guàrdia-Olmos, Joan

2014-01-01

Satisfaction with services represents a key component of the user's perspective, and user satisfaction surveys are the most commonly used approach to evaluate the aforementioned perspective. The aim of this discursive paper is to provide a critical overview of user satisfaction surveys in addiction treatment and harm reduction services, with a particular focus on opioid maintenance treatment as a representative case. We carried out a selective critical review and analysis of the literature on user satisfaction surveys in addiction treatment and harm reduction services. Most studies that have reported results of satisfaction surveys have found that the great majority of users (virtually all, in many cases) are highly satisfied with the services received. However, when these results are compared to the findings of studies that use different methodologies to explore the patient's perspective, the results are not as consistent as might be expected. It is not uncommon to find that "highly satisfied" patients report significant problems when mixed-methods studies are conducted. To understand this apparent contradiction, we explored two distinct (though not mutually exclusive) lines of reasoning, one of which concerns conceptual aspects and the other, methodological questions. User satisfaction surveys, as currently designed and carried out in addiction treatment and harm reduction services, do not significantly help to improve service quality. Therefore, most of the enthusiasm and naiveté with which satisfaction surveys are currently performed and interpreted - and rarely acted on in the case of nonoptimal results - should be avoided. A truly participatory approach to program evaluation is urgently needed to reshape and transform patient satisfaction surveys.

Dynorphin and the Pathophysiology of Drug Addiction

PubMed Central

Shippenberg, T.S.; Zapata, A.; Chefer, V.I.

2009-01-01

Drug addiction is a chronic relapsing disease in which drug administration becomes the primary stimulus that drives behavior regardless of the adverse consequence that may ensue. As drug use becomes more compulsive, motivation for natural rewards that normally drive behavior decreases. The discontinuation of drug use is associated with somatic signs of withdrawal, dysphoria, anxiety and anhedonia. These consequences of drug use are thought to contribute to the maintenance of drug use and to the reinstatement of compulsive drug use that occurs during the early phase of abstinence. Even, however, after prolonged periods of abstinence, 80-90% of human addicts relapse to addiction suggesting that repeated drug use produces enduring changes in brain circuits that subserve incentive motivation and stimulus-response (habit) learning. A major goal of addiction research is the identification of the neural mechanisms by which drugs of abuse produce these effects. This article will review data showing that the dynorphin/κ-opioid receptor system serves an essential function in opposing alterations in behavior and brain neurochemistry that occur as a consequence of repeated drug use and that aberrant activity of this system may not only contribute to the dysregulation of behavior that characterizes addiction but to individual differences in vulnerability to the pharmacological actions of cocaine and alcohol. We will provide evidence that the repeated administration of cocaine and alcohol up-regulates the dynorphin/κ-opioid receptor system and that pharmacological treatments that target this system may prove effective in the treatment of drug addiction. PMID:17868902

Comparison of the risks of shopping behavior and opioid abuse between tapentadol and oxycodone and association of shopping behavior and opioid abuse.

PubMed

Cepeda, M Soledad; Fife, Daniel; Kihm, Mary A; Mastrogiovanni, Greg; Yuan, Yingli

2014-12-01

This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone.

Comparison of the Risks of Shopping Behavior and Opioid Abuse Between Tapentadol and Oxycodone and Association of Shopping Behavior and Opioid Abuse

PubMed Central

Fife, Daniel; Kihm, Mary A.; Mastrogiovanni, Greg; Yuan, Yingli

2014-01-01

Objectives: This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. Materials and Methods: This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. Results: Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. Discussion: Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone. PMID:24370606

Buprenorphine implants in medical treatment of opioid addiction.

PubMed

Chavoustie, Steven; Frost, Michael; Snyder, Ole; Owen, Joel; Darwish, Mona; Dammerman, Ryan; Sanjurjo, Victoria

2017-08-01

Opioid use disorder is a chronic, relapsing disease that encompasses use of both prescription opioids and heroin and is associated with a high annual rate of overdose deaths. Medical treatment has proven more successful than placebo treatment or psychosocial intervention, and the partial µ-opioid receptor agonist and κ-opioid receptor antagonist buprenorphine is similar in efficacy to methadone while offering lower risk of respiratory depression. However, frequent dosing requirements and potential for misuse and drug diversion contribute to significant complications with treatment adherence for available formulations. Areas covered: This review describes the development of and preliminary data from clinical trials of an implantable buprenorphine formulation. Efficacy and safety data from comparative studies with other administrations of buprenorphine, including tablets and sublingual film, will be described. Key premises of the Risk Evaluation and Mitigation Strategy program for safely administering buprenorphine implants, which all prescribing physicians must complete, are also discussed. Expert commentary: Long-acting implantable drug formulations that offer consistent drug delivery and lower risk of misuse, diversion, or accidental pediatric exposure over traditional formulations represent a promising development for the effective treatment of opioid use disorder.

Between a rock and a hard place: Prescription opioid restrictions in the time of fentanyl and other street drug adulterants.

PubMed

Cheng, Tessa; DeBeck, Kora

2017-09-14

Non-medical prescription opioid use (NMPOU) has increased alarmingly across Canada and resulted in strict prescribing restrictions on opioids. Despite a clear need to reduce opioid prescriptions in response to this crisis, few other policies have been implemented and this singular focus is incongruent with the known characteristics of substance use disorders, negative effects of supply reduction policies, and realities of pain management. Given the recent rise of fentanyl and other dangerous adulterants in street drugs, this commentary argues that a comprehensive response to NMPOU that includes improvements to addiction management and harm-reduction services is urgently needed.

Bilateral Breast Reduction Without Opioid Analgesics: A Comparative Study.

PubMed

Parsa, Fereydoun Don; Cheng, Justin; Stephan, Brad; Castel, Nikki; Kim, Leslie; Murariu, Daniel; Parsa, Alan A

2017-09-01

Breast reduction has traditionally been performed under general anesthesia with adjunct opioid use. However, opioids are associated with a wide variety of adverse effects, including nausea, vomiting, constipation, postoperative sedation, dizziness, and addiction. This study compares bilateral breast reduction using a multimodal opioid-free pain management regimen vs traditional general anesthesia with adjunct opioids. A total of 83 female patients were enrolled in this study. Group 1 includes a retrospective series of 39 patients that underwent breast reduction via general anesthesia with adjunct opioid use. This series was compared to 2 prospective groups of patients who did not receive opioids either preoperatively or intraoperatively. In group 2, twenty-six patients underwent surgery under intravenous sedation and local anesthesia. In group 3, eighteen patients underwent surgery with general anesthesia. All patients in groups 2 and 3 received preoperative gabapentin and celecoxib along with infiltration of local anesthetics during the operation and prior to discharge to the Post-Anesthesia Care Unit (PACU). Primary outcome measures included the duration of surgery, time from end of operation to discharge home, postoperative opioid and antiemetic use, and unplanned postoperative hospitalizations. When compared to group 1, groups 2 and 3 experienced a shorter time from end of operation to discharge home (P < 0.05), fewer unplanned hospital admissions (P < 0.05), and highly significant decrease in postoperative opioid use (P < 0.001). This multimodal approach allows patients to safely undergo opioid-free bilateral breast reduction either under local or general anesthesia as an outpatient. This method resulted in significantly less morbidity, use of opioids postoperatively, as well as unplanned hospital admissions compared to "traditional" breast reduction under general anesthesia with the use of opioids. 3. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Latin-American guidelines for opioid use in chronic nononcologic pain.

PubMed

Lara-Solares, Argelia; Aguayo Zamora, Carlos; Amescua García, César; Garcia, João Batista Santos; Berenguel Cook, María Del Rosario; Bonilla Sierra, Patricia; Campos Kraychete, Durval; Flores Cantisani, José Alberto; Guerrero, Carlos; Guillén Núñez, María Del Rocío; Hernández Castro, John Jairo; Hernández Ortíz, Andrés; Jreige Iskandar, Aziza; Lech, Osvandré; Macías Guerra, Jacqueline; Ramírez Samayoa, Gerardo; Rangel Morillo, Edwin; Rico Pazos, María Antonieta; Sempértegui Gallegos, Manuel

2017-05-01

Latin-American experts in the use of opioids in patients with chronic nononcologic pain (CNOP) have updated existing recommendations to current Latin-American reality. Several key opinion leaders from Latin America participated in a face-to-face meeting in Guatemala (April 2015) to discuss the use of opioids in CNOP. Subgroups of experts worked on specific topics, reviewed the literature and shaped the final manuscript. The expert panel developed guidelines taking into consideration the utility of both opioid and nonopioid analgesics and factors pertaining to their efficacy, safety, adherence, administration and risks for abuse/addiction. Latin-American guidelines for the use of opioids in CNOP should improve pain relief and patients' quality of life by increasing access to these effective agents.

Age at onset typology in opioid dependent men: an exploratory study.

PubMed

De, Biswajit; Mattoo, Surendra K; Basu, Debasish

2002-04-01

This study attempted to apply age at onset typology in ICD-10 diagnosed opioid dependence. The sample comprised 80 men seeking treatment at an addiction clinic. The measures included socio-demographic and clinical profile, Severity of Opioid Dependence Questionnaire, Modified Sensation Seeking Scale, Multiphasic Personality Questionnaire (MPQ) and Family History Assessment Module. A cut-off age of 20/21 years for an early-onset late-onset typology of opioid dependence was obtained using two methods - the modal age at onset method and one-third sample by age at onset method. The early onset group showed significant differences in terms of it being more often younger, urban, unmarried, wage earning or students, using oral opioids (not heroin or injectables), showing higher lifetime use and dependence of sedatives, earlier onset of use and dependence of sedatives and tobacco, and higher global psychopathology in terms of MPQ. The early onset group also showed statistically insignificant trends for lesser use and dependence of alcohol, higher severity of opioid dependence, more legal and less social complications, higher sensation seeking (except boredom susceptibility), and more frequent substance dependence in first degree relatives. The age at onset typology in opioid dependence appears to be feasible and having some similarities to similar typology in alcoholism.

[Sugar triggers our reward-system. Sweets release opiates which stimulates the appetite for sucrose--insulin can depress it].

PubMed

Erlanson-Albertsson, Charlotte

The consumption of sweet food has increased in Sweden, as in other Western countries. The type of food item has changed. The sweet is dominated by soft drinks. Appetite regulation for sucrose has been described in experimental animal models. It has been found that opioids stimulate appetite for sucrose. At the same time sucrose releases endogenous opioids so that a triggering of sucrose consumption occurs. Insulin has been shown to decrease sucrose intake by blocking the opioid response. Sucrose addiction has been described in rat model. With a concentrated sucrose solution to drink an opioid dependence developed with 1) increased consumption of sucrose 2) abstinence symptoms with no sucrose and 3) anxiety with an opiate blocker. Sucrose addiction in man has not been described in the scientific literature. There is an increased liking of sweets with alcoholic persons, which may be significant to support a strongly rewarding effect of sucrose, also in man. We should limit the access to sweet foods, in particular the sweet drinks. Insulin and insulin sensitivity may be an important factor to restrict the intake of sweet food.

Employment-based reinforcement of adherence to depot naltrexone in unemployed opioid-dependent adults: a randomized controlled trial.

PubMed

Everly, Jeffrey J; DeFulio, Anthony; Koffarnus, Mikhail N; Leoutsakos, Jeannie-Marie S; Donlin, Wendy D; Aklin, Will M; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

2011-07-01

Naltrexone can be used to treat opioid dependence, but patients refuse to take it. Extended-release depot formulations may improve adherence, but long-term adherence rates to depot naltrexone are not known. This study determined long-term rates of adherence to depot naltrexone and whether employment-based reinforcement can improve adherence. Participants who were inducted onto oral naltrexone were assigned randomly to contingency (n = 18) or prescription (n = 17) groups. Participants were offered six depot naltrexone injections and invited to work at the therapeutic workplace on week days for 26 weeks, where they earned stipends for participating in job skills training. Contingency participants were required to accept naltrexone injections to maintain workplace access and to maintain maximum pay. Prescription participants could work independently of whether they accepted injections. The therapeutic workplace, a model employment-based intervention for drug addiction and unemployment. Opioid-dependent unemployed adults. Depot naltrexone injections accepted and opiate-negative urine samples. Contingency participants accepted significantly more naltrexone injections than prescription participants (81% versus 42%), and were more likely to accept all injections (66% versus 35%). At monthly assessments (with missing urine samples imputed as positive), the groups provided similar percentages of samples negative for opiates (74% versus 62%) and for cocaine (56% versus 54%). Opiate-positive samples were more likely when samples were also positive for cocaine. Employment-based reinforcement can maintain adherence to depot naltrexone. Future research should determine whether persistent cocaine use compromises naltrexone's effect on opiate use. Workplaces may be useful for promoting sustained adherence to depot naltrexone. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

[A girl with self-harm treated with N-acetylcysteine (NAC)].

PubMed

Rus, C P

Deliberate and recurrent self-harm could be regarded as addictive behaviour that can be treated with medication. In addiction, the dopaminergic mesolimbic reward system is activated. Pain caused by cutting stimulates the reward system through the opioid system. Glutamatergic neurotransmission follows the same pathway and plays a role in addiction as well. In this case-study a 17-year-old girl was successfully treated with N-acetylcysteine (nac) in order to reduce the frequency of self-cutting. In addition, in this case nac reduced the symptoms of attention deficit/hyperactivity disorder and depression. nac modulates the glutamatergic neurotransmission. This article provides possible explanations for the effect of nac in this case.

Neurobiology of addictive behaviors and its relationship to methadone maintenance.

PubMed

Stimmel, B; Kreek, M J

2000-01-01

Scientific information about the neurobiology of addictive behaviors provides an increasingly important rationale to support opioid agonist pharmacotherapy, primarily methadone maintenance treatment, for long-term heroin addiction. In late 1963 and 1964, the first research was performed at The Rockefeller Institute for Medical Research by Dole, Nyswander, and Kreek in an attempt to develop a new pharmacotherapy for opiate addiction. The hypothesis underlying that research was that heroin addiction was a disease. However, the evidence for heroin addiction being a disease was based primarily on clinical anecdotes and the natural history of opiate addiction. Until then chronic addiction was managed primarily using abstinence-based, medication-free behavioral approaches. Such approaches were uniformly successful in only a small percent of long-term heroin addicts. Subsequent research, both clinical research as well as laboratory-based research, using a variety of appropriate animal models as well as in vitro techniques, has shown that drugs of abuse in general, and specifically the short-acting opiates, such as heroin, may profoundly alter molecular and neurochemical indices, and thus physiologic functions. Also, research has shown that after chronic exposure to a short-acting opiate,these alterations may be persistent, or even permanent, and may contribute directly to the perpetuation of self-administration of opiates, and even the return to opiate use after achieving a drug-free and medication-free state. There is ample evidence now that disruption of several components of the endogenous opioid system, ranging from changes in gene expression to changes in behavior, may occur during cycles of short-acting opiate abuse. Also, there are very convincing studies that suggest that stress responsivity is profoundly altered by chronic abuse of short-acting opiates including: documentation of atypical hypo-responsivity to stressors during cycles of heroin addiction; evidence of sustained hyper-responsivity to stressors in the medication-free, illicit-opiate-free state; and in contrast, normalization of stress responsivity, as reflected by the hypothalamic-pituitary-adrenal axis function in long-term, methadone-maintained patients. Thus, both laboratory and clinical research studies provide firm documentation that the disruption of physiologic, as well as behavioral, functions occurs during chronic administration of short-acting opiates. Also, there is research evidence of an epidemiologic, and more recently of a molecular genetics type, that a genetic vulnerability to develop addictions in general, and opiate addiction specifically, may exist, and that early environmental factors may alter physiology to enhance vulnerability to develop opiate addiction when self-exposed.

Challenges to implementing opioid substitution therapy in Ukrainian prisons: Personnel attitudes toward addiction, treatment, and people with HIV/AIDS.

PubMed

Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A; Taxman, Faye S; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L

2015-03-01

Ukraine is experiencing one of the most volatile HIV epidemics globally, fueled primarily by people who inject drugs (PWIDs), and a parallel incarceration epidemic. Opioid substitution therapy (OST) is internationally recognized as one of the most effective forms of treatment for opioid dependence and is among the most effective HIV prevention strategies available, yet efforts to adopt it in Ukraine's Criminal Justice System (CJS) have been thwarted. To understand the reluctance of the Ukrainian CJS to adopt OST despite the overwhelming evidence pointing to its health benefits and improved criminal justice outcomes, we conducted the first survey of Ukrainian prison administrative, medical and custodial staff (N=243) attitudes towards addiction in general, OST, and people living with HIV/AIDS (PLWHA) in representative regions of Ukraine. Results revealed that Ukrainian CJS workers' attitudes toward OST, PLWHA, and drug addiction were universally negative, but differed substantially along geographic and occupational lines. Whereas geographic and cultural proximity to the European Union drove positive attitudes in the west, in the southern region we observed an identifiability effect, as workers who worked directly with prisoners held the most positive attitudes. We also found that knowledge mediated the effect of drug intolerance on OST attitudes. In Ukraine, adoption of OST is more influenced by myths, biases and ideological prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this study will help to direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse.

PubMed

Sushchyk, Sarah; Xi, Zheng-Xiong; Wang, Jia Bei

2016-05-01

Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects ofl-THP and LDN on cocaine self-administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination ofl-THP and LDN reduces drug-seeking behavior during reinstatement more potently thanl-THP alone. Additionally, the combination ofl-THP and LDN attenuates the sedative locomotor effect induced byl-THP. Furthermore, we revealed that treatment with the combination ofl-THP and LDN has an upregulatory effect on both plasmaβ-endorphin and hypothalamic POMC that was not observed inl-THP-treated groups. These results suggest that the combination ofl-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention. U.S. Government work not protected by U.S. copyright.

Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse

PubMed Central

Sushchyk, Sarah; Xi, Zheng-Xiong

2016-01-01

Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects of l-THP and LDN on cocaine self-administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination of l-THP and LDN reduces drug-seeking behavior during reinstatement more potently than l-THP alone. Additionally, the combination of l-THP and LDN attenuates the sedative locomotor effect induced by l-THP. Furthermore, we revealed that treatment with the combination of l-THP and LDN has an upregulatory effect on both plasma β-endorphin and hypothalamic POMC that was not observed in l-THP-treated groups. These results suggest that the combination of l-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention. PMID:26903543

Physicians' Knowledge of and Attitudes Toward Use of Opioids in Long-Term Care Facilities.

PubMed

Griffioen, Charlotte; Willems, Eva G; Kouwenhoven, Sanne M; Caljouw, Monique A A; Achterberg, Wilco P

2017-06-01

Insufficient pain management in vulnerable older persons living in long-term care facilities is common, and opiophobia might contribute to this. As opiophobia and its related factors have not been investigated in long-term care, this study evaluates the degree of knowledge of opioids among elderly-care physicians (ECPs) and ECP trainees, as well as their attitudes and other factors possibly influencing the clinical use of opioids in these facilities. A questionnaire was designed and distributed among ECPs and ECP trainees by email, regional symposia, and all three university training faculties for elderly-care medicine in the Netherlands. Respondents were 324 ECPs and 111 ECP trainees. Fear of addiction did not influence the prescription of opioids. Main barriers to the clinical use of opioids were patients' reluctance to take opioids (83.3%); unknown degree of pain (79.2%); and pain of unknown origin (51.4%). ECPs' average knowledge scores were sufficient: those who felt that their knowledge of opioids was poor scored lower than those who felt that their knowledge was good. Factors identified in this study may help provide better pain management for vulnerable older persons living in a long-term care facility. Also, more patient information on the pros and cons of opioid use is needed, as well as appropriate tools for better clinical assessment of pain in a long-term care population. © 2016 World Institute of Pain.

Abuse-Deterrent Opioid Formulations: Pharmacokinetic and Pharmacodynamic Considerations.

PubMed

Walter, Carmen; Knothe, Claudia; Lötsch, Jörn

2016-07-01

Abuse-deterrent formulations (ADFs) are technologically sophisticated pharmaceutical formulations that impede manipulation and extraction of opioids and/or provoke unpleasant effects when they are taken in excessive quantity. This is implemented by creating physical barriers, inseparably combining the opioid with an opioid antagonist or adding aversive agents to the formulation. These pharmaceutical changes may potentially alter the pharmacokinetics and consequently the pharmacodynamics of the opioid. In this review, comparative evidence on pharmacokinetic differences between abuse-deterrent and classical formulations of the same opioids is summarized; furthermore, pharmacodynamic differences, with a focus on analgesia and abuse-related symptoms, are addressed. Most of the 12 studies comparing opioid pharmacokinetics have judged the physically intact ADF as being bioequivalent to the corresponding classical formulation. Pharmacokinetic differences have, however, been reported with physically manipulated ADFs and have ranged from moderate deviations from bioequivalence to complete changes in the pharmacokinetic profile (e.g. from a sustained-release formulation to a fast-release formulation). Pharmacodynamic effects were assessed in 14 comparative studies, which reported that intact ADFs usually provided clinically equivalent analgesia and clear advantages with respect to their addiction potential. However, withdrawal symptoms could be induced by the ADFs, although rarely and, in particular, when the ADFs had been physically altered. This evidence suggests that opioid ADFs are a working concept resulting in mostly minor pharmacokinetic and pharmacodynamic differences in comparison with classical formulations; however, they may deviate from this equivalence when physically altered.

Introduction to the College on Problems of Drug Dependence special issue: contemporary advances in opioid neuropharmacology.

PubMed

Walsh, Sharon L; Unterwald, Ellen M; Izenwasser, Sari

2010-05-01

Opioid receptors are critical therapeutic targets for medications development relevant to the treatment of drug dependence and pain. With recent advances in molecular neurobiology, it has become evident that the functional activity of opioid receptors, as ligand-regulated protein complexes, is modulated by multifarious intracellular and extracellular events, that there is genetic variation in coding for receptors, and that the activity of endogenous opioid systems may underlie actions common to other addictive disorders. This supplemental issue of Drug and Alcohol Dependence, arising from an invited symposium at the 71st Annual Meeting of the College on Problems of Drug Dependence, provides a series of contemporary reviews focused on recent advances in opioid neuropharmacology. Each speaker provides herein an invited comprehensive review of the state of knowledge on a specific topic in opioid neuropharmacology. Evans and colleagues describe the multi-faceted control of the opioid G-protein coupled receptor as a dynamic "sensor" complex and identify novel targets for drug development. von Zastrow focuses on opioid receptor-mediated events regulated by endocytosis and membrane trafficking through the endocytic pathway and differential responses to opioid agonists. Blendy and colleague provide a review of human association studies on the functional relevance of the mu opioid receptor variant, A118G, and presents data from the A112G knock-in model, an analogous mouse variant to A118G. Finally, Maldonado and colleagues provide a broader systems review from genetic, pharmacologic and behavioral studies implicating the endogenous opioid systems as a substrate for the mediation of substance use disorders spanning pharmacological classes.

Psychostimulant addiction treatment

PubMed Central

Phillips, Karran A.; Epstein, David H.; Preston, Kenzie L.

2014-01-01

Treatment of psychostimulant addiction has been a major, and not fully met, challenge. For opioid addiction, there is strong evidence for the effectiveness of several medications. For psychostimulants, there is no corresponding form of agonist maintenance that has met criteria for regulatory approval or generally accepted use. Stimulant-use disorders remain prevalent and can result in both short-term and long-term adverse consequences. The mainstay of treatment remains behavioral interventions. In this paper, we discuss those interventions and some promising candidates in the search for pharmacological interventions. PMID:24727297

Adherence monitoring with chronic opioid therapy for persistent pain: a biopsychosocial-spiritual approach to mitigate risk.

PubMed

Matteliano, Deborah; St Marie, Barbara J; Oliver, June; Coggins, Candace

2014-03-01

Opioids represent a mainstay in the pharmacologic management of persistent pain. Although these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing "Position Statement on Pain Management in Patients with Substance Use Disorders" (2012) focuses on the intersection of persistent pain, substance use disorder (SUD), and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Training opioid addiction treatment providers to adopt contingency management: A prospective pilot trial of a comprehensive implementation science approach.

PubMed

Becker, Sara J; Squires, Daniel D; Strong, David R; Barnett, Nancy P; Monti, Peter M; Petry, Nancy M

2016-01-01

Few prospective studies have evaluated theory-driven approaches to the implementation of evidence-based opioid treatment. This study compared the effectiveness of an implementation model (Science to Service Laboratory; SSL) to training as usual (TAU) in promoting the adoption of contingency management across a multisite opioid addiction treatment program. We also examined whether the SSL affected putative mediators of contingency management adoption (perceived innovation characteristics and organizational readiness to change). Sixty treatment providers (39 SSL, 21 TAU) from 15 geographically diverse satellite clinics (7 SSL, 8 TAU) participated in the 12-month study. Both conditions received didactic contingency management training and those in the predetermined experimental region received 9 months of SSL-enhanced training. Contingency management adoption was monitored biweekly, whereas putative mediators were measured at baseline, 3 months, and 12 months. Relative to providers in the TAU region, treatment providers in the SSL region had comparable likelihood of contingency management adoption in the first 20 weeks of the study, and then significantly higher likelihood of adoption (odds ratios = 2.4-13.5) for the remainder of the study. SSL providers also reported higher levels of one perceived innovation characteristic (Observability) and one aspect of organizational readiness to change (Adequacy of Training Resources), although there was no evidence that the SSL affected these putative mediators over time. Results of this study indicate that a fully powered randomized trial of the SSL is warranted. Considerations for a future evaluation are discussed.

A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm.

PubMed

Cordery, Sarah F; Taverner, Alistair; Ridzwan, Irna E; Guy, Richard H; Delgado-Charro, M Begoña; Husbands, Stephen M; Bailey, Christopher P

2014-07-01

Concurrent use of cocaine and heroin is a major public health issue with no effective relapse prevention treatment currently available. To this purpose, a combination of buprenorphine and naltrexone, a mixed very-low efficacy mu-opioid receptor agonist/kappa-opioid receptor antagonist/nociceptin receptor agonist, was investigated. The tail-withdrawal and the conditioned place preference (CPP) assays in adult Sprague Dawley rats were used to show that naltrexone dose-dependently blocked the mu-opioid receptor agonism of buprenorphine. Furthermore, in the CPP assay, a combination of 0.3 mg/kg buprenorphine and 3.0 mg/kg naltrexone was aversive. A combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone was neither rewarding nor aversive, but still possessed mu-opioid receptor antagonist properties. In the CPP extinction and reinstatement method, a combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone completely blocked drug-primed reinstatement in cocaine-conditioned rats (conditioned with 3 mg/kg cocaine, drug prime was 3 mg/kg cocaine) and attenuated drug-primed reinstatement in morphine-conditioned rats (conditioned with 5 mg/kg morphine, drug prime was 1.25 mg/kg morphine). These data add to the growing evidence that a buprenorphine/naltrexone combination may be protective against relapse in a polydrug abuse situation. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

The proteins interacting with C-terminal of μ receptor are identified by bacterial two-hybrid system from brain cDNA library in morphine-dependent rats.

PubMed

Zhou, Peilan; Jiang, Jiebing; Dong, Zhaoqi; Yan, Hui; You, Zhendong; Su, Ruibin; Gong, Zehui

2015-12-15

Opioid addiction is associated with long-term adaptive changes in the brain that involve protein expression. The carboxyl-terminal of the μ opioid receptor (MOR-C) is important for receptor signal transduction under opioid treatment. However, the proteins that interact with MOR-C after chronic morphine exposure remain unknown. The brain cDNA library of chronic morphine treatment rats was screened using rat MOR-C to investigate the regulator of opioids dependence in the present study. The brain cDNA library from chronic morphine-dependent rats was constructed using the SMART (Switching Mechanism At 5' end of RNA Transcript) technique. Bacterial two-hybrid system was used to screening the rat MOR-C interacting proteins from the cDNA library. RT-qPCR and immunoblotting were used to determine the variation of MOR-C interacting proteins in rat brain after chronic morphine treatment. Column overlay assays, immunocytochemistry and coimmunoprecipitation were used to demonstrate the interaction of MOR-C and p75NTR-associated cell death executor (NADE). 21 positive proteins, including 19 known proteins were screened to interact with rat MOR-C. Expression of several of these proteins was altered in specific rat brain regions after chronic morphine treatment. Among these proteins, NADE was confirmed to interact with rat MOR-C by in vitro protein-protein binding and coimmunoprecipitation in Chinese hamster ovary (CHO) cells and rat brain with or without chronic morphine treatment. Understanding the rat MOR-C interacting proteins and the proteins variation under chronic morphine treatment may be critical for determining the pathophysiological basis of opioid tolerance and addiction. Copyright © 2015. Published by Elsevier Inc.

Exaggerated acquisition and resistance to extinction of avoidance behavior in treated heroin-dependent men.

PubMed

Sheynin, Jony; Moustafa, Ahmed A; Beck, Kevin D; Servatius, Richard J; Casbolt, Peter A; Haber, Paul; Elsayed, Mahmoud; Hogarth, Lee; Myers, Catherine E

2016-03-01

Addiction is often conceptualized as a behavioral strategy for avoiding negative experiences. In rodents, opioid intake has been associated with abnormal acquisition and extinction of avoidance behavior. Here, we tested the hypothesis that these findings would generalize to human opioid-dependent subjects. Adults meeting DSM-IV criteria for heroin dependence and treated with opioid medication (n = 27) and healthy controls (n = 26) were recruited between March 2013 and October 2013 and given a computer-based task to assess avoidance behavior. For this task, subjects controlled a spaceship and could either gain points by shooting an enemy spaceship or hide in safe areas to avoid on-screen aversive events. Hiding duration during different periods of the task was used to measure avoidance behavior. While groups did not differ on escape responding (hiding) during the aversive event, heroin-dependent men (but not women) made more avoidance responses during a warning signal that predicted the aversive event (analysis of variance, sex × group interaction, P = .007). Heroin-dependent men were also slower to extinguish the avoidance response when the aversive event no longer followed the warning signal (P = .011). This behavioral pattern resulted in reduced opportunity to obtain reward without reducing risk of punishment. Results suggest that, in male patients, differences in avoidance behavior cannot be easily explained by impaired task performance or by exaggerated motor activity. This study provides evidence for abnormal acquisition and extinction of avoidance behavior in opioid-dependent patients. Interestingly, data suggest that abnormal avoidance is demonstrated only by male patients. Findings shed light on cognitive and behavioral manifestations of opioid addiction and may facilitate development of therapeutic approaches to help affected individuals. © Copyright 2016 Physicians Postgraduate Press, Inc.

Opioid Analgesics for Chronic Non-Cancer Pain: A Guideline on Opioid Prescribing.

PubMed

Van Demark, Robert; Chang, Peter; Heinemann, Daniel

2016-01-01

Over the past decade, the use of opioid analgesics has risen dramatically both in the U.S. and South Dakota. Opioids have been increasingly used to treat chronic non-cancer pain; however, the utilization of opioids for this role has limited and questionable utility. The U.S. has also seen a rise of opioid abuse, addiction, misuse, and overdose. The various pharmacological and non-pharmacological strategies to help physicians manage chronic non-cancer pain and a guideline on appropriate opioid prescribing are presented. Before the decision is made to begin opioid therapy for chronic non-cancer pain, other pharmacological and non-pharmacological therapeutic strategies should be explored. The schema for responsible opioid prescribing can be dived into the following: the initial assessment, initiating opioid therapy, maintenance therapy, and the discontinuation of opioid treatment. These categories are explored, and a general approach to prescribing opioids for chronic non-cancer pain is presented. The Centers for Disease Control and Prevention (CDC) has declared opioid prescription abuse an "epidemic." There are a variety of methods clinicians can utilize to relieve chronic non-cancer pain. If opioid therapy is sought, clinicians should be mindful of the current state of opioid abuse and misuse. This guideline may aid clinicians in appropriate opioid prescribing.

Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies.

PubMed

Melichar, Jan K; Hume, Susan P; Williams, Tim M; Daglish, Mark R C; Taylor, Lindsay G; Ahmad, Rabia; Malizia, Andrea L; Brooks, David J; Myles, Judith S; Lingford-Hughes, Anne; Nutt, David J

2005-01-01

Substitute methadone prescribing is one of the main modes of treatment for opioid dependence with established evidence for improved health and social outcomes. However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome. We therefore examined the relationship between methadone dose and occupation of opioid receptors in brain using the positron emission tomography (PET) radioligand [(11)C]diprenorphine in humans and rats. Eight opioid-dependent subjects stable on their substitute methadone (18-90 mg daily) had an [(11)C]diprenorphine PET scan at predicted peak plasma levels of methadone. These were compared with eight healthy controls. No difference in [(11)C]diprenorphine binding was found between the groups, with no relationship between methadone dose and occupancy. Adult male Sprague-Dawley rats that had been given an acute i.v. injection of methadone hydrochloride (0.35, 0.5, 0.7, or 1.0 mg kg(-1)) before [(11)C]diprenorphine showed a dose-dependent increase in biodistribution but no reduction in [(11)C]diprenorphine binding. We suggest that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [(11)C]diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioid receptor occupancy. This has implications for understanding the actions of methadone in comparison with other opioid drugs such as partial agonists and antagonists.

Fatal opioid poisoning: a counterfactual model to estimate the preventive effect of treatment for opioid use disorder in England.

PubMed

White, Martin; Burton, Robyn; Darke, Shane; Eastwood, Brian; Knight, Jon; Millar, Tim; Musto, Virginia; Marsden, John

2015-08-01

A counterfactual model was used to estimate the number of fatal opioid-related poisonings prevented by public treatment services for opioid use disorder (OUD) in England between April 2008 and March 2011. Patient OUD treatment episode data recorded by the English National Drug Treatment Monitoring System were linked to data on opioid deaths recorded by the Office for National Statistics. The source population was the official estimate of non-medical opioid users (aged 15-64 years; approximately 260 000 each year). The target population was all individuals (aged 15-64 years) treated for OUD in the study period (n = 220 665). The outcome measure was fatal opioid-related poisoning (opioid death). The opioid death rate [per 100 person-years (PY)] and mortality rate ratios (MRR) were computed for study year, age group (15-24, 25-34, 35-64 years) and for three treatment-related states: time spent 'prior to treatment', 'during treatment' and 'after treatment'. Between April 2008 and March 2011, there were 3731 opioid deaths in the study: 741 during treatment (0.20 per 100 PY; referent category); 2722 prior to treatment [0.77 per 100 PY; MRR = 3.76, 95% confidence interval (CI) = 3.18-4.44]; and 268 after treatment (0.41 per 100 PY; MRR = 1.99, 95% CI = 1.64-2.41). By counterfactual estimation, national OUD treatment services prevented an average of 880 opioid deaths each year (95% CI = 702-1084). Between April 2008 and March 2011, a counterfactual model shows that the English public treatment system for opioid use disorder prevented an average of 880 deaths each year from opioid-related poisoning. Counterfactual models of mortality prevention can be used for outcome and performance monitoring of substance use disorder treatment systems. © 2015 Society for the Study of Addiction.

[Family typology and deterioration related to opioids use, in a methadone treatment patients group].

PubMed

Garrido Fernández, M; Torrado Val, E; Marcos Sierra, J A

2010-01-01

In this article the familiar functioning of subjects addict to opioids included in a maintenance programme with methadone will be analyzed, trying to identify whether belonging to one type of family (family typology) or another, according to Olson's Familiar Functioning Model, is related to the level of deterioration or severity of addiction of the different areas associated to consumption . The sample is composed by 69 subjects (N=69) users of the Servicio de Atención a las Drogodependencias (SAD) in Centro de Servicios Sociales Comunitarios del Ayuntamiento de Alcalá de Guadaíra (Seville). In order to evaluate the functioning and the family typology of these subjects the Escala de Cohesión y Adaptación Familiar--CAF-1--Spanish version of FACES III was used. In order to evaluate the level of deterioration, the Spanish version of the 5th edition of the personal, clinical semistructured interview Addiction Severity Index--ASI4--was applied. The results indicate that the subjects included in balanced families present more addiction severity in two dimensions of the ASI: Alcohol and Employment/Support and are, moreover, the ones that take greater doses of methadone.

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

PubMed Central

Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena

2015-01-01

Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

Psychiatric disorders in opioid dependants.

PubMed

Ahmadi, Jamshid; Toobaee, Shahin; Kharras, Mohammad; Radmehr, Mohammad

2003-09-01

Psychiatric disorders are common among substance dependants. The objectives of this study were to assess the rate of neurotic disorders among opioid addicts, and reassess the rate of those neurotic disorders two weeks after complete detoxification of the patients. Data were gathered from 500 (496 men and 4 women) opioid dependants, using DSM-IV criteria. The Middlesex Hospital Questionnaire (MHQ) was used to measure free-floating anxiety, depression, phobia, obsession, hysteria and somatization. Four hundred and ninety-six (99.2%) of the subjects were men of whom the majority (65.2%) were married, 26.4% single and the others were divorced or separated. Three hundred and thirty-four (66.8%) were in age range of 20 to 39 years. Of the subjects 154 (30.8) were self-employed, 116 (23.2%) were factory workers, 100 (20%) unemployed, 64 (12.8%) employees and 32 (6.4%) retailers. The majority, 322 (64.4%), reported elementary and high school as their level of education and only 20 (4%) were illiterate. The means for neurotic disorders (using the MHQ) before and two weeks after detoxification were 10.12 and 9.98 for anxiety, 7.54 and 7.41 for phobia, 10.10 and 9.76 for depression, 11.11 and 11.05 for obsession, 8.47 and 8.49 for hysteria and 9.82 and 9.46 for somatization, respectively. The mean difference was significant only for depression. Present findings indicated that the rate of neurotic disorders in opioid dependants is high and (except for depression) was not significantly different before detoxification and two weeks after detoxification. Opium was found to be the most prevalent form of opioid used. Also it can be concluded that during the last years some demographic characteristics of Iranian opioid addicts in this sample have changed. Cultural attitudes toward substance use quite likely affect the pattern of substance use. These findings can be considered when planning preventive and therapeutic programs.

Probuphine® (buprenorphine implant): a promising candidate in opioid dependence

PubMed Central

Barnwal, Preeti; Das, Saibal; Mondal, Somnath; Ramasamy, Anand; Maiti, Tanay; Saha, Arunava

2016-01-01

Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits. PMID:28348732

Probuphine® (buprenorphine implant): a promising candidate in opioid dependence.

PubMed

Barnwal, Preeti; Das, Saibal; Mondal, Somnath; Ramasamy, Anand; Maiti, Tanay; Saha, Arunava

2017-03-01

Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits.

PPARγ activation attenuates opioid consumption and modulates mesolimbic dopamine transmission.

PubMed

de Guglielmo, Giordano; Melis, Miriam; De Luca, Maria Antonietta; Kallupi, Marsida; Li, Hong Wu; Niswender, Kevin; Giordano, Antonio; Senzacqua, Martina; Somaini, Lorenzo; Cippitelli, Andrea; Gaitanaris, George; Demopulos, Gregory; Damadzic, Ruslan; Tapocik, Jenica; Heilig, Markus; Ciccocioppo, Roberto

2015-03-01

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 in 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.

The Addiction Recovery Clinic: A Novel, Primary-Care-Based Approach to Teaching Addiction Medicine.

PubMed

Holt, Stephen R; Segar, Nora; Cavallo, Dana A; Tetrault, Jeanette M

2017-05-01

Substance use is highly prevalent in the United States, but little time in the curriculum is devoted to training internal medicine residents in addiction medicine. In 2014, the authors developed and launched the Addiction Recovery Clinic (ARC) to address this educational gap while also providing outpatient clinical services to patients with substance use disorders. The ARC is embedded within the residency primary care practice and is staffed by three to four internal medicine residents, two board-certified addiction medicine specialists, one chief resident, and one psychologist. Residents spend one half-day per week for four consecutive weeks at the ARC seeing new and returning patients. Services provided include pharmacological and behavioral treatments for opioid, alcohol, and other substance use disorders, with direct referral to local addiction treatment facilities as needed. Visit numbers, a patient satisfaction survey, and an end-of-rotation resident evaluation were used to assess the ARC. From 2014 to 2015, 611 patient encounters occurred, representing 97 new patients. Sixty-one (63%) patients were seen for opioid use disorder. According to patient satisfaction surveys, 29 (of 31; 94%) patients reported that the ARC probably or definitely helped them to cope with their substance use. Twenty-eight residents completed the end-of-rotation evaluation; all rated the rotation highly. The ARC offers a unique primary-care-based approach to exposing internal medicine residents to the knowledge and skills necessary to diagnose, treat, and prevent unhealthy substance use. Future research will examine other clinical and educational outcomes.

A critical analysis of user satisfaction surveys in addiction services: opioid maintenance treatment as a representative case study

PubMed Central

Trujols, Joan; Iraurgi, Ioseba; Oviedo-Joekes, Eugenia; Guàrdia-Olmos, Joan

2014-01-01

Background Satisfaction with services represents a key component of the user’s perspective, and user satisfaction surveys are the most commonly used approach to evaluate the aforementioned perspective. The aim of this discursive paper is to provide a critical overview of user satisfaction surveys in addiction treatment and harm reduction services, with a particular focus on opioid maintenance treatment as a representative case. Methods We carried out a selective critical review and analysis of the literature on user satisfaction surveys in addiction treatment and harm reduction services. Results Most studies that have reported results of satisfaction surveys have found that the great majority of users (virtually all, in many cases) are highly satisfied with the services received. However, when these results are compared to the findings of studies that use different methodologies to explore the patient’s perspective, the results are not as consistent as might be expected. It is not uncommon to find that “highly satisfied” patients report significant problems when mixed-methods studies are conducted. To understand this apparent contradiction, we explored two distinct (though not mutually exclusive) lines of reasoning, one of which concerns conceptual aspects and the other, methodological questions. Conclusion User satisfaction surveys, as currently designed and carried out in addiction treatment and harm reduction services, do not significantly help to improve service quality. Therefore, most of the enthusiasm and naiveté with which satisfaction surveys are currently performed and interpreted – and rarely acted on in the case of nonoptimal results – should be avoided. A truly participatory approach to program evaluation is urgently needed to reshape and transform patient satisfaction surveys. PMID:24482571

Development of an opioid self-administration assay to study drug seeking in zebrafish.

PubMed

Bossé, Gabriel D; Peterson, Randall T

2017-09-29

The zebrafish (Danio rerio) has become an excellent tool to study mental health disorders, due to its physiological and genetic similarity to humans, ease of genetic manipulation, and feasibility of small molecule screening. Zebrafish have been shown to exhibit characteristics of addiction to drugs of abuse in non-contingent assays, including conditioned place preference, but contingent assays have been limited to a single assay for alcohol consumption. Using inexpensive electronic, mechanical, and optical components, we developed an automated opioid self-administration assay for zebrafish, enabling us to measure drug seeking and gain insight into the underlying biological pathways. Zebrafish trained in the assay for five days exhibited robust self-administration, which was dependent on the function of the μ-opioid receptor. In addition, a progressive ratio protocol was used to test conditioned animals for motivation. Furthermore, conditioned fish continued to seek the drug despite an adverse consequence and showed signs of stress and anxiety upon withdrawal of the drug. Finally, we validated our assay by confirming that self-administration in zebrafish is dependent on several of the same molecular pathways as in other animal models. Given the ease and throughput of this assay, it will enable identification of important biological pathways regulating drug seeking and could lead to the development of new therapeutic molecules to treat addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

“The chief of the services is very enthusiastic about it”: A qualitative study of the adoption of buprenorphine for opioid addiction treatment

PubMed Central

Green, Carla A.; McCarty, Dennis; Mertens, Jennifer; Lynch, Frances L.; Hilde, Anadam; Firemark, Alison; Weisner, Constance M.; Pating, David; Anderson, Bradley M.

2013-01-01

Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care. Transcripts were reviewed, coded, and analyzed. A strong leader championing the new treatment was critical for adoption in both health plans. Once clinicians began using buprenorphine, patients’ and other clinicians’ experiences affected decisions more than did the champion. With experience, protocols developed to manage unsuccessful patients and changed to support maintenance rather than detoxification. Diffusion outside addiction and mental health settings was nonexistent; primary care clinicians cited scope-of-practice issues and referred patients to specialty care. With greater diffusion came questions about long-term use and safety. Recognizing how implementation processes develop may suggest where, when, and how to best expend resources to increase adoption of such treatments. PMID:24268947

Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy.

PubMed

Li, Zijian; You, Yue; Griffin, Noreen; Feng, Juan; Shan, Fengping

2018-06-06

Naltrexone, a non-selective antagonist of opioid receptors, is mainly used as rehabilitation therapy for discharged opiate addicts to eliminate addiction in order to maintain a normal life and prevent or reduce relapse. In recent years, there have been some novel and significant findings on the off-label usage of naltrexone. Within a specific dosage window, LDN can act as an immunomodulator in multiple autoimmune diseases and malignant tumors as well as alleviate the symptoms of some mental disorders. The results of increasing studies indicate that LDN exerts its immunoregulatory activity by binding to opioid receptors in or on immune cells and tumor cells. These new discoveries indicate that LDN may become a promising immunomodulatory agent in the therapy for cancer and many immune-related diseases. In this article, we review the pharmacological functions and mechanisms of LDN as well as its clinical therapeutic potential as revealed by our team and other researchers. Copyright © 2018. Published by Elsevier B.V.

Opioid Use Disorder in Pregnancy: Health Policy and Practice in the Midst of an Epidemic

PubMed Central

Krans, Elizabeth E.; Patrick, Stephen W.

2016-01-01

Opioid abuse among pregnant women has reached epidemic proportions and has influenced maternal and child health policy at the federal, state and local levels. As a result, we review the current state of opioid use in pregnancy and evaluate recent legislative and health policy initiatives designed to combat opioid addiction in pregnancy. We emphasize the importance of safe and responsible opioid prescribing practices, expanding the availability and accessibility of medication-assisted treatment and standardizing care for infants at risk of neonatal abstinence syndrome. Efforts to penalize pregnant women and negative consequences for disclosing substance use to providers are harmful and may prevent women from seeking prenatal care and other beneficial health care services during pregnancy. Instead, providers should advocate for health policy informed by scientific research and evidence-based practice to reduce the burden of prenatal opioid abuse and optimize outcomes for mothers and their infants. PMID:27275812

Continuous delivery of naltrexone and nalmefene leads to tolerance in reducing alcohol drinking and to supersensitivity of brain opioid receptors.

PubMed

Korpi, Esa R; Linden, Anni-Maija; Hytönen, Heidi R; Paasikoski, Nelli; Vashchinkina, Elena; Dudek, Mateusz; Herr, Deron R; Hyytiä, Petri

2017-07-01

Opioid antagonist treatments reduce alcohol drinking in rodent models and in alcohol-dependent patients, with variable efficacy across different studies. These treatments may suffer from the development of tolerance and opioid receptor supersensitivity, as suggested by preclinical models showing activation of these processes during and after subchronic high-dose administration of the short-acting opioid antagonist naloxone. In the present study, we compared equipotent low and moderate daily doses of naltrexone and nalmefene, two opioid antagonists in the clinical practice for treatment of alcoholism. The antagonists were given here subcutaneously for 7 days either as daily injections or continuous osmotic minipump-driven infusions to alcohol-preferring AA rats having trained to drink 10% alcohol in a limited access protocol. One day after stopping the antagonist treatment, [ 35 S]GTPγS autoradiography on brain cryostat sections was carried out to examine the coupling of receptors to G protein activation. The results prove the efficacy of repeated injections over infused opioid antagonists in reducing alcohol drinking. Tolerance to the reducing effect on alcohol drinking and to the enhancement of G protein coupling to μ-opioid receptors in various brain regions were consistently detected only after infused antagonists. Supersensitivity of κ-opioid receptors was seen in the ventral and dorsal striatal regions especially by infused nalmefene. Nalmefene showed no clear agonistic activity in rat brain sections or at human recombinant κ-opioid receptors. The findings support the as-needed dosing practice, rather than the standard continual dosing, in the treatment of alcoholism with opioid receptor antagonists. © 2016 Society for the Study of Addiction.

Current and Potential Pharmacological Treatment Options for Maintenance Therapy in Opioid-Dependent Individuals

PubMed Central

Tetrault, Jeanette M.; Fiellin, David A.

2013-01-01

Opioid dependence, manifesting as addiction to heroin and pharmaceutical opioids is increasing. Internationally, there are an estimated 15.6 million illicit opioid users. The global economic burden of opioid dependence is profound both in terms of HIV and hepatitis C virus transmission, direct healthcare costs, and indirectly through criminal activity, absenteeism and lost productivity. Opioid agonist medications, such as methadone and buprenorphine, that stabilize neuronal systems and provide narcotic blockade are the most effective treatments. Prolonged provision of these medications, defined as maintenance treatment, typically produces improved outcomes when compared with short-duration tapers and withdrawal. The benefits of opioid agonist maintenance include decreased illicit drug use, improved retention in treatment, decreased HIV risk behaviours and decreased criminal behaviour. While regulations vary by country, these medications are becoming increasingly available internationally, especially in regions experiencing rapid transmission of HIV due to injection drug use. In this review, we describe the rationale for maintenance treatment of opioid dependence, discuss emerging uses of opioid antagonists such as naltrexone, and sustained-release formulations of naltrexone and buprenorphine, and provide a description of the experimental therapies. PMID:22235870

Post-marketing surveillance of methadone and buprenorphine in the United States.

PubMed

Dasgupta, Nabarun; Bailey, Elise J; Cicero, Theodore; Inciardi, James; Parrino, Mark; Rosenblum, Andrew; Dart, Richard C

2010-07-01

There have been recent increases in the use of methadone and buprenorphine in the United States. Methadone is increasingly being used for pain management, and buprenorphine use has expanded to include treatment for opioid addiction, leading to exposures of these drugs in new populations. There is a debate about the relative safety of these two drugs in routine outpatient medical use. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Programs were used to analyze rates of abuse, misuse, and diversion using the Drug Diversion, Key Informant, Poison Center and Opioid Treatment Programs, 2003-2007. National rate and rate ratios were calculated using population and person-time exposed denominators. Detailed data are presented on severity of medical outcome and drug formulations. Between 2003 and 2007, there were steady increases in the rates of abuse, misuse, and diversion of both methadone and buprenorphine. Rate ratios (per 100,000 population per quarter) of abuse, misuse, and diversion were consistently higher for methadone than buprenorphine. RADARS System poison centers received 7,476 calls for methadone and 1,117 calls for buprenorphine. After accounting for availability, there were higher rates of calls for methadone misuse, abuse, and diversion than buprenorphine in three of the four programs. The numbers of exposures requiring medical attention correspond to 46.8% and 25.8% of all calls, for methadone and buprenorphine, respectively. The most commonly diverted form of methadone was solid oral tablets (which are typically dispensed at pharmacies, not at opioid treatment programs), comprising 73% of cases. Buprenorphine appears to have a better safety profile than methadone during routine outpatient medical use. However, both medications have roles in the treatment of pain and opioid addiction, and further research into their respective benefits and risks should be conducted.

Novel Medications to Treat Addictive Disorders

PubMed Central

Montoya, Iván D.; Vocci, Frank

2008-01-01

Recent discoveries about the effects of drugs of abuse on the brain and the mechanisms of their addictions; new chemical compounds, including immunotherapies; and new actions of available medications are offering many opportunities for the discovery and development of novel medications to treat addictive disorders. Furthermore, advancements in the understanding of the genetic and epigenetic basis of drug addiction and the pharmacogenetics of the safety and/or efficacy of the medications are providing opportunities for more individualized pharmacotherapy approaches. Although multiple medications have been investigated for treating addictions, only a handful have shown acceptable safety and efficacy and are approved by the US Food and Drug Administration. This article reviews the current medications that are medically safe and have shown promising results for treating opioid, cocaine, methamphetamine, and cannabis addictions. PMID:18803912

Trait Mindfulness and Progression to Injection Use in Youth With Opioid Addiction.

PubMed

Wilson, J Deanna; Vo, Hoa; Matson, Pamela; Adger, Hoover; Barnett, Gabriela; Fishman, Marc

2017-09-19

Many youth initiate opioid misuse with prescription opioids and transition over time to more severe substance-using behaviors, including injection. Trait mindfulness is a potentially protective factor. This is a cross-sectional study characterizing a sample of opioid-using youth by level of mindfulness and examines the potential effect modification of emotion regulation on the relationship between mindfulness and progression to injection opioid use. A convenience sample of 112 youth (ages 14-24) was recruited during an episode of inpatient detoxification and residential treatment for opioid use disorders. We examined emotion regulation (Difficulties in Emotion Regulation Scale), mindfulness (Child Acceptance and Mindfulness Measure), and opioid use. We completed multivariable regressions stratified by degree of emotion regulation looking at relationship of mindfulness on time to injection use from age of first prescription opioid. Youth had difficulties in emotion regulation (m = 104.2; SD = 2.41) and low mindfulness (m = 19.1;SD = 0.59). While we found overall that mindfulness was associated with time to progression to injection opioid use, there was significant effect modification. Among youth with high levels of difficulty in emotion regulation, those with high mindfulness trait had quicker progressions to injection (-1.31 years; p =.003). In contrast, youth with normal emotion regulation and high mindfulness trait had a slower progression to injection (1.67 years; p =.041). Conclusion/Importance: Our study showed a majority of youth presenting with opioid use disorders have impairments in emotion regulation and deficits in trait mindfulness. The relationship between mindfulness and opioid use is impacted by emotion regulation capacity. More research is needed to understand the various facets of mindfulness and how they interact with emotion regulation in youth.

Impulsivity and risk for prescription opioid misuse in a chronic pain patient sample.

PubMed

Vest, Noel; Reynolds, Caleb J; Tragesser, Sarah L

2016-09-01

Misuse of, and addiction to, prescription opioid pain relievers is a growing concern, in both non-clinical samples and chronic pain patients receiving opioid analgesic therapy. Research is needed to identify which patients may be more prone to misuse or dependence on opioids in a chronic pain treatment setting. Based on literature showing the role of impulsivity in substance use disorders generally, we predicted that impulsivity may also be important to understanding which individuals may be at risk for opioid misuse when opioids are prescribed for pain. The present study examined associations between impulsivity facets and measures of prescription opioid misuse and symptoms. Four facets of impulsivity were examined: urgency, sensation seeking, lack of premeditation, and lack of perseverance. 143 patients receiving treatment for chronic pain at a regional pain clinic completed a series of questionnaires including the UPPS and measures of opioid risk and misuse. Consistent with predictions, urgency was associated with risk for future misuse (β=0.246, p<0.05), current misuse (β=0.253, p<0.01), and symptoms of current opioid use disorder (OUD; β=0.206, p<0.05). Sensation seeking was also associated with current misuse (β=0.279, p<0.01). These results suggest that identifying facets of impulsivity is important to understanding and assessing for risk of prescription opioid misuse in the context of chronic pain treatment. These data indicate that patients who react impulsively to negative mood states and cravings may be especially prone to developing aberrant use patterns when taking prescription opioids. This is the first known study to identify the role of urgency in predicting risk for OUDs in chronic pain patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deficits in social perception in opioid maintenance patients, abstinent opioid users and non-opioid users.

PubMed

McDonald, Skye; Darke, Shane; Kaye, Sharlene; Torok, Michelle

2013-03-01

This study aimed to compare emotion perception and social inference in opioid maintenance patients with abstinent ex-users and non-heroin-using controls, and determine whether any deficits in could be accounted for by cognitive deficits and/or risk factors for brain damage. Case-control. Sydney, Australia. A total of 125 maintenance patients (MAIN), 50 abstinent opiate users (ABST) and 50 matched controls (CON). The Awareness of Social Inference Test (TASIT) was used to measure emotion perception and social inference. Measures were also taken of executive function, working memory, information processing speed, verbal/non-verbal learning and psychological distress. After adjusting for age, sex, pre-morbid IQ and psychological distress, the MAIN group was impaired relative to CON (β = -0.19, P < 0.05) and ABST (β = -0.19, P < 0.05) on emotion perception and relative to CON (β = -0.25, P < 0.001) and ABST (β = -0.24, P < 0.01) on social inference. In neither case did the CON and ABST groups differ. For both emotion perception (P < 0.001) and social inference (P < 0.001), pre-morbid IQ was a significant independent predictor. Cognitive function was a major predictor of poor emotion perception (β = -0.44, P < 0.001) and social inference (β = -0.48, P < 0.001). Poor emotion recognition was also predicted by number of heroin overdoses (β = -0.14, P < 0.05). Neither time in treatment or type of maintenance medication (methadone or buprenorphine) were related to performance. People in opioid maintenance treatment may have an impaired capacity for emotion perception and ability to make inferences about social situations. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Primary care physicians’ perspectives on the prescription opioid epidemic*

PubMed Central

Kennedy-Hendricks, Alene; Busch, Susan H.; McGinty, Emma E.; Bachhuber, Marcus A.; Niederdeppe, Jeff; Gollust, Sarah E.; Webster, Daniel W.; Fiellin, David A.; Barry, Colleen L.

2016-01-01

Background Prescription opioid use disorder and overdose have risen substantially in the U.S. Primary care physicians are critical to many ongoing and proposed efforts to address the prescription opioid epidemic. Yet, little is known about their attitudes and beliefs surrounding this issue. This study aimed to determine primary care physicians’ perceptions of the seriousness of the problem, its causes, groups responsible for addressing it, attitudes toward individuals with prescription opioid use disorder, beliefs about the effectiveness of addiction treatments, and support for various policies. Methods We conducted a national web-based survey in 2014 among 1,010 primary care physicians. We gauged responses to attitude and belief items on 7-point Likert scales. We examined the proportion agreeing with each statement, and whether responses differed among physicians prescribing higher and lower volumes of opioids. Results Respondents largely attributed the causes of prescription opioid use disorder to individual-oriented factors and certain physician-oriented factors, and believed that individuals with prescription opioid use disorder and physicians were primarily responsible for addressing the problem. Negative attitudes toward people with prescription opioid use disorder were prevalent, but a majority believed that treatment could be effective. There was majority support for all measured policies, with the highest levels of support for policies to monitor prescribing among patients potentially at risk for an opioid use disorder and to improve physician education and training. Conclusions Given strong endorsement of recommended policies, physician support could be leveraged to advance efforts to curb prescription opioid use disorder and overdose. PMID:27261154

Psychological and physiological stress negatively impacts early engagement and retention of opioid-dependent individuals on methadone maintenance

PubMed Central

Jaremko, Kellie M.; Sterling, Robert C.; Van Bockstaele, Elisabeth J.

2014-01-01

The present study investigated whether psychological and/or physiological measures of stress would impede induction onto methadone maintenance and predict early (<6 months) discontinuation. Compared with controls, opioid-dependent subjects displayed increased distress on the perceived stress scale (PSS) and post-traumatic stress disorder checklist (PCLC); 60% exhibited abnormal cortisol. Addiction severity index (ASI), drug-use, and stress indices explained between 17–37% of the variance in engagement including attendance, opioid abstinence, and methadone stabilization. Participants who discontinued treatment displayed poor engagement, abnormal cortisol, elevated withdrawal symptoms, higher distress, and increased ongoing opioid use versus compliant individuals. Discontinuation was initially related to drug-use severity; however, by 6 months, retention depended primarily upon cortisol abnormalities, which increased an individual’s discontinuation risk by 7.7-fold. These findings support admission screening with the ASI/cortisol for drop out, and stress/drug-use indices for engagement that together may enable clinically-relevant early recognition and interventions for prevention of stress-induced relapse in opioid-dependent populations. PMID:25239858

Psychological and physiological stress negatively impacts early engagement and retention of opioid-dependent individuals on methadone maintenance.

PubMed

Jaremko, Kellie M; Sterling, Robert C; Van Bockstaele, Elisabeth J

2015-01-01

The present study investigated whether psychological and/or physiological measures of stress would impede induction onto methadone maintenance and predict early (<6 months) discontinuation. Compared with controls, opioid-dependent subjects displayed increased distress on the perceived stress scale (PSS) and post-traumatic stress disorder checklist (PCLC); 60% exhibited abnormal cortisol. Addiction severity index (ASI), drug-use, and stress indices explained between 17 and 37% of the variance in engagement including attendance, opioid abstinence, and methadone stabilization. Participants who discontinued treatment displayed poor engagement, abnormal cortisol, elevated withdrawal symptoms, higher distress, and increased ongoing opioid use versus compliant individuals. Discontinuation was initially related to drug-use severity; however, by 6 months, retention depended primarily upon cortisol abnormalities, which increased an individual's discontinuation risk by 7.7-fold. These findings support admission screening with the ASI/cortisol for drop out, and stress/drug-use indices for engagement that together may enable clinically-relevant early recognition and interventions for prevention of stress-induced relapse in opioid-dependent populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Global Supply and Demand of Opioids for Pain Management.

PubMed

Kunnumpurath, Sreekumar; Julien, Natasha; Kodumudi, Gopal; Kunnumpurath, Anamika; Kodumudi, Vijay; Vadivelu, Nalini

2018-04-04

The goal of this review is to evaluate the global supply and demand of opioids used for pain management and discuss how it relates to the utilization of opioids around the world. The purpose of the review is also to determine the factors that contribute to inappropriate pain management. The total global production of opium for opioid manufacturing is enough to supply the growing global demands. However, licit opioids are only consumed by 20% of the world population. Most people throughout the world had no access to opioid analgesics for pain relief in case of need. Opioid misuse and abuse is not only a phenomena plague by the USA but globally across many countries. Many countries have a lack of availability of opioids, contributing factors being strict government regulations limiting access, lack of knowledge of the efficacy of opioid analgesics in treating acute and chronic pain and palliative care, and the stigma that opioids are highly addictive. For the countries in which opioids are readily available and prescribed heavily, diversion, misuse, abuse, and the resurgence of heroin have become problems leading to morbidity and mortality. It is pertinent to find a balance between having opioids accessible to patients in need, with ensuring that opioids are regulated along with other illicit drugs to decrease abuse potential.

What's holding back abuse-deterrent opioid formulations? Considering 12 U.S. stakeholders.

PubMed

Pergolizzi, Joseph V; Taylor, Robert; LeQuang, Jo Ann; Raffa, Robert B

2018-06-01

There is no greater public health threat at this time in America than the opioid abuse crisis, and a systematic, level-headed, coherent, and unified approach is needed. Among the many things that have been proposed to help reduce opioid abuse is the development of opioid analgesic products in abuse-deterrent formulations (ADFs). This seems to make perfect sense. Areas covered: In this article, the viewpoints of 12 stakeholders (physicians, pain patients, payers, manufacturers, regulators, law enforcement, hospitals, first responders, elected officials, rehabilitation centers, opioid addicts, and the general public) were considered in terms of how ADF opioids are regarded and might contribute potential impediments to more widespread use. This is a narrative review based on the literature. Stakeholders were not surveyed directly. Expert opinion: Although abuse-deterrent technology for opioid analgesics has been available for several years, ADFs have not gained widespread acceptance. ADF products serve an important but limited purpose, but their incremental costs may serve as a 'mixed message' for many of the stakeholders concerned about cost containment.

Recent Advances in the Realm of Allosteric Modulators for Opioid Receptors for Future Therapeutics.

PubMed

Remesic, Michael; Hruby, Victor J; Porreca, Frank; Lee, Yeon Sun

2017-06-21

Opioids, and more specifically μ-opioid receptor (MOR) agonists such as morphine, have long been clinically used as therapeutics for severe pain states but often come with serious side effects such as addiction and tolerance. Many studies have focused on bringing about analgesia from the MOR with attenuated side effects, but its underlying mechanism is not fully understood. Recently, focus has been geared toward the design and elucidation of the orthosteric site with ligands of various biological profiles and mixed subtype opioid activities and selectivities, but targeting the allosteric site is an area of increasing interest. It has been shown that allosteric modulators play key roles in influencing receptor function such as its tolerance to a ligand and affect downstream pathways. There has been a high variance of chemical structures that provide allosteric modulation at a given receptor, but recent studies and reviews tend to focus on the altered cellular mechanisms instead of providing a more rigorous description of the allosteric ligand's structure-function relationship. In this review, we aim to explore recent developments in the structural motifs that potentiate orthosteric binding and their influences on cellular pathways in an effort to present novel approaches to opioid therapeutic design.

Implementation of the Provision of the Comprehensive Addiction and Recovery Act of 2016 Relating to the Dispensing of Narcotic Drugs for Opioid Use Disorder. Final rule.

PubMed

2018-01-23

The Comprehensive Addiction and Recovery Act (CARA) of 2016, which became law on July 22, 2016, amended the Controlled Substances Act (CSA) to expand the categories of practitioners who may, under certain conditions on a temporary basis, dispense a narcotic drug in Schedule III, IV, or V for the purpose of maintenance treatment or detoxification treatment. Separately, the Department of Health and Human Services, by final rule effective August 8, 2016, increased to 275 the maximum number of patients that a practitioner may treat for opioid use disorder without being separately registered under the CSA for that purpose. The Drug Enforcement Administration (DEA) is hereby amending its regulations to incorporate these statutory and regulatory changes.

A Systematic Review of Attention Biases in Opioid, Cannabis, Stimulant Use Disorders.

PubMed

Zhang, Melvyn; Ying, Jiangbo; Wing, Tracey; Song, Guo; Fung, Daniel S S; Smith, Helen

2018-06-01

Background : Opiates, cannabis, and amphetamines are highly abused, and use of these substances are prevalent disorders. Psychological interventions are crucial given that they help individuals maintain abstinence following a lapse or relapse into substance use. Advances in experimental psychology have suggested that automatic attention biases might be responsible for relapse. Prior reviews have provided evidence for the presence of these biases in addictive disorders and the effectiveness of bias modification. However, the prior studies are limited, as they failed to include trials involving participants with these prevalent addictive disorders or have failed to adopt a systematic approach in evidence synthesis. Objectives : The primary aim of this current systematic review is to synthesise the current evidence for attention biases amongst opioid use, cannabis use, and stimulant use disorders. The secondary aim is to determine the efficacy of attention bias modification interventions and other addictions related outcomes. Methods : A search was conducted from November 2017 to January 2018 on PubMed, MEDLINE, Embase, PsycINFO, Science Direct, Cochrane Central, and Scopus. The selection process of the articles was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A qualitative synthesis was undertaken. Risk of bias was assessed using the Cochrane Risk of Bias tool. Results : Six randomised trials were identified. The evidence synthesized from these trials have provided strong evidence that attentional biases are present in opioid and stimulant use disorders. Evidence synthesis for other secondary outcome measures could not be performed given the heterogeneity in the measures reported and the limited number of trials. The risk of bias assessment for the included trials revealed a high risk of selection and attrition bias. Conclusions : This review demonstrates the potential need for interventions targeting attention biases in opiate and cocaine use disorders.

Abuse of reformulated OxyContin: Updated findings from a sentinel surveillance sample of individuals assessed for substance use disorder.

PubMed

Cassidy, Theresa A; Thorley, Eileen; Black, Ryan A; DeVeaugh-Geiss, Angela; Butler, Stephen F; Coplan, Paul

To examine abuse prevalence for OxyContin and comparator opioids over a 6-year period prior to and following market entry of reformulated OxyContin and assess consistency in abuse across treatment settings and geographic regions. An observational study examining longitudinal changes using cross-sectional data from treatment centers for substance use disorder. A total of 874 facilities in 39 states in the United States within the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO®) surveillance system. Adults (72,060) assessed for drug problems using the Addiction Severity Index-Multimedia Version (ASI-MV®) from January 2009 through December 2015 who abused prescription opioids. Percent change in past 30-day abuse. OxyContin had significantly lower abuse 5 years after reformulation compared to levels for original OxyContin. Consistency of magnitude in OxyContin abuse reductions across geographic regions, ranging from 41 to 52 percent with differences in abuse reductions in treatment setting categories occurred. Changes in geographic region and treatment settings across study years did not bias the estimate of lower OxyContin abuse through confounding. In the postmarket setting, limitations and methodologic challenges in abuse measurement exist and it is difficult to isolate singular impacts of any one intervention given the complexity of prescription opioid abuse. Expectations for a reasonable threshold of abuse for any one ADF product or ADF opioids as a class are still uncertain and undefined. A significant decline in abuse prevalence of reformulated OxyContin was observed 5 years after its reformulation among this treatment sample of individuals assessed for substance use disorder that was lower historically for the original formulation of this product.

Delay discounting, impulsiveness, and addiction severity in opioid-dependent patients.

PubMed

Robles, Elias; Huang, B Emma; Simpson, Pippa M; McMillan, Donald E

2011-12-01

Individuals who abuse drugs show higher delay discounting (DD) rate and impulsiveness scores compared with controls; however, it is unclear if DD rate covaries with severity of the addiction or if an individual's discounting rate can be changed by effective substance abuse treatment. This study compared methadone maintenance treatment (MMT) patients (n = 30) who had not used illegal drugs for 2 years with drug-using MMT patients (n = 30) and controls (n = 25) in terms of addiction severity, DD rate, and impulsiveness. Methadone patients abstinent from illegal drugs scored significantly lower on a number of addiction severity measures than the drug-using methadone patients. In addition, both groups of MMT patients showed significantly higher rates of DD and impulsiveness than the control group; however, no differences in DD rate or impulsiveness were found between the groups of patients. Results suggest that DD rate and impulsiveness may not covary with indicators of addiction severity in MMT patients. Published by Elsevier Inc.

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage.

PubMed

Hurd, Yasmin L; Yoon, Michelle; Manini, Alex F; Hernandez, Stephanie; Olmedo, Ruben; Ostman, Maria; Jutras-Aswad, Didier

2015-10-01

Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ(9)-tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from "medical CBD" and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

Correlations Between Awareness of Illness (Insight) and History of Addiction in Heroin-Addicted Patients

PubMed Central

Maremmani, Angelo Giovanni Icro; Rovai, Luca; Rugani, Fabio; Pacini, Matteo; Lamanna, Francesco; Bacciardi, Silvia; Perugi, Giulio; Deltito, Joseph; Dell’Osso, Liliana; Maremmani, Icro

2012-01-01

In a group of 1066 heroin addicts, who were seeking treatment for opioid agonist treatment, we looked for differences in historical, demographic, and clinical characteristics, between patients with different levels of awareness of illness (insight). The results showed that, in the cohort studied, a majority of subjects lacked insight into their heroin-use behavior. Compared with the impaired-insight group, those who possessed insight into their illness showed significantly greater awareness of past social, somatic, and psychopathological impairments, and had a greater number of past treatment-seeking events for heroin addiction. In contrast with other psychiatric illnesses, the presence of awareness appears to be related to the passing of time and to the worsening of the illness. Methodologies to improve the insight of patients should, therefore, be targeted more directly on patients early in their history of heroin dependence, because the risk of lack of insight is greatest during this period. PMID:22787450

International Narcotics Research Conference-35th Meeting. Current developments in medicinal chemistry in the opioid field 17-24 July 2004, Kyoto, Japan.

PubMed

Kitchen, Ian

2004-09-01

Research in the opioid field underwent a lull in the 1990's but much new research has recently been stimulated, firstly by the cloning of all of the opioid receptors and then by the development of gene knockout mice and their phenotype characterization. These developments have led to a a reappraisal of the potential utility of opioid agonists and antagonists not only for the treatment of pain but also for mood-related conditions and peripheral indications. Medicinal chemistry groups are still moving the field forward, and the pharmaceutical industry continues to keep a watching brief. Opioids are no longer exclusively the province of pain scientists, and potential for treatment of limbic disorders, itch and addiction are only now beginning to be considered seriously.

Opioid withdrawal, craving, and use during and after outpatient buprenorphine stabilization and taper: A discrete survival and growth mixture model

PubMed Central

Stotts, Angela L.; Green, Charles; Potter, Jennifer S.; Marino, Elise N.; Walker, Robrina; Weiss, Roger D.; Trivedi, Madhukar

2014-01-01

Most patients relapse to opioids within one month of opioid agonist detoxification, making the antecedents and parallel processes of first use critical for investigation. Craving and withdrawal are often studied in relationship to opioid outcomes, and a novel analytic strategy applied to these two phenomena may indicate targeted intervention strategies. Specifically, this secondary data analysis of the Prescription Opioid Addiction Treatment Study used a discrete-time mixture analysis with time-to-first opioid use (survival) simultaneously predicted by craving and withdrawal growth trajectories. This analysis characterized heterogeneity among prescription opioid-dependent individuals (N=653) into latent classes (i.e., latent class analysis [LCA]) during and after buprenorphine/naloxone stabilization and taper. A 4-latent class solution was selected for overall model fit and clinical parsimony. In order of shortest to longest time-to-first use, the 4 classes were characterized as 1) high craving and withdrawal 2) intermediate craving and withdrawal 3) high initial craving with low craving and withdrawal trajectories and 4) a low initial craving with low craving and withdrawal trajectories. Odds ratio calculations showed statistically significant differences in time-to-first use across classes. Generally, participants with lower baseline levels and greater decreases in craving and withdrawal during stabilization combined with slower craving and withdrawal rebound during buprenorphine taper remained opioid-free longer. This exploratory work expanded on the importance of monitoring craving and withdrawal during buprenorphine induction, stabilization, and taper. Future research may allow individually tailored and timely interventions to be developed to extend time-to-first opioid use. PMID:25282598

Prescription Drug Abuse

MedlinePlus

... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include opioids, sedatives, ...

For Whom the Bell Tolls: A Special Journal Issue on Smoking Control and an Interview With Dr Harry Lando.

PubMed

Terry, Paul E

2018-06-01

Opioid addiction has been cast as a "disease of despair."1 I agree, but I wonder still: If tobacco and opioids were on a spectrum relative to the relief they provide from social, emotional, financial, and other sources of pain in the lives of the disenfranchised, could it be that they are indeed 2 sides of the same coin? For individuals in despair, pain relief is a complicit actor in what will become pleasure seeking and, for smokers, vice versa. Every year, almost as many people are dying by incidentally being near smokers as are dying by accidentally overdosing. Our opioid epidemic has been declared a national public health emergency, though the annual death toll from tobacco is 10 times greater. How should we reconcile this? As is extraordinarily represented in my interview with Dr Harry Lando and as is evident from the range of articles on tobacco control in this special issue, tobacco addiction research draws from every corner of psychology, sociology, philosophy, and other disciplines intent on understanding the human condition.

Safety and tolerability of the switch from buprenorphine to buprenorphine/naloxone in an Italian addiction treatment centre.

PubMed

Stimolo, Clementina; Favero, Valentina Del; Zecchinato, Giancarlo; Buson, Roberto; Cusin, Davide; Pellachin, Patrizia; Simonetto, Pamela

2010-01-01

Abuse and misuse of pharmacological therapies represent major challenges in the healthcare system, particularly in patients receiving long-acting opioid drugs for the treatment of heroin or opioid addiction. The partial mu-opioid receptor agonist buprenorphine is used to treat opioid dependence, but diversion and misuse may occur. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is associated with a reduced abuse potential, and has been shown to have promising efficacy for the treatment of opioid dependence. This observational study assessed the safety and efficacy of sublingual buprenorphine/naloxone combination therapy in patients with opioid dependence after therapeutic switch from buprenorphine monotherapy. A total of 94 patients being treated with buprenorphine monotherapy (average dose 8 mg/day; mean duration of therapy 840 days) were switched to buprenorphine/naloxone combination therapy. Patients were asked to rate their level of satisfaction with buprenorphine/naloxone combination treatment with respect to the management of withdrawal symptoms, and urinary toxicology tests were carried out before and 14 days after switching to combination therapy. Within 3 months, 75/94 patients (80%) previously treated with buprenorphine monotherapy had switched to sublingual buprenorphine/naloxone combination treatment (average dose buprenorphine 8 mg). Among patients receiving combination treatment for >3 months, 83% were receiving medication either weekly or fortnightly, based on the results of toxicological testing. A reduction in positive urinary toxicology tests was observed in patients within two weeks after being switched to combination treatment (before switch: 28, 9 and 2 positive tests for heroin, cocaine and heroin + cocaine, respectively vs 11, 3 and 1 after switch) and a total of 64 patients of the 75 who switched to combination therapy (85%) were satisfied with the management of withdrawal symptoms during buprenorphine/naloxone treatment. Few adverse events were reported and no patients dropped out of treatment. This study shows that switching from buprenorphine monotherapy to sublingual buprenorphine/naloxone combination therapy is effective and well tolerated, and associated with good control of withdrawal symptoms in the majority of patients. In addition, combination therapy reduced illicit drug use (based on negative urinary toxicology texts) and allowed the time between clinic visits to be increased.

Nicotine anxiogenic and rewarding effects are decreased in mice lacking beta-endorphin.

PubMed

Trigo, José M; Zimmer, Andreas; Maldonado, Rafael

2009-06-01

The endogenous opioid system plays an important role in the behavioral effects of nicotine. Thus, micro-opioid receptor and the endogenous opioids derived from proenkephalin are involved in the central effects of nicotine. However, the role played by the different endogenous opioid peptides in the acute and chronic effects of nicotine remains to be fully established. Mice lacking beta-endorphin were acutely injected with nicotine at different doses to evaluate locomotor, anxiogenic and antinociceptive responses. The rewarding properties of nicotine were evaluated by using the conditioned place-preference paradigm. Mice chronically treated with nicotine were acutely injected with mecamylamine to study the behavioral expression of nicotine withdrawal. Mice lacking beta-endorphin exhibited a spontaneous hypoalgesia and hyperlocomotion and a reduction on the anxiogenic and rewarding effects induced by nicotine. Nicotine induced similar antinociception and hypolocomotion in both genotypes and no differences were found in the development of physical dependence. The dissociation between nicotine rewarding properties and physical dependence suggests a differential implication of beta-endorphin in these addictive related responses.

The affective dimension of pain as a risk factor for drug and alcohol addiction.

PubMed

LeBlanc, Dana M; McGinn, M Adrienne; Itoga, Christy A; Edwards, Scott

2015-12-01

Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input. We hypothesize that a sensitization of brain mechanisms underlying the processing of persistent and maladaptive pain contributes to a composite negative affective state to drive the enduring, relapsing nature of addiction, particularly in the case of alcohol and opioid use disorder. At the neurochemical level, pain activates central stress-related neuropeptide signaling, including the dynorphin and corticotropin-releasing factor (CRF) systems, and by this process may facilitate negative affect and escalated drug and alcohol use over time. Importantly, the widespread prevalence of unresolved pain and associated affective dysregulation in clinical populations highlights the need for more effective analgesic medications with reduced potential for tolerance and dependence. The burgeoning epidemic of prescription opioid abuse also demands a closer investigation into the neurobiological mechanisms of how pain treatment could potentially represent a significant risk factor for addiction in vulnerable populations. Finally, the continuing convergence of sensory and affective neuroscience fields is expected to generate insight into the critical balance between pain relief and addiction liability, as well as provide more effective therapeutic strategies for chronic pain and addiction. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of opioid therapy on gonadal hormones: focus on buprenorphine.

PubMed

Varma, Anjali; Sapra, Mamta; Iranmanesh, Ali

2018-02-17

Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

Comorbid Post-Traumatic Stress Disorder and Opioid Dependence.

PubMed

Patel, Rikinkumar S; Elmaadawi, Ahmed; Nasr, Suhayl; Haskin, John

2017-09-03

Post-traumatic stress disorder (PTSD) is predominant amongst individuals addicted to opioids and obscures the course of illness and the treatment outcome. We report the case of a patient with major depressive disorder and opioid dependence, who experienced post-traumatic stress disorder symptoms during a recent visit to the inpatient unit. The similarity of symptoms between post-traumatic stress disorder and opioid dependence is so high that, sometimes, it is a challenge to differentiate between these conditions. Since opioid withdrawal symptoms mimic hyper vigilance, this results in an exaggeration of the response of patients with post-traumatic stress disorder. This comorbidity is associated with worse health outcomes, as its pathophysiology involves a common neurobiological circuit. Opioid substitution therapy and psychotherapeutic medications in combination with evidence-based cognitive behavioral therapy devised for individuals with comorbid post-traumatic stress disorder and opioid dependence may improve treatment outcomes in this population. Therefore, we conclude that the screening for post-traumatic stress disorder in the opioid-abusing population is crucial. To understand the underlying mechanisms for this comorbidity and to improve the treatment response, further research should be encouraged.

Evaluating the impact of a national naloxone programme on ambulance attendance at overdose incidents: a controlled time-series analysis.

PubMed

McAuley, Andrew; Bouttell, Janet; Barnsdale, Lee; Mackay, Daniel; Lewsey, Jim; Hunter, Carole; Robinson, Mark

2017-02-01

It has been suggested that distributing naloxone to people who inject drugs (PWID) will lead to fewer attendances by emergency medical services at opioid-related overdose incidents if peer administration of naloxone was perceived to have resuscitated the overdose victim successfully. This study evaluated the impact of a national naloxone programme (NNP) on ambulance attendance at opioid-related overdose incidents throughout Scotland. Specifically, we aimed to answer the following research questions: is there evidence of an association between ambulance call-outs to opioid-related overdose incidents and the cumulative number of 'take-home naloxone' (THN) kits in issue; and is there evidence of an association between ambulance call-outs to opioid-related overdose incidents in early adopter (pilot) or later adopting (non-pilot) regions and the cumulative number of THN kits issued in those areas? Controlled time-series analysis. Scotland, UK, 2008-15. Pre-NNP implementation period for the evaluation was defined as 1 April 2008 to 31 March 2011 and the post-implementation period as 1 April 2011 to 31 March 2015. In total, 3721 ambulance attendances at opioid-related overdose were recorded for the pre-NNP implementation period across 158 weeks (mean 23.6 attendances per week) and 5258 attendances across 212 weeks in the post-implementation period (mean 24.8 attendances per week). Scotland's NNP; formally implemented on 1 April 2011. Primary outcome measure was weekly incidence (counts) of call-outs to opioid-related overdoses at national and regional Health Board level. Data were acquired from the Scottish Ambulance Service (SAS). Models were adjusted for opioid replacement therapy using data acquired from the Information Services Division on monthly sums of all dispensed methadone and buprenorphine in the study period. Models were adjusted further for a control group: weekly incidence (counts) of call-outs to heroin-related overdose in the London Borough area acquired from the London Ambulance Service. There was no significant association between SAS call-outs to opioid-related overdose incidents and THN kits in issue for Scotland as a whole (coefficient 0.009, 95% confidence intervals = -0.01, 0.03, P = 0.39). In addition, the magnitude of association between THN kits and SAS call-outs did not differ significantly between pilot and non-pilot regions (interaction test, P = 0.62). The supply of take-home naloxone kits through a National Naloxone Programme in Scotland was not associated clearly with a decrease in ambulance attendance at opioid-related overdose incidents in the 4-year period after it was implemented in April 2011. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Use of buprenorphine for addiction treatment: perspectives of addiction specialists and general psychiatrists.

PubMed

Thomas, Cindy Parks; Reif, Sharon; Haq, Sayeda; Wallack, Stanley S; Hoyt, Alexander; Ritter, Grant A

2008-08-01

In 2002 buprenorphine (Suboxone or Subutex) was approved by the U.S. Food and Drug Administration for office-based treatment of opioid addiction. The goal of office-based pharmacotherapy is to bring more opiate-dependent people into treatment and to have more physicians address this problem. This study examined prescribing practices for buprenorphine, including facilitators and barriers, and the organizational settings that facilitate its being incorporated into treatment. Addiction specialists and other psychiatrists in four market areas were surveyed by mail and Internet in fall 2005 to examine prescribing practices for buprenorphine. Respondents included 271 addiction specialists (72% response rate) and 224 psychiatrists who were not listed as addiction specialists but who had patients with addictions in their practice (57% response rate). Three years after approval of buprenorphine for office-based addiction treatment, nearly 90% of addiction specialists had been approved to prescribe it and two-thirds treated patients with buprenorphine. However, fewer than 10% of non-addiction specialist psychiatrists prescribed it. Regression-adjusted factors predicting prescribing of buprenorphine included support of training and use of buprenorphine by the physician's main affiliated organization, less time in general psychiatry compared with addictions treatment, more time in group practice rather than solo, ten or more opiate-dependent patients, belief that drugs play a large role in addiction treatment, and patient demand. Office-based pharmacotherapy offers a promising path to improved access to addictions treatment, but prescribing has expanded little beyond the addiction specialist community.

Opioid Stewardship in Otolaryngology: State of the Art Review.

PubMed

Cramer, John D; Wisler, Brad; Gouveia, Christopher J

2018-05-01

Objective The United States is facing an epidemic of opioid addiction. Deaths from opioid overdose have quadrupled in the past 15 years and now surpass annual deaths during the height of the human immunodeficiency virus epidemic. There is a link between opioid prescriptions after surgery, opioid misuse, opioid diversion, and use of other drugs of abuse. As surgeons, otolaryngologists contribute to this crisis. Our objective is to outline the risk of abuse from opioids in the management of acute postoperative pain in otolaryngology-head and neck surgery (OHNS) and strategies to avoid misuse. Data Sources PubMed/MEDLINE. Review Methods We conducted a review of the literature on the rate of opioid abuse after surgery, methods of safe opioid use, and strategies to minimize the dangers of opioids. Conclusions Otolaryngologists have a responsibility to treat pain. This begins preoperatively by discussing perioperative pain control and developing a personalized pain control plan. Patients should be aware that opioids carry significant risks of adverse events and abuse. Perioperative use of multimodal nonopioid agents enables pain control and avoidance of opioids in many otolaryngologic cases. When this approach is inadequate, opioids should be used in short duration under close surveillance. Institutional standards for opioid prescribing after common procedures can minimize misuse. Implications for Practice Otolaryngologists need to acknowledge the potential harm that opioids cause. It is essential that we evaluate our practices to ensure that opioids are used responsibly. Furthermore, opioid stewardship should become a priority in otolaryngology.

Genetic and pharmacological antagonism of NK1 receptor prevents opiate abuse potential.

PubMed

Sandweiss, A J; McIntosh, M I; Moutal, A; Davidson-Knapp, R; Hu, J; Giri, A K; Yamamoto, T; Hruby, V J; Khanna, R; Largent-Milnes, T M; Vanderah, T W

2017-05-09

Development of an efficacious, non-addicting analgesic has been challenging. Discovery of novel mechanisms underlying addiction may present a solution. Here we target the neurokinin system, which is involved in both pain and addiction. Morphine exerts its rewarding actions, at least in part, by inhibiting GABAergic input onto substance P (SP) neurons in the ventral tegmental area (VTA), subsequently increasing SP release onto dopaminergic neurons. Genome editing of the neurokinin 1 receptor (NK 1 R) in the VTA renders morphine non-rewarding. Complementing our genetic approach, we demonstrate utility of a bivalent pharmacophore with dual activity as a μ/δ opioid agonist and NK 1 R antagonist in inhibiting nociception in an animal model of acute pain while lacking any positive reinforcement. These data indicate that dual targeting of the dopaminergic reward circuitry and pain pathways with a multifunctional opioid agonist-NK 1 R antagonist may be an efficacious strategy in developing future analgesics that lack abuse potential.Molecular Psychiatry advance online publication, 9 May 2017; doi:10.1038/mp.2017.102.

Classification and Short-Term Course of DSM-IV Cannabis, Hallucinogen, Cocaine, and Opioid Disorders in Treated Adolescents

ERIC Educational Resources Information Center

Chung, Tammy; Martin, Christoper S.

2005-01-01

This study examined the latent class structure of Diagnostic and Statistical Manual of Mental Disorders (text rev.; DSM-IV; American Psychiatric Association, 2000) symptoms used to diagnose cannabis, hallucinogen, cocaine, and opiate disorders among 501 adolescents recruited from addictions treatment. Latent class results were compared with the…

Evaluation of 6 remote First Nations community-based buprenorphine programs in northwestern Ontario: Retrospective study.

PubMed

Mamakwa, Solomon; Kahan, Meldon; Kanate, Dinah; Kirlew, Mike; Folk, David; Cirone, Sharon; Rea, Sara; Parsons, Pierre; Edwards, Craig; Gordon, Janet; Main, Fiona; Kelly, Len

2017-02-01

To evaluate established opioid addiction treatment programs that use traditional healing in combination with buprenorphine-naloxone maintenance treatment in 6 First Nations communities in the Sioux Lookout region of northwestern Ontario. Retrospective cohort study. Six First Nations communities in northwestern Ontario. A total of 526 First Nations participants in opioid-dependence treatment programs. Buprenorphine-naloxone substitution therapy and First Nations healing programming. Retention rates and urine drug screening (UDS) results. Treatment retention rates at 6, 12, and 18 months were 84%, 78%, and 72%, respectively. We estimate that the rate at 24 months will also be more than 70%. The UDS programming varied and was implemented in only 1 community. Initially urine testing was voluntary and it then became mandatory. Screening with either method found the proportion of urine samples with negative results for illicit opioids ranged between 84% and 95%. The program's treatment retention rates and negative UDS results were higher than those reported for most methadone and buprenorphine-naloxone programs, despite a patient population where severe posttraumatic stress disorder is endemic, and despite the programs' lack of resources and addiction expertise. Community-based programs like these overcome the initial challenge of cultural competence. First Nations communities in other provinces should establish their own buprenorphinenaloxone programs, using local primary care physicians as prescribers. Sustainable core funding is needed for programming, long-term aftercare, and trauma recovery for such initiatives. Copyright© the College of Family Physicians of Canada.

How Can Prescription Drug Addiction Be Treated?

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Principles of Substance Abuse Prevention for Early Chil... Marijuana: Facts Parents Need to Know Marijuana: Facts for ...

Psychological predictors of retention in a low-threshold methadone maintenance treatment for opioid addicts: a 1-year follow-up study.

PubMed

Perreault, Michel; Julien, Dominic; White, Noe Djawn; Rabouin, Daniel; Lauzon, Pierre; Milton, Diana

2015-01-01

This study investigated the role of psychological variables and judicial problems in treatment retention for a low-threshold methadone program in Montreal, Canada. Logistic regression analyses were computed to examine associations between psychological variables (psychological distress, self-esteem, stages of change), criminal justice involvement, and treatment retention for 106 highly-disorganized opioid users. Higher methadone dosage was associated with increased odds of treatment retention, whereas criminal charges and lower self-esteem decreased these odds. Psychological variables could be identified early in treatment and targeted to increase potential treatment retention. Financial support for this study was provided by the Fonds de Recherche en Santé du Québec.

A text-mining analysis of the public's reactions to the opioid crisis.

PubMed

Glowacki, Elizabeth M; Glowacki, Joseph B; Wilcox, Gary B

2017-07-19

Opioid abuse has become an epidemic in the United States. On August 25, 2016, the former Surgeon General of the United States sent an open letter to care providers asking for their help with combatting this growing health crisis. Social media forums such as Twitter allow for open discussions among the public and up-to-date exchanges of information about timely topics such as opioids. Therefore, the goal of the current study is to identify the public's reactions to the opioid epidemic by identifying the most popular topics tweeted by users. A text miner, algorithmic-driven statistical program was used to capture 73,235 original tweets and retweets posted within a 2-month time span 15 (August 15, 2016, through October 15, 2016). All tweets contained references to "opioids," "turnthetide," or similar keywords. The sets of tweets were then analyzed to identify the most prevalent topics. The most discussed topics had to do with public figures addressing opioid abuse, creating better treatment options for teen addicts, using marijuana as an alternative for managing pain, holding foreign and domestic drug makers accountable for the epidemic, promoting the "Rx for Change" campaign, addressing double standards in the perceptions and treatment of black and white opioid users, and advertising opioid recovery programs. Twitter allows users to find current information, voice their concerns, and share calls for action in response to the opioid epidemic. Monitoring the conversations about opioids that are taking place on social media forums such as Twitter can help public health officials and care providers better understand how the public is responding to this health crisis.

The Impact of Social Support and Attachment Style on Quality of Life and Readiness to Change in a Sample of Individuals Receiving Medication-Assisted Treatment for Opioid Dependence.

PubMed

Cavaiola, Alan A; Fulmer, Barbara A; Stout, David

2015-01-01

A basic principle within the addictions treatment field is that social support is a vital ingredient in the recovery process. This study examines the nature of social support in a sample of opioid-dependent men and women who are currently being treated in a medication-assisted treatment program (methadone). This research examines the types of social support behaviors that the opioid-dependent individuals consider helpful and explores whether attachment style (i.e., secure, ambivalent, or anxious attachment) was a determining factor in whether social support was perceived as helpful. The dependent variables included readiness to change addictive behaviors and abstinence from other mood-altering drugs. Participants (N = 159) completed a demographic questionnaire, the Significant Others Scale, the Experiences in Close Relationships Scale, the Multidimensional Scale of Perceived Social Support Assessment, the Readiness to Change Scale, and an Attachment Style Questionnaire. The demographic questionnaire included subjective ratings of self-improvement. Social support predicted perceived improvement in all of the areas examined (e.g., health, family/social relationships) and abstinence; however, attachment style did not predict improvement or with readiness to change. Social support is an important factor in one's recovery from substance use disorders. Yet attachment style (i.e., anxious, avoidant, or secure) did not predict abstinence or overall improvement in functioning.

Current Research on Opioid Receptor Function

PubMed Central

Feng, Yuan; He, Xiaozhou; Yang, Yilin; Chao, Dongman; Lazarus, Lawrence H.; Xia, Ying

2012-01-01

The use of opioid analgesics has a long history in clinical settings, although the comprehensive action of opioid receptors is still less understood. Nonetheless, recent studies have generated fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Three major opioid receptors (μ-opioid receptor, MOR; δ-opioid receptor, DOR; and κ-opioid receptor, KOR) have been cloned in many species. Each opioid receptor is functionally sub-classified into several pharmacological subtypes, although, specific gene corresponding each of these receptor subtypes is still unidentified as only a single gene has been isolated for each opioid receptor. In addition to pain modulation and addiction, opioid receptors are widely involved in various physiological and pathophysiological activities, including the regulation of membrane ionic homeostasis, cell proliferation, emotional response, epileptic seizures, immune function, feeding, obesity, respiratory and cardiovascular control as well as some neurodegenerative disorders. In some species, they play an essential role in hibernation. One of the most exciting findings of the past decade is the opioid-receptor, especially DOR, mediated neuroprotection and cardioprotection. The up-regulation of DOR expression and DOR activation increase the neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers (depending on stress duration and severity) different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of homeostasis and increased pro-survival signaling (e.g., PKC-ERK-Bcl 2) and anti-oxidative capacity. In the heart, PKC and KATP channels are involved in the opioid receptor-mediated cardioprotection. The DOR-mediated neuroprotection and cardioprotection have the potential to significantly alter the clinical pharmacology in terms of prevention and treatment of life-threatening conditions like stroke and myocardial infarction. The main purpose of this article is to review the recent work done on opioids and their receptor functions. It shall provide an informative reference for better understanding the opioid system and further elucidation of the opioid receptor function from a physiological and pharmacological point of view. PMID:22204322

Polyglycerol-opioid conjugate produces analgesia devoid of side effects.

PubMed

González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph

2017-07-04

Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

PubMed Central

Chou, Roger; Fanciullo, Gilbert J.; Fine, Perry G.; Adler, Jeremy A.; Ballantyne, Jane C.; Davies, Pamela; Donovan, Marilee I.; Fishbain, David A.; Foley, Kathy M.; Fudin, Jeffrey; Gilson, Aaron M.; Kelter, Alexander; Mauskop, Alexander; O'Connor, Patrick G.; Passik, Steven D.; Pasternak, Gavril W.; Portenoy, Russell K.; Rich, Ben A.; Roberts, Richard G.; Todd, Knox H.; Miaskowski, Christine

2014-01-01

Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices. Perspective: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel following a systematic review of the evidence. PMID:19187889

National estimates of exposure to prescription drugs with addiction potential in community-dwelling elders.

PubMed

Simoni-Wastila, Linda; Zuckerman, Ilene H; Singhal, Puneet K; Briesacher, Becky; Hsu, Van Doren

2005-03-01

The use of prescription drugs with addiction potential is an overlooked and growing problem among today's elderly. This paper provides national prevalence estimates of exposure to prescription drugs with addiction potential among community-dwelling elders and explores risk factors for such exposure. Using the Medicare Current Beneficiary Survey, a nationally-representative database of Medicare eligibles, we calculated the prevalence of abusable prescription drug use, overall, by therapeutic class, and by drug. Nearly 22% (7.22 million) of all community-dwelling Medicare elders used at least one prescription medication with addiction potential. Opioid analgesics were used most frequently (14.9%; 95% CI 14.0, 15.8%); central nervous system (CNS) depressants were used by 10.4% of the nation's elders (95% CI 9.5, 10.8%). Using logistic regression analysis, we examined the association of explanatory variables with three outcome variables: any controlled substances use, any opioid analgesic use, and any CNS depressant use. We found that females, whites, those aged 65-79, and those with non-spousal others, were significantly more likely to use one or more prescription drugs with addiction potential, controlling for health status and severity-of-illness. The significance and magnitude of several explanatory variables, including age, race, ethnicity, living arrangement, and health status, varied by therapeutic category. This paper provides an important first step in acknowledging the widespread use of abusable prescription drugs in elders, and provides a foundation for future research and practical solutions to preventing subsequent problem use of prescription drugs.

The effect of bundling medication-assisted treatment for opioid addiction with mHealth: study protocol for a randomized clinical trial.

PubMed

Gustafson, David H; Landucci, Gina; McTavish, Fiona; Kornfield, Rachel; Johnson, Roberta A; Mares, Marie-Louise; Westergaard, Ryan P; Quanbeck, Andrew; Alagoz, Esra; Pe-Romashko, Klaren; Thomas, Chantelle; Shah, Dhavan

2016-12-12

Opioid dependence has devastating and increasingly widespread consequences and costs, and the most common outcome of treatment is early relapse. People who inject opioids are also at disproportionate risk for contracting the human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This study tests an approach that has been shown to improve recovery rates: medication along with other supportive services (medication-assisted treatment, or MAT) against MAT combined with a smartphone innovation called A-CHESS (MAT + A-CHESS). This unblinded study will randomly assign 440 patients to receive MAT + A-CHESS or MAT alone. Eligible patients will meet criteria for having an opioid use disorder of at least moderate severity and will be taking methadone, injectable naltrexone, or buprenorphine. Patients with A-CHESS will have smartphones for 16 months; all patients will be followed for 24 months. The primary outcome is the difference between patients in the two arms in percentage of days using illicit opioids during the 24-month intervention. Secondary outcomes are differences between patients receiving MAT + A-CHESS versus MAT in other substance use, quality of life, retention in treatment, health service use, and, related to HIV and HCV, screening and testing rates, medication adherence, risk behaviors, and links to care. We will also examine mediators and moderators of the effects of MAT + A-CHESS. We will measure variables at baseline and months 4, 8, 12, 16, 20, and 24. At each point, patients will respond to a 20- to 30-min phone survey; urine screens will be collected at baseline and up to twice a month thereafter. We will use mixed-effects to evaluate the primary and secondary outcomes, with baseline scores functioning as covariates, treatment condition as a between-subject factor, and the outcomes reflecting scores for a given assessment at the six time points. Separate analyses will be conducted for each outcome. A-CHESS has been shown to improve recovery for people with alcohol dependence. It offers an adaptive and extensive menu of services and can attend to patients nearly as constantly as addiction does. This suggests the possibility of increasing both the effectiveness of, and access to, treatment for opioid dependence. ClinicalTrials.gov, NCT02712034 . Registered on 14 March 2016.

Use of Photovoice in addiction.

PubMed

Miller Heery, Gretchen Hope

2013-09-01

The addiction to narcotic substances is an increasing public health problem. Addiction relapse is preventable. Photovoice may increase the success rate by offering a deeper perspective, insight, dimension of feeling, and perception connecting with those who feel disconnected. This process uses cameras, discussion groups, storyboards, and interaction to thread through difficult discussion points created by the participant. Understanding the process of recovery from opioid substance abuse creates an opportunity to maintain socially acceptable behaviors and decreases the risk of participating in illegal activities and making poor choices. Photovoice allows for creative expression of thought by bypassing cognitive defenses. Copyright © 2013 Elsevier Inc. All rights reserved.

Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain.

PubMed

Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

2005-09-01

Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (degrees C), as well as suprathreshold tonic heat pain intensity (46.5 degrees C for 1 min) measured by 0-10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI -8.8, 42.8), P = 0.19), pressure (2.2 mmHg (-28.7, 33.2), P = 0.89) and heat (-0.3 degrees C (-1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities -0.4 NPS units (95% CI -1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the 'weak' opioid-treated subgroup and the 'strong' opioid-treated subgroup again revealed insignificant results. These results suggest that the administration of 'commonly used' dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients receiving non-opioid analgesia.

Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment

PubMed Central

Bagley, Elena E.

2014-01-01

Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1) currents in periaqueductal gray (PAG) neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than Ek. Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1 effector. PMID:25009497

Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment.

PubMed

Bagley, Elena E

2014-01-01

Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1) currents in periaqueductal gray (PAG) neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than E k . Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1 effector.

Distinct Mu, Delta, and Kappa Opioid Receptor Mechanisms Underlie Low Sociability and Depressive-Like Behaviors During Heroin Abstinence

PubMed Central

Lutz, Pierre-Eric; Ayranci, Gulebru; Chu-Sin-Chung, Paul; Matifas, Audrey; Koebel, Pascale; Filliol, Dominique; Befort, Katia; Ouagazzal, Abdel-Mouttalib; Kieffer, Brigitte L

2014-01-01

Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse. PMID:24874714

Simultaneous determination of 18 abused opioids and metabolites in human hair using LC-MS/MS and illegal opioids abuse proven by hair analysis.

PubMed

Kim, Jihyun; Ji, Dajeong; Kang, Soyoung; Park, Meejung; Yang, Wonkyung; Kim, Eunmi; Choi, Hwakyung; Lee, Sooyeun

2014-02-01

Natural and synthetic opioids have efficient analgesic activity but can also be addictive. Thus, the determination of opioids and their metabolites in biological specimens is of interest in clinical and forensic toxicology laboratories. The analysis of drugs in hair provides valuable information on previous chronic drug use and has been successfully applied to the diagnosis of drug abuse, tolerance, compliance and gestational drug exposure. Despite the abuse of prescription opioids along with heroin and other illegal opiates, few studies have been conducted on the simultaneous determination of the broad range of opioids covering those drugs in hair. In the present study, an analytical method for the simultaneous detection in hair of 18 opioids and metabolites considered to have a high abuse risk based on the results of urine drug screening was established and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the purpose of clinical and forensic applications. The drugs and metabolites were extracted from hair using methanol and analyzed using LC-MS/MS. The validation results proved that the method was selective, accurate and precise with acceptable linearity within calibration ranges. No significant variation was observed by different sources of matrices. The limits of detection and the limits of quantification ranged from 0.05 to 0.25ng/10mg hair and from 0.05 to 0.5ng/10mg hair, respectively. The developed method was successfully applied to 15 hair samples from opioids users. This method will be very useful for monitoring the inappropriate use of opioid drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Opioid withdrawal, craving, and use during and after outpatient buprenorphine stabilization and taper: a discrete survival and growth mixture model.

PubMed

Northrup, Thomas F; Stotts, Angela L; Green, Charles; Potter, Jennifer S; Marino, Elise N; Walker, Robrina; Weiss, Roger D; Trivedi, Madhukar

2015-02-01

Most patients relapse to opioids within one month of opioid agonist detoxification, making the antecedents and parallel processes of first use critical for investigation. Craving and withdrawal are often studied in relationship to opioid outcomes, and a novel analytic strategy applied to these two phenomena may indicate targeted intervention strategies. Specifically, this secondary data analysis of the Prescription Opioid Addiction Treatment Study used a discrete-time mixture analysis with time-to-first opioid use (survival) simultaneously predicted by craving and withdrawal growth trajectories. This analysis characterized heterogeneity among prescription opioid-dependent individuals (N=653) into latent classes (i.e., latent class analysis [LCA]) during and after buprenorphine/naloxone stabilization and taper. A 4-latent class solution was selected for overall model fit and clinical parsimony. In order of shortest to longest time-to-first use, the 4 classes were characterized as 1) high craving and withdrawal, 2) intermediate craving and withdrawal, 3) high initial craving with low craving and withdrawal trajectories and 4) a low initial craving with low craving and withdrawal trajectories. Odds ratio calculations showed statistically significant differences in time-to-first use across classes. Generally, participants with lower baseline levels and greater decreases in craving and withdrawal during stabilization combined with slower craving and withdrawal rebound during buprenorphine taper remained opioid-free longer. This exploratory work expanded on the importance of monitoring craving and withdrawal during buprenorphine induction, stabilization, and taper. Future research may allow individually tailored and timely interventions to be developed to extend time-to-first opioid use. Copyright © 2014 Elsevier Ltd. All rights reserved.

NEURAL SUBSTRATES OF CUE-REACTIVITY: ASSOCIATION WITH TREATMENT OUTCOMES AND RELAPSE

PubMed Central

Courtney, Kelly E.; Schacht, Joseph P.; Hutchison, Kent; Roche, Daniel J.O.; Ray, Lara A.

2016-01-01

Given the strong evidence for neurological alterations at the basis of drug dependence, functional magnetic resonance imaging (fMRI) represents an important tool in the clinical neuroscience of addiction. fMRI cue-reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the reward/motivation system in addiction and potentially offer a translational mechanism by which interventions and behavioral predictions can be tested. Thus, this review summarizes the research that has applied fMRI cue-reactivity paradigms to the study of adult substance use disorder treatment responses. Studies utilizing fMRI cue-reactivity paradigms for the prediction of relapse, and as a means to investigate psychosocial and pharmacological treatment effects on cue-elicited brain activation are presented within four primary categories of substances: alcohol, nicotine, cocaine, and opioids. Lastly, suggestions for how to leverage fMRI technology to advance addiction science and treatment development are provided. PMID:26435524

The development of a comprehensive risk-management program for prescription opioid analgesics: researched abuse, diversion and addiction-related surveillance (RADARS).

PubMed

Cicero, Theodore J; Dart, Richard C; Inciardi, James A; Woody, George E; Schnoll, Sidney; Muñoz, Alvaro

2007-03-01

OBJECTIVE. Beginning in the late 1990's a marked increase in abuse of OxyContin emerged, which led to the development and establishment of a proactive surveillance program to monitor and characterize abuse, named the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS) System. The main goal of RADARS was to develop proactive, timely and geographically sensitive methods to assess the abuse and diversion of OxyContin, along with a number of other Schedule II and III opioids with the aim of using this information to guide risk reduction interventions. Thus, its major focus was the detection of abuse of OxyContin and other commonly prescribed opioid analgesics at the three-digit ZIP code level across the country utilizing a number of different detection systems. The detection systems selected were: (1) Quarterly-surveys of drug abuse experts who are knowledgeable about cases of prescription drug abuse; (2) Surveys of law enforcement agencies that detect diversion of prescription drugs; and (3) Poison Control Center reports of intentional misuse or abuse of prescription opioids. Collectively, the three systems provide overlapping coverage of over 80% of the nation's 973 three-digit ZIP codes. Preliminary results indicate that prescription drug abuse is prevalent nationwide, but it seems to be heavily localized in rural, suburban and small urban areas. Our results also indicate that hydrocodone and extended and immediate release oxycodone products are by far the most widely abused drugs in the country, but the abuse of all prescription opioids seems to have grown over the 14 quarters since the inception of RADARS. The next step in these studies is to develop regionally specific, risk-minimization-strategies, which is the goal of all risk-management programs. If successful, RADARS will serve as a prototype of such programs for any new drug approved that has measurable abuse potential.

75 FR 82036 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

... Treatment for Opioid Addiction State Profiles.'' These publications will be used by the Federal government...-7285. Dated: January 22, 2010. Elaine Parry, Director, Office of Management, Technology and Operations...

Gender issues in the pharmacotherapy of opioid-addicted women: buprenorphine.

PubMed

Unger, Annemarie; Jung, Erika; Winklbaur, Bernadette; Fischer, Gabriele

2010-04-01

Gender, a biological determinant of mental health and illness, plays a critical role in determining patients' susceptibility, exposure to mental health risks, and related outcomes. Regarding sex differences in the epidemiology of opioid dependence, one third of the patients are women of childbearing age. Women have an earlier age of initiation of substance use and a more rapid progression to drug involvement and dependence than men. Generally few studies exist which focus on the special needs of women in opioid maintenance therapy. The aim of this paper is to provide an overview of treatment options for opioid-dependent women, with a special focus on buprenorphine, and to look at recent findings related to other factors that should be taken into consideration in optimizing the treatment of opioid-dependent women. Issues addressed include the role of gender in the choice of medication assisted treatment, sex differences in pharmacodynamics and pharmacokinetics of buprenorphine drug interactions, cardiac interactions, induction of buprenorphine in pregnant patients, the neonatal abstinence syndrome and breastfeeding. This paper aims to heighten the awareness for the need to take gender into consideration when making treatment decisions in an effort to optimize services and enhance the quality of life of women suffering from substance abuse.

The availability of ancillary counseling in the practices of physicians prescribing buprenorphine

PubMed Central

Barry, Declan T.; Fazzino, Tera; Necrason, Emily; Ginn, Joel; Fiellin, Lynn E.; Fiellin, David A.; Moore, Brent A.

2016-01-01

Objectives We set out to examine physicians’ perceptions of the provision of ancillary services for opioid dependent patients receiving buprenorphine. Methods An email invitation describing the study was sent out by the American Society of Addiction Medicine to its membership (approximately 3,700 physicians) and other entities (for a total of approximately 7,000 email addresses). Email recipients were invited to participate in a research study funded by the National Institutes on Drug Abuse involving completion of an online survey; 346 physicians completed the survey. Results The majority of the 346 respondents were internal or family medicine (37%) or addiction medicine providers (30%) who were practicing in urban (57%) or suburban settings (27%). Most respondents reported either offering (66%) or referring patients for ancillary counseling (31%). Interventions that were most frequently offered or referrals provided were individual counseling (51%) and self-help groups (63%), respectively. Counseling availability differed significantly by provider specialization for any, individual, group, family or couples, and self-help groups. Conclusions Generally, respondents reported compliance with ancillary counseling requirements for buprenorphine treatment of opioid use disorder. In addition to examining the efficacy of a variety of ancillary counseling services for patients receiving opioid agonist treatment, further research should examine physicians’ attitudes toward the role of such counseling in buprenorphine treatment. While the study sample was relatively large, the generalizability of the findings is unclear, suggesting that further investigation of the availability of ancillary counseling in buprenorphine treatment among a larger nationally representative sample of providers may be warranted. PMID:27504926

Mu-opioid receptors modulate the stability of dendritic spines

PubMed Central

Liao, Dezhi; Lin, Hang; Law, Ping Yee; Loh, Horace H.

2005-01-01

Opioids classically regulate the excitability of neurons by suppressing synaptic GABA release from inhibitory neurons. Here, we report a role for opioids in modulating excitatory synaptic transmission. By activating ubiquitously clustered μ-opioid receptor (MOR) in excitatory synapses, morphine caused collapse of preexisting dendritic spines and decreased synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Meanwhile, the opioid antagonist naloxone increased the density of spines. Chronic treatment with morphine decreased the density of dendritic spines even in the presence of Tetrodotoxin, a sodium channel blocker, indicating that the morphine's effect was not caused by altered activity in neural network through suppression of GABA release. The effect of morphine on dendritic spines was absent in transgenic mice lacking MORs and was blocked by CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2), a μ-receptor antagonist. These data together with others suggest that endogenous opioids and/or constitutive activity of MORs participate in maintaining normal morphology and function of spines, challenging the classical model of opioids. Abnormal alteration of spines may occur in drug addiction when opioid receptors are overactivated by exogenous opiates. PMID:15659552

Affective neuroscientific and neuropsychoanalytic approaches to two intractable psychiatric problems: why depression feels so bad and what addicts really want.

PubMed

Zellner, Margaret R; Watt, Douglas F; Solms, Mark; Panksepp, Jaak

2011-10-01

The affective foundations of depression and addictions are discussed from a cross-species - animal to human - perspective of translational psychiatric research. Depression is hypothesized to arise from an evolutionarily conserved mechanism to terminate protracted activation of separation-distress (PANIC/GRIEF) systems of the brain, a shutdown mechanism which may be in part mediated by down-regulation of dopamine based reward-SEEKING resources. This shutdown of the brain's core motivational machinery is organized by shifts in multiple peptide systems, particularly increased dynorphin (kappa opioids). Addictions are conceived to be primarily mediated by obsessive behaviors sustained by reward-SEEKING circuits in the case of psychostimulant abuse, and also powerful consummatory-PLEASURE responses in the case of opioid abuse, which in turn capture SEEKING circuits. Both forms of addiction, as well as others, eventually deplete reward-SEEKING resources, leading to a state of dysphoria which can only temporarily be reversed by drugs of abuse, thereby promoting a negative affect that sustains addictive cycles. In other words, the opponent affective process - the dysphoria of diminished SEEKING resources - that can be aroused by sustained over-arousal of separation-distress (PANIC/GRIEF) as well as direct pharmacological over-stimulation and depletion of SEEKING resources, may be a common denominator for the genesis of both depression and addiction. Envisioning the foundation of such psychiatric problems as being in imbalances of the basic mammalian emotional systems that engender prototype affective states may provide more robust translational research strategies, coordinated with, rather than simply focusing on, the underlying molecular dynamics. Emotional vocalizations might be one of the best ways to monitor the underlying affective dynamics in commonly used rodent models of psychiatric disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

PubMed

Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

2016-01-01

Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning. © 2014 Society for the Study of Addiction.

Expression of NMDA receptor subunits in human blood lymphocytes: A peripheral biomarker in online computer game addiction.

PubMed

Sadat-Shirazi, Mitra-Sadat; Vousooghi, Nasim; Alizadeh, Bentolhoda; Makki, Seyed Mohammad; Zarei, Seyed Zeinolabedin; Nazari, Shahrzad; Zarrindast, Mohammad Reza

2018-05-23

Background and aims Repeated performance of some behaviors such as playing computer games could result in addiction. The NMDA receptor is critically involved in the development of behavioral and drug addictions. It has been claimed that the expression level of neurotransmitter receptors in the brain may be reflected in peripheral blood lymphocytes (PBLs). Methods Here, using a real-time PCR method, we have investigated the mRNA expression of GluN2A, GluN2D, GluN3A, and GluN3B subunits of the NMDA receptor in PBLs of male online computer game addicts (n = 25) in comparison with normal subjects (n = 26). Results Expression levels of GluN2A, GluN2D, and GluN3B subunits were not statistically different between game addicts and the control group. However, the mRNA expression of the GluN3A subunit was downregulated in PBLs of game addicts. Discussion and conclusions Transcriptional levels of GluN2A and GluN2D subunits in online computer game addicts are similar to our previously reported data of opioid addiction and are not different from the control group. However, unlike our earlier finding of drug addiction, the mRNA expression levels of GluN3A and GluN3B subunits in PBLs of game addicts are reduced and unchanged, respectively, compared with control subjects. It seems that the downregulated state of the GluN3A subunit of NMDA receptor in online computer game addicts is a finding that deserves more studies in the future to see whether it can serve as a peripheral biomarker in addiction studies, where the researcher wants to rule out the confusing effects of abused drugs.

Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria.

PubMed

McDonald, Rebecca; Strang, John

2016-07-01

Fatal outcome of opioid overdose, once detected, is preventable through timely administration of the antidote naloxone. Take-home naloxone provision directly to opioid users for emergency use has been implemented recently in more than 15 countries worldwide, albeit mainly as pilot schemes and without formal evaluation. This systematic review assesses the effectiveness of take-home naloxone, with two specific aims: (1) to study the impact of take-home naloxone distribution on overdose-related mortality; and (2) to assess the safety of take-home naloxone in terms of adverse events. PubMed, MEDLINE and PsychINFO were searched for English-language peer-reviewed publications (randomized or observational trials) using the Boolean search query: (opioid OR opiate) AND overdose AND prevention. Evidence was evaluated using the nine Bradford Hill criteria for causation, devised to assess a potential causal relationship between public health interventions and clinical outcomes when only observational data are available. A total of 1397 records (1164 after removal of duplicates) were retrieved, with 22 observational studies meeting eligibility criteria. Due to variability in size and quality of the included studies, meta-analysis was dismissed in favour of narrative synthesis. From eligible studies, we found take-home naloxone met all nine Bradford Hill criteria. The additional five World Health Organization criteria were all either met partially (two) or fully (three). Even with take-home naloxone administration, fatal outcome was reported in one in 123 overdose cases (0.8%; 95% confidence interval = 0.4, 1.2). Take-home naloxone programmes are found to reduce overdose mortality among programme participants and in the community and have a low rate of adverse events. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Cocaine Addiction: Neurobiology and Related Current Research in Pharmacotherapy.

PubMed

Panikkar, Gopakumar P.

1999-09-01

In this article, recent research studies in the field of cocaine addiction are reviewed, with an eye toward emergent options for treatment innovation. Particular attention is paid to the neurobiology and specific neurotransmitter and receptor mechanisms involved in cocaine abuse, dependence, and other unique phenomena of addiction such as sensitization, craving, compulsive drug use, and withdrawal. The vicissitudes in the dopamine theory of brain reward mechanisms, dopaminergic effects of cocaine, and emerging roles of GABA, serotonin, glutamate, and nitric oxide in cocaine addiction and its sequelae are discussed. Neuroanatomic findings elicited with imaging studies using PET and functional MRI are summarized. These findings support the role of specific brain regions within the dopaminergic system such as the ventral tegmentum and nucleus accumbens in the induction of the cocaine "high" and craving, respectively. Research approaches to the problem of developing effective pharmacotherapeutic options to render cocaine ineffective and modalities under study, such as dopamine uptake inhibitors and immunotherapy, are also discussed in the context of a variety of practical problems faced by these experimental therapies. Pharmacotherapeutic strategies and new directions in this research, such as the adaptive changes of the opioid system in cocaine addiction, are reviewed. Potential areas for further study are brought forth for further debate and possible clinical evaluation.

DEVELOPING A VACCINE AGAINST MULTIPLE PSYCHOACTIVE TARGETS: A CASE STUDY OF HEROIN

PubMed Central

Stowe, G. Neil; Schlosburg, Joel E.; Vendruscolo, Leandro F.; Edwards, Scott; Misra, Kaushik K.; Schulteis, Gery; Zakhari, Joseph S.; Koob, George F.; Janda, Kim D.

2012-01-01

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin’s effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as it is metabolized to multiple psychoactive molecules of differing lipophilicity, with differing abilities to cross the blood brain barrier. In this review, we discuss the opiate scaffolding and hapten design considerations to confer immunogenicity as well as the specificity of the immune response towards structurally similar opiates. In addition, we detail different strategies employed in the design of immunoconjugates for a vaccine-based therapy for heroin addiction treatment. PMID:22229311

Noribogaine is a G-protein biased κ-opioid receptor agonist.

PubMed

Maillet, Emeline L; Milon, Nicolas; Heghinian, Mari D; Fishback, James; Schürer, Stephan C; Garamszegi, Nandor; Mash, Deborah C

2015-12-01

Noribogaine is the long-lived human metabolite of the anti-addictive substance ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to 20 μM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine displays atypical opioid-like components in vivo, anti-addictive effects and potent modulatory properties of the tolerance to opiates for which the mode of action remained uncharacterized thus far. Our binding experiments and computational simulations indicate that noribogaine may bind to the orthosteric morphinan binding site of the opioid receptors. Functional activities of noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid receptors were characterized. Noribogaine was a weak mu antagonist with a functional inhibition constants (Ke) of 20 μM at the G-protein and β-arrestin signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) but only 12% as efficacious at recruiting β-arrestin, which could contribute to the lack of dysphoric effects of noribogaine. In turn, noribogaine functionally inhibited dynorphin-induced kappa β-arrestin recruitment and was more potent than its G-protein agonistic activity with an IC50 of 1 μM. This biased agonist/antagonist pharmacology is unique to noribogaine in comparison to various other ligands including ibogaine, 18-MC, nalmefene, and 6'-GNTI. We predict noribogaine to promote certain analgesic effects as well as anti-addictive effects at effective concentrations>1 μM in the brain. Because elevated levels of dynorphins are commonly observed and correlated with anxiety, dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant functional inhibition bias to endogenously released dynorphins by noribogaine might be worthy of consideration for treating anxiety and substance related disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The risks of opioid treatment: Perspectives of primary care practitioners and patients from safety-net clinics

PubMed Central

Hurstak, Emily E.; Kushel, Margot; Chang, Jamie; Ceasar, Rachel; Zamora, Kara; Miaskowski, Christine; Knight, Kelly

2017-01-01

Background Patients with a history of substance use are more likely than those without substance use to experience chronic noncancer pain (CNCP), to be prescribed opioids, and to experience opioid misuse or overdose. Primary care practitioners (PCPs) in safety-net settings care for low-income patients with CNCP and substance use, usually without specialist consultation. To inform communication related to opioid risk, we explored PCPs’ and patients’ perceptions of the risks of chronic opioid therapy. Methods We conducted semistructured interviews with 23 PCPs and 46 of their patients, who had a history of CNCP and substance use. We recruited from 6 safety-net health care settings in the San Francisco Bay Area. We transcribed interviews verbatim and analyzed transcripts using grounded theory methodology. Results (1) PCPs feared harming patients and the community by opioid prescribing. PCPs emphasized fear of opioid overdose. (2) Patients did not highlight concerns about the adverse health consequences of opioids, except for addiction. (3) Both patients and PCPs were concerned about PCPs’ medicolegal risks related to opioid prescribing. (4) Patients reported feeling stigmatized by policies aimed at reducing opioid misuse. Conclusion We identified differences in how clinicians and patients perceive opioid risk. To improve the informed consent process for opioid therapy, patients and PCPs need to have a shared understanding of the risks of opioids and engage in discussions that promote patient autonomy and safety. As clinics implement opioid prescribing policies, clinicians must develop effective communication strategies in order to educate patients about opioid risks and decrease patients’ experiences of stigma and discrimination. PMID:28394752

Nicotine anxiogenic and rewarding effects are decreased in mice lacking β-endorphin

PubMed Central

Trigo, José M.; Zimmer, Andreas; Maldonado, Rafael

2009-01-01

The endogenous opioid system plays an important role in the behavioral effects of nicotine. Thus, μ-opioid receptor and the endogenous opioids derived from proenkephalin are involved in the central effects of nicotine. However, the role played by the different endogenous opioid peptides in the acute and chronic effects of nicotine remains to be fully established. Mice lacking β-endorphin were acutely injected with nicotine at different doses to evaluate locomotor, anxiogenic and antinociceptive responses. The rewarding properties of nicotine were evaluated by using the conditioned place-preference paradigm. Mice chronically treated with nicotine were acutely injected with mecamylamine to study the behavioral expression of nicotine withdrawal. Mice lacking β-endorphin exhibited a spontaneous hypoalgesia and hyperlocomotion and a reduction on the anxiogenic and rewarding effects induced by nicotine. Nicotine induced similar antinociception and hypolocomotion in both genotypes and no differences were found in the development of physical dependence. The dissociation between nicotine rewarding properties and physical dependence suggests a differential implication of β-endorphin in these addictive related responses. PMID:19376143

A nontoxic pain killer designed by modeling of pathological receptor conformations.

PubMed

Spahn, V; Del Vecchio, G; Labuz, D; Rodriguez-Gaztelumendi, A; Massaly, N; Temp, J; Durmaz, V; Sabri, P; Reidelbach, M; Machelska, H; Weber, M; Stein, C

2017-03-03

Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide-binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3',5'-monophosphate inhibition in vitro . It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential. Copyright © 2017, American Association for the Advancement of Science.

Protocol: changes in rates of opioid overdose and poisoning events in an integrated health system following the introduction of a formulation of OxyContin® with abuse-deterrent properties.

PubMed

Janoff, Shannon L; Perrin, Nancy A; Coplan, Paul M; Chilcoat, Howard D; Campbell, Cynthia I; Green, Carla A

2016-05-14

Addiction, overdoses and deaths resulting from prescription opioids have increased dramatically over the last decade. In response, several manufacturers have developed formulations of opioids with abuse-deterrent properties. For many of these products, the Food and Drug Administration (FDA) recognized the formulation with labeling claims and mandated post-marketing studies to assess the abuse-deterrent effects. In response, we assess differences in rates of opioid-related overdoses and poisonings prior to and following the introduction of a formulation of OxyContin® with abuse-deterrent properties. To assess effects of this formulation, electronic medical record (EMR) data from Kaiser Permanente Northwest (KPNW) and Kaiser Permanente Northern California (KPNC) are linked to state death data and compared to chart audits. Overdose and poisoning events will be categorized by intentionality and number of agents involved, including illicit drugs and alcohol. Using 6-month intervals over a 10-year period, trends will be compared in rates of opioid-related overdoses and poisoning events associated with OxyContin® to rates of events associated with other oxycodone and opioid formulations. Qualitative interviews with patients and relatives of deceased patients will be conducted to capture circumstances surrounding events. This study assesses and tracks changes in opioid-related overdoses and poisoning events prior to and following the introduction of OxyContin® with abuse-deterrent properties. Public health significance is high because these medications are designed to reduce abuse-related behaviors that lead to important adverse outcomes, including overdoses and deaths.

Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease progression and neuropathogenesis

PubMed Central

Banerjee, Anupam; Strazza, Marianne; Wigdahl, Brian; Pirrone, Vanessa; Meucci, Olimpia

2013-01-01

About one third of acquired immunodeficiency syndrome cases in the USA have been attributed to the use of injected addictive drugs, frequently involving opioids like heroin and morphine, establishing them as significant predisposing risk factors for contracting human immuno-deficiency virus type 1 (HIV-1). Accumulating evidence from in vitro and in vivo experimental systems indicates that opioids act in concert with HIV-1 proteins to exacerbate dysregulation of neural and immune cell function and survival through diverse molecular mechanisms. In contrast, the impact of opioid exposure and withdrawal on the viral life cycle and HIV-1 disease progression itself is unclear, with conflicting reports emerging from the simian immunodeficiency virus and simian–human immunodeficiency virus infection models. However, these studies suggest a potential role of opioids in elevated viral production. Because human microglia, astrocytes, CD4+ T lymphocytes, and monocyte-derived macrophages express opioid receptors, it is likely that intracellular signaling events triggered by morphine facilitate enhancement of HIV-1 infection in these target cell populations. This review highlights the biochemical changes that accompany prolonged exposure to and withdrawal from morphine that synergize with HIV-1 proteins to disrupt normal cellular physiological functions especially within the central nervous system. More importantly, it collates evidence from epidemiological studies, animal models, and heterologous cell systems to propose a mechanistic link between such physiological adaptations and direct modulation of HIV-1 production. Understanding the opioid–HIV-1 interface at the molecular level is vitally important in designing better treatment strategies for HIV-1-infected patients who abuse opioids. PMID:21735315

Challenges to Implementing Opioid Substitution Therapy in Ukrainian Prisons: Personnel Attitudes Toward Addiction, Treatment, and People With HIV/AIDS

PubMed Central

Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A.; Taxman, Faye S.; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L.

2015-01-01

Background Ukraine is experiencing one of the most volatile HIV epidemics globally, fueled primarily by people who inject drugs (PWIDs), and a parallel incarceration epidemic. Opioid substitution therapy (OST) is internationally recognized as one of the most effective forms of treatment for opioid dependence and is among the most effective HIV prevention strategies available, yet efforts to adopt it in Ukraine’s Criminal Justice System (CJS) have been thwarted. Methods To understand the reluctance of the Ukrainian CJS to adopt OST despite the overwhelming evidence pointing to its health benefits and improved criminal justice outcomes, we conducted the first survey of Ukrainian prison administrative, medical and custodial staff (N=243) attitudes towards addiction in general, OST, and people living with HIV/AIDS (PLWHA) in representative regions of Ukraine. Results Results revealed that Ukrainian CJS workers’ attitudes toward OST, PLWHA, and drug addiction were universally negative, but differed substantially along geographic and occupational lines. Whereas geographic and cultural proximity to the European Union drove positive attitudes in the west, in the southern region we observed an identifiability effect, as workers who worked directly with prisoners held the most positive attitudes. We also found that knowledge mediated the effect of drug intolerance on OST attitudes. Conclusion In Ukraine, adoption of OST is more influenced by ideological biases and prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this assessment will help direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. PMID:25620732

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

PubMed

Butelman, Eduardo Roque; Bacciardi, Silvia; Maremmani, Angelo Giovanni Icro; Darst-Campbell, Maya; Correa da Rosa, Joel; Kreek, Mary Jeanne

2017-09-01

Addictions to heroin or to cocaine are associated with substantial psychiatric comorbidity, including depression. Poly-drug self-exposure (eg, to heroin, cocaine, cannabis, or alcohol) is also common, and may further affect depression comorbidity. This case-control study examined the relationship of exposure to the above drugs and depression comorbidity. Participants were recruited from methadone maintenance clinics, and from the community. Adult male and female participants (n = 1,201) were ascertained consecutively by experienced licensed clinicians. The instruments used were the SCID-I, and Kreek-McHugh-Schluger-Kellogg (KMSK) scales, which provide a rapid dimensional measure of maximal lifetime self-exposure to each of the above drugs. This measure ranges from no exposure to high unit dose, high frequency, and long duration of exposure. A multiple logistic regression with stepwise variable selection revealed that increasing exposure to heroin or to cocaine was associated greater odds of depression, with all cases and controls combined. In cases with an opioid dependence diagnosis, increasing cocaine exposure was associated with a further increase in odds of depression. However, in cases with a cocaine dependence diagnosis, increasing exposure to either cannabis or alcohol, as well as heroin, was associated with a further increase in odds of depression. This dimensional analysis of exposure to specific drugs provides insights on depression comorbidity with addictive diseases, and the impact of poly-drug exposure. A rapid analysis of exposure to drugs of abuse reveals how specific patterns of drug and poly-drug exposure are associated with increasing odds of depression. This approach detected quantitatively how different patterns of poly-drug exposure can result in increased odds of depression comorbidity, in cases diagnosed with opioid versus cocaine dependence. (Am J Addict 2017;26:632-639). © 2017 American Academy of Addiction Psychiatry.

Evaluation of 6 remote First Nations community-based buprenorphine programs in northwestern Ontario

PubMed Central

Mamakwa, Solomon; Kahan, Meldon; Kanate, Dinah; Kirlew, Mike; Folk, David; Cirone, Sharon; Rea, Sara; Parsons, Pierre; Edwards, Craig; Gordon, Janet; Main, Fiona; Kelly, Len

2017-01-01

Abstract Objective To evaluate established opioid addiction treatment programs that use traditional healing in combination with buprenorphine-naloxone maintenance treatment in 6 First Nations communities in the Sioux Lookout region of northwestern Ontario. Design Retrospective cohort study. Setting Six First Nations communities in northwestern Ontario. Participants A total of 526 First Nations participants in opioid-dependence treatment programs. Intervention Buprenorphine-naloxone substitution therapy and First Nations healing programming. Main outcome measures Retention rates and urine drug screening (UDS) results. Results Treatment retention rates at 6, 12, and 18 months were 84%, 78%, and 72%, respectively. We estimate that the rate at 24 months will also be more than 70%. The UDS programming varied and was implemented in only 1 community. Initially urine testing was voluntary and it then became mandatory. Screening with either method found the proportion of urine samples with negative results for illicit opioids ranged between 84% and 95%. Conclusion The program’s treatment retention rates and negative UDS results were higher than those reported for most methadone and buprenorphine-naloxone programs, despite a patient population where severe posttraumatic stress disorder is endemic, and despite the programs’ lack of resources and addiction expertise. Community-based programs like these overcome the initial challenge of cultural competence. First Nations communities in other provinces should establish their own buprenorphinenaloxone programs, using local primary care physicians as prescribers. Sustainable core funding is needed for programming, long-term aftercare, and trauma recovery for such initiatives. PMID:28209683

Maternal-Fetal Monitoring of Opioid-Exposed Pregnancies: Analysis of a Pilot Community-Based Protocol and Review of the Literature.

PubMed

Ryan, Gareth; Dooley, Joe; Windrim, Rory; Bollinger, Megan; Gerber Finn, Lianne; Kelly, Len

2017-06-01

To describe/analyse a novel, community-based prenatal monitoring protocol for opioid-exposed pregnancies developed by our centre in 2014 to optimize prenatal care for this population. A literature review of published monitoring protocols for this population is also presented. Retrospective comparison of pre-protocol (n = 215) and post-protocol (n = 251) cohorts. Medline and Embase were searched between 2000-2016 using MeSH terms: [fetal monitoring OR prenatal care] AND [opioid-related disorders OR substance-related disorders] in Medline and [fetal monitoring OR prenatal care] AND [opiate addiction OR substance abuse] in Embase, producing 518 results. Thirteen studies included protocols for monitoring opioid-exposed pregnancies. No comprehensive monitoring protocols with high-quality supporting evidence were found. We evaluated 466 opioid-exposed pregnancies, 215 before and 251 after introduction of the protocol. Since implementation, there was a significant increase in the number of opioid-exposed patients who have underwent urine drug screening (72.6% to 89.2%, P < 0.0001); a significant reduction in the number of urine drug screenings positive for illicit opioids (50.2% to 29.1%, P < 0.0001); and a significant increase in the number of patients who discontinued illicit opioid use by the time of delivery (24.7% to 39.4%, P < 0.01). There was no difference in the CS rate (27.4% vs. 26.3%, P > 0.05). There were no observed differences in the rate of preterm birth, birth weight <2500 g, or Apgar score <7 (P > 0.05). Care of women with increased opioid use during pregnancy is an important but under-studied health issue. A novel protocol for focused antenatal care provision for women with opioid-exposed pregnancies improves standard of care and maternal/fetal outcomes. Copyright © 2017. Published by Elsevier Inc.

Analgesia or addiction?: implications for morphine use after spinal cord injury.

PubMed

Woller, Sarah A; Moreno, Georgina L; Hart, Nigel; Wellman, Paul J; Grau, James W; Hook, Michelle A

2012-05-20

Opioid analgesics are among the most effective agents for treatment of moderate to severe pain. However, the use of morphine after a spinal cord injury (SCI) can potentiate the development of paradoxical pain symptoms, and continuous administration can lead to dependence, tolerance, and addiction. Although some studies suggest that the addictive potential of morphine decreases when it is used to treat neuropathic pain, this has not been studied in a SCI model. Accordingly, the present studies investigated the addictive potential of morphine in a rodent model of SCI using conditioned place preference (CPP) and intravenous self-administration paradigms. A contusion injury significantly increased the expression of a CPP relative to sham and intact controls in the acute phase of injury. However, contused animals self-administered significantly less morphine than sham and intact controls, but this was dose-dependent; at a high concentration, injured rats exhibited an increase in drug-reinforced responses over time. Exposure to a high concentration of morphine impeded weight gain and locomotor recovery. We suggest that the increased preference observed in injured rats reflects a motivational effect linked in part to the drug's anti-nociceptive effect. Further, although injured rats exhibited a suppression of opiate self-administration, when given access to a high concentration, addictive-like behavior emerged and was associated with poor recovery.

History of reported sexual or physical abuse among long-term heroin users and their response to substitution treatment.

PubMed

Oviedo-Joekes, Eugenia; Marchand, Kirsten; Guh, Daphne; Marsh, David C; Brissette, Suzanne; Krausz, Michael; Anis, Aslam; Schechter, Martin T

2011-01-01

Opioid-dependent individuals with a history of abuse have exhibited worse mental and physical health compared to those without such a history; however, the evidence regarding the influence of abuse histories on addiction treatment outcomes are conflicting. In the present study, we identified history of physical or sexual abuse at treatment initiation in relation to drug use and health among long-term opioid-dependent individuals and we determined the relationship of abuse histories with treatment outcomes following substitution treatment. We analyzed data from a randomized controlled trial that compared the effectiveness of opioid-agonists in the treatment of chronic opioid dependence. The North American Opiate Medication Initiative (NAOMI) was conducted in Vancouver and Montreal (Canada) and provided oral methadone, injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A total of 112 (44.6%) participants reported a history of physical or sexual abuse at baseline. Participants with an abuse history reported a significantly higher number of chronic medical problems, suicide attempts, and previous drug treatments and had poorer psychiatric, family and social relations, and quality of life status compared to those without abuse histories. No differences in current and past substance use were found between those with and without abuse histories. Following 12 months of treatment, the participants with abuse histories improved to a similar degree as those without a history of abuse in all of the European Addiction Severity Index sub-scales, with the exception of medical status. The findings suggest that individuals with abuse histories were able to achieve similar outcomes as those without abuse histories following treatment despite having poorer scores in physical and mental health, social status and quality of life at treatment initiation. These findings suggest that the substitution treatments as provided in this study can benefit the most vulnerable and access needs to be expanded to reach this population. Copyright © 2010 Elsevier Ltd. All rights reserved.

Sex-dependent effects of periadolescent exposure to the cannabinoid agonist CP-55,940 on morphine self-administration behaviour and the endogenous opioid system.

PubMed

Biscaia, Miguel; Fernández, Beatriz; Higuera-Matas, Alejandro; Miguéns, Miguel; Viveros, Maria-Paz; García-Lecumberri, Carmen; Ambrosio, Emilio

2008-04-01

Early cannabinoid consumption may predispose individuals to the misuse of addictive drugs later in life. However, there is a lack of experimental evidence as to whether cannabinoid exposure during adolescence might differently affect opiate reinforcing efficacy and the opioid system in adults of both sexes. Our aim was to examine whether periadolescent chronic exposure to the cannabinoid agonist CP-55,940 could exert sex-dependent effects on morphine reinforcing and the opioid system in adulthood. Morphine reinforcing was studied under a progressive ratio (PR) reinforcement schedule in adult male and female rats that previously acquired morphine self-administration under a fixed ratio 1 (FR1) schedule. Binding levels and functionality of mu-opioid receptors were also evaluated. Periadolescent cannabinoid exposure altered morphine self-administration and the opioid system in adult rats in a sex-dependent manner. CP-55,940-exposed males exhibited higher self-administration rates under a FR1, but not under a PR schedule. In females, CP-55,940 did not modify morphine self-administration under either schedule. Moreover, CP-55,940 also increased mu-opioid receptor levels in the subcallosal streak of pre-treated animals and decreased mu-opioid receptor functionality in the nucleus accumbens shell but again, only in males. Our data indicate that adult male rats exposed to the cannabinoid in adolescence self-administer more morphine than females, but only when the demands required by the schedule of reinforcement are low, which might be related to the decrease in mu-opioid receptor functionality in the NAcc-shell observed in these animals.

Pain, opioids, and sleep: implications for restless legs syndrome treatment.

PubMed

Trenkwalder, Claudia; Zieglgänsberger, Walter; Ahmedzai, Sam H; Högl, Birgit

2017-03-01

Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described. By targeting pain and its consequences, opioids are the first-line treatment in many diseases and conditions with both acute and chronic pain and have thus been used in both acute and chronic pain conditions over the last 40 years. Addiction, dependence, and tolerability of opioids show a wide variability interindividually, as the response to opioids is influenced by a complex combination of genetic, molecular, and phenotypic factors. Although several trials have now addressed opioid treatment in RLS, hyperalgesia as a complication of long-term opioid treatment, or opioid-opioid interaction have not received much attention so far. Therapeutic opioids may act not only on opioid receptors but also via histamine or N-methyl-d-aspartate (NMDA) receptors. In patients with RLS, one of the few studies investigating opioid bindings found that possible brain regions involved in the severity of RLS symptoms are similar to those known to be involved in chronic pain, such as the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex, and orbitofrontal cortex). The results of this diprenorphine positron emission tomography study suggested that the more severe the RLS, the greater the release of endogenous opioids. Since 1993, when the first small controlled study was performed with oxycodone in RLS, opioids have been considered an efficacious off-label therapy in patients with severe RLS. A recent trial has proved the efficacy of a combination of prolonged release oxycodone/naloxone in patients with severe RLS as second-line therapy, with a mean dosage of 10/5 mg twice daily (mean difference of International Restless Legs Syndrome Study Group Rating Scale (IRLS) score between groups at 12 weeks: 8.15), and has now been licensed as the first opioid therapy in Europe. The current results from both short- and long-term trials and studies with opioids encourage optimism in alleviating RLS symptoms in patients with severe RLS, or possibly during or after augmentation. Copyright © 2016 Elsevier B.V. All rights reserved.

Sex Differences and the Effects of Stress on Subsequent Opioid Consumption in Adult Rats Following Adolescent Nicotine Exposure: A Psychopharmacologic Examination of the Gateway Hypothesis

DTIC Science & Technology

1997-07-18

sign of fentanyl addiction is death by drug overdose (David Hester, personal communication, 1996). The addiction and abuse liability offentanyl is high...rats, not exposed to stress, died of apparent fentanyl overdose . These two rats also had been exposed to 12 mg nicotinelkglday and died despite lower...nicotinelkglday) during adolescence was related to increased, subsequent fentanyl self-administration in non-stressed male rats. Exposure to immobilization stress

Patterns of analgesic use to relieve tooth pain among residents in British Columbia, Canada

PubMed Central

2017-01-01

The use of prescription opioids has increased dramatically in Canada in recent decades. This rise in opioid prescriptions has been accompanied by increasing rates of opioid-related abuse and addiction, creating serious public health challenges in British Columbia (BC), one of Canada's most populated provinces. Our study explores the relationship between dental pain and prescription opioid use among residents in BC. We used data from the 2003 Canadian Community Health Survey (CCHS), which asked respondents about their use of specific analgesic medications, including opioids, and their history of tooth pain in the past month. We used logistic regression, controlling for potential confounding variables, to identify the predictive value of socioeconomic factors, oral health-related variables, and dental care utilization indicators. The Relative Index of Inequality (RII) was calculated to assess the magnitude of socioeconomic inequalities in the use of particular analgesics by incorporating income-derived ridit values into a binary logistic regression model. Our results showed that conventional non-opioid based analgesics (such as aspirin or Tylenol) and opioids were more likely to be used by those who had experienced a toothache in the past month than those who did not report experiencing a toothache. The use of non-opioid painkillers to relieve tooth pain was associated with more recent and more frequent dental visits, better self-reported oral health, and a greater income. Conversely, a lower household income was associated with a preference for opioid use to relieve tooth pain. The RII for recent opioid use and conventional painkiller use were 2.06 (95% CI: 1.75–2.37) and 0.62 (95% CI: 0.35–0.91), respectively, among those who experienced recent tooth pain, suggesting that adverse socioeconomic conditions may influence the need for opioid analgesics to relieve dental pain. We conclude that programs and policies targeted at improving the dental health of the poor may help to reduce the use of prescription opioids, thereby narrowing health inequalities within the broader society. PMID:28459825

Addiction and substance abuse in anesthesiology.

PubMed

Bryson, Ethan O; Silverstein, Jeffrey H

2008-11-01

Despite substantial advances in our understanding of addiction and the technology and therapeutic approaches used to fight this disease, addiction still remains a major issue in the anesthesia workplace, and outcomes have not appreciably changed. Although alcoholism and other forms of impairment, such as addiction to other substances and mental illness, impact anesthesiologists at rates similar to those in other professions, as recently as 2005, the drug of choice for anesthesiologists entering treatment was still an opioid. There exists a considerable association between chemical dependence and other psychopathology, and successful treatment for addiction is less likely when comorbid psychopathology is not treated. Individuals under evaluation or treatment for substance abuse should have an evaluation with subsequent management of comorbid psychiatric conditions. Participation in self-help groups is still considered a vital component in the therapy of the impaired physician, along with regular monitoring if the anesthesiologist wishes to attempt reentry into clinical practice.

Testing use of payers to facilitate evidence-based practice adoption: protocol for a cluster-randomized trial

PubMed Central

2013-01-01

Background More effective methods are needed to implement evidence-based findings into practice. The Advancing Recovery Framework offers a multi-level approach to evidence-based practice implementation by aligning purchasing and regulatory policies at the payer level with organizational change strategies at the organizational level. Methods The Advancing Recovery Buprenorphine Implementation Study is a cluster-randomized controlled trial designed to increase use of the evidence-based practice buprenorphine medication to treat opiate addiction. Ohio Alcohol, Drug Addiction, and Mental Health Services Boards (ADAMHS), who are payers, and their addiction treatment organizations were recruited for a trial to assess the effects of payer and treatment organization changes (using the Advancing Recovery Framework) versus treatment organization changes alone on the use of buprenorphine. A matched-pair randomization, based on county characteristics, was applied, resulting in seven county ADAMHS boards and twenty-five treatment organizations in each arm. Opioid dependent patients are nested within cluster (treatment organization), and treatment organization clusters are nested within ADAMHS county board. The primary outcome is the percentage of individuals with an opioid dependence diagnosis who use buprenorphine during the 24-month intervention period and the 12-month sustainability period. The trial is currently in the baseline data collection stage. Discussion Although addiction treatment providers are under increasing pressure to implement evidence-based practices that have been proven to improve patient outcomes, adoption of these practices lags, compared to other areas of healthcare. Reasons frequently cited for the slow adoption of EBPs in addiction treatment include, regulatory issues, staff, or client resistance and lack of resources. Yet the way addiction treatment is funded, the payer’s role—has not received a lot of attention in research on EBP adoption. This research is unique because it investigates the role of payers in evidence-based practice implementation using a randomized controlled design instead of case examples. The testing of the Advancing Recovery Framework is designed to broaden the understanding of the impact payers have on evidence-based practice (EBP) adoption. Trial registration http://NCT01702142 (ClinicalTrials.gov registry, USA) PMID:23663749

Prescription of opioid analgesics for nontraumatic dental conditions in emergency departments.

PubMed

Okunseri, Christopher; Dionne, Raymond A; Gordon, Sharon M; Okunseri, Elaye; Szabo, Aniko

2015-11-01

Opioid analgesics prescribed for nontraumatic dental conditions (NTDCs) by emergency physicians continue to receive attention because of the associated potential for misuse, abuse and addiction. This study examined rates of prescription of opioid analgesics and types of opioid analgesics prescribed for NTDC visits in U.S. emergency departments. Data from the National Hospital Ambulatory Medical Care Survey from 2007 to 2010 were analyzed. Descriptive statistics and logistic regression analysis were performed and adjusted for the survey design. NTDCs made up 1.7% of all ED visits from 2007 to 2010. The prescription of opioid analgesics was 50.3% for NTDC and 14.8% for non-NTDC visits. The overall rate of opioid analgesics prescribed for NTDCs remained fairly stable from 2007 through 2010. Prescription of opioids was highest among patients aged 19-33 years (56.8%), self-paying (57.1%), and non-Hispanic Whites (53.2%). The probability of being prescribed hydrocodone was highest among uninsured patients (68.7%) and for oxycodone, it was highest among private insurance patients (33.6%). Compared to 34-52 year olds, children 0-4 years were significantly more likely to be prescribed codeine and less likely to be prescribed oxycodone. Compared to non-Hispanic Whites, non-Hispanic Blacks had significantly higher odds of been prescribed codeine and somewhat lower odds of been prescribed oxycodone, but it was not statistically significant. There was no significant change in the rates of opioid analgesics prescribed over time for NTDC visits to EDs. Age, payer type and race/ethnicity were significant predictors for the prescription of different opioid analgesics by emergency physicians for NTDC visits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Problem drinking and low-dose naltrexone-assisted opioid detoxification.

PubMed

Mannelli, Paolo; Peindl, Kathleen; Patkar, Ashwin A; Wu, Li-Tzy; Tharwani, Haresh M; Gorelick, David A

2011-05-01

The influence of alcohol use on opioid dependence is a major problem that warrants a search for more effective treatment strategies. The addition of very-low-dose naltrexone (VLNTX) to methadone taper was recently associated with reduced withdrawal intensity during detoxification. In a secondary analysis of these data, we sought to determine whether problem drinking affects detoxification outcomes and whether symptoms are influenced by VLNTX use. Opioid-dependent patients (N = 174) received naltrexone (0.125 or 0.250 mg/day) or placebo in a double-blind, randomized design during methadone-based, 6-day inpatient detoxification. Alcohol consumption was assessed at admission using the Addiction Severity Index and selfreport. Outcome measures were opioid withdrawal intensity, craving, and retention in treatment. Problem drinking-opioid dependent patients (n = 79) showed episodic heavy alcohol use and reported increased subjective opioid withdrawal intensity (p = .001), craving (p = .001), and significantly lower rate of retention in treatment (p = .02). Individuals with problem drinking and opioid dependence who were treated with VLNTX (n = 55) showed reduced withdrawal (p = .05) and a lower rate of treatment discontinuation (p = .03), resuming alcohol intake in smaller numbers the day following discharge (p = .03). Treatment effects were more pronounced on anxiety, perspiration, shakiness, nausea, stomach cramps, and craving. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Heavy drinking is associated with worse opioid detoxification outcomes. The addition of VLNTX is safe and is associated with reduced withdrawal symptoms and better completion rate in these patients. Further studies should explore the use of VLNTX in detoxification and long-term treatment of combined alcohol-opioid dependence and alcohol dependence alone.

Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats.

PubMed

Escobar, Angélica P; González, Marcela P; Meza, Rodrigo C; Noches, Verónica; Henny, Pablo; Gysling, Katia; España, Rodrigo A; Fuentealba, José A; Andrés, María E

2017-08-01

Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of quinpirole, a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist. The mechanism underlying kappa opioid receptor potentiation of quinpirole-induced locomotor sensitization remains to be elucidated. Immunofluorescence anatomical studies were undertaken in mice brain slices and rat presynaptic synaptosomes to reveal kappa opioid receptor and D2R pre- and postsynaptic colocalization in the nucleus accumbens. Tonic and phasic dopamine release in the nucleus accumbens of rats repeatedly treated with U69593 and quinpirole was assessed by microdialysis and fast scan cyclic voltammetry. Anatomical data show that kappa opioid receptor and D2R colocalize postsynaptically in medium spiny neurons of the nucleus accumbens and the highest presynaptic colocalization occurs on the same dopamine terminals. Significantly reduced dopamine levels were observed in quinpirole, and U69593-quinpirole treated rats, explaining sensitization of D2R. Presynaptic inhibition induced by kappa opioid receptor and D2R of electrically evoked dopamine release was faster in U69593-quinpirole compared with quinpirole-repeatedly treated rats. Pre- and postsynaptic colocalization of kappa opioid receptor and D2R supports a role for kappa opioid receptor potentiating both the D2R inhibitory autoreceptor function and the inhibitory action of D2R on efferent medium spiny neurons. Kappa opioid receptor co-activation accelerates D2R sensitization by contributing to decrease dopamine release in the nucleus accumbens. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Barriers to access to opioid medicines for patients with opioid dependence: a review of legislation and regulations in eleven central and eastern European countries.

PubMed

Vranken, Marjolein J M; Mantel-Teeuwisse, Aukje K; Jünger, Saskia; Radbruch, Lukas; Scholten, Willem; Lisman, John A; Subataite, Marija; Schutjens, Marie-Hélène D B

2017-06-01

Barriers linked to drug control systems are considered to contribute to inequitable access to controlled medicines, leaving millions of people in pain and suffering. Most studies focus on access to opioids for the treatment of severe (cancer) pain. This study aims to identify specific access barriers for patients with opioid dependence in legislation and regulations of 11 central and eastern European countries. This study builds on a previous analysis of legislation and regulations as part of the EU 7th Framework Access To Opioid Medication in Europe (ATOME) project. An in-depth analysis was undertaken to determine specific barriers for patients with opioid dependence in need of opioid analgesics or opioid agonist therapy (OAT). For each country, the number and nature of specific potential barriers for these patients were assessed according to eight categories: prescribing; dispensing; manufacturing; usage; trade and distribution; affordability; penalties; and other. An additional keyword search was conducted to minimize the omission of barriers. Barriers in an additional category, language, were recorded qualitatively. Countries included Bulgaria, Cyprus, Estonia, Greece, Hungary, Latvia, Lithuania, Serbia, Slovakia, Slovenia and Turkey. Ten of the 11 countries (all except Estonia) showed specific potential barriers in their legislation and regulations. The total number of barriers varied from two (Slovenia) to 46 (Lithuania); the number of categories varied from one (Slovenia) to five (Lithuania). Most specific potential barriers were shown in the categories 'prescribing', 'usage' and 'other'. The total number in a single category varied from one to 18 (Lithuania, prescribing). Individual differences between countries in the same specific potential barrier were shown; for example, variation in minimum age criteria for admission to OAT ranging from 15 (Lithuania, in special cases) to 20 years (Greece). All countries had stigmatizing language in their legislation. Patients with opioid dependence are likely to experience specific barriers to accessing opioids in addition to those experienced by other non-dependent patients. © 2017 Society for the Study of Addiction.

Dynorphin/Kappa Opioid Receptor Signaling in Preclinical Models of Alcohol, Drug, and Food Addiction.

PubMed

Karkhanis, Anushree; Holleran, Katherine M; Jones, Sara R

2017-01-01

The dynorphin/kappa opioid receptor (KOR) system is implicated in the "dark side" of addiction, in which stress exacerbates maladaptive responses to drug and alcohol exposure. For example, acute stress and acute ethanol exposure result in an elevation in dynorphin, the KOR endogenous ligand. Activation of KORs results in modulation of several neurotransmitters; however, this chapter will focus on its regulatory effects on dopamine in mesolimbic areas. Specifically, KOR activation has an inhibitory effect on dopamine release, thereby influencing reward processing. Repeated stimulation of KORs, for example, via chronic drug and/or stress exposure, results in increased function of the dynorphin/KOR system. This augmentation in KOR function shifts the homeostatic balance in favor of an overall reduction in dopamine signaling via either by reducing dopamine release or by increasing dopamine transporter function. This chapter examines the effects of chronic ethanol exposure on KOR function and the downstream effects on dopamine transmission. Additionally, the impact of chronic cocaine exposure and its effects on KOR function will be explored. Further, KORs may also be involved in driving excessive consumption of food, contributing to the risk of developing obesity. While some studies have shown that KOR agonists reduce drug intake, other studies have shown that antagonists reduce addiction-like behaviors, demonstrating therapeutic potential. For example, KOR inhibition reduces ethanol intake in dependent animals, motivation to self-administer cocaine in chronic stress-exposed animals, and food consumption in obese animals. This chapter will delve into the mechanisms by which modulation of the dynorphin/KOR system may be therapeutic. © 2017 Elsevier Inc. All rights reserved.

Acute pain management in opioid-tolerant patients: a growing challenge.

PubMed

Huxtable, C A; Roberts, L J; Somogyi, A A; MacIntyre, P E

2011-09-01

In Australia and New Zealand, in parallel with other developed countries, the number of patients prescribed opioids on a long-term basis has grown rapidly over the last decade. The burden of chronic pain is more widely recognised and there has been an increase in the use of opioids for both cancer and non-cancer indications. While the prevalence of illicit opioid use has remained relatively stable, the diversion and abuse of prescription opioids has escalated, as has the number of individuals receiving methadone or buprenorphine pharmacotherapy for opioid addiction. As a result, the proportion of opioid-tolerant patients requiring acute pain management has increased, often presenting clinicians with greater challenges than those faced when treating the opioid-naïve. Treatment aims include effective relief of acute pain, prevention of drug withdrawal, assistance with any related social, psychiatric and behavioural issues, and ensuring continuity of long-term care. Pharmacological approaches incorporate the continuation of usual medications (or equivalent), short-term use of sometimes much higher than average doses of additional opioid, and prescription of non-opioid and adjuvant drugs, aiming to improve pain relief and attenuate opioid tolerance and/or opioid-induced hyperalgesia. Discharge planning should commence at an early stage and may involve the use of a 'Reverse Pain Ladder' aiming to limit duration of additional opioid use. Legislative requirements may restrict which drugs can be prescribed at the time of hospital discharge. At all stages, there should be appropriate and regular consultation and liaison with the patient, other treating teams and specialist services.

Effect of prison-based opioid substitution treatment and post-release retention in treatment on risk of re-incarceration.

PubMed

Larney, Sarah; Toson, Barbara; Burns, Lucy; Dolan, Kate

2012-02-01

People who use heroin are frequently incarcerated multiple times. Reducing re-incarceration of this group is important for reducing both health risks associated with incarceration and the costs of correctional administration. Opioid substitution treatment (OST) in prisons may help to reduce re-incarceration, but research findings on this topic have been mixed. In this study, we examined the effect of OST in prison and after release on re-incarceration. Longitudinal cohort study. SETTING, PARTICIPANTS AND MEASUREMENTS: Data on OST and incarceration were linked for a cohort of 375 male heroin users recruited originally in prisons in New South Wales, Australia. Data were linked for the period 1 June 1997-31 December 2006. Re-incarceration was examined using recurrent-event survival analysis models. Model 1 examined the effect of OST status at release from prison (i.e. in treatment versus out of treatment on the day of release) on re-incarceration. Model 2 considered the effect of remaining in OST after release on risk of re-incarceration. Ninety per cent of participants were re-incarcerated following their first observed release. Pre-incarceration cocaine use was associated with a 13% increase in the average risk of re-incarceration. There was no significant association between simply being in OST at the time of release and risk of re-incarceration; however, in the model taking into account post-release retention in treatment, the average risk of re-incarceration was reduced by 20% while participants were in treatment. In New South Wales, Australia, opioid substitution treatment after release from prison has reduced the average risk of re-incarceration by one-fifth. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Proceedings from Bridging Health Disparities to Address the Opioid Epidemic: A Symposium at the Warren Alpert Medical School of Brown University.

PubMed

Dumenco, Luba; Monteiro, Kristina; Mello, Michael; Collins, Sally; Operario, Don; Scanlan, Karen; Dollase, Richard; George, Paul

2017-04-03

In response to the unprecedented rates of illicit drug use, including opioid addiction and overdose in Rhode Island, local healthcare institutions, led by the Warren Alpert Medical School (AMS) of Brown University, collaborated to present "Bridging Health Disparities to Address the Opioid Epidemic." This symposium sought to educate a wide array of healthcare providers and professionals around opioid use disorder, including the state of the opioid crisis in Rhode Island, national efforts around opioid misuse and how providers can work together to stem the opioid crisis in the state. The symposium included a keynote session which aimed to increase knowledge and decrease stigma. This was followed by two rounds of breakout sessions which focused on various components of opioid disorder treatment. We elicited feedback from participants in order to plan further interventions to educate providers in Rhode Island around the opioid epidemic. Primary Results: Initial feedback was positive. More importantly, this workshop allowed us to identify gaps in knowledge amongst healthcare providers in Rhode Island in order to plan further interventions for healthcare providers, including physicians, around opioid misuse, in Rhode Island. This symposium is one of the first steps that a consortium of healthcare institutions, including AMS, will take to address the opioid crisis in Rhode Island. Feedback from the event was elicited to identify gaps in healthcare provider knowledge and will be used to design and implement further interventions. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp].

Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain

PubMed Central

Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

2005-01-01

Aims Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. Methods The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (°C), as well as suprathreshold tonic heat pain intensity (46.5 °C for 1 min) measured by 0–10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. Results No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI −8.8, 42.8), P = 0.19), pressure (2.2 mmHg (−28.7, 33.2), P = 0.89) and heat (−0.3 °C (−1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities −0.4 NPS units (95% CI −1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the ‘weak’ opioid-treated subgroup and the ‘strong’ opioid-treated subgroup again revealed insignificant results. Conclusions These results suggest that the administration of ‘commonly used’ dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients receiving non-opioid analgesia. PMID:16120071

Opioid activation of Toll-Like receptor 4 contributes to drug reinforcement

PubMed Central

Hutchinson, M.R.; Northcutt, A.L.; Hiranita, T.; Wang, X.; Lewis, S.; Thomas, J.; van Steeg, K.; Kopajtic, T.A.; Loram, L.; Sfregola, C.; Galer, E.; Miles, N.E.; Bland, S.T.; Amat, J.; Rozeske, R.R.; Maslanik, T.; Chapman, T.; Strand, K.; Fleshner, M.; Bachtell, R.K.; Somogyi, A.A.; Yin, H.; Katz, J.L.; Rice, K.C.; Maier, S.F.; Watkins, L.R.

2012-01-01

Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, Toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the non-opioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knockouts of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4 −/− mice had reduced oxycodone-induced p38 and JNK phosphorylation, whilst displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system which amplifies opioid-induced elevations in extracellular dopamine levels and therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward. PMID:22895704

A Scientometric Study of Iranian Scientific Productions in the Field of Substance Use and Addiction Research in the Years 2008 to 2012.

PubMed

Rahimi-Movaghar, Afarin; Amin-Esmaeili, Masoumeh; Safarcherati, Anousheh; Sarami, Hamid; Rafiey, Hassan

2015-01-01

We aimed to evaluate the current status of scientific production in the field of substance use and addiction in Iran, to determine its trend and pattern during a 5 years period (2008-2012). Using relevant keywords, we searched three international databases (Web of Science, Medline, and Scopus) and two local databases (SID and Iranmedex) to locate the papers published in the field of addiction by Iranian researchers during 2008-2012. The results indicated a significant increase in the number of studies published in the field during the 5 years study period, with more than half of the papers published in the last 2 years. Results also indicated that over half (53.5%) of the papers were published in Persian-language Iranian Journals, but the rate of increase in the number of papers published in English was slightly higher than that of Persian ones. Opioid substances were found to be the topic of approximately 75% of the papers. Studies on key topics, including national surveys, evaluation of current programs, addiction in women and children, and so forth, were found to be highly lacking. Results suggested a significant growth in the scientific production of Iran in the field of substance use and addiction. However, considering the significance of substance use and dependence in the country, and compared to the scientific production of developed countries, the amount of research conducted in the field of addiction in Iran is still limited.

Addressing Stigma in Medication Treatment of Adolescents With Opioid Use Disorder.

PubMed

Bagley, Sarah M; Hadland, Scott E; Carney, Brittany L; Saitz, Richard

: In September 2016, the American Academic of Pediatrics released a policy statement that adolescents with opioid use disorder should be offered pharmacotherapy with buprenorphine/naloxone, methadone, or naltrexone. In our clinical practice, however, we have encountered the perception among patients, families, and clinicians alike that medications should be used as a last resort. That we should wait until things get worse is a discarded approach. As addiction specialists, it is imperative that we prevent and identify risky use and use disorders, then intervene early and offer timely, evidence-based treatment. We suggest that adolescents deserve special attention and that specific efforts should be made to reduce the stigma associated with treating adolescents with opioid use disorder with medications to optimize those efforts.

The Growing Popularity of Prescription Opioid Injection in Downtown Montréal: New Challenges for Harm Reduction

PubMed Central

Roy, Élise; Arruda, Nelson; Bourgois, Phillipe

2011-01-01

Starting in 2007, a 2-year study based on ethnographic methodology was carried out downtown Montréal, Canada. A thematic analysis of observational and interview-based notes was conducted. Illicit prescription opioid (PO) use was widespread among street-based participants. Injection was the main mode of PO administration observed among users. Some injection practices such as “doing a wash” could pose new challenges in terms of prevention of infections. More research is needed to examine the role of illicit PO use in the development of opiate addiction and to better understand drug-using contexts that put PO users at risk of infections. The study’s limitations are noted. PMID:21370963

Cocaine Modulates the Expression of Opioid Receptors and miR-let-7d in Zebrafish Embryos

PubMed Central

López-Bellido, Roger; Barreto-Valer, Katherine; Sánchez-Simón, Fátima Macho; Rodríguez, Raquel E.

2012-01-01

Prenatal exposure to cocaine, in mammals, has been shown to interfere with the expression of opioid receptors, which can have repercussions in its activity. Likewise, microRNAs, such as let-7, have been shown to regulate the expression of opioid receptors and hence their functions in mammals and in vitro experiments. In light of this, using the zebrafish embryos as a model our aim here was to evaluate the actions of cocaine in the expression of opioid receptors and let-7d miRNA during embryogenesis. In order to determine the effects produced by cocaine on the opioid receptors (zfmor, zfdor1 and zfdor2) and let-7d miRNA (dre-let-7d) and its precursors (dre-let-7d-1 and dre-let-7d-2), embryos were exposed to 1.5 µM cocaine hydrochloride (HCl). Our results revealed that cocaine upregulated dre-let-7d and its precursors, and also increased the expression of zfmor, zfdor1 and zfdor2 during early developmental stages and decreased them in late embryonic stages. The changes observed in the expression of opioid receptors might occur through dre-let-7d, since DNA sequences and the morpholinos of opioid receptors microinjections altered the expression of dre-let-7d and its precursors. Likewise, opioid receptors and dre-let-7d showed similar distributions in the central nervous system (CNS) and at the periphery, pointing to a possible interrelationship between them. In conclusion, the silencing and overexpression of opioid receptors altered the expression of dre-let-7d, which points to the notion that cocaine via dre-let-7 can modulate the expression of opioid receptors. Our study provides new insights into the actions of cocaine during zebrafish embryogenesis, indicating a role of miRNAs, let-7d, in development and its relationship with gene expression of opioid receptors, related to pain and addiction process. PMID:23226419

Reward loss and addiction: Opportunities for cross-pollination.

PubMed

Ortega, Leonardo A; Solano, José L; Torres, Carmen; Papini, Mauricio R

2017-03-01

Paradigms used to study the response to and consequences of exposure to reward loss have been underutilized in approaches to the psychobiology of substance use disorders. We propose here that bringing these two areas into contact will help expanding our understanding of both reward loss and addictive behavior, hence opening up opportunities for cross-pollination. This review focuses on two lines of research that point to parallels. First, several neurochemical systems involved in addiction are also involved in the modulation of the behavioral effects of reward loss, including opioid, GABA, and dopamine receptors. Second, there are extensive overlaps in the brain circuitry underlying both reward loss and addiction. Common components of this system include, at least, the amygdala, ventral and dorsal striatum, and various prefrontal cortex regions. Four emerging avenues of research that benefit from emphasis on the common ground between reward loss and addiction are reviewed, namely, the neural circuitry involved in reward devaluation, the influence of genetic and reward history on the behavioral vulnerability and resilience, the role of competing natural rewards, and emotional self-medication. An understanding of the role of reward loss in addiction will point to a deeper understanding of the initiation and maintenance of substance use disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Rates of Mortality and Serious Adverse Effects Among Commonly Prescribed Opioid Analgesics.

PubMed

Murphy, David L; Lebin, Jacob A; Severtson, Stevan G; Olsen, Heather A; Dasgupta, Nabarun; Dart, Richard C

2018-03-26

The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics. The common assumption that more potent opioid analgesics are associated with higher rates of adverse outcomes has not been adequately substantiated. We compared the rate of serious adverse events among commonly prescribed opioid analgesics of varying potency. Serious adverse events (SAEs; defined as death, major medical effect, or hospitalization) resulting from exposure to tablets containing seven opioid analgesics (oxycodone, hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol) captured by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS ® ) System Poison Center Program were evaluated from 2010 through 2016. Rates of SAEs were adjusted for availability through outpatient dispensing data and regressed on morphine milligram equivalents (MME). There were 19,480 cases of SAE during the 7-year study period. Hydrocodone and oxycodone contributed to 77% of SAE cases. Comparing rates of outcome by relative potency, a hierarchy was observed with hydromorphone (8.02 SAEs/100 kg) and tapentadol (0.27 SAE/100 kg) as the highest and lowest rates, reflecting a 30-fold difference among individual opioid products. SAE rate and potency were related linearly-SAEs increased 2.04 per 100 kg drug dispensed for each 1-unit rise in MME (p = 0.004). Linear regression of SAE/100 kg drug dispensed and drug potency identified that MME comprised 96% of the variation observed. In contrast, potency did not explain variation seen using other study denominators (prescriptions dispensed, dosage units dispensed, and the number of individuals filling a prescription). Potency of a prescription opioid analgesic demonstrates a significant, highly positive linear relationship with exposures resulting in SAEs per 100 kg drug dispensed reported to poison centers. Potency should be carefully considered from both individual provider and public health perspectives.

Opioid maintenance therapy restores CD4+ T cell function by normalizing CD4+CD25(high) regulatory T cell frequencies in heroin user.

PubMed

Riss, Gina-Lucia; Chang, Dae-In; Wevers, Carolin; Westendorf, Astrid M; Buer, Jan; Scherbaum, Norbert; Hansen, Wiebke

2012-08-01

There is an increasing body of evidence that heroin addiction is associated with severe alterations in immune function, which might contribute to an increased risk to contract infectious diseases like hepatitis B and C or HIV. However, the impact of heroin consumption on the CD4(+) T cell compartment is not well understood. Therefore, we analyzed the frequency and functional phenotype of CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells (Tregs) isolated from the peripheral blood of opiate addicts currently abusing heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected a significant increase in the percentage of CD4(+)CD25(high) Tregs in the peripheral blood of heroin addicted patients in contrast to patients in OMT. The proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti-CD28 antibodies was significantly decreased in heroin users, but could be restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to similar values as observed from healthy controls and patients in OMT. These results suggest that impaired immune responses observed in heroin users are related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be restored by OMT. Copyright © 2012 Elsevier Inc. All rights reserved.

Changes in quality of life (WHOQOL-BREF) and addiction severity index (ASI) among participants in opioid substitution treatment (OST) in low and middle income countries: an international systematic review.

PubMed

Feelemyer, Jonathan P; Jarlais, Don C Des; Arasteh, Kamyar; Phillips, Benjamin W; Hagan, Holly

2014-01-01

Opioid substitution treatment (OST) can increase quality of life (WHOQOL-BREF) and reduce addiction severity index (ASI) scores among participants over time. OST program participants have noted that improvement in quality of life is one of the most important variables to their reduction in drug use. However, there is little systematic understanding of WHOQOL-BREF and ASI domain changes among OST participants in low and middle-income countries (LMIC). Utilizing PRISMA guidelines we conducted a systematic literature search to identify OST program studies documenting changes in WHOQOL-BREF or ASI domains for participants in buprenorphine or methadone programs in LMIC. Standardized mean differences for baseline and follow-up domain scores were compared along with relationships between domain scores, OST dosage, and length of follow-up. There were 13 OST program studies with 1801 participants from five countries eligible for inclusion in the review. Overall, statistically significant changes were noted in all four WHOQOL-BREF domain and four of the seven ASI domain scores (drug, psychological, legal, and family) documented in studies. Dosage of pharmacologic medication and length of follow-up did not affect changes in domain scores. WHOQOL-BREF and ASI domain scoring is a useful tool in measuring overall quality of life and levels of addiction among OST participants. Coupled with measurements of blood-borne infection, drug use, relapse, and overdose, WHOQOL-BREF and ASI represent equally important tools for evaluating the effects of OST over time and should be further developed as integrated tools in the evaluation of participants in LMIC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Interaction of biogenic amines with ethanol.

PubMed

Smith, A A

1975-01-01

Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids.

Addicted to palatable foods: comparing the neurobiology of Bulimia Nervosa to that of drug addiction.

PubMed

Hadad, Natalie A; Knackstedt, Lori A

2014-05-01

Bulimia nervosa (BN) is highly comorbid with substance abuse and shares common phenotypic and genetic predispositions with drug addiction. Although treatments for the two disorders are similar, controversy remains about whether BN should be classified as addiction. Here, we review the animal and human literature with the goal of assessing whether BN and drug addiction share a common neurobiology. Similar neurobiological features are present following administration of drugs and bingeing on palatable food, especially sugar. Specifically, both disorders involve increases in extracellular dopamine (DA), D1 binding, D3 messenger RNA (mRNA), and ΔFosB in the nucleus accumbens (NAc). Animal models of BN reveal increases in ventral tegmental area (VTA) DA and enzymes involved in DA synthesis that resemble changes observed after exposure to addictive drugs. Additionally, alterations in the expression of glutamate receptors and prefrontal cortex activity present in human BN or following sugar bingeing in animals are comparable to the effects of addictive drugs. The two disorders differ in regards to alterations in NAc D2 binding, VTA DAT mRNA expression, and the efficacy of drugs targeting glutamate to treat these disorders. Although additional empirical studies are necessary, the synthesis of the two bodies of research presented here suggests that BN shares many neurobiological features with drug addiction. While few Food and Drug Administration-approved options currently exist for the treatment of drug addiction, pharmacotherapies developed in the future, which target the glutamate, DA, and opioid systems, may be beneficial for the treatment of both BN and drug addiction.

Addicted to Palatable Foods: Comparing the Neurobiology of Bulimia Nervosa to that of Drug Addiction

PubMed Central

Hadad, Natalie A.; Knackstedt, Lori A.

2014-01-01

Rationale: Bulimia Nervosa (BN) is highly comorbid with substance abuse and shares common phenotypic and genetic predispositions with drug addiction. Although treatments for the two disorders are similar, controversy remains about whether BN should be classified as addiction. Objectives: Here we review the animal and human literature with the goal of assessing whether BN and drug addiction share a common neurobiology. Results: Similar neurobiological features are present following administration of drugs and bingeing on palatable food, especially sugar. Specifically, both disorders involve increases in extracellular dopamine (DA), D1 binding, D3 mRNA, and ΔFosB in the nucleus accumbens (NAc). Animal models of BN reveal increases in ventral tegmental area (VTA) DA and enzymes involved in DA synthesis that resemble changes observed after exposure to addictive drugs. Additionally, alterations in the expression of glutamate receptors and prefrontal cortex activity present in human BN or following sugar bingeing in animals are comparable to the effects of addictive drugs. The two disorders differ in regards to alterations in NAc D2 binding, VTA DAT mRNA expression, and the efficacy of drugs targeting glutamate to treat these disorders. Conclusions: Although additional empirical studies are necessary, the synthesis of the two bodies of research presented here suggests that BN shares many neurobiological features with drug addiction. While few FDA-approved options currently exist for the treatment of drug addiction, pharmacotherapies developed in the future which target the glutamate, DA, and opioid systems may be beneficial for the treatment of both BN and drug addiction. PMID:24500676

Risk factors for severe respiratory depression from prescription opioid overdose.

PubMed

Fox, Lindsay M; Hoffman, Robert S; Vlahov, David; Manini, Alex F

2018-01-01

Prescription opioid overdose is a leading cause of injury-related morbidity and mortality in the United States. We aimed to identify characteristics associated with clinical severity in emergency department patients with prescription opioid overdose. This was a secondary data analysis of adult prescription opioid overdoses from a large prospective cohort of acute overdoses. We examined elements of a typical emergency department evaluation using a multivariable model to determine which characteristics were associated with clinical severity, specifically severe respiratory depression (SRD). This study was conducted at two urban academic emergency departments in New York City, USA. Adult patients who presented with acute prescription opioid overdose between 2009 and 2013 were included in the current study. We analyzed 307 patients (mean age = 44.7, 42% female, 2.0% mortality). Patient demographics, reported substances ingested, suspected intent for ingesting the substance, vital signs, laboratory data, treatments including antidotes and intubation and outcome of death were recorded by trained research assistants. Intent was categorized into four mutually exclusive categories: suicide, misuse, therapeutic error and undetermined. The primary outcome was SRD, defined as administration of either (a) naloxone or (b) endotracheal intubation (ETI). A total of 109 patients suffered SRD with 90 patients receiving naloxone alone, nine ETI alone and 10 both naloxone and ETI. The most common opioids were oxycodone (n = 124) and methadone (n = 116). Mean age was higher in patients with SRD (51.1 versus 41.1, P < 0.001). Opioid misuse was associated with SRD in the multivariable analysis [odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.21-3.55]. The unadjusted relative risk of SRD was high for fentanyl (83.3% SRD) and lowest for codeine (3.6% SRD). In emergency department patients in the United States with prescription opioid overdose, worse clinical severity was associated with opioid misuse, increased with age and was widely variable, depending on the specific opioid medication involved. © 2017 Society for the Study of Addiction.

Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills.

PubMed

Chai, Peter R; Carreiro, Stephanie; Innes, Brendan J; Chapman, Brittany; Schreiber, Kristin L; Edwards, Robert R; Carrico, Adam W; Boyer, Edward W

2017-12-01

Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction. We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion. In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3-9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest opioids at 1 week. There was substantial variability in ingestion patterns between individuals. The utilization patterns of individuals with acute fracture pain could be captured using a digital pill system and revealed a median opioid ingestion of 45-mg morphine equivalents for acute pain over 7 days. Seven participants ceased using opioids within 4 days after discharge from the emergency department, although operative repair was associated with longer use. This digital pill system was able to measure changes in and patterns of opioid self-dosing, which varied between patients.

National addictions vigilance intervention and prevention program (NAVIPPRO): a real-time, product-specific, public health surveillance system for monitoring prescription drug abuse.

PubMed

Butler, Stephen F; Budman, Simon H; Licari, Andrea; Cassidy, Theresa A; Lioy, Katherine; Dickinson, James; Brownstein, John S; Benneyan, James C; Green, Traci Craig; Katz, Nathaniel

2008-12-01

The National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) is a scientific, comprehensive risk management program for scheduled therapeutics. NAVIPPRO provides post-marketing surveillance, signal detection, signal verification and prevention and intervention programs. Here we focus on one component of NAVIPPRO surveillance, the Addiction Severity Index-Multimedia Version (ASI-MV) Connect, a continuous, real-time, national data stream that assesses pharmaceutical abuse by patients entering substance abuse treatment by collecting product-specific, geographically-detailed information. We evaluate population characteristics for data collected through the ASI-MV Connect in 2007 and 2008 and assess the representativeness, geographic coverage, and timeliness of report of the data. Analyses based on 41,923 admissions to 265 treatment centers in 29 states were conducted on product-specific opioid abuse rates, source of drug, and route of administration. ASI-MV Connect data revealed that 11.5% of patients reported abuse of at least one opioid analgesic product in the 30 days prior to entering substance abuse treatment; differences were observed among sub-populations of prescription opioid abusers, among products, and also within various geographic locations. The ASI-MV Connect component of NAVIPPRO represents a potentially valuable data stream for post-marketing surveillance of prescription drugs. Analyses conducted with data obtained from the ASI-MV Connect allow for the characterization of product-specific and geospatial differences for drug abuse and can serve as a tool to monitor responses of the abuse population to newly developed "abuse deterrent" drug formulations. Additional data, evaluation, and comparison to other systems are important next steps in establishing NAVIPPRO as a comprehensive, post-marketing surveillance system for prescription drugs. Copyright (c) 2008 John Wiley & Sons, Ltd.

The Laboratory’s Role in Opioid Pain Medication Monitoring

PubMed Central

2012-01-01

Opioid analgesics are the most potent pain medications therefore they are often used for the treatment of chronic malignant and non-malignant pain. Their strong addictive potential requires close monitoring of patients on opioid therapy for possible non-compliance with prescriptions, for drug diversion, and for proof of avoidance of non-prescribed or illicit opioids. Monitoring can be performed by urine drug screens or qualitative or quantitative drug confirmation assays. Natural, semi-synthetic and synthetic opioids have dissimilar chemical structures and they undergo extensive metabolism. Phase one metabolic reactions of opioids can produce other opioids with similar structures to other, non-prescribed medications. Only detailed and concurrent analysis of parent drugs and metabolites can provide accurate clinical information regarding patient compliance. Traditional immunoassays, often used for urine drug screening, react with only a small number of opioids or only with a single medication and they exhibit variable cross reactivity with their phase two metabolites. Additionally the limit of detection of these immunoassays may not be sufficient for medical purposes, therefore clinical interpretation of immunoassay test results can be challenging. Recently liquid chromatography, mass spectrometry (LCMSMS) based assays have been adapted by many clinical laboratories. These LCMSMS tests can provide information about the presence of several opioids and their metabolites in a single sample at clinically meaningful detection limits, allowing accurate assessment of patient compliance. This review article will investigate in details the various opioids, their metabolism and the challenges the testing laboratories and ordering clinicians face. PMID:27683413

The prescription opioid epidemic: an overview for anesthesiologists.

PubMed

Alam, Asim; Juurlink, David N

2016-01-01

The objectives for preparing this article were to review the historical context and epidemiology surrounding the North American prescription opioid crisis, to summarize the evidence regarding the benefits and harms of long-term opioid therapy for non-cancer pain, and to outline ways in which anesthesiologists may help ameliorate the problem. We searched PubMed, Google Scholar, and EMBASE™ for relevant articles using various search terms, including pain, opioid epidemic, history of opioid use, perioperative care, and addiction. Related citations were further explored and searched depending on the specific subtopic of interest. In the 1980s and early 1990s, opioids were infrequently used for the treatment of chronic pain. Thereafter, however, physicians were gradually inculcated with the message that long-term opioid therapy was a safe and effective treatment option for patients with chronic non-cancer pain. Pharmaceutical companies supported this growing movement and employed aggressive and sometimes misleading marketing strategies for new opioid formulations. As a result, the practice of prescribing opioids flourished in the late 1990s. The surge in prescribing opioids was accompanied by a marked increase in opioid-related morbidity and mortality. This change in practice transpired despite the absence of randomized trials showing clinically significant benefit from the long-term use of opioids. Subsequently, however, a large and growing body of evidence has emerged quantifying the harms associated with long-term opioid therapy. Anesthesiologists widely prescribe opioids for acute and chronic pain; yet, as a group, they may be largely unaware of the current state of this growing epidemic and what role they can play to rectify this problem. Anesthesiologists are well positioned to take a leadership role in the management of postoperative discharge opioid therapy in an effort to curb the overutilization of opioids. Furthermore, anesthesiologists who regularly prescribe opioids for chronic pain patients should appreciate the limited evidence base for this practice and communicate the risks of opioid therapy to their patients.

Prevalence, Diagnosis, and Treatment Rates of Mood Disorders among Opioid Users under Criminal Justice Supervision.

PubMed

Mbaba, Mary; Brown, Shan-Estelle; Wooditch, Alese; Kiss, Marissa; Murphy, Amy; Kumari, Suneeta; Taxman, Faye; Altice, Frederick; Lawson, William B; Springer, Sandra A

2018-01-15

Individuals involved in the criminal justice system have disproportionately high rates of psychiatric disorders when compared to the general U.S. If left untreated, the likelihood of subsequent arrest increases and risk for adverse health consequences is great, particularly among opioid users. To explore the prevalence, characteristics, and treatment of mood disorders among justice involved opioid-dependent populations. The current study enrolled 258 treatment-seeking opioid-dependent individuals under community-based criminal justice supervision (e.g., probation, parole) screened from the larger parent study, Project STRIDE, a seek/test/treat randomized control trial (RCT) examining HIV and opioid use treatment. During baseline, individuals were screened for depression using the Patient Health Questionnaire-9 (PHQ-9) and screened for bipolar disorder using the Mood Disorder Questionnaire (MDQ) tool. Overall, 78 (30%) participants screened positive for moderate to severe depression and 54 (21%) screened positive for bipolar disorder. Participants self-reported mood disorders at higher rates than they screened positive for these conditions. Participants screening positive for these conditions experienced significantly greater family, legal, and medical problems on the Addiction Severity Index-Lite (ASI-Lite) than those who did not screen positive. Incidence of a lifetime suicide attempt was found to be associated with a positive screen for both mood disorders. Prescribed psychotropic treatment utilization was similar among those who screened positive for depression or bipolar disorder with approximately 38% reporting taking medication. Findings suggest universal mood disorder screening to improve comprehensive psychiatric care and treatment of opioid-dependent justice-involved individuals.

Attitude and knowledge of physicians about cancer pain management: young doctors of South Korea in their early career.

PubMed

Kim, Myung-Hyun; Park, Hyeonggeun; Park, Eun Chul; Park, Keeho

2011-06-01

This study is aimed at evaluating the attitude and knowledge about the optimal use of opioids and finding out the barriers to cancer pain management especially for young doctors in South Korea. A survey through questionnaire form was conducted on 1204 physicians. Physicians were grouped by their medical specialties and personal characteristics. Specialties were grouped into internal medicine and family medicine doctors, surgeons, anesthesiologists, pediatricians, other board holders and general physicians. Personal characteristics were grouped by their past experiences and current surroundings. Though many doctors thought that they were fairly well educated for pain management strategy, a large population of physicians showed a negative attitude and inadequate knowledge status about cancer pain management. The degree of attitude and knowledge status was different as their specialties and personal experiences. The factors that affected doctors' attitude and knowledge were: (i) medical specialty, (ii) past history of using practical pain assessment tool, (iii) self-perception of knowledge status about pain management, (iv) experience of prescribing opioids, (v) experience of education for cancer pain management. Although many physicians had a passive attitude in prescribing opioid analgesics, they are willingly open to use opioids for cancer pain management in the future. The most important perceived barriers to optimal cancer pain management were the fear for risk of tolerance, drug addiction, side effects of opioid analgesics and knowledge deficit about opioid analgesics. From this study, we found that further education and practical training will be needed for adequate cancer pain management for young physicians in their early career.

Caveat emptor: Erroneous safety information about opioids in online drug-information compendia.

PubMed

Talwar, Sonia R; Randhawa, Amarita S; Dankiewicz, Erica H; Crudele, Nancy T; Haddox, J David

2016-01-01

Healthcare professionals and consumers refer to online drug-information compendia (eg, Epocrates and WebMD) to learn about prescription medications, including opioid analgesics. With the significant risks associated with opioids, including abuse, misuse, and addiction, any of which can result in life-threatening overdose, it is important for those seeking information from online compendia to have access to current, accurate, and complete drug information to help support clinical treatment decisions. Although compendia are informative, readily available, and user friendly, studies have shown that they may contain errors. To review and identify misinformation in drug summaries of online drug-information compendia for selected opioid analgesic products and submit content corrections to the respective editors. Between 2011 and 2013, drug summaries for Purdue's prescription opioid analgesic products from seven leading online drug-information compendia were systematically reviewed, and the requests for corrections were retrospectively categorized and classified. At least 2 months following requests, the same compendia were then reexamined to assess the degree of error resolution. A total of 859 errors were identified, with the greatest percentage in Safety and Patient Education categories. Across the seven compendia, the complete or partial resolution of errors was 34 percent; therefore, nearly two thirds of the identified errors remain. The results of this analysis, consistent with past studies, demonstrate that online drug-information compendia may contain inaccurate information. Healthcare professionals and consumers must be informed of potential misinformation so they may consider using multiple resources to obtain accurate and current drug information, thereby helping to ensure safer use of prescription medications, such as opioids.

The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction.

PubMed

Burkett, James P; Young, Larry J

2012-11-01

Love has long been referred to as an addiction in literature and poetry. Scientists have often made comparisons between social attachment processes and drug addiction, and it has been suggested that the two may share a common neurobiological mechanism. Brain systems that evolved to govern attachments between parents and children and between monogamous partners may be the targets of drugs of abuse and serve as the basis for addiction processes. Here, we review research on drug addiction in parallel with research on social attachments, including parent-offspring attachments and social bonds between mating partners. This review focuses on the brain regions and neurochemicals with the greatest overlap between addiction and attachment and, in particular, the mesolimbic dopamine (DA) pathway. Significant overlap exists between these two behavioral processes. In addition to conceptual overlap in symptomatology, there is a strong commonality between the two domains regarding the roles and sites of action of DA, opioids, and corticotropin-releasing factor. The neuropeptides oxytocin and vasopressin are hypothesized to integrate social information into attachment processes that is not present in drug addiction. Social attachment may be understood as a behavioral addiction, whereby the subject becomes addicted to another individual and the cues that predict social reward. Understandings from both fields may enlighten future research on addiction and attachment processes.

Maintenance of reinforcement to address the chronic nature of drug addiction

PubMed Central

Silverman, Kenneth; DeFulio, Anthony; Sigurdsson, Sigurdur O.

2012-01-01

Background Drug addiction can be a chronic problem. Abstinence reinforcement can initiate drug abstinence, but as with other treatments many patients relapse after the intervention ends. Abstinence reinforcement can be maintained to promote long-term drug abstinence, but practical means of implementing long-term abstinence reinforcement are needed. Methods We reviewed 8 clinical trials conducted in Baltimore, MD from 1996 through 2010 that evaluated the therapeutic workplace as a vehicle for maintaining reinforcement for the treatment of drug addiction. The therapeutic workplace uses employment-based reinforcement in which employees must provide objective evidence of drug abstinence or medication adherence to work and earn wages. Results Employment-based reinforcement can initiate (3 of 4 studies) and maintain (2 studies) cocaine abstinence in methadone patients, although relapse can occur even after long-term exposure to abstinence reinforcement (1 study). Employment-based reinforcement can also promote abstinence from alcohol in homeless alcohol dependent adults (1 study), and maintain adherence to extended-release naltrexone in opioid dependent adults (2 studies). Conclusion Treatments should seek to promote life-long effects in patients. Therapeutic reinforcement may need to be maintained indefinitely to prevent relapse. Workplaces could be effective vehicles for the maintenance of therapeutic reinforcement contingencies for drug abstinence and adherence to addiction medications. PMID:22668883

The Association between the Level of Plasma Oxytocin and Craving among Former Heroin Users.

PubMed

Lin, Shih-Hsien; Chen, Po See; Lee, Lan-Ting; Lee, Sheng-Yu; Tsai, Hsin Chun; Chen, Wei Tseng; Chen, Kao Chin; Lee, I Hui; Lu, Ru-Band; Yang, Yen Kuang

2018-06-14

Animal studies have demonstrated that oxytocin can influence addiction behaviors and might interact with the dopaminergic system, which is a key component of addiction behaviors. However, related evidence from clinical studies is scarce. The aim of our study was to explore the relationship between plasma oxytocin level and heroin craving among patients receiving methadone maintenance treatment, and to ascertain whether this relationship is moderated by novelty-seeking. The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan. Seventy-seven patients with heroin addiction were enrolled. Plasma oxytocin was measured using an ELISA kit. Craving was assessed using an established instrument, the Chinese Craving Scale. A significant negative association was found between the plasma oxytocin level and craving score, which remained robust after controlling the effects of social support and low-density lipoprotein cholesterol. An interaction between oxytocin and novelty-seeking indicated that this relationship was stronger among patients with a lower level of novelty-seeking. This finding may be taken into account in future studies and may provide a basis for the development of potential treatment for addiction. The effect of oxytocin for the treatment of opioid dependence might be modulated by some psychological factors. © 2018 S. Karger AG, Basel.

Treatment options for chronic pain management: opioids revisited.

PubMed

Lipman, Arthur G

2007-02-01

Pain is a public health disaster. Although it remains largely undertreated, pharmacists and pharmacy managers can do much to correct the problem. Change will require the education of patients and health care professionals on the facts pertaining to addiction, drug dependence, and drug tolerance. Evidence-based resources, including guidelines published by the APS, should be consulted. A variety of short- and long-acting drugs are available, not the least of which are the opioids. Fears regarding addiction and uncertainty about tolerance have precluded the comprehensive use of these drugs, and varying dose requirements complicate the picture. What is known, however, is that dose titration must be performed with the goal of preventing breakthrough pain. Fortunately, sufficient drug formulae have been developed to accommodate this need. Pain is the primary reason why people come into the health care system, and it is incumbent upon health care professionals to eliminate insufficient pain control, using the drugs available to the patient's best advantage.

Treatment Strategies for the Opioid-Dependent Patient.

PubMed

Teckchandani, Shweta; Barad, Meredith

2017-09-20

This review is intended to help the headache physician think through and plan for management issues concerning the use of opioids. We ask the headache physician to consider if there are instances where prescribing or continuing prescriptions of opiates is plausible, and if so, how can the physician proceed as safely as possible. Our goal is to start a conversation regarding the inevitable encounter with a patient on opiates or requesting opiates. The use of opiates in our society has reached a crisis in staggering death and addiction rates. Recent guideline published by the CDC can assist us in developing an algorithmic approach towards opiate use. Recent advances in addiction medicine can also assist us in protecting our patients. Every headache physician will undoubtedly encounter patients on opiates. There still are appropriate reasons to treat patients with opiates. Every headache physician may need to prescribe opiates and they may be indicated. It is important to learn the correct way to approach, manage, and treat patients on opiates.

Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine

PubMed Central

Hill, Rob; Lyndon, Abi; Withey, Sarah; Roberts, Joanne; Kershaw, Yvonne; MacLachlan, John; Lingford-Hughes, Anne; Kelly, Eamonn; Bailey, Chris; Hickman, Matthew; Henderson, Graeme

2016-01-01

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths. PMID:26171718

In Their Own Voices: Breaking the Vicious Cycle of Addiction, Treatment and Criminal Justice Among People who Inject Drugs in Ukraine.

PubMed

Mazhnaya, Alyona; Bojko, Martha J; Marcus, Ruthanne; Filippovych, Sergii; Islam, Zahedsul; Dvoriak, Sergey; Altice, Frederick L

To understand how perceived law enforcement policies and practices contribute to the low rates of utilization of opioid agonist therapies (OAT) among people who inject drugs (PWIDs) in Ukraine. Qualitative data from 25 focus groups (FGs) with 199 opioid-dependent PWIDs in Ukraine examined domains related to lived or learned experiences with OAT, police, arrest, incarceration, and criminal activity were analyzed using grounded theory principles. Most participants were male (66%), in their late 30s, and previously incarcerated (85%) mainly for drug-related activities. When imprisoned, PWIDs perceived themselves as being "addiction-free". After prison-release, the confluence of police surveillance, societal stress contributed to participants' drug use relapse, perpetuating a cycle of searching for money and drugs, followed by re-arrest and re-incarceration. Fear of police and arrest both facilitated OAT entry and simultaneously contributed to avoiding OAT since system-level requirements identified OAT clients as targets for police harassment. OAT represents an evidence-based option to 'break the cycle', however, law enforcement practices still thwart OAT capacity to improve individual and public health. In the absence of structural changes in law enforcement policies and practices in Ukraine, PWIDs will continue to avoid OAT and perpetuate the addiction cycle with high imprisonment rates.

Methadone enhances human influenza A virus replication.

PubMed

Chen, Yun-Hsiang; Wu, Kuang-Lun; Tsai, Ming-Ta; Chien, Wei-Hsien; Chen, Mao-Liang; Wang, Yun

2017-01-01

Growing evidence has indicated that opioids enhance replication of human immunodeficiency virus and hepatitis C virus in target cells. However, it is unknown whether opioids can enhance replication of other clinically important viral pathogens. In this study, the interaction of opioid agonists and human influenza A/WSN/33 (H1N1) virus was examined in human lung epithelial A549 cells. Cells were exposed to morphine, methadone or buprenorphine followed by human H1N1 viral infection. Exposure to methadone differentially enhanced viral propagation, consistent with an increase in virus adsorption, susceptibility to virus infection and viral protein synthesis. In contrast, morphine or buprenorphine did not alter H1N1 replication. Because A549 cells do not express opioid receptors, methadone-enhanced H1N1 replication in human lung cells may not be mediated through these receptors. The interaction of methadone and H1N1 virus was also examined in adult mice. Treatment with methadone significantly increased H1N1 viral replication in lungs. Our data suggest that use of methadone facilitates influenza A viral infection in lungs and might raise concerns regarding the possible consequence of an increased risk of serious influenza A virus infection in people who receive treatment in methadone maintenance programs. © 2015 Society for the Study of Addiction.

Deaths of opiate/opioid misusers involving dihydrocodeine, UK, 1997–2007

PubMed Central

Zamparutti, Giuliano; Schifano, Fabrizio; Corkery, John M; Oyefeso, Adenekan; Ghodse, A Hamid

2011-01-01

AIMS Although its effectiveness is somewhat controversial, it appears that dihydrocodeine (DHC) is still prescribed in the UK as an alternative to both methadone and buprenorphine for the treatment of opiate addiction. METHODS Data covering the period 1997–2007 voluntarily supplied by coroners were analysed. All cases pertaining to victims with a clear history of opiate/opioid misuse and in which DHC, either on its own or in combination, was identified at post-mortem toxicology and/or implicated in death, were extracted from the database. RESULTS Dihydrocodeine, either alone or in combination, was identified in 584 fatalities meeting the selection criteria. In 44% of cases it was directly implicated in the cause of death. These cases represented about 6.8% of all opiate/opioid-related deaths during this period. Typical DHC cases identified were White males in their early thirties. Accidental deaths (96%) were likely to involve DHC in combination with other psychoactives, mainly heroin/morphine, hypnotics/sedatives and methadone. Both paracetamol and antidepressants were found in proportionately more suicide cases than in accidental overdoses. DHC had been prescribed to the decedent in at least 45% of cases. CONCLUSIONS Opiate/opioid misusers should be educated about risks associated with polydrug intake. More in particular, co-administration of DHC with heroin, methadone and benzodiazepines may increase the risk of accidental fatal overdose. Prescribers should carefully consider pharmacological intervention alternative to DHC (e.g. methadone, buprenorphine) when managing and treating opiate addiction. More resources are required to do prospective research in this area. PMID:21235617

NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction.

PubMed

Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee

2013-04-01

Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States

PubMed Central

Iwanicki, Janetta L.; Severtson, S. Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J.; Ellis, Matthew S.; Kurtz, Steven P.; Buttram, Mance E.; Dart, Richard C.

2016-01-01

Background Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Methods Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. Results From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). Conclusions Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations. PMID:27936038

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States.

PubMed

Iwanicki, Janetta L; Severtson, S Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J; Ellis, Matthew S; Kurtz, Steven P; Buttram, Mance E; Dart, Richard C

2016-01-01

Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations.

Factors associated with contingency management adoption among opioid treatment providers receiving a comprehensive implementation strategy.

PubMed

Becker, Sara J; Kelly, Lourah M; Kang, Augustine W; Escobar, Katherine I; Squires, Daniel D

2018-03-29

Contingency management (CM) is an evidence-based behavioral intervention for opioid use disorders (OUDs); however, CM adoption in OUD treatment centers remains low due to barriers at patient, provider, and organizational levels. In a recent trial, OUD treatment providers who received the Science to Service Laboratory (SSL), a multilevel implementation strategy developed by a federally funded addiction training center, had significantly greater odds of CM adoption than providers who received training as usual. This study examined whether CM adoption frequency varied as a function of provider sociodemographic characteristics (i.e., age, race/ethnicity, licensure) and perceived barriers to adoption (i.e., patient-, provider-, organization-level) among providers receiving the SSL in an opioid treatment program. Thirty-nine providers (67% female, 77% non-Hispanic white, 72% with specialty licensure, M age = 42 [SD = 11.46]) received the SSL, which consisted of didactic training, performance feedback, specialized training of internal change champions, and external coaching. Providers completed a comprehensive baseline assessment and reported on their adoption of CM biweekly for 52 weeks. Providers reported using CM an average of nine 2-week intervals (SD = 6.35). Hierarchical multiple regression found that providers identifying as younger, non-Hispanic white, and without addiction-related licensure all had higher levels of CM adoption frequency. Higher perceived patient-level barriers predicted lower levels of CM adoption frequency, whereas provider- and organization-level barriers were not significant predictors. The significant effect of age on CM adoption frequency was consistent with prior research on predictors of evidence-based practice adoption, whereas the effect of licensure was counter to prior research. The finding that CM adoption frequency was lower among racially/ethnically diverse providers was not expected and suggests that the SSL may require adaptation to meet the needs of diverse opioid treatment providers. Entities using the SSL may also wish to incorporate a more explicit focus on patient-level barriers.

Effectiveness of Scotland's National Naloxone Programme for reducing opioid-related deaths: a before (2006-10) versus after (2011-13) comparison.

PubMed

Bird, Sheila M; McAuley, Andrew; Perry, Samantha; Hunter, Carole

2016-05-01

To assess the effectiveness for Scotland's National Naloxone Programme (NNP) by comparison between 2006-10 (before) and 2011-13 (after NNP started in January 2011) and to assess cost-effectiveness. This was a pre-post evaluation of a national policy. Cost-effectiveness was assessed by prescription costs against life-years gained per opioid-related death (ORD) averted. Scotland, in community settings and all prisons. Brief training and standardized naloxone supply became available to individuals at risk of opioid overdose. ORDs as identified by National Records of Scotland. Look-back determined the proportion of ORDs who, in the 4 weeks before ORD, had been (i) released from prison (primary outcome) and (ii) released from prison or discharged from hospital (secondary). We report 95% confidence intervals for effectiveness in reducing the primary (and secondary) outcome in 2011-13 versus 2006-10. Prescription costs were assessed against 1 or 10 life-years gained per averted ORD. In 2006-10, 9.8% of ORDs (193 of 1970) were in people released from prison within 4 weeks of death, whereas only 6.3% of ORDs in 2011-13 followed prison release (76 of 1212, P < 0.001; this represented a difference of 3.5% [95% confidence interval (CI) = 1.6-5.4%)]. This reduction in the proportion of prison release ORDs translates into 42 fewer prison release ORDs (95% CI = 19-65) during 2011-13, when 12,000 naloxone kits were issued at current prescription cost of £225,000. Scotland's secondary outcome reduced from 19.0 to 14.9%, a difference of 4.1% (95% CI = 1.4-6.7%). Scotland's National Naloxone Programme, which started in 2011, was associated with a 36% reduction in the proportion of opioid-related deaths that occurred in the 4 weeks following release from prison. © 2015 The Authors. Addiction published by JohnWiley & Sons Ltd on behalf of Society for the Study of Addiction.

Synthesis of conolidine, a potent non-opioid analgesic for tonic and persistent pain

NASA Astrophysics Data System (ADS)

Tarselli, Michael A.; Raehal, Kirsten M.; Brasher, Alex K.; Streicher, John M.; Groer, Chad E.; Cameron, Michael D.; Bohn, Laura M.; Micalizio, Glenn C.

2011-06-01

Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (-)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain.

Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior.

PubMed

Váradi, András; Marrone, Gina F; Eans, Shainnel O; Ganno, Michelle L; Subrath, Joan J; Le Rouzic, Valerie; Hunkele, Amanda; Pasternak, Gavril W; McLaughlin, Jay P; Majumdar, Susruta

2015-11-18

3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 double bond and various N-17 alkyl substituents. The structural modifications resulted in analogs with picomolar affinities for opioid receptors. The lead compound (MP1104) was found to exhibit approximately 15-fold greater antinociceptive potency (ED50 = 0.33 mg/kg) compared with morphine, mediated through the activation of kappa- and delta-opioid receptors. Despite its kappa agonism, this lead derivative did not cause place aversion or preference in mice in a place-conditioning assay, even at doses 3 times the analgesic ED50. However, pretreatment with the lead compound prevented the reward behavior associated with cocaine in a conditioned place preference assay. Together, these results suggest the promise of dual acting kappa- and delta-opioid receptor agonists as analgesics and treatments for cocaine addiction.

Micromorphological changes in cardiac tissue of drug-related deaths with emphasis on chronic illicit opioid abuse

PubMed Central

Seltenhammer, Monika H; Marchart, Katharina; Paula, Pia; Kordina, Nicole; Klupp, Nikolaus; Schneider, Barbara; Fitzl, Christine; Risser, Daniele U

2013-01-01

Aims The main intention of this retrospective study was to investigate whether chronic illicit drug abuse, especially the intravenous use of opioids (heroin), could potentially trigger the development of myocardial fibrosis in drug addicts. Design A retrospective case–control study was performed using myocardial tissue samples from both drug-related deaths (DRD) with verifiable opioid abuse and non-drug-related deaths in the same age group. Setting Department of Forensic Medicine, Medical University of Vienna, Austria (1993–94). Participants Myocardial specimens were retrieved from 76 deceased intravenous opioid users and compared to those of 23 deceased non-drug users. Measurements Drug quantification was carried out using the enzyme-multiplied immunoassay technique (EMIT), followed by [gas chromatography–mass spectrometry (GC–MS), MAT 112®], and analysed using the Integrator 3390A by Hewlett Packard® and LABCOM.1 computer (MSS-G.G.). The amount of fibrous connective tissue (FCT) in the myocardium was determined by using the morphometric software LUCIA Net version 1.16.2©, Laboratory Imaging, with NIS Elements 3.0®. Findings Drug analysis revealed that 67.11% were polydrug users and the same proportion was classified as heroin addicts (6-monoacetylmorphine, 6-MAM)—32.89% were users of pure heroin. In 76.32% of DRD cases, codeine was detected. Only 2.63% consumed cocaine. The mean morphine concentrations were 389.03 ng/g in the cerebellum and 275.52 ng/g in the medulla oblongata, respectively. Morphometric analysis exhibited a strong correlation between DRD and myocardial fibrosis. The mean proportion of FCT content in the drug group was 7.6 ± 2.9% (females: 6.30 ± 2.19%; males: 7.91 ± 3.01%) in contrast to 5.2 ± 1.7% (females: 4.45 ± 1.23%; males: 5.50 ± 1.78%) in the control group, indicating a significant difference (P = 0.0012), and a significant difference in the amount of FCT between females and males (P = 0.0383). There was no significant interaction of age and FCT (P = 0.8472). Conclusions There is a long-term risk of cardiac dysfunction following chronic illicit drug abuse with opioids as a principal component. Regular cardiological examination of patients receiving substitution treatment with morphine is strongly recommended. PMID:23297783

Social networking online to recover from opioid use disorder: A study of community interactions.

PubMed

D'Agostino, Alexandra R; Optican, Allison R; Sowles, Shaina J; Krauss, Melissa J; Escobar Lee, Kiriam; Cavazos-Rehg, Patricia A

2017-12-01

Social media has increasingly become a venue for health discourse and support, particularly for vulnerable individuals. This study examines user-generated content of an online Reddit community targeting individuals recovering from opiate addiction. 100 Reddit posts and their comments were collected from the online community on August 19, 2016. Posts were qualitatively coded for opioid use disorder (OUD) criteria as outlined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), as well as other common themes. Comments were coded for expression of distinct therapeutic factors (i.e., instillation of hope, universality, imparting information, and altruism). All posts and comments were coded for addiction phase of the author (i.e., using, withdrawing, recovering). 73 unique usernames authored the 100 posts. Among the 73 usernames, 33% (24/73) described enough symptoms in their posts to meet DSM-V criteria for OUD (16/73 or 22% mild severity, 7/73 or 10% moderate severity, and 1/73 or 1% high severity. Among the 100 posts, advice was requested in 43% (43/100) of the posts and support was sought in 24% (24/100) of the posts. There were 511 comments made on the 100 posts, nearly all of which contained at least one distinct therapeutic factor (486/511, 95%) with altruism being the most common (341/511, 67%). This research provides validity to the supportive content generated on an online recovery-oriented community, while also revealing discussions of self-reported struggles with OUD among group members. Future research should explore the feasibility of incorporating social media-based peer support into traditional addiction treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

A Scientometric Study of Iranian Scientific Productions in the Field of Substance Use and Addiction Research in the Years 2008 to 2012

PubMed Central

Rahimi-Movaghar, Afarin; Amin-Esmaeili, Masoumeh; Safarcherati, Anousheh; Sarami, Hamid; Rafiey, Hassan

2015-01-01

Background We aimed to evaluate the current status of scientific production in the field of substance use and addiction in Iran, to determine its trend and pattern during a 5 years period (2008-2012). Methods Using relevant keywords, we searched three international databases (Web of Science, Medline, and Scopus) and two local databases (SID and Iranmedex) to locate the papers published in the field of addiction by Iranian researchers during 2008-2012. Findings The results indicated a significant increase in the number of studies published in the field during the 5 years study period, with more than half of the papers published in the last 2 years. Results also indicated that over half (53.5%) of the papers were published in Persian-language Iranian Journals, but the rate of increase in the number of papers published in English was slightly higher than that of Persian ones. Opioid substances were found to be the topic of approximately 75% of the papers. Studies on key topics, including national surveys, evaluation of current programs, addiction in women and children, and so forth, were found to be highly lacking. Conclusion Results suggested a significant growth in the scientific production of Iran in the field of substance use and addiction. However, considering the significance of substance use and dependence in the country, and compared to the scientific production of developed countries, the amount of research conducted in the field of addiction in Iran is still limited. PMID:26885346

Effects of a Rhodiola rosea L. extract on the acquisition, expression, extinction, and reinstatement of morphine-induced conditioned place preference in mice.

PubMed

Mattioli, Laura; Titomanlio, Federica; Perfumi, Marina

2012-05-01

Opioid addiction is a chronic, recurrent brain disease that is characterised by compulsive drug seeking and a high rate of relapse even after long periods of abstinence. Prevention of relapse is the primary goal of addiction treatment and is still the major limitation in drug therapy. The present study investigated the effects of a Rhodiola rosea L. hydroalcoholic extract (RHO), a well-known traditional oriental medicine, on establishment and reinstatement of morphine-induced conditioned place preference (CPP) in mice. CPP was induced by intraperitoneal injection of morphine (10 mg/kg) as an 8-day conditioning schedule. The effects of RHO on the rewarding properties of morphine were tested in mice receiving oral administration of RHO (10, 15, and 20 mg/kg) 60 min prior to each morphine injection (acquisition) or prior to the CPP test on day 9 (expression). Once established, CPP was extinguished by repeated testing, during which conditioned mice were injected daily with different doses of RHO. Finally, the efficacy of RHO in blocking reinstatement of CPP provoked by priming injections and physical stress was also evaluated. RHO administration showed dose dependency for prevention of establishment of CPP and was effective in facilitating extinction of morphine-induced CPP. RHO suppressed both priming- and stress-induced reinstatement of CPP in a dose-dependent manner. In conclusion, as RHO was effective for reducing craving and vulnerability to relapse, it might be a very effective natural remedy for the treatment of opioid addiction.

Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

PubMed

Bucher Bartelson, Becki; Le Lait, M Claire; Green, Jody L; Cepeda, M Soledad; Coplan, Paul M; Maziere, Jean-Yves; Wedin, Gregory P; Dart, Richard C

2017-09-01

An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends. Copyright © 2017 John Wiley & Sons, Ltd.