Background: Despite the many harms and limited efficacy of opioids in managing chronic noncancer pain (CNCP), they are commonly prescribed for these patients in North America. One of the harms associated with prolonged opioid use is opioid use disorder (OUD); however, the risk of addiction is uncertain. We systematically reviewed observational studies to establish the prevalence of (OUD), and to explore factors associated with OUD in patients with CNCP. Methods: We searched MEDLINE, EMBASE, CINAHL, Cochrane Library, and PsycINFO from inception to December 2018 to identify studies that explored the prevalence of OUD or risk factors for OUD in patients with CNCP. Two specialists in addiction medicine reviewed each potentially eligible study, blinded to results, to ensure their outcome met DSM-5 criteria for OUD. We pooled estimates of OUD across eligible studies using random-effects models. When possible, we pooled estimates of association with OUD for all independent variables reported by more than one study. Results: Twenty-two studies reported the prevalence of OUD, and six studies reported the association of 36 factors with OUD in patients with CNCP. The pooled prevalence of OUD was 20% (95% CI: 15% to 25%); however, we found evidence for small study effects (interaction p<0.001). When restricted to larger studies (≥900 patients), the pooled prevalence of OUD was 5.8% (95% CI: 2.8% to 9.5%; moderate certainty evidence). The prevalence of OUD was not associated with level of certainty of OUD criteria, under- or overestimation of instruments compared to DSM-5 criteria, severity of OUD, or risk of bias (interaction p values ranged from 0.34 to 0.92). Moderate certainty evidence demonstrated an association between OUD and male sex (OR 1.50 [95% CI: 1.05 to 2.14]; absolute risk increase (ARI) 2.7% [95% CI: 0.3% more to 5.8% more]), current smokers (OR 1.63; [95% CI: 1.25 to 2.12]; ARI 3.3% [1.3% more to 5.7% more]), and a history of mental health disorders (OR 1.49 [95% CI: 1.17 to 1.89]; ARI 2.6% [95% CI: 0.9% more to 4.6% more]). Low certainty evidence demonstrated an association between OUD and younger age (OR for every 10-year decrement, 1.60 [95% CI: 1.11 to 2.30]; ARI, 3.2% for every 10-year decrement [95% CI: 0.6% more to 6.6% more]). Moderate certainty evidence suggested no association between OUD and a history of alcohol abuse/dependence (OR 1.32 [95% CI: 0.84 to 2.07]; ARI 1.7% [95% CI: 0.9% less to 5.5% more]), and low certainty evidence suggested no association between OUD and a history of drug abuse (OR 1.51 [95% CI: 0.75 to 3.02]; ARI 2.7% [95% CI: 1.4% less to 9.9% more]). Conclusion: Moderate certainty evidence suggests that 6% of CNCP patients prescribed opioids will develop OUD. Younger men who smoke, with a history of mental health disorders, are at higher risk. Additional research is needed to establish the association between OUD and a history of drug or alcohol abuse. / Thesis / Master of Science (MSc) / Opioids are commonly prescribed for patients with chronic pain that is not due to cancer; however, long-term opioid use inevitably leads to physical dependence and may result in addiction. Prior studies have reported extremely variable rates of opioid use disorder (OUD) following prescription for chronic noncancer pain, ranging from less than 1% to more than 50%, which has led to considerable confusion. My systematic review found moderate certainty evidence that the prevalence of OUD following prescription for chronic pain is 5.8% (95% CI: 2.8% to 9.5%). Patients who were younger, current smokers, males, and had a history of mental health disorders, had a higher risk of developing OUD. These findings will help support shared care decision-making between patients with chronic pain considering opioid therapy and their healthcare providers.

Heroin dependence, which is escalating within South Africa, has become a symbol of the social disorder of the times - associated with materialism, poverty, crime, the problems of a society in transition, the disadvantaged, and the inner cities. However, that is not to say that all those who misuse heroin develop a problem or become dependent. In reality, only a small minority of heroin users develop a dependence, but for those who do it can result in unpleasant and potentially terrifying experiences/consequences, that can often be extremely difficult to escape from. That is not to say that recovery from dependence to heroin is not possible. Indeed, contrary to the beliefs of many people, the reality is that many people do eventually recover. Despite the vast sums of money devoted to treatment intervention of heroin dependants in the South Africa and worldwide, the processes by which recovery occur remain fairly unclear. Moreover, relatively little is known about the contribution of interventions and processes in facilitating such recovery. The statistical and content analysis of the data revealed that one of the most important factors identified in allowing successful behaviour modification and promoting recovery was psychosocial and pharmacological intervention, which seemed to produce a range of positive effects that facilitated natural healing processes. However, a range of other factors alongside intervention were also important in promoting behaviour modification. This study has provided important information, from forty recovering heroin dependants themselves, on the many factors that are important in achieving abstinence, in allowing recovery to be maintained in the longer term, and in potentially allowing an eventual exit from heroin dependence. A number of difficulties encountered in intervention were also identified. The statistical findings of the study support the `maturing out' hypothesis of heroin dependence (c² = 16.841; r = 0.001; df = 3). Ethnicity, highest level of education, employment status, marital status, biological parents' marital status or whether biological parents were deceased or not did not relate to any of the identified behavioural indices associated with heroin dependence recovery. A framework for the development of a contextual heroin dependence recovery model is also discussed. / Psychology / (M.A.(Psychology))

Heroin dependence, which is escalating within South Africa, has become a symbol of the social disorder of the times - associated with materialism, poverty, crime, the problems of a society in transition, the disadvantaged, and the inner cities. However, that is not to say that all those who misuse heroin develop a problem or become dependent. In reality, only a small minority of heroin users develop a dependence, but for those who do it can result in unpleasant and potentially terrifying experiences/consequences, that can often be extremely difficult to escape from. That is not to say that recovery from dependence to heroin is not possible. Indeed, contrary to the beliefs of many people, the reality is that many people do eventually recover. Despite the vast sums of money devoted to treatment intervention of heroin dependants in the South Africa and worldwide, the processes by which recovery occur remain fairly unclear. Moreover, relatively little is known about the contribution of interventions and processes in facilitating such recovery. The statistical and content analysis of the data revealed that one of the most important factors identified in allowing successful behaviour modification and promoting recovery was psychosocial and pharmacological intervention, which seemed to produce a range of positive effects that facilitated natural healing processes. However, a range of other factors alongside intervention were also important in promoting behaviour modification. This study has provided important information, from forty recovering heroin dependants themselves, on the many factors that are important in achieving abstinence, in allowing recovery to be maintained in the longer term, and in potentially allowing an eventual exit from heroin dependence. A number of difficulties encountered in intervention were also identified. The statistical findings of the study support the `maturing out' hypothesis of heroin dependence (c² = 16.841; r = 0.001; df = 3). Ethnicity, highest level of education, employment status, marital status, biological parents' marital status or whether biological parents were deceased or not did not relate to any of the identified behavioural indices associated with heroin dependence recovery. A framework for the development of a contextual heroin dependence recovery model is also discussed. / Psychology / (M.A.(Psychology))

Through changes in the code of statutes, SOSFS 2009:27 (M), opioid addicts are excluded since March 1 2010 from possibilities to be accepted for substitution treatment. Opiate addicts are solitary admitted for substitution treatment from that date. Opioid addicts are excluded admission for treatment regardless of the fact that they fulfil the ICD-10 diagnosis F.11.2, i.e. opioid/opiate addictive criteria. The alteration in the statutes was carried out in reference to the fact that evidence for this kind of treatment intended for opioid addicts was missing. Both groups i.e. opiate – and opioid addicts, are nevertheless experienced in clinical work , to have extensive problems with addiction, health, social situation along with the risk of premature death.     The purpose with this study is to identify what differences and/or similarities there are in background varieties and the severity of the problems  between the groups. This is conducted with the use of a population (n=127) with comparable background material, e.g. collected Addictions Severe Index- interviews, scientifically survey and compare background factors and the severity of the problems.      The main discovery in this study is that one can demonstrate great similarities between the groups regarding background as well as the severity of the problems. It is therefore of great interest, on a individual as well as a social oriented level, that pursued studies regarding diagnostic safety and on processes in substitution program are needed to generate further knowledge as a foundation for development of future care and changes in the code of statutes.

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Dr. Robert Pack, associate dean for Academic Affairs in ETSU’s College of Public Health, joined leaders from public health schools in four other states in the Appalachian region to discuss with members of the U.S. Congress the complex and dynamic processes at work in the opioid crisis. Pack joined his colleagues in sharing findings on unique approaches to address the course of the epidemic as well as discuss how university-based public health experts are assisting affected communities by bringing traditional and novel epidemic control strategies to bear on the disease.

This study investigated the role of opioid, adenosine, bradykinin, and calcitonin-gene related peptide (CGRP) receptors, and potential ‘cross-talk’ among suspected G-protein coupled receptors in a humoral model of remote ischemic preconditioning (rIPC) cardioprotection. Compared to Control dialysate (from non-preconditioned donor rabbit blood), rIPC dialysate (from remotely preconditioned blood) reduced cell death in rabbit cardiomyocytes following simulated ischemia and reperfusion. Non-selective, δ-, or κ-opioid receptor blockade and non-selective adenosine receptor blockade abolished rIPC dialysate protection; whereas, bradykinin B2 and CGRP receptor blockade had no effect. Non-selective adenosine receptor blockade fully and partially abolished protection by κ- and δ-opioid receptors, respectively. Multiple reaction monitoring mass spectrometry detected low levels of adenosine, and other preconditioning substances, in the dialysate. An increase in extracellular adenosine was not detected during opioid-induced preconditioning to explain this cross-talk. These results suggest that δ-opioid, κ-opioid, adenosine receptors, and opioid-adenosine cross-talk are involved in rIPC of freshly isolated cardiomyocytes.

This study investigated the role of opioid, adenosine, bradykinin, and calcitonin-gene related peptide (CGRP) receptors, and potential ‘cross-talk’ among suspected G-protein coupled receptors in a humoral model of remote ischemic preconditioning (rIPC) cardioprotection. Compared to Control dialysate (from non-preconditioned donor rabbit blood), rIPC dialysate (from remotely preconditioned blood) reduced cell death in rabbit cardiomyocytes following simulated ischemia and reperfusion. Non-selective, δ-, or κ-opioid receptor blockade and non-selective adenosine receptor blockade abolished rIPC dialysate protection; whereas, bradykinin B2 and CGRP receptor blockade had no effect. Non-selective adenosine receptor blockade fully and partially abolished protection by κ- and δ-opioid receptors, respectively. Multiple reaction monitoring mass spectrometry detected low levels of adenosine, and other preconditioning substances, in the dialysate. An increase in extracellular adenosine was not detected during opioid-induced preconditioning to explain this cross-talk. These results suggest that δ-opioid, κ-opioid, adenosine receptors, and opioid-adenosine cross-talk are involved in rIPC of freshly isolated cardiomyocytes.

Opioid Receptors (ORs) are involved in the pathophysiology of several neuropsychiatric conditions yet remain an untapped therapeutic resource. Although only mu-, delta-, and kappa-OR types have been cloned, additional subtypes result from complexes generated by direct receptor-receptor interactions. Mu- and delta-ORs form a heteromeric receptor complex with unique pharmacological and signalling properties distinct from those of mu- and delta-OR homomers. In these studies, we sought to characterize the ligand binding pocket and agonist-induced internalization profile of the mu-delta heteromer, to investigate mu-delta heteromer-specific signalling in brain, and to interrogate the contribution of this receptor complex to opioid-mediated behavioural effects. In competition radioligand binding studies, delta-agonists displaced high affinity mu-agonist binding from the mu-delta heteromer but not the muOR homomer, suggestive of delta-agonists occupying or allosterically modulating the muOR ligand binding pocket within the heteromer. Delta-agonists induced internalization of the mu-delta heteromer in a dose-dependent, pertussis toxin resistant, and muOR- and deltaOR-dependent manner from the cell surface via the clathrin and dynamin endocytic machinery. Agonist-induced internalization of the mu-delta heteromer persisted following chronic morphine treatment conditions which desensitized the muOR homomer. Using Galpha-specific GTPgammaS binding assays, we demonstrated that mu-delta heteromer signalling previously characterized in cell lines was present in the striatum and hippocampus, and did not desensitize following prolonged morphine treatment conditions which desensitized muOR homomer-mediated signalling. Since delta-agonists which also target the mu-delta heteromer possess antidepressant-like and anxiolytic-like properties, we investigated the role of this receptor complex in mood regulation. We devised a strategy to selectively analyze the effects of the mu-delta heteromer by dissociating it using a specific interfering peptide aimed at a sequence implicated in mu-delta heteromerization. The interfering peptide abolished the unique pharmacological and trafficking properties of delta-agonists at the mu-delta heteromer and dissociated this receptor complex in vitro. Intra-accumbens administration of the interfering peptide disrupted the mu-delta interaction in vivo and allowed for isolation of the mu-delta heteromer contribution to the mood-regulatory effects of a delta-agonist with activity at the heteromer. Activation of the mu-delta heteromer in the nucleus accumbens produced antidepressant-like and anxiolytic-like actions in animal models of depression and anxiety.