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

Shirley and Stephan Hatos Center for Neuropharmacology, Semel Institute, Los Angeles, CA 90024-1759, USA.
Drug and alcohol dependence (Impact Factor: 3.42). 02/2010; 108(3):156-65. DOI: 10.1016/j.drugalcdep.2010.01.001
Source: PubMed


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.

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Available from: Wendy Walwyn, Jan 21, 2014
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    • "The opioid system plays a key role in reward and motivation, and regulates emotional responses and cognition. The system also modulates nociception, neuroendocrine physiology and autonomic functions (see Walwyn et al., 2010; Feng et al., 2012). The involvement of the three opioid receptors in pain control, drug abuse and mood disorders has been extensively studied and has been the focus of recent reviews (Bruchas et al., 2010; Gaveriaux-Ruff and Kieffer, 2011; Pradhan et al., 2011; Raehal et al., 2011; Lutz and Kieffer, 2012; 2013; Nadal et al., 2013; Charbogne et al., 2014). "
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    ABSTRACT: Unlabelled: Opioid receptors are highly homologous GPCRs that modulate brain function at all levels of neural integration, including autonomous, sensory, emotional and cognitive processing. Opioid receptors functionally interact in vivo, but the underlying mechanisms involving direct receptor-receptor interactions, affecting signalling pathways or engaging different neuronal circuits, remain unsolved. Heteromer formation through direct physical interaction between two opioid receptors or between an opioid receptor and a non-opioid one has been postulated and can be characterized by specific ligand binding, receptor signalling and trafficking properties. However, despite numerous studies in heterologous systems, evidence for physical proximity in vivo is only available for a limited number of opioid heteromers, and their physiopathological implication remains largely unknown mostly due to the lack of appropriate tools. Nonetheless, data collected so far using endogenous receptors point to a crucial role for opioid heteromers as a molecular entity that could underlie human pathologies such as alcoholism, acute or chronic pain as well as psychiatric disorders. Opioid heteromers therefore stand as new therapeutic targets for the drug discovery field. Linked articles: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit
    Full-text · Article · Mar 2014 · British Journal of Pharmacology
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    • "The opioid system modulates a wide range of physiological states, of which nociception, reward, mood, stress, neuroendocrine physiology , immunity, autonomic functions such as gastro-intestinal transit (Kieffer and Evans, 2009; Walwyn et al., 2010; Chu Sin Chung and Kieffer, 2013; Lutz and Kieffer, 2013). Opioid receptors are members of the class A GPCR family, mu (MOP), delta (DOP) and kappa (KOP) opioid receptors couple to inhibitory heterotrimeric inhibitory G protein, and have high sequence homology (Akil et al., 1998). "
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    ABSTRACT: G protein-coupled receptors (GPCRs) modulate most physiological functions but are also critically involved in numerous pathological states. Approximately a third of marketed drugs target GPCRs, which places this family of receptors in the main arena of pharmacological pre-clinical and clinical research. The complexity of GPCR function demands comprehensive appraisal in native environment to collect in-depth knowledge of receptor physiopathological roles and assess the potential of therapeutic molecules. Identifying neurons expressing endogenous GPCRs is therefore essential to locate them within functional circuits whereas GPCR visualization with subcellular resolution is required to get insight into agonist-induced trafficking. Both remain frequently poorly investigated because direct visualization of endogenous receptors is often hampered by the lack of appropriate tools. Also, monitoring intracellular trafficking requires real-time visualization to gather in-depth knowledge. In this context, knock-in mice expressing a fluorescent protein or a fluorescent version of a GPCR under the control of the endogenous promoter not only help to decipher neuroanatomical circuits but also enable real-time monitoring with subcellular resolution thus providing invaluable information on their trafficking in response to a physiological or a pharmacological challenge. This review will present the animal models and discuss their contribution to the understanding of the physiopathological role of GPCRs. We will also address the drawbacks associated with this methodological approach and browse future directions.
    Full-text · Article · Jan 2014 · Frontiers in Pharmacology
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    • "There is strong evidence that drug substitution therapy facilitates the prevention of HIV transmission as highlighted by Sorensen and Copeland [2]. In Hong Kong, the prevalence of HIV among opioid abusers remains low since the introduction of methadone as drug substitution therapy in 1980s [4]. "
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    ABSTRACT: Background Methadone Maintenance Therapy (MMT) is one of the popular choices for drug substitution therapy and is fairly new in Malaysia. Aside from its role in harm reduction against HIV infection, MMT programme may potentially enhances clients’ quality of life. This study aims to identify the impact of MMT programme on clients’ quality of life after 6 months in treatment and to explore factors that may be associated with changes in their quality of life. Methods In this retrospective report review, 122 subjects from 2 government MMT clinics were selected from the district of Tampin, Negeri Sembilan, Malaysia. The raw score from the WHO Quality of Life questionnaire (WHOQOL-BREF), at baseline and 6 months after therapy were collected and converted to 0–100 scale form to give quality of life scores for four domains; physical, psychological, social relationships and environment. Other variables of interest were socio-demography, age when joining MMT programme, age and duration of illicit drug use, HIV and Hepatitis C status, and the Opiate Treatment Index (OTI) score on drug use, sexual and social aspect at the baseline. Statistical analysis used the SPSS version 16. Results There was significant improvement in all four domains of quality of life, after 6 months of MMT. The largest improvement was for psychological domain (mean score difference 15.54 ± 20.81). Multivariable linear regression analysis showed that, for the physical domain, there was no significant predictor. For both the psychological and social domains, having tertiary education is a significant predictor for improvement in both aspects of quality of life. Negative HIV status is associated with improvement for the environment domain. Conclusions There was a significant short term improvement in the quality of life of MMT clients who stayed in the programme for at least 6 months in the district of Tampin, Negeri Sembilan, Malaysia.
    Full-text · Article · Aug 2012 · Substance Abuse Treatment Prevention and Policy
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