Disease relevance of Opioid-Related Disorders

• BACKGROUND: Methadone maintenance treatments (MMTs) are the commonest substitution treatments offered to opiate addiction in Switzerland, in order to reduce criminal behaviour, infectious disease transmission and overdose death [1].
• These findings are consistent with the view that the molecular mechanisms of opiate dependence is the hypertrophy of a neuronal cyclic AMP system in compensation for the inhibition by opiate of an adenylate cyclase [2].

Psychiatry related information on Opioid-Related Disorders

• Therapeutic communities vs methadone maintenance. A prospective controlled study of narcotic addiction treatment: design and one-year follow-up [3].
• 'Craving is generally considered a significant factor in opiate addiction that is associated with drug-dependence and in relapse to drug use after treatment'-ARC expert consensus (Pickens and Johanson, Drug and Alcohol Dependence 30: 127-131) [4].
• Treatment of opiate addiction is generally directed at the suppression of withdrawal symptoms through maintenance of the 'addicted' state with methadone [5].
• SAM/SAM (test/retest) agreement was excellent for alcohol and opiate dependence, good for cocaine dependence, and fair for cannabis dependence [6].
• Overall, concordance among the three assessments was good for alcohol and opiate dependence, fair to good for cocaine and sedative dependence, and low for amphetamine dependence [7].

High impact information on Opioid-Related Disorders

• 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 [8].
• Thus, CREB-dependent gene transcription is a factor in the onset of behavioral manifestations of opiate dependence [9].
• Altered neuroadaptation in opiate dependence and neurogenic inflammatory nociception in alpha CGRP-deficient mice [10].
• Controlled clinical evaluation of diacetyl morphine for treatment of intractable opiate dependence [11].
• Cortical and limbic dopamine (on opiate addiction): do not mix before use [12]!

Chemical compound and disease context of Opioid-Related Disorders

• Therapeutic usefulness of propoxyphene napsylate in narcotic addiction [13].
• Evaluation of propranolol in opiate dependence [14].
• Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance [15].
• Onset preceded the onset of cocaine dependence in 72.0% of the patients (and preceded onset of opiate dependence in 44.4%) [16].
• A clinical, controlled study of l-alpha-acetylmethadol in the treatment of narcotic addiction [17].

Biological context of Opioid-Related Disorders

• Together, these findings provide the first direct evidence that CREB mediates the morphine-induced upregulation of specific components of the cAMP pathway in the LC that contribute to physical opiate dependence [18].
• Lack of an effect of atazanavir on steady-state pharmacokinetics of methadone in patients chronically treated for opiate addiction [19].
• This downregulation and the aberrant hyperphosphorylation of NF-H proteins might have important consequences in the development of neural plasticity associated with opiate addiction in humans [20].
• This under-representation of poor metabolizers (Fisher's exact test, p < or = 0.05) in people dependent on oral opiates suggests that the CYP2D6 defective genotype is a pharmacogenetic protection factor for oral opiate dependence (estimated odds ratio > 7) [21].
• Further, genetic variation in the genes encoding galanin and its receptors could be associated with altered susceptibility to opiate dependence [22].

Anatomical context of Opioid-Related Disorders

• In the course of investigating effects of chronic morphine on the cAMP pathway in the locus coeruleus, a brain region important for opiate addiction, we found that levels of CREB immunoreactivity and CRE binding were increased by chronic morphine administration [23].
• Striking dynamic alterations include a pronounced increase in levels of proenkephalin mRNA in the corpus striatum after blockade of dopamine receptors, but changes in opioid peptide mRNA after opiate addiction are less clear [24].
• Mean red blood cell volume, narcotic addiction, and glucose tolerance [25].
• The lasting nature of the reduced dopamine release at the level of dopaminergic nerve terminals and the concomittant enhanced excitability of neurons tonically inhibited by released dopamine, such as cholinergic interneurons, could play an important role in the maintenance of opiate dependence [26].
• The results reported herein coupled with similar findings for alpha-interferon and cyclosporine, suggest that opiate dependence may involve the immune system [27].

Gene context of Opioid-Related Disorders

• This study reveals a cardinal role for CRF/CRF1 receptor pathways in the negative affective states of opiate withdrawal and suggests therapeutic strategies for the treatment of opiate addiction [28].
• Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence [21].
• The abnormalities of MAPK signalling might have important consequences in the long term development of various forms of neural plasticity associated with opiate addiction in humans [29].
• The authors describe the use of moclobemide in a 27-year-old patient with comorbid opiate addiction and ADHD (residual type) [30].
• In contrast to data obtained in adult animals, NMDA receptor antagonists are neither effective in blocking the development of opiate dependence nor the expression of opiate withdrawal in neonatal rats [31].

Analytical, diagnostic and therapeutic context of Opioid-Related Disorders

• The biochemical status of human brain G protein subunits during opiate dependence was studied by means of immunoblotting techniques [32].
• We have been conducting studies both in humans and in animal models focused on the role of disruption of the stress responsive hypothalamic-pituitary-adrenal axis in opiate addiction, cocaine dependency and alcoholism [33].
• The results are discussed in terms of novel mechanisms underlying denervation supersensitivity, and may have important implications for the relation between dopamine dysfunction in mental illness and opiate addiction [34].
• Previous cell culture studies have demonstrated significant basal, spontaneous MOR signaling activity, but its relevance to narcotic addiction remained unclear [35].
• Pharmacotherapies utilizing long-acting agonists and mixed function agonists-antagonists have been successful in the treatment of opiate addiction but no comparable treatment exists for cocaine abuse [36].

References