Treatment Of Narcotic Addiction Research Articles

Narcotic Addiction in Failed Back Surgery Syndrome.

Back pain is a common health problem that reduces the quality of life for human beings worldwide. Several treatment modalities have been reported as effective for pain relief. Generally, patients often undergo surgical interventions as pain becomes intractable, after conservative treatment. With advances in surgical techniques, those choosing spinal surgery as an option have increased over time, and instrumentation is more popular than it was years ago. However, some patients still have back pain after spinal operations. The number of patients classified as having failed back surgery syndrome (FBSS) has increased over time as has the requirement for patients receiving long-term analgesics. Because pain relief is regarded as a human right, narcotics were prescribed more frequently than before. Narcotic addiction in patients with FBSS has become an important issue. Here, we review the prevalence of FBSS, the mechanism of narcotic addiction, and their correlations. Additionally, several potentially effective strategies for the prevention and treatment of narcotic addiction in FBSS patients are evaluated and discussed.

Mechanism-Based Inactivation of Cytochrome P450 2B6 by Methadone through Destruction of Prosthetic Heme

Methadone is a μ-opioid receptor agonist widely used in the treatment of narcotic addiction and chronic pain conditions. Methadone is metabolized predominantly in the liver by cytochromes P450 to its pharmacologically inactive primary metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. Initial in vitro data suggested that CYP3A4 is the major isoform responsible for the in vivo clearance of methadone in humans. However, recent clinical data have indicated that CYP2B6 is actually the major isoform responsible for methadone metabolism and clearance in vivo. In this study, methadone was shown to act as a mechanism-based inactivator of CYP2B6. Methadone inactivates CYP2B6 in a time-, concentration-, and NADPH-dependent manner with a K(I) = 10.0 μM and k(inact) = 0.027 min⁻¹. The loss of CYP2B6 activity in the presence of methadone and NADPH occurred with concomitant loss of the reduced CO spectrum of the P450. Moreover, there was good correlation between the loss of CYP2B6 activity and the loss of the CO-binding spectrum. High-performance liquid chromatography analysis of the native heme of the inactivated CYP2B6 demonstrated that approximately 75% loss of heme was accompanied by comparable inactivation of CYP2B6. Liquid chromatography-mass spectrometry analysis did not reveal the formation of a protein adduct during the inactivation. The evidence strongly suggests that destruction of prosthetic heme is the underlying mechanism leading to the inactivation of CYP2B6 by methadone.

Electrochemical determination of naltrexone on the surface of glassy carbon electrode modified with Nafion-doped carbon nanoparticles: Application to determinations in pharmaceutical and clinical preparations

A new sensitive and selective electrochemical sensor was developed for determination of naltrexone (NAL) in pharmaceutical dosage form and human plasma. Naltrexone is an opioid antagonist which is commonly used for the treatment of narcotic addiction and alcohol dependence. A voltammetric study of naltrexone has been carried out at the surface of glassy carbon electrode (GCE) modified with Nafion-doped carbon nanoparticles (CNPs). The electrochemical oxidation of naltrexone was investigated by cyclic and differential pulse voltammetric techniques. The dependence of peak currents and potentials on pH, concentration and the potential scan rate was investigated. The electrode characterization by electrochemical methods and atomic force microscopy (AFM) showed that CNPs enhanced the electroactive surface area and accelerated the rate of electron transfer. Application of the modified electrode resulted in a sensitivity enhancement of more than 20 times, relative to the bare GCE, in detection of NAL and a considerable negative shift in peak potential was achieved. Two linear dynamic ranges of 1–10 μM and 10–100 μM with a detection limit of 0.1 μM was obtained in phosphate buffer of pH = 3. Differential pulse voltammetry as a simple, rapid, sensitive and selective method was developed for the determination of NAL in dosage form and human plasma without any treatments. No electroactive interferences were found in biological fluids from the endogenous substances and additives present in capsules.

Understanding our drugs and our diseases.

Analysis of mouse genetic models of human disease-associated traits has provided important insight into the pathogenesis of human disease. As one example, analysis of a murine genetic model of osteoporosis demonstrated that genetic variation within the 15-lipoxygenase (Alox15) gene affected peak bone mass, and that treatment with inhibitors of this enzyme improved bone mass and quality in rodent models. However, the method that has been used to analyze mouse genetic models is very time consuming, inefficient, and costly. To overcome these limitations, a computational method for analysis of mouse genetic models was developed that markedly accelerates the pace of genetic discovery. It was used to identify a genetic factor affecting the rate of metabolism of warfarin, an anticoagulant that is commonly used to treat clotting disorders. Computational analysis of a murine genetic model of narcotic drug withdrawal suggested a potential new approach for treatment of narcotic drug addiction. Thus, the results derived from computational mouse genetic analysis can suggest new treatment strategies, and can provide new information about currently available medicines.

LES TRAITEMENTS DE SUBSTITUTION A L’HEROÏNE. ANALYSE DES SOLUTIONS ACTUELLES, EVOLUTIONS ET PERSPECTIVES.

Drugs used for treatment of narcotic addicts (buprenorphin at high concentration or methadone) have different advantages and disadvantages. The author has tried to insist on what can be complementary between both treatments. Two new formulations of buprenorphin at high concentration (Suboxone and Subutex NF) are described and proposed to replace Subutex®.

Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence.

The mu opioid receptor, MOR, displays spontaneous agonist-independent (basal) G protein coupling in vitro. To determine whether basal MOR signaling contributes to narcotic dependence, antagonists were tested for intrinsic effects on basal MOR signaling in vitro and in vivo, before and after morphine pretreatment. Intrinsic effects of MOR ligands were tested by measuring GTPgammaS binding to cell membranes and cAMP levels in intact cells. beta-CNA, C-CAM, BNTX, and nalmefene were identified as inverse agonists (suppressing basal MOR signaling). Naloxone and naltrexone were neutral antagonists (not affecting basal signaling) in untreated cells, whereas inverse agonistic effects became apparent only after morphine pretreatment. In contrast, 6alpha- and 6beta-naltrexol and -naloxol, and 6beta-naltrexamine were neutral antagonists regardless of morphine pretreatment. In an acute and chronic mouse model of morphine-induced dependence, 6beta-naltrexol caused significantly reduced withdrawal jumping compared to naloxone and naltrexone, at doses effective in blocking morphine antinociception. This supports the hypothesis that naloxone-induced withdrawal symptoms result at least in part from suppression of basal signaling activity of MOR in morphine-dependent animals. Neutral antagonists have promise in treatment of narcotic addiction.

Implementation of the methadone treatment quality assurance system. findings from the feasibility study.

This article describes the development and large-scale testing of the Methadone Treatment Quality Assurance System (MTQAS). MTQAS originated as a NIDA (National Institute on Drug Abuse) funded study to assess the feasibility and utility of implementing a performance-based feedback reporting system for narcotic addiction treatment programs. After several years of research to identify a set of valid, reliable, and clinically useful indicators of program performance using patients' in-treatment outcomes, MTQAS was tested in a feasibility study with more than 70 methadone treatment clinics in seven states. For each of nine quarters, participating clinics received a report summarizing their patient outcomes; reports also included summary data permitting comparisons across states, across clinics within a state, and within a clinic over time. In addition, MTQAS included a case-mix adjustment strategy that permitted fair comparisons of performance among programs with systematically different patient caseloads. The structure and operation of MTQAS, selected analyses of the data, and lessons for future performance measurement systems are discussed.

Access to Narcotic Addiction Treatment and Medical Care

Methadone maintenance treatment (MMT) for opioid addiction is safe and effective but underutilized because of inaccessibility, under-financing and the stigma generally attached to maintenance therapies. In addition, cumbersome regulation of methadone prescription and treatment impedes the delivery of care and retards expansion of methadone maintenance into office practice settings. Exaggeration of the problem of methadone diversion further hinders development of MMT. Despite obstacles, methadone maintenance has been successfully expanded and extended into primary care settings abroad. Initial trials in the U.S. have shown that methadone maintenance in physician office-based settings yields positive results with some advantages over care in large methadone clinics. Alternatives to methadone, such as buprenor-phine, are also being explored in primary care settings. With implementation of the NIH Consensus Statement on Effective Medical Treatment of Heroin Addiction, including training of primary care physicians, methadone maintenance treatment could reach many more patients, achieve higher success rates, and substantially reduce the deleterious effects of opioid addiction in the U.S.

A study of reversibly inactivated lipases for use in a morphine-triggered naltrexone delivery system.

A key component of an implant that can be triggered by external morphine to release naltrexone is an inactivated enzyme that can be activated by morphine and which can then rapidly remove a protective coating surrounding a bioerodible polymer containing dispersed naltrexone. In this article we describe a lipase that has been conjugated with O3-carboxymethylmorphine, morphine-beta-3-glucuronide and O3-carboxypropylmorphine. The enzyme conjugate was then inactivated by complexation with affinity-purified goat polyclonal antimorphine antibodies. Antibody lipase interactions were measured by pH Stat and ELISA techniques. Affinity constants of the antibodies determined by radioimmunoassay using tritium-labeled morphine were 4.10 x 10(6), 3.18 x 10(6) and 3.38 x 10(7), respectively. While a concentration of 10(-5)M morphine was required to restore lipase activity, it is likely that a combination of correct morphine tether and correct affinity-purified antibody can increase sensitivity to the desired 10(-8)10(-9)M morphine level. Thus, a functioning device can almost certainly be constructed. However, it is unlikely that reactivation times of 1-2 h necessary for clinical usefulness in treatment of narcotic addiction can be achieved.

On Federal Regulation of Methadone Treatment

A RECENT report from the Institute of Medicine (an affiliate of the National Academy of Sciences) provides an authoritative review of the history and consequences of federal regulation of methadone treatment.¹It examines the assumptions that justified imposition of special restrictions on prescription of methadone and the effects of enforced guidelines on the function of treatment programs. Since the Narcotic Addict Treatment Act (1974) authorized an unprecedented restriction of the right of physicians to prescribe an approved drug, the experience of the past 20 years can be seen as a major experiment in governmental regulation of medical practice. Given the controversial nature of the subject, both the government and the medical profession in general are fortunate to have had the results of this experiment evaluated at the highest scientific level. Quite properly, I was not included in the deliberations for the Institute of Medicine report. My views on the

Including Narcotic Addiction Treatment in an Office-Based Practice

THE REGULATION of narcotic medications used in narcotic addiction treatment is unique in medical therapeutics. Physicians who want to administer or dispense opioid drugs for either narcotic maintenance or detoxification treatment by federal law must first obtain an additional annual registration from the Drug Enforcement Administration (DEA). This registration is separate from the registration familiar to physicians who prescribe other controlled medications. The additional registration is contingent on compliance both with the DEA's security regulations (inventory, record keeping, and physical security) as well as with annual certification from the US Department of Health and Human Services (DHHS). DHHS certification is contingent on approval by individual state drug authorities and compliance with treatment regulations jointly promulgated by the Food and Drug Administration (FDA) and the National Institute on Drug Abuse. Authority for this separate registration emanates from the Narcotic Addict Treatment Act (NATA) of 1974,¹which was enacted to give

Including narcotic addiction treatment in an office-based practice

Including narcotic addiction treatment in an office-based practice

Federal Regulation of Clinical Practice in Narcotic Addiction Treatment: Purpose, Status, and Alternatives

The regulation of narcotic medications used in narcotic addiction treatment is unique in medical therapeutics. Physicians who want to use narcotics for this indication must obtain a separate annual registration from the Drug Enforcement Administration(DEA).Annual registration is contingent on compliance with both the DEA's security regulations (inventory, record-keeping, andphysical security) as well as treatment regulations jointly promulgated by the Food and Drug Administration(FDA)and the National Institute on Drug Abuse(NIDA).During the last decade, a number of events have occurred that persuadedNIDAthat it is time to reevaluate the current method by which the Department of Health and Human Services(HHS)regulates methadone treatment. As a result of research during the past twenty years, we have learned about the effective components of methadone treatment. In comparison to other available treatment modalities for opioid addiction, methadone treatment is uniquely effective when administered by well-trained medical staffs.

Methadone maintenance: Predictors of outcome in a Canadian milieu

This hypothesis-generating study attempts to identify patient characteristics predicting the successful outcome of methadone maintenance in the treatment of narcotic addiction. The sociodemographic characteristics as well as the general emotional health of 51 addicted individuals in Montreal were studied at entry into the program and are correlated with success one year after entry. The success of the Montreal program, defined as retention in the program and urine samples negative for opiates, is comparable to results reported from many North American clinics. A history of foster care before age 15 is the only characteristic significantly correlated with both retention and negative urines. Emotional health, previous treatment experiences, job status, and level of education do not correlate with success. All addicted individuals applying to a treatment program should therefore be accepted for a trial of treatment while further research on greater numbers of subjects may eventually identify predictors of successful outcome.

Medico-legal aspects of treatment and prophylactic care of narcotic drug addicts

L'article presente quelques aspects medico-legaux du traitement et des soins prophylactiques destines aux toxicomanes utilisant des narcotiques

Narcotic addiction and family process: Death wish or countertransference

This article critically examines the literature which suggests that families of narcotic addicts push their addicted member toward death. Following an overview of the conventional literature on the family treatment of drug addiction, an alternative perspective is proposed to more fully understand how these families are preoccupied with death. The “suicide-like” quality of addiction is probed both in terms of the intention to die and the countertransference possibilities. The notion of a family “death wish” has the potential to be misinterpreted by the countertransference response of an unseasoned treatment provider. Clinicians are cautioned that this notion can be a potential threat to the patient's life. Implications are presented for the supervision of the family treatment of narcotic addiction.

Narcotic Addiction and Methadone Treatment in Hong Kong: Lessons for the United States

ze qtion on the basis of policies of Imperial China, which > severely curtailed access of English goods to the Chinese market. As a result, British purchases of silk and tea were offset only minimally by the sale of English products, and instead had to be paid for primarily with silver. In order to contain this drain on bullion, the British began trading with opium, which was grown readily in India. The sale of opium to China was also illegal, but was accomplished readily through overt corruption among Chinese officials, and was fostered by the large and rapidly growing demand for the product. The entire trade with China was carried out through Macau, the only Chinese port open to foreign ships until Hong Kong was ceded to Britain in 1842. China was resistant to repeated suggestions that the importation of opium be legalized. The Tao Kowng Emperor stated in 1843: "It is true, I cannot prevent the introduction of the flowing poison; gain-seeking and corrupt men will, for profit and sensuality, defeat my wishes; but nothing will induce me to derive a revenue from the vice and misery of my people" (1). Even in England there developed a sentiment against the Government-condoned sale of opium to China. In response, the Hong Kong Colonial Surgeon sought to downplay the effect of opium on the Chinese population by saying in 1881: "Opium smoking does not do 1 /loooth part of the harm to either the individual or his family that alcohol does at home" (2). Comparisons between the relative harm caused by narcotic abuse and alcoholism, and competition for dollars to combat the respective problems, continue to this day in the United States and elsewhere.

Historical introduction and review of chemistry.

A historical introduction and review of the chemistry of the agonist-antagonist analgesics is presented. This development of strong analgesics with a lowered abuse potential from nalorphine to the clinically useful agonist-antagonists pentazocine, butorphanol, nalbuphine and buprenorphine is discussed in detail. The discovery of the pure antagonist naloxone and naltrexone is described. The possible use of cyclazocine and later naltrexone in treatment of post-dependent narcotic addicts is also described. Finally, structure-activity relationships are summarized relating changes in N-alkylation to the production of narcotic antagonist activity over all of the structural types of opioids.

Biofeedback treatment of narcotic addiction: A double-blind study

This is a report on the double-blind study on EMG biofeedback for 37 narcotic addicts in an outpatient methadone clinic. Patients were randomly assigned to either the experimental group ( N = 24) receiving a contingent EMG biofeedback or a control group ( N = 13) receiving non-contingent preaped “pseudo-biofeedback”. All patients were stabilized on a study dose of methadone and the mean daily amount did not differ between groups. All were experiencing a significant degree of anxiety at the time of evaluation. The evaluation consisted of the patient's self-report, which comprised the Beck Depression Inventory, anxiety checklist, withdrawal sickness rating, drug references, and the psychiatrist's rating of depression, namely the Hamilton Depression Scale, Hamilton Anxiety Scale, and BPRS. In addition, an evaluation of progress was obtained from the patient and his counselor which included the current job or school status and brief ratings of drug use, psychiatric symptoms, social adjustment, and illegal activity. All patients had at least one urine sample analyzed weekly for illicit drug use. Evaluation was done at the beginning, and at the end of the treatment and at a follow-up one month later. Termination status was assessed only for subjects who completed the course of 15 biofeedback sessions ( N = 19). Patients attended five sessions per week for thirty minutes just prior to receiving the methadone. Fifteen sessions were scheduled over a three-week period. The results indicated that the two study groups did not differ and there was a significant improvement ( p < 0.05) on several variables for the total patient sample. All the psychiatric ratings of anxiety, depression, psychopathology were significantly reduced. In addition, self-rated craving for narcotics and self-rated anxiety were lower and there were fewer drug avoidance responses on the sentence completion test. But there were no meaningful differences in the two groups in improvement as reflected in the psychometric instruments.

Effects of parenteral morphine and oral methadone on self-stimulation in the rat

Facilitation of self-stimulation has been reported following the administration of various opiates. Methadone, a synthetic narcotic used in the treatment of narcotic addiction, has recently been demonstrated to facilitate self-stimulation when administered parenterally. The present study examined the effects of orally administered methadone (20 and 30 mg/kg), the route of administration used clinically, on MFB-LH self-stimulation at 2.5, 5, 8, 12, 17, and 24 hours post-administration. reliable facilitation was observed at 2.5 hours post-administration. However, the effect of methadone was less pronounced than that observed with a dose of parenteral morphine which was approximately equivalent in terms of analgesic potency.