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A conjugate vaccine attenuates morphine- and heroin-induced behavior in rats.

Pub Med: Keyword Buprenorphine - December 19, 2014 - 6:30am

A conjugate vaccine attenuates morphine- and heroin-induced behavior in rats.

Int J Neuropsychopharmacol. 2014 Dec 7;

Authors: Li Q, Sun C, Luo Y, Xue Y, Meng S, Xu L, Chen N, Deng J, Zhai H, Kosten TR, Shi J, Lu L, Sun H

Abstract
BACKGROUND: Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies.
METHODS: A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized, with 6-glutarylmorphine as the hapten and a lengthened linker of six carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed.
RESULTS: After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse.
CONCLUSION: These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.

PMID: 25522425 [PubMed - as supplied by publisher]

The A6V polymorphism of the human μ-opioid receptor negatively impacts signalling of morphine and endogenous opioids in vitro.

Pub Med: Keyword Buprenorphine - December 19, 2014 - 6:30am

The A6V polymorphism of the human μ-opioid receptor negatively impacts signalling of morphine and endogenous opioids in vitro.

Br J Pharmacol. 2014 Dec 17;

Authors: Knapman A, Santiago M, Connor M

Abstract
BACKGROUND AND PURPOSE: Polymorphisms of the μ-opioid receptor (MOPr) may contribute to the variation in responses to opioid drugs in clinical and unregulated situations. The A6V variant of MOPr (MOPr-A6V) is present in up to 20% of individuals in some populations, and may be associated with heightened susceptibility to drug abuse. There are no functional studies examining the acute signalling of MOPr-A6V in vitro, so we investigated potential functional differences between MOPr and MOPr-A6V at several signalling pathways using structurally distinct opioid ligands.
EXPERIMENTAL APPROACH: CHO and AtT-20 cells stably expressing MOPr and MOPr-A6V used. Adenylyl cyclase (AC) inhibition and ERK1/2 phosphorylation assays were conducted in CHO cells, assays of K channel activation in AtT-20 cells.
KEY RESULTS: Buprenorphine did not inhibit AC or stimulate ERK1/2 phosphorylation in CHO cells expressing MOPr-A6V, but buprenorphine activation of K channels in AtT-20 cells was preserved. DAMGO, morphine and β-endorphin inhibition of AC was significantly reduced via MOPr-A6V, as was signalling of all opioids to ERK1/2. However, there was little effect of the A6V variant on K channel activation.
CONCLUSIONS AND IMPLICATIONS: This study shows that signalling to AC and ERK via MOPr-A6V is reduced for many opioids, including the clinically significant drugs morphine, buprenorphine and fentanyl, as well endogenous opioids. The MOPr-A6V variant can be common and this compromised signalling may affect individual responses to opioid therapy, while the possible disruption of the endogenous opioid system may contribute to susceptibility to substance abuse.

PMID: 25521224 [PubMed - as supplied by publisher]

Failure to identify or effectively manage prescription opioid dependence acted as a gateway to heroin use-buprenorphine/naloxone treatment and recovery in a surgical patient.

Pub Med: Keyword Buprenorphine - December 19, 2014 - 6:30am

Failure to identify or effectively manage prescription opioid dependence acted as a gateway to heroin use-buprenorphine/naloxone treatment and recovery in a surgical patient.

BMJ Case Rep. 2014;2014

Authors: Conroy S, Hill D

Abstract
The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9 years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16 mg/naloxone 4 mg in conjunction with social and psychological support.

PMID: 25519865 [PubMed - as supplied by publisher]

Evaluation of Opioid Modulation in Major Depressive Disorder.

Pub Med: Keyword Buprenorphine - December 19, 2014 - 6:30am

Evaluation of Opioid Modulation in Major Depressive Disorder.

Neuropsychopharmacology. 2014 Dec 18;

Authors: Ehrich E, Turncliff R, Du Y, Leigh-Pemberton R, Fernandez E, Jones R, Fava M

Abstract
Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ opioid partial agonist, buprenorphine (BUP), and a potent μ opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent one-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments and self-report questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs. placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in MADRS total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist-antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders.Neuropsychopharmacology accepted article preview online, 18 December 2014. doi:10.1038/npp.2014.330.

PMID: 25518754 [PubMed - as supplied by publisher]

Pathological video-gaming among youth: A prospective study examining dynamic protective factors

MedWorm Addiction Feeds - December 19, 2014 - 5:08am
Addiction Research & Theory, Ahead of Print. (Source: Addiction Research and Theory)

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Group solidarity in a hostile milieu: Immigrant experiences in a street-based drug scene

MedWorm Addiction Feeds - December 19, 2014 - 5:01am
Drugs: education, prevention, and policy, Ahead of Print. (Source: Drugs: Education, Prevention, and Policy)

Serotonin 5-HT2 Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder.

MedWorm Addiction Feeds - December 19, 2014 - 4:10am
Authors: Howell LL, Cunningham KA Abstract Cocaine exhibits prominent abuse liability, and chronic abuse can result in cocaine use disorder with significant morbidity. Major advances have been made in delineating neurobiological mechanisms of cocaine abuse; however, effective medications to treat cocaine use disorder remain to be discovered. The present review will focus on the role of serotonin (5-HT; 5-hydroxytryptamine) neurotransmission in the neuropharmacology of cocaine and related abused stimulants. Extensive research suggests that the primary contribution of 5-HT to cocaine addiction is a consequence of interactions with dopamine (DA) neurotransmission. The literature on the neurobiological and behavioral effects of cocaine is well developed, so the focus of the review will...

Conceptualizing nonsuicidal self-injury as a process addiction: review of research and implications for counselor training and practice - Buser TJ, Buser JK.

MedWorm Addiction Feeds - December 18, 2014 - 11:55pm
Nonsuicidal self-injury (NSSI) may be characterized as a process addiction for some individuals who self-injure. The authors review findings on the addictive features of NSSI, including compulsivity, loss of control, continued use despite negative conseque... (Source: SafetyLit: All (Unduplicated))

681: Prenatal nicotine exposure is associated with alterations of the postnatal offspring epigenome

MedWorm Addiction Feeds - December 18, 2014 - 8:04pm
How the fetus responds to and adapts to nicotine exposure is a major public health issue. Fetal exposure to nicotine is not limited to maternal tobacco smoke: pregnant women who utilize nicotine replacement therapy or electronic cigarettes similarly expose their fetus. Primate studies have shown that nicotine exposure in utero renders offspring susceptible to asthma as well as learning and memory deficits later in life, and nicotine exposure in adult mice potentitates cocaine addiction. The molecular mechanisms underlying these observations are poorly understood. (Source: American Journal of Obstetrics and Gynecology)

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The Danger of Drinking to Blackout

MedWorm Addiction Feeds - December 18, 2014 - 3:47pm
Someone who has had a blackout while drinking cannot remember part of their drinking episode. Unfortunately, most people do not understand how dangerous blackouts are, yet up to 50% of drinkers may have an alcohol-related blackout (ARB). read more (Source: Psychology Today Addiction Center)

Minister Ambrose Takes Steps to Address Safe Prescribing Practices for Drugs Prone to Abuse

MedWorm Addiction Feeds - December 18, 2014 - 1:15pm
The Honourable Rona Ambrose, Minister of Health, today issued a national Call for Proposals to improve the prescribing practices for prescription drugs that have a high risk of abuse or addiction. (Source: Government of Canada News - Health Canada)

Minister Ambrose co-hosts symposium on prescription drug abuse

MedWorm Addiction Feeds - December 18, 2014 - 1:15pm
Minister of Health, the Honourable Rona Ambrose, co-hosted a symposium in Toronto today, attended by over 40 people, including officials from different levels of government, doctors, pharmacists, First Nations representatives, law enforcement and addictions specialists to discuss prescription drug abuse. (Source: Government of Canada News - Health Canada)

Renu Kapoor Appointed to the Canadian Centre for Substance Abuse Board of Directors - Government of Canada working to address addiction and drug abuse in Canada

MedWorm Addiction Feeds - December 18, 2014 - 1:15pm
Health Minister Rona Ambrose announced the appointment of Ms. Renu Kapoor to the Canadian Centre for Substance Abuse (CCSA) Board of Directors for a three-year term. (Source: Government of Canada News - Health Canada)

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MT-45: a new, dangerous legal high.

MedWorm Addiction Feeds - December 18, 2014 - 1:03pm
Authors: Coppola M, Mondola R PMID: 25508990 [PubMed - in process] (Source: Journal of Opioid Management)

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Alpha-pyrrolidinovalerophenone (alpha-PVP): Self-administration and acute drug challenges in rats

MedWorm Addiction Feeds - December 18, 2014 - 1:00pm
Aims: Assess the abuse liability of alpha-PVP (a drug often found in “bath salts”) in preclinical animal models of reward/reinforcement and physiology. (Source: Drug and Alcohol Dependence)

Sexual relationship power, victimization, and HIV risky sexual behavior in substance abusing African American women

MedWorm Addiction Feeds - December 18, 2014 - 1:00pm
Aims: The goal of the current study was to assess the associations between victimization (physical, adult sexual, and child sexual abuse), sexual relationship power (SRP), and unprotected sex occasions (USO) in substance abusing African American (AA) women. It is hypothesized that SRP moderates the relationship between victimization and USO. Specifically, as SRP increases, the relationship between reported victimization and HIV risk behaviors will decrease. (Source: Drug and Alcohol Dependence)

Primary drug use types and intervention-related self-monitoring in HIV patients

MedWorm Addiction Feeds - December 18, 2014 - 1:00pm
Aims: In HIV primary care patients, drug abuse is a common problem; brief, effective interventions are needed. Self-monitoring is an evidence-based element of brief intervention. In a randomized trial of “HealthCall,” a technology-assisted self-monitoring intervention to reduce non-injection drug use (NIDU), patients’ primary drug varied, as did their engagement in self-monitoring. A better understanding of patient characteristics associated with primary drug type can help tailor interventions for this population; understanding correlates of patient engagement in HealthCall-assisted self-monitoring can assist counselors in improving personalized feedback, engagement and treatment outcomes. (Source: Drug and Alcohol Dependence)

Gender differences in polysubstance use among those who misuse prescription opioids

MedWorm Addiction Feeds - December 18, 2014 - 1:00pm
Aims: This analysis explores gender differences in polysubstance use amongst those who misuse opioids prescribed to them and those who use prescription opioids without a prescription. (Source: Drug and Alcohol Dependence)

Addiction services for women in Eastern Europe: What is available and where?

MedWorm Addiction Feeds - December 18, 2014 - 1:00pm
This study examined addiction services for women (including pregnant women) in 8 Eastern European countries. (Source: Drug and Alcohol Dependence)

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Evaluation of the effectiveness of drug prevention programs: Analysis of the international scientific production (2002–2011)

MedWorm Addiction Feeds - December 18, 2014 - 1:00pm
The objective was to analyze the international scientific production in the period 2002–2011 of articles that assess the effectiveness of drug use prevention programs by means of bibliometric methods through the Web of Knowledge and Scopus databases. (Source: Drug and Alcohol Dependence)

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