- Neurochemical and metabolic effects of acute and chronic alcohol in the human brain: Studies with positron emission tomography. [Review]
- NNeuropharmacology 2017 Jan 17
- The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding effe...
The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding effects, the neuroadaptations from chronic exposure that contribute to tolerance and withdrawal, and the changes in fronto-striatal circuits that lead to loss of control and enhanced motivation to drink that characterize alcohol use disorders (AUD). These include studies showing that alcohol's reinforcing effects may result not only from its enhancement of dopaminergic, GABAergic and opioid signaling but also from its caloric properties. Studies in those suffering from an AUD have revealed significant alterations in dopamine (DA), GABA, cannabinoids, opioid and serotonin neurotransmission and in brain energy utilization (glucose and acetate metabolism) that are likely to contribute to compulsive alcohol taking, dysphoria/depression, and to alcohol-associated neurotoxicity. Studies have also evaluated the effects of abstinence on recovery of brain metabolism and neurotransmitter function and the potential value of some of these measures to predict clinical outcomes. Finally, PET studies have started to provide insights about the neuronal mechanisms by which certain genes contribute to the vulnerability to AUD. These findings have helped identify new strategies for prevention and treatment of AUD.
- Implementation of methadone therapy for opioid use disorder in Russia - a modeled cost-effectiveness analysis. [Journal Article]
- SASubst Abuse Treat Prev Policy 2017 Jan 20; 12(1):4
- CONCLUSIONS: Our study indicated that implementing opioid agonist therapy with methadone to treat OUD at existing facilities in Russia is highly cost-effective.
- Lorcaserin suppresses oxycodone self-administration and relapse vulnerability in rats. [Journal Article]
- ACACS Chem Neurosci 2017 Jan 20
- Opioid use disorder (OUD) is a major public health problem. High relapse rates and poor treatment retention continue to pose major challenges in OUD treatment. Of the abused opioids, oxycodone is wel...
Opioid use disorder (OUD) is a major public health problem. High relapse rates and poor treatment retention continue to pose major challenges in OUD treatment. Of the abused opioids, oxycodone is well described to maintain self-administration and evoke the durable conditioned responses ("cue reactivity") that result from pairing of opioid-related stimuli (e.g., paraphernalia) with repeated abuse. Serotonin (5-HT) neurotransmission, particularly through the 5-HT2C receptor (5-HT2CR), regulates psychostimulant reward and cue reactivity, and in the present experiments, we investigated the hypothesis that the selective 5-HT2CR agonist lorcaserin, which is FDA-approved for the treatment of obesity, will suppress oxycodone self-administration and oxycodone-associated cue reactivity in rats. We found that lorcaserin inhibited oxycodone intake, an effect blocked by the selective 5-HT2CR antagonist SB242084. Lorcaserin also decreased responding for the discrete cue complex ("cue reactivity") previously associated with delivery of oxycodone (i.e., stimulus lights, infusion pump sounds) in both abstinence and extinction-reinstatement models. The selected dose range of lorcaserin (0.25-1 mg/kg) does not overtly alter spontaneous behaviors nor operant responding on inactive levers in the present study. Taken together, the ability of lorcaserin to reduce the oxycodone self-administration and decrease cue reactivity associated with relapse highlights the therapeutic potential for lorcaserin in the treatment of OUD.
- An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life. [Journal Article]
- ACACS Chem Biol 2017 Jan 20; 12(1):36-40
- Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of...
Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design. Administration of these vaccines resulted in a significant blockade of opioid analgesic activity, along with an unprecedented increase in drug serum half-life and protection against lethal overdose.
- Defined daily doses (DDD) do not accurately reflect opioid doses used in contemporary chronic pain treatment. [Journal Article]
- PDPharmacoepidemiol Drug Saf 2017 Jan 19
- CONCLUSIONS: For many opioids, there are key differences between the actual doses used in clinical practice and the WHO's DDDs. The interpretation of opioid utilisation studies using population-level DDDs may be limited, and a recalibration of the DDD for many opioids or the reporting of opioid utilisation in oral morphine equivalent doses is recommended. Copyright © 2017 John Wiley & Sons, Ltd.
- Prescription Drug Monitoring Programs Produce a Limited Impact on Painkiller Prescribing in Medicare Part D. [Journal Article]
- HSHealth Serv Res 2017 Jan 18
- CONCLUSIONS: Prescription drug monitoring programs have a modest effect targeted at the high-profile drug oxycodone among the Medicare Part D population and an even smaller effect for hydrocodone and opioids in general. The findings suggest some substitution toward lower schedule opioids. Substantially addressing the widespread opioid abuse problem will require enhancing existing PDMPs or implementing new policies.
- Characterization and Management of Patients with Heroin versus Non-Heroin Opioid Overdoses: Experience at an Academic Medical Center. [Journal Article]
- PPharmacotherapy 2017 Jan 18
- CONCLUSIONS: This study indicates that the incidence of heroin overdoses has significantly increased over the last several years, and the rates of hepatitis C virus infection 4-fold since the start of the study period. Patients admitted for non-heroin opioid overdose were more likely to be admitted to the hospital and intensive care unit compared with those admitted for heroin overdose. The rise in overdose events only further illustrates that there is a gap in our understanding of the cycle of addiction, drug abuse, and overdose events. This article is protected by copyright. All rights reserved.
- Postmortem and Toxicological Findings in a Series of Furanylfentanyl-Related Deaths. [Journal Article]
- JAJ Anal Toxicol 2017 Jan 17
- Over the course of 4 months in 2015 and 2016, a cluster of seven fatal intoxications involving the opioid-analogue furanylfentanyl occurred in Sweden; toxicological analysis showed presence of furany...
Over the course of 4 months in 2015 and 2016, a cluster of seven fatal intoxications involving the opioid-analogue furanylfentanyl occurred in Sweden; toxicological analysis showed presence of furanylfentanyl either as the only drug or in combination with other illicit substances. Previous publications have only reported non-lethal furanylfentanyl intoxications. In the cases presented here, furanylfentanyl intoxication-alone or in combination with other drugs-was determined to be the cause of death by the responsible pathologist. All victims were young (24-37 years old) males, five of which had a well-documented history of drug abuse. Femoral blood concentration of furanylfentanyl ranged from 0.41 ng/g to 2.47 ng/g blood. Five cases presented a complex panel of drugs of abuse and prescription drugs. Moreover, in five cases the concurrent presence of pregabalin corroborates previous observations indicating pregabalin as a possible contributing factor in polydrug intoxications. We conclude that it is difficult to establish a specific lethal concentration of furanylfentanyl, due to incompletely known effects of possible pharmacokinetic and pharmacodynamic interactions with other drugs, as well as to the unknown degree of tolerance to opioids. We suggest that a full toxicological screening-to assess the possibility of drug interactions-together with segmental hair analysis regarding opioids-to estimate the level of opioid tolerance-be carried out to assist in the interpretation of cases involving synthetic opioids such as furanylfentanyl.
- New-onset depression following stable, slow, and rapid rate of prescription opioid dose escalation. [Journal Article]
- PAINPain 2017; 158(2):306-312
- Recent studies suggest that longer durations of opioid use, independent of maximum morphine equivalent dose (MED) achieved, is associated with increased risk of new-onset depression (NOD). Conversely...
Recent studies suggest that longer durations of opioid use, independent of maximum morphine equivalent dose (MED) achieved, is associated with increased risk of new-onset depression (NOD). Conversely, other studies, not accounting for duration, found that higher MED increased probability of depressive symptoms. To determine whether rate of MED increase is associated with NOD, a retrospective cohort analysis of Veterans Health Administration data (2000-2012) was conducted. Eligible patients were new, chronic (>90 days) opioid users, aged 18 to 80, and without depression diagnoses for 2 years before start of follow-up (n = 7051). Mixed regression models of MED across follow-up defined 4 rate of dose change categories: stable, decrease, slow increase, and rapid increase. Cox proportional hazard models assessed the relationship of rate of dose change and NOD, controlling for pain, duration of use, maximum MED, and other confounders using inverse probability of treatment-weighted propensity scores. Incidence rate for NOD was 14.1/1000PY (person-years) in stable rate, 13.0/1000PY in decreasing, 19.3/1000PY in slow increasing, and 27.5/1000PY in rapid increasing dose. Compared with stable rate, risk of NOD increased incrementally for slow (hazard ratio = 1.22; 95% confidence interval: 1.05-1.42) and rapid (hazard ratio = 1.58; 95% confidence interval: 1.30-1.93) rate of dose increase. Faster rates of MED escalation contribute to NOD, independent of maximum dose, pain, and total opioid duration. Dose escalation may be a proxy for loss of control or undetected abuse known to be associated with depression. Clinicians should avoid rapid dose increase when possible and discuss risk of depression with patients if dose increase is warranted for pain.
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- Long-term use of opioids for nonmalignant pain among community-dwelling persons with and without Alzheimer disease in Finland: a nationwide register-based study. [Journal Article]
- PAINPain 2017; 158(2):252-260
- Persons with Alzheimer disease (AD) commonly present with chronic nonmalignant pain, but long-term use of opioids among this population has not been studied previously. Our aim was to investigate the...
Persons with Alzheimer disease (AD) commonly present with chronic nonmalignant pain, but long-term use of opioids among this population has not been studied previously. Our aim was to investigate the prevalence of long-term (≥180 days) use of opioids for nonmalignant pain and associated factors among community-dwelling persons with AD and to compare the prevalence with a matched cohort without AD. The Medication use and Alzheimer's disease (MEDALZ) cohort was used for this study, comprising all community-dwelling persons diagnosed with AD in Finland during 2005 to 2011 and their matched comparison persons without AD. After exclusion of persons with active cancer treatment, 62,074 persons with and 62,074 persons without AD were included in this study. Data were collected from nationwide registers. Opioids were used by 13,111 persons with and by 16,659 without AD. Overall long-term opioid use was more common among persons without AD (8.7%) than among persons with AD (7.2%, P < 0.0001). However, among opioid users, prevalence of long-term opioid use was slightly higher among persons with AD than among those without AD (34.2% vs 32.3%, respectively, P = 0.0004). Long-term use of transdermal opioids was more than 2-fold among opioid users with AD (13.2%) compared with users without AD (5.5%). Factors associated with long-term opioid use included AD, age ≥80 years, female sex, rheumatoid arthritis, osteoporosis, low socioeconomic position, history of substance abuse, and long-term benzodiazepine use. Prevalence of long-term opioid use was somewhat similar among both groups. Among persons with AD, long-term opioid use was strongly associated with transdermal opioids.