Guidance for the pharmacological management of substance misuse among young people.

Until now there has been no formal guidance to help clinicians to manage substance dependence among young people. This has left practitioners concerned that their practice may not accord with the developing evidence base. This guidance document describes good practice on the best ways to manage a clinically complex condition

Prisons and Drugs: A global review of incarceration, drug use and drug services. Report 12

Prisons play an important role in drug policy. They are used to punish people who break drug laws and they also hold a large number of people who have experience of drug use and drug problems. They therefore have an important part to play in attempts to reduce the harm caused by drugs. Imprisonment itself can be seen as one type of harm, as it causes problems for prisoners and their families and creates a large financial burden for taxpayers. Theseharms and costs are difficult to calculate, but there is little evidence that large scale imprisonment of drug offenders has had the desired results in deterring drug use or reducing drug problems (Bewley- Taylor, Trace, & Stevens, 2005). In this paper, we examine the international prevalence of drug users, drug use and related problems in prisons and we report on the problems that are related to the issue of drugs in prison. We go on to examine the international guidelines and effective responses that have been developed in this area in the last decade. The paper is a review of the literature, based on a search of bibliographic databases, including Medline, PubMed, ISI as well as EMBASE and contacts with researchers and practitioners in the field up to January 2007

Microfluidic blood-milk barrier and physiologically based pharmacokinetic model to predict lofexidine secretion into breast milk

Introduction: Lofexidine (LUCEMYRA ®) is the only FDA-approved, non-opioid, non-addictive treatment for opioid withdrawal symptoms, crucial for postpartum and pregnant women affected by the opioid crisis. Despite its clinical importance, data on its secretion into breast milk is limited. This study aims to develop a novel, microfluidic-based blood-milk-barrier on a chip model, a static human mammary cell transwell model, and a physiologically based pharmacokinetic (PBPK) lactation model to estimate the breast milk secretion of lofexidine, thereby ensuring maternal and infant safety and improving withdrawal management. Methods: A novel microfluidic device was developed to build a mammary epithelium-on-a-chip model, and a transwell plate was used to develop a static mammary epithelium using a human noncarcinogenic mammary epithelial cell (MEC) population that can form an integrated barrier with tight junctions. Both models were used to evaluate the transfer of lofexidine through the in vitro mammary cell barrier. The fraction of unbound lofexidine in the breast milk was determined by a Rapid Equilibrium Dialysis (RED) assay. Eleven approaches, including a novel, previously published in vitro to in vivo extrapolation (IVIVE) approach and various other approaches, were used to estimate milk-to-plasma (M/P) ratios of lofexidine. A whole-body lactation PBPK model was built using Simcyp® simulator v22 and used to predict the concentration-time profiles of lofexi-dine in both human plasma and breast milk. Results: A subpopulation of human normal mammary epithelial MCF10A cells (named MCF10A-TJ) was identified to form an integrated barrier that reaches trans-epithelial electrical resistance (TEER) values of over 1000 Ω-cm2 by culturing with in-house designed maintenance and boosting medium. The microfluidic device-based mammary epithelium-on-a-chip model generated slightly higher lofexidine permeability values than the static transwell mammary epithelial cell model. The predicted milk-to-plasma (M/P) ratio of lofexidine ranged from 0.40 to 15.88. Four approaches estimated an M/P ratio below 1, while seven predicted values above 1, mostly between 1.35 and 5.48. The whole-body lactation PBPK model predicted the concentration-time profile of lofexidine in breast milk, with an estimated M/P ratio of approximately 2.0. This value falls within the mid-range of the predictions obtained from all eleven methods. Conclusion: This study introduces comprehensive and novel approaches to predict lofexidine secretion into breast milk. Most predictions suggest higher lofexidine concentration in milk than in plasma, raising potential safety concerns for opioid withdrawal management. Further pharmacokinetic clinical lactation studies are needed to validate these predictions

Treatment of Opiate Abuse: Increasing Patient Self-Efficacy and Engagement in Treatment Through Education of Providers

Opiate abuse is one of the fastest growing public health concerns in the United States and has far reaching ramifications that effect individual patients and their families, communities, and the healthcare system (U.S. Department of Justice National Drug Intelligence Center, 2010). It has been shown that there is significant gap in knowledge among healthcare providers surrounding the topic of opiate abuse and dependence as well as the available pharmacologic treatments that are available to help relieve withdrawal as well as help maintain heal truer lifestyles. In addition to this lack in knowledge there appears to be a gap in recognizing and addressing th.is issue with patients (National Center on Addiction and Substance Abuse, 2000 & Hoffman & Heinemann, 1987). Several studies have shown that self-efficacy is a strong determinant in predicting outcomes of persons with addiction problems and that the use of pharmacologic intervention has increased self-efficacy (Hser, 2007, Rielly, Sees et.al., 1995, & Barta, Kurth, Stein, Tennen, and Kiene, 2009). This project proposes that enhancing the education of healthcare providers in truss area will be enable providers to provide better care. This, in tum will help opiate dependent patients manage their addiction and by doing so decrease the ill effects of this disease. Provided in this paper is an overview of opiate use in the United States and how this use effects our patients and the healthcare system, a brief explanation of the cellular physiology involved in opiate dependence and withdrawal, a discussion of how Bandura\u27s self-efficacy theory is related to opiate use and its treatment, and a comprehensive literature review of pharmacologic treatments available to treat opiate addiction

Exploring Novel Pharmacotherapy Candidates for Cannabis Use Disorder: Uncovering Promising Agents on the Horizon by Mechanism of Action

With rapid expansion of cannabis legalization worldwide, rates of cannabis use and cannabis use disorder (CUD) are increasing; the need for safe and effective medications to treat CUD is urgent. This narrative review evaluates evidence for promising pharmacotherapies to treat CUD from randomized, placebo-controlled trials. Pharmacotherapies for CUD are categorized based on compound targets (e.g., cannabinoid receptor 1 [CB1] agonists such as nabilone, serotonergic compounds such as bupropion, GABAergic compounds such as zolpidem) and outcomes are organized by predetermined withdrawal symptoms, cannabis craving, and cannabis relapse/use. Most promising pharmacotherapies for CUD are drugs that act on the endocannabinoid system and specifically at the CB1 receptor. Priority populations such as females, certain racial/ethnic groups, and age groups experience a different course of CUD progression, symptoms, and drug effects that are important to consider when evaluating outcomes related to CUD. Possible explanations for these disparities are explored, along with the clinical trials that explore these demographics in treating CUD with pharmacotherapies

Recent Changes in Drug Abuse Scenario: The Novel Psychoactive Substances (NPS) Phenomenon

copyright 2019 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND.Final Published versio

Pharmacotherapies for treatment of opioid use disorder: a narrative review and cost-effectiveness analysis

Opioid use disorder (OUD) has become a global concern with the rapid increase in the use of illicit and prescription opioids. North America is in the midst of the opioid crisis, which requires effective (both clinically and economically) treatment interventions. Several evidence-based treatment options are available for the treatment of OUD. However, little is known about patients’ perspectives on the pharmacotherapies used for OUD treatment. Additionally, with the advent of novel and more expensive treatment options, an economic evaluation against conventional treatment is warranted. The aim of this thesis is two-fold: first, to conduct a narrative review of patients’ perceptions and experiences with OUD pharmacotherapies and second, to compare the cost-effectiveness of the newer pharmacotherapies with conventional treatments. The thesis follows a manuscript style with the following chapters: Chapter 1 provides an introduction; Chapter 2 provides a narrative review of patients’ perceptions and experiences with the pharmacotherapies for OUD treatment; Chapter 3 is the cost-effectiveness analysis of the newer pharmacotherapies compared against the usual treatment; and, Chapter 4 concludes. In the narrative review, we conducted a systematic search of relevant literature on patients’ perceptions and experiences with OUD pharmacotherapies. The data are coded to develop overarching themes. The findings are narratively described under these themes for the outcomes of perceptions and experiences. We critically appraised the included studies to assess their quality. We found evidence of both patient-reported positive and negative aspects of the treatments. Other key findings of this review study are lack of patient knowledge on the available treatment options, many patients seeking harm reduction treatment strategy with opioid agonist treatment (OAT), while others seeking abstinence-based treatment interventions, and the role of patient inclusive treatment decisions to optimize treatment outcomes. In the cost-effectiveness study, we compared five treatment strategies using the US healthcare perspective: 1) methadone-lofexidine for detoxification and buprenorphine-naloxone for maintenance; 2) methadone-lofexidine for detoxification and extended-release naltrexone for maintenance; 3) buprenorphine-naloxone for detoxification and extended-release buprenorphine for maintenance; 4) buprenorphine-naloxone for detoxification and maintenance (i.e., usual treatment); and, 5) no treatment. Effectiveness outcomes are presented in quality-adjusted life-years (QALYs), treatment retention and opioid-free days. Detoxification with methadone-lofexidine and subsequent buprenorphine-naloxone maintenance yield greater effectiveness than usual treatment but are not cost-effective at the willingness-to-pay threshold of US$100,000 per QALY gained due to the high cost of lofexidine. Usual treatment with buprenorphine-naloxone is found to be cost-effective at the conventional willingness-to-pay threshold

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse