IUPHAR Review: New strategies for medications to treat substance use disorders.

Substance use disorders (SUDs) and drug overdose are a public health emergency and safe and effective treatments are urgently needed. Developing new medications to treat them is expensive, time-consuming, and the probability of a compound progressing to clinical trials and obtaining FDA-approval is low. The small number of FDA-approved medications for SUDs reflects the low interest of pharmaceutical companies to invest in this area due to market forces, characteristics of the population (e.g., stigma, and socio-economic and legal disadvantages), and the high bar regulatory agencies set for new medication approval. In consequence, most research on medications is funded by government agencies, such as the National Institute on Drug Abuse (NIDA). Multiple scientific opportunities are emerging that can accelerate the discovery and development of new medications for SUDs. These include fast and efficient tools to screen new molecules, discover new medication targets, use of big data to explore large clinical data sets and artificial intelligence (AI) applications to make predictions, and precision medicine tools to individualize and optimize treatments. This review provides a general description of these new research strategies for the development of medications to treat SUDs with emphasis on the gaps and scientific opportunities. It includes a brief overview of the rising public health toll of SUDs; the justification, challenges, and opportunities to develop new medications; and a discussion of medications and treatment endpoints that are being evaluated with support from NIDA.

Evaluation of the New England Office Based Addiction Treatment ECHO: A Tool for Strengthening the Addiction Workforce.

INTRODUCTION: Reducing substance-related morbidity requires an educated and well-supported workforce. The New England Office Based Addiction Treatment Extension for Community Healthcare Outcomes (NE OBAT ECHO) began in 2019 to support community-based addiction care teams through virtual mentoring and case-based learning. We sought to characterize the program's impact on the knowledge and attitudes of NE OBAT ECHO participants. METHODS: We conducted an 18-month prospective evaluation of the NE OBAT ECHO. Participants registered for 1 of 2 successive ECHO clinics. Each 5-month clinic included ten 1.5-hour sessions involving brief didactic lectures and de-identified patient case presentations. Participants completed surveys at Month-0, -6, -12, and -18 to assess attitudes about working with patients who use drugs and evidence based practices (EBPs), stigma toward people who use drugs, and addiction treatment knowledge. We compared outcomes using 2 approaches: (i) between-groups, which involved comparing the first intervention group to the delayed intervention (comparison) group, and (ii) within-groups, which involved comparing outcomes at different time points for all participants. In the within-group approach, each participant acted as their own control. RESULTS: Seventy-six health professionals participated in the NE OBAT ECHO, representing various roles in addiction care teams. Approximately half (47% [36/76]) practiced primary care, internal, or family medicine. The first intervention group reported improved job satisfaction and openness toward EBPs compared to the delayed intervention group. Within-group analyses revealed that ECHO participation was associated with increased positive perceptions of role adequacy, support, legitimacy, and satisfaction 6 months following program completion. No changes were identified in willingness to adopt EBPs or treatment knowledge. Stigma toward people who use drugs was persistent in both groups across time points. CONCLUSIONS: NE OBAT ECHO may have improved participants' confidence and satisfaction providing addiction care. ECHO is likely an effective educational tool for expanding the capacity of the addiction workforce.

Randomized Trial of Reduced-Nicotine Standards for Cigarettes.

BACKGROUND: The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS: We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. RESULTS: A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. CONCLUSIONS: In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.).

A Survey of Payer Perspectives on Cannabis Use Disorder.

BACKGROUND: Cannabis use disorder (CUD) as described/defined in DSM 5, is characterized by impaired control of marijuana use and related personal, health, and legal consequences. CUD is a serious public health problem, affecting nearly 6 million individuals in the United States. There are no FDA approved medications to treat this disorder. The lack of available treatment options contributes to uncertainties by drug sponsors about formulary and reimbursement decision-making for CUD pharmacotherapies. OBJECTIVE: To addresses this gap by presenting the first findings on managed care payers' perceptions of CUD treatments and clinical trial end points. METHODS: An online survey was conducted with 50 payers from managed care organizations. The survey inquired about perceptions of unmet need in CUD treatment, relevant clinical trial end points, disease knowledge, and likelihood of review of new pharmacotherapies. RESULTS: The majority of payers (62%) reported that they were at least moderately familiar with CUD treatment end points. Most (80%) rated the unmet need for new pharmacotherapies for CUD as at least moderately important. Payers rated the most important end points for clinical trials as abstinence and decreased resource utilization. Most participants said an FDA approved CUD treatment would be formally reviewed by payers within 6 months (58%) or a year (36%). CONCLUSIONS: Based on these findings, payers see an unmet need for CUD treatment. Furthermore, FDA-approved pharmacotherapies for CUD will likely be reviewed quickly by payers, especially if data are provided on the likelihood of achieving abstinence and reduced resource utilization.

Optical and Electrical Properties of TTF-MPcs (M = Cu, Zn) Interfaces for Optoelectronic Applications.

Sandwich structures were fabricated by a vacuum deposition method using MPc (M = Cu, Zn), with a Tetrathiafulvalene (TTF) derivative, and Indium Tin Oxide (ITO) and aluminum electrodes. The structure and morphology of the deposited films were studied by IR spectroscopy, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The absorption spectra of TTF derivative-MPc (M = Cu, Zn) thin films deposited at room temperature were recorded in the spectral range 200-1000 nm. The optical band gap of the thin films was determined from the (αhν)(1/2) vs. hν plot. The direct-current (DC) electrical properties of the glass/ITO/TTFderiv-MPc (M = Cu, Zn)/Al structures were also investigated. Changes in conductivity of the derivative-TTF-enriched Pc compounds suggest the formation of alternative paths for carrier conduction. At low voltages, forward current density obeys an ohmic I-V relationship; at higher voltages, conduction is mostly due to a space-charge-limited conduction (SCLC) mechanism.

Effect of pH on hydroxyapatite coatings obtained by spray pyrolysis and their use as matrices for antibiotic adsorption by spin coating and release properties.

Calcium phosphate materials, particularly hydroxyapatite (HA), are extensively used in biomedical applications because of their prominence as primary inorganic constituents of human hard tissues. This study investigates the synthesis of HA coatings via spray pyrolysis using various precursors, including HA derived from bovine bone. The effects of pH on the formation and properties of HA coatings were systematically examined. Samples exposed to acidic conditions or left without pH adjustment led to the formation of HA, contrasting with the outcomes observed through dissolution methods. Different characterization techniques, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD), were employed to evaluate the quality and crystallinity of the coatings. Among the samples, those exhibiting superior crystallinity and nanostructured features, including bovine HA, were selected for further surface functionalization with the antibiotic enrofloxacin using spin coating. As expected, the antibiotic loading on each material's surface depended on the amount of HA deposited on the substrate. However, the desorption results indicated that, in all cases, desorption persisted beyond 38 h, implying that HA-loaded matrices could be effective systems for controlled and prolonged drug release, which could be useful in dental or orthopedic implants for inhibiting the growth of bacterial biofilms.

Cost of start-up activities to implement a community-level opioid overdose reduction intervention in the HEALing Communities Study.

BACKGROUND: Communities That HEAL (CTH) is a novel, data-driven community-engaged intervention designed to reduce opioid overdose deaths by increasing community engagement, adoption of an integrated set of evidence-based practices, and delivering a communications campaign across healthcare, behavioral-health, criminal-legal, and other community-based settings. The implementation of such a complex initiative requires up-front investments of time and other expenditures (i.e., start-up costs). Despite the importance of these start-up costs in investment decisions to stakeholders, they are typically excluded from cost-effectiveness analyses. The objective of this study is to report a detailed analysis of CTH start-up costs pre-intervention implementation and to describe the relevance of these data for stakeholders to determine implementation feasibility. METHODS: This study is guided by the community perspective, reflecting the investments that a real-world community would need to incur to implement the CTH intervention. We adopted an activity-based costing approach, in which resources related to hiring, training, purchasing, and community dashboard creation were identified through macro- and micro-costing techniques from 34 communities with high rates of fatal opioid overdoses, across four states-Kentucky, Massachusetts, New York, and Ohio. Resources were identified and assigned a unit cost using administrative and semi-structured-interview data. All cost estimates were reported in 2019 dollars. RESULTS: State-level average and median start-up cost (representing 8-10 communities per state) were $268,657 and $175,683, respectively. Hiring and training represented 40%, equipment and infrastructure costs represented 24%, and dashboard creation represented 36% of the total average start-up cost. Comparatively, hiring and training represented 49%, purchasing costs represented 18%, and dashboard creation represented 34% of the total median start-up cost. CONCLUSION: We identified three distinct CTH hiring models that affected start-up costs: hospital-academic (Massachusetts), university-academic (Kentucky and Ohio), and community-leveraged (New York). Hiring, training, and purchasing start-up costs were lowest in New York due to existing local infrastructure. Community-based implementation similar to the New York model may have lower start-up costs due to leveraging of existing infrastructure, relationships, and support from local health departments.

Economic benefits of substance use disorder treatment: A systematic literature review of economic evaluation studies from 2003 to 2021.

INTRODUCTION: The economic burden of substance use disorder (SUD) is significant, comprising costs of health care and social services, criminal justice resources, loss of productivity, and premature mortality. This study assembles and synthesizes two decades of evidence describing the benefits of SUD treatment across five main outcome domains; 1) health care utilization; 2) self-reported criminal activity by offense type; 3) criminal justice involvement collected from administrative records or self-reported; 4) productivity assessed through working hours or wages earned; and 5) social services (e.g., a day spent in transitional housing). METHODS: This review included studies if they reported the monetary value of the intervention outcomes, most commonly through a cost-benefit or cost-effectiveness framework. The search included studies from 2003 to the present day as of this writing (up to October 15, 2021). Summary cost estimates were adjusted using the US Consumer Price Index (CPI) to reflect the 12-month benefits per client in USD 2021. We followed the PRISMA methodology for study selection and assessed quality using the Checklist for Health Economic Evaluation Reporting Standards (CHEERS). RESULTS: The databases yielded 729 studies after removing duplicates, and we ultimately selected 12 for review. Studies varied widely regarding analytical approaches, time horizons, outcome domains, and other methodological factors. Among the ten studies that found positive economic benefits, reductions in criminal activity or criminal justice costs represented the largest or second largest component of these benefits (range $621 to $193,440 per client). CONCLUSIONS: Consistent with previous findings, a reduction in criminal activity costs is driven by the relatively high societal cost per criminal offense, notably for violent crimes, such as aggravated assault and rape/sexual assault. Accepting the economic rationale for increased investment in SUD interventions will require recognizing that more benefits accrue to individuals by avoiding being victims of a crime than to governments through budget offsets resulting from savings in non-SUD program expenses. Future studies should explore individually tailored interventions to optimize care management, which may yield unexpected economic benefits to services utilization, and criminal activity data to estimate economic benefits across a broad range of interventions.

Budget impact tool for the incorporation of medications for opioid use disorder into jail/prison facilities.

BACKGROUND: Given the personal and public consequences of untreated/undertreated OUD among persons involved in the justice system, an increasing number of jails and prisons are incorporating medication for opioid use disorder (MOUD) into their system. Estimating the costs of implementing and sustaining a particular MOUD program is vital to detention facilities, which typically face modest, fixed health care budgets. We developed a customizable budget impact tool to estimate the implementation and sustainment costs of numerous MOUD delivery models for detention facilities. METHODS: The aim is to describe the tool and present an application of a hypothetical MOUD model. The tool is populated with resources required to implement and sustain various MOUD models in detention facilities. We identified resources via micro-costing techniques alongside randomized clinical trials. The resource-costing method is used to assign values to resources. Resources/costs are categorized as (a) fixed, (b) time-dependent, and (c) variable. Implementation costs include (a), (b), and (c) over a specified timeframe. Sustainment costs include (b) and (c). The MOUD model example entails offering all three FDA-approved medications, with methadone and buprenorphine provided by vendors, and naltrexone by the jail/prison facility. RESULTS: Fixed resources/costs are incurred only once, including accreditation fees and trainings. Time-dependent resources/costs are recurring, but fixed over a given time-period; e.g., medication delivery and staff meetings. Variable resources/costs are those that are a direct function of the number of persons treated, such as the medication provided to each patient. Using nationally representative prices, we estimated fixed/sustainment costs to be $2919/patient, over 1 year. This article estimates annual sustainment costs to be $2885/patient. CONCLUSION: The tool will serve as a valuable asset to jail/prison leadership, policymakers, and other stakeholders interested in identifying/estimating the resources and costs associated with alternative MOUD delivery models, from the planning stages through sustainment.

Selegiline transdermal system (STS) as an aid for smoking cessation.

INTRODUCTION: This study examined the efficacy and safety of selegiline transdermal system (STS) and brief repeated behavioral intervention (BRBI) for smoking cessation in heavy smokers. We hypothesized that the quit rate of subjects who received STS and BRBI would be significantly greater than that of those who received placebo patch and BRBI. METHODS: This was a double-blind, placebo-controlled parallel-group study in which 246 men and women were randomized to receive either STS (n = 121) or placebo patch (n =125) for 9 weeks. Recruitment targeted heavy smokers, defined as individuals with self-reported use of ≥15 cigarettes/day in the 30 days prior to enrollment, who had smoked cigarettes for the past 5 years, and had an expired CO level ≥9 ppm during screening. RESULTS: Although STS was well tolerated, the overall results indicated that STS with BRBI was not more effective than placebo plus BRBI for smoking cessation (p = .58). CONCLUSIONS: The results are discussed in relation to interventions for heavy smokers. Although 2 trials using oral selegiline both showed trends toward improved abstinence, these results indicate that STS with BRBI was not an effective aid for smoking cessation at the end of treatment (10 weeks), 14, or 26 weeks.

Advances in the development of biologics to treat drug addictions and overdose.

Drug addictions are complex disorders that require multiple approaches, including the use of pharmacotherapies. Currently, these therapies are based on "small" molecules or chemicals that penetrate the blood-brain barrier, reach the brain, and produce their effects on neurotransmitter systems. Unfortunately, they often do not have the desired efficacy or may cause undesirable side effects, especially at the central nervous system (CNS) level. A novel approach is the use of biologics to treat drug addictions. Biologics are usually complex and "large" molecules, which do not cross the blood-brain barrier and, thus, have no CNS effects. In principle, it appears that the efficacy of biologics to treat drug addiction is by preventing the access of the drug of abuse to the brain, preventing the activation of brain reward systems, and eventually producing the extinction of addiction. Biologic therapeutics includes immunotherapies, such as vaccines or antibodies, as well as enzymes. New products as well as new and more efficient methods of production, are offering vast opportunities to advance the discovery and development of biologics to treat addictions as well as drug overdose. These products include new vaccines with greater specificity and ability to produce antibodies, new methods and techniques to produce vaccines and antibodies, as well as new enzymes with high efficiency to metabolize cocaine. The purpose of the article is to provide a general overview of the development of biologics for the treatment of drug addictions and overdose.

Casiopeinas® third generation, with indomethacin: synthesis, characterization, DFT studies, antiproliferative activity, and nanoencapsulation.

Seven new Casiopeinas® were synthesized and properly characterized. These novel compounds have a general formula [Cu(N-N)(Indo)]NO3, where Indo is deprotonated indomethacin and N-N is either bipyridine or phenanthroline with some methyl-substituted derivatives, belonging to the third generation of Casiopeinas®. Spectroscopic characterization suggests a square-based pyramid geometry and voltammetry experiments indicate that the redox potential is strongly dependent on the N-N ligand. All the presented compounds show high cytotoxic efficiency, and most of them exhibit higher efficacy compared to the well-known cisplatin drug and acetylacetonate analogs of the first generation. Computational calculations show that antiproliferative behavior can be directly related to the volume of the molecules. Besides, a chitosan (CS)-polyacrylamide (PNIPAAm) nanogel was synthesized and characterized to examine the encapsulation and release properties of the [Cu(4,7-dimethyl-1,10-phenanthroline)(Indo)]NO3 compound. The results show good encapsulation performance in acidic conditions and a higher kinetic drug release in acidic media than at neutral pH. This result can be described by the Peppas-Sahlin model and indicates a release mechanism predominantly by Fick diffusion.

Health economic analyses of the justice community opioid innovation network (JCOIN).

The Justice Community Opioid Innovation Network (JCOIN) will generate real-world evidence to address the unique needs of people with opioid use disorder (OUD) in justice settings. Evidence regarding the economic value of OUD interventions in justice populations is limited. Moreover, the variation in economic study designs is a barrier to defining specific interventions as broadly cost-effective. The JCOIN Health Economics Analytic Team (HEAT) has worked closely with the Measures Committee to incorporate common economic measures and instruments across JCOIN studies, which will: a) ensure rigorous economic evaluations within each trial; b) enhance comparability of findings across studies; and c) allow for cross-study analyses of trials with similar designs/settings (e.g., pre-reentry MOUD), to assess questions beyond the scope of a single study, while controlling for and evaluating the effect of intervention-, organizational-, and population-level characteristics. We describe shared trial characteristics relevant to the economic evaluations, and discuss potential cross-study economic analyses.

Drugs of abuse: management of intoxication and antidotes.

Illicit drug intoxications are an increasing public health problem for which, in most cases, no antidotes are clinically available. The diagnosis and treatment of these intoxications requires a trained clinician with experience in recognizing the specific signs and symptoms of intoxications to individual drugs as well as polydrug intoxications, which are more the rule than the exception. To make the diagnosis, the clinical observation and a urine toxicology test are often enough. Evaluating the blood levels of drugs is frequently not practical because the tests can be expensive and results may be delayed and unavailable to guide the establishment of a treatment plan. Other laboratory tests may be useful depending on the drug or drugs ingested and the presence of other medical complications. The treatment should be provided in a quiet, safe and reassuring environment. Vital signs should be closely monitored. Changes in blood pressure, respiratory frequency and temperature should be promptly treated, particularly respiratory depression (in cases of opiate intoxication) or hyperthermia (in cases of cocaine or amphetamine intoxication). Intravenous fluids should be administered as soon as possible. Other psychiatric and medical complication should receive appropriate symptomatic treatment. Research on immunotherapies, including vaccines, monoclonal and catalytic antibodies, seems to be a promising approach that may yield specific antidotes for drugs of abuse, helping to ameliorate the morbidity and mortality associated with illicit drug intoxications.

The state of clinical outcome assessments for cannabis use disorder clinical trials: A review and research agenda.

There is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding optimal outcomes may have hindered development and approval of new pharmacotherapies. The goal of this paper is to summarize an evaluation of assessment measures and clinical endpoints for CUD clinical trials, and propose a research agenda and priorities to improve CUD clinical outcome assessments. The primary recommendation is that sustained abstinence from cannabis should not be considered the primary outcome for all CUD clinical trials as it has multiple limitations. However, there are multiple challenges to the development of a reliable and valid indicator of cannabis reduction, including the lack of a standard unit of measure for the various forms of cannabis and products and the limitations of currently available biological and self-report assessments. Development of a core toolkit of assessments is needed to both allow flexibility for study design, while facilitating interpretation of outcomes across trials. Four primary agenda items for future research are identified to expedite development of improved clinical outcome assessments for this toolkit: (1) determine whether minimally invasive biologic assays could identify an acute level of cannabis use associated with psychomotor impairment or other cannabis-related harms; (2) create an indicator of quantity of cannabis use that is consistent across product types; (3) examine the presence of cannabis-specific functional outcomes; and (4) identify an optimal duration to assess changes in CUD diagnostic criteria.

Genome-wide association for nicotine dependence and smoking cessation success in NIH research volunteers.

Phenotypes related to both nicotine dependence and ability to successfully quit smoking display substantial heritabilities in classical and molecular genetic studies. Twin studies suggest that some genetic components for dependence overlap with genetic components of ability to quit, but that many components do not overlap. Initial genome-wide association (GWA) studies have demonstrated haplotypes that distinguish nicotine-dependent from nondependent smokers. These haplotypes overlap partially with those that distinguish individuals who successfully quit smoking from those who were not able to quit smoking in clinical trials for smoking cessation. We now report novel genome-wide association results from National Institutes of Health research volunteers who reported smoking histories, symptoms of nicotine dependence, and ability to successfully quit smoking outside the context of a clinical trial. These results buttress data from several prior GWA studies. The data from these volunteers support the idea that previously reported studies of genes associated with smoking cessation success in clinical trial participants may also apply to smokers who are more or less able to initiate and sustain abstinence outside of clinical trial settings.

Craving and opioid use disorder: A scoping review.

INTRODUCTION: The subjective experience of drug craving is a prominent and common clinical phenomenon for many individuals diagnosed with opioid use disorder (OUD), and could be a valuable clinical endpoint in medication development studies. The purpose of this scoping review is to provide an overview and critical analysis of opioid craving assessments located in the published literature examining OUD. METHOD: Studies were identified through a search of PubMed, Embase, and PsychInfo databases and included for review if opioid craving was the focus and participants were diagnosed with or in treatment for OUD. RESULTS: Fifteen opioid craving assessment instruments were identified across the 87 studies included for review. The most common were the Visual Analog Scale (VAS, 41 studies), Desires for Drug Questionnaire (DDQ, 12 studies), Heroin Craving Questionnaire (HCQ, 10 studies), and Obsessive-Compulsive Drug Use Scale (OCDUS, 10 studies). Craving assessments varied considerably in their format, content, time frame, and underlying subscales, and only 6 of 15 had been psychometrically evaluated. DISCUSSION: This review identified a variety of opioid craving assessments, but few had been evaluated for their psychometric properties making it difficult to ascertain whether craving is being assessed optimally in studies of OUD. Thus, the development of a reliable and valid opioid craving assessment would be worthwhile and could be guided by recently published Food and Drug Administration Clinical Outcome Assessment (COA) guidelines. Importantly, a COA focused on opioid craving could be a valuable addition to research studies designed to evaluate novel treatments for OUD.

A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.

CONTEXT: Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. OBJECTIVE: To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. DESIGN: An inpatient, Phase 3, placebo-controlled, double-blind, randomized multi-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (days 4-8), and (3) post detoxification/medication phase (days 9-11). SUBJECTS: Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. MAIN OUTCOME MEASURE: Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day). RESULTS: Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5+/-2.1 versus 30.9+/-2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). CONCLUSIONS: Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification.

Novel medications to treat addictive disorders.

Recent discoveries about the effects of drugs of abuse on the brain and the mechanisms of their addictions; new chemical compounds, including immunotherapies; and new actions of available medications are offering many opportunities for the discovery and development of novel medications to treat addictive disorders. Furthermore, advancements in the understanding of the genetic and epigenetic basis of drug addiction and the pharmacogenetics of the safety and/or efficacy of the medications are providing opportunities for more individualized pharmacotherapy approaches. Although multiple medications have been investigated for treating addictions, only a handful have shown acceptable safety and efficacy and are approved by the US Food and Drug Administration. This article reviews the current medications that are medically safe and have shown promising results for treating opioid, cocaine, methamphetamine, and cannabis addictions.