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Alcohol abuse and dependence, referred to as alcohol-use disorders (AUDs), affect 76.3 million people worldwide and account for 1.8 million deaths per year. AUDs affect 18.3 million Americans (7.3% of the population), and up to 40% of hospitalized patients have AUDs. This review discusses the development and progression of critical illness in patients with AUDs. In contrast to acute intoxication, AUDs have been linked to increased severity of illness in a number of studies. In particular, surgical patients with AUDs experience higher rates of postoperative hemorrhage, cardiac complications, sepsis, and need for repeat surgery. Outcomes from trauma are worse for patients with chronic alcohol abuse, whereas burn patients who are acutely intoxicated may not have worse outcomes. AUDs are linked to not only a higher likelihood of community-acquired pneumonia and sepsis but also a higher severity of illness and higher rates of nosocomial pneumonia and sepsis. The management of sedation in patients with AUDs may be particularly challenging because of the increased need for sedatives and opioids and the difficulty in diagnosing withdrawal syndrome. The health-care provider also must be watchful for the development of dangerous agitation and violence, as these problems are not uncommonly seen in hospital ICUs. Despite studies showing that up to 40% of hospitalized patients have AUDs, relatively few guidelines exist on the specific management of the critically ill patient with AUDs. AUDs are underdiagnosed, and a first step to improving patient outcomes may lie in systematically and accurately identifying AUDs. [ABSTRACT FROM AUTHOR] more...

Objective: To explore prevalence of aberrant medication-taking behaviors (AMTB) among headache patients and treating physician's awareness of such behaviors. Methods: Fifty patientphysician dyads were surveyed on patients' AMTB. Results: The most frequently endorsed behaviors by patients and physicians, respectively, were going to the ER for pain medication (n = 19) and continuing to take pain medication despite minimal relief (n = 23). For the majority of AMTB, phi coefficients indicating level of patient-physician agreement were equal to chance. Conclusions: Headache patients perform a wide range of AMTB. Low rates of patient-physician agreement indicate that physicians possess limited knowledge of patients' AMTB. [ABSTRACT FROM AUTHOR] more...

Studies show that symptom-triggered dosing is best for treatment of alcohol withdrawal in patients on chemical dependence wards without other illness. On general medical hospital wards, withdrawal may be affected by comorbid medical illness. A clinical trial was undertaken to determine whether there is a difference between symptom-triggered (ST) and fixed-schedule (FS) dosing of lorazepam in patients hospitalized on general medical wards at a university medical center. One hundred eighty-three subjects were assessed by their nurses with the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. Subjects in the ST arm received lorazepam doses based on CIWA-Ar score. Subjects in the FS arm received scheduled lorazepam with tapering over 4 days. Symptom-triggered dosing for alcohol withdrawal for general medicine inpatients results in less lorazepam given with similar reduction in CIWA-Ar scores for the first 2 days, but a higher proportion of protocol errors. [ABSTRACT FROM AUTHOR] more...

OBJECTIVES: To assess hepatitis C virus (HCV) serostatus, risk factors, and desire for education about HCV among methadone maintenance treatment (MMT) patients. METHODS: We surveyed 200 MMT patients and reviewed charts for 276 patients. RESULTS: The self-report HCV seroprevalence was 34%, adjusted to 52%. The chart review HCV seroprevalence was 70%. Most participants had risk factors for contracting or spreading HCV. CONCLUSIONS: There is discrepancy in HCV seroprevalence by self-report versus serum test results among MMT patients. Some HCV+ MMT patients engage in high-risk behaviors for HCV transmission and may not disclose HCV+ status. MMT patients want HCV education. [ABSTRACT FROM AUTHOR] more...

Patients with a history of drug or alcohol addiction may present to physicians with pain complaints. The medical literature is weak on the treatment of pain with opioids in patients in recovery or active addiction. This is because inconsistent criteria were used to define addiction and the types of chronic pain. There are clear differences between physical dependence, tolerance, and addiction. Addiction is different from pseudoaddiction and must be determined by the patient's behavior after appropriate pain management. Long-acting opioids are often the medications of choice for moderate to severe pain control. Short-acting opioids can be used for breakthrough pain. There are many other medications that can enhance pain control as adjunctive analgesics. Drug-seeking behavior may be seen with either active addiction or pseudoaddiction, or as part of deviant behavior such as drug diversion. A way to distinguish between these conditions is by giving the patient appropriate pain medication and observing the pattern of behavior to determine which is causing the drug-seeking behavior. Safe prescribing of medications with abuse potential includes use of a medication agreement, setting goals with the patient, giving appropriate amounts of pain medication, monitoring with pill counts and drug screens, and careful documentation. Even patients with a history of addiction can benefit from opioid pain medications if monitored appropriately. [ABSTRACT FROM AUTHOR] more...

Abstract: Despite the decline in the prevalence of e-cigarette use among youth during the coronavirus disease 2019 pandemic, more than 2.5 million of US high and middle schoolers are still using e-cigarettes. Furthermore, those who use e-cigarettes are starting at a younger age and are using them more intensely, reflecting, at least in part, a high addiction liability of modern e-cigarettes. Beyond addiction, accumulating evidence suggests that, in the short-term, e-cigarettes are associated with cardiovascular and pulmonary effects, whereas the long-term effects of e-cigarette use are yet to be established. The aim of this review is to synthesize current knowledge on e-cigarette use among youth, including established and potential risks and efforts to date to curb youth exposure to e-cigarettes. In addition, we provide recommendations for health care providers, researchers, and other stakeholders to address this significant public health issue., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.) more...

Background: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1., Method: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists., Results: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed., Discussion: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.) more...

Introduction: Methamphetamine (MA) use is marked by high rates of comorbid tobacco smoking, which is associated with more severe drug use and worse clinical outcomes compared to single use of either drug. Research has shown the combination of naltrexone plus oral bupropion (NTX-BUP) improves smoking cessation outcomes in non-MA-using populations. In the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) study, NTX-BUP successfully reduced MA use. Our aim in this secondary data analysis was to examine changes in cigarette smoking among the subgroup of participants reporting comorbid tobacco use in the ADAPT-2 trial., Methods: The multi-site ADAPT-2 study used a randomized, double blind, sequential parallel comparison design to evaluate treatment with extended-release injectable NTX (380 mg every 3 weeks) combined with once-daily oral extended-release BUP (450 mg/day) vs matching injectable and oral placebo in outpatients with moderate or severe MA use disorder. The study assessed smoking outcomes, based on self-reported timeline followback (TLFB) data, twice/week for 13 weeks., Results: Of the 403 participants in the ADAPT-2 trial, 290 reported being current cigarette smokers (71.9 %). The study found significant differences (p's < 0.0001) for each smoking outcome indicating greater change in the proportion of nonsmoking days, number of cigarettes smoked per week, and consecutive nonsmoking days, all favoring the group receiving NTX-BUP versus placebo., Conclusions: NTX-BUP was associated with significant reductions in self-reported cigarette smoking in the context of concurrent treatment for MA use disorder. These off-target medication effects warrant prospective investigation using biochemically confirmed measures of smoking abstinence. The development of NTX-BUP as a co-addiction treatment strategy has a potential for high public health impact., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Madhukar Trivedi: Within the past 12 months, Dr. Trivedi has provided consulting services to Axsome Therapeutics, Biogen MA Inc., Cerebral Inc., Circular Genomics Inc, Compass Pathfinder Limited, Daiichi Sankyo Inc, GH Research Limited, Heading Health Inc, Janssen, Legion Health Inc, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc, Merck Sharp & Dhome LLC, Naki Health, Ltd., Neurocrine Biosciences Inc, Otsuka American Pharmaceutical Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Praxis Precision Medicines Inc, Relmada Therapeutics, Inc, SAGE Therapeutics, Signant Health, Sparian Biosciences Inc, Takeda Pharmaceutical Company Ltd, and WebMD. He sits on the Scientific Advisory Board of Alto Neuroscience Inc, Cerebral Inc., Compass Pathfinder Limited, Heading Health, GreenLight VitalSign6 Inc, Legion Health Inc, and Merck Sharp & Dohme Corp. He holds stock in Alto Neuroscience Inc, Cerebral Inc, Circular Genomics Inc, GreenLight VitalSign6 Inc, Legion Health Inc. Additionally, he has received editorial compensation from American Psychiatric Association, and Oxford University Press. Dr. Thomas Carmody: Dr. Carmody has served as a consultant for Alkermes, Inc. Dr. Stephen Shoptaw: Dr. Shoptaw has received clinical supplies for this research from Alkermes, Inc., (Copyright © 2023. Published by Elsevier Inc.) more...

Cocaine use remains a serious public health problem associated with a marked increase in overdose deaths in the past decade. No medications have yet been proven to be effective for the treatment of cocaine use disorder (CUD). Among the highly promising medications have been glucagon-like peptide 1 receptor agonists (GLP-1RA) that are currently used for the treatment of type 2 diabetes mellitus and weight management. Preclinically, GLP-1RAs have been shown to attenuate cocaine self-administration, however, this has not yet been demonstrated in a human laboratory study. The GLP-1RA extended-release exenatide is given as a once-weekly injection, which may be clinically advantageous for addressing medication nonadherence among individuals with CUD. Here, we assess feasibility and safety by reporting on 3 cases of patients with CUD who received 6 weeks of exenatide 2 mg subcutaneously once-weekly in an open-label fashion, along with standard individual drug counseling. We observed excellent attendance and compliance, along with positive end-of-study satisfaction ratings. The medication was well tolerated and without unexpected or severe adverse events. Results for cocaine use and related clinical effects were more mixed, yet encouraging. Future empirical testing of exenatide for treating CUD should utilize a randomized controlled trial design and longer treatment duration., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.) more...

Introduction: Obesity and smoking are the two leading causes of preventable death in the USA. Unfortunately, most smokers gain weight after quitting. Postcessation weight gain (PCWG) is frequently cited as one of the primary barriers to a quit attempt and a common cause of relapse. Further, excessive PCWG may contribute to the onset or progression of metabolic conditions, such as hyperglycaemia and obesity. The efficacy of the current treatments for smoking cessation is modest, and these treatments have no clinically meaningful impact on mitigating PCWG. Here, we outline a novel approach using glucagon-like peptide 1 receptor agonists (GLP-1RA), which have demonstrated efficacy in reducing both food and nicotine intake. This report describes the design of a double-blind, placebo-controlled, randomised clinical trial that evaluates the effects of the GLP-1RA exenatide as an adjunct to nicotine patches on smoking abstinence and PCWG., Methods and Analysis: The study will be conducted at two university-affiliated research sites in Houston, Texas, the UTHealth Center for Neurobehavioral Research on Addiction and Baylor College of Medicine Michael E. DeBakey VA Medical Centre. The sample will consist of 216 treatment-seeking smokers with pre-diabetes (haemoglobin A1c of 5.7%-6.4%) and/or overweight (body mass index of 25 kg/m 2 or above). Participants will be randomised (1:1) to receive subcutaneous injections of placebo or 2 mg exenatide, once weekly for 14 weeks. All participants will receive transdermal nicotine replacement therapy and brief smoking cessation counselling for 14 weeks. The primary outcomes are 4-week continuous abstinence and changes in body weight at the end of treatment. The secondary outcomes are (1) abstinence and changes in body weight at 12 weeks post end of treatment and (2) changes in neuroaffective responses to cigarette-related and food-related cues as measured by electroencephalogram., Ethics and Dissemination: The study has been approved by the UTHealth Committee for the Protection of Human Subjects (HSC-MS-21-0639) and Baylor College of Medicine Institutional Review Board (H-50543). All participants will sign informed consent. The study results will be disseminated via peer-reviewed publications and conference presentations., Trial Registration Number: NCT05610800., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This paper describes the design of a mechanism-focused phase 2 randomized clinical trial that aims first to evaluate the effects of pioglitazone on targeted mechanisms related to white matter integrity, cognitive function, and cocaine craving; and second, to evaluate the extent to which improvements on target mechanisms predict CBT response. Positive results will support pioglitazone as a potential cognitive enhancing agent to advance to later stage medication development research., (Copyright © 2021 Elsevier Inc. All rights reserved.) more...

Background: COVID-19 and resulting mitigation measures in the United States (US) brought about limited access to medical care that has been linked to increases in mental health problems, excessive substance use, and drug overdoses. The increase in co-prescription of benzodiazepines and opioids may indicate population-level changes in health behaviors that can be exacerbated by limited access, hence necessitating the tracking of these drugs during COVID-19. We evaluated the impact of the declaration of COVID-19 as a US national emergency on prescription patterns in 2020., Methods: Prescriptions of benzodiazepines and opioids were analyzed using data aggregated on a weekly basis across 38 states over the January 2019-December 2020 period. Data were from Bamboo Health Prescription Drug Monitoring Program and covered all individuals regardless of insurance status. Generalized additive models estimated the effects of the March 13, 2020 declaration on proportion of prescriptions to all controlled substances by comparing volumes before to after the week of March 13 in 2020 (range: January 27-May 24) and comparing this trend to its 2019 counterpart., Results: When comparing the January 27-March 9 period to the March 16-May 24 period in 2020, there was a statistically significant 2.0% increase in the proportion of benzodiazepine dispensations to all controlled substances, and a significant 1.7% mean decrease in proportion of opioid dispensations to all controlled substances. A significant return approaching pre-declaration levels was observed only for opioids (beginning week of May 18, 2020)., Conclusions: The results suggest significant impacts of the COVID-19 pandemic on dispensations of benzodiazepines and opioids across the US. Continued monitoring of prescription trends and maintenance of adequate and accessible access to mental healthcare are important for understanding public health crises related to substance use., (Copyright © 2021 Elsevier B.V. All rights reserved.) more...

Background: The response time speed-accuracy trade-off (SATO) is an established index of information processing ability, but rarely examined as a variable in association with treatment of substance use disorder (SUD)., Aim: The purpose of this study was to test baseline information-processing ability differences between individuals who respond to treatment for cocaine use disorder v. those who do not., Methods: Eighty patients enrolled in a clinical trial for cocaine use disorder completed a baseline drug-specific eye-tracking (anti-saccade) assessment prior to treatment, which included trials with both cocaine-related and neutral stimuli. SATO functions were computed for treatment responders v. non-responders., Results: Unexpectedly, responders demonstrated statistically different SATO functions, showing poorer accuracy when executing faster response times. This difference was present on trials that presented cocaine stimuli only., Conclusions: SATO during performance of an eye-movement task may be useful for predicting differential response to substance use disorder treatment. However, in the present study, results were specific to cocaine cues rather than an overall SATO performance decrement. more...

Rationale: Current evidence and literature reviews provide a strong justification for examining the orexin receptor (OXR) system as a therapeutic target in substance use disorders, including cocaine and other psychostimulants., Objectives: In this preliminary, proof-of-concept examination of orexin modulation in humans with cocaine use disorder, we measured changes in domains tied to relapse: stress, sleep, cue reactivity, and inhibitory control. Additionally, mood symptoms (anxiety, depression), medication compliance, and side effects were assessed., Methods: Twenty non-treatment seeking subjects with cocaine use disorder (CUD) received either the OX 1 R / OX 2 R antagonist suvorexant PO or placebo at 10 PM daily for two weeks (10 mg week 1, 20 mg week 2). Using psychometrics, smart-watch actigraphy, a cold-pressor stress challenge, and eye-tracking technology, the following domains were examined: sleep, stress/anxiety, cue-reactivity (attentional bias, craving), and inhibitory control. Psychometric data were collected every M/W/F (7 time points). Laboratory data were collected weekly (3 time points)., Results: Bayesian and frequentist generalized linear models were employed in parallel to examine the effects of suvorexant compared to placebo, with a Bayesian posterior probability threshold >80% as evidence of a signal for suvorexant. Notable results favoring suvorexant over placebo included fewer total anti-saccade errors, improved sleep actigraphy (sleep/awake periods), pre/post cold-pressor change in heart rate and salivary cortisol (all posterior probabilities >94%), and craving (posterior probability >87%)., Conclusions: Initial but restricted evidence is provided supporting the orexin system as a modulator of relapse-related processes in cocaine use disorder. Baseline differences in the main outcome variables were not experimentally controlled and differences in craving were observed at baseline. This, in combination with a limited sample size, constrain the nature of the project. The results may serve to inform more comprehensive future research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.) more...

Background: An association between first-episode presentation of bipolar mania and concurrent cannabis use disorder has been well established in the current literature (Bally et al., 2014, Baethge et al., 2008). Previous studies have shown that 30-70% of patients admitted for a first manic episode had concurrent cannabis use (Bally et al., 2014). The exact mechanism of this association has yet to be confirmed., Aims: We aim to evaluate the prevalence of cannabis use in patients with bipolar disorder (BD) admitted to UTHealth Harris County Psychiatric Center (HCPC) for a first manic episode., Methods: In this retrospective cohort study, 15,969 inpatient records of patients admitted to HCPC between 2012-2013 were examined to identify patients admitted with a first manic episode according to ICD-9 criteria (single episode mania). The prevalence of multiple sociodemographic and clinical variables including cannabis positivity in urine drug screening (UDS) were examined., Results: Twenty patients were admitted for a first manic episode. Half of the patients were females; mean age was 28.65 ± 10.56 years and mean length of stay (LOS) was 7.15 ± 3.72 days. Fifteen patients received a UDS. Of these fifteen, seven were positive for cannabinoids (47%). One patient was positive for phencyclidine (in addition to cannabis) and one patient was positive for amphetamine (but not cannabis)., Conclusions: The prevalence of cannabis use was higher in first-episode mania patients compared to the general population. The influence of cannabis on the first episode of mania requires additional study., Competing Interests: Declaration of Competing Interest No conflict of interest or funding disclosure declared by any author., (Copyright © 2019. Published by Elsevier B.V.) more...

Cocaine use disorder (CUD) is a significant public health issue. Behavioral interventions such as contingency management (CM) have been demonstrated to be highly effective in promoting cocaine abstinence. However, identifying individual characteristics associated with cocaine relapse may help improve treatment outcomes. Cocaine demand is a behavioral economic measure that shares a scientific foundation with CM. In the current study, we assessed baseline cocaine demand using a hypothetical cocaine purchasing task. Participants ( N = 58) consisted of treatment-seeking individuals with CUD. All participants received 1 month of CM treatment for cocaine abstinence, and treatment responders were defined as presenting 6 consecutive cocaine negative urine samples from thrice weekly clinic visits. Demand data were well described by the exponentiated demand model. Indices of demand (intensity of demand [ Q ₀], elasticity [α]) were significantly associated with recent (last 30 days) cocaine use. Importantly, linear regression revealed that CM treatment nonresponders presented significantly higher Q ₀ (p = .025). Subsequent quantile regression analyses examining the relationship between CM treatment response and Q ₀ revealed statistically reliable effects of being a nonresponder across 3 of the lower percentiles (i.e., 15, 25, and 30). Overall, these findings provide further support for the utility of exponentiated demand model. To our knowledge, this is the first study to demonstrate an association between baseline demand and contingency management response and systematically extend the findings of prior demand research to a novel drug class, cocaine. (PsycINFO Database Record (c) 2020 APA, all rights reserved). more...

Individuals with cannabis use disorders (CUD) show inhibitory control deficits and differential attention toward marijuana (MJ) stimuli. The robustness and utility of these measures in the CUD literature are somewhat equivocal. The present study was designed to increase measurement sensitivity by capitalizing on (a) individually calibrated stimulus selection based on cue reactivity patterns and (2) eye-tracking based measurement. CUD (n = 42) and non-CUD controls (n = 11) served as subjects. Subjects were first exposed to MJ and neutral pictures while measuring physiological and subjective responses on a trial by trial basis. A single reactivity index was created for each stimulus (L2 vector norm). Subject-unique high-reactivity MJ and low-reactivity neutral stimuli were then used in an eye-tracking task (pro-/antisaccade). The stimulus calibration procedure produced large reactivity differences between high/MJ and low/neutral stimuli (p < .001, effect size >7). CUD subjects made more overall antisaccade errors than controls (inhibitory control, p < .02, effect size >1), and CUD subjects (but not controls) made more errors on MJ trials versus neutral trials (attentional bias, p < .002, effect size >1). Within CUD subjects, L2 vector norm scores were associated with antisaccade errors (p < .04), and antisaccade errors were correlated with the Perceived Stress Scale (p < .03) and marginally with CUD severity (p < .07). Because of precise understanding of the neural circuitry governing antisaccades (a marker in several neuro/psychiatric disorders), eye movement-based measures combined with individually determined stimuli may provide an efficient and robust marker in CUD research. (PsycINFO Database Record (c) 2019 APA, all rights reserved). more...

Introduction: Prescription psychotherapeutic medication misuse is a growing problem in the United States, but no method exists to routinely screen for this in primary care. Our study sought to (1) describe the prevalence of prescription psychotherapeutic medication misuse in primary care and the characteristics of patients who misuse and (2) compare 2 screening instruments modified to identify prescription medication misuse in primary care., Methods: Primary care patients from underserved, urban clinics within a health system completed anonymous computer-directed health screens that included standard questions about prescription medication misuse. They were also administered the 4-item Cut down, Annoyed, Guilty, and Eye-opener questionnaire modified to focus on prescription medications (RxCAGE) and a 6-item Prescription Opioid Misuse Index (POMI-e) expanded to include other prescription medications., Results: Of 2,339 respondents, 15.3% were positive for at least 2 items on the RxCAGE and 18.6% were positive for at least 2 items on the POMI-e. Using our computer-directed health screen as a comparison, we found that POMI-e had a higher area under the curve (0.63). A positive POMI-e was associated with being male, white and unemployed, having depression and anxiety, and currently using illicit substances, smoking, and misusing alcohol., Conclusions: Rates of prescription medication misuse were substantial with both RxCAGE and POMI-e showing promise as screening instruments. Future studies are needed to test prescription medication misuse screening tools in broader populations and pilot interventions for those screening positive., Competing Interests: Conflict of interest: none declared., (© Copyright 2019 by the American Board of Family Medicine.) more...

Drug addiction is a chronic, devastating, but treatable disorder. A core principle of drug addiction treatment states that no single treatment is appropriate for everyone (NIDA, 2012); treatments need to adjust based on patient characteristics and response in order to be maximally effective. For cocaine use disorders (CUD), specifically, the most potent intervention currently available for initiating abstinence is behavior therapy using contingency management (CM) procedures, with early cessation being a robust predictor of future abstinence. This raises two key questions for treatment development research: First, can we significantly improve initial CM response rates with targeted adjunctive interventions? Second, for individuals who fail to achieve initial abstinence with CM, is pharmacotherapy an effective augmentation strategy? This paper describes how a sequential, multiple assignment, randomized trial (SMART) design has advantages over a fixed-intervention approach when it comes to collecting data needed to answer both questions. The first aim will examine whether Acceptance and Commitment Therapy (ACT) in combination with CM increases initial abstinence response rates (i.e., 2 consecutive weeks of cocaine-negative urine screens). The second aim will examine whether ACT+CM in combination with modafinil promotes abstinence achievement in initial non-responders. Results are expected to inform how we tailor treatment of CUD to maximize outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.) more...

Background and Aims: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance and tolerability were evaluated., Design: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC)., Setting: Single-site out-patient treatment research clinic in Houston, TX, USA., Participants: Thirty treatment-seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10 = PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre-/post-treatment., Intervention: Study medication was dispensed at thrice weekly visits along with once-weekly cognitive behavioral therapy for 12 weeks., Measurements: Measures of target engagement mechanisms of interest included cocaine craving assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity. Feasibility measures included number completing treatment, medication compliance (riboflavin detection) and tolerability (side effects, serious adverse events)., Findings: Target engagement change in mechanisms of interest, defined as a ≥ 0.75 Bayesian posterior probability of an interaction existing favoring PIO over PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed by fractional anisotropy (FA) values. Outcomes indicated greater decrease in craving and greater increase in FA values in the PIO group. Feasibility was demonstrated by high completion rates among those starting treatment (21/26 = 80%) and medication compliance (≥ 80%). There were no reported serious adverse events for PIO., Conclusions: Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine use disorder., (© 2017 Society for the Study of Addiction.) more...

Sedatives are widely prescribed for anxiety or insomnia and include benzodiazepines, selective benzodiazepine receptor subtype agonists (z-drugs), and barbiturates. These sedatives are controlled substances due to their potential for misuse and abuse. Misuse is often self-medication (chemical coping) of psychological symptoms in ways unauthorized by the prescriber, usually as dose escalation leading to requests for early refills. Sedatives are abused for euphoric effects, which may have dangerous consequences. Some sedative overdoses can be treated with flumazenil, a reversal agent, along with supportive care. Sedative withdrawal syndrome is treated by tapering the sedative and may require hospitalization. Long-term treatment of sedative addiction requires counseling, often with the help of an addiction-treatment professional. more...

Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs. more...

Editor's Note The journal is delighted to introduce a new feature in this issue that focuses on the complex and multifaceted issue of managing pain and related symptoms while responsibly attending to minimizing substance abuse. How should the seemingly disparate disciplines of drug abuse and symptom control interact? Should these be two separate fields or should practitioners/investigators in one also be qualified in the other? Is that even feasible? We are honored to have two leading, academically based clinician scientists coordinating this new feature. Peggy Compton is Professor and Associate Dean for Academic Affairs at the School of Nursing & Health Studies, Georgetown University in Washington, DC. Many readers know of Peggy's work from her years on the faculty of the University of California at Los Angeles (UCLA). Peggy brings both clinical and scientific addictionology expertise as well as the invaluable perspective of nursing to this arena. Her collaborator is Michael F. Weaver. Mike is Professor of Psychiatry and Behavioral Sciences, and Medical Director of the Center for Neurobehavioral Research on Addictions, at the University of Texas Health Sciences Center at Houston. Prior to moving to Texas, Dr. Weaver became internationally known for his work in addiction medicine at the Medical College of Virginia. We look forward to detailed explorations of many interacting issues in symptom control and substance abuse in the articles featured in this new journal feature in coming issues. The commentary below, the article by Kanouse and Compton, the Issue Brief issued by the U.S. Department of Health and Human Services, and my editorial, all of which appear in this journal issue, introduce the new feature, which I am confident will make valuable contributions to the pain management and substance abuse literature. Arthur G. Lipman, Editor ABSTRACT Abusers of prescription opioids represent two distinct populations: those who develop addiction via opioids prescribed for pain, and those for whom prescription opioids represent a primary drug of abuse. Regardless of the pathway to abuse, outcomes for patients with untreated opioid addiction are poor, and consideration of the contextual factors surrounding their problematic use is critical to effective treatment. Reviewed are patterns of prescription opioid abuse among particularly vulnerable populations in underserved rural communities, and in an effort to prevent problematic use, principles of responsible opioid prescription for chronic pain are outlined so as to decrease the risk for developing addiction. more...

Introduction: Clinical laboratory work among intermittent and daily waterpipe tobacco smokers has revealed significant risks for tobacco dependence and disease associated with waterpipe tobacco smoking (WTS). No studies have compared these groups directly. This study examined whether WTS frequency was associated with differential puff topography, toxicant exposure, and subjective response using a placebo-control design., Methods: Eighty participants reporting WTS of 2-5 episodes (LOW; n = 63) or ≥20 episodes (HIGH; n = 17) per month for ≥6 months completed 2 double-blind, counterbalanced 2-hr sessions that were preceded by ≥12hr of tobacco abstinence. Sessions differed by product smoked ad libitum for 45+ min: preferred brand/flavor of waterpipe tobacco (active) or a flavor-matched tobacco-free waterpipe product (placebo). Outcomes included puff topography, plasma nicotine, carboxyhemoglobin (COHb), and subjective response., Results: HIGH users had more puffs, shorter inter-puff-intervals, and a higher total puff volume for placebo relative to active, as well as relative to LOW users during placebo. Plasma nicotine concentrations increased when smoking active (but not placebo) with no significant differences between groups at 25min post-product administration. COHb increased significantly during all conditions; the largest increase was for HIGH users when smoking placebo. There was some evidence of higher baseline scores for nicotine/tobacco nicotine abstinence symptomology., Conclusions: Higher frequency waterpipe users may be more sensitive to the effects of waterpipe smoke nicotine content. Among HIGH users, higher baseline nicotine/tobacco abstinence symptoms may indicate greater nicotine dependence. These data support continued surveillance of WTS and development of dependence measures specific to this product., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...

Recent designer drugs, also known as "legal highs," include substituted cathinones (e.g., mephedrone, methylone, and methylenedioxypyrovalerone, often referred to as "bath salts"); synthetic cannabinoids (SCs; e.g., Spice); and synthetic hallucinogens (25I-NBOMe, or N-bomb). Compound availability has evolved rapidly to evade legal regulation and detection by routine drug testing. Young adults are the primary users, but trends are changing rapidly; use has become popular among members of the military. Acute toxicity is common and often manifests with a constellation of psychiatric and medical effects, which may be severe (e.g., anxiety, agitation, psychosis, and tachycardia), and multiple deaths have been reported with each of these types of designer drugs. Clinicians should keep designer drugs in mind when evaluating substance use in young adults or in anyone presenting with acute neuropsychiatric complaints. Treatment of acute intoxication involves supportive care targeting manifesting signs and symptoms. Long-term treatment of designer drug use disorder can be challenging and is complicated by a lack of evidence to guide treatment. more...

Aims:   To provide an initial abuse liability assessment of an electronic cigarette (EC) in current tobacco cigarette smokers., Design:   The first of four within-subject sessions was an EC sampling session that involved six, 10-puff bouts (30 seconds inter-puff interval), each bout separated by 30 minutes. In the remaining three sessions participants made choices between 10 EC puffs and varying amounts of money, 10 EC puffs and a varying number of own brand cigarette (OB) puffs, or 10 OB puffs and varying amounts of money using the multiple-choice procedure (MCP). The MCP was completed six times at 30-minute intervals, and one choice was reinforced randomly at each trial., Setting:   Clinical laboratory., Participants:   Twenty current tobacco cigarette smokers., Measurements:   Sampling session outcome measures included plasma nicotine, cardiovascular response and subjective effects. Choice session outcome was the cross-over value on the MCP., Findings:   EC use resulted in significant nicotine delivery, tobacco abstinence symptom suppression and increased product acceptability ratings. On the MCP, participants chose to receive 10 EC puffs over an average of $1.06 or three OB puffs and chose 10 OB puffs over an average of $1.50 (P < 0.003)., Conclusions:   Electronic cigarettes can deliver clinically significant amounts of nicotine and reduce cigarette abstinence symptoms and appear to have lower potential for abuse relative to traditional tobacco cigarettes, at least under certain laboratory conditions., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.) more...

Background: Waterpipe tobacco smoking usually involves heating flavored tobacco with charcoal and inhaling the resulting smoke after it has passed through water. Waterpipe tobacco smoking increases heart rate and produces subjective effects similar to those reported by cigarette smokers. These responses are thought to be nicotine-mediated, though no placebo-control studies exist. Accordingly, this double-blind, placebo-control study compared the acute physiological and subjective effects of waterpipe tobacco smoking to those produced when participants used a waterpipe to smoke a flavor-matched, tobacco-free preparation., Methods: Occasional waterpipe tobacco smokers (n = 37; 2-5 monthly smoking episodes for ≥ 6 months) completed two double-blind, counterbalanced sessions that differed by product: preferred brand/flavor of waterpipe tobacco or flavor-matched, tobacco-free preparation. For each 45-min, ad lib smoking episode blood and expired air CO were sampled, cardiovascular and respiratory response were measured, and subjective response was assessed., Results: Waterpipe tobacco smoking significantly increased mean (± SEM) plasma nicotine concentration (3.6 ± 0.7 ng/ml) and heart rate (8.6 ± 1.4 bpm) while placebo did not (0.1 ± 0.0 ng/ml; 1.3 ± 0.9b pm). For carboxyhemoglobin (COHb) and expired air CO, significant increases were observed for tobacco (3.8 ± 0.4%; 27.9 ± 2.6 ppm) and for placebo (3.9 ± 0.4%; 27.7 ± 3.3 ppm) with no differences across condition. Independent of condition, symptoms of nicotine/tobacco abstinence (e.g., "urges to smoke", "anxious") were reduced and direct effects (e.g., "dizzy", "satisfy") increased., Discussion: These results from the first placebo-control study of waterpipe tobacco smoking demonstrate that waterpipe-induced heart rate increases are almost certainly mediated by nicotine though the subjective effects observed in these occasional smokers were not., (Published by Elsevier Ireland Ltd.) more...

Introduction: Waterpipe tobacco smoking is increasing worldwide and is believed by many users to be less harmful and addictive than cigarette smoking. In fact, waterpipe tobacco and cigarette smoke contain many of the same chemicals, and users are exposed to the dependence-producing drug nicotine as well as other smoke toxicants. The subjective effect profile of these 2 tobacco use methods has not been compared directly, though this information is relevant to understanding the risk of dependence development., Methods: Fifty-four participants who reported waterpipe and cigarette smoking completed 2, 45-min, counter-balanced sessions in which they completed a waterpipe use episode (mean smoking time = 43.3 min) or a cigarette (mean = 6.1 min). Outcome measures included plasma nicotine, carboxyhemoglobin (COHb), and subjective effects, including those relevant to predicting dependence potential., Results: Mean (±SEM) peak plasma nicotine concentration did not differ by session (waterpipe = 9.8 ± 1.0 ng/ml; cigarette = 9.4 ± 1.0 ng/ml). Mean peak COHb concentration differed significantly (waterpipe = 4.5% ± 0.3%; cigarette = 1.2% ± 0.1%). Subjective effect changes for waterpipe and cigarette were comparable in magnitude but often longer lived for waterpipe., Conclusions: Relative to a cigarette, waterpipe tobacco smoking was associated with similar peak nicotine exposure, 3.75-fold greater COHb, and 56-fold greater inhaled smoke volume. Waterpipe and cigarette influenced many of the same subjective effect measures. These findings are consistent with the conclusion that waterpipe tobacco smoking presents substantial risk of dependence, disease, and death, and they can be incorporated into prevention interventions that might help deter more adolescents and young adults from experimenting with an almost certainly lethal method of tobacco use. more...

Background: Non-combustible potential reduced exposure products (PREPs; eg, Star Scientific's Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs for smokers., Methods: 28 overnight abstinent cigarette smokers (17 men, 14 non-white) each completed seven, Latin-squared ordered, approximately 2.5 h laboratory sessions that differed by product administered: Ariva, Marlboro Snus (Philip Morris, USA), Camel Snus (RJ Reynolds, Winston-Salem, North Carolina, USA), Commit nicotine lozenge (GlaxoSmithKline; 2 mg), own brand cigarettes, Quest cigarettes (Vector Tobacco; delivers very low levels of nicotine) and sham smoking (ie, puffing on an unlit cigarette). In each session, the product was administered twice (separated by 60 min), and plasma nicotine levels, expired air CO and subjective effects were assessed regularly., Results: Non-combustible products delivered less nicotine than own brand cigarettes, did not expose smokers to CO and failed to suppress tobacco abstinence symptoms as effectively as combustible products., Conclusions: While decreased toxicant exposure is a potential indicator of harm reduction potential, a failure to suppress abstinence symptoms suggests that currently marketed non-combustible PREPs may not be a viable harm reduction strategy for US smokers. This study demonstrates how clinical laboratory methods can be used to evaluate the short-term effects of non-combustible PREPs for smokers. more...

Objectives: We examined the impact of smoking cessation on weight change in a population of women prisoners., Methods: Women prisoners (n = 360) enrolled in a smoking cessation intervention; 250 received a 10-week group intervention plus transdermal nicotine replacement., Results: Women who quit smoking had significant weight gain at 3- and 6-month follow-ups, with a net difference of 10 pounds between smokers and abstainers at 6 months. By the 12-month follow-up, weight gain decreased among abstainers., Conclusions: We are the first, to our knowledge, to demonstrate weight gain associated with smoking cessation among women prisoners. Smoking cessation interventions that address postcessation weight gain as a preventative measure may be beneficial in improving health and reducing the high prevalence of smoking in prisoner populations. more...

Background: Electronic "cigarettes" are marketed to tobacco users as potential reduced exposure products (PREP), albeit with little information regarding electronic cigarette user toxicant exposure and effects. This information may be obtained by adapting clinical laboratory methods used to evaluate other PREPs for smokers., Methods: Thirty-two smokers participated in four independent Latin-square ordered conditions that differed by product: own brand cigarette, "NPRO" electronic cigarettes (NPRO EC; 18 mg cartridge), "Hydro" electronic cigarettes (Hydro EC; 16 mg cartridge), or sham (unlit cigarette). Participants took 10 puffs at two separate times during each session. Plasma nicotine and carbon monoxide (CO) concentration, heart rate, and subjective effects were assessed., Results: Own brand significantly increased plasma nicotine and CO concentration and heart rate within the first five minutes of administration whereas NPRO EC, Hydro EC, and sham smoking did not. Own brand, NPRO EC, and Hydro EC (but not sham) significantly decreased tobacco abstinence symptom ratings and increased product acceptability ratings. The magnitude of symptom suppression and increased acceptability was greater for own brand than for NPRO EC and Hydro EC., Conclusions: Under these acute testing conditions, neither of the electronic cigarettes exposed users to measurable levels of nicotine or CO, although both suppressed nicotine/tobacco abstinence symptom ratings., Impact: This study illustrates how clinical laboratory methods can be used to understand the acute effects of these and other PREPs for tobacco users. The results and methods reported here will likely be relevant to the evaluation and empirically based regulation of electronic cigarettes and similar products., ((c)2010 AACR.) more...

Female inmates (N = 655) of a large prison facility in the southeastern United States were surveyed about their substance use, social histories, and demographics. Multinomial logistic regression was used to identify predictors of injection drug use. The sample was primarily young (M = 34 +/- 9 years), and evenly split on race (45.3% White and 44.6% Black). Four predictors were identified as significant risk factors for injection drug use: being White, having a prior history of substance user treatment, having a prior drug-related charge, and being a problem drinker. Implications, limitations, and future directions are discussed. more...

Introduction: This study replicated prior observations of racial differences in smoking cessation in which Black smokers have demonstrated lower smoking cessation rates than White smokers., Methods: The study used data from a smoking cessation intervention and compared White and Black female prisoners (N = 233) on a 10-week intervention of group psychotherapy and nicotine replacement (patch). Generalized estimating equations were used to model smoking cessation across the 12-month follow-up., Results: Compared with an untreated control group, both Black and White smokers benefited from the cessation treatment. However, after controlling for potential confounds, White smokers had significantly higher overall smoking cessation rates across time compared with Black smokers (e.g., 30% vs. 24% abstinent at 6 weeks; 13% vs. 10% abstinent at 12 months). Smoking mentholated cigarettes was not associated with these differences in quit rates., Discussion: Understanding differential treatment responses can lead to the development of more tailored and efficacious smoking cessation interventions that may reduce the morbidity and mortality associated with smoking in prison populations. more...

Objective: Several risk factors for juvenile justice involvement have been identified in previous research among delinquents and include mental illness, substance use, trauma and abuse, family dysfunction, poor parenting, school problems, and aggressive behavior. However, most of these predictors resulted from studies among adolescents incarcerated in the juvenile justice system. We were interested in finding out the prevalence rates of juvenile justice involvement among psychiatric inpatient adolescents and determining predictors of juvenile justice involvement in this high-risk group., Methods: Six hundred and thirty-six medical records from adolescents ages 12-17 years who were consecutively admitted to one of two psychiatric inpatient units between July 1, 2003 and June 30, 2004 were examined., Results: Almost half (43.6%) of hospitalized adolescents had a history of juvenile justice involvement. Logistic regression analysis was conducted to determine predictors of juvenile justice involvement. Significant predictors of juvenile justice involvement included being male, parental legal history, family substance abuse history, disruptive disorder, cocaine use, being sexually active, and having a history of aggressive behavior., Conclusions: Adolescents in mental health or substance abuse treatment settings should be screened for juvenile justice involvement and appropriate referrals made to prevent worsening problems for at-risk youth. more...

Introduction: The authors hypothesized that Internal Medicine (IM) residents experience a lack of preparation, confidence, and reward when managing patients with chronic nonmalignant pain (CNMP) in their continuity clinic and that they exhibit deficiencies in CNMP management practices, particularly when opioids are prescribed., Methods: As part of a quality improvement project in the IM resident continuity clinic, the authors performed a needs assessment through a self-administered resident questionnaire and a retrospective chart review., Results: Fifty-seven percent of respondents rated their CNMP preparation as "fair" or "poor," 89 percent reported that their experience was "much less" or "somewhat less" rewarding than managing patients with other chronic conditions, and 58 percent reported that CNMP management "negatively" or "very negatively" affected their view of primary care as a career. Twenty-eight charts of patients receiving opioids during a 1-year study period were reviewed. Although residents were likely to document pain diagnoses (93 percent) and pain scores (82 percent) as well as utilize medication agreements (82 percent), they were less likely to document illicit substance use (39 percent), document legal history (32 percent), or obtain prior medical records (39 percent). Few urine drug screens were ordered (18 percent) and 25 percent of patients had fewer than four face-to-face visits during the year., Discussion: The questionnaire indicated that IM residents lack preparation in managing CNMP, which results in lack of confidence and reward. The chart review revealed management practice deficiencies in risk assessment and prescription drug misuse monitoring. As a result, the authors have implemented curricular interventions, integrated a pain clinic within the continuity clinic, optimized residency program clinic scheduling, and developed tools for consistency in management practices. more...

Transdermal nicotine (TN) is an efficacious smoking cessation pharmacotherapy thought to work, in part, by attenuating the effects of tobacco/nicotine abstinence and the effects of concurrently smoked cigarettes. Clinical trials suggest that TN may be less efficacious for women. This study explored the possibility of TN-related gender differences in > or = 8 hour abstinent smokers (54 women, 70 men) who completed four within-subject, double-blind, placebo-controlled sessions corresponding to 0, 7, 14, and 21 mg TN. In each approximately 6.5-hr long session participants smoked an own-brand cigarette 4 hours after TN administration and physiological and subjective outcomes were examined throughout each session. Results revealed that TN suppressed some signs and symptoms of tobacco abstinence and attenuated some effects of smoking, and these effects were not dependent on gender. Women were more sensitive to the direct effects of nicotine (e.g., ratings of Nauseous) and, independent of TN dose, self-administered less nicotine when smoking and rated smoking as less rewarding. Thus, although this study does not shed light on clinical observations that TN is less effective for women, results suggest that TN might need to be combined with other interventions to supplement its effects on tobacco/nicotine abstinence and concurrent smoking. more...

The tobacco industry markets potential reduced exposure products (PREPs) to smokers, including oral products that are intended to be used in situations where cigarettes cannot. For example, Ariva, marketed by Star Scientific, is a tablet made from compressed tobacco powder and is intended for "adult smokers in situations where they cannot or choose not to smoke." No objective data are available regarding Ariva's effects in smokers, including its nicotine delivery, cardiovascular profile, or subjective effects. In this single-session, clinical laboratory study, 10 overnight-abstinent cigarette smokers were administered one Ariva tablet, followed 90 min later by two Ariva tablets, followed 90 min later by three Ariva tablets. Participants allowed each dose to dissolve in their mouths according to package instructions. Blood was sampled, heart rate monitored, and subjective effects assessed regularly. Ariva delivered nicotine in a dose-dependent manner; mean (SD) nicotine levels increased from 2.4 ng/ml (0.9) at baseline, to 3.4 ng/ml (1.4) 45 min post-1 tablet, 7.3 ng/ml (4.0) 45 min post-2 tablets, and 9.7 ng/ml (4.4) 45 min post-3 tablets. Heart rate increased after tablet administration, independent of dose. The tablets also significantly decreased subjective ratings of craving and urge, and increased ratings of nausea. Based on this short-term laboratory evaluation, Ariva exposes users to nicotine and may suppress some symptoms of tobacco abstinence, though its nausea-inducing characteristics may limit initial acceptability. more...

This study sought to characterize adolescent psychiatric inpatient populations from two sites and to determine correlates of substance use disorders (SUD). Screening procedures for SUD differ substantially between these sites. A retrospective review of adolescent inpatients (n=636) revealed that the populations were similar in gender, race and age. Rates of SUD at the site with a formalized SUD screening regimen were higher (39%) than those at the other site (16.5%). Similar correlates of SUD were observed across sites, including older age, legal involvement, sexual activity, childhood disruptive disorder, and tobacco use. These results suggest that SUD is a major issue in adolescent psychiatric patients. More rigorous screening for SUD and its correlates may facilitate earlier detection of substance use in this vulnerable population. more...

Background: Experience suggests that patients with alcohol and other drug use disorders (AOD) are commonly cared for in our intensive care units (ICU's) and require more sedation. We sought to determine the impact of AOD on sedation requirement and mechanical ventilation (MV) duration., Methods: Retrospective review of randomly selected records of adult patients undergoing MV in the medical ICU. Diagnoses of AOD were identified using strict criteria in Diagnostic and Statistical Manual of Mental Disorders, and through review of medical records and toxicology results., Results: Of the 70 MV patients reviewed, 27 had AOD (39%). Implicated substances were alcohol in 22 patients, cocaine in 5, heroin in 2, opioids in 2, marijuana in 2. There was no difference between AOD and non-AOD patients in age, race, or reason for MV, but patients with AOD were more likely to be male (21 versus 15, p < 0.0001) and had a lower mean Acute Physiology and Chronic Health Evaluation II (22 versus 26, p = 0.048). While AOD patients received more lorazepam equivalents (0.5 versus 0.2 mg/kg.day, p = 0.004), morphine equivalents (0.5 versus 0.1 mg/kg.day, p = 0.03) and longer duration of infusions (16 versus 10 hours/day. medication, p = 0.002), they had similar sedation levels (Richmond Agitation-Sedation Scale (RASS) -2 versus -2, p = 0.83), incidence of agitation (RASS > or = 3: 3.0% versus 2.4% of observations, p = 0.33), and duration of MV (3.6 versus 3.9 days, p = 0.89) as those without AOD., Conclusion: The prevalence of AOD among medical ICU patients undergoing MV is high. Patients with AOD receive higher doses of sedation than their non-AOD counterparts to achieve similar RASS scores but do not undergo longer duration of MV. more...

Breath carbon monoxide (CO) is a convenient, widely used method for abstinence validation, with cutoffs of 8-10 ppm commonly employed. The goal of the present study was to determine an appropriate CO cutoff to differentiate nonsmokers and smokers within a large sample (N = 374) of female prisoners incarcerated at a correctional facility in Virginia. Mean age of the population was 34.5 years, 49.2% were White, and 29% had less than a high school education. Smoking prevalence was 74.1% within the prison population. Examination of CO levels versus smoking self-report using a receiver operator characteristic (ROC) analysis revealed that a CO cutoff of 3 ppm resulted in the best sensitivity (98.1%) and specificity (95.8%). Overall ROC area under the curve was 99% (95% CI = 98.2%-99.9%). This same cutoff was optimal for smoking subgroups including Black and light (<10 cigarettes/day) smokers. Results suggest that CO cutoffs higher than 3 ppm may misclassify some smokers as nonsmokers and underestimate the prevalence of smoking. more...

An aversive tobacco abstinence syndrome, thought to reflect an underlying level of nicotine dependence, contributes to cigarette smokers' failed quit attempts. Nicotine replacement therapy (NRT) suppresses tobacco abstinence, but high relapse rates suggest room for improvement. Improving NRT's efficacy might begin with identifying factors that influence tobacco abstinence symptom suppression. Two such factors are smokers' gender and NRT dose. The purpose of this study was to determine the dose-related effects of transdermal nicotine (TN) on tobacco abstinence symptoms in 75 men and 53 women who regularly smoked cigarettes but who had abstained from smoking for at least 8-12 hr. Participants completed 4 double-blind, randomized 6.5-hr laboratory sessions that differed by TN dose (0, 7, 21, or 42 mg). Each session included blood sampling for plasma nicotine level, measurement of heart rate, participants' ratings of tobacco abstinence symptoms and effects of nicotine, and psychomotor performance. Increases in plasma nicotine level were related to TN dose and were independent of gender. TN-induced abstinence symptom suppression was dose-related for items assessing craving and urge to smoke and largely was independent of gender. TN increased heart rate and ratings of aversive side effects (e.g., nausea, lightheadedness) in a dose-related manner, and women were more sensitive at higher doses. Results from this laboratory study support the continued use of TN as a pharmacotherapy. Higher doses may ameliorate some abstinence symptoms, although the side effect profile, at least in the short term, may limit effectiveness, especially for women. more...

The use of opioid medications for analgesia is associated with concerns about adverse side effects and the potential for development of physical dependence, tolerance, or addiction. Pain often is undertreated, which may provoke drug-seeking behavior by patients. Physicians must assess requests for more pain medication as stemming from either undertreatment of pain, development of physical tolerance, or addiction. Important tools for addiction screening include the use of questionnaires, patient interviews, and lab tests. In this study, the physiological and behavioral consequences of chronic pain and its treatment with opioids, along with guidelines for prescribing opioid pain medication, are presented. more...

Analgesic medications are often tested in clinical laboratory studies by observing their ability to reduce the pain produced by noxious stimuli presented to healthy skin. These medications may then be used clinically to reduce disease-related hyperalgesia. This article describes a clinical laboratory model useful for testing a medication's ability to reduce hyperalgesia in humans. Results demonstrate that ultraviolet (UV) light induces hyperalgesia, commonly prescribed analgesic medications reduce UV-induced hyperalgesia, and this UV-induced hyperalgesia model can be used to assess the time course of a medication's antihyperalgesia effects. Coupled with participant-rated measures of drug liking and mood, this model may prove useful for predicting the clinical efficacy and side-effect profile of novel analgesic medications in cost-efficient and statistically powerful laboratory studies. more...

Patients with substance abuse problems are common in general medical practice and include people of all ages and socioeconomic groups. Initial diagnosis and treatment of addiction problems are often done by the primary care practitioner before referral to a specialist. This article provides information to help in recognition of addiction, guidelines for treatment of intoxication and withdrawal of various drugs of abuse (such as opioids, sedative-hypnotics, stimulants, hallucinogens, and volatile inhalants), and techniques for brief intervention as well as long-term care of substance-abusing patients. The physician can be a powerful influence for getting the patient to accept treatment, especially when the physician is empathic without being judgmental. Addiction is a chronic disorder with remissions and relapses like any other chronic disease, so exacerbations should not be seen as failures but as time to intensify treatment. Patients with substance abuse problems can be frustrating to treat, but it can also be a rewarding experience when a physician helps a substance-abusing patient return to normal and productive functioning in society. more...

This study was designed to determine if morphine administered intrathecally (IT) interacts with serotonergic or noradrenergic nerve terminals in the spinal cord to produce analgesia on the spinally mediated tail-flick test. Male Sprague-Dawley rats were fitted with IT catheters. One week later, animals were spinally pretreated with receptor antagonists selective for opioid, serotonin or alpha-adrenoceptors, and the ability of these agents to alter spinal morphine-induced antinociception was assessed. Morphine dose-dependently elevated tail-flick latency in a naltrexone-reversible manner. The serotonin receptor antagonists spiroxatrine (5-HT1A), pindolol (5-HT1B), ritanserin (5-HT2) and ICS 205-930 (5-HT3) attenuated the spinal analgesic effects of morphine. In contrast, the alpha 1 and alpha 2-adrenoceptor antagonists prazosin and yohimbine, respectively, did not alter morphine-induced elevations in tail-flick latency. These data substantiate earlier reports that spinal morphine-induced antinociception relies on an opioid receptor-mediated component in addition to a local serotonergic component. The finding that the alpha-adrenoceptor antagonists did not alter the antinociceptive effects of IT morphine suggests that spinal norepinephrine does not contribute to the analgesic effects of the opiate. more...