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1.
J Addict Med ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498621

RESUMO

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.

2.
Drug Alcohol Depend ; 256: 111078, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38309089

RESUMO

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.


Assuntos
Terapia de Aceitação e Compromisso , Transtornos Relacionados ao Uso de Cocaína , Cocaína , Humanos , Teorema de Bayes , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Transtornos Relacionados ao Uso de Cocaína/psicologia , Resultado do Tratamento , Cocaína/uso terapêutico , Modafinila/uso terapêutico , Poliésteres/uso terapêutico
3.
J Addict Med ; 17(4): 481-484, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37579116

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Exenatida/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Estudos de Viabilidade , Peptídeos/efeitos adversos , Peçonhas/efeitos adversos , Hemoglobinas Glicadas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico
4.
BMJ Open ; 13(6): e072707, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316311

RESUMO

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/m2 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.


Assuntos
Estado Pré-Diabético , Abandono do Hábito de Fumar , Humanos , Sobrepeso/tratamento farmacológico , Dispositivos para o Abandono do Uso de Tabaco , Exenatida , Fumantes , Estado Pré-Diabético/tratamento farmacológico , Nicotina , Aumento de Peso , Obesidade/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
J Subst Use Addict Treat ; 151: 208987, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36822269

RESUMO

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.


Assuntos
Fumar Cigarros , Metanfetamina , Humanos , Naltrexona/uso terapêutico , Bupropiona/uso terapêutico , Antagonistas de Entorpecentes , Metanfetamina/efeitos adversos , Estudos Prospectivos
6.
Drug Alcohol Depend ; 229(Pt A): 109176, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808468

RESUMO

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.


Assuntos
Analgésicos Opioides , COVID-19 , Analgésicos Opioides/uso terapêutico , Benzodiazepinas , Substâncias Controladas , Prescrições de Medicamentos , Humanos , Pandemias , SARS-CoV-2 , Estados Unidos/epidemiologia
7.
Contemp Clin Trials ; 111: 106603, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34688917

RESUMO

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.


Assuntos
Cocaína , Substância Branca , Animais , Cocaína/farmacologia , Humanos , Neuroproteção , Recidiva , Prevenção Secundária/métodos
8.
J Psychopharmacol ; 35(5): 611-614, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33586502

RESUMO

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.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Sinais (Psicologia) , Movimentos Sacádicos/fisiologia , Adulto , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Medições dos Movimentos Oculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação
9.
Brain Res ; 1731: 146359, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31374218

RESUMO

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 OX1R / OX2R 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.


Assuntos
Azepinas/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/prevenção & controle , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Antagonistas dos Receptores de Orexina/administração & dosagem , Prevenção Secundária/métodos , Triazóis/administração & dosagem , Adulto , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Inibição Psicológica , Masculino , Pessoa de Meia-Idade , Psicometria , Recidiva , Sono/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico
10.
Psychol Addict Behav ; 34(1): 164-174, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31233323

RESUMO

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 [Q0], elasticity [α]) were significantly associated with recent (last 30 days) cocaine use. Importantly, linear regression revealed that CM treatment nonresponders presented significantly higher Q0 (p = .025). Subsequent quantile regression analyses examining the relationship between CM treatment response and Q0 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).


Assuntos
Terapia Comportamental/métodos , Fumar Cocaína/terapia , Transtornos Relacionados ao Uso de Cocaína/terapia , Adulto , Cocaína , Fumar Cocaína/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína Crack , Economia Comportamental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
11.
J Affect Disord ; 263: 289-291, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31818791

RESUMO

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.


Assuntos
Transtorno Bipolar , Cannabis , Abuso de Maconha , Adolescente , Adulto , Transtorno Bipolar/epidemiologia , Feminino , Humanos , Classificação Internacional de Doenças , Mania , Estudos Retrospectivos , Adulto Jovem
12.
Exp Clin Psychopharmacol ; 27(6): 578-587, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30907601

RESUMO

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).


Assuntos
Atenção/fisiologia , Viés de Atenção , Movimentos Oculares , Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
13.
J Am Board Fam Med ; 32(2): 272-278, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30850465

RESUMO

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.


Assuntos
Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Psicotrópicos/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Inquéritos e Questionários/normas , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/estatística & dados numéricos , Psicotrópicos/efeitos adversos
14.
Contemp Clin Trials ; 65: 109-115, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29287664

RESUMO

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.


Assuntos
Terapia Comportamental/métodos , Transtornos Relacionados ao Uso de Cocaína/terapia , Adolescente , Adulto , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila/uso terapêutico , Assistência Centrada no Paciente , Adulto Jovem
15.
Addiction ; 112(10): 1861-1868, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28498501

RESUMO

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.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Fissura/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , PPAR gama/agonistas , Tiazolidinedionas/uso terapêutico , Substância Branca/efeitos dos fármacos , Adolescente , Adulto , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pioglitazona , Resultado do Tratamento , Adulto Jovem
16.
J Pain Palliat Care Pharmacother ; 29(3): 281-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26375198

RESUMO

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.


Assuntos
Analgésicos Opioides/farmacocinética , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Neurotransmissores/metabolismo , Nicotina/farmacocinética , Fumar/fisiopatologia , Dor Crônica/epidemiologia , Sistema Enzimático do Citocromo P-450/metabolismo , Dopamina/metabolismo , Interações Medicamentosas , Humanos , Receptores Colinérgicos/metabolismo , Receptores Nicotínicos/metabolismo , Receptores Opioides/metabolismo , Medição de Risco , Índice de Gravidade de Doença , Fumar/epidemiologia , Produtos do Tabaco
17.
Yale J Biol Med ; 88(3): 247-56, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26339207

RESUMO

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.


Assuntos
Aconselhamento Diretivo/métodos , Flumazenil/administração & dosagem , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Automedicação/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Antídotos/administração & dosagem , Terapia Combinada/métodos , Medicina Baseada em Evidências , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Resultado do Tratamento
19.
J Pain Palliat Care Pharmacother ; 29(2): 166-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26095489

RESUMO

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.


Assuntos
Analgésicos Opioides/uso terapêutico , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Humanos , Transtornos Relacionados ao Uso de Opioides/etiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Manejo da Dor/efeitos adversos , Manejo da Dor/ética , Manejo da Dor/métodos , Uso Indevido de Medicamentos sob Prescrição/ética
20.
Addict Sci Clin Pract ; 10: 8, 2015 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-25928069

RESUMO

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.


Assuntos
Drogas Desenhadas/farmacologia , Psicotrópicos/farmacologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/terapia , Alcaloides/farmacologia , Canabinoides/farmacologia , Terapia Cognitivo-Comportamental , Aconselhamento , Drogas Desenhadas/efeitos adversos , Alucinógenos/farmacologia , Humanos , Hipnóticos e Sedativos/uso terapêutico , Monitorização Fisiológica , Educação de Pacientes como Assunto , Psicotrópicos/efeitos adversos , Detecção do Abuso de Substâncias
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