RESUMO
BACKGROUND: Cocaine use disorder (CUD) is a common problem in the United States and worldwide. The mechanisms by which cocaine induces acute cardiovascular toxicity are various. When systemically absorbed through inhaled or intravenous routes, cocaine induces an acute rise in the heart rate (HR) and blood pressure (BP) leading to a significant increase in the cardiac output (CO) and myocardial oxygen demand. Subjects with chronic CUD represent a special population that has experienced long-term cocaine exposure, often without showing signs of cardiovascular disease. We herein present prospectively collected data on the acute hemodynamic effects of intravenous cocaine in a cohort of nontreatment-seeking individuals with CUD without cardiovascular disease. METHODS AND RESULTS: Baseline physiologic data were collected while participants underwent infusion of escalating doses of cocaine (10, 20, and 40 mg administered over 2 minutes) at baseline and after receiving single-blind placebo treatment. Continuous noninvasive hemodynamic monitoring was performed throughout the infusion sessions using the ccNexfin finger cuffs (Edwards Lifesciences Corp, Irvine, CA). The recorded arterial BP tracings allowed for the measurement of beat-to-beat changes in HR, BP, stroke volume, CO, and systemic vascular resistance (SVR). None of the subjects experienced a treatment-related serious adverse event. Cocaine produced significant dose-dependent increases in median HR, BP, CO, and +dP/dt (a measure of cardiac contractility) and a significant dose-dependent reduction in median SVR. CONCLUSIONS: Intravenous cocaine in a cohort of otherwise healthy subjects with CUD produced dose-dependent increases in CO, largely explained by an increase in HR, accompanied by a dose-dependent decrease in SVR.
Assuntos
Pressão Arterial/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Cocaína/efeitos adversos , Dedos/irrigação sanguínea , Frequência Cardíaca/efeitos dos fármacos , Monitorização Hemodinâmica , Resistência Vascular/efeitos dos fármacos , Adulto , Monitorização Ambulatorial da Pressão Arterial , Estimulantes do Sistema Nervoso Central/administração & dosagem , Cocaína/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Método Simples-Cego , Fatores de Tempo , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVES: Substance misuse is increasing in the older population, which may have differing effects on behavior compared to younger substance participants. Differences in trait and state impulsivity were assessed in younger and older cocaine-dependent participants. METHODS: Thirty-one younger cocaine-dependent participants (n = 31) and 21 older cocaine-dependent participants (n = 21) were assessed using the Barrett Impulsiveness Scale-11 and the Immediate Memory Task. RESULTS: Younger participants showed higher trait impulsivity than older participants (p =.027). However, older participants demonstrated higher state impulsivity than younger participants (p =.018). CONCLUSION: Higher state impulsivity in older cocaine participants suggests that cocaine use may have accelerating effects on the aging brain. SCIENTIFIC SIGNIFICANCE: This preliminary study adds the limited research on how cocaine use affects normal aging. Current treatments are based on younger adults, therefore the needs of older adults should be taken into consideration and studied more. (Am J Addict 2018;27:557-559).
Assuntos
Envelhecimento , Tomada de Decisões/efeitos dos fármacos , Comportamento Impulsivo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Adulto , Fatores Etários , Envelhecimento/efeitos dos fármacos , Envelhecimento/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise e Desempenho de TarefasRESUMO
OBJECTIVE: To determine if elevated rapid-response impulsivity after blast exposure (as a putative marker of ventral prefrontal cortex [vPFC] damage) is predictive of future elevated affective symptomatology in blast-exposed service members. DESIGN: Longitudinal design with neurocognitive testing at initial assessment and 1-year follow-up assessment of psychiatric symptomatology by telephone interview. SETTING: Veterans Administration medical centers and postdeployment assessment centers at military bases. PARTICIPANTS: Blast-exposed U.S. military personnel (N=84) ages 19 to 39 years old. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Center for Epidemiological Studies-Depression Scale (CES-D) scores, Posttraumatic Stress Disorder Checklist Version 5 (PCL-5) scores, and Alcohol Use Disorders Identification Test-C (AUDIT-C) scores at the 12-month follow-up telephone interview. RESULTS: After controlling for age and affective symptom scores reported at the initial assessment, commission errors on the Continuous Performance Test-II of the initial assessment were predictive of higher symptom scores on the CES-D and PCL-5 at follow-up, but were not predictive of AUDIT-C scores. CONCLUSIONS: Elevated rapid-response impulsivity, as a behavioral marker of reduced top-down frontocortical control, is a risk factor for elevated mood and posttraumatic stress disorder symptoms over time in blast-exposed individuals. Future longitudinal studies with predeployment neurobehavioral testing could enable attribution of this relation to blast-related vPFC damage.
Assuntos
Traumatismos por Explosões/epidemiologia , Lesões Encefálicas Traumáticas/epidemiologia , Depressão/epidemiologia , Comportamento Impulsivo/fisiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Campanha Afegã de 2001- , Biomarcadores , Traumatismos por Explosões/fisiopatologia , Lesões Encefálicas Traumáticas/fisiopatologia , Depressão/fisiopatologia , Feminino , Seguimentos , Humanos , Guerra do Iraque 2003-2011 , Masculino , Militares , Testes Neuropsicológicos , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estados Unidos , Adulto JovemRESUMO
Smoking remains one of the most preventable causes of morbidity and mortality in the United States (1). A number of factors contribute to the initiation and maintenance of smoking behavior, including psychosocial influences (2,3), neurobehavioral traits (4), and genetic susceptibility (5-7). Prevalence rates of tobacco dependence among individuals with mental health issues are strikingly high when compared to the general population, particularly among individuals with depression and anxiety disorders (8). There are well-established relationships between impulsivity, cue reactivity, and tobacco use in the literature (9). However, the interaction between these relationships remains unclear. The primary goal of this paper is to provide an overview of the existing literature across these domains and explore their interrelationship and subsequent impact on smoking initiation and tobacco dependence. Further, the clinical implications regarding the development of potential targeted smoking cessation strategies for this population are presented.
Assuntos
Abandono do Hábito de Fumar/métodos , Fumar/psicologia , Tabagismo/reabilitação , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/epidemiologia , Sinais (Psicologia) , Depressão/complicações , Depressão/epidemiologia , Diagnóstico Duplo (Psiquiatria) , Predisposição Genética para Doença , Humanos , Comportamento Impulsivo , Prevalência , Fumantes/psicologia , Fumar/epidemiologia , Abandono do Hábito de Fumar/psicologia , Tabagismo/genética , Tabagismo/psicologia , Estados UnidosRESUMO
Background and Objectives: Preclinical studies show serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonists reduce cocaine-seeking and cocaine intake. This study examined safety of the 5-HT2CR agonist lorcaserin administered with cocaine in participants with cocaine use disorder (CocUD). Secondarily, subjective response to cocaine and choice of cocaine vs. money were examined. Methods: A double-blind, randomized, placebo-controlled trial of 25 inpatient non-treatment seeking participants with CocUD. Participants were randomized to either lorcaserin (n = 17) or placebo (n = 8). Primary outcome measures included cardiovascular measures and plasma cocaine levels. Secondary measures of subjective response to cocaine were assessed using a visual analog scale (VAS) and cocaine vs. money progressive ratio choice sessions. Results: Thirteen randomized participants were included in the final analysis. No serious or unexpected adverse events were related to lorcaserin. There were no significant interactions between cocaine and lorcaserin on cardiovascular measures, plasma cocaine, or subjective ratings. After multiple comparisons correction, cocaine significantly increased blood pressure, heart rate, and QTc. Lorcaserin significantly decreased VAS ratings of "feel irritable," "feel hungry," and "I am craving." For the cocaine vs. money choice procedure, there was a significant interaction between choice (cocaine vs. money) and lorcaserin. Participants treated with lorcaserin were more likely to choose cocaine. Discussion and Conclusions: This study showed safety of lorcaserin administered with cocaine but lack of efficacy to reduce the reinforcing effects of cocaine. Scientific Significance: This study is the first to show a disconnect between effects of 5-HT2CR agonists on craving and cocaine choice in human cocaine users.
RESUMO
The United States is currently in the midst of an opioid epidemic. Barriers to treatment in the emergency department can lead to missed opportunities for helping prevent overdose and relapse in individuals with opioid use disorder. The administration of buprenorphine in the emergency department can potentially lead to better treatment outcomes for these individuals.
Assuntos
Buprenorfina/uso terapêutico , Overdose de Drogas/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Antagonistas de Entorpecentes/uso terapêutico , Overdose de Drogas/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Humanos , Estados UnidosRESUMO
In military populations, traumatic brain injury (TBI) also holds potential to increase impulsivity and impair mood regulation due to blast injury effects on ventral frontal cortex - to put military personnel at risk for suicide or substance abuse. We assessed a linkage between depression and impaired behavioral inhibition in 117 blast-exposed service members (SM) and veterans with post-concussion syndrome (PCS), where PCS was defined using a Rivermead Postconcussive Symptom Questionnaire (RPQ) modified to clarify whether each symptom worsened compared to pre-blast. Center for Epidemiological Studies-Depression Scale (CES-D) scores, PTSD Checklist 5 (PCL-5) scores, and RPQ raw subscale scores correlated positively with commission and perseverative errors on the continuous performance test II (CPT-II). In contrast, the number of RPQ symptoms ostensibly worsened post-blast did not correlate with impulsive errors on the CPT-II. These data replicate earlier findings that link increased affective symptomatology to impaired behavior inhibition in military TBI populations, but where additional effects on impulsivity from the blast itself remain equivocal.
Assuntos
Traumatismos por Explosões/fisiopatologia , Depressão/fisiopatologia , Comportamento Impulsivo/fisiologia , Militares , Síndrome Pós-Concussão/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Cocaine dependence (CD) is associated with several cognitive deficits. Accumulating evidence, based on human and animal studies, has led to models for interpreting the neural basis of cognitive functions as interactions between functionally related brain regions. In this review, we focus on magnetic resonance imaging (MRI) studies using brain connectivity techniques as related to CD. The majority of these brain connectivity studies indicated that cocaine use is associated with altered brain connectivity between different structures, including cortical-striatal regions and default mode network. In cocaine users some of the altered brain connectivity measures are associated with behavioral performance, history of drug use, and treatment outcome. The implications of these brain connectivity findings to the treatment of CD and the pros and cons of the major brain connectivity techniques are discussed. Finally potential future directions in cocaine use disorder research using brain connectivity techniques are briefly described.