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1.
J Subst Abuse Treat ; 118: 108102, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32854983

RESUMO

The current coronavirus disease (COVID-19) pandemic has rapidly spread across the world. Individuals with stimulant use disorder are a vulnerable population, who are particularly at risk of negative outcomes during this pandemic due to several risk factors, including mental and physical comorbidities, weakened immune responses, high-risk behaviors, and barriers to healthcare access. Engaging patients with stimulant use disorder in regular treatment has become even more difficult during this pandemic, which has resulted in many cuts to addiction treatment programs. The most effective treatment options for stimulant use disorder are psychosocial interventions, which rely heavily on in-person interactions, posing an added challenge during physical distancing. In particular, contingency management (CM) is a behavioral therapy that utilizes tangible reinforcements to incentivize targeted behavior changes, and is an effective treatment intervention used for stimulant use disorder. This paper highlights the treatment challenges for individuals with stimulant use disorder and the importance of adapting CM programs during COVID-19. We present strategies for how CM can be adapted and its role expanded in a safe way during the COVID-19 pandemic to help prevent infection spread, stimulant use relapse, and worsened psychosocial consequences.


Assuntos
Terapia Comportamental/métodos , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Populações Vulneráveis
2.
PLoS One ; 15(5): e0233010, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396581

RESUMO

Methamphetamine use has increased over the past decade and the first use of methamphetamine is most often when women are of reproductive age. Methamphetamine accumulates in the liver; however, little is known about the effect of methamphetamine use on hepatic drug metabolism. Methamphetamine was administered on 3 occassions to female Dunkin Hartley guinea pigs of reproductive age, mimicking recreational drug use. Low doses of test drugs caffeine and midazolam were administered after the third dose of methamphetamine to assess the functional activity of cytochrome P450 1A2 and 3A, respectively. Real-time quantitative polymerase chain reaction was used to quantify the mRNA expression of factors involved in glucocorticoid signalling, inflammation, oxidative stress and drug transporters. This study showed that methamphetamine administration decreased hepatic CYP1A2 mRNA expression, but increased CYP1A2 enzyme activity. Methamphetamine had no effect on CYP3A enzyme activity. In addition, we found that methamphetamine may also result in changes in glucocorticoid bioavailability, as we found a decrease in 11ß-hydroxysteroid dehydrogenase 1 mRNA expression, which converts inactive cortisone into active cortisol. This study has shown that methamphetamine administration has the potential to alter drug metabolism via the CYP1A2 metabolic pathway in female guinea pigs. This may have clinical implications for drug dosing in female methamphetamine users of reproductive age.


Assuntos
Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP3A/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metanfetamina/administração & dosagem , Animais , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/toxicidade , Citocromo P-450 CYP1A2/genética , Feminino , Cobaias , Humanos , Taxa de Depuração Metabólica , Redes e Vias Metabólicas/efeitos dos fármacos , Metanfetamina/sangue , Metanfetamina/toxicidade , Modelos Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
3.
Psychopharmacology (Berl) ; 237(7): 1989-2005, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388619

RESUMO

RATIONALE: Abuse of the psychostimulant methamphetamine (METH) can cause long-lasting damage to brain monoaminergic systems and is associated with profound mental health problems for users, including lasting cognitive impairments. Animal models of METH exposure have been useful in dissecting the molecular effects of the drug on cognition, but many studies use acute, non-contingent "binge" administrations of METH which do not adequately approximate human METH use. Long-term METH exposure via long-access (LgA) self-administration paradigms has been proposed to more closely reflect human use and induce cognitive impairments. OBJECTIVE: To better understand the role of contingency and patterns of exposure in METH-induced cognitive impairments, we analyzed behavioral and neurochemical outcomes in adult male rats, comparing non-contingent "binge" METH administration with contingent (LgA) METH self-administration and non-contingent yoked partners. RESULTS: Binge METH (40 mg/kg, i.p., over 1 day) dramatically altered striatal and hippocampal dopamine, DOPAC, 5-HT, 5-HIAA, BDNF, and TrkB 75 days after drug exposure. In contrast, 6-h LgA METH self-administration (cumulative 24.8-48.9 mg METH, i.v., over 16 days) altered hippocampal BDNF in both contingent and yoked animals but reduced striatal 5-HIAA in only contingent animals. Neurochemical alterations following binge METH administration were not accompanied by cognitive deficits in Morris water maze, novel object recognition, or Y-maze tests. However, contingent LgA METH self-administration resulted in impaired spatial memory in the water maze. CONCLUSIONS: Overall, substantial differences in neurochemical markers between METH exposure and self-administration paradigms did not consistently translate to deficits in cognitive tasks, highlighting the complexity of correlating METH-induced neurochemical changes with cognitive outcomes.


Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Cognição/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Metanfetamina/administração & dosagem , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Cognição/fisiologia , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Ratos , Ratos Wistar , Autoadministração/psicologia
4.
Compr Psychiatry ; 100: 152178, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32386957

RESUMO

BACKGROUND: Emotional dysregulation (ED) and callous unemotional (CU) traits can be associated with ADHD in youth, influencing its natural history and outcome, but their effect on medication efficacy is unexplored. We examined whether two measures of baseline ED and CU traits, the Child Behavior Checklist-Dysregulation Profile (CBCL-DP) and the Antisocial Process Screening Device (APSD), respectively, were predictors of change of ADHD-Rating Scale (ADHD-RS) after a 4-week methylphenidate (MPH) monotherapy. METHODS: 43 patients (37 males, 8-16 years, mean 9.9 ± 2.7 years) were included. Hierarchical linear regression models were used to explore whether CBCL-DP and APSD might predict ADHD-RS score, controlling for baseline severity. RESULTS: Baseline CBCL-DP predicted higher post-treatment ADHD-RS scores in total and hyperactivity-impulsivity, but not in inattention subscale. Baseline APSD was not significantly related to ADHD-RS scores at the follow-up. LIMITATIONS: Small sample size, lack of gender diversity, non-blind design and short period of observation. CONCLUSION: ED, assessed with that CBCL-DP, might be a negative predictor of change of hyperactive-impulsive symptoms after MPH treatment and should be systematically assessed at baseline.


Assuntos
Transtorno da Personalidade Antissocial/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Emoções/efeitos dos fármacos , Metilfenidato/efeitos adversos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Cognição , Feminino , Humanos , Comportamento Impulsivo , Masculino , Metilfenidato/administração & dosagem , Metilfenidato/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Public Health Rep ; 135(3): 383-392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32311304

RESUMO

OBJECTIVE: The opioid epidemic in the United States increasingly affects women of reproductive age and has resulted in a rise in concurrent polydrug use. The objective of this study was to investigate the effect of this polydrug use on preterm birth in a multiethnic birth cohort. METHODS: We analyzed data from 8261 mothers enrolled in the Boston Birth Cohort from 1998 to 2018 in Boston, Massachusetts. We grouped substances used during pregnancy based on their primary effects (stimulant or depressant) and assessed independent and combined associations with smoking on preterm birth. RESULTS: Of 8261 mothers, 131 used stimulant drugs and 193 used depressant drugs during pregnancy. The preterm birth rate was 27.5% (2271 of 8261) in the sample. Mothers who smoked had 35% increased odds of preterm birth across adjusted models. Mothers who used stimulant drugs without smoking were not at increased risk of preterm delivery compared with mothers who used neither (odds ratio [OR] = 0.69; 95% confidence interval [CI], 0.19-1.98), whereas mothers who used depressant drugs without smoking had more than twice the odds of having preterm delivery (OR = 2.31; 95% CI, 1.19-4.44), and infants were at risk of a 1-week reduction in gestational age (OR = -1.05; 95% CI, -2.07 to -0.03). Concurrently smoking and using depressant drugs was associated with increased odds of preterm birth (OR = 1.83; 95% CI, 1.28-2.61), as was concurrently smoking and using stimulant drugs (OR = 1.73; 95% CI, 1.14-2.59). CONCLUSIONS: Using stimulant drugs and depressant drugs during pregnancy is a risk factor for preterm birth. The individual and combined effects of using these drugs with smoking must be considered together to reduce the risk of preterm birth in the United States.


Assuntos
Nascimento Prematuro/etnologia , Transtornos Relacionados ao Uso de Substâncias/etnologia , Adulto , Boston , Depressores do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Grupos Étnicos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Razão de Chances , Pobreza , Gravidez , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/etnologia , Fatores de Risco , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Fumar Tabaco/etnologia , Estados Unidos , Adulto Jovem
6.
Psychopharmacology (Berl) ; 237(6): 1795-1812, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32206828

RESUMO

RATIONALE: With repeated administration, the psychomotor activating effects of drugs such as cocaine or amphetamine can change in very different ways-showing sensitization or tolerance-depending on whether they are administered more or less intermittently. This behavioral plasticity is thought to reflect, at least in part, changes in dopamine (DA) neurotransmission, and therefore, may provide insights into the development of substance use disorders. Indeed, the most widely used preclinical model of cocaine addiction, which involves Long Access (LgA) self-administration procedures, is reported to produce tolerance to cocaine's psychomotor activating effects and effects on DA activity. In contrast, Intermittent Access (IntA) cocaine self-administration is more effective than LgA in producing addiction-like behavior, but sensitizes DA neurotransmission. There is, however, very little information concerning the effects of IntA experience on the psychomotor activating effects of cocaine. OBJECTIVE: The objective of this study was to determine whether IntA experience produces psychomotor sensitization with similar characteristics to that produced by the intermittent, noncontingent administration of cocaine. RESULTS: IntA to cocaine did indeed produce psychomotor sensitization that (1) was greater after a long (30 days) vs. short (1 day) period of withdrawal, (2) was greater in females than males, and (3) resulted in cross-sensitization to another psychomotor stimulant drug, amphetamine. CONCLUSION: The tolerance sometimes associated with LgA cocaine self-administration has been cited in support of the idea that, in addiction, drug-seeking and drug-taking is motivated to overcome a DA deficiency and associated anhedonia. In contrast, the neurobehavioral sensitization associated with IntA cocaine self-administration favors an incentive-sensitization view.


Assuntos
Comportamento Aditivo/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/psicologia , Administração Intravenosa , Animais , Comportamento Aditivo/fisiopatologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Inibidores da Captação de Dopamina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Masculino , Motivação/efeitos dos fármacos , Motivação/fisiologia , Desempenho Psicomotor/fisiologia , Ratos , Ratos Sprague-Dawley , Autoadministração , Fatores Sexuais , Síndrome de Abstinência a Substâncias/fisiopatologia
7.
Psychopharmacology (Berl) ; 237(5): 1481-1491, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32034449

RESUMO

RATIONALE: In previous studies, we have demonstrated that seized samples of a smokable form of cocaine, also known as coca paste (CP), induced behavioral sensitization in rats. Interestingly, this effect was accelerated and enhanced when the samples were adulterated with caffeine. While the cocaine phenomenon is associated with persistent functional and structural alterations in the prefrontal cortex (PFC) and nucleus accumbens (NAc), the molecular mechanisms underlying the CP sensitization and the influence of caffeine remains still unknown. OBJECTIVE: We examined the gene expression in NAc and mPFC after the expression caffeine-adulterated and non-adulterated CP locomotor sensitization. METHODS: The locomotor sensitization was established in C57BL/6 mice, repeatedly treated with a CP-seized sample adulterated with caffeine (CP-2) and a non-adulterated one (CP-1). We then assessed the mRNA expression of receptor subunits of the dopaminergic and glutamatergic systems in the medial PFC (mPFC) and NAc. Other molecular markers (e.g., adenosinergic, endocannabinoid receptor subunits, and synaptic plasticity-associated genes) were also analyzed. RESULTS: Only CP-2-treated mice expressed locomotor sensitization. This phenomenon was associated with increased Drd1a, Gria1, Cnr1, and Syn mRNA expression levels in the NAc. Drd3 mRNA expression levels were only significantly increased in mPFC of CP-2-treated group. CONCLUSIONS: Our results demonstrated that caffeine actively collaborates in the induction of the molecular changes underlying CP sensitization. The present study provides new knowledge on the impact of active adulterants to understand the early dependence induced by CP consumption.


Assuntos
Cafeína/administração & dosagem , Cocaína/administração & dosagem , Contaminação de Medicamentos , Locomoção/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Animais , Estimulantes do Sistema Nervoso Central/administração & dosagem , Coca , Dopamina/metabolismo , Inibidores da Captação de Dopamina/administração & dosagem , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos
8.
Lancet ; 395(10222): 450-462, 2020 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-31982036

RESUMO

Attention-deficit hyperactivity disorder (ADHD), like other psychiatric disorders, represents an evolving construct that has been refined and developed over the past several decades in response to research into its clinical nature and structure. The clinical presentation and course of the disorder have been extensively characterised. Efficacious medication-based treatments are available and widely used, often alongside complementary psychosocial approaches. However, their effectiveness has been questioned because they might not address the broader clinical needs of many individuals with ADHD, especially over the longer term. Non-pharmacological approaches to treatment have proven less effective than previously thought, whereas scientific and clinical studies are starting to fundamentally challenge current conceptions of the causes of ADHD in ways that might have the potential to alter clinical approaches in the future. In view of this, we first provide an account of the diagnosis, epidemiology, and treatment of ADHD from the perspective of both the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the eleventh edition of the International Classification of Diseases. Second, we review the progress in our understanding of the causes and pathophysiology of ADHD on the basis of science over the past decade or so. Finally, using these discoveries, we explore some of the key challenges to both the current models and the treatment of ADHD, and the ways in which these findings can promote new perspectives.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Humanos , Guias de Prática Clínica como Assunto
9.
Expert Opin Pharmacother ; 21(4): 417-426, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31971448

RESUMO

Introduction: Attention-deficit/hyperactivity disorder (ADHD) commonly occurs in children, adolescents, and adults. Although symptoms of ADHD often respond robustly to treatment with stimulants (amphetamine or methylphenidate), not all patients are appropriate candidates for treatment with these drugs. Guanfacine extended-release (GXR) is a non-stimulant alternative drug approved for the treatment of ADHD in the United States (U.S.), Canada, and Europe.Areas covered: The chemistry, pharmacokinetics, mechanism of action and dosage of GXR are presented. Efficacy and safety data obtained in clinical trials with subjects aged 6-17 years for both GXR monotherapy and use in combination with stimulants are described. Meta-analyses comparing GXR to other drugs are presented. MedWatch surveillance data collected for GXR since approval in the U.S. are also discussed.Expert opinion: Although GXR is effective for the treatment of ADHD and has a different side effect profile than stimulants, it is not as impressive in reducing symptoms. Despite the availability of multiple pharmacological treatments for ADHD, there remains an unmet need for formulations as potent as stimulants but with fewer adverse effects. Several pharmacological agents for ADHD treatment are in development. It is not clear that any of these compounds will replace currently available formulations as first-line alternatives.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Guanfacina/uso terapêutico , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Preparações de Ação Retardada , Composição de Medicamentos , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Guanfacina/administração & dosagem , Guanfacina/efeitos adversos , Humanos , Metilfenidato/uso terapêutico , Estados Unidos
11.
J Vet Pharmacol Ther ; 43(1): 91-95, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31769075

RESUMO

Frogs have permeable skin, so transdermal delivery provides a practical alternative to traditional dosing routes. However, little is known about how frog skin permeability differs interspecifically, and there are different reported clinical outcomes following topical application of the same chemical in different frog species. This study collated in vitro absorption kinetic data previously reported for two frog species: the green tree frog (Litoria caerulea) and the cane toad (Rhinella marina), and used linear mixed-effects modelling to produce a model of absorption. Histology of skin samples from each species was performed to observe morphological differences that may affect absorption. Absorption kinetics differed significantly between species, with the logP of the applied chemical a better predictor of permeability than molecular weight. Application site also influenced permeability, with dorsal permeability consistently higher in cane toads. Ventral permeability was more consistent between species. Skin thickness differed between species and skin regions, and this may explain the differences in absorption kinetics. Guidelines for selecting chemicals and dosing site when treating frogs are presented. The permeability differences identified may explain the poor reproducibility reported in the treatment of disease across frog species, and reinforces the importance of considering interspecies differences when designing therapeutic treatments for frogs.


Assuntos
Anuros , Ácido Benzoico/farmacocinética , Cafeína/farmacocinética , Ibuprofeno/farmacocinética , Pele , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/farmacocinética , Ácido Benzoico/administração & dosagem , Ácido Benzoico/química , Cafeína/administração & dosagem , Cafeína/química , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/farmacocinética , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Permeabilidade , Absorção Cutânea , Especificidade da Espécie
12.
J Infect Dis ; 221(2): 243-250, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31504660

RESUMO

BACKGROUND: With the nation's focus on the opioid crisis, methamphetamine has made a comeback, potentially increasing risk for hepatitis B. We examined factors associated with hepatitis B virus (HBV) exposure among people who reported ever using methamphetamine in a nationally representative survey. METHODS: We used the National Health and Nutrition Examination Survey to examine factors associated with HBV exposure among participants who reported ever using methamphetamine using bivariate and multivariable logistic regression. RESULTS: Overall, 847 participants met the study inclusion criteria. In multivariable logistic regression, female sex (adjusted odds ratio, 3.83; 95% confidence interval, 1.65-8.90), living below the poverty threshold (3.17; 1.39-7.21), injection drug use (4.89; 1.95-12.26), active hepatitis C virus infection (3.39; 1.10-12.26), and identifying as men who have sex with men (28.21; 5.19-153.38) were significantly associated with HBV exposure. CONCLUSIONS: The odds of HBV exposure for female participants who reported using methamphetamine were 4 times than that for male participants. Poverty, injection drug use, and hepatitis C virus infection were also associated. As methamphetamine use increases, it is critical to identify those at risk of acquiring HBV infections in order to target testing and vaccination.


Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Hepatite B/transmissão , Metanfetamina/administração & dosagem , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B/isolamento & purificação , Humanos , Drogas Ilícitas , Masculino , Pessoa de Meia-Idade , Medição de Risco , Adulto Jovem
13.
Dev Psychobiol ; 62(2): 170-180, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31456229

RESUMO

Methylphenidate (MP) is a commonly prescribed psychostimulant to individuals with Attention Deficit Hyperactivity Disorder, and is often used illicitly among healthy individuals with intermittent breaks to coincide with breaks from school. This study examined how intermittent abstinence periods impact the physiological and behavioral effects of chronic oral MP self-administration in rats, and whether these effects persist following prolonged abstinence from the drug. Rats were treated orally with water, low-dose (LD), or high-dose (HD) MP, beginning at PND 28. This daily access continued for three consecutive weeks followed by a 1-week abstinence; after three repeats of this cycle, there was a 5-week abstinence period. Throughout the study, we examined body weight, food intake, locomotor activity, and anxiety- and depressive-like behaviors. During the treatment phase, HD MP decreased body weight, food intake, and depressive- and anxiety-like behaviors, while it increased locomotor activity. During intermittent abstinence, the effects of MP on locomotor activity were eliminated. During prolonged abstinence, most of the effects of HD MP were ameliorated to control levels, with the exception of weight loss and anxiolytic effects. These findings suggest that intermittent exposure to chronic MP causes physiological and behavioral effects that are mostly reversible following prolonged abstinence.


Assuntos
Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Metilfenidato/farmacologia , Animais , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Masculino , Metilfenidato/administração & dosagem , Ratos , Ratos Sprague-Dawley
14.
J Perinatol ; 40(2): 288-293, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31758062

RESUMO

OBJECTIVE: To assess site variability and concomitant respiratory support related to the timing of caffeine discontinuation, and compare clinical characteristics of infants who discontinued caffeine before vs. within the last week of hospitalization. STUDY DESIGN: Cohort study of 81,110 infants <35 weeks gestational age and <1500 g birth weight discharged from 304 neonatal intensive care units from 2001-2016. RESULTS: The mean postmenstrual age at caffeine discontinuation ranged from 32 to 37 weeks among sites. Respiratory support at the time of discontinuation was common, but variable, with 0-57% of infants receiving positive airway pressure at caffeine discontinuation by site. Infants who discontinued caffeine within the last week of hospitalization had longer total duration of caffeine, but were discharged from the hospital at an earlier postmenstrual age. CONCLUSION: There was substantial variability among sites in the timing of caffeine discontinuation before discharge and respiratory support at the time of caffeine discontinuation.


Assuntos
Apneia/tratamento farmacológico , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Citratos/administração & dosagem , Doenças do Prematuro/tratamento farmacológico , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Apneia/terapia , Estudos de Coortes , Terapia Combinada , Esquema de Medicação , Feminino , Hospitalização , Humanos , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Doenças do Prematuro/terapia , Recém-Nascido de muito Baixo Peso/fisiologia , Masculino , Respiração com Pressão Positiva , Respiração
15.
Psychopharmacology (Berl) ; 237(3): 655-667, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31758209

RESUMO

RATIONALE: Vaccines have been developed as a potential treatment for methamphetamine (meth) use disorder (MUD). Immunization with the meth vaccine IXT-v100 has previously been shown to elicit antibodies with high affinity for meth and thus may be an effective treatment for MUD. OBJECTIVES: These studies were designed to determine the efficacy of IXT-v100 on meth-taking and meth-seeking behaviors in rats. METHODS: In the acquisition and maintenance study, male and female rats were trained to self-administer meth (0.06 mg/kg/infusion) over an 8-week period following vaccination. In the last 4 weeks, the dose of meth was increased or decreased each week. To assess meth-seeking behavior, the meth-primed reactivity model was used. Rats were trained to self-administer meth for 5 weeks, followed by a 5-week or 11-week forced abstinence period during which the animals were vaccinated. Rats were then placed back into the self-administration chamber immediately after being injected with meth (1 mg/kg, i.p.) but did not receive meth during the session. Responses were recorded and used as a measure of meth seeking. RESULTS: Results from the acquisition and maintenance study in Wistar rats show that vaccination with IXT-v100 adjuvanted with glucopyranosyl lipid A stable emulsion decreases the percentage of animals that will self-administer a moderate level of meth. In the meth-primed reactivity studies, results from males showed that vaccination significantly attenuates meth-seeking behavior. CONCLUSION: Together, these results suggest vaccination with IXT-v100 may be effective at decreasing meth-taking and meth-seeking behaviors in humans suffering with MUD.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metanfetamina/administração & dosagem , Metanfetamina/efeitos adversos , Vacinas/administração & dosagem , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Animais , Relação Dose-Resposta a Droga , Comportamento de Procura de Droga/efeitos dos fármacos , Comportamento de Procura de Droga/fisiologia , Feminino , Masculino , Ratos , Ratos Wistar , Autoadministração , Resultado do Tratamento
16.
Anesth Analg ; 130(1): 66-75, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31274603

RESUMO

BACKGROUND: Residency training in anesthesiology involves care of hospitalized patients and necessitates overnight work, resulting in altered sleep patterns and sleep deprivation. Caffeine consumption is commonly used to improve alertness when fatigued after overnight work, in preparation for the commute home. METHODS: We studied the impact of drinking a caffeinated energy drink (160 mg of caffeine) on driving performance in a high-fidelity, virtual reality driving simulator (Virginia Driving Safety Laboratory using the Driver Guidance System) in anesthesiology resident physicians immediately after 6 consecutive night-float shifts. Twenty-six residents participated and were randomized to either consume a caffeinated or noncaffeinated energy drink 60 minutes before the driving simulation session. After a subsequent week of night-float work, residents performed the same driving session (in a crossover fashion) with the opposite intervention. Psychomotor vigilance task (PVT) testing was used to evaluate reaction time and lapses in attention. RESULTS: After 6 consecutive night-float shifts, anesthesiology residents who consumed a caffeinated energy drink had increased variability in driving for throttle, steering, and speed during the first 10 minutes of open-road driving but proceeded to demonstrate improved driving performance with fewer obstacle collisions (epoch 2: 0.65 vs 0.87; epoch 3: 0.47 vs 0.95; P = .03) in the final 30 minutes of driving as compared to driving performance after consumption of a noncaffeinated energy drink. Improved driving performance was most apparent during the last 30 minutes of the simulated drive in the caffeinated condition. Mean reaction time between the caffeine and noncaffeine states differed significantly (278.9 ± 29.1 vs 294.0 ± 36.3 milliseconds; P = .021), while the number of major lapses (0.09 ± 0.43 vs 0.27 ± 0.55; P = .257) and minor lapses (1.05 ± 1.39 vs 2.05 ± 3.06; P = .197) was not significantly different. CONCLUSIONS: After consuming a caffeinated energy drink on conclusion of 6 shifts of night-float work, anesthesiology residents had improved control of driving performance variables in a high-fidelity driving simulator, including a significant reduction in collisions as well as slightly faster reaction times.


Assuntos
Anestesiologistas/psicologia , Anestesiologia/educação , Condução de Veículo/psicologia , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Educação de Pós-Graduação em Medicina , Bebidas Energéticas , Internato e Residência , Jornada de Trabalho em Turnos , Carga de Trabalho , Acidentes de Trânsito/prevenção & controle , Adulto , Anestesiologistas/educação , Nível de Alerta/efeitos dos fármacos , Cafeína/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estudos Cross-Over , Bebidas Energéticas/efeitos adversos , Feminino , Treinamento com Simulação de Alta Fidelidade , Humanos , Masculino , Tempo de Reação/efeitos dos fármacos , Análise e Desempenho de Tarefas , Fatores de Tempo
17.
Psychopharmacology (Berl) ; 237(3): 825-832, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31832721

RESUMO

RATIONALE AND OBJECTIVE: Poor inhibitory control is a well-established risk factor for alcohol use disorder (AUD). Similarly, greater sensitivity to the stimulant effects and less sensitivity to the sedative effects of alcohol are also strongly linked to risk for AUD. Traditionally, these two risk factors have been considered to be orthogonal, and thus they have been studied independently. However, recent evidence from animal and human studies suggests that they may be related. The current study examined the relationship between inhibitory control and subjective responses to alcohol in a sample of healthy young adults. METHODS: Moderate social drinkers (N = 69) first completed the stop signal task to assess inhibitory control. They then participated in four sessions in which they received an oral dose of ethanol (0.8 g/kg) or placebo in alternating order, providing self-report measures of stimulation and sedation on the Biphasic Alcohol Effects Scale (BAES) at regular intervals. RESULTS: Linear mixed effects models showed that poor inhibitory control was associated with greater stimulation and less sedation following alcohol compared with placebo. CONCLUSION: These findings provide the first direct evidence that individuals with poor inhibitory control experience greater sensitivity to the rewarding, stimulant effects of alcohol, and less sensitivity to the negative, sedative effects. These findings suggest that inhibition and subjective response to alcohol are not independent risk factors, and that together they constitute a heightened profile of risk for AUD.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Inibição Psicológica , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/tendências , Alcoolismo/etiologia , Alcoolismo/psicologia , Método Duplo-Cego , Etanol/efeitos adversos , Feminino , Humanos , Masculino , Recompensa , Autorrelato , Adulto Jovem
18.
AIDS Behav ; 24(6): 1865-1875, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31834542

RESUMO

Amphetamine use is higher among men who have sex with men (MSM) compared with other men, and is associated with sexual behavior linked to HIV transmission. No national estimates of amphetamine use among MSM with HIV have been published. We used data from the Medical Monitoring Project, a nationally representative sample of persons with diagnosed HIV, to describe patterns in amphetamine use in the past 12 months among MSM during 2015-2016 (N = 3796). Prevalence of amphetamine use in this population was 9.6% (95% CI 7.6, 11.6%) in the past 12 months. MSM who used amphetamines were more likely to have condomless sex with partners without HIV or of unknown serostatus (PR 1.87; 95% CI 1.62, 2.16) and less likely to be durably virally suppressed (PR 0.81; 95% CI 0.71, 0.91). Interventions to address amphetamine use and associated transmission risk behaviors among MSM living with HIV may decrease transmission.


Assuntos
Anfetaminas , Estimulantes do Sistema Nervoso Central , Infecções por HIV , Homossexualidade Masculina , Minorias Sexuais e de Gênero , Anfetaminas/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Prevalência , Assunção de Riscos , Comportamento Sexual , Parceiros Sexuais , Estados Unidos/epidemiologia
19.
Eur J Clin Pharmacol ; 76(2): 229-237, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786618

RESUMO

PURPOSE: The primary aim of this study was to explore the potential of alternative sampling matrices for methylphenidate by assessing the correlations between dl-threo-methylphenidate and dl-threo-ritalinic acid concentrations in exhaled breath and oral fluid with those in plasma, in repeated samples collected after a single oral dose of methylphenidate. The secondary aim was to study the enantioselective pharmacokinetics of methylphenidate in plasma, with a focus on interindividual variability in the metabolism of methylphenidate to ritalinic acid. METHODS: Twelve healthy volunteers received a single oral dose of dl-threo-methylphenidate (Ritalin® capsules, 20 mg). Venous blood samples were collected for 24 h, and plasma analyzed for threo-enantiomers of methylphenidate and ritalinic acid with LC-MS/MS. Repeated sampling of exhaled breath, using a particle filter device, and of non-stimulated oral fluid, using a felt pad device, was also performed. Exhaled breath and oral fluid were analyzed with a non-enantioselective LC-MS/MS method for dl-threo-methylphenidate and dl-threo-ritalinic acid. RESULTS: In all subjects, d-threo-methylphenidate was detectable in plasma for at least 15 h after the dose with a biphasic profile. l-threo-Methylphenidate was measurable in only five subjects and in most cases in low concentrations. However, one female subject displayed a biphasic concentration-time profile for l-threo-methylphenidate. This subject also had the highest d-threo-methylphenidate AUC (191 ng*h/mL versus 32-119 ng*h/mL in the other subjects). d-threo-Ritalinic acid concentrations were on average 25-fold higher (range 6-126) than the corresponding d-threo-methylphenidate concentrations. Single-time point plasma concentration ratios between d-threo-ritalinic acid and d-threo-methylphenidate 1.5-12 h after dose correlated highly (r = 0.88-0.98) with the d-threo-ritalinic acid AUC/d-threo-methylphenidate AUC ratio. In eleven subjects, dl-threo-methylphenidate in oral fluid mirrored the biphasic profile of methylphenidate (sum of d- and l-threo-enantiomers) in plasma, but the concentrations in oral fluid were on average 1.8 times higher than in plasma. dl-threo-Methylphenidate was detected in exhaled breath in all subjects, but there was no consistent concentration-time pattern. CONCLUSIONS: In some subjects, the pharmacologically less active l-threo-enantiomer may contribute to the total plasma methylphenidate concentrations. Monitoring methylphenidate concentrations without enantiomeric determination carries the risk of missing such subjects, which might affect how the plasma concentrations of methylphenidate are interpreted and used for clinical decision making. The use of exhaled breath and oral fluid to assess medication adherence to MPH in patients with ADHD warrants further studies.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacocinética , Metilfenidato/farmacocinética , Administração Oral , Adulto , Área Sob a Curva , Testes Respiratórios/métodos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Cromatografia Líquida , Feminino , Humanos , Masculino , Adesão à Medicação , Metilfenidato/administração & dosagem , Metilfenidato/análogos & derivados , Estereoisomerismo , Espectrometria de Massas em Tandem , Adulto Jovem
20.
Drug Alcohol Depend ; 206: 107776, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31812878

RESUMO

BACKGROUND: Preclinical studies suggest that the non-selective phosphodiesterase inhibitor, Ibudilast (IBUD) may contribute to the treatment of methamphetamine (METH) use disorder through the attenuation of METH-induced inflammatory markers such as adhesion molecules, sICAM-1 and sVCAM-1, and cytokines, IL-6 and TNF-α. OBJECTIVE: The present study aimed to test whether treatment with IBUD can attenuate peripheral markers of inflammation during a METH challenge in an inpatient clinical trial of 11 patients. METHODS: This trial followed a randomized, within-subjects crossover design where participants received a METH challenge, during which five participants were treated with placebo then with IBUD, while the remaining six participants were treated with IBUD prior to placebo. Mixed effects regression modeled changes in peripheral markers of inflammation-sICAM-1, sVCAM-1, TNF-α, IL-6, MIF, and cathepsin D-by treatment condition, with measurements at baseline, 60 min post-METH infusion, and 360 min post-METH infusion. RESULTS: While on placebo, sICAM-1, sVCAM-1, and cathepsin D significantly increased by 60 min post-METH infusion, while IL-6 significantly increased 360 min post-METH infusion. Treatment with IBUD significantly reduced METH-induced levels of sICAM-1, sVCAM-1, and cathepsin D at 60 min post-METH infusion. CONCLUSIONS: Our findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/sangue , Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/sangue , Metanfetamina/efeitos adversos , Piridinas/uso terapêutico , Adulto , Animais , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estudos Cross-Over , Feminino , Humanos , Infusões Intravenosas , Masculino , Metanfetamina/administração & dosagem , Pessoa de Meia-Idade , Inibidores de Fosfodiesterase/farmacologia , Inibidores de Fosfodiesterase/uso terapêutico , Piridinas/farmacologia
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