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1.
Science ; 368(6487): 197-201, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32273471

RESUMO

Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in the midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in the VTA. By reducing H3Q5dop in the VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated dopamine release in the nucleus accumbens, and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in the VTA.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína/efeitos adversos , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Comportamento de Procura de Droga , Histonas/metabolismo , Área Tegmentar Ventral/metabolismo , Animais , Transtornos Relacionados ao Uso de Cocaína/genética , Regulação da Expressão Gênica , Glutamina/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Núcleo Accumbens/metabolismo , Ratos , Ratos Sprague-Dawley , Transmissão Sináptica
2.
Invest Educ Enferm ; 37(2)2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31487440

RESUMO

OBJECTIVES: To understand the family experience regarding the trajectory of crack users for the street situation. METHODS: Qualitative study using the systemic approach as the theoretical referential and the narrative as methodological referential. We conducted interviews with eleven family members of crack users with street situation experience cared for at a community mental health service. We analyzed the interviews using the inductive content analysis technique. RESULTS: The family members understood the trajectory of the crack users for the street situation from two perspectives. One before the street situation process, for which they described a problematic childhood, the presence of stressor traumas/events, vulnerabilities in the family environment, and their family members' encounter with the drug world. Moreover, another posterior to the street situation, for which they narrated the perception of alterations in the users, the discovery of crack use, the deepening of the individuals' relationship with the streets, and the adoption of coping strategies. CONCLUSIONS: It was made evident that the family adopts an explicative model for the behavior of drug use and contact with the streets based on the life history of the crack user family member.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Serviços Comunitários de Saúde Mental/organização & administração , Cocaína Crack , Família/psicologia , Adaptação Psicológica , Adulto , Brasil , Relações Familiares , Feminino , Pessoas em Situação de Rua/psicologia , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade
3.
Psychopharmacology (Berl) ; 236(8): 2359-2371, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31372665

RESUMO

RATIONALE: Drug addiction has been suggested to develop through drug-induced changes in learning and memory processes. Whilst the initiation of drug use is typically goal-directed and hedonically motivated, over time, drug-taking may develop into a stimulus-driven habit, characterised by persistent use of the drug irrespective of the consequences. Converging lines of evidence suggest that stimulant drugs facilitate the transition of goal-directed into habitual drug-taking, but their contribution to goal-directed learning is less clear. Computational modelling may provide an elegant means for elucidating changes during instrumental learning that may explain enhanced habit formation. OBJECTIVES: We used formal reinforcement learning algorithms to deconstruct the process of appetitive instrumental learning and to explore potential associations between goal-directed and habitual actions in patients with cocaine use disorder (CUD). METHODS: We re-analysed appetitive instrumental learning data in 55 healthy control volunteers and 70 CUD patients by applying a reinforcement learning model within a hierarchical Bayesian framework. We used a regression model to determine the influence of learning parameters and variations in brain structure on subsequent habit formation. RESULTS: Poor instrumental learning performance in CUD patients was largely determined by difficulties with learning from feedback, as reflected by a significantly reduced learning rate. Subsequent formation of habitual response patterns was partly explained by group status and individual variation in reinforcement sensitivity. White matter integrity within goal-directed networks was only associated with performance parameters in controls but not in CUD patients. CONCLUSIONS: Our data indicate that impairments in reinforcement learning are insufficient to account for enhanced habitual responding in CUD.


Assuntos
Encéfalo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Aprendizagem por Discriminação/fisiologia , Hábitos , Teorema de Bayes , Transtornos Relacionados ao Uso de Cocaína/psicologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Motivação/fisiologia , Estimulação Luminosa/métodos
4.
Molecules ; 24(14)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315244

RESUMO

Currently, there are no approved pharmacotherapies for addiction to cocaine and other psychostimulant drugs. Several studies have proposed that cannabidiol (CBD) could be a promising treatment for substance use disorders. In the present work, the authors describe the scarce preclinical and human research about the actions of CBD on the effects of stimulant drugs, mainly cocaine and methamphetamine (METH). Additionally, the possible mechanisms underlying the therapeutic potential of CBD on stimulant use disorders are reviewed. CBD has reversed toxicity and seizures induced by cocaine, behavioural sensitization induced by amphetamines, motivation to self-administer cocaine and METH, context- and stress-induced reinstatement of cocaine and priming-induced reinstatement of METH seeking behaviours. CBD also potentiated the extinction of cocaine- and amphetamine-induced conditioned place preference (CPP), impaired the reconsolidation of cocaine CPP and prevented priming-induced reinstatement of METH CPP. Observational studies suggest that CBD may reduce problems related with crack-cocaine addiction, such as withdrawal symptoms, craving, impulsivity and paranoia (Fischer et al., 2015). The potential mechanisms involved in the protective effects of CBD on addiction to psychostimulant drugs include the prevention of drug-induced neuroadaptations (neurotransmitter and intracellular signalling pathways changes), the erasure of aberrant drug-memories, the reversion of cognitive deficits induced by psychostimulant drugs and the alleviation of mental disorders comorbid with psychostimulant abuse. Further, preclinical studies and future clinical trials are necessary to fully evaluate the potential of CBD as an intervention for cocaine and methamphetamine addictive disorders.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Canabidiol/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Resiliência Psicológica , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Animais , Canabidiol/farmacologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Comportamentos de Risco à Saúde/efeitos dos fármacos , Humanos , Metanfetamina/toxicidade , Camundongos , Estudos Observacionais como Assunto , Síndrome de Abstinência a Substâncias/tratamento farmacológico
5.
Psychopharmacology (Berl) ; 236(7): 2155-2171, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161451

RESUMO

RATIONALE: Exercise shows promise as a treatment option for addiction; but in order to prevent relapse, it may need to be introduced early in the course of treatment. OBJECTIVE: We propose that exercise, by upregulating dorsal medial prefrontal cortex (dmPFC)-nucleus accumbens (NAc) transmission, offsets deficits in pathways targeting glutamate, BDNF, and dopamine during early abstinence, and in doing so, normalizes neuroadaptations that underlie relapse. METHODS: We compared the effects of exercise (wheel running, 2-h/day) during early (days 1-7), late (days 8-14), and throughout abstinence (days 1-14) to sedentary conditions on cocaine-seeking and gene expression in the dmPFC and NAc core of male rats tested following 24-h/day extended-access cocaine (up to 96 infusions/day) or saline self-administration and protracted abstinence (15 days). Based on these data, we then used site-specific manipulation to determine whether dmPFC metabotropic glutamate receptor5 (mGlu5) underlies the efficacy of exercise. RESULTS: Exercise initiated during early, but not late abstinence, reduced cocaine-seeking; this effect was strongly associated with dmPFC Grm5 expression (gene encoding mGlu5), and modestly associated with dmPFC Grin1 and Bdnf-IV expression. Activation of mGlu5 in the dmPFC during early abstinence mimicked the efficacy of early-initiated exercise; however, inhibition of these receptors prior to the exercise sessions did not block its efficacy indicating that there may be redundancy in the mechanisms through which exercise reduces cocaine-seeking. CONCLUSION: These findings indicate that addiction treatments, including exercise, should be tailored for early versus late phases of abstinence since their effectiveness will vary over abstinence due to the dynamic nature of the underlying neuroadaptations.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/terapia , Cocaína/administração & dosagem , Condicionamento Físico Animal/fisiologia , Córtex Pré-Frontal/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Animais , Comportamento Aditivo/metabolismo , Comportamento Aditivo/prevenção & controle , Comportamento Aditivo/psicologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtornos Relacionados ao Uso de Cocaína/psicologia , Inibidores da Captação de Dopamina/administração & dosagem , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/psicologia , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Recidiva , Corrida/fisiologia , Corrida/psicologia , Autoadministração
6.
PLoS One ; 14(6): e0218334, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31226126

RESUMO

Crack cocaine use disorder (CUD) has been related to sex differences. This work aimed to compare the severity of drug use and the severity of other negative related outcomes in males and females with CUD. A total of 1344 inpatients (798 males and 546 females) with crack cocaine use disorder (CUD) were evaluated by a detailed multidimensional clinical assessment, including addiction severity and trauma exposure. Linear regression predicted higher drug use severity (ß = 0.273, p < 0.001) and more problems in domains related to childcare issues (ß = 0.321), criminal involvement (ß = 0.108), work-related problems (ß = 0.281) and social support impairments (ß = 0.142) for females, all with p < 0.001. Alcohol problems were predicted to be higher in males (ß = -0.206, P < 0.001). Females had higher rates of other mental disorders, particularly trauma and stress-related disorders (OR: 3.206, CI: 2.22, 4.61). Important sex differences also emerged in trauma history and HIV infection prevalence. CUD has a more severe clinical presentation among females facing early abstinence. Sex differences in the CUD course indicate the need for consideration of sex-specific interventions and research.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Cocaína Crack/efeitos adversos , Caracteres Sexuais , Adulto , Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Comorbidade , Feminino , Hospitalização , Humanos , Modelos Lineares , Masculino
7.
Neuron ; 103(1): 80-91.e7, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31101395

RESUMO

Craving for cocaine progressively increases in cocaine users during drug-free periods, contributing to relapse. The projection from the infralimbic cortex to the nucleus accumbens shell (IL-NAc) is thought to inhibit cocaine seeking. However, it is not known whether and how IL-NAc neurons contribute to the increased motivation associated with a drug-free period. We first performed cellular resolution imaging of IL-NAc neurons in rats during a drug-seeking test. This revealed neurons with spatial selectivity within the cocaine-associated context, a decrease in activity around the time of cocaine seeking, and an inverse relationship between cocaine-seeking activity and subsequent cocaine motivation. All these properties were reduced by a drug-free period. Next, we transiently activated this projection, which resulted in reduced drug seeking, regardless of the drug-free period. Taken together, this suggests that altered IL-NAc activity after a drug-free period may enhance cocaine motivation without fundamentally altering the projection's ability to inhibit drug seeking.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Motivação , Neurônios , Núcleo Accumbens/fisiopatologia , Animais , Sinalização do Cálcio , Transtornos Relacionados ao Uso de Cocaína/psicologia , Fissura , Comportamento de Procura de Droga , Extinção Psicológica , Masculino , Núcleo Accumbens/citologia , Optogenética , Ratos , Ratos Long-Evans , Autoadministração , Percepção Espacial
8.
Drug Alcohol Depend ; 200: 50-58, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31085378

RESUMO

BACKGROUND: Prenatal cocaine exposure (PCE) is associated with arousal dysregulation, but interactions between exposure and age are rarely investigated directly with longitudinal study designs. Our previous study had examined task-elicited emotional arousal and noted persistently high amygdala activations in the development of adolescents with PCE. However, while externally imposed emotional arousal could be considered a "state" effect depending on specific task stimuli, it is still unclear whether similar developmental alterations extend to intrinsic functional connectivity (FC), reflecting more of a "trait" effect. METHODS: We used a longitudinal design and analyzed resting-state functional magnetic resonance imaging data acquired twice from 25 adolescents with PCE and 16 non-exposed controls. Both groups were each scanned first at the mean age of 14.3 and then again at 16.6 years. Seeding in bilateral amygdalae and comparing the 2nd scan with the 1st, we examined the interaction effect between PCE and age on FCs in the emotional network. RESULTS: Compared with the younger age, we observed a generally decreased FC in the emotional network of the control group at the older age, but these FCs were generally increased at the older age in this same network of the PCE group. Additionally, this interaction effect of exposure by age in the right fusiform was positively correlated with the emotional interference imposed by external task stimuli. CONCLUSIONS: These results provided additional data directly characterizing developmental changes in the emotional network of adolescents with PCE, complementing and extending the notion of a PCE-associated long-term teratogenic effect on arousal regulation.


Assuntos
Tonsila do Cerebelo/diagnóstico por imagem , Nível de Alerta/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Cocaína/efeitos adversos , Rede Nervosa/diagnóstico por imagem , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Adolescente , Adulto , Tonsila do Cerebelo/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/psicologia , Emoções/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Masculino , Rede Nervosa/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/psicologia
9.
Psychiatry Res ; 276: 283-289, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31128488

RESUMO

Psychiatric comorbidity can negatively impact the course of addictions. Psychiatric features of patients who continued treatment after the first stage of an addiction program have not been sufficiently analysed. Therefore, only these patients were included in order to compare psychiatric comorbidity and clinical factors between patients who were able or not to complete a long term substance-free program. Treatment-completion status of 245 patients was systematically recorded. Addiction severity, psychiatry comorbidity, and psychological symptoms were evaluated. No significant differences were found regarding comorbid psychiatric diagnoses and the completion of the treatment. Longer treatment duration (OR: 1.22; p < 0.01), higher educational level (OR: 2.37; p = 0.02), and cocaine dependence as main substance (OR: 3.68; p < 0.01) were found to be related to increased likelihood in completing the treatment. Patients with higher severity of alcohol consumption (OR: 0.06; p = 0.02) and more depressive symptoms (OR: 0.95; p = 0.01) completed the treatment less frequently. Moreover, differences regarding employment problems, treatment facilities, anxiety symptoms, dysfunctional impulsivity, and mental HRQoL were found. It is concluded that comorbid psychiatric diagnoses do not determine treatment outcomes. However, therapeutic and psychological factors have a major influence on the likelihood to complete a long-term treatment program.


Assuntos
Assistência de Longa Duração/psicologia , Transtornos Mentais/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Cooperação e Adesão ao Tratamento/psicologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Comorbidade , Feminino , Nível de Saúde , Humanos , Masculino , Transtornos Mentais/psicologia , Qualidade de Vida , Centros de Tratamento de Abuso de Substâncias/estatística & dados numéricos , Resultado do Tratamento
10.
Psychopharmacology (Berl) ; 236(9): 2785-2796, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31115612

RESUMO

RATIONALE: Early life stress (ELS), including childhood maltreatment, is a predictive factor for the emergence of cocaine use disorders (CUDs) in adolescence. OBJECTIVE: Accordingly, we examined whether post-pubertal male and female rhesus macaques that experienced infant maltreatment (maltreated, n = 7) showed greater vulnerability to cocaine self-administration in comparison with controls (controls, n = 7). METHODS: Infant emotional reactivity was measured to assess differences in behavioral distress between maltreated and control animals as a result of early life caregiving. Animals were then surgically implanted with indwelling intravenous catheters and trained to self-administer cocaine (0.001-0.3 mg/kg/infusion) under fixed-ratio schedules of reinforcement. Days to acquisition, and sensitivity to (measured by the EDMax dose of cocaine) and magnitude (measured by response rates) of the reinforcing effects of cocaine were examined in both groups. RESULTS: Maltreated animals demonstrated significantly higher rates of distress (e.g., screams) in comparison with control animals. When given access to cocaine, control males required significantly more days to progress through terminal performance criteria compared with females and acquired cocaine self-administration slower than the other three experimental groups. The dose that resulted in peak response rates did not differ between groups or sex. Under 5-week, limited-access conditions, males from both groups had significantly higher rates of responding compared with females. CONCLUSIONS: In control monkeys, these data support sex differences in cocaine self-administration, with females being more sensitive than males. These findings also suggest that ELS may confer enhanced sensitivity to the reinforcing effects of cocaine, especially in males.


Assuntos
Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Esquema de Reforço , Caracteres Sexuais , Maturidade Sexual/efeitos dos fármacos , Estresse Psicológico/psicologia , Animais , Transtornos Relacionados ao Uso de Cocaína/psicologia , Relação Dose-Resposta a Droga , Feminino , Macaca mulatta , Masculino , Distribuição Aleatória , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Autoadministração , Maturidade Sexual/fisiologia
11.
Epidemiol Serv Saude ; 28(1): e2018304, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30970076

RESUMO

OBJECTIVE: to analyze variation in craving levels according to individual and behavioral characteristics of crack cocaine users at two public treatment services in Pelotas, Rio Grande do Sul, Brazil. METHODS: this was a cross sectional study with a sample of 133 participants; the Cocaine Craving Questionnaire scale was used to verify craving levels. RESULTS: 86% of interviewees had moderate and severe craving levels; regarding individual factors, a higher level of severe craving was found in women (45%), those with brown skin color/"mestizos" (60%), low schooling (46%) and minor psychiatric disorders (59%); regarding behavioral factors, the level of severe craving was higher in users who divorced the last year (44%), those who had problems with the Law (61%), those who practiced violence acts (57%), those using more than four psychoactive substances (67%), and those with heavy crack consumption (57%). CONCLUSION: almost all crack users were found to have high craving levels; these were proportionally higher in some individual and behavioral variables.


Assuntos
Comportamento Aditivo/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Cocaína Crack/administração & dosagem , Fissura , Adulto , Brasil/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Violência/estatística & dados numéricos , Adulto Jovem
12.
Psychiatry Res Neuroimaging ; 287: 56-59, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-30991248

RESUMO

The current study investigated the combined effects of N-acetylcysteine and working memory (WM) training on behavioral and neural mechanisms of cue reactivity and WM in cocaine users in a randomized, double-blind design. Twenty-four of 38 cocaine-using men completed a 25-day treatment with either 2400 mg/day NAC or placebo. Both groups performed WM-training. During pre- and post-test lab-visits, neural mechanisms of cue reactivity and WM, and cue-induced craving and WM performance were assessed. Additionally, exploratory whole brain analyses were performed. Overall, the hypotheses were not confirmed, possibly due to small sample size, low WM-training adherence and/or ongoing substance use.


Assuntos
Acetilcisteína/farmacologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína/efeitos adversos , Memória de Curto Prazo , Encéfalo/efeitos dos fármacos , Cognição , Sinais (Psicologia) , Método Duplo-Cego , Humanos , Masculino
13.
Actas Esp Psiquiatr ; 47(2): 37-44, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31017271

RESUMO

INTRODUCTION: Cocaine dependence is a disorder where relapses are frequently presented and many factors are involved. Furthermore, cocaine dependence is associated with poor health-related quality of life (HRQoL) outcomes. This study aims to explore perceived HRQoL as an indicator of drug relapse in cocaine-dependent patients (CDP). SUBJECTS AND METHODS: A longitudinal study was carried out in CDP during 23 weeks. A consecutive sampling method was applied, 39 participants composed the initial sample (mean age 35.6 years), only 15 participants completed outpatient follow-up period. CDP were assessed with psychiatric and HRQoL instruments (SCID-I, SCID-II, BDI, STAI scale and SF-36) in different points of the study. The patients were followed up, and cocaine relapses were assessed. The sample was divided according with the relapse (early vs. late relapse). Data were compared and analyzed in order to evaluate whether HRQoL measure could be related to cocaine relapse. RESULTS: There are differences in perceived HRQoL measures between CDP with/without early relapse, especially in Mental health and Social functioning dimensions (p<0.05). Furthermore, Late/relapse-patients have higher improvement of HRQoL than patients with early relapse. CONCLUSIONS: Perceived HRQoL might predict early relapse and could be a possible predictor tool of potential future relapses. More research in this field is needed.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Qualidade de Vida/psicologia , Adulto , Cocaína , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Recidiva , Índice de Gravidade de Doença , Adulto Jovem
14.
Actas esp. psiquiatr ; 47(2): 37-44, mar.-abr. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-181338

RESUMO

Introducción. Las recaídas son frecuentes en la dependencia a cocaína, múltiples factores están involucrados en ellas. Además, la dependencia a cocaína se relaciona con un peor pronóstico en relación a la calidad de vida relacionada con la salud (CVRS). Este estudio explora la CVRS percibida como un indicador de recaída en pacientes con dependencia a cocaína. Metodología. Se llevó a cabo un estudio longitudinal en pacientes con dependencia a cocaína durante 23 semanas. En total 39 pacientes participaron (edad media 35,6 años), aunque solamente 15 completaron el periodo de seguimiento. Se utilizaron varias escalas e instrumentos psicométricos (SCID-I, SCID-II, BDI, STAI y la SF-36) en diferentes puntos del estudio. Los pacientes fueron seguidos y se evaluaron las recaídas. La muestra fue dividida de acuerdo con el momento de recaída (temprano vs. tardía). La información fue comparada y analizada para poder evaluar si la CVRS se podía relacionar con la recaída de cocaína. Resultados. Hubo diferencias en la CVRS percibida entre los pacientes con y sin recaída temprana, especialmente en las dimensiones de Salud Mental y Funcionamiento Social (p<0,05). Además, los pacientes con recaídas tardías presentaban una mejoría de la CVRS percibida si se comparaba con los que recaían de forma temprana. Conclusiones. La CVRS percibida podría predecir parcialmente las recaídas tempranas y su medición podría ser una herramienta para evaluar posibles recaídas en el futuro. Sin embargo, es necesaria más investigación en esta área


Introduction. Cocaine dependence is a disorder where relapses are frequently presented and many factors are involved. Furthermore, cocaine dependence is associated with poor health-related quality of life (HRQoL) outcomes. This study aims to explore perceived HRQoL as an indicator of drug relapse in cocaine-dependent patients (CDP). Subjects and Methods. A longitudinal study was carried out in CDP during 23 weeks. A consecutive sampling method was applied, 39 participants composed the initial sample (mean age 35.6 years), only 15 participants completed outpatient follow-up period. CDP were assessed with psychiatric and HRQoL instruments (SCID-I, SCID-II, BDI, STAI scale and SF-36) in different points of the study. The patients were followed up, and cocaine relapses were assessed. The sample was divided according with the relapse (early vs. late relapse). Data were compared and analyzed in order to evaluate whether HRQoL measure could be related to cocaine relapse. Results. There are differences in perceived HRQoL measures between CDP with/without early relapse, especially in Mental health and Social functioning dimensions (p<0.05). Furthermore, Late/relapse-patients have higher improvement of HRQoL than patients with early relapse. Conclusions. Perceived HRQoL might predict early relapse and could be a possible predictor tool of potential future relapses. More research in this field is needed


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Fumar Cocaína/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Qualidade de Vida/psicologia , Estudos Longitudinais , Recidiva , Prognóstico , Psicometria/métodos , Ansiedade/diagnóstico , Ansiedade/psicologia , Depressão/diagnóstico , Depressão/psicologia , Transtornos Relacionados ao Uso de Cocaína/terapia
15.
Psychopharmacology (Berl) ; 236(4): 1145-1157, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30820634

RESUMO

A key question in addiction research concerns how, in some individuals, initial recreational or casual patterns of drug use may change brain and psychological function in ways that promote a transition to the problematic patterns of use that define substance use disorders (addiction). In preclinical studies, this is modeled using self-administration procedures. However, most cocaine self-administration procedures produce continuously high brain concentrations of drug, whereas in people, bouts of use are thought to be more intermittent. Here, we ask whether such temporal pharmacokinetic factors matter, by comparing and contrasting the neuropsychological consequences of intermittent vs. long access cocaine self-administration experience. It turns out, the temporal pattern of cocaine use has profound effects on a number of outcomes. First, despite much less total drug consumption, intermittent access to cocaine is more effective in producing addiction-like behavior. Second, intermittent and long access cocaine self-administration change the brain in very different ways to influence motivated behavior. We argue that intermittent access self-administration procedures might be better suited than traditional self-administration procedures for isolating drug-induced changes in neuropsychological function that contribute to the transition to cocaine addiction.


Assuntos
Encéfalo/metabolismo , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Cocaína/administração & dosagem , Cocaína/farmacocinética , Modelos Animais de Doenças , Animais , Comportamento Aditivo/metabolismo , Comportamento Aditivo/psicologia , Encéfalo/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/psicologia , Humanos , Motivação/efeitos dos fármacos , Motivação/fisiologia , Ratos Sprague-Dawley , Autoadministração
16.
Psychopharmacology (Berl) ; 236(7): 2143-2153, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30877326

RESUMO

RATIONALE: Cocaine use disorder (CUD) is associated with cognitive deficits that have been linked to poor treatment outcomes. An improved understanding of cocaine's deleterious effects on cognition may help optimize pharmacotherapies. Emerging evidence implicates abnormalities in glutamate neurotransmission in CUD and drugs that normalize glutamatergic homeostasis (e.g., N-acetylcysteine [NAC]) may attenuate CUD-related relapse behavior. OBJECTIVES: The present studies examined the impact of chronic cocaine exposure on touchscreen-based models of learning (repeated acquisition) and cognitive flexibility (discrimination reversal) and, also, the ability of NAC to modulate cocaine self-administration and its capacity to reinstate drug-seeking behavior. METHODS: First, stable repeated acquisition and discrimination reversal performance was established. Next, high levels of cocaine-taking behavior (2.13-3.03 mg/kg/session) were maintained for 150 sessions during which repeated acquisition and discrimination reversal performance was probed periodically. Finally, the effects of NAC treatment were examined on cocaine self-administration and, subsequently, extinction and reinstatement. RESULTS: Cocaine self-administration significantly impaired performance under both cognitive tasks; however, discrimination reversal was disrupted considerably more than acquisition. Performance eventually approximated baseline levels during chronic exposure. NAC treatment did not perturb ongoing self-administration behavior but was associated with significantly quicker extinction of drug-lever responding. Cocaine-primed reinstatement did not significantly differ between groups. CONCLUSIONS: The disruptive effects of cocaine on learning and cognitive flexibility are profound but performance recovered during chronic exposure. Although the effects of NAC on models of drug-taking and drug-seeking behavior in monkeys are less robust than reported in rodents, they nevertheless suggest a role for glutamatergic modulators in CUD treatment programs.


Assuntos
Acetilcisteína/administração & dosagem , Cocaína/administração & dosagem , Cognição/efeitos dos fármacos , Aprendizagem por Discriminação/efeitos dos fármacos , Comportamento de Procura de Droga/efeitos dos fármacos , Animais , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cognição/fisiologia , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Aprendizagem por Discriminação/fisiologia , Inibidores da Captação de Dopamina/administração & dosagem , Relação Dose-Resposta a Droga , Comportamento de Procura de Droga/fisiologia , Extinção Psicológica/efeitos dos fármacos , Extinção Psicológica/fisiologia , Depuradores de Radicais Livres/administração & dosagem , Masculino , Estimulação Luminosa/métodos , Primatas , Saimiri , Autoadministração
17.
Cien Saude Colet ; 24(3): 1091-1099, 2019 Mar.
Artigo em Português, Inglês | MEDLINE | ID: mdl-30892529

RESUMO

This paper aims to describe the dream content of crack cocaine users as per their view and analyze its interference in the drug withdrawal process. This is a qualitative research with 21 crack cocaine users. Consuming crack cocaine during the dream meant a proof of failure or compensatory pleasure or warning of potential relapse; not consuming the crack cocaine meant the emergence of withdrawal symptoms or the success at overcoming drug dependence. Dream interpretation may lead users to craving and relapse. The outcomes may contribute to effective therapeutic interventions.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína Crack , Fissura , Sonhos/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
18.
Drug Alcohol Depend ; 198: 126-132, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30921648

RESUMO

BACKGROUND: Substantial efforts have been made to identify clinically meaningful non-abstinence cocaine use outcomes by establishing associations between targeted drug use outcomes and long-term functional improvements. Psychiatric symptomatology is prevalent among those seeking treatment for cocaine use disorder (CUD). Establishing an association between cocaine use outcomes and improvements in psychiatric symptomatology would support clinical validity to these outcome measures. METHOD: With data pooled from 5 clinical trials evaluating treatment for CUD (n = 474) multiple linear mixed models were conducted to determine how five specific cocaine use outcome measures performed in terms of improvements in psychiatric symptomatology assessed with the Brief Symptom Inventory (BSI) at baseline, end-of-treatment and 6-month follow-up. RESULTS: Three outcome measures performed comparably well (maximum days of consecutive abstinence, 3 or more weeks of abstinence and end-of-treatment abstinence), in that they consistently predicted improvements in several BSI composite scores at the end-of-treatment and follow-up. The poorer-performing outcome measures were complete abstinence during treatment, percentage of negative urinalysis results and percentage of days abstinent. Improvements in the BSI's global index of distress, positive symptom total, as well as depression, interpersonal sensitivity, obsessive-compulsion, phobic-anxiety and psychoticism dimensions were consistently associated with outcome effects, while anxiety, hostility, paranoid ideation and somatization were not. CONCLUSION: The consistent short and long-term association of three outcome measures evaluated here (maximum days of consecutive abstinence, 3 or more weeks of abstinence and end-of-treatment abstinence) with improvements psychiatric symptomatology adds support to their clinical relevance as well as their adoption in trials and treatments for CUD.


Assuntos
Ansiedade/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/terapia , Depressão/epidemiologia , Adulto , Ansiedade/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Depressão/psicologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Prevalência , Fatores de Tempo , Resultado do Tratamento
19.
Drug Alcohol Depend ; 197: 255-261, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30875646

RESUMO

BACKGROUND: The severity of substance use disorder (SUD) is currently defined by the sum of DSM-5 criteria. However, little is known about the validity of this framework or the role of additional severity indicators in relapse prediction. This study aimed to investigate the relationship between DSM-5 criteria, neurocognitive functioning, substance use variables and cocaine relapse among inpatients with cocaine use disorder (CUD). METHODS: 128 adults aged between 18 and 45 years were evaluated; 68 (59 males, 9 females) had CUD and 60 (52 males, 8 females) were healthy controls. For the group with CUD, the use of other substances was not an exclusion criterion. Participants were tested using a battery of neurocognitive tests. Cocaine relapse was evaluated 3 months after discharge. RESULTS: Scores for attention span and working memory were worse in patients compared to controls. Earlier onset and duration of cocaine use were related to poorer inhibitory control and global executive functioning, respectively; recent use was related to worse performance in inhibitory control, attention span and working memory. More DSM-5 criteria at baseline were significantly associated with relapse. CONCLUSIONS: Recent cocaine use was the most predictive variable for neurocognitive impairments, while DSM-5 criteria predicted cocaine relapse at three months post treatment. The integration of neurocognitive measures, DSM-5 criteria and cocaine use variables in CUD diagnosis could improve severity differentiation. Longitudinal studies using additional biomarkers are needed to disentangle the different roles of severity indicators in relapse prediction and to achieve more individualized and effective treatment strategies for these patients.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Neurocognitivos/induzido quimicamente , Índice de Gravidade de Doença , Adolescente , Adulto , Atenção/efeitos dos fármacos , Estudos de Casos e Controles , Manual Diagnóstico e Estatístico de Transtornos Mentais , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Recidiva , Adulto Jovem
20.
J Acquir Immune Defic Syndr ; 81(1): 78-82, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30730359

RESUMO

BACKGROUND: Concomitant use of cocaine and HIV pre-exposure prophylaxis (PrEP) raises important clinical questions around adherence, retention in care, and renal toxicity. METHODS: We assessed the associations of confirmed cocaine use with PrEP adherence (both ascertained through objective measures), care engagement, and renal function in the iPrEx open-label extension. Cocaine use was measured in scalp hair samples and categorized as light (500-3000 pg/mg) and moderate to heavy (>3000 pg/mg). PrEP adherence in the first 3 months was measured through plasma tenofovir concentrations. Disengagement from PrEP care was defined as a gap in follow-up greater than 4 months. Serum creatinine was assessed at baseline and quarterly visits. RESULTS: Of the 400 participants included in this analysis, 90% were men who have sex with men, 10% transgender women, 74% Hispanic/Latino; 21% tested positive for cocaine use in the last 3 months. In adjusted analysis, light cocaine use [adjusted odds ratio 2.10 (95% confidence interval: 1.07 to 4.14)] and moderate to heavy use [adjusted odds ratio 2.32 (1.08 to 5.00)] were associated with greater odds of having plasma tenofovir concentrations below the level of quantitation. Participants with moderate to heavy use had a nearly 3-fold higher rate of disengagement from PrEP care compared with nonusers (adjusted hazard ratio 2.90 [1.48 to 5.66]). We found no statistically or clinically significant differences in creatinine clearance and serum creatinine between participants who tested positive for cocaine and those who did not. CONCLUSIONS: Cocaine use decreases PrEP adherence and care engagement. Comprehensive approaches are needed to reduce cocaine use and enhance engagement along the PrEP care continuum.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/complicações , Rim/efeitos dos fármacos , Adesão à Medicação/estatística & dados numéricos , Participação do Paciente/estatística & dados numéricos , Profilaxia Pré-Exposição , Adulto , Fármacos Anti-HIV/efeitos adversos , Cocaína/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/psicologia , Infecções por HIV/prevenção & controle , Humanos , Masculino , Adesão à Medicação/psicologia , Participação do Paciente/psicologia , Profilaxia Pré-Exposição/métodos , Adulto Jovem
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