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1.
Forensic Sci Int ; 306: 110093, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31816483

RESUMO

Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004-2017) and Wuhan (2005-2017). Chi-square/Fisher's exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson regression models were used to estimate the rate ratios ("RRs") and annual percentage changes ("APCs"). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, -16.1; 95 % CI, -18.4 to -11.3) and Wuhan (APC, -16.0; 95 % CI, -18.9 to -10.6), whereas methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95 % CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.


Assuntos
Analgésicos Opioides/envenenamento , Ketamina/envenenamento , Metanfetamina/envenenamento , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Adolescente , Adulto , Distribuição por Idade , Analgésicos Opioides/efeitos adversos , Intoxicação por Monóxido de Carbono/mortalidade , China/epidemiologia , Feminino , Heroína/efeitos adversos , Heroína/envenenamento , Humanos , /envenenamento , Ketamina/efeitos adversos , Masculino , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Distribuição por Sexo , Suicídio/estatística & dados numéricos , Adulto Jovem
2.
Nat Commun ; 10(1): 4140, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515501

RESUMO

Persistent transcriptional and morphological events in the nucleus accumbens (NAc) and other brain reward regions contribute to the long-lasting behavioral adaptations that characterize drug addiction. Opiate exposure reduces the density of dendritic spines on medium spiny neurons of the NAc; however, the underlying transcriptional and cellular events mediating this remain unknown. We show that heroin self-administration negatively regulates the actin-binding protein drebrin in the NAc. Using virus-mediated gene transfer, we show that drebrin overexpression in the NAc is sufficient to decrease drug seeking and increase dendritic spine density, whereas drebrin knockdown potentiates these effects. We demonstrate that drebrin is transcriptionally repressed by the histone modifier HDAC2, which is relieved by pharmacological inhibition of histone deacetylases. Importantly, we demonstrate that heroin-induced adaptations occur only in the D1+ subset of medium spiny neurons. These findings establish an essential role for drebrin, and upstream transcriptional regulator HDAC2, in opiate-induced plasticity in the NAc.


Assuntos
Proteínas dos Microfilamentos/metabolismo , Neuropeptídeos/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Heroína/efeitos adversos , Histona Desacetilase 2/metabolismo , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuropeptídeos/genética , Núcleo Accumbens/metabolismo , Alcaloides Opiáceos/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Dor/metabolismo , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos , Sinapses/metabolismo
4.
Chem Biol Interact ; 308: 130-136, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129131

RESUMO

Substance addiction is a chronic, relapsing mental disorder Characterized by compulsive drug seeking, and loss of control over drug intake and relapse after prolonged abstinence. Genetics has been shown to contribute towards an individual's vulnerability to addiction. Acetylecholine (ACh), a cholinergic neurotransmitter hydrolyzed by acetylcholinesterase (AChE), is an essential neurotransmitter and neuromodulator in central and peripheral nervous system and has regulatory influence on numerous neuronal functions including addiction. The present study was carried out to investigate the role of acetylcholinesterase (AChE) in addiction through measurement of enzyme activity and to find potential association of ACHE gene 3'UTR variants rs17228602 and rs17228616 in heroin, hashish and poly drug addicts. Both SNPs are located within microRNA (miRNA) recognition sites with potential to affect miRNA/transcript interaction. A total of 122 addicts of heroin, hashish and polydrug were recruited from local rehabilitation centers to participate in this study. AChE activity was measured in blood by Ellman's method. SNP genotyping was performed by restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. The AChE activity was found significantly higher (p ≤ 0.005) in addicted cohort (mean ±â€¯standard error of mean 0.020 ±â€¯0.001 µmol/L/min; 95% confidence interval (CI) 0.018-0.022) in comparison to non-addicted healthy subjects (0.011 ±â€¯0.001 µmol/L/min; 95% confidence interval CI 0.010-0.013). A statistically significant association of ACHE rs17228602 SNP with addiction vulnerability in dominant (DM: Odd's ratio OR = 2.095, 95% CI = 1.157-3.807 p = 0.009) and allelic genetic models (OR = 1.854 95% CI = 1.082-3.187, p = 0.016) was observed. However, no statistically significant association of rs17228616 SNP with substance abuse disorder was found. The data presented here shows that AChE could play significant role in substance addiction. Further studies with larger sample size and other variants of AChE are recommended to identify novel therapeutic approaches for cholinergic based treatment of addiction.


Assuntos
Acetilcolinesterase/genética , Grupo com Ancestrais do Continente Asiático/genética , Transtornos Relacionados ao Uso de Substâncias/patologia , Regiões 3' não Traduzidas , Acetilcolinesterase/metabolismo , Alelos , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Heroína/efeitos adversos , Humanos , Cinética , MicroRNAs/química , MicroRNAs/metabolismo , Razão de Chances , Paquistão , Polimorfismo de Nucleotídeo Único , Transtornos Relacionados ao Uso de Substâncias/genética
5.
Health Secur ; 17(2): 162-165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964342

RESUMO

From the Field is a semi-regular column that explores what it means to be a local health professional on the front lines of an emergency. Typically, National Association of County and City Health Officials (NACCHO) members share their stories of preparing for and responding to disasters, epidemics, and other major health issues. Through exploring the analysis of the challenges faced and the solutions developed, readers can learn how these public health champions keep their communities safe even in extreme situations. Readers may submit topics of interest to jfox46@jhu.edu .


Assuntos
Governo Local , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Saúde Pública/legislação & jurisprudência , Overdose de Drogas/epidemiologia , Fentanila/efeitos adversos , Heroína/efeitos adversos , Humanos , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Administração em Saúde Pública/métodos , Washington
6.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936344

RESUMO

Heroin-related myelopathy is an uncommon but often devastating complication of heroin intake. It is usually reported in individuals exposed to intravenous heroin after a variable drug-free period, leading to acute and complete spinal cord injury with poor long-term outcome. We describe an original case of acute longitudinally extensive transverse myelopathy following single heroin and cocaine intravenous exposure after a long period of abstinence confirmed by toxicological hair and retrospective urine drug analysis. This case could provide new insights in the understanding of this rare neurological complication.


Assuntos
Cocaína/administração & dosagem , Incontinência Fecal/fisiopatologia , Cabelo/química , Heroína/efeitos adversos , Mielite Transversa/diagnóstico , Paraplegia/fisiopatologia , Abuso de Substâncias por Via Intravenosa/complicações , Anti-Inflamatórios/uso terapêutico , Cocaína/efeitos adversos , Extinção Psicológica , Incontinência Fecal/etiologia , Feminino , Heroína/administração & dosagem , Humanos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Mielite Transversa/complicações , Mielite Transversa/fisiopatologia , Mielite Transversa/terapia , Paraplegia/etiologia , Índice de Gravidade de Doença , Punção Espinal , Detecção do Abuso de Substâncias/métodos , Resultado do Tratamento
8.
Neuropharmacology ; 151: 219-226, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30735692

RESUMO

Opioid drugs are important tools to alleviate pain of different origins, but they have strong addictive potential and their abuse at higher doses often results in serious health complications. Respiratory depression that leads to brain hypoxia is perhaps the most dangerous symptom of acute intoxication with opioids, and it could result in lethality. The development of substrate-specific sensors coupled with amperometry made it possible to directly evaluate physiological and drug-induced fluctuations in brain oxygen levels in awake, freely-moving rats. The goal of this review paper is to consider changes in brain oxygen levels induced by several opioid drugs (heroin, fentanyl, oxycodone, morphine). While some of these drugs are widely used in clinical practice, they all are abused, often at doses exceeding the clinical range and often resulting in serious health complications. First, we consider some basic knowledge regarding brain oxygen, its physiological fluctuations, and mechanisms involved in regulating its entry into brain tissue. Then, we present and discuss data on brain oxygen changes induced by each opioid drug within a wide range of doses, from low, behaviorally relevant, to high, likely to be self-administered by drug users. These data allowed us to compare the effects of these drugs on brain oxygen in terms of their potency, time-course, and their potential danger when used at high doses via rapid-onset administration routes. While most data discussed in this work were obtained in rats, we believe that these data have clear human relevance in addressing the alarming rise in lethality associated with the opioid abuse.


Assuntos
Analgésicos Opioides/efeitos adversos , Fentanila/efeitos adversos , Heroína/efeitos adversos , Hipóxia Encefálica/induzido quimicamente , Morfina/efeitos adversos , Oxicodona/efeitos adversos , Insuficiência Respiratória/induzido quimicamente , Analgésicos Opioides/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Fentanila/farmacologia , Heroína/farmacologia , Humanos , Morfina/farmacologia , Oxicodona/farmacologia , Ratos
9.
AIDS Educ Prev ; 31(1): 1-16, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742480

RESUMO

This article examined the differences in causes and health consequences between synthetic drug and heroin abuse in urban China. Two-group comparisons were conducted to quantify differences in individual characteristics, causes of drug use, and HIV/STI risky sexual behavior between synthetic drug and heroin users; logistic regressions were employed to assess the net effect of synthetic drug use on risky sexual behavior. Results revealed that causes of synthetic drug use differed from those of heroin use; a combination of the knowledge gap concerning the harmful impact of synthetic drugs and the lesser punishment for their use appeared a main reason behind the shift from heroin to synthetic drugs; and synthetic drug use was a significant and powerful risk factor for HIV/STI risky sexual behavior. Educational and behavioral interventions are urgently needed to prevent the initiation of synthetic drug use among users to reduce their HIV/STI risky sexual behavior.


Assuntos
Usuários de Drogas/estatística & dados numéricos , Dependência de Heroína/epidemiologia , Heroína/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Medicamentos Sintéticos/efeitos adversos , População Urbana , Adulto , China/epidemiologia , Feminino , Infecções por HIV/prevenção & controle , Heroína/administração & dosagem , Dependência de Heroína/psicologia , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Assunção de Riscos , Comportamento Sexual , Medicamentos Sintéticos/administração & dosagem
10.
Orthop Nurs ; 38(2): 95-108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30768537

RESUMO

The United States is in the midst of a nationwide public health emergency: an epidemic of opioid misuse and abuse that has been called the deadliest drug crisis in American history. This article reviews the current status of the opioid epidemic, the trends over the last 30-40 years that may have contributed to the epidemic, and a population health approach to addressing the epidemic. The epidemic is conceptualized from a population health perspective-an upstream and midstream perspective focusing on prevention and a downstream perspective targeting access to evidence-based interventions and maximizing health whether using or abstaining. Within the context of acute care, this approach will include patient screening for opioid use and other risk factors for addiction, use of opioid-sparing analgesics, and follow-up care that addresses pain and pain relief without opioids. For individuals who need addiction treatment, a gradualism philosophy is put forward. Gradualism recognizes the incremental nature of behavior change and recommends strategies to maximize health and functioning-through harm reduction-at all points along the journey to overcome addiction. Working within communities to address the broad factors that contribute to opioid-related substance use disorder is also essential.


Assuntos
Analgésicos Opioides/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Saúde da População/estatística & dados numéricos , Adulto , Analgésicos Opioides/uso terapêutico , Dor Crônica , Feminino , Fentanila/efeitos adversos , Heroína/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/mortalidade , Manejo da Dor , Fatores de Risco , Estados Unidos/epidemiologia
11.
J Clin Pharm Ther ; 44(3): 397-399, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30636175

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The exponential increase in chronic opioid consumers resulted in more challenges regarding post-operative pain management. Considering the usual hyperalgesic response to pain and the increased opioid-tolerance, a multidrug approach should be desirable. CASE DESCRIPTION: We described the strategy in pain management of a patient receiving methadone maintenance treatment, who underwent surgery associated with moderate post-operative pain. The combination of balanced general anaesthesia and intraoperative continuous low-dose infusion of ketamine assured an appropriate control of post-operative pain without increasing opioid consumption. Besides, it was not associated with psychomimetic effects. WHAT IS NEW AND CONCLUSION: Ketamine can effectively reduce opioid requirements in chronic opioid users on methadone maintenance therapy and should therefore be considered promptly as part of a multimodal perioperative analgesia management in this category of patients.


Assuntos
Heroína/efeitos adversos , Hiperalgesia/prevenção & controle , Metadona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/complicações , Analgésicos Opioides/uso terapêutico , Humanos , Ketamina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Assistência Perioperatória , Período Pós-Operatório
12.
Psychiatr Genet ; 29(1): 18-25, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30260900

RESUMO

OBJECTIVES: Susceptibility to heroin dependence is strongly influenced by genetic factors with heritability estimates as high as 0.7. A number of genes, as well as environmental factors, are likely to contribute to its etiology. Not all individuals who have ever tried heroin at some stage during their lifetime become dependent on heroin. It has been suggested that genetic factors might be more important in the transition stage to heroin dependence rather than in environmental exposures and experimenting with heroin. As the features of substance dependence and memory formation have been found to be strikingly similar, we have focused on a key enzyme involved in long-term potentiation and synaptic plasticity, namely the calcium-dependent/calmodulin-dependent protein kinase IIα (CAMKIIa). We hypothesized, that CamK2A genetic variation may play a role in the transition from occasional to regular heroin use. MATERIALS AND METHODS: Using quantitative trait association analysis, we addressed this hypothesis by correlating the self-reported time interval between occasional and regular heroin use with the frequency of 12 single nucleotide polymorphisms located within the genomic region of the CamK2A gene. A sample of 570 Caucasian patients was available for analysis. RESULTS: Single marker association analysis (rs10066581, P=0.007), as well as haplotype analysis (global P=0.005), suggested an association with the quantitative trait 'time interval from occasional to regular heroin use.' CONCLUSION: Our results propose that genetic variants located in the genomic region of the CamK2A gene may be involved in transition time from occasional to regular heroin use.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Dependência de Heroína/genética , Adolescente , Adulto , Austrália , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Haplótipos/genética , Heroína/efeitos adversos , Humanos , Desequilíbrio de Ligação/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Adulto Jovem
13.
J Pharmacol Exp Ther ; 368(1): 106-115, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30361238

RESUMO

Escalating opioid use among fertile women has increased the number of children being exposed to opioids during fetal life. Furthermore, accumulating evidence links prenatal opioid exposure, including opioid maintenance treatment, to long-term negative effects on cognition and behavior, and presses the need to explore novel treatment strategies for pregnant opioid users. The present study examined the potential of a monoclonal antibody (mAb) targeting heroin's first metabolite, 6-acetylmorphine (6-AM), in providing fetal protection against harmful effects of prenatal heroin exposure in mice. First, we examined anti-6-AM mAb's ability to block materno-fetal transfer of active metabolites after maternal heroin administration. Next, we studied whether maternal mAb pretreatment could prevent adverse effects in neonatal and adolescent offspring exposed to intrauterine heroin (3 × 1.05 mg/kg). Anti-6-AM mAb pretreatment of pregnant dams profoundly reduced the distribution of active heroin metabolites to the fetal brain. Furthermore, maternal mAb administration prevented hyperactivity and drug sensitization in adolescent female offspring prenatally exposed to heroin. Our findings demonstrate that passive immunization with a 6-AM-specific antibody during pregnancy provides fetal neuroprotection against heroin metabolites, and thereby prevents persistent adverse behavioral effects in the offspring. An immunotherapeutic approach to protect the fetus against long-term effects of prenatal drug exposure has not been reported previously, and should be further explored as prophylactic treatment of pregnant heroin users susceptible to relapse.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Heroína/efeitos adversos , Locomoção/efeitos dos fármacos , Derivados da Morfina/antagonistas & inibidores , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Animais , Animais Recém-Nascidos , Anticorpos Monoclonais/farmacologia , Feminino , Heroína/administração & dosagem , Locomoção/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Distribuição Aleatória
14.
Acta Pharmacol Sin ; 40(3): 365-373, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29967454

RESUMO

Cannabinoid CB1 receptors (CB1Rs) have been shown to be a promising target in medication development for the treatment of addiction. However, clinical trials with SR141716A (rimonabant, a selective CB1R antagonist/inverse agonist) for the treatment of obesity and smoking cessation failed due to unwanted side effects, such as depression, anxiety, and suicidal tendencies. Recent preclinical studies suggest that the neutral CB1R antagonist AM4113 may retain the therapeutic anti-addictive effects of SR141716A in nicotine self-administration models and possibly has fewer unwanted side effects. However, little is known about whether AM4113 is also effective for other drugs of abuse, such as opioids and psychostimulants, and whether it produces depressive side effects similar to SR141716A in experimental animals. In this study, we demonstrated that systemic administration of AM4113 (3 and 10 mg/kg) dose-dependently inhibited the self-administration of intravenous heroin but not cocaine or methamphetamine, whereas SR141716A (3 and 10 mg/kg) dose-dependently inhibited the self-administration of heroin and methamphetamine but not cocaine. In the electrical brain-stimulation reward (BSR) paradigm, SR141716A (3 and 10 mg/kg) dose-dependently increased the BSR stimulation threshold (i.e., decreased the stimulation reward), but AM4113 had no effect on BSR at the same doses, suggesting that SR141716A may produce aversive effects while AM4113 may not. Together, these findings show that neutral CB1R antagonists such as AM4113 deserve further research as a new class of CB1R-based medications for the treatment of opioid addiction without SR141716A-like aversive effects.


Assuntos
Antagonistas de Receptores de Canabinoides/farmacologia , Depressão/prevenção & controle , Comportamento de Procura de Droga/efeitos dos fármacos , Dependência de Heroína/prevenção & controle , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Animais , Comportamento Animal/efeitos dos fármacos , Cocaína/efeitos adversos , Condicionamento Operante/efeitos dos fármacos , Heroína/efeitos adversos , Dependência de Heroína/psicologia , Masculino , Metanfetamina/efeitos adversos , Ratos Long-Evans , Recompensa , Rimonabanto/efeitos adversos , Rimonabanto/farmacologia , Autoadministração
16.
Psychopharmacology (Berl) ; 235(12): 3451-3464, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30310961

RESUMO

RATIONALE: Non-medical prescription opioid use (NMPOU) has become a major public health issue in the USA and is also increasing in Europe. However, little is known about neuropsychological associations of NMPOU-specifically regarding social cognition, which is essential for social functioning and treatability of opioid dependence. Previous studies with heroin users and opioid-substituted patients reported deficits in various cognitive functions, but these results are likely confounded by comorbid physical and psychiatric diseases, overdose-associated hypoxia, and adulteration of street heroin. Therefore, the purpose of the present study was to investigate social and non-social cognition in a relatively pure NMPOU sample taking opioid analgesics or antitussives. METHODS: We assessed 23 individuals with NMPOU objectively confirmed by hair analyses and 29 opioid-naïve, healthy controls, employing a comprehensive neuropsychological test battery. RESULTS: Significant impairments were found between NMPOU individuals and controls regarding the cognitive domains of attention (p < .01, Hedge's g = .85), declarative memory (p < .05, g = .66), and global cognitive empathy (p < .01, g = 0.99)-the latter included problems with emotion recognition from faces, voices, and complex scenes. Opioid hair concentrations transformed to morphine equivalents were negatively correlated with global cognitive empathy (r = - 0.52, p < .01), suggesting dose-dependent deficits. CONCLUSION: In contrast to stimulant users primarily displaying deficits in emotional empathy, opioid users showed relatively selective impairments in measures of cognitive empathy, with dose-dependent effects suggesting potential opioid-induced deficits and involvement of the opioid-system in processes of cognitive empathy. These results have important implications for future interventions of opioid dependence targeting social functioning and consequently enhancing therapy outcome and preventing relapse.


Assuntos
Analgésicos Opioides/efeitos adversos , Cognição/efeitos dos fármacos , Empatia/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides/psicologia , Comportamento Social , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Cognição/fisiologia , Empatia/fisiologia , Feminino , Heroína/administração & dosagem , Heroína/efeitos adversos , Humanos , Masculino , Morfina/administração & dosagem , Morfina/efeitos adversos , Testes Neuropsicológicos , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto Jovem
17.
Elife ; 72018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30373717

RESUMO

The dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we monitor genetically encoded DA and calcium indicators as well as cFos in mice to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Heroína/efeitos adversos , Núcleo Accumbens/fisiologia , Animais , Dopamina/metabolismo , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Optogenética , Autoadministração , Área Tegmentar Ventral/fisiologia
18.
Drug Alcohol Depend ; 192: 80-87, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30243143

RESUMO

BACKGROUND: Since 2000, heroin use patterns have shifted within the United States. How this change may relate to polydrug use among local heroin users is unknown. Although polydrug use has been studied, user perceptions of drug use in terms of health risks, arrest risk, availability, cost, liking, and dependence have not been considered. METHODS: Data are presented from a brief, face-to-face survey conducted in 2016 of 200 non-in-treatment heroin users from Cleveland, OH. We assessed the use of and attitudes on alcohol, marijuana, methamphetamine, heroin, crack cocaine, powder cocaine, and prescription drugs. We estimated polydrug (concurrent past month) use with cluster analysis and latent profiles. Regression analysis estimated the strength of relationships between attitudes and frequency of use. RESULTS: We identified five clusters: Cluster 1 used heroin concomitantly with alcohol and occasionally crack; Cluster 2 used heroin and crack cocaine daily; Cluster 3 used heroin daily and almost exclusively; Cluster 4 used heroin and marijuana daily; and Cluster 5 were part-time drug users. Drug use frequency was associated with liking and being anxious when drugs could not be obtained. High perceived availability of heroin and cocaine and low cost facilitated polydrug use. CONCLUSIONS: Understanding polydrug use clusters among heroin users is important for addressing the larger opioid epidemic. Users' perceptions of a drug's availability and cost appeared to facilitate polydrug use and justify more detailed future research on drug access.


Assuntos
Usuários de Drogas , Dependência de Heroína/diagnóstico , Dependência de Heroína/epidemiologia , Adulto , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Alcoolismo/psicologia , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Analgésicos Opioides/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína Crack/efeitos adversos , Usuários de Drogas/psicologia , Feminino , Heroína/efeitos adversos , Dependência de Heroína/psicologia , Humanos , Masculino , Abuso de Maconha/diagnóstico , Abuso de Maconha/epidemiologia , Abuso de Maconha/psicologia , Pessoa de Meia-Idade , Ohio/epidemiologia , Autorrelato , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia
19.
Subst Abuse Treat Prev Policy ; 13(1): 29, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30134921

RESUMO

BACKGROUND: Cognitions associated with craving and substance use are important contributors for the psychological theories of Substance use disorders (SUD), as they may affect the course and treatment. In this study, we aimed to validate Turkish version of two major scales 'Beliefs About Substance Use'(BSU) and 'Craving Beliefs Questionnaire'(CBQ) in patients with heroin use disorder and define the interaction of these beliefs with patient profile, depression and anxiety symptoms, with an aim to use these thoughts as targets for treatment. METHODS: One hundred seventy-six inpatients diagnosed with heroin use disorder and 120 participants in the healthy comparison group were evaluated with CBQ, BSU, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and sociodemographic data questionnaire. Patient group was also evaluated with Addiction Profile Index. Reliability and validity analysis for scales were conducted. Linear regression analysis was conducted to evaluate the determinants of BSU and CBQ scores. RESULTS: Cronbach alpha level was 0.93 for BSU and 0.94 for CBQ. Patient group showed significantly higher CBQ, BSU, BAI and BDI scores (p < 0.001). BSU score significantly correlated with API-substance use profile score, API-diagnosis, BAI, BDI and CBQ (p < 0.005), whereas CBQ scores significantly correlated with API-diagnosis, API-impact on life, API-craving, API-total score, BSU, BAI, BDI and amount of cigarette smoking (p < 0.002). Number of previous treatments and age of onset for substance use were not correlated with either BSU or CBQ. BAI and BDI scores significantly predicted BSU score, however only BDI score predicted CBQ score (p < 0.003). CONCLUSIONS: Craving beliefs were highly correlated with addiction profile. Anxiety and depression are significant modulators for patients' beliefs about substance use and depression is a modulator for craving and maladaptive beliefs, validating emotion-cognition interplay in addiction.


Assuntos
Cognição , Fissura , Emoções , Escalas de Graduação Psiquiátrica/normas , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Ansiedade/complicações , Ansiedade/psicologia , Estudos de Casos e Controles , Depressão/complicações , Depressão/psicologia , Feminino , Heroína/efeitos adversos , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Transtornos Relacionados ao Uso de Substâncias/complicações , Turquia , Adulto Jovem
20.
Brain Behav Immun ; 73: 698-707, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30075289

RESUMO

Repeated pairings of heroin and a context results in Pavlovian associations which manifest as heroin-conditioned appetitive responses and peripheral immunomodulation upon re-exposure to heroin-paired conditioned stimuli (CS). The dorsal hippocampus (DH) plays a key role in the neurocircuitry governing these context-heroin associations. Within the DH, expression of the pro-inflammatory cytokine interleukin-1ß (IL-1ß) is required for heroin-conditioned peripheral immunomodulation to occur. However, the role of signaling via IL-1 receptor type 1 (IL-1R1) has not been examined. Furthermore, it has not been evaluated whether the involvement of IL-1 in associative learning extends to classically conditioned appetitive behaviors, such as conditioned place preference (CPP). The first set of experiments investigated whether DH IL-1R1 signaling during CS re-exposure modulates heroin-conditioned immunomodulation and heroin-CPP. The second set of experiments employed chemogenetic techniques to examine whether DH astroglial signaling during CS re-exposure alters the same Pavlovian responses. This line of investigation is based on previous research indicating that astrocytes support hippocampal-dependent learning and memory through the expression of IL-1ß protein and IL-1R1. Interestingly, IL-1R1 antagonism disrupted heroin-conditioned suppression of peripheral immune parameters but failed to alter heroin-CPP. Similarly, chemogenetic stimulation of Gi-signaling in DH astrocytes attenuated heroin-conditioned peripheral immunomodulation but failed to alter heroin-CPP. Collectively our data show that both IL-1R1 stimulation and astrocyte signaling in the DH are critically involved in the expression of heroin-conditioned immunomodulation but not heroin-CPP. As such these findings strongly suggest hippocampal neuroimmune signaling differentially regulates Pavlovian immunomodulatory and appetitive behaviors.


Assuntos
Heroína/efeitos adversos , Imunomodulação/efeitos dos fármacos , Receptores de Interleucina-1/efeitos dos fármacos , Animais , Astrócitos/metabolismo , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Heroína/metabolismo , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Masculino , Entorpecentes/efeitos adversos , Entorpecentes/metabolismo , Ratos , Ratos Endogâmicos Lew , Transdução de Sinais/efeitos dos fármacos , Lobo Temporal/metabolismo
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