RESUMO
RATIONALE: Cocaine addiction is a chronic relapsing disorder that lacks of an effective treatment. Isoflavones are a family of compounds present in different plants and vegetables like soybeans that share a common chemical structure. Previous studies have described that synthetic derivatives from the natural isoflavone daidzin can modulate cocaine addiction, by a mechanism suggested to involve aldehyde-dehydrogenase (ALDH) activities. OBJECTIVES: Based on these previous studies, we investigated the effects of three natural isoflavones, daidzin, daidzein, and genistein, on the modulation of the cocaine reinforcing effects and on cue-induced reinstatement in an operant mouse model of cocaine self-administration. RESULTS: Chronic treatment with daidzein or genistein decreased operant responding to obtain cocaine intravenous infusions. On the other hand, daidzein and daidzin, but not genistein, were effective in decreasing cue-induced cocaine reinstatement. Complementary studies revealed that daidzein effects on cocaine reinforcement were mediated through a mechanism that involved dopamine type-2/3 receptors (DA-D2/3) activities. CONCLUSIONS: Our results suggest that these natural compounds alone or in combination can be a potential therapeutic approach for cocaine addiction. Further clinical studies are required in order to ascertain their potential therapeutic use.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Cocaína/administração & dosagem , Sinais (Psicologia) , Isoflavonas/administração & dosagem , Fitoestrógenos/administração & dosagem , Reforço Psicológico , Animais , Transtornos Relacionados ao Uso de Cocaína/psicologia , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Inibidores da Captação de Dopamina/administração & dosagem , Relação Dose-Resposta a Droga , Extinção Psicológica/efeitos dos fármacos , Extinção Psicológica/fisiologia , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Camundongos , AutoadministraçãoRESUMO
Cocaine abuse remains a public health threat around the world. There are no pharmacological treatments approved for cocaine use disorder. Cannabis has received growing attention as a treatment for many conditions, including addiction. Most cannabis-based medication development has focused on cannabinoid CB1 receptor (CB1R) antagonists (and also inverse agonists) such as rimonabant, but clinical trials with rimonabant have failed due to its significant side-effects. Here we sought to determine whether a novel and selective CB2R inverse agonist, Xie2-64, has similar therapeutic potential for cocaine use disorder. Computational modeling indicated that Xie2-64 binds to CB2R in a way similar to SR144528, another well-characterized but less selective CB2R antagonist/inverse agonist, suggesting that Xie2-64 may also have CB2R antagonist profiles. Unexpectedly, systemic administration of Xie2-64 or SR144528 dose-dependently inhibited intravenous cocaine self-administration and shifted cocaine dose-response curves downward in rats and wild-type, but not in CB2R-knockout, mice. Xie2-64 also dose-dependently attenuated cocaine-enhanced brain-stimulation reward maintained by optical stimulation of ventral tegmental area dopamine (DA) neurons in DAT-Cre mice, while Xie2-64 or SR144528 alone inhibited optical brain-stimulation reward. In vivo microdialysis revealed that systemic or local administration of Xie2-64 into the nucleus accumbens reduced extracellular dopamine levels in a dose-dependent manner in rats. Together, these results suggest that Xie2-64 has significant anti-cocaine reward effects likely through a dopamine-dependent mechanism, and therefore, deserves further study as a new pharmacotherapy for cocaine use disorder.
Assuntos
Derivados de Benzeno/uso terapêutico , Agonistas de Receptores de Canabinoides/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/prevenção & controle , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Agonismo Inverso de Drogas , Receptor CB2 de Canabinoide/agonistas , Sulfonamidas/uso terapêutico , Animais , Derivados de Benzeno/química , Derivados de Benzeno/farmacologia , Agonistas de Receptores de Canabinoides/química , Agonistas de Receptores de Canabinoides/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/psicologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Knockout , Estrutura Secundária de Proteína , Ratos , Ratos Long-Evans , Receptor CB2 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/metabolismo , Roedores , Autoadministração , Sulfonamidas/química , Sulfonamidas/farmacologiaRESUMO
BACKGROUND: Numerous studies suggest that exercise may be an effective adjunct treatment for substance use disorders. It has been suggested that exercise-induced improvements in inhibitory control may reduce craving for the substance of abuse. However, this potential mechanism has seldom been researched. OBJECTIVES: The aim of the ExAlCo Study is to examine how acute bouts of exercise, at varying intensities, impact on craving for cocaine or alcohol. Cerebral haemodynamic responses during cognitive tests of inhibitory control, and exposure to substance-related cue imagery, will also be assessed using functional near-infrared spectroscopy. DESIGN: The study is a crossover randomised controlled trial. Participants will be recruited from inpatient and outpatient psychiatric treatment centres, on the approval of their treating physician. A healthy control group will be recruited using online advertising. All participants will undergo each of three conditions in randomised order: 20 min of cycle ergometry at 50-60% of maximum heart rate; 20 min of exercise at 70-80% of maximum heart rate; and 20 min of quiet reading. Immediately before and after each condition, participants will be asked to complete a computerised Stroop test, watch a film containing substance-related images and self-report craving levels. During the Stroop test and film viewing, participants' neural activity will be measured via functional near-infrared spectroscopy. OUTCOMES: The primary outcome measures are self-reported craving, inhibitory control and cerebral haemodynamic response to the Stroop test and a substance-related film. It is hoped that the findings from this study will shed more light on the role of exercise in the treatment of substance use disorders, particularly its scope in preventing relapse through reduced craving severity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03502486 . Registered retrospectively on 5 April 2018.
Assuntos
Consumo de Bebidas Alcoólicas/prevenção & controle , Alcoolismo/terapia , Ondas Encefálicas , Encéfalo/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/terapia , Fissura , Terapia por Exercício/métodos , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/fisiopatologia , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/diagnóstico , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Ciclismo , Circulação Cerebrovascular , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Estudos Cross-Over , Sinais (Psicologia) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filmes Cinematográficos , Inibição Neural , Ensaios Clínicos Controlados Aleatórios como Assunto , Espectroscopia de Luz Próxima ao Infravermelho , Teste de Stroop , Suíça , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Enhanced drug-related reward sensitivity accompanied by impaired sensitivity to non-drug related rewards in the mesolimbic dopamine system are thought to underlie the broad motivational deficits and dysfunctional decision-making frequently observed in cocaine use disorder (CUD). Effective approaches to modify this imbalance and reinstate non-drug reward responsiveness are urgently needed. Here, we examined whether cocaine users (CU) can use mental imagery of non-drug rewards to self-regulate the ventral tegmental area and substantia nigra (VTA/SN). We expected that obsessive and compulsive thoughts about cocaine consumption would hamper the ability to self-regulate the VTA/SN activity and tested if real-time fMRI (rtfMRI) neurofeedback (NFB) can improve self-regulation of the VTA/SN. METHODS: Twenty-two CU and 28 healthy controls (HC) were asked to voluntarily up-regulate VTA/SN activity with non-drug reward imagery alone, or combined with rtfMRI NFB. RESULTS: On a group level, HC and CU were able to activate the dopaminergic midbrain and other reward regions with reward imagery. In CU, the individual ability to self-regulate the VTA/SN was reduced in those with more severe obsessive-compulsive drug use. NFB enhanced the effect of reward imagery but did not result in transfer effects at the end of the session. CONCLUSION: CU can voluntary activate their reward system with non-drug reward imagery and improve this ability with rtfMRI NFB. Combining mental imagery and rtFMRI NFB has great potential for modifying the maladapted reward sensitivity and reinstating non-drug reward responsiveness. This motivates further work to examine the use of rtfMRI NFB in the treatment of CUD.
Assuntos
Transtornos Relacionados ao Uso de Cocaína , Imaginação , Imageamento por Ressonância Magnética , Substância Negra , Área Tegmentar Ventral , Adulto , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Feminino , Humanos , Masculino , Substância Negra/diagnóstico por imagem , Substância Negra/fisiopatologia , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/fisiopatologiaRESUMO
BACKGROUND: Many studies have investigated how cognitive control may be compromised in cocaine addiction. Here, we extend this literature by employing spatial Independent Component Analysis (ICA) to describe circuit dysfunction in relation to impairment in response inhibition in cocaine addiction. METHODS: Fifty-five cocaine-dependent (CD) and 55 age- and sex-matched non-drug-using healthy control individuals (HC) participated in the study. Task-relatedness of 40 independent components (ICs) was assessed using multiple regression analyses of component time courses with the modeled time courses of hemodynamic activity convolved with go success (GS), stop success (SS) and stop error (SE). This procedure produced beta-weights that represented the degree to which each IC was temporally associated with, or 'engaged', by each task event. RESULTS: Behaviorally, CD participants showed prolonged stop signal reaction times (SSRTs) as compared to HC participants (p < 0.01). ICA identified two networks that showed differences in engagement related to SS between CD and HC (p < 0.05, FDR-corrected). The activity of the fronto-striatal-thalamic network was negatively correlated with SSRTs in HC but not in CD, suggesting a specific role of this network in mediating deficits of response inhibition in CD individuals. In contrast, the engagement of the fronto-parietal-temporal network did not relate to SSRTs, was similarly less engaged for both SS and SE trials, and may reflect attentional dysfunction in cocaine addiction. CONCLUSIONS: This study highlights the utility of ICA in identifying neural circuitry engagement related to SST performance and suggests that specific networks may represent important targets in remedying executive-control impairment in cocaine addiction.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Lobo Frontal/diagnóstico por imagem , Inibição Psicológica , Tempo de Reação/fisiologia , Tálamo/diagnóstico por imagem , Adulto , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Corpo Estriado/fisiopatologia , Função Executiva/fisiologia , Feminino , Lobo Frontal/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Estimulação Luminosa/métodos , Tálamo/fisiopatologiaRESUMO
Previous studies have shown that individuals with heroin and cocaine addiction prefer to use these drugs in distinct settings: mostly at home in the case of heroin and mostly outside the home in the case of cocaine. Here we investigated whether the context would modulate the affective and neural responses to these drugs in a similar way. First, we used a novel emotional task to assess the affective state produced by heroin or cocaine in different settings, based on the recollections of male and female drug users. Then we used fMRI to monitor neural activity during drug imagery (re-creating the setting of drug use) in male drug users. Consistent with our working hypothesis, the majority of participants reported a shift in the affective valence of heroin from mostly pleasant at home to mostly unpleasant outside the home (p < 0.0001). The opposite shift was observed for cocaine; that is, most participants who found cocaine pleasant outside the home found it unpleasant when taken at home (p < 0.0014). Furthermore, we found a double dissociation, as a function of drug and setting imagery, in BOLD signal changes in the left PFC and caudate, and bilaterally in the cerebellum (all p values <0.01), suggesting that the fronto-striatal-cerebellar network is implicated in the contextualization of drug-induced affect. In summary, we report that the same setting can influence in opposite directions the affective and neural response to psychostimulants versus opiates in humans, adding to growing evidence of distinct substrates for the rewarding effects of these two drug classes.SIGNIFICANCE STATEMENT The rewarding effects of addictive drugs are often thought to depend on shared substrates. Yet, environmental influences can unmask striking differences between psychostimulants and opiates. Here we used emotional tasks and fMRI to explore the influence of setting on the response to heroin versus cocaine in individuals with addiction. Simply moving from one setting to another significantly decreased heroin pleasure but increased cocaine pleasure, and vice versa. Similar double dissociation was observed in the activity of the fronto-striatal-cerebellar network. These findings suggest that the effects of opiates and psychostimulants depend on dissociable psychological and neural substrates and that therapeutic approaches to addiction should take into account the peculiarities of different drug classes and the settings of drug use.
Assuntos
Afeto/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/patologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Meio Ambiente , Dependência de Heroína/patologia , Dependência de Heroína/psicologia , Neurônios/efeitos dos fármacos , Adulto , Mapeamento Encefálico , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/efeitos dos fármacos , Cerebelo/diagnóstico por imagem , Cerebelo/efeitos dos fármacos , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiologia , Humanos , Imaginação/efeitos dos fármacos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/efeitos dos fármacos , Estimulação Luminosa , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Meio SocialRESUMO
Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the "anti-relapse" potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity. Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen. CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history. The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.
Assuntos
Canabidiol/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Administração Cutânea , Alcoolismo/tratamento farmacológico , Alcoolismo/psicologia , Animais , Ansiedade/psicologia , Encéfalo/metabolismo , Canabidiol/administração & dosagem , Canabidiol/farmacocinética , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Transtornos Relacionados ao Uso de Cocaína/psicologia , Comportamento de Procura de Droga/efeitos dos fármacos , Comportamento Impulsivo , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Recidiva , Estresse Psicológico/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
BACKGROUND: Brazil is among the nations with the greatest rates of annual cocaine usage. Pharmacological treatment of cocaine addiction is still limited, opening space for nonconventional interventions. Homeopathic Q-potencies of opium and Erythroxylum coca have been tested in the integrative treatment of cocaine craving among homeless addicts, but this setting had not proven feasible, due to insufficient recruitment. OBJECTIVE: This study investigates the effectiveness and tolerability of homeopathic Q-potencies of opium and E. coca in the integrative treatment of cocaine craving in a community-based psychosocial rehabilitation setting. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A randomized, double-blind, placebo-controlled, parallel-group, eight-week pilot trial was performed at the Psychosocial Attention Center for Alcohol and Other Drugs (CAPS-AD), Sao Carlos/SP, Brazil. Eligible subjects included CAPS-AD patients between 18 and 65â¯years of age, with an International Classification of Diseases-10 diagnosis of cocaine dependence (F14.2). The patients were randomly assigned to two treatment groups: psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca (homeopathy group), and psychosocial rehabilitation plus indistinguishable placebo (placebo group). MAIN OUTCOME MEASURES: The main outcome measure was the percentage of cocaine-using days. Secondary measures were the Minnesota Cocaine Craving Scale and 12-Item Short-Form Health Survey scores. Adverse events were reported in both groups. RESULTS: The study population comprised 54 patients who attended at least one post-baseline assessment, out of the 104 subjects initially enrolled. The mean percentage of cocaine-using days in the homeopathy group was 18.1% (standard deviation (SD): 22.3%), compared to 29.8% (SD: 30.6%) in the placebo group (Pâ¯<â¯0.01). Analysis of the Minnesota Cocaine Craving Scale scores showed no between-group differences in the intensity of cravings, but results significantly favored homeopathy over placebo in the proportion of weeks without craving episodes and the patients' appraisal of treatment efficacy for reduction of cravings. Analysis of 12-Item Short-Form Health Survey scores found no significant differences. Few adverse events were reported: 0.57 adverse events/patient in the homeopathy group compared to 0.69 adverse events/patient in the placebo group (Pâ¯=â¯0.41). CONCLUSIONS: A psychosocial rehabilitation setting improved recruitment but was not sufficient to decrease dropout frequency among Brazilian cocaine treatment seekers. Psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca were more effective than psychosocial rehabilitation alone in reducing cocaine cravings. Due to high dropout rate and risk of bias, further research is required to confirm our findings, with specific focus on strategies to increase patient retention. TRIAL REGISTRATION: RBR-2xzcwz (http://www.ensaiosclinicos.gov.br).
Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Relacionados ao Uso de Cocaína/terapia , Homeopatia , Adolescente , Adulto , Idoso , Cocaína/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Fissura/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ópio/uso terapêutico , Projetos Piloto , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Polydrug use may challenge effective treatment for substance use disorders. We evaluate whether secondary substance use modifies the association between treatment and primary drug use among primary heroin, cocaine and methamphetamine (MA) users. METHODS: Data were obtained from prospective cohort studies on people who use illicit drugs (PWUD) in California, USA. Using repeated monthly data on self-reported secondary substance use (heroin, cocaine, MA, alcohol or marijuana; ≥1day in a month), primary drug use (≥1day in a month), and treatment participation, collected via timeline follow-back, we fitted generalized linear mixed multiple regression models controlling for potential confounders to examine the interactions between treatment and secondary substance use on the odds of primary heroin, cocaine and MA use, respectively. RESULTS: Included in our study were 587 primary heroin, 444 primary MA, and 501 primary cocaine users, with a median of 32.4, 13.3 and 18.9 years of follow-up, respectively. In the absence of secondary substance use, treatment was strongly associated with decreased odds of primary drug use (adjusted odds ratios (aORs): 0.25, 95% CI: 0.24, 0.27, 0.07 (0.06, 0.08), and 0.07 (0.07, 0.09)) for primary heroin, MA, and cocaine users, respectively. Secondary substance use of any kind moderated these associations (0.82 (0.78, 0.87), 0.25 (0.21, 0.30) and 0.53 (0.45, 0.61), respectively), and these findings were consistent for each type of secondary substance considered. Moreover, we observed different associations in terms of direction and magnitude between secondary substance use and primary drug use during off-treatment periods across substance types. CONCLUSION: This study demonstrates secondary substance use moderates the temporal associations between treatment and primary drug use among primary heroin, MA and cocaine users. Disparate patterns of polydrug use require careful measurement and analysis to inform targeted treatment for polydrug users.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Transtornos Relacionados ao Uso de Anfetaminas/reabilitação , Estimulantes do Sistema Nervoso Central , Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Dependência de Heroína/psicologia , Dependência de Heroína/reabilitação , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Adolescente , Adulto , Idade de Início , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Transtornos Relacionados ao Uso de Cocaína/complicações , Estudos de Coortes , Feminino , Dependência de Heroína/complicações , Humanos , Drogas Ilícitas , Masculino , Abuso de Maconha/complicações , Abuso de Maconha/psicologia , Abuso de Maconha/reabilitação , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The Drug User Comprehensive Care Policy establishes that care practices should cover biopsychosocial realms. However, evidence reveals an institutionalized practice, in which families prioritize the subject's seclusion from its context of use. This study aimed to understand the implications of psychosocial care and institutionalization in meeting the needs of adolescent crack users and their families. Eleven teenagers and six relatives narrated their experiences through in-depth interviews, which were analyzed in the light of Paul Ricoeur's Phenomenological Hermeneutics. A flow was observed in which teenagers seeking care are initially institutionalized and then referred to replacement services. Thus, there is an urgent need to strengthen the psychosocial care network so that adolescent crack users' care is offered comprehensively, ensuring respect for their fundamental rights, such as the right to freedom and to experience family or community life.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/reabilitação , Cocaína Crack , Usuários de Drogas/psicologia , Adolescente , Criança , Transtornos Relacionados ao Uso de Cocaína/psicologia , Humanos , Institucionalização , Entrevistas como Assunto , Masculino , Serviços de Saúde Mental/organização & administração , Aceitação pelo Paciente de Cuidados de Saúde , Direitos do Paciente , Adulto JovemRESUMO
AIMS: Chronic drug abuse leads to sex-specific changes in drug cue and stress physiologic and neuroendocrine reactivity as well as in neural responses to stress and cue-related challenges and in executive function such as inhibitory control, cognitive flexibility and self control. Importantly, these functions have been associated with high risk of relapse and treatment. Alpha-2 agonism may enhance inhibitory cognitive processes in the face of stress with sex-specific effects, however this has not been previously assessed in cocaine dependence. METHOD: Forty inpatient treatment-seeking cocaine dependent individuals (13F/27M) were randomly assigned to receive either placebo or up to 3mgs of Guanfacine. Three laboratory sessions were conducted following 3-4 weeks of abstinence, where patients were exposed to three 10-min personalized guided imagery conditions (stress, drug cue, combined stress/cue), one per day, on consecutive days in a random, counterbalanced order. The Stroop task was administered at baseline and immediately following imagery exposure. RESULTS: Guanfacine treated women improved their performance on the Stroop task following exposure to all 3 imagery conditions compared with placebo women (p=0.02). This improvement in cognitive inhibitory performance was not observed in the men. CONCLUSIONS: Enhancing the ability to cognitively regulate in the face of stress, drug cues and combined stress and drug cue reactivity may be key targets for medications development in cocaine dependent women.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Cocaína/uso terapêutico , Guanfacina/farmacologia , Caracteres Sexuais , Transtornos Relacionados ao Uso de Cocaína/psicologia , Sinais (Psicologia) , Feminino , Humanos , Masculino , Estresse Psicológico/psicologia , Teste de StroopRESUMO
Resumo A Política de Atenção Integral ao Usuário de Drogas determina que as práticas de cuidado abranjam as dimensões biopsicossociais. Evidências, entretanto, revelam uma prática institucionalizante, na qual as famílias priorizam o afastamento do sujeito de seu contexto de uso. Este estudo objetivou compreender as implicações da atenção psicossocial e da institucionalização no atendimento às necessidades de adolescentes em situação de uso de crack e de seus familiares. Onze adolescentes e seis familiares narraram suas experiências, por meio de entrevistas em profundidade, as quais foram analisadas à luz da Hermenêutica Fenomenológica, de Paul Ricoeur. Observou-se um fluxo, no qual os adolescentes, na busca pelo cuidado, inicialmente, são institucionalizados para, em seguida, serem encaminhados aos serviços substitutivos. Urge, portanto, a necessidade do fortalecimento da rede de atenção psicossocial para que o cuidado ao adolescente usuário de crack seja ofertado de forma integral, garantindo o respeito aos direitos fundamentais dos adolescentes, como o direito à liberdade e à convivência familiar e comunitária.
Abstract The Drug User Comprehensive Care Policy establishes that care practices should cover biopsychosocial realms. However, evidence reveals an institutionalized practice, in which families prioritize the subject's seclusion from its context of use. This study aimed to understand the implications of psychosocial care and institutionalization in meeting the needs of adolescent crack users and their families. Eleven teenagers and six relatives narrated their experiences through in-depth interviews, which were analyzed in the light of Paul Ricoeur's Phenomenological Hermeneutics. A flow was observed in which teenagers seeking care are initially institutionalized and then referred to replacement services. Thus, there is an urgent need to strengthen the psychosocial care network so that adolescent crack users' care is offered comprehensively, ensuring respect for their fundamental rights, such as the right to freedom and to experience family or community life.
Assuntos
Humanos , Masculino , Criança , Adolescente , Adulto Jovem , Cocaína Crack , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Usuários de Drogas/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Entrevistas como Assunto , Transtornos Relacionados ao Uso de Cocaína/psicologia , Direitos do Paciente , Institucionalização , Serviços de Saúde Mental/organização & administraçãoRESUMO
Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence.
Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Tálamo/fisiopatologia , Adulto , Encéfalo/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/psicologia , Função Executiva/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Análise Multivariada , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiopatologia , Tálamo/efeitos dos fármacosRESUMO
Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects ofl-THP and LDN on cocaine self-administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination ofl-THP and LDN reduces drug-seeking behavior during reinstatement more potently thanl-THP alone. Additionally, the combination ofl-THP and LDN attenuates the sedative locomotor effect induced byl-THP. Furthermore, we revealed that treatment with the combination ofl-THP and LDN has an upregulatory effect on both plasmaß-endorphin and hypothalamic POMC that was not observed inl-THP-treated groups. These results suggest that the combination ofl-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention.
Assuntos
Alcaloides de Berberina/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Animais , Transtornos Relacionados ao Uso de Cocaína/psicologia , Quimioterapia Combinada , Comportamento de Procura de Droga/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Pró-Opiomelanocortina/metabolismo , Ratos , Ratos Wistar , Recidiva , Autoadministração , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/psicologia , beta-Endorfina/sangue , beta-Endorfina/metabolismoRESUMO
OBJECTIVES: Fluctuations in progesterone levels during the menstrual cycle have been shown to affect physiological and subjective effects of cocaine. Furthermore, our laboratory has demonstrated that following drug-cue exposure, cocaine dependent women with high levels of circulating progesterone display lower diastolic and systolic blood pressure responses and report lower levels of anxiety and drug craving compared to cocaine dependent women with low levels of progesterone. In the current study we examined the role of the progesterone derived neuroactive steroid allopregnanolone (ALLO) on stress arousal, inhibitory control and drug craving in cocaine dependent subjects. METHODS: Plasma levels of ALLO were measured using GC/MS in 46 treatment-seeking cocaine dependent men and women on day 5 of a 7-day treatment regimen of micronized progesterone (15M/8F) (400mg/day) or placebo (14M/9F) administered in a double blind, randomized manner. As a control, levels of the testosterone derived neurosteroid androstanediol (ADIOL) were also measured. All subjects participated in laboratory sessions on days 5-7 of progesterone/placebo administration in which they were exposed to a series of 5-min personalized guided imagery of either a stressful situation, cocaine use or of a neutral setting and dependent variables including subjective craving, mood, Stroop task as a measure of inhibitory control performance and plasma cortisol were assessed. Participants were grouped by high or low ALLO level and levels of dependent variables compared between ALLO groups. RESULTS: Progesterone relative to placebo significantly increased ALLO levels with no sex differences. There were no effects of micronized progesterone on the testosterone derived ADIOL. Individuals in the high versus the low ALLO group showed decreased levels of cortisol at baseline, and a higher cortisol response to stress; higher positive mood scores at baseline and improved Stroop performance in the drug-cue and stress conditions, and reduced cocaine craving across all imagery conditions. CONCLUSIONS: As expected, cocaine dependent individuals administered progesterone showed significantly higher ALLO plasma levels. High levels of ALLO appeared to normalize basal and stress response levels of cortisol, decrease cocaine craving and also contribute to improvements in positive emotion and Stroop performance in response to stress and drug-cue exposures. These findings suggest that the neuroactive steroid ALLO plays a significant role in mediating the positive effects of progesterone on stress arousal, cognitive performance and drug craving in cocaine dependence.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/sangue , Transtornos Relacionados ao Uso de Cocaína/terapia , Fissura/efeitos dos fármacos , Pregnanolona/sangue , Progesterona/uso terapêutico , Estresse Psicológico/sangue , Estresse Psicológico/tratamento farmacológico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Método Duplo-Cego , Emoções/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Estresse Psicológico/etiologiaRESUMO
BACKGROUND: Prenatal cocaine exposure (PCE) is associated with increased rates of illicit-substance use during adolescence. In addition, both PCE and illicit-substance use are associated with alterations in cortico-striato-limbic neurocircuitry, development of which is ongoing throughout adolescence. However, the relationship between illicit-substance use, PCE and functional neural responses has not previously been assessed concurrently. METHODS: Sixty-eight adolescents were recruited from an ongoing longitudinal study of childhood and adolescent development. All participants had been followed since birth. Functional magnetic resonance imaging (fMRI) data were acquired during presentation of personalized stressful, favorite-food and neutral/relaxing imagery scripts and compared between 46 PCE and 22 non-prenatally-drug-exposed (NDE) adolescents with and without lifetime illicit-substance use initiation. Data were analyzed using multi-level ANOVAs (pFWE<.05). RESULTS: There was a significant three-way interaction between illicit-substance use, PCE status and cue condition on neural responses within primarily cortical brain regions, including regions of the left and right insula. Among PCE versus NDE adolescents, illicit-substance use was associated with decreased subcortical and increased cortical activity during the favorite-food condition, whereas the opposite pattern of activation was observed during the neutral/relaxing condition. Among PCE versus NDE adolescents, illicit-substance use during stress processing was associated with decreased activity in cortical and subcortical regions including amygdala, hippocampus and prefrontal cortex. Neural activity within cortico-striato-limbic regions was significantly negatively associated with subjective ratings of anxiety and craving among illicit-substance users, but not among non-users. CONCLUSIONS: These findings suggest different neural substrates of experimentation with illicit drugs between adolescents with and without in utero cocaine exposure.
Assuntos
Fissura , Drogas Ilícitas , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estresse Psicológico/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Criança , Cocaína/administração & dosagem , Cocaína/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Estudos de Coortes , Fissura/efeitos dos fármacos , Feminino , Humanos , Drogas Ilícitas/efeitos adversos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/psicologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
OBJECTIVES: Relapse to drug misuse may follow exposure to drug cues that elicit craving. The learned associations, or "emotional memories," that underlie responses to cues may be attenuated or erased by the ß-adrenergic antagonist propranolol during a "reconsolidation window" shortly after the memories are reactivated by cues. METHODS: We evaluated the effects of propranolol on cue-induced drug cravings in healthy opioid-dependent individuals who used cocaine while receiving methadone maintenance (nâ=â33). Participants were asked to recall specific cocaine use and neutral events in an interview; these events were used to develop personalized auditory script/cue sets. Approximately 1 week later, propranolol (40 mg) or placebo (random assignment, double blind) was administered orally before presentation of the script/cue sets; the presentation of the script/cue sets were tested 1 week and 5 weeks after the propranolol/placebo session. Ongoing drug use was monitored via urine screens and self-report in twice-weekly visits. RESULTS: Cue reactivity, as assessed by craving scales and physiological responses, was unexpectedly greater in the propranolol group than in the placebo group. This counterhypothesized group difference was present acutely during propranolol administration and seemed to persist (without reaching statistical significance) during the subsequent test sessions. CONCLUSIONS: Our results do not support the use of propranolol for cue-induced cocaine craving in opioid-maintained patients.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/psicologia , Fissura/efeitos dos fármacos , Sinais (Psicologia) , Rememoração Mental/efeitos dos fármacos , Propranolol/administração & dosagem , Adolescente , Adulto , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Método Duplo-Cego , Emoções , Feminino , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos , Adulto JovemRESUMO
OBJECTIVE: to understand the contributions of ludic care in nursing by stimulating the acceptance of chemical detoxification from crack on the perception of people in the detoxification process. METHODS: an exploratory, descriptive study with a qualitative approach, performed with five people hospitalized for chemical detoxification from crack, from March to July 2013 in a chemical detox unit of a midsize hospital in the central region of Rio Grande do Sul. Data was collected using a semi-structured interview and was subjected to content analysis. RESULTS: Two categories emerged: Ludic care in nursing as a stimulus to the acceptance of chemical detoxification; Ludic care in nursing in the promotion for healthy living after chemical detoxification. CONCLUSION: ludic care in nursing proved to enhance the acceptance of chemical detoxification from crack in the reality investigated.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/enfermagem , Cocaína Crack/efeitos adversos , Cuidados de Enfermagem/métodos , Educação de Pacientes como Assunto/métodos , Ludoterapia , Terapia Recreacional , Adolescente , Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Transtornos Relacionados ao Uso de Cocaína/terapia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Motivação , Papel do Profissional de Enfermagem , Aceitação pelo Paciente de Cuidados de Saúde , Ludoterapia/métodos , Jogos e Brinquedos , Psicologia do Adolescente , Pesquisa Qualitativa , Terapia Recreacional/psicologia , Centros de Tratamento de Abuso de SubstânciasRESUMO
BACKGROUND: Cholinergic transmission is altered by drugs of abuse and contributes to psychostimulant reinforcement. In particular, acetylcholinesterase inhibitors, like huperzine A, may be effective as treatments for cocaine use disorder. METHODS: The current report describes results from a double-blind, placebo-controlled study in which participants (n=14-17/group) were randomized to huperzine A (0.4 or 0.8 mg) or placebo. Participants received randomized infusions of cocaine (0 and 40 mg, IV) on days 1 and 9. On day 10, participants received noncontingent, randomized infusions of cocaine (0 and 20mg, IV) before making 5 choices to receive additional infusions. RESULTS: Huperzine A was safe and well-tolerated and compared with placebo, treatment with huperzine A did not cause significant changes in any cocaine pharmacokinetic parameters (all P>.05). Time-course and peak effects analyses show that treatment with 0.4 mg of huperzine A significantly attenuated cocaine-induced increases of "Any Drug Effect," "High," "Stimulated," "Willing to Pay," and "Bad Effects" (all P>.05). CONCLUSIONS: The current study represents a significant contribution to the addiction field since it serves as the first published report on the safety and potential efficacy of huperzine A as a treatment for cocaine use disorder.
Assuntos
Alcaloides/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Administração Intravenosa , Administração Oral , Adulto , Alcaloides/efeitos adversos , Alcaloides/farmacocinética , Pressão Sanguínea/efeitos dos fármacos , Inibidores da Colinesterase/efeitos adversos , Inibidores da Colinesterase/farmacocinética , Cocaína/administração & dosagem , Cocaína/sangue , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Autoadministração , Sesquiterpenos/efeitos adversos , Sesquiterpenos/farmacocinética , Resultado do TratamentoRESUMO
La cocaína es la droga responsable de más muertes en España. A pesar de una disminución del consumo en los últimos años, la prevalencia continúa siendo alta y es común hallarla en la práctica clínica. Si unimos a ello la peligrosidad del tóxico por su alta capacidad adictiva, las frecuentes y graves complicaciones que acarrea y la dificultad para su abandono, tenemos motivos de sobra para plantear una revisión tanto de su origen como de su estado actual, su abordaje clínico, y los retos para un futuro (AU)
Cocaine is the drug responsible for more deaths in Spain. Despite a decrease in consumption in recent years, the prevalence remains high and is common to find it in clinical practice. If you join it the danger of toxic because it´s addictive high capacity, frequent and serious complications involved and the difficulty of abandonment, we have every reason to propose a revision of both its origin and its present, its clinical approach, and challenges for the future (AU)