RESUMO
Italy has had the highest prevalence of hepatitis C virus (HCV) infection and mortality from HCV-related liver cancer in Europe. Although direct-acting antivirals (DAA) were initially restricted to persons with advanced fibrosis, their use has since been extended to all infected individuals; more than 244 000 persons have been treated to date. HCV liver-related mortality is expected to decline by 75% by 2030, achieving the World Health Organization target for mortality. However, Italy risks failing to meet the overall goal of eliminating HCV infection by 2030. In this light, 71.5 million have been allocated for screening initially specific target populations (persons who inject drugs, prison inmates, and the 1969-1989 birth cohort). Herein, we outline the challenges and recommendations for how to move Italy toward HCV elimination, including expanding screening programs in other populations, increasing awareness through strategic communication, sustaining DAA access, and tailoring care models to meet the needs of key populations.
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Usuários de Drogas , Hepatite C Crônica , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Hepacivirus , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Itália/epidemiologiaRESUMO
BACKGROUND: It has been estimated that the incidence of chronic hepatitis C virus (HCV) will not decline over the next 10 years despite the improved efficacy of antiviral therapy because most patients remain undiagnosed and/or untreated. This study aimed to investigate the opinion of relevant target populations on the practicability, effectiveness and best modalities of the test-and-treat approach in the fight against HCV in Italy. METHODS: A survey was delivered to patients with HCV from the general population, patients from drug addiction services, hospital physicians and healthcare providers for drug addiction services. RESULTS: For both hospital clinicians and SerD HCPs, tolerability is shown as the most important feature of a suitable treatment. Time to treatment (the time from first contact to initiation of treatment) is deemed important to the success of the strategy by all actors. While a tolerable treatment was the main characteristic in a preferred care pathway for general patients, subjects from drug addiction services indicated that a complete Meet-Test-Treat pathway is delivered within the habitual care center as a main preference. This is also important for SerD HCPs who are a strong reference for their patients; hospital clinicians were less aware of the importance of the patient-HCP relationship in this process. CONCLUSION: The health system is bound to implement suitable pathways to facilitate HCV eradication. A Meet-Test-Treat program within the drug addiction services may provide good compliance from subjects mainly concerned with virus transmission.
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Hepatite C Crônica , Hepatite C , Transtornos Relacionados ao Uso de Substâncias , Antivirais/uso terapêutico , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hospitais , Humanos , Incidência , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológicoRESUMO
BACKGROUND: Prisoners constitute a high-risk population, particularly for infectious diseases. The aim of this study was to estimate the level of infectious risk in the prisons of five different European countries by measuring to what extent the prison system adheres to WHO/UNODC recommendations. METHODS: Following the methodology used in a previous French survey, a postal/electronic questionnaire was sent to all prisons in Austria, Belgium, Denmark and Italy to collect data on the availability of several recommended HIV-HCV prevention interventions and HBV vaccination for prisoners. A score was built to compare adherence to WHO/UNODC recommendations (considered a proxy of environmental infectious risk) in those 4 countries. It ranged from 0 (no adherence) to 12 (full adherence). A second score (0 to 9) was built to include data from a previous French survey, thereby creating a 5-country comparison. RESULTS: A majority of prisons answered in Austria (100 %), France (66 %) and Denmark (58 %), half in Belgium (50 %) and few in Italy (17 %), representing 100, 74, 89, 47 and 23 % coverage of the prison populations, respectively. Availability of prevention measures was low, with median adherence scores ranging from 3.5 to 4.5 at the national level. These results were confirmed when using the second score which included France in the inter-country comparison. Overall, the adherence score was inversely associated with prison overpopulation rates (p = 0.08). CONCLUSIONS: Using a score of adherence to WHO/UNODC recommendations, the estimated environmental infectious risk remains extremely high in the prisons of the 5 European countries assessed. Public health strategies should be adjusted to comply with the principle of equivalence of care and prevention with the general community.
Assuntos
Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Redução do Dano , Prisioneiros/estatística & dados numéricos , Prisões/estatística & dados numéricos , Adulto , Áustria , Bélgica , Dinamarca , Europa (Continente)/epidemiologia , Feminino , França , Humanos , Internacionalidade , Itália , Masculino , Inquéritos e Questionários , Nações Unidas , Organização Mundial da SaúdeRESUMO
Purpose: Hepatitis C virus (HCV) spreads from contact with blood of an infected person. HCV infections are common among people who use drugs (PWUDs), when sharing needles, syringes, or other equipment for injected drugs. The advent of pangenotypic direct-antiviral agents (DAA) in 2017 transformed the treatment landscape for HCV, but PWUDs remain a complex and hard-to-treat population with high risk of HCV reinfection. The aim of this real-world analysis was to characterize the demographic and clinical features of PWUDs in Italy, also focusing on comorbidity profile, treatment with DAAs, resource consumptions for the National Health System (NHS). Patients and Methods: During 01/2011-06/2020, administrative databases of Italian healthcare entities, covering 3,900,000 individuals, were browsed to identify PWUDs with or without HCV infection. Among HCV+ patients, a further stratification was made into treated and untreated with DAAs. The date of PWUD or HCV first diagnosis or DAA first prescription was considered as index-date. Patients were then followed-up for one year. Alcohol-dependency was also investigated. Results: Total 3690 PWUDs were included, of whom 1141 (30.9%) PWUD-HCV+ and 2549 (69.1%) PWUD-HCV-. HCV-positive were significantly older (43.6 vs 38.5 years, p < 0.001), had a worse comorbidity profile (Charlson-index: 0.8 vs 0.4, p < 0.001), and high rates of psychiatric, respiratory, dermatological, musculoskeletal diseases and genitourinary (sexually transmitted) infections. Moreover, they received more drug prescriptions (other than DAAs, like anti-acids, antiepileptics, psycholeptics) and had undergone more frequent hospitalization, predominantly for hepatobiliary, respiratory system and mental disorders. DDA-untreated had significantly higher Charlson-index than DAA-treated (0.9 vs 0.6, p = 0.003). Alcoholism was found in 436 (11.8%) cases. Conclusion: This Italian real-world analysis suggests that PWUDs with HCV infection, especially those untreated with DAAs, show an elevated drug consumption due to their complex clinical profile. These findings could help to ameliorate the healthcare interventions on PWUDs with HCV infection.
RESUMO
Although Italy has been on track for Hepatitis C Virus (HCV) elimination since 2019, it fell off track due to the decrease in the number of treated patients. HCV elimination in Italy will be possible if immediate action is taken. A health policy was implemented beginning in 2021, consisting of screening among key populations and birth cohorts (1969-1989), estimated to have a high prevalence of undiagnosed individuals. The active screening requires regional governance that manages the processes' complexity integrating a well-organized network between territory assistance and hospital to achieve an effective HCV care cascade. This document aims to support the regional decision-making process by defining paths for screening and linkage-to-care. Implementing active screening strategies beyond a risk-based approach is required as a General Practitioners' task. Simplified paths must be drawn for the key populations screening. The infrastructure built for COVID-19 vaccination could be used also for HCV screening. According to a multidisciplinary care delivery, screening should be supplemented with rapid linkage-to-care and treatment of newly diagnosed patients. The realization of the proactive screening during the first two years is vital because it will define the tracks for the whole HCV cost-effective screening of 1948-1988 birth cohorts in Italy.
Assuntos
Vacinas contra COVID-19/administração & dosagem , Erradicação de Doenças/organização & administração , Política de Saúde , Hepatite C/diagnóstico , Programas de Rastreamento/organização & administração , Vacinação em Massa/organização & administração , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Humanos , Itália/epidemiologiaRESUMO
Significant steps must be taken to reduce the global incidence and prevalence of hepatitis C virus (HCV) and mortality from HCV infection to achieve the WHO goal of eliminating viral hepatitis as a public health threat by 2030. Proper epidemiological surveillance of the full continuum of care is essential for monitoring progress and identifying gaps that need to be addressed. The tools required for elimination have largely been established, and the issue at hand is more how they should best be implemented in different settings around the world. Documenting good practices allows for knowledge exchange to prevent transmission and improve health outcomes for people with HCV. This review found 13 well documented HCV good practices that have become the standard of care or that should become the standard of care as soon as possible. In 2013, highly effective direct-acting antiviral therapy became available, which has cure rates of over 95%. Together with this new therapy, evidence-based good practices can help countries eliminate viral hepatitis C.
Assuntos
Hepatite C , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Padrão de CuidadoRESUMO
Introduction: Sodium oxybate (SMO) has been approved in Italy and in Austria for the treatment of alcohol use disorder (AUD). This study describes the cumulative postmarketing and clinical safety experience with SMO in AUD.Areas covered: Safety data for SMO at approved posology in AUD were identified from: (i) the clinical trial registries of the US National Institutes of Health (NIH) and the European Medicines Agency (EMA), (ii) reports from the biomedical literature and (iii) available pharmacovigilance safety information from the EMA.Expert opinion: Safety data from 3 recent large randomized clinical studies (520 participants) and 43 earlier clinical studies (2547 participants) showed that SMO has a good safety profile in AUD patients. The safety profile was confirmed by pharmacovigilance data resulting from 299 013 patients exposed to SMO in Austria and Italy. Main adverse events were transitory dizziness and vertigo. Serious adverse events were rare. No death attributable to SMO has been reported. Risks of abuse or dependence are low in patients without psychiatric comorbidities or poly-drug use. The adverse events of SMO are transitory and do not require discontinuation of treatment. SMO abuse or dependence are extremely rare in patients without psychiatric comorbidities or poly-drug use.
Assuntos
Alcoolismo/tratamento farmacológico , Oxibato de Sódio/administração & dosagem , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Oxibato de Sódio/efeitos adversosRESUMO
PURPOSE: Gender inequality and sexism are often at the root of domestic violence against women and children, with both serving to justify male domination. This runs in parallel with mother-blaming bias, which constitutes a pervasive common sense and scientific error derived from the myth of the good and the bad mother, characterising a large part of studies on deviance. The purpose of this paper is to consider the possible role of sexism in prisoners' deviant biographies; for this, the authors considered the role of the mother in the biographies of prisoners, and the results lend support to the idea that mother-blaming is a serious fallacy. Starting from a critical psychology point of view and following the retrospective methodology, the authors interviewed 22 drug-addicted prisoners through Interpretative Phenomenological Analysis (IPA) regarding their biographies and their relationships with parents and partners. DESIGN/METHODOLOGY/APPROACH: In the survey, the authors followed the same intention, and the results lend support to the idea that mother-blaming is a serious fallacy. The authors interviewed 22 drug-addicted prisoners through IPA concerning their biographies and their relationships with parents and partners. FINDINGS: The main result of this qualitative study was the recognition of a fundamental sexism assumed by participants, characterised by a paradox between the representation of the mother and the representation of the ideal woman. Despite the mother being their positive affective referent, and battered by her husband/partner, the same participants had been witnesses of domestic violence, and sometimes victims, they interiorised from their father an ambivalent sexism: benevolent sexism with regard to their mother and exhibited hostile sexism with their partner. On the one hand, it emerged that female empowerment was desirable with respect to the mothers. On the other hand, the ideal woman was exactly as their mother was, that is, being absolutely subordinated to men (a patient, caring, submissive housewife, totally dedicated to her children and her husband). RESEARCH LIMITATIONS/IMPLICATIONS: From a mainstream psychological perspective, the limits of the research are linked to the utilisation of the narrative method. Also, this methodology does not verify any hypotheses, so quotations from the participants are used to illustrate themes, and thus, it is difficult to report the informational complexities arising from the dialogues. However, the literature has emphasised that these limitations do not invalidate qualitative research findings, despite the difficulties in generalising the results of the qualitative studies. Thereafter, the critical analysis moved within the intersection of experience-centred approaches and the culturally oriented treatment of narratives, so that the focus on the stories of the prisoners makes meaning because it applies structure to experience, albeit, with the form and content of the texts. This research did not permit us to measure and evaluate post-hoc any post-traumatic hypotheses, which, in turn, would give room for further research. Another limitation of the research was that the relationship between culture of origin and gender biases, especially with participants from non-European countries, was not analysed. This topic would require an important in-depth study, which encompasses how women are treated in different countries and its effects on social maladjustment for immigrants in Italy. PRACTICAL IMPLICATIONS: The outcome of this study suggests that within similar structures in the Institute of Mitigated Custody, the theme of sexism should be considered in more depth. Since sexism justifies violence against women, and is therefore a factor that can cause recidivism in the antisocial behaviour of prisoners once they have served their sentences. It is important to allow them to analyse the relationship between their sexist attitudes, witnessing violence in childhood and the possibility of changing moral values of reference in favour of equality. This type of psychological intervention must necessarily be based not only on the elaboration of traumas suffered during childhood with an abusive father, but also on issues related to gender equality and the theme of social inclusion. SOCIAL IMPLICATIONS: The study suggests the idea that male sexism can be a factor responsible for suffering and maladjustment for men and that therefore an education that promotes equality of gender differences can also help prevent the social distress associated with drug addiction and deviance. ORIGINALITY/VALUE: The paper considers some cogent issues inherent to ambivalent sexism that pervades prisoners' aspirations for their future.
Assuntos
Violência Doméstica/psicologia , Relações Familiares/psicologia , Sexismo/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Relações Pai-Filho , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Relações Mãe-Filho , Pesquisa Qualitativa , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
Opioid use disorder (OUD) is a major public health issue that has reached epidemic levels in some parts of the world. It is a chronic and complex neurobiological disease associated with frequent relapse to drug taking. Craving, defined as an overwhelmingly strong desire or need to use a drug, is a central component of OUD and other substance use disorders. In this review, we describe the neurobiological and neuroendocrine pathways that underpin craving in OUD and also focus on the importance of assessing and treating craving in clinical practice. Craving is strongly associated with patients returning to opioid misuse and is therefore an important treatment target to reduce the risk of relapse and improve patients' quality of life. Opioid agonist therapies (OAT), such as buprenorphine and methadone, can significantly reduce craving and relapse risk, and it is essential that patients are treated optimally with these therapies. There is also evidence to support the benefits of non-pharmacological approaches, such as cognitive behavioral therapy and mindfulness-based interventions, as supplementary treatments to opioid agonist therapies. However, despite the positive impact of these treatments on craving, many OUD patients continue to suffer with negative affect and dysphoria. There is a clear need for further studies to progress our understanding of the neurobiological basis of craving and addiction and to identify novel therapeutic strategies as well as to optimize the use of existing treatments to improve outcomes for the growing numbers of patients affected by OUD.
RESUMO
INTRODUCTION AND AIMS: People who inject drugs (PWID) constitute the largest reservoir of hepatitis C virus (HCV). Although effective medications are available and access to care is universal in Italy, the proportion of PWID receiving appropriate care remains low. DESIGN AND METHODS: To identify the major barriers for PWID to HCV treatment we surveyed a large sample of practitioners working in outpatient addiction centres (SerDs). The survey was conducted in two stages and involved 30.3% of SerDs operating in Italy. In the first, SerD physicians completed a questionnaire designed with a Delphi structure. In the second, SerD practitioners completed a targeted questionnaire to identify barriers to four SerD services in HCV management: screening, referral, treatment and harm reduction. RESULTS: The first-stage questionnaire, in which a Delphi and RAND-UCLA method was used, revealed a lack of agreement among the physicians about barriers to health care. The more detailed second-stage questionnaire indicated the barriers to delivering specific SerD services. As regarded the delivery of all four services, the major reasons for treating <50% of patients were: physician and nurse understaffing, technical, economic and logistic issues. In contrast, the practitioners who responded that they follow protocol recommendations often deliver all four services to >50% of patients. DISCUSSION AND CONCLUSIONS: HCV treatment remains out of reach for many PWID attending a drug treatment centre in Italy. To meet the World Health Organisation (WHO) target, there is a need to increase economic, technical and staff support at treatment centres using the protocols and the universal health care already in place.
Assuntos
Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adolescente , Instituições de Assistência Ambulatorial , Redução do Dano , Humanos , Itália/epidemiologia , Adulto JovemRESUMO
An open randomized study lasting 12 months was performed to evaluate the efficacy of methadone or buprenorphine to suppress alcohol use in two hundred and eighteen heroin addicts with alcohol dependence. Daily maintenance doses of methadone were 80, 120, 160, and 200 mg/day, while doses of buprenorphine were 8, 16, 24, and 32 mg/day. As expected, both treatments were able to reduce both heroin use and addiction severity (measured with ASI interview). However, although both medications were able to suppress alcohol use, the highest dose of buprenorphine was better than the highest dose of methadone, in reducing alcohol craving, ethanol intake (measured as daily number of drinks), and the ASI subscale of alcohol use. The mechanism underlying the effects of the opioid maintenance therapy on the reduction of alcohol intake is still unclear. The results of the present study may represent the first clinical evidence of the potential effective use of the highest doses of buprenorphine for the suppression of ethanol intake in heroin addicts with alcohol dependence.
Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo/tratamento farmacológico , Buprenorfina/uso terapêutico , Dependência de Heroína/tratamento farmacológico , Metadona/uso terapêutico , Entorpecentes/uso terapêutico , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/complicações , Alcoolismo/psicologia , Análise de Variância , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Feminino , Dependência de Heroína/complicações , Humanos , Masculino , Estudos Prospectivos , Adulto JovemRESUMO
The hypothalamic-pituitary-adrenal (HPA) axis activity is usually altered by heroin use. In the present study we evaluated in one hundred twenty-one heroin addicts the effects of marijuana smoking on the normalization of HPA axis upon methadone treatment. The study showed that in heroin addicts who are chronic cannabis smokers a treatment with methadone lasting 12 months was able to normalize both plasma corticotropin (ACTH) and cortisol levels, as well as to control both heroin withdrawal symptoms and opioid craving. As expected in the same group of patients marijuana smoking and its craving were not reduced by methadone treatment. Our data confirm that methadone treatment outcomes are not modified by cannabis use and they add in the literature the evidence that chronic cannabis use is not able to affect the normalization of HPA axis upon methadone treatment in heroin addicts.
Assuntos
Dependência de Heroína/fisiopatologia , Dependência de Heroína/reabilitação , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Abuso de Maconha/complicações , Abuso de Maconha/fisiopatologia , Metadona/uso terapêutico , Entorpecentes/uso terapêutico , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Adulto , Interações Medicamentosas , Ensaio de Imunoadsorção Enzimática , Feminino , Dependência de Heroína/psicologia , Humanos , Hidrocortisona/sangue , Masculino , Abuso de Maconha/urina , Escalas de Graduação Psiquiátrica , Detecção do Abuso de Substâncias , Resultado do TratamentoRESUMO
Drug addiction is a major care and safety challenge in prison context. Nowadays, rehabilitation and specific therapeutic programs are suggested to improve health and well-being of inmates during their detention time and to reduce substance abuse relapse after release from prison. Among these programs, several studies reported the benefits for inmates coming from animal assisted interventions. In this pilot controlled study, we investigated the efficacy of a dog assisted therapy program addressed to 22 drug addicted male inmates housed in an attenuated custody institute in Italy. The study lasted six months, the treated group (12 inmates) was involved once a week for one hour in 20 dog assisted therapy sessions, whereas the control group (10 inmates) followed the standard rehabilitation program. One week before the beginning and one week after the end of the sessions, all inmates involved were submitted to symptom checklist-90-revised and Kennedy axis V. Inmates involved in the dog assisted therapy sessions significantly improved their social skills, reducing craving, anxiety and depression symptoms compared to the control group. Despite the limitation due to the small number of inmates enrolled and to the absence of follow up, we found these results encouraging to the use of dog assisted therapy as co-therapy in drug addicted inmates rehabilitation programs, and we claim the need of more extensive study on this subject.
Assuntos
Terapia Assistida com Animais/estatística & dados numéricos , Ansiedade/terapia , Fissura , Depressão/terapia , Usuários de Drogas/estatística & dados numéricos , Habilidades Sociais , Adulto , Animais , Cães , Humanos , Itália , Masculino , Projetos Piloto , Prisioneiros/estatística & dados numéricos , Adulto JovemRESUMO
Twelve-month treatment of heroin addicts with methadone or buprenorphine normalized plasma cortisol levels, and controlled withdrawal symptoms as well as craving. During treatment, the time course of plasma cortisol levels and craving was not strictly correlated: heroin craving was more elevated at 12 than at 3 months. The results suggest a correlation between hypercortisolism, withdrawal symptoms and heroin use and suppose a more complex role for craving and its components in drug-taking behaviour. The main goal of the pharmacological treatment of opioid-dependence should be addressed at the normalization of hypothalamic-pituitary-adrenocortical (HPA) axis more than at the control of craving.
Assuntos
Buprenorfina/uso terapêutico , Dependência de Heroína/sangue , Dependência de Heroína/reabilitação , Heroína/efeitos adversos , Hidrocortisona/sangue , Metadona/uso terapêutico , Motivação , Entorpecentes/uso terapêutico , Síndrome de Abstinência a Substâncias/sangue , Adulto , Feminino , Seguimentos , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Estatística como Assunto , Síndrome de Abstinência a Substâncias/diagnósticoRESUMO
An open randomized study was conducted to compare different treatments of alcoholism on ethanol intake, craving, and on biochemical measures of alcohol consumptions. Eighty-six alcoholics were abstinent for a mean of two weeks prior to random assignment to g-hydroxybutyrate (GHB, 50 mg/kg of body weight t.i.d), naltrexone (NTX, 50 mg/day) or disulfiram (DSF, 200 mg/ day) treatment for 12 months. All treatments were equally effective in reducing alcohol intake and in maintaining abstinence. In all patients, the treatments were able to reduce both craving and the altered biological markers of alcohol abuse. The maximum effects were observed in GHB-treated patients. The results of the present study suggest that GHB might act both as anticraving and cellular protector agent.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/metabolismo , Alcoolismo/psicologia , Adulto , Dissuasores de Álcool/efeitos adversos , Dissuasores de Álcool/uso terapêutico , Alcoolismo/tratamento farmacológico , Biomarcadores , Dissulfiram/efeitos adversos , Dissulfiram/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/efeitos adversos , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/efeitos adversos , Antagonistas de Entorpecentes/uso terapêutico , Escalas de Graduação Psiquiátrica , Oxibato de Sódio/efeitos adversos , Oxibato de Sódio/uso terapêutico , TemperançaRESUMO
Recent studies suggest that the endocannabinoid system modulates feeding. Despite the existence of central mechanisms for the regulation of food intake by endocannabinoids, evidence indicates that peripheral mechanisms may also exist. To test this hypothesis, we investigated (1) the effects of feeding on intestinal anandamide accumulation; (2) the effects of central (intracerebroventricular) and peripheral (intraperitoneal) administration of the endocannabinoid agonist anandamide, the synthetic cannabinoid agonist R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate (WIN55,212-2), and the CB1-selective antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716A) on food intake in rats; and (3) the effects of sensory deafferentation on the modulation of feeding by cannabinoids. Food deprivation produced a sevenfold increase in anandamide content in the small intestine but not in the brain or stomach. Refeeding normalized intestinal anandamide levels. Peripheral but not central administration of anandamide or WIN55,212-2 promoted hyperphagia in partially satiated rats. Similarly, peripheral but not central administration of SR141716A reduced food intake. Capsaicin deafferentation abolished the peripheral effects of both cannabinoid agonists and antagonists, suggesting that these agents modulate food intake by acting on CB1 receptors located on capsaicin-sensitive sensory terminals. Oleoylethanolamide, a noncannabinoid fatty ethanolamide that acts peripherally, prevented hyperphagia induced by the endogenous cannabinoid anandamide. Pretreatment with SR141716A enhanced the inhibition of feeding induced by intraperitoneal administration of oleoylethanolamide. The results reveal an unexpected role for peripheral CB1 receptors in the regulation of feeding.
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Comportamento Alimentar/fisiologia , Ácidos Oleicos , Receptores de Droga/metabolismo , Animais , Regulação do Apetite/efeitos dos fármacos , Regulação do Apetite/fisiologia , Ácidos Araquidônicos/metabolismo , Ácidos Araquidônicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Benzoxazinas , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Moduladores de Receptores de Canabinoides , Capsaicina/farmacologia , Denervação , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Ingestão de Alimentos/efeitos dos fármacos , Endocanabinoides , Comportamento Alimentar/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Hiperfagia/induzido quimicamente , Hiperfagia/tratamento farmacológico , Injeções Intraperitoneais , Injeções Intraventriculares , Intestino Delgado/metabolismo , Masculino , Morfolinas/farmacologia , Naftalenos/farmacologia , Ácido Oleico/farmacologia , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptores de Canabinoides , Receptores de Droga/agonistas , Receptores de Droga/antagonistas & inibidores , Rimonabanto , Resposta de Saciedade/efeitos dos fármacosRESUMO
Drug addiction and alcoholism are behavioural disorders characterized by a profound alteration of several brain circuits induced by chronic drug use. Their treatment is yet based on empiricism and today only few pharmacological strategies are fully effective to control both drug use and relapse. The present paper reviews the most updated pharmacotherapies able to contrast both alcoholism and drug addiction including the new patented drugs and the future therapeutic trends.
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Alcoolismo/tratamento farmacológico , Neurotransmissores/uso terapêutico , Receptores de Neurotransmissores/antagonistas & inibidores , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Alcoolismo/patologia , Animais , Encéfalo/efeitos dos fármacos , Humanos , Neurotransmissores/farmacologia , Transtornos Relacionados ao Uso de Substâncias/patologiaRESUMO
In 42 alcoholic inpatients we performed an open randomized study to compare the effects of diazepam and gamma-hydroxybutyrate (GHB) on the suppression of severe alcohol withdrawal syndrome and hypercortisolism. Both diazepam (.5 mg/kg bodyweight, q.i.d.) and GHB (50 mg/kg bodyweight, q.i.d.) were orally administered for three weeks. During all study period, GHB was more able than diazepam in reducing both withdrawal syndrome and hypercortisolism. These effects were evident during the first week of treatment and persisted throughout the study period. The results confirm a strict correlation between high levels of plasma cortisol and alcohol withdrawal symptoms and they show a slight superiority of GHB over diazepam in the suppression of both ethanol withdrawal and hypercortisolism. Taken together, our data suggest that GHB may act as potent anti-withdrawal agent in severe abstinent alcoholics.