Uso de sustancias psicoactivas como tratamiento de la psicosis / Use of psychoactive substances as a treatment for psychosis

Introducción: Los trastornos psicóticos se consideran problemas crónicos de salud mental. Aunque se ha demostrado que estos trastornos pueden presentarse con sintomatologías muy heterogéneas, el tratamiento farmacológico se basa en el uso de antipsicóticos típicos y atípicos, cuyo mecanismo de acción principal es el bloqueo dopaminérgico, limitando su efecto a la mejora de los síntomas positivos, sin mejorar el resto de la sintomatología y presentando una gran cantidad de efectos adversos graves. Por este motivo se están estudiando nuevas dianas terapéuticas distintas al sistema dopaminérgico. El objetivo principal de esta revisión es comprobar si estas sustancias psicoactivas utilizadas en la práctica clínica podrían aportar beneficios adicionales como tratamiento complementario para personas con trastornos psicóticos. Desarrollo: Para esta revisión sistemática se realizó una búsqueda bibliográfica en las bases de datos PsycINFO, Medline, Psicodoc, PubMed y Google Scholar. Se incluyeron 28 artículos en la revisión. Entre los principales resultados encontramos que el cannabidiol es más efectivo para mejorar los síntomas positivos y la psicopatología; el modafinilo, para los síntomas cognitivos, el funcionamiento motor y emocional y la calidad de vida; y la ketamina, para los síntomas negativos. Además, todas las sustancias presentaron un buen perfil de tolerabilidad y seguridad, especialmente en comparación con los antipsicóticos. Conclusión: Con los resultados obtenidos, se abre la posibilidad de tener una guía de actuación para los clínicos/profesionales de la salud sobre el uso del cannabidiol, el modafinilo y la ketamina como tratamiento adyuvante para pacientes con cuadros psicóticos.(AU)

Introduction: Psychotic disorders are considered chronic mental health issues. Although it has been demonstrated that these disorders can present with a wide range of symptoms, pharmacological treatment is based on the use of typical and atypical antipsychotics, whose main mechanism of action is dopaminergic blockade, limiting their effect to the improvement of positive symptoms, without improving the rest of the symptoms and giving rise to a large number of serious adverse effects. For this reason, new therapeutic targets other than the dopaminergic system are being studied. The main objective of this review is to test whether these psychoactive substances used in clinical practice could provide additional benefits as an adjunctive treatment for people with psychotic disorders. Development: For this systematic review, a literature search was conducted in the databases PsycINFO, Medline, Psicodoc, PubMed and Google Scholar. Altogether 28 articles were included in the review. One of the main findings is that cannabidiol is more effective for improving positive symptoms and psychopathology; modafinil, for cognitive symptoms, motor and emotional functioning and quality of life; and ketamine, for negative symptoms. In addition, all the substances showed a good tolerability and safety profile, especially in comparison to antipsychotics. Conclusion: The results obtained open up the possibility of having a guideline for clinicians/health professionals on the use of cannabidiol, modafinil and ketamine as adjunctive treatment for patients with psychotic conditions.(AU)

[Use of psychoactive substances as a treatment for psychosis]. / Uso de sustancias psicoactivas como tratamiento de la psicosis.

INTRODUCTION: Psychotic disorders are considered chronic mental health issues. Although it has been demonstrated that these disorders can present with a wide range of symptoms, pharmacological treatment is based on the use of typical and atypical antipsychotics, whose main mechanism of action is dopaminergic blockade, limiting their effect to the improvement of positive symptoms, without improving the rest of the symptoms and giving rise to a large number of serious adverse effects. For this reason, new therapeutic targets other than the dopaminergic system are being studied. The main objective of this review is to test whether these psychoactive substances used in clinical practice could provide additional benefits as an adjunctive treatment for people with psychotic disorders. DEVELOPMENT: For this systematic review, a literature search was conducted in the databases PsycINFO, Medline, Psicodoc, PubMed and Google Scholar. Altogether 28 articles were included in the review. One of the main findings is that cannabidiol is more effective for improving positive symptoms and psychopathology; modafinil, for cognitive symptoms, motor and emotional functioning and quality of life; and ketamine, for negative symptoms. In addition, all the substances showed a good tolerability and safety profile, especially in comparison to antipsychotics. CONCLUSION: The results obtained open up the possibility of having a guideline for clinicians/health professionals on the use of cannabidiol, modafinil and ketamine as adjunctive treatment for patients with psychotic conditions.

TITLE: Uso de sustancias psicoactivas como tratamiento de la psicosis.Introducción. Los trastornos psicóticos se consideran problemas crónicos de salud mental. Aunque se ha demostrado que estos trastornos pueden presentarse con sintomatologías muy heterogéneas, el tratamiento farmacológico se basa en el uso de antipsicóticos típicos y atípicos, cuyo mecanismo de acción principal es el bloqueo dopaminérgico, limitando su efecto a la mejora de los síntomas positivos, sin mejorar el resto de la sintomatología y presentando una gran cantidad de efectos adversos graves. Por este motivo se están estudiando nuevas dianas terapéuticas distintas al sistema dopaminérgico. El objetivo principal de esta revisión es comprobar si estas sustancias psicoactivas utilizadas en la práctica clínica podrían aportar beneficios adicionales como tratamiento complementario para personas con trastornos psicóticos. Desarrollo. Para esta revisión sistemática se realizó una búsqueda bibliográfica en las bases de datos PsycINFO, Medline, Psicodoc, PubMed y Google Scholar. Se incluyeron 28 artículos en la revisión. Entre los principales resultados encontramos que el cannabidiol es más efectivo para mejorar los síntomas positivos y la psicopatología; el modafinilo, para los síntomas cognitivos, el funcionamiento motor y emocional y la calidad de vida; y la ketamina, para los síntomas negativos. Además, todas las sustancias presentaron un buen perfil de tolerabilidad y seguridad, especialmente en comparación con los antipsicóticos. Conclusión. Con los resultados obtenidos, se abre la posibilidad de tener una guía de actuación para los clínicos/profesionales de la salud sobre el uso del cannabidiol, el modafinilo y la ketamina como tratamiento adyuvante para pacientes con cuadros psicóticos.

Critical behaviour in the optimal generation of multipartite entanglement.

Two systems whose correlations cannot be classically accounted for display the simplest instance of quantum entanglement. Although this two-party association has caused a revolution in the foundations and uses of quantum mechanics, genuine entanglement among several parties unveils a whole new class of phenomena and applications. In this work we suggest a way to prepare Dicke states from a tunable source of bipartite entanglement to investigate foundational issues. The scheme has the following distinctive features: (i) it relies on controlled information loss and unentangled measurements; (ii) irrespective of the source entanglement, whenever a Dicke state is produced, it is ideal; (iii) the optimal entanglement of the bipartite source undergoes a second-order-like transition depending on the parameters of the Dicke state to be produced. These properties lead to asymptotic results on the entanglement between any qubit belonging to a Dicke state and the remaining qubits.

Sulfasalazine prevents the increase in TGF-ß, COX-2, nuclear NFκB translocation and fibrosis in CCl4-induced liver cirrhosis in the rat.

It has been demonstrated that this sulfasalazine (SF) inhibits the nuclear factor κB (NFκB) pathway, which regulates important genes during inflammation and immune answer. The aim of this work was to evaluate the effects of SF on carbon tetrachloride (CCl(4))-induced liver fibrosis. We formed the following experimental groups of rats: controls, damage induced by chronic CCl(4) (0.4 g/kg, intraperitoneally, three times a week for 8 weeks) administration and CCl(4) + SF (100 mg/kg/day, postoperatively for 8 weeks) administration. We determined the activities of alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), cyclooxygenase (COX)-1 and COX-2, lipid peroxidation, glutathione levels, collagen content, expression of transforming growth factor-ß (TGF-ß) and nuclear translocation of NFκB. SF was capable to inhibit the ALT and γ-GTP elevated levels induced with the CCl(4) administration. SF had antioxidant properties, prevented the lipid peroxidation and the imbalance of reduced and oxidized glutathione produced by CCl(4). Importantly, SF blocked the accumulation of collagen in the liver, the expression of TGF-ß, the nuclear translocation of NFκB and the activity of COX-2, all induced with the administration of CCl(4) in the rat. These results show that SF has strong antifibrotic properties because of its antioxidant properties and its ability to prevent nuclear translocation of NFκB and consequently the expression of TGF-ß and the activity of COX-2.

Short-term effects of thalidomide analogs on hepatic glycogen and nitric oxide in endotoxin-challenged rats.

Hepatic glycogen metabolism is altered by nitric oxide (NO) during endotoxic shock. Thalidomide analogs immunomodulate the endotoxin-induced cytokines which regulate the NO release. We analyzed the short-term effects of some thalidomide analogs on the hepatic glycogen store and on the plasma and hepatic NO in an acute model of endotoxic challenge in rat. An endotoxin dose selection was performed. Rats received vehicle, thalidomide or analogs orally and, two hours after last dose, they were injected with endotoxin (5 mg/kg). Animals were sacrificed 2 h after challenge. Liver glycogen was quantified by the anthrone technique. Plasma and hepatic NO was determined by Griess reagent and HPLC. Hepatic interferon-gamma, a NO co-inducer, was measured by ELISA. Endotoxin caused inverse dose-dependent effects on plasma NO and on glycogen.Thalidomide analogs showed short-term regulatory effects on glycogen, some of them increased it. Plasma NO was almost unaffected by analogs but hepatic NO was strikingly modulated. Analogs slightly up-regulated the liver interferon-gamma and two of them increased it significantly. Thalidomide analogs may be used as a pharmacological tool due to their short-term regulatory effects on glycogen and NO during endotoxic shock. Drugs that increase glycogen may improve liver injury in early sepsis.

Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiológicos Latinoamérica) Collaborative Group.

BACKGROUND: Several trials have been performed in the past using glucose, insulin, and potassium infusion (GIK) for the treatment of acute myocardial infarction (AMI). Because of continuing uncertainty about the potential role of this therapeutic intervention, we conducted a randomized trial to evaluate the impact of a GIK solution during the first hours of AMI. METHODS AND RESULTS: Four hundred seven patients with suspected AMI admitted within 24 hours of symptoms onset were enrolled. In a ratio of 2:1, 268 patients were allocated to receive GIK (high- or low-dose) and 139 to receive control. Phlebitis and serum changes in the plasma concentration of glucose or potassium were observed more often with GIK. A trend toward a nonsignificant reduction in major and minor in-hospital events was observed in patients allocated to GIK. In 252 patients (61.9%) treated with reperfusion strategies, a statistically significant reduction in mortality (relative risk [RR] 0.34; 95% CI: 0.15 to 0.78; 2P=0.008) and a consistent trend toward fewer in-hospital events in the GIK group were observed. CONCLUSIONS: Our results confirm that a metabolic modulation strategy in the first hours of an AMI is feasible, applicable worldwide, and has mild side effects. The statistically significant mortality reduction in patients who underwent a reperfusion strategy might have important implications for the management of AMI patients. It is now essential to perform a large-scale trial to reliably determine the magnitude of benefit.

Remission of liver fibrosis by interferon-alpha 2b.

Fibrosis is a dynamic process associated with the continuous deposition and resorption of connective tissue, mainly collagen. Therapeutic strategies are emerging by which this dynamic process can be modulated. Since interferons are known to inhibit collagen production, the aim of this study was to investigate if the administration of interferon-alpha 2b (IFN-alpha) can restore the normal hepatic content of collagen in rats with established fibrosis. Fibrosis was induced by prolonged bile duct ligation. IFN-alpha (100,000 IU/rat/day; s.c.) was administered to fibrotic rats for 15 days. Bile duct ligation increased liver collagen content 6-fold. In addition, serum and liver markers of hepatic injury increased significantly; liver histology showed an increase in collagen deposition, and the normal architecture was lost, with large zones of necrosis being observed frequently. IFN-alpha administration reversed to normal the values of all the biochemical markers measured and restored the normal architecture of the liver. Our results demonstrated that IFN-alpha is useful in reversing fibrosis and liver damage induced by biliary obstruction in the rat. However, further investigations are required to evaluate the therapeutic relevance of interferons on non-viral fibrosis and cholestasis.