Adicción a cannabis: bases neurobiológicas y consecuencias médicas

La adicción a los preparados de cannabis sativa es un problema relevante en nuestra sociedad, con especial importancia durante la adolescencia. Su fácil disponibilidad y los episodios adversos asociados a su abuso y/o dependencia han incrementado la demanda de tratamiento derivada por su consumo. En los últimos 20 años se ha podido avanzar mucho sobre la farmacología del cannabis y de sus principios activos, moléculas grasas que actúan a través de un sistema de señalización endógeno denominado sistema endocannabinoide implicado en el desarrollo y la plasticidad cerebrales. Su estimulación crónica puede inducir no sólo dependencia y adicción, sino también derivar en consecuencias neurobiológicas que tienen repercusión clínica. Así, por un lado se puede encontrar el incremento de trastornos mentales tanto primarios como inducidos (trastornos del estado de ánimo, trastornos de ansiedad y trastornos psicóticos) y por el otro, alteraciones en los procesos cognitivos (memoria, atención, toma de decisiones, asunción de riesgos, control de impulsos). Estas consecuencias son más graves si el consumo se realiza en la adolescencia. Algunos de estos efectos son permanentes y el conocimiento de los mismos necesario para una correcta atención sanitaria.Addiction to products derived from the plant cannabis sativa has become a relevant problem in western societies. Its prevalence in both teenagers and young adults has grown in the last decade. The problem is aggravated by the availability of plant derivatives with a high THC content. Today, the number of cannabis users requesting medical treatment is growing, as well as the incidence and variety of the adverse effects associated with its chronic consumption. On the other hand, the last 20 years' research have revealed the hidden pharmacology of the active principles of cannabis. Cannabinoids, the psychoactive chemicals of the plant, exert their pharmacological actions through their interaction with an endogenous signaling system, the endocannabinoid system. This system is involved in brain development, plasticity and repair, and its chronic stimulation can induce not only dependence/addiction, but also result in adverse clinical effects. The negative side of cannabis use has greatest impact in the adolescent period. The main adverse effects of chronic cannabis use include the increase in the incidence of mental disorders (mainly psychosis), as well as alterations in cognitive processes including memory, attention, decision-making, risk behaviors as well as impulsivity. Some of these effects are permanent and information and research on their nature is greatly needed in order to achieve a correct public health approach to cannabis use

Hyperactivity induced by the dopamine D2/D3 receptor agonist quinpirole is attenuated by inhibitors of endocannabinoid degradation in mice

The present study was designed to investigate the effect of pharmacological inhibition of endocannabinoid degradation on behavioural actions of the dopamine D2/D3 receptor agonist quinpirole in male C57Bl/6J mice. In addition, we studied the effects of endocannabinoid degradation inhibition on both cocaine-induced psychomotor activation and behavioural sensitization. We analysed the effects of inhibition of the two main endocannabinoid degradation enzymes: fatty acid amide hydrolase (FAAH), using inhibitor URB597 (1 mg/kg); monoacylglycerol lipase (MAGL), using inhibitor URB602 (10 mg/kg). Administration of quinpirole (1 mg/kg) caused a temporal biphasic response characterized by a first phase of immobility (0–50 min), followed by enhanced locomotion (next 70 min) that was associated with the introduction of stereotyped behaviours (stereotyped jumping and rearing). Pretreatment with both endocannabinoid degradation inhibitors did not affect the hypoactivity actions of quinpirole. However, this pretreatment resulted in a marked decrease in quinpirole-induced locomotion and stereotyped behaviours. Administration of FAAH or MAGL inhibitors did not attenuate the acute effects of cocaine. Furthermore, these inhibitors did not impair the acquisition of cocaine-induced behavioural sensitization or the expression of cocaine-induced conditioned locomotion. Only MAGL inhibition attenuated the expression of an already acquired cocaine-induced behavioural sensitization. These results suggest that pharmacological inhibition of endocannabinoid degradation might exert a negative feedback on D2/D3 receptor-mediated hyperactivity. This finding might be relevant for therapeutic approaches for either psychomotor disorders (dyskinesia, corea) or disorganized behaviours associated with dopamine-mediated hyperactivity.Fil: Luque Rojas, María Jesús. Fundación IMABIS; EspañaFil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Suarez, Juan . Fundación IMABIS; EspañaFil: Araos, Pedro. Fundación IMABIS; EspañaFil: Santín Nuñez, Luis Javier. Universidad de Malaga; EspañaFil: Rodríguez de Fonseca, Fernando. Fundación IMABIS; EspañaFil: Blanco Calvo, Eduardo. Fundación IMABIS; España. Universidad de Malaga; Españ

Educación superior y emociones, bases epistemológicas de Maturana

I Plan Propio de Investigación, Transferencia y Divulgación Científica; Plan Propio Integral de Docencia de la Universidad de Málaga.Introducción. Las emociones serán entendidas como las disposiciones corporales que especifican el dominio de acción en que ese mueve el organismo. Son el fundamento de muchos aspectos de la vida y la educación es parte de esta influencia. La educación es un proceso para toda la vida y con cambios graduales de transformación. Es progresiva, pues la educación primaria y secundaria incidirá en la educación superior del sujeto. Es en la educación superior donde se da valor a lo que el estudiante pudo aprender a aceptar y respetar al otro en esos espacios de convivencia primarios. Objetivos. El objetivo de este trabajo es reflexionar sobre la obra de Humberto Maturana y relacionar sus postulados a la educación superior. Método La metodología utilizada ha sido de carácter cualitativa derivada de dos obras sobre educación y emociones. Resultados. Los resultados de este estudio nos dicen que es en la educación superior donde damos valor o no al aprendizaje de valores, al respeto por el otro, a la legitimación del otro, a la reflexión metódica, a desincentivar la competitividad y a colaborar en procesos de aprendizajes sin subordinación. Conclusión. Hay mucho por hacer. La competitividad se mantiene en muchos entornos, los espacios reflexivos aún son insuficientes, también el aprender a escuchar al otro y enseñar a escuchar, las relaciones de poder se mantienen rígidas durante años, y esto nos lleva a fomentar relaciones de subordinación. Lo importante es la confianza en los estudiantes y el profesorado. Lo emocional es la clave, y con qué emoción vivo la relación dentro del aula, ¿de poder o de mutuo respeto? Promover a los estudiantes al cambio o crear contextos de cambios y mirar la diferencia como un valor y no como un problema.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

¿Podemos realizar una actividad de discusión grupal en un entorno virtual?

I Plan Propio de Investigación, Transferencia y Divulgación Científica; Plan Propio Integral de Docencia de la Universidad de Málaga.Introducción. La adaptación de la docencia universitaria a los entornos virtuales, debido a la pandemia de la COVID-19, puede resultar más compleja en el caso de actividades que requieren una interacción dinámica entre el alumnado. Objetivos. En este trabajo desemaos evaluar y analizar una experiencia de discusión grupal realizada en un aula virtual (plataforma Microsoft Teams) para una asignatura del Grado en Psicología, explicando la metodología seguida para su desarrollo. Método. Valoramos que, en términos generales, la actividad logró fomentar la participación del alumnado y fortalecer el aprendizaje de los contenidos del tema. Reflexionamos sobre algunos aspectos que han contribuido al éxito de la actividad, como el hecho de emplear la herramienta de chat, la cual resultó la vía de comunicación y participación preferida por los/las estudiantes. Así mismo, consideramos que el tener que cumplimentar un cuestionario de evaluación al término de la sesión, es un potente incentivo para la participación, fomentando la necesidad del alumnado de aclarar sus dudas y llegar a conclusiones certeras por medio de la discusión y debate con sus iguales. Resultados. Aunque la participación se incrementó notablemente durante esta actividad -en comparación con la participación en sesiones de clase magistral-, no participaron el total de estudiantes asistentes. Conclusión. En futuras experiencias, puede resultar adecuado incluir la cantidad y contenido de las participaciones como aspectos evaluables. No obstante, en ese caso habría que valorar si el forzar la participación conllevaría que las aportaciones fuesen menos reflexivas y significativas.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Plasma Concentrations of Neurofilament Light Chain Protein and Brain-Derived Neurotrophic Factor as Consistent Biomarkers of Cognitive Impairment in Alcohol Use Disorder

For a long time, Substance Use Disorders (SUDs) were not considered a component in the etiology of dementia. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders introduced substance-induced neurocognitive disorders, incorporating this notion to clinical practice. However, detection and monitoring of neurodegenerative processes in SUD patients remain a major clinical challenge, especially when early diagnosis is required. In the present study, we aimed to investigate new potential biomarkers of neurodegeneration that could predict cognitive impairment in SUD patients: the circulating concentrations of Neurofilament Light chain protein (NfL) and Brain-Derived Neurotrophic Factor (BDNF). Sixty SUD patients were compared with twenty-seven dementia patients and forty healthy controls. SUD patients were recruited and assessed using the Psychiatric Research Interview for Substance and Mental (PRISM) and a battery of neuropsychological tests, including the Montreal Cognitive Assessment test for evaluation of cognitive impairment. When compared to healthy control subjects, SUD patients showed increases in plasma NfL concentrations and NfL/BDNF ratio, as well as reduced plasma BDNF levels. These changes were remarkable in SUD patients with moderate–severe cognitive impairment, being comparable to those observed in dementia patients. NfL concentrations correlated with executive function and memory cognition in SUD patients. The parameters “age”, “NfL/BDNF ratio”, “first time alcohol use”, “age of onset of alcohol use disorder”, and “length of alcohol use disorder diagnosis” were able to stratify our SUD sample into patients with cognitive impairment from those without cognitive dysfunction with great specificity and sensibility. In conclusion, we propose the combined use of NfL and BDNF (NfL/BDNF ratio) to monitor substance-induced neurocognitive disorder.Instituto de Salud Carlos III (ISCIII], Ministerio de Ciencia e Innovación and European Regional Development Funds-European Union (ERDF-EU] grants “Proyectos de Investigación en Salud” PI19/01577, PI19/00886, PI20/01399 and PI22/00427; Grants Programa RICORS RIAPAD (Red de Investigación en Atención Primaria en Adicciones), Programa RETICS Red de Trastornos Adictivos, (RD16/0017/000); Ministerio de Sanidad, Delegación de Gobierno para el Plan Nacional sobre Drogas (PND 2022I020, PND2020/048, PND 2019/040]; Consejería de Salud y Familia, Junta de Andalucía (Neuro-RECA, RIC-0111-2019]. FJP (CPII19/00022] and AS (CPII19/00031] hold “Miguel Servet II” research contracts from the National System of Health, ISCIII, ERDF-EU. FJP also holds a “Nicolas Monardes” contract from Servicio Andaluz de Salud, Consejería de Salud y Familia, Junta de Andalucía (C1-0049-2019]. PA has a research contract (UMA-FEDERJA-076) funded by the Ministry of Economy and Knowledge—Regional Government of Andalucía and ERDF-EU. The funding sources had no further role in the study design; in the collection, analysis, and interpretation of data; in writing of the report; or in the decision to submit the paper for publication

Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUDPartial funding for open access charge: Universidad de Málag

Experiencia de uso de un cómic (“Arrugas”) como material didáctico en el aula universitaria.

En la actualidad, existen pocas experiencias docentes que incorporen el cómic al entorno universitario. En este trabajo hemos explorado la utilidad de un cómic (“Arrugas”, de Paco Roca) para mejorar el proceso de enseñanza-aprendizaje de contenidos relacionados con la vejez y la demencia, en una asignatura del Grado en Psicología.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006-May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 x 10(9) cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables

Scribble Deficiency Promotes Pancreatic Ductal Adenocarcinoma Development and Metastasis.

Perturbation of cell polarity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) progression. Scribble (SCRIB) is a well characterized polarity regulator that has diverse roles in the pathogenesis of human neoplasms. To investigate the impact of SCRIB deficiency on PDAC development and progression, Scrib was genetically ablated in well-established mouse models of PDAC. Scrib loss in combination with KrasG12D did not influence development of pancreatic intraepithelial neoplasms (PanIN) in mice. However, Scrib deletion cooperated with KrasG12D and concomitant Trp53 heterozygous deletion to promote invasive PDAC and metastatic dissemination, leading to reduced overall survival. Immunohistochemical and transcriptome analyses revealed that Scrib-null tumors display a pronounced reduction of collagen content and cancer associated fibroblast (CAF) abundance. Mechanistically, interleukin 1α (IL1α) levels were reduced in Scrib deficient tumors, and Scrib knockdown downregulated IL1α in mouse PDAC organoids (mPDOs), which impaired CAF activation. Furthermore, Scrib loss increased YAP activation in mPDOs and established PDAC cell lines, enhancing cell survival. Clinically, SCRIB expression was decreased in human PDAC, and SCRIB mislocalization was associated with poorer patient outcome. These results indicate that SCRIB deficiency enhances cancer cell survival and remodels the tumor microenvironment to accelerate PDAC development and progression, establishing the tumor suppressor function of SCRIB in advanced pancreatic cancer

Associations of hypomagnesemia in patients seeking a first treatment of alcohol use disorder

Introduction: Hypomagnesemia (hypoMg) has not yet been extensively studied in alcohol use disorder (AUD) . We hypothesize that chronic, excessive alcohol consumption favors oxidative stress and pro-inflammatory alterations that may be exacerbated by hypoMg. The objective of this study was to analyze the prevalence and associations of hypoMg in AUD.Patients and Methods: Cross-sectional study in patients admitted for a first treatment of AUD in six tertiary centers between 2013 and 2020. Socio-demographic, alcohol use characteristics, and blood parameters were ascertained at admission.Results: 753 patients (71% men) were eligible; age at admission was 48 years [IQR, 41-56 years]. Prevalence of hypoMg was 11.2%, higher than that observed for hypocalcemia (9.3%), hyponatremia (5.6%), and hypokalemia (2.8%). HypoMg was associated with older age, longer duration of AUD, anemia, higher erythrocyte sedimen-tation rate, gamma-glutamyl transpeptidase, glucose levels, advanced liver fibrosis (FIB-4 >= 3.25) and estimated glomerular filtration rate (eGFR) < 60 mL/min. In multivariate analysis, advanced liver fibrosis (OR, 8.91; 95% CI, 3.3-23.9) and eGFR < 60 mL (OR, 5.2; 95% CI, 1.0-26.2) were the only factors associated with hypoMg.Conclusions: Mg deficiency in AUD is associated with liver damage and glomerular dysfunction suggesting that both comorbidities should be assessed in the course of serum hypoMg