Polimorfismos genéticos humanos y adicción a drogas de abuso: implicación del SNP C385 del gen FAAH en el consumo de riesgo de alcohol en jóvenes adultos

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Psicología, leída el 05/11/2014Fac. de PsicologíaTRUEunpu

Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies

Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption

The genetics of self-reported trait impulsivity: Contribution of catecholaminergic gene variants in European ancestry individuals

Increased trait impulsivity is a core element in several mental disorders. Given the durable and consistent nature of trait impulsivity, studies have explored its relation to stable biological measures. Variation in catecholaminergic neurotransmission by genetic variants could be one of these biological substrates. Here, 905 participants of European-ancestry completed the Barratt Impulsiveness Scale–11 and were genotyped in three single nucleotide polymorphisms related to catecholaminergic neurotransmission: the DRD2/ ANKK Taq1A, the C957T DRD2 and the Val158Met of the COMT gene. We found significant main effects of Val158Met and C957T on BIS-11 score. Also, interactions with gender were significant in both SNPs with a tendency to slightly different genotype and allele associations with the BIStotal score between male and female participants. Whereas in females, higher impulsivity scores were obtained by participants with the Val158Met heterozygous genotype (Met/Val), data indicate a trend towards a higher impulsivity score in male Val-allele carriers. In the case of C957T, only a tentative association between male Tallele carriers and higher impulsivity scores in comparison to CC genotype carriers could be established. No significant associations were found between BIS-11 and Taq1A. We provide further evidence for a gender-specific implication of Val158Met and C957T in trait impulsivity

Psicothema

Resumen tomado de la publicaciónAsociaciones entre el uso experimental de sustancias, variaciones del gen FAAH, impulsividad y búsqueda de sensaciones. Antecedentes: el uso experimental de sustancias en los jóvenes está relacionada con factores individuales que incluyen rasgos de personalidad, como impulsividad o búsqueda de sensaciones, y variaciones genéticas, como polimorfismos de un solo nucleótido (SNPs) del gen amida hidrolasa de ácidos grasos (FAAH). El objetivo de este estudio es analizar la relación entre estos tres conjuntos de variables. Método: estudiantes universitarios voluntarios (N = 861, 76% mujeres, M = 20,7 años) rellenaron un cuestionario ad hoc de variables relacionadas con el consumo de alcohol, tabaco, cannabis, drogas sintéticas y cocaína. Además, 591 de ellos rellenaron las escalas BIS-11 y SSS-V. Se genotipó a todos ellos en SNP FAAH C385A y su variante proxy rs12075550. Resultados: como se esperaba, la impulsividad y la búsqueda de sensaciones estuvieron asociadas con la mayor parte de las variables relativas al uso experimental de sustancias. Además, encontramos por primera vez evidencia de una asociación entre rs12075550 y algunos de estos fenotipos de consumo. Sin embargo, no encontramos asociaciones significativas entre SNPs e impulsividad o búsqueda de sensaciones. Conclusiones: los resultados resaltan la importancia de tener en cuenta las diferencias genéticas y las de personalidad, junto con los factores contextuales, al analizar el uso de sustancias.Universidad de Oviedo. Biblioteca de Psicología; Plaza Feijoo, s/n.; 33003 Oviedo; Tel. +34985104146; Fax +34985104126; [email protected]

The genetics of self-reported trait impulsivity: Contribution of catecholaminergic gene variants in European ancestry individuals

Increased trait impulsivity is a core element in several mental disorders. Given the durable and consistent nature of trait impulsivity, studies have explored its relation to stable biological measures. Variation in catecholaminergic neurotransmission by genetic variants could be one of these biological substrates. Here, 905 participants of European-ancestry completed the Barratt Impulsiveness Scale–11 and were genotyped in three single nucleotide polymorphisms related to catecholaminergic neurotransmission: the DRD2/ANKK Taq1A, the C957T DRD2 and the Val158Met of the COMT gene. We found significant main effects of Val158Met and C957T on BIS-11 score. Also, interactions with gender were significant in both SNPs with a tendency to slightly different genotype and allele associations with the BIS-total score between male and female participants. Whereas in females, higher impulsivity scores were obtained by participants with the Val158Met heterozygous genotype (Met/Val), data indicate a trend towards a higher impulsivity score in male Val-allele carriers. In the case of C957T, only a tentative association between male T-allele carriers and higher impulsivity scores in comparison to CC genotype carriers could be established. No significant associations were found between BIS-11 and Taq1A. We provide further evidence for a gender-specific implication of Val158Met and C957T in trait impulsivityThis research was supported by the National Plan on Drug Abuse, Ministry of Health (Spain) (grant PNSD2018-050 to JALM) and Ministry of Universities and European Union- NextGenerationEU (Margarita Salas, UCM CT31/21) (to IRR

The immune system through the lens of alcohol intake and gut microbiota

© 2021 by the authors.The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted mucosal immunity. This damage to the permeability of the intestinal membrane allows bacteria and their components to enter the blood tissue, reaching other organs such as the liver or the brain. Although chronic heavy drinking has harmful effects on the immune system cells at the systemic level, this review focuses on the effect produced on gut, brain and liver, because of their significance in the link between alcohol consumption, gut microbiota and the immune system.This work was supported by National Plan on Drug Abuse, Ministerio de Sanidad of Spain (grant PNSD2018-050 to J.A.L.M.), the Fondo de Investigación Sanitaria (Red de Trastornos Adictivos, FEDER, RD16/0017/0008 to J.A.L.M.; RD16/0017/0001 to F.R.D.F.) and the Instituto de Salud Carlos III (Sara Borrell research contract CD17/00125 to V.E.A.)

Nalmefene is effective at reducing alcohol seeking, treating alcohol-cocaine interactions and reducing alcohol-induced histone deacetylases gene expression in blood

BACKGROUND AND PURPOSE: The opioid antagonist nalmefene (selincro®) was approved for alcohol-related disorders by the European Medicines Agency in 2013. However, there have been no studies regarding the effectiveness of nalmefene when alcohol is used in combination with cocaine. EXPERIMENTAL APPROACH: Using operant alcohol self-administration in Wistar rats and qRT-PCR, we evaluated (i) the dose-response curve for s.c. and p.o. nalmefene; (ii) the effects of nalmefene with increasing concentrations of alcohol; (iii) the efficacy of nalmefene on cocaine-potentiated alcohol responding; and (iv) the gene expression profiles of histone deacetylases (Hdac1-11) in peripheral blood in vivo and in the prefrontal cortex, heart, liver and kidney post mortem. KEY RESULTS: S.c. (0.01, 0.05, 0.1 mg·kg(-1) ) and p.o. (10, 20, 40 mg·kg(-1) ) nalmefene dose-dependently reduced alcohol-reinforced responding by up to 50.3%. This effect of nalmefene was not dependent on alcohol concentration (10, 15, 20%). Cocaine potentiated alcohol responding by approximately 40% and nalmefene (0.05 mg·kg(-1) ) reversed this effect of cocaine. Alcohol increased Hdac gene expression in blood and nalmefene prevented the increases in Hdacs 3, 8, 5, 7, 9, 6 and 10. In the other tissues, alcohol and nalmefene either did not alter the gene expression of Hdacs, as in the prefrontal cortex, or a tissue-Hdac-specific effect was observed. CONCLUSIONS AND IMPLICATIONS: Nalmefene might be effective as a treatment for alcohol-dependent patients who also use cocaine. Also, the expression of Hdacs in peripheral blood might be useful as a biomarker of alcohol use and drug response.This work was supported by The European Foundation for Alcohol Research (to J.A.L.M., F.R.d.F., R.M. and R.N.), the Fondo de Investigación Sanitaria (Red de Trastornos Adictivos, FEDER, RD12/0028/0015 to J.A.L.M., RD12/0028/001 to F.R.d.F., RD12/0028/023 to R.M., RD12/0028/0014 to R.N.) and Ministerio de Ciencia e Innovación (SAF2011-26818 to J.A.L.M.)

The immune system through the lens of alcohol intake and gut microbiota.

The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted mucosal immunity. This damage to the permeability of the intestinal membrane allows bacteria and their components to enter the blood tissue, reaching other organs such as the liver or the brain. Although chronic heavy drinking has harmful effects on the immune system cells at the systemic level, this review focuses on the effect produced on gut, brain and liver, because of their significance in the link between alcohol consumption, gut microbiota and the immune system

Red Bull® energy drink increases consumption of higher concentrations of alcohol

Data de publicació electrònica: 22-09-2017Mixing alcohol with caffeinated energy drinks is a common practice, especially among young people. In humans, the research on this issue has mainly focused on the use of the mass-marketed energy drinks themselves, whereas in animal models, it has focused on the individual effects of their active ingredients (i.e. caffeine). Here, we have characterized how Red Bull®, one of the most consumed caffeinated energy drink worldwide, modulates operant alcohol self-administration in Wistar rats. We found that animals readily and steadily responded for Red Bull (mean: 90 responses, 30 minutes and fixed-ratio 1), which was accompanied by locomotor stimulating effects (26 percent increase). The higher the concentration of alcohol (3-20 percent), the higher the consumption of alcohol (g/kg) and associated blood alcohol levels (91.76 percent) in the mixed Red Bull-alcohol group (60 percent increase). Blood caffeine levels in the Red Bull group were 4.69 μg/ml and 1.31 μg/ml in the Red Bull-alcohol group after the 30-minute session. Because Red Bull also contains 11 percent sucrose, we examined the time course of blood glucose as well as insulin and corticosterone. The correlation between intake of Red Bull and blood glucose levels was higher at 90 minutes than 5 minutes after its consumption, and there was no relationship with blood insulin or blood corticosterone levels. Red Bull did not alter extinction and reacquisition of responding for alcohol nor did it affect relapse-like drinking. Overall, our results suggest that Red Bull might be a vulnerability factor to develop alcoholism given that it intensifies the consumption of higher concentrations of alcohol