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

Tratamientos farmacológicos en la coadministración de alcohol y cocaína: efectos en la expresión de genes en el córtex prefrontal de la rata

El consumo de sustancias psicoactivas, y en concreto el consumo simultáneo de alcohol y cocaína, es una práctica frecuente en la población general. Así mismo, se ha visto que el consumo de cocaína incrementa el riesgo de desarrollar dependencia de alcohol, y viceversa. Actualmente existen 4 tratamientos farmacológicos aprobados para la dependencia de alcohol, siendo el disulfiram el primer tratamiento aprobado, posteriormente lo fueron la naltrexona y el acamprosato, y recientemente el nalmefeno. Por otra parte, estudios clínicos recientes han señalado que el topiramato, un fármaco aprobado para el tratamiento de la epilepsia y la prevención de la migraña, podría ser efectivo para el tratamiento de la dependencia de alcohol o cocaína. Sin embargo, para esta última no existe aún ninguna terapia farmacológica aprobada, y se conoce muy poco acerca de la eficacia de estas farmacoterapias en la codependencia de alcohol y cocaína..

<i>Lactiplantibacillus (Lactobacillus) plantarum</i> as a Complementary Treatment to Improve Symptomatology in Neurodegenerative Disease: A Systematic Review of Open Access Literature

This systematic review addresses the use of Lactiplantibacillus (Lactobacillus) plantarum in the symptomatological intervention of neurodegenerative disease. The existence of gut microbiota dysbiosis has been associated with systemic inflammatory processes present in neurodegenerative disease, creating the opportunity for new treatment strategies. This involves modifying the strains that constitute the gut microbiota to enhance synaptic function through the gut–brain axis. Recent studies have evaluated the beneficial effects of the use of Lactiplantibacillus plantarum on motor and cognitive symptomatology, alone or in combination. This systematic review includes 20 research articles (n = 3 in human and n = 17 in animal models). The main result of this research was that the use of Lactiplantibacillus plantarum alone or in combination produced improvements in symptomatology related to neurodegenerative disease. However, one of the studies included reported negative effects after the administration of Lactiplantibacillus plantarum. This systematic review provides current and relevant information about the use of this probiotic in pathologies that present neurodegenerative processes such as Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis

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 influence of dopaminergic polymorphisms on selective stopping

Depto. de Psicobiología y Metodología en Ciencias del ComportamientoFac. de PsicologíaTRUEpu

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

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.Depto. de Psicobiología y Metodología en Ciencias del ComportamientoFac. de PsicologíaTRUEpu

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

© 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.)

Low Phytanic Acid-Concentrated DHA Prevents Cognitive Deficit and Regulates Alzheimer Disease Mediators in an ApoE^−/− Mice Experimental Model

Alzheimer&#8217;s disease (AD) is the main cause of dementia and cognitive impairment. It has been associated with a significant diminution of omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) levels in the brain. Clinical trials with DHA as a treatment in neurological diseases have shown inconsistent results. Previously, we reported that the presence of phytanic acid (PhA) in standard DHA compositions could be blunting DHA&#8217;s beneficial effects. Therefore, we aimed to analyze the effects of a low PhA-concentrated DHA and a standard PhA-concentrated DHA in Apolipoprotein E knockout (ApoE&#8722;/&#8722;) mice. Behavioral tests and protein expression of pro-inflammatory, pro-oxidant, antioxidant factors, and AD-related mediators were evaluated. Low PhA-concentrated DHA decreased A&#946;, &#223;-amyloid precursor protein (APP), p-tau, Ca2+/calmodulin-dependent protein kinase II (CAMKII), caspase 3, and catalase, and increased brain derived neurotrophic factor (BDNF) when compared to standard PhA-concentrated DHA. Low PhA-concentrated DHA decreased interleukin (IL)-6 and tumor necrosis factor alpha (TNF-&#945;) protein expression in ApoE&#8722;/&#8722; mice when compared to standard PhA-concentrated DHA. No significant differences were found in p22phox, inducible nitric oxide synthase (iNOS), glutathione peroxidase (GPx), superoxide dismutase 1 (SOD-1), and tau protein expression. The positive actions of a low PhA-concentrated DHA were functionally reflected by improving the cognitive deficit in the AD experimental model. Therefore, reduction of PhA content in DHA compositions could highlight a novel pathway for the neurodegeneration processes related to AD