Role of cannabinoids in alcohol-induced neuroinflammation

García-Baos, Alba; Alegre-Zurano, Laia; Cantacorps, Lídia; Martín‐Sánchez, Ana; Valverde, Olga

doi:10.1016/j.pnpbp.2020.110054

Cited by 21 publications

(19 citation statements)

References 173 publications

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“…Cannabinoids represent an alternative anti-inflammatory strategy to treat several diseases [14,51]. Indeed, they might exert positive or negative effects on squeals caused by excessive alcohol use, depending on the cannabinoid compound [15]. Although the detrimental consequences of CB1R agonists on developing brain have been well established [52,53], CBD has recently emerged as promising candidate for several pathological conditions, including alcohol-related harms [54].…”

Section: Discussionmentioning

confidence: 99%

“…In the last decades, studies have shown that some cannabinoids have a neuroprotective pharmacological profile through multiple mechanisms [14]. These compounds exhibit a potential therapeutic role in the context of neuroinflammatory and neurodegenerative disorders, including the alcohol-induced neuroinflammation [15]. Among phytocannabinoids, cannabidiol (CBD) is able to interact with multiple targets within the central nervous system (CNS) exerting distinct pharmacological effects [14].…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cannabidiol attenuates cognitive deficits and neuroinflammation induced by early alcohol exposure in a mice model

Puig

Algar

Valverde

et al. 2021

Preprint

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Foetal alcohol spectrum disorder (FASD) is the umbrella term used to describe the physical and mental disabilities induced by alcohol exposure during development. Early alcohol exposure induces cognitive impairments resulting from damage to the central nervous system (CNS). The neuroinflammatory response accompanied by neurodegenerative mechanisms contribute to those detrimental alterations. Cannabidiol (CBD) has recently emerged as an anti-inflammatory drug that might be useful to treat several neuropsychiatric disorders. In our study, we assessed the effects of CBD on long-lasting cognitive deficits induced by early alcohol exposure. Furthermore, we analysed long-term pro-inflammatory and apoptotic markers within the prefrontal cortex and hippocampus. To model alcohol binge drinking during gestational and lactation periods, we used pregnant C57BL/6 female mice with time-limited access to 20% v/v alcohol solution. Following the prenatal and lactation alcohol exposure (PLAE), we treated the male and female offspring with CBD from post-natal day (PD) 25 until PD34, and we evaluated their cognitive performance at PD60. Our results showed that CBD treatment during peri-adolescence period ameliorates cognitive deficits observed in our FASD-like mouse model, without sex differences. Moreover, CBD restores the PLAE-induced increased levels of TNFα and IL-6 in the hippocampus. Thus, our study provides new insights for CBD as a therapeutic agent to counteract cognitive impairments and neuroinflammation caused by early alcohol exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cannabidiol attenuates cognitive deficits and neuroinflammation induced by early alcohol exposure in a mice model

Puig

Algar

Valverde

et al. 2021

Preprint

Self Cite

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“…Furthermore, CBDRs were found to be functional at an early stage of development during the time of ontogeny of other neuronal systems [ 191 ]. Additionally, CBDRs were found to be expressed in microglia and immune cells, especially CBDRs2, and several previous studies indicated the anti-inflammatory and neuroprotection roles of cannabinoids [ 184 , 189 , 192 , 193 ]. In agreement with other neuromodulator systems mentioned above, exogenous cannabinoid can be used to treat some neuropsychiatric disorders despite their damaging effects during prenatal stages.…”

Section: Endogenous Neuromodulators and Pharmacological Agents In Bra...mentioning

confidence: 99%

Role of Brain Modulators in Neurodevelopment: Focus on Autism Spectrum Disorder and Associated Comorbidities

et al. 2022

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Autism spectrum disorder (ASD) and associated neurodevelopmental disorders share similar pathogenesis and clinical features. Pathophysiological changes in these diseases are rooted in early neuronal stem cells in the uterus. Several genetic and environmental factors potentially perturb neurogenesis and synaptogenesis processes causing incomplete or altered maturation of the brain that precedes the symptomology later in life. In this review, the impact of several endogenous neuromodulators and pharmacological agents on the foetus during pregnancy, manifested on numerous aspects of neurodevelopment is discussed. Within this context, some possible insults that may alter these modulators and therefore alter their role in neurodevelopment are high-lighted. Sometimes, a particular insult could influence several neuromodulator systems as is supported by recent research in the field of ASD and associated disorders. Dopaminergic hy-pothesis prevailed on the table for discussion of the pathogenesis of schizophrenia (SCH), atten-tion-deficit hyperactivity disorder (ADHD) and ASD for a long time. However, recent cumulative evidence suggests otherwise. Indeed, the neuromodulators that are dysregulated in ASD and comorbid disorders are as diverse as the causes and symptoms of this disease. Additionally, these neuromodulators have roles in brain development, further complicating their involvement in comorbidity. This review will survey the current understanding of the neuromodulating systems to serve the pharmacological field during pregnancy and to minimize drug-related insults in pa-tients with ASD and associated comorbidity disorders, e.g., SCH or ADHD.

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“…Early preclinical data focused mainly on the therapeutic potential of the prototypical cannabinoid-1 receptor (CB1R) antagonists that cross the blood–brain barrier. Accordingly, blockade of CB1R has been shown to reduce alcohol consumption [ 27 ], its rewarding properties [ 28 , 29 ], and to diminish inflammation in the central nervous system (CNS) [ 30 ] and in the gut [ 31 ]. However, clinical trials to counteract metabolic obesity with SR14716A (rimonabant), the prototype brain penetrant CB1R receptor antagonist/inverse agonist, showed that it produced serious neuropsychiatric adverse events [ 32 ], which halted the therapeutic development of this class of compounds.…”

Section: Introductionmentioning

confidence: 99%

Effects of a Peripherally Restricted Hybrid Inhibitor of CB1 Receptors and iNOS on Alcohol Drinking Behavior and Alcohol-Induced Endotoxemia

et al. 2021

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Alcohol consumption is associated with gut dysbiosis, increased intestinal permeability, endotoxemia, and a cascade that leads to persistent systemic inflammation, alcoholic liver disease, and other ailments. Craving for alcohol and its consequences depends, among other things, on the endocannabinoid system. We have analyzed the relative role of central vs. peripheral cannabinoid CB1 receptors (CB1R) using a “two-bottle” as well as a “drinking in the dark” paradigm in mice. The globally acting CB1R antagonist rimonabant and the non-brain penetrant CB1R antagonist JD5037 inhibited voluntary alcohol intake upon systemic but not upon intracerebroventricular administration in doses that elicited anxiogenic-like behavior and blocked CB1R-induced hypothermia and catalepsy. The peripherally restricted hybrid CB1R antagonist/iNOS inhibitor S-MRI-1867 was also effective in reducing alcohol consumption after oral gavage, while its R enantiomer (CB1R inactive/iNOS inhibitor) was not. The two MRI-1867 enantiomers were equally effective in inhibiting an alcohol-induced increase in portal blood endotoxin concentration that was caused by increased gut permeability. We conclude that (i) activation of peripheral CB1R plays a dominant role in promoting alcohol intake and (ii) the iNOS inhibitory function of MRI-1867 helps in mitigating the alcohol-induced increase in endotoxemia.

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Role of cannabinoids in alcohol-induced neuroinflammation

Cited by 21 publications

References 173 publications

Cannabidiol attenuates cognitive deficits and neuroinflammation induced by early alcohol exposure in a mice model

Cannabidiol attenuates cognitive deficits and neuroinflammation induced by early alcohol exposure in a mice model

Role of Brain Modulators in Neurodevelopment: Focus on Autism Spectrum Disorder and Associated Comorbidities

Effects of a Peripherally Restricted Hybrid Inhibitor of CB1 Receptors and iNOS on Alcohol Drinking Behavior and Alcohol-Induced Endotoxemia

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