The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic–ischemic brain damage in mice is mediated by CB2 and adenosine receptors

Castillo, Ana Isabel; Tolón, M.R.; Fernández‐Ruiz, Javier; Romero, Julián; Martı́nez-Orgado, José

doi:10.1016/j.nbd.2009.10.023

Cited by 225 publications

(199 citation statements)

References 37 publications

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“…These results demonstrate that CBD can exert an antiarrhythmic effect, possibly mediated by the adenosine A 1 receptor [36]. In addition to effects on the A 1 receptor, A 2 receptor-mediated effects of CBD have also been reported and claimed to mediate antiinflammatory effects of CBD [10,31,37,38]. The effects of CBD on inflammatory signaling cascades have also been examined (Table 1) [37].…”

Section: Adenosinementioning

confidence: 85%

“…More recently, a statistical meta-analysis of all extant data describing direct effects of CBD at CB 1 R and CB 2 R concluded that there is no direct CBD-CB 1 R interaction that can account for the reported changes in endocannabinoid signaling [16]. Indeed, the pharmacology of CBD at cannabinoid receptors is not only complex and highly variable [31][32][33], but also typically occurs at supraphysiological concentrations in vitro, so rendering any contribution to behavioral effects unlikely. These clear discrepancies between in vitro and in vivo studies are a warning to pharmacologists that predicted pharmacology from molecular assay systems is not always replicated at a system level.…”

Section: Cannabinoid Receptorsmentioning

confidence: 99%

“…However, it was noted that the adenosine A 2 -mediated response was only partially responsible for the antiinflammatory observations, again through use of the adenosine A 2 antagonist ZM241385. Studies have suggested that neuroprotective effects of CBD are mediated via adenosine A 2 receptor modulation [31]. However, this has also been contested where species differences and animal developmental stages in the methodology of these conflicting studies may underlie the different conclusions drawn [38].…”

Section: Adenosinementioning

confidence: 99%

“…Although possible evidence that CBD might act, in part, via this system was suggested by the observation that in brain slices taken from a newborn mouse hypoxia model that A 2A and A 1A receptor antagonists inhibited a protective CBD effect, the most significant effect was only observed at 100 μM-a physiologically implausible concentration [31]. In contrast, Mecha et al [10], using a virally induced mouse inflammatory model of MS, demonstrated that an antagonist of the A 2A receptor partially blocked the in vivo ability of CBD to suppress inflammation and immune cell infiltration in the brains of infected mice; the administration of the antagonist on its own had no effect.…”

Section: Cbd Transporter Targets In Neurodegenerationmentioning

confidence: 99%

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Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

425

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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Section: Adenosinementioning

confidence: 85%

Section: Cannabinoid Receptorsmentioning

confidence: 99%

Section: Adenosinementioning

confidence: 99%

Section: Cbd Transporter Targets In Neurodegenerationmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

425

323

View full text Add to dashboard Cite

show abstract

“…Moreover, the use of CB2 receptor agonists has revealed promising results in different paradigms of neonatal hypoxic-ischemic brain injury [133,150] , reducing cell death, accompanied by modulations of glutamate release, cytokine production, and cyclooxygenase-2 and iNOS expression, supporting the hypothesis that the protective effect of CB2 receptor relies mostly on its anti-inflammatory effects. This provides new hints on its possible use as a neuroprotective target after perinatal asphyxia.…”

Section: Therapeutic Potential Of Cannabinoid After Hypoxia-ischemiamentioning

confidence: 88%

Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury

2011

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Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. Because of the fact that there is still no specific treatment for perinatal brain lesions due to the complexity of neonatal hypoxic-ischemic pathophysiology, the search of new neuroprotective therapies is of great interest.In this regard, therapeutic possibilities of the endocannabinoid system have grown lately. The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant. Concerning perinatal asphyxia, the neuroprotective role of this endogenous system is emerging these years. The present review mainly focused on the current knowledge of the cannabinoids as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.

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Sturge–Weber syndrome: Updates in pathogenesis, diagnosis, and treatment

Valery,

Comi

2023

Annals of the Child Neurology Society

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We summarize the current knowledge of Sturge–Weber syndrome (SWS) including genetic involvement, difficulties in diagnosis, symptoms caused by the vascular malformations, treatments, and future areas of research. PubMed searches were completed between October and December of 2022 including the following search terms: Sturge–Weber neuroimaging, Sturge–Weber ocular involvement, Sturge–Weber G‐protein alpha q subunit (GNAQ), Sturge–Weber presymptomatic treatment, and Sturge–Weber quantitative EEG. Clinically relevant articles and case reports were reviewed and summarized, with emphasis placed on reports from the last 20 years. Literature suggests that early identification of brain involvement is essential for optimal medical care. Infants with a port‐wine birthmark on the forehead, temple, or eyelids are at risk for SWS brain and eye involvement. Neuroimaging findings include leptomeningeal enhancements, cortical calcifications, and brain atrophy, and diagnosis requires magnetic resonance imaging with and without contrast. Before 1 year of age, neuroimaging has low sensitivity and may underestimate the extent of involvement; imaging after 1 year of age is needed to exclude brain involvement. The most common underlying cause for SWS is a somatic mosaic mutation in GNAQ. Neurological symptoms include seizures, stroke or stroke‐like episodes, headaches, and cognitive deficits. Recommended treatment for SWS brain involvement includes aggressive seizure control with antiepileptic medications; low‐dose aspirin is also frequently but not universally utilized. Current literature suggests that children with SWS may benefit from presymptomatic treatment; further study of this approach is ongoing. SWS is a rare neurovascular disorder usually signaled by a facial port‐wine birthmark. Early diagnosis and appropriate treatment may improve outcomes.

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The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic–ischemic brain damage in mice is mediated by CB2 and adenosine receptors

Cited by 225 publications

References 37 publications

Molecular Targets of Cannabidiol in Neurological Disorders

Molecular Targets of Cannabidiol in Neurological Disorders

Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury

Sturge–Weber syndrome: Updates in pathogenesis, diagnosis, and treatment

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