Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria

Campos, Alline C.; Brant, Fátima; Miranda, Aline Silva de; Machado, Fabiana S.; Teixeira, Antônio Lúcio

doi:10.1016/j.neuroscience.2014.12.051

Cited by 71 publications

(73 citation statements)

References 81 publications

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“…It is important to point out that, in the report on P. berghei ANKA, the treatment with CBD in addition to the antimalarial drug artesunate prevented cognitive deficiencies associated with malaria [100]. These results may indicate that, where parasitic infections are concerned, cannabinoid compound treatments are able to damage the parasites, and in some cases, when given together with parasitic agents, can prevent collateral damage in parasitic infections, with some exceptions (depending on the etiological agent).…”

Section: Discussionmentioning

confidence: 99%

“…Plasmodium is the parasite responsible for malaria, a disease characterized by acute fever and the potential development of cerebral malaria, which can be fatal due to the rupture of the hematoencephalic barrier and brain inflammation. CBD, along with the antimalarial drug artesunate, is able to increase the survival rate of mice infected with Plasmodium berghei ANKA, and can prevent cognitive deficiency associated with the infection [100]. Interestingly, another study demonstrated that CB2 activation had no beneficial effect in an experimental murine model for cerebral malaria, as CB2 knockout mice presented with a higher survival rate due to a lower parasite load in the brain and lower expression of proinflammatory cytokines such as TNF-α and IFN-γ, in addition to lower hematoencephalic barrier disruption [101].…”

Section: Plasmodium Bergheimentioning

confidence: 99%

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Immunoregulatory Role of Cannabinoids during Infectious Disease

Hernández-Cervantes

Méndez-Dı́az²,

Prospéro-Garcı́a³

et al. 2017

Neuroimmunomodulation

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Although the endocannabinoid system (ECS) is involved in the regulation of several physiological processes, including sleep and the immune response, its role during infections has not been fully studied. It is well known that the use of this drug increases susceptibility to infections because of the impact on the modulation of the immune system. Concerning the medicinal or recreational use of marijuana, its influence on the course of an infection, whether this has been caused by bacteria, viruses, parasites, and to a lesser degree, fungi, has been reported. Furthermore, there is evidence suggesting the involvement of the ECS in the control and elimination of infectious agents such as bacteria, viruses, and some protozoa; in the case of fungi, few studies are available so far. The purpose of this review is to present the existing studies related to infections and the ECS, the microbicidal effects of compounds isolated from Cannabis sativa, and the association between marijuana use and the development of rare pathologies in specific diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Plasmodium Bergheimentioning

confidence: 99%

Immunoregulatory Role of Cannabinoids during Infectious Disease

Hernández-Cervantes

Méndez-Dı́az²,

Prospéro-Garcı́a³

et al. 2017

Neuroimmunomodulation

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“…Given the current trends in cannabinoid research, combining THC with cannabidiol may work to reduce these deficits. Cannabidiol is recognized for its lack of psychoactive effects, stimulation of hippocampal cell proliferation and neurogenesis, and has been demonstrated to reduce novel object memory impairment in other models that produce neuroinflammation (Pertwee, 2008; Fagherazzi et al, 2012; Fishbein-Kaminietsky et al, 2014; Campos et al, 2015; Schiavon et al, 2016). With the use of medical cannabis on the rise, it is important to understand how the addition of cannabidiol to THC may mediate negative side effects.…”

Section: Discussionmentioning

confidence: 99%

Acute and long-term effects of Δ9-tetrahydrocannabinol on object recognition and anxiety-like activity are age- and strain-dependent in mice

Kasten

Zhang

Boehm

2017

Pharmacology Biochemistry and Behavior

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Use of exogenous cannabinoids disrupts the fine-tuned endocannabinoid receptor system, possibly leading to alterations in cognition, memory, and emotional processes that endure long after cannabinoid use has stopped. Long-term adolescent use may uniquely disrupt these behaviors when compared to adult use. The current study explored the acute and long-term behavioral effects of six 10 mg/kg Δ9-tetrahydrocannabinol (THC) injections across the adolescent or early adult period in male inbred C57Bl/6J and DBA/2J mice. The acute and prolonged effects of THC on object memory using the novel object recognition task, unconditioned anxiety in the elevated plus maze and open field, and sedative effects in the open field were examined. Acute THC treatment resulted in anxiogenic activity in both strains, but only caused sedation in B6 mice. Repeated THC treatment resulted in a protracted effect on object recognition, but not unconditioned anxiety, assessed 4 weeks later. In both strains, an adolescent history of THC treatment disrupted later object recognition. Interestingly, in B6 mice an adult history of THC exposure appeared to rescue a deficit in object recognition observed in vehicle-treated adults. Repeated THC administration also produced a protracted effected on CB1R protein expression. Animals treated with THC in adolescence maintained increased levels of CB1R protein expression compared to their adult THC-treated counterparts at five weeks following the last injection. These results indicate that THC use may have long-lasting effects with adolescence being a unique period of susceptibility.

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“…These agents are also active in hypoxic encephalopathy, a stroke parallel in newborns [208, 209], a condition associated with raised inflammatory cytokines and glutamate [210]. Not surprisingly, therefore, cannabinoids, whether synthetic, endogenous, or of plant origin, have proven to be established anti-TNF agents in vitro and in vivo, in the sense that they reduce its production by the usual recognized stimuli [211–214]. This list includes treating the murine malarial encephalopathy (cerebral malaria) [214], a condition in which, as discussed below, 6-diazo-5-oxo-norleucine is also efficacious for a related and predictable reason concerned with lowering extracellular cerebral glutamate [215].…”

Section: Cannabinoidsmentioning

confidence: 99%

Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents

Clark

Vissel

2016

J Neuroinflammation

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The basic mechanism of the major neurodegenerative diseases, including neurogenic pain, needs to be agreed upon before rational treatments can be determined, but this knowledge is still in a state of flux. Most have agreed for decades that these disease states, both infectious and non-infectious, share arguments incriminating excitotoxicity induced by excessive extracellular cerebral glutamate. Excess cerebral levels of tumor necrosis factor (TNF) are also documented in the same group of disease states. However, no agreement exists on overarching mechanism for the harmful effects of excess TNF, nor, indeed how extracellular cerebral glutamate reaches toxic levels in these conditions. Here, we link the two, collecting and arguing the evidence that, across the range of neurodegenerative diseases, excessive TNF harms the central nervous system largely through causing extracellular glutamate to accumulate to levels high enough to inhibit synaptic activity or kill neurons and therefore their associated synapses as well. TNF can be predicted from the broader literature to cause this glutamate accumulation not only by increasing glutamate production by enhancing glutaminase, but in addition simultaneously reducing glutamate clearance by inhibiting re-uptake proteins. We also discuss the effects of a TNF receptor biological fusion protein (etanercept) and the indirect anti-TNF agents dithio-thalidomides, nilotinab, and cannabinoids on these neurological conditions. The therapeutic effects of 6-diazo-5-oxo-norleucine, ceptriaxone, and riluzole, agents unrelated to TNF but which either inhibit glutaminase or enhance re-uptake proteins, but do not do both, as would anti-TNF agents, are also discussed in this context. By pointing to excess extracellular glutamate as the target, these arguments greatly strengthen the case, put now for many years, to test appropriately delivered ant-TNF agents to treat neurodegenerative diseases in randomly controlled trials.

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Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria

Cited by 71 publications

References 81 publications

Immunoregulatory Role of Cannabinoids during Infectious Disease

Immunoregulatory Role of Cannabinoids during Infectious Disease

Acute and long-term effects of Δ9-tetrahydrocannabinol on object recognition and anxiety-like activity are age- and strain-dependent in mice

Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents

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