Cannabinoids for the treatment of dementia

Krishnan, Sarada; Cairns, Ruth; Howard, Robert

doi:10.1002/14651858.cd007204.pub2

Cited by 69 publications

(51 citation statements)

References 28 publications

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“…Huntington's disease [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. The neuroprotective effects of cannabinoids are mediated through CB1 receptors, located in neurons, which modulate neuronal function, and CB2 receptors, mostly located in microglia, which play an important role in neuroinflammation.…”

Section: Mj Casarejos Et Al / Pk −/− /Tau Vlw Mice and Phytocannabmentioning

confidence: 99%

Natural Cannabinoids Improve Dopamine Neurotransmission and Tau and Amyloid Pathology in a Mouse Model of Tauopathy

Casarejos

Perucho

Gómez

et al. 2013

JAD

108

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Abstract. Cannabinoids are neuroprotective in models of neurodegenerative dementias. Their effects are mostly mediated through CB1 and CB2 receptor-dependent modulation of excitotoxicity, inflammation, oxidative stress, and other processes. We tested the effects of Sativex ® , a mixture of 9 -tetrahydrocannabinol and cannabidiol, acting on both CB1 and CB2 receptors, in parkin-null, human tau overexpressing (PK −/− /Tau VLW ) mice, a model of complex frontotemporal dementia, parkinsonism, and lower motor neuron disease. The animals received Sativex ® , 4.63 mg/kg, ip, daily, for one month, at six months of age, at the onset of the clinical symptoms. We evaluated the effects of Sativex ® on behavior, dopamine neurotransmission, glial activation, redox state, mitochondrial activity, and deposition of abnormal proteins. PK −/− /Tau VLW mice developed the neurological deficits, but those treated with Sativex ® showed less abnormal behaviors related to stress, less auto and hetero-aggression, and less stereotypy. Sativex ® significantly reduced the intraneuronal, MAO-related free radicals produced during dopamine metabolism in the limbic system. Sativex ® also decreased gliosis in cortex and hippocampus, increased the ratio reduced/oxidized glutathione in the limbic system, reduced the levels of iNOS, and increased those of complex IV in the cerebral cortex. With regard to tau and amyloid pathology, Sativex ® reduced the deposition of both in the hippocampus and cerebral cortex of PK −/− /Tau VLW mice and increased autophagy. Sativex ® , even after a short administration in animals with present behavioral and pathological abnormalities, improves the phenotype, the oxidative stress, and the deposition of proteins in PK −/− /Tau VLW mice, a model of complex neurodegenerative disorders.

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Section: Mj Casarejos Et Al / Pk −/− /Tau Vlw Mice and Phytocannabmentioning

confidence: 99%

Natural Cannabinoids Improve Dopamine Neurotransmission and Tau and Amyloid Pathology in a Mouse Model of Tauopathy

Casarejos

Perucho

Gómez

et al. 2013

JAD

108

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“…Although there is no current evidence of benefit to AD patients in using cannabinoids, extensive studies have not been done, and further research is warranted (Krishnan et al 2009). …”

Section: Drugs In Trialmentioning

confidence: 99%

The role of inflammatory processes in Alzheimer’s disease

Broussard

Mytar

et al. 2012

Inflammopharmacol

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It has become increasingly clear that inflammatory processes play a significant role in the pathophysiology of Alzheimer's disease (AD). Neuroinflammation is characterized by the activation of astrocytes and microglia and the release of proinflammatory cytokines and chemokines. Vascular inflammation, mediated largely by the products of endothelial activation, is accompanied by the production and the release of a host of inflammatory factors which contribute to vascular, immune, and neuronal dysfunction. The complex interaction of these processes is still only imperfectly understood, yet as the mechanisms continue to be elucidated, targets for intervention are revealed. Although many of the studies to date on therapeutic or preventative strategies for AD have been narrowly focused on single target therapies, there is accumulating evidence to suggest that the most successful treatment strategy will likely incorporate a sequential, multifactorial approach, addressing direct neuronal support, general cardiovascular health, and interruption of deleterious inflammatory pathways.

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“…In humans, preliminary results suggest that cannabidiol can have beneficial effects in the treatment of Parkinson's disorder (Zuardi et al 2009) and a double-blind, placebo-controlled trial is currently underway to evaluate this possibility. However, it is still necessary to investigate the effects of cannabidiol on cognitive deficits associated with neurodegenerative disorders (Krishnan et al 2009;Iuvone et al 2009;. Thus, in the present study, we aimed to investigate the effects of acute and chronic cannabidiol administration on recognition memory impairment associated with iron treatment.…”

Section: Introductionmentioning

confidence: 99%