Cannabidiol and Other Cannabinoids Reduce Microglial Activation In Vitro and In Vivo: Relevance to Alzheimer's Disease

Martín‐Moreno, Ana M.; Reigada, David; Ramírez, Belén G.; Mechoulam, Raphael; Innamorato, Nadia G.; Cuadrado, Antonio; Ceballos, Marı́a L. de

doi:10.1124/mol.111.071290

Cited by 315 publications

(282 citation statements)

References 36 publications

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“…A second possible explanation, based on research into animal models of Parkinson's disease and Alzheimer's disease (Ramirez et al, 2005;Chung et al, 2011;Martìn-Moreno et al, 2011), suggests that some cannabinoids have a neuroprotective action which may help to prevent psychosis-related cognitive decline (Jockers-Scherübl et al, 2007;Løberg and Hugdahl, 2009).…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Cannabis users have higher premorbid IQ than other patients with first onset psychosis

Ferraro

Russo

O’Connor

et al. 2013

Schizophrenia Research

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a b s t r a c t a r t i c l e i n f oBackground: A number of studies have reported that patients with psychosis who use cannabis have better cognitive performance than those who do not. This is surprising as cannabis can impair cognition in healthy subjects. An obvious question is whether the better current performance of psychotic patients who have used cannabis is a reflection of their having a higher premorbid IQ than those psychotic patients who haven't used cannabis. Aim: In a sample of patients at their first episode of psychosis, we tested the hypothesis that patients who smoked cannabis would have a higher premorbid IQ than patients who did not. Methodology: 279 participants (119 patients and 160 healthy controls) were assessed in order to obtain current and premorbid IQ measures and detailed information on cannabis use. We examined the association between cannabis use and both premorbid and current IQ in patients and controls. Results: Patients who had ever smoked cannabis had significantly higher current (p b .001) and premorbid IQ (p = .004) compared to patients who had never used cannabis. This difference was not found among controls. Conclusions: These findings suggest that the better cognitive performance of patients with their first episode of psychosis who have used cannabis compared with those who haven't is due to the better premorbid IQ of the former.

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Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Cannabis users have higher premorbid IQ than other patients with first onset psychosis

Ferraro

Russo

O’Connor

et al. 2013

Schizophrenia Research

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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%

“…The extracts were dissolved in ethanol and mixed 1:1 to make a 20 mg/ml Sativex ® stock solution in siliconed tubes and covered in order to protect it from direct light. The Sativex ® solution was prepared as previously described [2,10,17]. The total dose of cannabinoid administered was always 4.63 mg/kg of Sativex ® (equivalent to 1.5 mg/kg of pure CBD and 1.5 mg/kg of pure THC), which is within the range of effective doses of both compounds when they were administered in pure form in other experimental models of neurodegenerative diseases [2,10,17] and in human studies [30].…”

Section: Transgenic Animals Cannabinoid Treatment and Tissue Collecmentioning

confidence: 99%

“…The Sativex ® solution was prepared as previously described [2,10,17]. The total dose of cannabinoid administered was always 4.63 mg/kg of Sativex ® (equivalent to 1.5 mg/kg of pure CBD and 1.5 mg/kg of pure THC), which is within the range of effective doses of both compounds when they were administered in pure form in other experimental models of neurodegenerative diseases [2,10,17] and in human studies [30]. This was also the effective dose in a previous study with Sativex ® -like combination of phytocannabinoids in a model of Huntington's disease [17].…”

Section: Transgenic Animals Cannabinoid Treatment and Tissue Collecmentioning

confidence: 99%

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

Casarejos

Perucho

Gómez

et al. 2013

JAD

103

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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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“…7L) and 1 mM HU210 (48%; p , 0.01; Fig. 7L) in MPP + -treated cocultures of mesencephalic neurons and microglia, indicative of microglia CB 1 receptor involvement (48).…”

Section: Win55212-2 and Hu210 Protect Da Neurons From Microglia-derimentioning

confidence: 99%

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

106

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This study examined whether the cannabinoid receptor type 1 (CB1) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB1 receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB1 receptor. The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

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Cannabidiol and Other Cannabinoids Reduce Microglial Activation In Vitro and In Vivo: Relevance to Alzheimer's Disease

Cited by 315 publications

References 36 publications

Cannabis users have higher premorbid IQ than other patients with first onset psychosis

Cannabis users have higher premorbid IQ than other patients with first onset psychosis

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

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

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