Tag Archives: CBD

Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement

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“CBD blunted neuroinflammation sustained by astrocytes through PPARγ selective activation in vitro and in vivo.

Results from the present study prove the selective involvement of PPARγ in the anti-inflammatory and neuroprotective effects of CBD here observed either in vitro and in vivo. In addition, CBD significantly promoted neurogenesis in Aβ injured rat hippocampi, much expanding its already wide spectrum of beneficial actions exerted in AD models, a non negligible effect, due to its capability to activate PPARγ.

In conclusion, results of the present research demonstrate that CBD may exert protective functions through a PPARγ dependent activation, which leads to a reduction in reactive gliosis and consequently in neurodegeneration. Moreover, in the current experimental conditions this phytocannabinoid appears to stimulate neurogenesis since it increases DCX immunopositive cell proliferation rate in rat DG.

Innovative therapeutic approaches which could significantly improve AD course require new molecules that will be able to have an impact on different pathological pathways, which converge at the progressive neurological decline. CBD has shown a capability to profoundly reduce reactive astrogliosis and to guarantee both direct and indirect neuronal protection in Aβ induced neuroinflammation/neurodegeration. So far, the lack of understanding of the precise molecular mechanism involved in CBD pharmacological actions, has had limited interest and has puzzled investigators.

Currently, findings of the present study throw some light on the issue, and frame CBD as a new PPARγ activator.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/

Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells.

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“Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. We previously showed that the psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways.

CONCLUSIONS AND IMPLICATIONS:

These observations indicated that CBD, but much less than THC, induced a cellular stress response in microglial cells and suggested that this effect could underlie its anti-inflammatory activity.”

http://www.ncbi.nlm.nih.gov/pubmed/21542829

Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells

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“Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. Δ9-Tetrahydrocannabinol (THC)is a major constituent of Cannabis and serves as an agonist of the cannabinoid receptors CB1 and CB2.

The second major constituent of Cannabis extract is cannabidiol (CBD). CBD lacks the psychoactive effects that accompany the use of THC. Moreover, CBD was demonstrated to antagonize some undesirable effects of THC, including intoxication, sedation, and tachycardia, while sharing neuroprotective, anti-oxidative, anti-emetic, and anti-carcinogenic properties. Both THC and CBD have been shown to exert anti-inflammatory properties and to modulate the function of immune cells…

In summary, our results show that although both THC and CBD exert anti-inflammatory effects, the two compounds engage different, although to some extent overlapping, intracellular pathways. Both THC and CBD decrease the activation of proinflammatory signaling…

 The cannabinoids by moderating or disrupting these signaling networks may show promise as anti-inflammatory agents.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804319/

Contrasting protective effects of cannabinoids against oxidative stress and amyloid-β evoked neurotoxicity in vitro.

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“Cannabinoids have been widely reported to have neuroprotective properties in vitro and in vivo. In this study we compared the effects of CB1 and CB2 receptor-selective ligands, the endocannabinoid anandamide and the phytocannabinoid cannabidiol, against oxidative stress and the toxic hallmark Alzheimer’s protein, β-amyloid (Aβ)…

 …the endocannabinoid anandamide protects neuronal cells from Aβ exposure via a pathway unrelated to CB1 or CB2 receptor activation…protective effect of cannabidiol against oxidative stress…

…divergent pathways for neuroprotection of these two cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/22233683

Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity

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“Creutzfeldt–Jakob disease (CJD) in humans belongs to a group of fatal neurodegenerative disorders called transmissible spongiform encephalopathies (TSEs) or prion diseases. No therapeutic treatments against TSEs are currently available. The urgent need to find effective anti-prion therapies has been strengthened by the emergence of variant CJD (vCJD) caused by contaminated beef consumption …

Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection. When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.

Overall, CBD is a promising therapeutic drug against the TSEs because it combines several crucial characteristics. It has a low toxicity and lack of psychotropic side effects as well as in vivo neuroprotective, anti-inflammatory, and anti-PrPres properties. Because CBD easily crosses the BBB, it also has the potential to be effective after prion infection has reached the CNS. Finally, prolonged treatments with CBD do not induce tolerance, a phenomenon frequently observed with THC. Additional investigations should be performed to define the optimal dose, route, frequency, and duration of the in vivo CBD treatment necessary to prevent TSE infection…”

http://www.jneurosci.org/content/27/36/9537.full

The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells.

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“Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. A massive accumulation of beta-amyloid (Abeta) peptide aggregates has been proposed as pivotal event in AD. Abeta-induced toxicity is accompanied by a variegated combination of events including oxidative stress… Cannabidiol, a non-psychoactive marijuana component, has been recently proposed as an antioxidant neuroprotective agent in neurodegenerative diseases. Moreover, it has been shown to rescue PC12 cells from toxicity induced by Abeta peptide. Here, we report that cannabidiol inhibits hyperphosphorylation of tau protein in Abeta-stimulated PC12 neuronal cells, which is one of the most representative hallmarks in AD… These results provide new molecular insight regarding the neuroprotective effect of cannabidiol and suggest its possible role in the pharmacological management of AD, especially in view of its low toxicity in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/16389547

 

Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement.

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“In view of the pro-inflammatory scenario observed in Alzheimer’s disease, in the recent years anti-inflammatory drugs have been proposed as potential therapeutic agents. We have previously shown that cannabidiol, the main non-psychotropic component from Cannabis sativa, possess a variegate combination of anti-oxidant and anti-apoptotic effects that protect PC12 cells from Abeta toxicity. In parallel, cannabidiol has been described to have anti-inflammatory properties in acute models of inflammation …

The here reported data increases our knowledge about the possible neuroprotective mechanism of cannabidiol, highlighting the importance of this compound to inhibit beta-amyloid induced neurodegeneration, in view of its low toxicity in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/16490313

The therapeutic potential of the endocannabinoid system for Alzheimer’s disease.

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“Based on the complex pathology of AD, a preventative, multimodal drug approach targeting a combination of pathological AD symptoms appears ideal. Importantly, cannabinoids show anti-inflammatory, neuroprotective and antioxidant properties and have immunosuppressive effects. Thus, the cannabinoid system should be a prime target for AD therapy. The cannabinoid receptor 2 appears to be a promising candidate but its role in AD has to be investigated cautiously. Furthermore, the phytocannabinoid cannabidiol is of particular interest as it lacks the psychoactive and cognition-impairing properties of other cannabinoids. In conclusion, future research should focus on the evaluation of the effects of manipulations to the endocannabinoid system in established animal models for AD, combined with early-phase studies in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/22448595

Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson’s disease

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“Previous findings have indicated that a cannabinoid, such as Δ(9)-THCV, which has antioxidant properties and the ability to activate CB(2) receptors but to block CB(1) , might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson’s disease (PD).

…Given its antioxidant properties and its ability to activate CB(2) but to block CB(1) receptors, Δ(9)-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms…

Conclusion

In summary, given its antioxidant properties and its ability to activate CB2 but block CB1 receptors at a dose of 2 mg·kg−1, Δ9-THCV seems to have an interesting and therapeutically promising pharmacological profile. Thus, in contrast to other phytocannabinoids that have been investigated to date, it shows promise both for the treatment of disease progression in PD and for the relief of PD symptoms. This represents an important advance in the search for potential novel anti-parkinsonian agents, since Δ9-THCV administered alone or in combination with CBD may provide a much needed improved treatment for PD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165958/

Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson’s disease: importance of antioxidant and cannabinoid receptor-independent properties.

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Abstract

“We have recently demonstrated that two plant-derived cannabinoids, Delta9-tetrahydrocannabinol and cannabidiol (CBD), are neuroprotective in an animal model of Parkinson’s disease (PD), presumably because of their antioxidant properties. To further explore this issue, we examined the neuroprotective effects of a series of cannabinoid-based compounds, with more selectivity for different elements of the cannabinoid signalling system, in rats with unilateral lesions of nigrostriatal dopaminergic neurons caused by local application of 6-hydroxydopamine. We used the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the CB2 receptor agonist HU-308, the non-selective agonist WIN55,212-2, and the inhibitors of the endocannabinoid inactivation AM404 and UCM707, all of them administered i.p. Daily administration of ACEA or WIN55,212-2 did not reverse 6-hydroxydopamine-induced dopamine (DA) depletion in the lesioned side, whereas HU-308 produced a small recovery that supports a possible involvement of CB2 but not CB1 receptors. AM404 produced a marked recovery of 6-hydroxydopamine-induced DA depletion and tyrosine hydroxylase deficit in the lesioned side. Possibly, this is caused by the antioxidant properties of AM404, which are derived from the presence of a phenolic group in its structure, rather than by the capability of AM404 to block the endocannabinoid transporter, because UCM707, another transporter inhibitor devoid of antioxidant properties, did not produce the same effect. None of these effects were observed in non-lesioned contralateral structures. We also examined the timing for the effect of CBD to provide neuroprotection in this rat model of PD. We found that CBD, as expected, was able to recover 6-hydroxydopamine-induced DA depletion when it was administered immediately after the lesion, but it failed to do that when the treatment started 1 week later. In addition, the effect of CBD implied an upregulation of mRNA levels for Cu,Zn-superoxide dismutase, a key enzyme in endogenous defenses against oxidative stress. In summary, our results indicate that those cannabinoids having antioxidant cannabinoid receptor-independent properties provide neuroprotection against the progressive degeneration of nigrostriatal dopaminergic neurons occurring in PD. In addition, the activation of CB2 (but not CB1) receptors, or other additional mechanisms, might also contribute to some extent to the potential of cannabinoids in this disease.”

http://www.ncbi.nlm.nih.gov/pubmed/17196181