Tag Archives: treatment

Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

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“Parkinson’s disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons.

The current treatment is symptomatic and mainly involves replacement of dopamine deficiency. This therapy improves only motor symptoms of Parkinson’s disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD.

Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review we examine the potential benefits of medical marijuana and related compounds in the treatment of both motor and nonmotor symptoms as well as in slowing the progression of the disease. The potential for cannabis to enhance the quality of life of Parkinson’s patients is explored.

Marijuana has been shown to improve nonmotor symptoms of PD such as depression, pain, sleep, and anxiety. Moreover, components of cannabis have been demonstrated to have neuroprotective effect due to their anti-inflammatory, antioxidative, and antiexcitotoxic properties.

Due to combination of the above mentioned beneficial effects, cannabis may provide a viable alternative or addition to the current treatment of Parkinson’s disease.”  https://www.hindawi.com/journals/pd/2016/1279042/

“Marijuana: Could it slow Parkinson’s disease progression? Parkinson’s disease is the second most common neurological illness in the United States, causing tremors, slowness of movement, postural instability, and impaired balance and coordination. But findings from a new review suggest symptoms of the condition could be improved with marijuana.”  http://www.medicalnewstoday.com/articles/314648.php

“Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy.” https://www.ncbi.nlm.nih.gov/pubmed/28050308

Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells.

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“Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions.

In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol(CBD) can influence their expression profile, improving the therapeutic potential of this cell culture.

In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.”

https://www.ncbi.nlm.nih.gov/pubmed/27932991

Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells.

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“In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties.

This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate towards neuronal precursor cells.

From our results we hypothesize that human gingiva-derived MSCs conditioned with CBD could represent a valid method for improving the hGMSCs phenotype and thus might be a potential therapeutic tool in the treatment of neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/27918106

Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

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“Marijuana has been used for thousands of years as a treatment for medical conditions.

However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G protein βγ subunits.

Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories.

Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition.

These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.”

http://www.cell.com/cell/abstract/S0092-8674(13)01360-3

“Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis.” https://www.ncbi.nlm.nih.gov/pubmed/18556441

Smoking cannabis ‘helps addicts give up heroin’, study finds

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Smoking cannabis ‘helps addicts give up heroin’, study finds

“Smoking weed helps patients give up opiates such as heroin, a new study has found.

Researchers at Columbia University monitored patients undergoing treatment for opiate addiction – and found that patients who smoked weed were more able to sleep, less anxious, and more likely to complete their course.

 The researchers also found that dosing patients with dronabinol – a drug consisting of the ‘active’ ingredient in cannabis, THC – helped with withdrawal symptoms.”

http://metro.co.uk/2015/12/02/smoking-cannabis-helps-addicts-give-up-heroin-study-finds-5538896/

Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader-Willi syndrome.

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“Extreme obesity is a core phenotypic feature of Prader-Willi syndrome (PWS).

Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R) blockade reverses obesity both in animals and humans.

The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects.

CONCLUSIONS:

Dysregulation of the eCB/CB1R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB1R antagonists may be an effective strategy for the management of severe obesity in PWS.”

https://www.ncbi.nlm.nih.gov/pubmed/27900261

Treatment with tetrahydrocannabinol (THC) prevents infertility in male cystic fibrosis mice.

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“Cystic fibrosis (CF) is a hereditary disease caused by mutations of the gene encoding a channel protein CFTR, conducting Cl- and HCO3 – ions. The disease is characterized by disturbances in most physiological systems, and more than 95% of men are infertile. The mechanism underlying the etiology of CF is associated with an imbalance of fatty acids.

It has been suggested that the function of the endocannabinoid system is also disturbed in CF, because endocannabinoids are derivatives of fatty acids. We assumed, therefore, that endocannabinoid activity, which plays an important role in fertility, is disrupted in CF and could be one of the causes of infertility.

The aim of the present study was to test the hypothesis that stimulation of endocannabinoid receptors in infancy would normalize their function and prevent infertility in adulthood.

Knockout male mice (cftr-/-) were treated with tetrahydrocannabinol (THC), endocannabinoid receptors agonist, in infancy from days 7 until 28, daily.

CF males treated with THC were fully fertile, producing offspring comparable by the number of litters and the number of pups with wild-type mice. CF males that were not treated with THC were completely infertile.

The present study shows that (i) endocannabinoid function is impaired in CF mice, as evidenced by the regenerating effect of its stimulation on the fertility of otherwise infertile males, (ii) endocannabinoid system dysfunction is apparently the determining factor causing infertility in CF, and (iii) mild stimulation of the endocannabinoid system in infancy and adolescence appears to normalize many reproductive processes and thereby prevent infertility in CF males.”

https://www.ncbi.nlm.nih.gov/pubmed/22865360

Behavioral alterations in cystic fibrosis mice are prevented by cannabinoid treatment in infancy.

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“Substantial data have been accumulated regarding the molecular basis of cystic fibrosis (CF) pathogenesis, whereas the influence of biochemical impairments on brain processes has been the focus of much less attention. We have studied some behavioral parameters, such as motor activity and anxiety level, in a mice model of CF.

We have assumed that functioning of the endocannabinoid system could be impaired in CF (endocannabinoids are fatty acid derivatives, and fatty acid deficiency is considered a major factor in CF etiology). We have suggested that chronic treatment with cannabinoid receptors agonist during infancy would balance cannabinoid levels and prevent CF-related behavioral alterations.

Motor activity and anxiety level were studied in naïve adult CF mice (cftr-deficient mice) and compared with wild-type mice and to CF mice treated chronically with Δ9-tetrahydrocannabinol (Δ9-THC; endocannabinoid receptor agonist) during infancy (from days 7 to 28). Motor activity was tested in the tetrad, and level of anxiety in the plus maze, a month after cessation of treatment.

Motor activity decrease and elevated anxiety level were found in adult naïve CF mice compared with wild-type mice. CF mice treated with THC in infancy showed normal motor activity and anxiety levels in adulthood. Motor function alteration and elevated anxiety levels in CF can result from lack of CFTR-channel in neurons and disturbed activity of various brain areas, as well as being secondary and mediated by fatty acids deficiency, altered levels of endocannabinoids and their receptors.

It can be suggested that chronic treatment during infancy restores endocannabinoid function and thus prevents behavioral alterations.”

https://www.ncbi.nlm.nih.gov/pubmed/22865361

Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis.

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“This study was aimed to investigate whether treatment with purified cannabidiol (CBD) may counteract the development of experimental multiple sclerosis (MS), by targeting the PI3K/Akt/mTOR pathway.

Our results showed a clear downregulation of the PI3K/Akt/mTOR pathway following EAE induction. CBD treatment was able to restore it, increasing significantly the phosphorylation of PI3K, Akt and mTOR. Also, an increased level of BNDF in CBD-treated mice seems to be involved in the activation of PI3K/Akt/mTOR pathway.

In addition, our data demonstrated that therapeutic efficacy of CBD treatment is due to reduction of pro-inflammatory cytokines, like IFN-γ and IL-17 together with an up-regulation of PPARγ. Finally, CBD was found to promote neuronal survival by inhibiting JNK and p38 MAP kinases.

These results provide an interesting discovery about the regulation of the PI3K/Akt/mTOR pathway by cannabidiol administration, that could be a new potential therapeutic target for MS management.”

https://www.ncbi.nlm.nih.gov/pubmed/27890794

Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia.

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“This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic phytochemical present in Cannabis sativa, on the cognitive and emotional impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice.

Using a multi-tiered behavioral testing battery during 21days, we found that BCCAO mice exhibited long-lasting functional deficits reflected by increase in anxiety-like behavior (day 9), memory impairments (days 12-18) and despair-like behavior (day 21).

Short-term CBD 10mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO.

In addition, ischemic mice treated with CBD exhibited an increase in the hippocampal brain derived neurotrophic factor (BDNF) protein levels.

CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO animals.

Collectively, the present results demonstrate that short-term CBD treatment results in global functional recovery in ischemic mice and impacts multiple and distinct targets involved in the pathophysiology of brain ischemic injury.”

https://www.ncbi.nlm.nih.gov/pubmed/27889412