Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK.

Posted on June 13, 2017 by David

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“Melanogenesis plays a critical role in the protection of skin against external stresses such as ultraviolet irradiation and oxidative stressors. This study was aimed to investigate the effects of cannabidiol on melanogenesis and its mechanisms of action in human epidermal melanocytes. We found that cannabidiol increased both melanin content and tryrosinase activity. The mRNA levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP) 1, and TRP2 were increased following cannabidiol treatment. Likewise, cannabidiol increased the protein levels of MITF, TRP 1, TRP 2, and tyrosinase. Mechanistically, we found that cannabidiol regulated melanogenesis by upregulating MITF through phosphorylation of p38 mitogen-activated protein kinase (MAPK) and p42/44 MAPK, independent of cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling. In addition, the melanogenic effect of cannabidiol was found to be mediated by cannabinoid CB₁ receptor, not by CB₂receptor. Taken together, these findings indicate that cannabidiol-induced melanogenesis is cannabinoid CB₁ receptor-dependent, and cannabidiol induces melanogenesis through increasing MITF gene expression which is mediated by activation of p38 MAPK and p42/44 MAPK. Our results suggest that cannabidiol might be useful as a protective agent against external stresses.”

https://www.ncbi.nlm.nih.gov/pubmed/28601556

http://www.sciencedirect.com/science/article/pii/S0009279716304343

Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?

Posted on February 16, 2017 by David

“Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/28197175

“The endocannabinoid system in amyotrophic lateral sclerosis. There is increasing evidence that cannabinoids and manipulation of the endocannabinoid system may have therapeutic value in ALS. Cannabinoids exert anti-glutamatergic and anti-inflammatory actions through activation of the CB(1) and CB(2) receptors. The ability of cannabinoids to target multiple neurotoxic pathways in different cell populations may increase their therapeutic potential in the treatment of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/18781981

“Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis (ALS). Our data suggest that cannabinoid CB1 receptors might be potential therapeutic targets for this dramatic disease.” http://www.ncbi.nlm.nih.gov/pubmed/19452308

“Cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis. Cannabinoid CB2 receptor-selective compounds may be the basis for developing new drugs for the treatment of ALS and other chronic neurodegenerative diseases.” http://www.ncbi.nlm.nih.gov/pubmed/16781706

“Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. The cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/15204022

“Δ9-Tetrahydrocannabinol (Δ9-THC) is the main psychoactive constituent in the plant Cannabis sativa (marijuana) and produces its effects by activation of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) cannabinoid receptors. Administration of the non-selective partial cannabinoid agonists Δ9-THC or cannabinol are successful in delaying motor impairment and prolonging survival in mice after the onset of symptoms. Collectively, these studies suggest that cannabinoid receptors might serve as novel therapeutic targets for ALS drug development. CB2 agonists may slow motor neuron degeneration and preserve motor function, and represent a novel therapeutic modality for treatment of ALS.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819701/

“Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS)” http://www.ncbi.nlm.nih.gov/pubmed/22594565

“Therapeutic options for amyotrophic lateral sclerosis (ALS) remain limited. Evidence suggests that cannabinoids, the bioactive ingredients of marijuana (Cannabis sativa) might have some therapeutic benefit in this disease. We found that this treatment significantly delays disease onset. Cannabinoids might be useful in ameliorating symptoms in ALS.” http://www.ncbi.nlm.nih.gov/pubmed/16183560

“Marijuana is a substance with many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). These include analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. In addition, marijuana has now been shown to have strong antioxidative and neuroprotective effects. Marijuana should be considered in the pharmacological management of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/11467101

“Ideally, a multidrug regimen would be required to comprehensively address the known pathophysiology of ALS. REMARKABLY, cannabis appears to have activity in all of those areas. Cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. Cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.” http://www.ncbi.nlm.nih.gov/pubmed/20439484

“In light of the above findings, there is a valid rationale to propose the use of cannabinoid compounds in the pharmacological management of ALS patients. Cannabinoids indeed are able to delay ALS progression and prolong survival.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270417/

http://www.thctotalhealthcare.com/category/amyotrophic-lateral-sclerosis-als-lou-gehrigs-disease/

Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons.

Posted on January 23, 2017 by David

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“Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury.

In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen-glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line.

This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.”

https://www.ncbi.nlm.nih.gov/pubmed/28110213

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

Posted on December 13, 2016 by David

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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

Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism.

Posted on July 18, 2016 by David

Journal of Pharmacology and Experimental Therapeutics

“Serum is required for the survival and growth of most animal cells. In serum-free medium, B lymphoblastoid cells and fibroblasts die after 2 days.

We report that submicromolar concentrations of Delta(9)-tetrahydrocannabinol (THC), Delta(8)-THC, cannabinol, or cannabidiol, but not WIN 55,212-2, prevented serum-deprived cell death. Delta(9)-THC also synergized with platelet-derived growth factor in activating resting NIH 3T3 fibroblasts.

The cannabinoids‘ growth supportive effect did not correlate with their ability to bind to known cannabinoid receptors and showed no stereoselectivity, suggesting a nonreceptor-mediated pathway.

Direct measurement of oxidative stress revealed that cannabinoids prevented serum-deprived cell death by antioxidation.

The antioxidative property of cannabinoids was confirmed by their ability to antagonize oxidative stress and consequent cell death induced by the retinoid anhydroretinol.

Therefore, cannabinoids act as antioxidants to modulate cell survival and growth of B lymphocytes and fibroblasts.”

http://www.ncbi.nlm.nih.gov/pubmed/10869379/

“Marijuana has been known for centuries to be a psychoactive medicinal plant. Cannabinoids, especially the nonpsychoactive cannabinoids, may become clinically useful antioxidants in preventing and treating the oxidative stress-related diseases.” http://jpet.aspetjournals.org/content/293/3/807.long

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.

Posted on April 26, 2016 by David

“The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common.

Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required.

In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia.

In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia.

We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/27110749

Polyphenolic Compounds and Antioxidant Activity of Cold-Pressed Seed Oil from Finola Cultivar of Cannabis sativa L.

Posted on April 15, 2016 by David

“The aim of this study was to characterize the polyphenolic compounds and antioxidant activity of cold-pressed seed oil from Finola cultivar of industrial hemp (Cannabis sativa L.).

Several methodologies have been employed to evaluate the in vitro antioxidant activity of Finola hempseed oil (FHSO) and both lipophilic (LF) and hydrophilic fractions (HF). The qualitative and quantitative composition of the phenolic fraction of FHSO was performed by HPLC analyses.

From the results is evident that FHSO has high antioxidative activity, as measured by DPPH radical (146.76 mmol of TE/100 g oil), inhibited β-carotene bleaching, quenched a chemically generated peroxyl radical in vitro and showed high ferrous ion chelating activity. Reactivity towards 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical cation and ferric-reducing antioxidant power values were 695.2 µmol of TE/100g oil and 3690.6 µmol of TE/100 g oil respectively.

FHSO contains a significant amount of phenolic compounds of which 2780.4 mg of quercetin equivalent/100 g of total flavonoids.

The whole oil showed higher antioxidant activity compared with LF and HF.

Our findings indicate that the significant antioxidant properties shown from Finola seed oil might generally depend on the phenolic compounds, especially flavonoids, such as flavanones, flavonols, flavanols and isoflavones.”

http://www.ncbi.nlm.nih.gov/pubmed/27076277

The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications.

Posted on April 23, 2015 by David

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“Oxidative stress and inflammation play critical roles in the development of diabetes and its complications.

Recent studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions.

The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications.

This review focuses on the role of the endocannabinoid system in primary diabetes and its effects on various diabetic complications, such as diabetic cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy, particularly highlighting the mechanisms beyond the metabolic consequences of the activation of the endocannabinoid system.

The therapeutic potential of targeting the endocannabinoid system and certain plant-derived cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabivarin, which are devoid of psychotropic effects and possess potent anti-inflammatory and/or antioxidant properties, in diabetes and diabetic complications is also discussed.

Although there is much controversy in the field of EC research, experimental evidence and clinical trials have clearly shown that ECS plays a key role in the development of primary diabetes and various diabetic complications. Although inhibition of CB1 receptors has proven to be effective in clinical trials of obesity and metabolic syndrome, this approach has ultimately failed because of increasing patient anxiety. However, recent preclinical studies clearly showed that peripherally restricted CB1 antagonists may represent a viable therapeutic strategy to avoid the previously mentioned adverse effects.

Importantly, CB1 inhibition, as discussed in this review, may also directly attenuate inflammatory responses and ROS and reactive nitrogen species generation in endothelial, immune, and other cell types, as well as in target tissues of diabetic complications, far beyond its known beneficial metabolic consequences. The main effects of CB1 receptor activation on the development of diabetes and diabetic complications are summarized in Figure 1. CB2 agonists may exert beneficial effects on diabetes and diabetic complications by attenuating inflammatory response and ensuing oxidative stress (Figure 2).

Natural cannabinoids, such as CBD and THCV, also have tremendous therapeutic potential.

CBD is a potent antioxidant and anti-inflammatory agent that does not appear to exert its beneficial effects through conventional CB receptors and is already approved for human use.

THCV and its derivatives, which may combine the beneficial effects of simultaneous CB1 inhibition and CB2 stimulation, are still under intense preclinical investigation. It will be interesting to see how newly developed, peripherally restricted CB1 receptor antagonists and/or CB2 receptor agonists and certain natural cannabinoids, such as CBD and THCV, will influence the clinical outcomes of diabetic patients.

We hope that some of these new approaches will be useful in clinical practice in the near future to aid patients with diabetes.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349875/

http://www.thctotalhealthcare.com/category/diabetes/

Cannabidiol: an overview of some pharmacological aspects.

Posted on January 18, 2013 by David

“Over the past few years, considerable attention has focused on cannabidiol (CBD), a major nonpsychotropic constituent of cannabis.

The authors present a review on the chemistry of CBD and discuss the anticonvulsive, antianxiety, antipsychotic, antinausea, and antirheumatoid arthritic properties of CBD.

CBD does not bind to the known cannabinoid receptors, and its mechanism of action is yet unknown. It is possible that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its antioxidative effect.”

http://www.ncbi.nlm.nih.gov/pubmed/12412831

Cannabis May Offer Alzheimer’s Hope, Study Says

Posted on January 9, 2013 by David

“Marijuana compounds offer an alternative approach for treating the neurodegeneration associated with Alzheimer’s disease (AD)…

Investigators at the Trinity College, Institute for Neuroscience, in Dublin report that cannabinoids have been shown to protect neurons from the deleterious effects of amyloid plaque – the primary pathological hallmark of Alzheimer’s. Cannabinoids also demonstrate a propensity to reduce oxidative stress and inflammation, while also promoting neurogenesis (the birth of new neuronal cells), authors report.

Authors write: “In recent years the proclivity of cannabinoids to exert a neuroprotective influence has received substantial interest as a means to mitigate the symptoms of neurodegenerative conditions. … [C]annabinoids offer a multi-faceted approach for the treatment of Alzheimer’s disease by providing neuroprotection and reducing neuroinflammation, whilst simultaneously supporting the brain’s intrinsic repair mechanisms by augmenting neurotrophin expression and enhancing neurogenesis. … Manipulation of the cannabinoid pathway offers a pharmacological approach for the treatment of AD that may be efficacious than current treatment regimens.”

Preclinical studies have demonstrated that cannabinoids can delay disease progression in animal models of several neurodegenerative diseases, including multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig’s disease).”-

Paul Armentano, NORML http://norml.org/news/2007/09/20/cannabis-may-offer-alzheimers-hope-study-says

Full text of the study, “Alzheimer’s disease; taking the edge off with cannabinoids?” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190031/