Perturbations of the endocannabinoid system in mantle cell lymphoma: correlations to clinical and pathological features.

“The cannabinoid receptors are upregulated in many types of cancers, including mantle cell lymphoma (MCL) and have been suggested to constitute novel therapeutic targets.

…  the relative expression of the anandamide synthesizing and metabolizing enzymes in MCL is heavily perturbed.

This finding, together with high expression of cannabinoid receptors, could favor enhanced anandamide signaling and suggest that targeting the endocannabinoid system might be considered as part of lymphoma therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25594062

“We have previously shown that exposure of MCL cells to cannabinoids induces cell death in vitro and reduces tumor growth in xenograft mouse models… cancer tissues express higher levels of cannabinoid receptors than the non-malignant counterparts and the endocannabinoid system is therefore considered as a potential novel therapeutic target in cancer therapy.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278325/

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

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.

“Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance.

Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS).

In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator.

…we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion.

Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.”

http://www.ncbi.nlm.nih.gov/pubmed/25590811

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

 

 

Neural Effects of Cannabinoid CB1 Neutral Antagonist Tetrahydrocannabivarin (THCv) on Food Reward and Aversion in Healthy Volunteers.

“Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders.

We previously showed that the cannabis receptor (CB1) inverse agonist rimonabant, an anti-obesity drug withdrawn due to depressogenic side effects, diminished neural reward responses yet increased aversive responses. Unlike rimonabant, tetrahydrocannabivarin (THCv) is a neutral CB1 receptor antagonist and may therefore produce different modulations of the neural reward system…

Conclusions: Our findings are the first to show that treatment with the CB1 neutral antagonist THCv increases neural responding to rewarding and aversive stimuli.

This effect profile suggests therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25542687

http://www.thctotalhealthcare.com/category/obesity-2/

Re-branding cannabis: the next generation of chronic pain medicine?

“The field of pain medicine is at a crossroads given the epidemic of addiction and overdose deaths from prescription opioids. Cannabis and its active ingredients, cannabinoids, are a much safer therapeutic option.

Despite being slowed by legal restrictions and stigma, research continues to show that when used appropriately, cannabis is safe and effective for many forms of chronic pain and other conditions, and has no overdose levels.

Current literature indicates many chronic pain patients could be treated with cannabis alone or with lower doses of opioids.

To make progress, cannabis needs to be re-branded as a legitimate medicine and rescheduled to a more pharmacologically justifiable class of compounds.

This paper discusses the data supporting re-branding and rescheduling of cannabis.”

http://www.ncbi.nlm.nih.gov/pubmed/25537695

http://www.thctotalhealthcare.com/category/chronic-pain/

Drug discovery strategies that focus on the endocannabinoid signaling system in psychiatric disease.

“The endocannabinoid (eCB) system plays an important role in the control of mood, and its dysregulation has been implicated in several psychiatric disorders.

Targeting the eCB system appears to represent an attractive and novel approach to the treatment of depression and other mood disorders.

…the review provides discussion on compounds and drugs that target this system and might prove to be successful for the treatment of mood-related psychiatric disorders.

The discovery of increasingly selective modulators of CB receptors should enable the identification of optimal therapeutic strategies.

It should also maximize the likelihood of developing safe and effective treatments for debilitating psychiatric disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25488672

Involvement of central and peripheral cannabinoid receptors on antinociceptive effect of tetrahydrocannabinol in muscle pain.

“Cannabinoid (CB) receptors have emerged as an attractive therapeutic target for pain management in recent years and the interest in the use of cannabinoids is gradually increasing, particularly in patients where conventional treatments fail…

This study suggests that THC could be a future pharmacological option in the treatment of muscle pain.

The local administration of THC could be an interesting option to treat this type of pain avoiding the central adverse effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25446925

http://www.thctotalhealthcare.com/category/pain-2/

Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases.

“Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug.

In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies.

To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms.

Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders.

This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated.”

http://www.ncbi.nlm.nih.gov/pubmed/25407719

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

“Cannabis contains over 60 different terpeno-phenol compounds…

cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV) are known as non-psychoactive components of cannabis.

These compounds have shown anti-inflammatory, immunosuppressive, analgesic, anxiolytic and anti-cancer effects…

Cannabinoids may play a role in neuroprotection in disorders such as stroke, Parkinson’s disease, traumatic brain injury and epilepsy…

It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury…

Accumulating data now suggest that cannabinoid CB1 receptors contribute to neuroprotection… Emerging data now support the evidence of the anti-inflammatory action of CBD…

 We have previously reported that CBD  has a potent and long-lasting neuroprotective effect when administered both pre- and post-ischemia, whereas only pre-ischemic treatment with delta9-THC reduced the infarction size…

These results suggest that CBD may prevent post-ischemic injury progressively induced by ischemic stroke….

…anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis.

The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance.

In the last 10 years, it has been possible to demonstrate that CBD has the following unique therapeutic profile: 1) a cannabinoid receptor-independent mechanism, 2) long-lasting cerebro- protective effect after ischemic stroke, and lack of development of tolerance.

Moreover, CBD has almost no side effects, including psychotropic activity.

Preliminary studies highlight the fact that the multifunctional actions of CBD may lead to benefits in more complex systems within the brain after ischemic stroke.

CBD offers new therapeutic possibilities for treating ischemic stroke…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036658/

http://www.thctotalhealthcare.com/category/stroke-2/

Cannabinoid inhibition of macrophage migration to the trans-activating (Tat) protein of HIV-1 is linked to the CB(2) cannabinoid receptor.

“Macrophages and macrophage-like cells are important targets of HIV-1 infection at peripheral sites and in the central nervous system…

 

Collectively, the pharmacological and biochemical knockdown data indicate that cannabinoid-mediated modulation of macrophage migration to the HIV-1 Tat protein is linked to the CB(2)cannabinoid receptor.

Furthermore, these results suggest that the CB(2) cannabinoid receptor has potential to serve as a therapeutic target for ablation of HIV-1-associated untoward inflammatory response.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846023/

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

 

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

Image result for immunopharmacology and immunotoxicology

“We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI).

In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation.

The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant.

Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI.

Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25356537