Tag Archives: therapy

Cannabinoids for Symptom Management and Cancer Therapy: The Evidence.

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“Cannabinoids bind not only to classical receptors (CB1 and CB2) but also to certain orphan receptors (GPR55 and GPR119), ion channels (transient receptor potential vanilloid), and peroxisome proliferator-activated receptors. Cannabinoids are known to modulate a multitude of monoamine receptors. Structurally, there are 3 groups of cannabinoids.

Multiple studies, most of which are of moderate to low quality, demonstrate that tetrahydrocannabinol (THC) and oromucosal cannabinoid combinations of THC and cannabidiol (CBD) modestly reduce cancer pain.

Dronabinol and nabilone are better antiemetics for chemotherapy-induced nausea and vomiting (CINV) than certain neuroleptics, but are not better than serotonin receptor antagonists in reducing delayed emesis, and cannabinoids have largely been superseded by neurokinin-1 receptor antagonists and olanzapine; both cannabinoids have been recommended for breakthrough nausea and vomiting among other antiemetics. Dronabinol is ineffective in ameliorating cancer anorexia but does improve associated cancer-related dysgeusia.

Multiple cancers express cannabinoid receptors directly related to the degree of anaplasia and grade of tumor.

Preclinical in vitro and in vivo studies suggest that cannabinoids may have anticancer activity.

Paradoxically, cannabinoid receptor antagonists also have antitumor activity.

There are few randomized smoked or vaporized cannabis trials in cancer on which to judge the benefits of these forms of cannabinoids on symptoms and the clinical course of cancer. Smoked cannabis has been found to contain Aspergillosis. Immunosuppressed patients should be advised of the risks of using “medical marijuana” in this regard.”

http://www.ncbi.nlm.nih.gov/pubmed/27407130

Endocannabionoid System in Neurological Disorders.

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“Several studies support the evidence that the endocannabinoid system and cannabimimetic drugs might have therapeutic potential in numerous pathologies. These pathologies range from neurological disorders, atherosclerosis, stroke, cancer to obesity/metabolic syndrome and others.

In this paper we review the endocannabinoid system signaling and its alteration in neurodegenerative disorders like multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and Huntington’s disease and discuss the main findings about the use of cannabinoids in the therapy of these pathologies.

Despite different etiologies, neurodegenerative disorders exhibit similar mechanisms like neuro-inflammation, excitotoxicity, deregulation of intercellular communication, mitochondrial dysfunction and disruption of brain tissue homeostasis.

Current treatments ameliorate the symptoms but are not curative.

Interfering with the endocannabinoid signaling might be a valid therapeutic option in neuro-degeneration.

To this aim, pharmacological intervention to modulate the endocannabinoid system and the use of natural and synthetic cannabimimetic drugs have been assessed. CB1 and CB2 receptor signaling contributes to the control of Ca2+ homeostasis, trophic support, mitochondrial activity, and inflammatory conditions.

Several studies and patents suggest that the endocannabinoid system has neuro-protective properties and might be a target in neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27364363

Pharmacological hypothermia: a potential for future stroke therapy?

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“Mild physical hypothermia after stroke has been associated with positive outcomes.

Pharmacologically induced hypothermia has been explored as a possible treatment option following stroke in animal models.

Currently, there are eight classes of pharmacological agents/agonists with hypothermic effects affecting a multitude of systems including cannabinoid, opioid, transient receptor potential vanilloid 1 (TRPV1), neurotensin, thyroxine derivatives, dopamine, gas, and adenosine derivatives.

This review offers the opinion that these agents may be useful in combination therapies with physical hypothermia to achieve faster and more stable temperature control in hypothermia.”

http://www.ncbi.nlm.nih.gov/pubmed/27320243

Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing.

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“Previous studies showed that cannabinoid 2 (CB2) receptor is expressed in multiple effector cells during skin wound healing. Meanwhile, its functional involvement in inflammation, fibrosis, and cell proliferation in other organs and skin diseases implied CB2 receptor might also regulate skin wound healing.

These results, taken together, indicate that activating CB2 receptor could ameliorate wound healing by reducing inflammation, accelerating re-epithelialization, and attenuating scar formation.

Thus, CB2 receptor agonist might be a novel perspective for skin wound therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27268717

Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis

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“Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive.

One of the receptors, CB receptor 1 (CB1), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB2) is expressed primarily by immune cells.

Theoretically, selective CB2 agonists should be devoid of psychoactive effects.

In this study, we investigated therapeutic effects of a selective CB2 agonist on arthritis.

The present study suggests that a selective CB2 agonist could be a new therapy for RA that inhibits production of inflammatory mediators from FLS, and osteoclastogenesis.

This is the first report of therapeutic effect of a selective CB2 agonist on CIA.

Although the effect was mild, optimization of dosage and/or treatment protocol might enhance the effect.

Perhaps, more potent selective CB2agonists might solve this problem.

Cannabinoids are pharmacologically active components of Cannabis sativa.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243420/

Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent

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“Breast cancer is the leading cause of cancer-related deaths among women aged 34–50 worldwide, and is the most commonly diagnosed metastasizing tumor in women of all ages. Despite advances in understanding breast cancer as a disease, there remains a critical need for novel disease-modifying therapeutics.

Nonspecific cannabinoids, cannabinoid receptor 2 (CB2)-selective, as well as cannabinoid receptor 1 (CB1)-selective compounds have yielded similar antitumor results in several tumor models. The lack of neuronal expression of CB2 receptors precludes CB2 selective compounds from inducing the psychotropic effects that typically accompany CB1 activation.

 Our group and others have shown that CB2 agonists displaying selectivity for the CB2 receptor can decrease tumor cell viability and significantly attenuate cancer-induced bone pain without displaying psychoactive or addictive properties.

…antitumor effects of cannabinoids have been demonstrated in a variety of tumor models…

The antiproliferative effects of a CB2 agonist along with our previous work demonstrating significant efficacy in inhibiting bone cancer pain and slowing bone loss in a murine model of advanced breast cancer strongly suggest that CB2 agonists should be investigated in humans as adjunct therapy for advanced stages of breast cancer.

 Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems.
The results of this work characterize the actions of a CB2-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor.
Several groups have shown that both nonselective cannabinoid and CB2-specific compounds decrease breast cancer viability in vitro and in vivo: Δ9-tetrahydrocannabinol and CB2-selective agonist, JWH-133, have been demonstrated to exert considerable antitumoral effects…”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847606/

Cannabinoid receptors in mantle cell lymphoma

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“Mantle cell lymphoma (MCL) is a non-curable B cell lymphoma that in several independent studies have been shown to express higher levels of CB1 and CB2 than non-malignant B cells.

The endocannabinoid system is dysregulated in many types of cancer and is involved in the regulation of survival and proliferation of cancer cells and cancer stem cells, in cancer metabolism, as well as in pro-metastatic events such as angiogenesis, migration and invasion.

Previous in vitro studies of MCL cell lines and primary ex vivo isolated tumor cells have demonstrated that high concentrations of cannabinoid receptor ligands induced proliferation arrest and programmed cell death.

All together, the data suggest that perturbations in the endocannabinoid system participate in the regulation of multi-functional cell responses regarding proliferation, migration and cell death control.

Therefore, it can be concluded that further studies on pharmacological modulation of endocannabinoid accumulation and/or signaling offers an interesting option for novel anti-lymphoma therapy.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353235/

Stimulated CB1 Cannabinoid Receptor Inducing Ischemic Tolerance and Protecting Neuron from Cerebral Ischemia.

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“Anandamide system is mainly made up of cannabinoid receptors, their endogenous ligands and some related enzymes. Activation of the system mediates various molecular events, thereafter leading to vasodilation, bradycardia and anti-inflammation.

The stimulated cannabinoid receptors may take part in protection of endothelial cells from injury and therefore can be potential targets in therapy for some diseases, especially cardio or cerebral vascular disturbances.

Cerebral ischemia is a deadly disease that modern people have to face and will probably face for a long period of time. Ischemic tolerance has the protective effect of brain as an endogenous event in cerebral ischemia, in which variety of inducers such as transient cerebral ischemia, hypoxia, hypothermia and drug agents are involved.

Most of cannabinoid 1 receptors (CB1Rs), a member in G protein-coupled receptor family, exist in central nervous systems.

Mechanism of neuroprotection mediated by the receptor is considered through facilitating neurotransmitter release and regulating other molecular events. In this review, advance of the neuroprotection against cerebral ischemia and the mechanism of the action are overviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/27142423

“Cerebral ischemia or brain ischemia, is a condition that occurs when there isn’t enough blood flow to the brain to meet metabolic demand. This leads to limited oxygen supply or cerebral hypoxia and leads to the death of brain tissue, cerebral infarction, or ischemic stroke. It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage. There are two kinds of ischemia: focal ischemia: confined to a specific region of the brain; global ischemia: encompasses wide areas of brain tissue.”  http://www.columbianeurosurgery.org/conditions/cerebral-ischemia/

Anticancer mechanisms of cannabinoids.

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“In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer.

They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals.

In this review, we discuss the current understanding of cannabinoids as antitumour agents, focusing on recent discoveries about their molecular mechanisms of action, including resistance mechanisms and opportunities for their use in combination therapy.

Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents.”

http://www.ncbi.nlm.nih.gov/pubmed/27022311

Nabilone for the Management of Pain.

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“Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education.

Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent.”

http://www.ncbi.nlm.nih.gov/pubmed/26923810