CANNABINOIDS INCREASE LUNG CANCER CELL LYSIS BY LYMPHOKINE-ACTIVATED KILLER CELLS VIA UPREGULATION OF ICAM-1.

“Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action…

Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody…

ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ9-tetrahydrocannabinol (THC) and R(+)-methanandamide, a stable endocannabinoid analogue…

Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell susceptibility to LAK cell-mediated cytolysis.

These findings provide proof for a novel antitumorigenic mechanism of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/25069049

http://www.thctotalhealthcare.com/category/lung-cancer/

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Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

CBD prevents excessive lipogenesis induced by “pro-acne agents&#x...

“Acne vulgaris is the most common human skin disease, affecting quality of life of millions worldwide…

Investigation of the cutaneous cannabinoid system seems to be a promising choice when searching for novel therapeutic possibilities…

“Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris…

These data, together with our current findings, point to a promising, cost-effective, and, likely, well-tolerated new strategy for treating acne vulgaris, the most common human skin disease…

…given the extensively documented accumulation of phytocannabinoids from smoked marijuana in the pilosebaceous unit (where they become incorporated into the hair shaft), it is very likely that CBD can reach the sebaceous glands as well, can accumulate, and may well reach “therapeutically sufficient” concentrations there.

Moreover, it is very important to note that, besides the systemic application, one should keep in mind the possibility of the topical administration.”

 http://www.jci.org/articles/view/64628

“Schematic overview of the cellular “anti-acne trinity” of CBD and its proposed mechanism of action.”

Schematic overview of the cellular “anti-acne trinity” of ...

 

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The non-psychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability.

“Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy.

Since the two non-psychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity.

These data suggest that CBDV anti-epileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/25029033

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Long-Term Cannabidiol Treatment Prevents the Development of Social Recognition Memory Deficits in Alzheimer’s Disease Transgenic Mice.

“Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer’s disease (AD).

Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo…

This study is the first to demonstrate CBD’s ability to prevent the development of a social recognition deficit in AD transgenic mice.

Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.”

http://www.ncbi.nlm.nih.gov/pubmed/25024347

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Marijuana Compound CBD Can Effectively Treat Schizophrenia

Marijuana Plant

“Cannabidiol (CBD) is a known marijuana compound, and might just be better than antipsychotics at treating schizophrenia.

A preliminary trial has shown this form of treatment to have fewer side effects than traditional methods of treatment…

Since CBD comes from the marijuana plant, political issues are likely to compromise its availability. Extracting the compound from the plant is also expensive.

But the biggest issue scientists face is that CBD is a natural compound, and can’t be patented the way new drugs are. Pharmaceutical companies are therefore not likely to develop it.”

http://www.designntrend.com/articles/14675/20140529/marijuana-compound-cbd-effectively-treat-schizophrenia.htm

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

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Chemicals in Marijuana May Help Stroke Victims

NewsBriefs

“Scientists at the National Institute of Mental Health (NIMH) said a chemical in marijuana may protect the brain from damage inflicted by a stroke.

Their study was reported in the Proceedings of the National Academy of Sciences (Aidan Hampson, et al., “Cannabidiol and Delta-9-tetrahydrocannabinol Are Neuroprotective Antioxidants,” Proceedings of the National Academy of Sciences, July 7, 1998, Vol. 95, Issue 14, p. 8268; “Pot Chemicals Might Inhibit Breast Tumors, Stroke Damage,” Dallas Morning News, July 13, 1998; Vanessa Thorpe, “Chemicals Help Brain Damage After Stroke,” The Independent (UK), July 19, 1998).

NIMH scientists researched the effects of two cannabinoids, cannabidiol and THC, on the brains of rats. THC is the ingredient in marijuana that causes a psychoactive effect. However, cannabidiol is “a better candidate,” in part, because it does not cause a “high” in the patient, said Aidan Hampson, a neuropharmacologist at NIMH who led the study.

The cannabinoids block a neurochemical, known as glutamate, that leads to the formation of toxic oxidizing molecules that kill brain cells. Glutamate is produced in the brain if the oxygen supply is cut off, for example, as the result of blood clot leading to a stroke.

Researchers found that cannabidiol is a more effective antioxidant than vitamins A and E, which already are known to block the damaging effects of glutamate.”

http://www.ndsn.org/julaug98/medmj1.html

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The Inhibitory Effects of Cannabidiol on Systemic Malignant Tumors

“Cannabidiol may attenuate tumor growth in a number of other systemic malignancies.

Decreased tumor growth in pulmonary malignancies is seen after administration of cannabidiol.

Tumor metastasis also is markedly attenuated.

Similar attenuation of tumor growth is seen in breast malignancies.

The above examples clearly illustrate the significant antineoplastic effects of cannabidiol. Hopefully, the next few years will see increased studies to fully and further evaluate these antineoplastic effects.”

http://www.jpsmjournal.com/article/S0885-3924(13)00115-2/fulltext#article-outline

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

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COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.

Figure 7.

“Within the last decade, evidence has been accumulated to suggest an antitumorigenic action of cannabinoids elicited via induction of apoptosis and alternative anticarcinogenic mechanisms… cannabidiol has been shown to elicit pronounced proapoptotic or autophagic effects on different types of tumor cells

This study investigates the role of COX-2 and PPAR-γ in cannabidiol’s proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis… our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ…

Collectively, our data strengthen the notion that activation of PPAR-γ may present a promising target for lung cancer therapy.

In addition and to the best of our knowledge, this is the first report to provide an inhibitor-proven tumor-regressive mechanism of cannabidiolin vivo as well as a proapoptotic mechanism confirmed by use of primary lung tumor cells.

Against this background and considering recent findings supporting a profound antimetastatic action of cannabidiol, this cannabinoid may represent a promising anticancer drug.”

http://mct.aacrjournals.org/content/12/1/69.long

http://www.thctotalhealthcare.com/category/lung-cancer/

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Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease (Cannabis-SCD) -ClinicalTrials.gov Identifier: NCT01771731

“Cannabinoid-Based Therapy and Approaches to Quantify Pain in Sickle Cell Disease.

Our primary objective is to assess whether inhaling vaporized cannabis ameliorates chronic pain in patients with sickle cell disease (SCD). As these patients will all be on chronic opioid analgesics, the investigators will also assess the possible synergistic affect between inhaled cannabis and opioids.

The investigators will also assess the clinical safety of the concomitant use of cannabinoids and these opioids in patients with SCD by monitoring the short-term side effects associated with combined therapy.

Finally, the investigators will evaluate the short-term effects of inhaled cannabis on markers of inflammation and disease progression in patients with SCD.

Hypotheses are as follows:

  1. Inhaled cannabis will significantly reduce chronic pain in patients with SCD.
  2. Inhaled cannabis will significantly alter the short-term side effects experienced by patients who take opioids for SCD.
  3. Inhaled cannabis will significantly alter markers of inflammation and disease progression in patients with SCD compared to placebo.
Subjects will complete a 5-day pain diary prior to admission to the Clinical Research Center (CRC) to establish a baseline of pain. They will then be assigned to inhale either vaporized cannabis of mixed THC/CBD content (4.7% THC/5.1% CBD) or placebo cannabis (0% THC/0% CBD). Participants and personnel will be blinded as to assignment. Pain will be evaluated during the 5-day inpatient exposure. Participants will be asked to participate in two such 5-day sessions separated by at least a 2-week washout so that each will be exposed to the two experimental conditions.
Detailed Description:

This is a proof-of-principle investigation of the safety and potential effectiveness of inhaled vaporized cannabis when added to a stable analgesic regimen in sickle cell disease (SCD) patients with chronic pain. The study will be comprised of two 5-day intervention periods in the inpatient setting (the Clinical Research Center at SFGH), with completion of a 5-day daily pain diary prior to admission to establish an outpatient baseline. Participants will be randomly assigned, in double-blind fashion, to treatment with (A) vaporized cannabis with an approximately 1:1 ration of delta-9-tetrahydrocannabinol:cannabidiol or (B) vaporized placebo. Those who receive treatment A during the first admission will receive treatment B in the second, and those who receive treatment B during the first admission will receive treatment A in the second. The two admissions will be spaced at least 14 days apart.

On Day 1 of each admission, subjects will provide blood samples for baseline markers of inflammation and SCD disease progression. They will undergo assessments of pain, mood, and quality of life. At 12 pm on Day 1, they will inhale vaporized study agent (equivalent to 1 cannabis/placebo cigarette) using the Volcano® vaporizer; on Days 2-4 they will inhale study agent at 8 am, 2 pm, and 8 pm, and they will inhale their final dose on Day 5 at 8 am. Subjects will continue their pre-study analgesic regimen while in the study. If additional analgesia is required, supplemental therapy will be administered and the dose recorded. Pain measurements by visual analogue scale will be obtained every 2 hours while subjects are awake. On Day 5 a second set of blood samples for inflammation markers and disease progression will be obtained, and subjects will again complete pain, mood, and quality of life assessments.”

http://www.clinicaltrials.gov/ct2/show/study/NCT01771731#contacts

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Targeting multiple cannabinoid antitumor pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

“The psychoactive cannabinoid Δ9 -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol(CBD) can both reduce cancer progression each through distinct antitumor pathways.

Our goal was to discover a compound that could efficiently target both cannabinoid antitumor pathways.

KEY RESULTS:

CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogs that could co-target cannabinoid antitumor pathways (CBD- and THC-associated) and discovered the compound O-1663. This analog inhibited Id1, produced a marked stimulation of ROS, upregulated autophagy, and induced apoptosis. Of all compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo.

CONCLUSIONS AND IMPLICATIONS:

O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid antitumor pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/24910342

“Anti-cancer effects of resorcinol derivatives on ascitic and solid forms of Ehrlich carcinoma in mice.” http://www.ncbi.nlm.nih.gov/pubmed/13774935

“Ardisiphenol D, a resorcinol derivative identified from Ardisia brevicaulis, exerts antitumor effect through inducing apoptosis in human non-small-cell lung cancer A549 cells.” http://www.ncbi.nlm.nih.gov/pubmed/24392814

“Antitumor effect of resorcinol derivatives from the roots of Ardisia brevicaulis by inducing apoptosis.” http://www.ncbi.nlm.nih.gov/pubmed/21751842

“Resorcinol derivatives from Ardisia maculosa.”  http://www.ncbi.nlm.nih.gov/pubmed/17885843

http://www.thctotalhealthcare.com/category/breast-cancer/

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