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

“Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions.” https://www.ncbi.nlm.nih.gov/pubmed/28412918

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

Man Uses Cannabis Oil to Successfully Treat Another Incurable Disease – COPD

marijuana jeff waters 263x164 Man Uses Cannabis Oil to Successfully Treat Another Incurable Disease – COPD

“COPD, or Chronic Obstructive Pulmonary Disease, ranks third in disease death rates, behind only heart disease and cancer. COPD creates constricted airways in one’s lungs or renders small lung sacks within inelastic and unable to fully accommodate breathing cycles, thus the lungs are obstructed. The pharmaceuticals prescribed for treating symptoms often have side effects that cause more problems, so maybe it’s time to shed light on alternative solutions – marijuana.

Maybe It’s Medical Marijuana Time?

The treatment situation is so bleak with mainstream medicine that those desperate to breathe normally and experience less coughing with mucus have turned to medical marijuana for at least some relief without negative side effects.

Smoking marijuana joints is shunned for obvious reasons, but many claim that vaping, or using a vaporizer to inhale cannabis, is useful for COPD without exacerbating the lungs’ inflammatory condition.

Even better results have been achieved by ingesting cannabis…

A COPD/Cannabis Success Story

At the young age of 36, Jeff Waters was diagnosed with COPD. Eight years later he had to be rushed to an ER during another bout with bronchitis. Lung scarring was discovered and his condition was raised to stage 2 COPD. While prescribing several pharmaceuticals, the doctor told him it would continue to get worse and eventually kill him.

Jeff continued to get worse. He was unable to climb a flight of stairs and wound up as a stage 3 COPD with an oxygen tank to prove it. Showering and shaving turned out to be almost impossible. An allergic reaction to a prescribed high blood pressure medication put him into life support in ICU with severe pneumonia for a month. After his recovery, he resolved to handle his COPD without mainstream medical interventions.

Jeff found COPD sufferers online who had resolved their COPD issues with cannabis oil, so he networked with them and found his own sources for cannabis oil. After only two months of using the oil, Jeff went off oxygen and all the pharmaceuticals he had been prescribed. He now walks two to five miles daily and claims cannabis oil has allowed him “to get his life back”.”

http://naturalsociety.com/cannabis-oil-proving-successful-another-incurable-disease-copd/

“Personal Testimony: Cannabis Vs. COPD, meet Jeff”  http://heavens2betsey.com/personal-testimony-cannabis-vs-copd-meet-jeff/

copd

http://www.thctotalhealthcare.com/category/copd-chronic-obstructive-pulmonary-disease/

Cannabis oil from marijuana is having success treating COPD

COPD

“COPD is the often used term for “Chronic Obstructive Pulmonary Disease,” a rather clumsy and vague description for most of us. It includes a few different lung issues, such as emphysema, bronchiectasis and chronic bronchitis. The scary part is that it’s a mystery to our pharmaceutical-dependent medical system. And it gets progressively worse, often leading to death.

It’s third in disease death rates, behind only heart disease and cancer. COPD creates constricted airways in one’s lungs or renders small lung sacks inelastic and unable to fully accommodate breathing cycles; thus, there is obstruction.

COPD symptoms include some or all of the following: losing one’s breath with minor activity, chronic coughing, increased sputum, chest tightness or pain with difficulty breathing, increased lung infections and fatigue. It has been observed to have four stages. Many of those lugging oxygen canisters around are in the last two stages.

The pharmaceuticals prescribed for treating symptoms often have side effects that cause more problems. Big Pharma is still fishing for cures, while COPD diagnoses rates continue rising in our toxic environment.

Medical marijuana to the rescue once again

The treatment situation is so bleak and harmful with mainstream medicine that those desperate to breathe normally and cough up less mucus have desperately turned to medical marijuana for at least some relief without negative side effects.

Smoking marijuana cigarettes is shunned for obvious reasons, but many claim that vaping, or using a vaporizer to inhale cannabis, is useful for COPD without exacerbating the lungs’ inflammatory condition.

But better results have been achieved by ingesting cannabis, especially the potent, highly condensed oil extract that Rick Simpson pioneered in Canada and now in Eastern Europe. Many medical marijuana advocates, especially those in medical-cannabis-friendly states, have learned to make the oil and provide it to those in need.

Most of the cannabis treatment publicity has gone toward cancer, Crohn’s disease, chronic epileptic seizures and glaucoma. Even Parkinson’s disease and multiple sclerosis victims have experienced positive results from various cannabis products with THC applications.

Pharmaceutical-dependent mainstream medicine hasn’t been able to cure any of these diseases or even alleviate symptoms without creating complications, some fatal.

More COPD patients have hopped on the cannabis cure bandwagon with positive results lately. These results include folks with late-stage COPD and severe emphysema.

An anecdotal sampling

At the relatively young age of 36, Jeff Waters was diagnosed with COPD. Eight years later he had to be rushed to an ER during another bout with bronchitis.

Lung scarring was discovered, and his condition was raised to stage 2 COPD. While prescribing several pharmaceuticals, the doctor told him that it would continue to get worse and eventually kill him.

Jeff did continue to get worse. He was unable to climb a flight of stairs and he wound up with stage 3 COPD and an oxygen canister to prove it. Showering and shaving without his oxygen supply turned out to be almost too arduous of a task.

Then an allergic reaction to a prescribed high blood pressure medication put him on life support in ICU with severe pneumonia for a month. After his recovery, he resolved to handle his COPD without mainstream medical interventions.

Jeff found COPD sufferers online who had resolved their COPD issues with cannabis oil. He networked with them and found his own sources for cannabis oil.

After only two months of using the oil, Jeff went off oxygen and all the pharmaceuticals he had been prescribed. He now walks two to five miles daily and claims that cannabis oil has allowed him “to get his life back.””

http://www.naturalnews.com/044664_cannabis_oil_copd_marijuana.html

http://www.thctotalhealthcare.com/category/copd-chronic-obstructive-pulmonary-disease/

Smoking Marijuana Relieves Symptoms of Multiple Sclerosis in Patients, with Minor Cognitive Effects

marijuana

“Smoking marijuana has been shown to relieve muscle tightness, called spasticity, and painful symptoms in patients with multiple sclerosis, who have been resistant to conventional MS therapies, according to a new study.

“We found that smoked cannabis was superior to placebo in reducing symptoms and pain in patients with treatment-resistant spasticity, or excessive muscle contractions,” Researcher Dr. Jody Corey-Bloom, director of the University of California, San Diego Multiple Sclerosis Center said in a journal news release.”

http://www.medicaldaily.com/smoking-marijuana-relieves-symptoms-multiple-sclerosis-patients-minor-cognitive-effects-240433

“Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394820/

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Marijuana Helps Relieve MS Pain

“Researchers from the University of California, San Diego School of Medicine have found that smoking marijuana can help relieve pain, and muscle tightness “spasticity” in individuals with multiple sclerosis (MS). The study is published in the Canadian Medical Association Journal (CMAJ).”

http://www.medicalnewstoday.com/articles/245430.php

“Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394820/

Antagonism of cannabinoid receptor 2 pathway suppresses IL-6-induced immunoglobulin IgM secretion.

“Cannabinoid receptor 2 (CB2) is expressed predominantly in the immune system, particularly in plasma cells, raising the possibility that targeting the CB2 pathway could yield an immunomodulatory effect.

Although the role of CB2 in mediating immunoglobulin class switching has been reported, the effects of targeting the CB2 pathway on immunoglobulin secretion per se remain unclear…

These results uncover a novel function of CB2 antagonists and suggest that CB2 ligands may be potential modulators of immunoglobulin secretion.”

Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia

Figure 1

“Although cannabinoids have been used for millennia for treating pain and other symptoms, their mechanisms of action remain obscure.

With the heralded identification of multiple G-protein-coupled receptors (GPCRs) mediating cannabinoid effects nearly two decades ago, the mystery of cannabinoid pharmacology was thought to be solved…

Despite the wealth of information on cannabinoid-induced peripheral antihyperalgesic and antinociceptive effects in many pain models, the molecular mechanism(s) for these actions remains unknown.

Although metabotropic cannabinoid receptors have important roles in many pharmacological actions of cannabinoids, recent studies have led to the recognition of a family of at least five ionotropic cannabinoid receptors (ICRs). The known ICRs are members of the family of transient receptor potential (TRP) channels and include TRPV1, TRPV2, TRPV4, TRPM8 and TRPA1.

Cannabinoid activation of ICRs can result in desensitization of the TRPA1 and TRPV1 channel activities, inhibition of nociceptors and antihyperalgesia and antinociception in certain pain models.

Thus, cannabinoids activate both metabotropic and ionotropic mechanisms to produce peripheral analgesic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863326/

TRP Channel Cannabinoid Receptors in Skin Sensation, Homeostasis, and Inflammation.

“In the skin, cannabinoid lipids, whether of endogenous or exogenous origin, are capable of regulating numerous sensory, homeostatic and inflammatory events.

Although many of these effects are mediated by metabotropic CB receptors, a growing body of evidence has revealed that multiple members of the transient receptor potential (TRP) ion channel family can act as “ionotropic cannabinoid receptors”.

Furthermore, many of these same TRP channels are intimately involved in cutaneous processes that include the initiation of pain, temperature, and itch perception, the maintenance of epidermal homeostasis, the regulation of hair follicles and sebaceous glands, and the modulation of dermatitis.

Ionotropic cannabinoid receptors therefore represent potentially attractive targets for the therapeutic use of cannabinoids to treat sensory and dermatological diseases.

Furthermore, the interactions between neurons and other cell types that are mediated by cutaneous ionotropic cannabinoid receptors are likely to be recapitulated during physiological and pathophysiological processes in the central nervous system and elsewhere, making the skin an ideal setting in which to dissect general complexities of cannabinoid signaling.”

http://www.ncbi.nlm.nih.gov/pubmed/24915599

Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders.

Publication cover image

“Immune system responsiveness results from numerous factors, including endogenous cannabinoid signaling in immunocytes termed the “immunocannabinoid” system. This system can be an important signaling pathway for immune modulation.

To assess the immunomodulating role of the cannabinoid 2 (CB2) receptor, we sought polymorphisms in the human gene, identified a common dinucleotide polymorphism, and investigated its effect on endocannabinoid-induced inhibition of T lymphocyte proliferation.

Collectively, these results demonstrate reduced endogenous fatty acid amide immunomodulatory responses in individuals with the CB2 188-189 GG/GG genotype and suggest that this CB2 gene variation may be a risk factor for autoimmunity.

The results also support the proposition that the CB2 receptor may represent a novel pharmacological target for selective agonists designed to suppress autoreactive immune responses”

https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.0205111

https://www.ncbi.nlm.nih.gov/pubmed/15845647

Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoimmune Disease.

“The impact of the endogenous cannabinoids (AEA, 2-AG, PEA, and virodamine) on the immune cell expressed cannabinoid receptors (CB1, CB2, TRPV-1, and GPR55) and consequent regulation of immune function is an exciting area of research with potential implications in the prevention and treatment of inflammatory and autoimmune diseases.

Despite significant advances in understanding the mechanisms through which cannabinoids regulate immune functions, not much is known about the role of endocannabinoids in the pathogenesis or prevention of autoimmune diseases.

Inasmuch as CB2 expression on immune cells and its role has been widely reported, the importance of CB1 in immunological disorders has often been overlooked especially because it is not highly expressed on naive immune cells.

Therefore, the current review aims at delineating the effect of endocannabinoids on CB1 receptors in T cell driven autoimmune diseases. This review will also highlight some autoimmune diseases in which there is evidence indicating a role for endocannabinoids in the regulation of autoimmune pathogenesis.

Overall, based on the evidence presented using the endocannabinoids, specifically AEA, we propose that the peripheral CB1 receptor is involved in the regulation and amelioration of inflammation associated with autoimmune diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/24911431