Endocannabinoid System, Cannabinoid Receptors, and Cannabinoids CURING Cancer

Cannabis holds many healing properties that are slowly being unraveled.  Since the 60’s it has been known that the human body contains an Endocannabinoid system that interacts with cannabis.  Since then science has discovered many things and continues in the search for the key to unlocking the cure.  Many believe in the power of cannabis to cure many things including cancer.  Scientists are hard at work trying to prove the very same thing.  Below you will see studies that show how science has unlocked some mysteries.  These are valid published medical studies dealing with out endocannabinoid system please feel free to share ~ Cherry Girl

Cannabinoids In the Treatment of Cancer
Cannabinoids, the active components of the hemp plant Cannabis sativa, along with their endogenous counterparts and synthetic derivatives, have elicited anti-cancer effects in many different in vitro and in vivo models of cancer. While the various cannabinoids have been examined in a variety of cancer models, recent studies have focused on the role of cannabinoid receptor agonists (both CB(1) and CB(2)) in the treatment of estrogen receptor-negative breast cancer. This review will summarize the anti-cancer properties of the cannabinoids, discuss their potential mechanisms of action, as well as explore controversies surrounding the results.

Changes In the Endocannabinoid System May Give Insight Into New and Effective Treatments For Cancer
Marijuana and its derivatives have been used in medicine for centuries, however, it was not until the isolation of the psychoactive component of Cannabis sativa (Δ9-tetrahydrocannabinol; Δ9-THC) and the subsequent discovery of the endogenous cannabinoid signaling system that research into the therapeutic value of this system reemerged. Ongoing research is determining that regulation of theendocannabinoid system may be effective in the treatment of pain, glaucoma, and neurodegenerative disorders such as Parkinson’s disease and multiple sclerosis. In addition, cannabinoids might be effective anti-tumoral agents because of their ability to inhibit the growth of various types of cancer cell lines.   In conclusion, the endocannabinoid system exerts a myriad of effects on tumor cell growth, progression, angiogenesis, and migration. With a notable few exceptions, targeting the endocannabinoid system with agents that activate cannabinoid receptors or increase the endogenous levels of AEA may prove to have therapeutic benefit in the treatment of various cancers. Further studies into the downstream consequences of AEA treatment are required and may illuminate other potential therapeutic targets.

The Endocannabinoid System and Cancer: Therapeutic Implication
Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis-like compounds offer therapeutic potential for the treatment of breast, prostate and bone cancer in patients.

Endocannabinoids As Emerging Suppressors of Angiogenesis and Tumor Invasion
The medicinal properties of extracts from the hemp plant Cannabis sativa have been known for centuries but only in the 90s membrane receptors for the Cannabis major principle were discovered in mammalian cells…endocannabinoids are now emerging as suppressors of angiogenesis and tumor spreading since they have been reported to inhibit angiogenesis, cell migration and metastasis in different types of cancer, pointing to a potential role of the endocannabinoid system as a target for a therapeutic approach of such malignant diseases. The potential use of cannabinoids to retard tumor growth and spreading is even more appealing considering that they show a good safety profile, regarding toxicity, and are already used in cancer patients as palliatives to stimulate appetite and to prevent devastating effects such as nausea, vomiting and pain.

Therapeutic Target-In-Waiting
CB(2) cannabinoid receptor agonists hold promise as a new class of therapeutics for indications as diverse as pain, neuroinflammation, immune suppression and osteoporosis. These potential indications are supported by strong preliminary data from multiple investigators using diverse preclinical models.

Cannabidiol Inhibits Lung Cancer Cell Invasion and Metastasis Via Intercellular Adhesion Molecule-1
Overall, our data indicate that cannabinoids induce ICAM-1, thereby conferring TIMP-1 induction and subsequent decreased cancer cell invasiveness.

Cannabinoid Receptor 1 is A Potential Drug Target For Treatment of Translocation-Positive Rhabdomyosarcoma
Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma.Our study shows that treatment with the cannabinoid receptor agonists HU210 and Delta(9)-tetrahydrocannabinol lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis.These results support the notion that cannabinoid receptor agonists represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma.

PAX3-FOXO1 Induces Cannabinoid Receptor 1 to Enhance Cell Invasion and Metastasis
Alveolar rhabdomyosarcoma (ARMS) is a muscle-derived childhood tumor characterized by production of oncogenic PAX3/7-FOXO1 chimeric transcription factors…Genetic or pharmacologic abrogation of (Cnr1/Cb1) inhibited the enhanced basement membrane invasion induced by PAX3-FOXO1. Cnr1 loss by either route also dramatically reduced lung metastasis formation. Taken together, our findings strongly implicate Cnr1 as a novel tractable target to inhibit ARMS invasion and metastasis.

The Endocannabinoid System In Cancer-Potential Therapeutic Target?
Endogenous arachidonic acid metabolites with properties similar to compounds of Cannabis sativa Linnaeus, the so-called endocannabinoids, have effects on various types of cancer. Although endocannabinoids and synthetic cannabinoids may have pro-proliferative effects, predominantly inhibitory effects on tumor growth, angiogenesis, migration and metastasis have been described. Remarkably, these effects may be selective for the cancer cells, while normal cells and tissues are spared. Such apparent tumor cell selectivity makes the endocannabinoid system an attractive potential target for cancer therapy.

 

 

Targeting Our Endocannabinoid System:Search For Nature’s Cure

The endocannabinoid system was discovered in the 1960’s and since then scientists have been hard at work trying to unravel the mysteries.  Below you will see studies showing how the endocannabinoid system within the human body is at the center for learning how to treat many illnesses and diseases. Please feel free to share the truth about the CURE ~ Cherry Girl

Endocannabinoids In The Immune System and Cancer
Although its action as an immunomodulatory molecule requires further characterization, modulation of the endocannabinoid system interferes with cancer cell proliferation either by inhibiting mitogenic autocrine/paracrine loops or by directly inducing apoptosis.   In conclusion, further investigations are needed to elucidate the function of endocannabinoids as immunosuppressant and antiproliferative/cytotoxic agents. The experimental evidence reviewed in this article argues in favor of the therapeutic potential of these compounds in immune disorders and cancer.

Endocannabinoid System Modulation In Cancer Biology and Therapy
The discovery of the endocannabinoid system and the recognition of its impact in a plethora of pathological conditions, led to the development of therapeutic agents related to either the stimulation or antagonism of CB1 and CB2 cannabinoid receptors…Endocannabinoid-related agents have been reported to affect multiple signaling pathways and biological processes involved in the development of cancer, displaying an interesting anti-proliferative, pro-apoptotic, anti-angiogenic and anti-metastatic activity both in vitro and in vivo in several models of cancer. Emerging evidence suggests that agonists of cannabinoid receptors, which share the useful property to discern between tumor cells and their non-transformed counterparts, represent novel tumor-selective tools to treat cancer in addition to their already exploited use as palliative drugs to treat chemotherapy-induced nausea, pain and anorexia/weight loss in cancer patients.

Possible Endocannabinoid Control Of Colorectal Cancer Growth
CONCLUSIONS: Endocannabinoid levels are enhanced in transformed colon mucosa cells possibly to counteract proliferation via CBRs. Inhibitors of endocannabinoid inactivation may prove useful anticancer agents

Cannabinoids, Endocannabinoids, and Cancer
Modulation of the endocannabinoid system by pharmacological agents in various cancer types reveals that it can mediate antiproliferative and apoptotic effects by both cannabinoid receptor-dependent and -independent pathways…the endocannabinoid system is a promising target for the development of novel chemotherapeutics to treat cancer.

The Endocannabinoid System As A Target For The Development Of New Drugs For Cancer Therapy
stimulation of cannabinoid receptors by either THC or the endocannabinoids influence the intracellular events controlling the proliferation and apoptosis of numerous types of cancer cells, thereby leading to anti-tumour effects both in vitro and in vivo

Newly Released Studies That Show Medical Value Of Cannabis 2011

As we see this year come to a close it is time to look back over 2011 and view the studies that were released this year that show cannabis to be a treatment option or a cure for an illness.  Please share the truth about cannabis ~ Cherry Girl

Cannabinoid Receptor Type 1 (CB1) Activation Inhibits Small GTPase RhoA Activity and Regulates Motility of Prostate Carcinoma Cells 
Cannabinoid receptor 1 activation stops and controls the growth of prostate cancer cells.

Cannabinoid Receptor 1 Gene is Associated With Alcohol Dependence
Cannabinoid receptor 1 is involved in alcoholism. CB1 is the target for treatment.

CB(1) Receptor Activation Inhibits Neuronal and Astrocytic Intermediary Metabolism in the Rat Hippocampus
In conclusion, CB(1)Rs are able to control hippocampal intermediary metabolism in both neuronal and glial compartments, which suggests new alternative mechanisms by which CB(1)Rs control cell physiology and afford neuroprotection.

Prevention and Treatment of Alzheimer’s Disease With Cannabis

It is estimated that 5.1 million Americans may have Alzheimer’s disease. Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks.  Alzheimer’s disease is the most common cause of dementia among older people. Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—and behavioral abilities.  Scientists have been working on finding a cure for this debilitating disease.  One option was cannabis.  Below you will find several studies where cannabis was studied for Alzheimer’s Disease please share the truth about the CURE ~ Cherry Girl

Alzheimer’s Disease; Taking the Edge Off With Cannabinoids?
Manipulation of the cannabinoid pathway offers a novel pharmacological approach for the treatment of AD that may be more efficacious than current treatment regimes. Cannabinoids can reduce the oxidative stress, neuroinflammation and apoptosis that is evoked by Aβ, while promoting the brain’s intrinsic repair mechanisms.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190031/?tool=pubmed

Multi-Target-Directed Ligands in Alzheimer’s Disease Treatment.
AD is related to increased levels of the amyloid β peptide (A β) and the hyperphosphorylated tau protein, along with loss of neurons and synapses. Moreover, there is some evidence pointing to the role of oxidative stress, metal ion deregulation, inflammation and cell cycle regulatory failure in its pathogenesis. There are many attractive targets for the development of anti-AD drugs, and the multi-factor nature of this disease calls for multi-target-directed compounds which can be beneficial for AD treatment.
http://www.ncbi.nlm.nih.gov/pubmed/22050745

The Endocannabinoid System and Alzheimer’s Disease.
If you want to understand why CANNABINOIDS CURE, you need to know about the endoCANNABINOID SYSTEM. Cannabinoids CURE because of cannabinoid receptors and the endoCANNABINOID SYSTEM. Cannabis CURES ALzheimer’s and more, via the endoCANNABINOID SYSTEM: “Data obtained for this disease and in human samples seem to corroborate the notion that the activation of the ECS, through the use of agonists or by enhancing the endogenous cannabinoid tone, may induce beneficial effects on the evolution of this disease.
http://www.ncbi.nlm.nih.gov/pubmed/17952652

Cannabinoid System in Neurodegeneration: New Perspectives In Alzheimer’s Disease 
Alzheimer’s disease is a chronic and progressive neurodegenerative disorder. The presence of functional cannabinoid CB2 receptors in central nervous system (CNS) has provoked that this receptor and its agonist ligands are now considered as promising pharmacological targets for neurological diseases.
http://www.ncbi.nlm.nih.gov/pubmed/19456285

Cannabinoids As Therapeutic Agents For Ablating Neuroinflammatory Disease
Ablate means to remove or destroy biologically. Keep that in mind when reading this: “Cannabinoids may serve as ideal agents for adjunct treatment of pathological processes that have a neuroinflammatory component.As highly lipophilic molecules, they readily access the brain.Furthermore, they have relatively low toxicity and can be engineered to selectively target cannabinoid receptors. The cannabinoid-cannabinoid receptor system may prove therapeutically manageable in ablating neuropathogenic disorders such as Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, HIV encephalitis, closed head injury, and granulomatous amebic encephalitis.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750822/?tool=pubmed

The Role of the Endocannabinoid System in Alzheimer’s Disease: Facts and Hypotheses
There is evidence, from in vivo studies on beta-amyloid-induced neurotoxicity, also for a possible causative role of endocannabinoids in the impairment in memory retention, which is typical of AD. This might open the way to the use of cannabinoid receptor antagonists as therapeutic drugs for the treatment of cognitive deficits in the more advanced phases of this disorder. The scant, but nevertheless important literature on the regulation and role of the endocannabinoid system in AD, and on the potential treatment of this disorder with cannabinoids and endocannabinoid-based drugs, are discussed in this mini-review.
http://www.ncbi.nlm.nih.gov/pubmed/18781980

Role of CB2 Receptors in Neuroprotective Effects of Cannabinoids
Given the lack of psychoactivity demonstrated by selective CB2 receptor agonists, this receptor becomes an interesting target for the treatment of neurological diseases, in particular, certain neurodegenerative disorders in which induction/up-regulation of CB2 receptors has been demonstrated. These disorders include Alzheimer’s disease and others. In experimental models, the activation of CB2 receptors has been related to a delayed progression of neurodegenerative events. The present article will review the evidence supporting that CB2 receptors might represent a key element in the endogenous response against different types of cytotoxic events, and that this receptor type may be a clinically promising target for the control of brain damage in neurodegenerative disorders.
http://www.ncbi.nlm.nih.gov/pubmed/18291574

Stimulation of Cannabinoid Receptor 2 (CB2) Suppresses Microglial Activation
Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer’s disease (AD). Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB2). These results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB2 modulation in neurodegenerative diseases, particularly AD.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1352348/?tool=pubmed

Effects of Cannabinoids on the Immune System and Central Nervous System: Therapeutic Implications
‎1999: “Cannabinoids possess immunomodulatory activity, are neuroprotective in vivo and in vitro and can modify the production of inflammatory mediators… Cannabinoid-induced immunosuppression may have implications for the treatment of neurological disorders that are associated with excess immunological activity, such as multiple sclerosis and Alzheimer’s disease.There is anecdotal evidence thatcannabis use improves the symptoms of multiple sclerosis, and studies with animal models are beginning to provide evidence for the mechanism of such effects. The development of nonpsychotropic cannabinoid analogues and modulators of the metabolism of endogenous cannabinoid ligands may lead to novel approaches to the treatment of neurodegenerative disorders.
http://www.ncbi.nlm.nih.gov/pubmed/18031185

A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology
A link between the endocannabinoid system and Alzheimer’s disease has been discovered which has provided a new therapeutic target for the treatment of patients suffering from Alzheimer’s disease.New targets for this debilitating disease are critical as Alzheimer’s disease afflicts over 20 million people worldwide, with the number of diagnosed cases continuing to rise at an exponential rate.These studies have demonstrated the ability of cannabinoids to provide neuroprotection against β-amyloid peptide (Aβ) toxicity.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/?tool=pubmed

Cannabidiol: From An Inactive Cannabinoid to A Drug With Wide Spectrum of Action
The last five years have shown a remarkable increase in publications on cannabidiol mainly stimulated by the discovery of its anti-inflammatory, anti-oxidative and neuroprotective effects. Studies have suggested a wide range of therapeutic effects of cannabidiol on several conditions, including Alzheimer’s disease, cancer, etc…In the last 45 years it has been possible to demonstrate that CBD has a wide range of pharmacological effects, many of which being of great therapeutic interest, but still waiting to be confirmed by clinical trials.
http://www.ncbi.nlm.nih.gov/pubmed/18833429

Delta-9-tetrahydrocannabinol For Nighttime Agitation In Severe Dementia
Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today. Current treatment options are few and limited due to substantial side effects. CONCLUSIONS: The study suggests that THC (Dronabinol) was able to reduce nocturnal motor activity and agitation in severely demented patients. Thus, it appears that THC (Dronabinol) may be a safe new treatment option for behavioral and circadian disturbances in dementia.
http://www.ncbi.nlm.nih.gov/pubmed/16521031

The Seek of Neuroprotection: Introducing Cannabinoids
2007: The Endocannabinoid System (ECS) is emerging as a natural system of neuroprotection. This consideration is based on properties of cannabinoids as vasodilatory effect, inhibition of the release of excitotoxic amino acids and cytokines, and the modulation of oxidative stress and toxic production of nitric oxide. Such effects have been demonstrated in models of acute and chronic neurodegenerative conditions, and postulate cannabinoids as valuable neuroprotective agents. Patents related to cannabinoid receptors are also discussed.
http://www.ncbi.nlm.nih.gov/pubmed/18221224

CB2 Receptors in the Brain: Role in Central Immune Function – Cebral
The topic is neuroinflammation, which is relevant to Alzheimer’s and more. Ablation means removing or destroying biologically: “Selective targeting of the Cannabinoid Receptor 2 (CB2R) could lead to ablation of neuropathological processes while minimizing psychotropic effects that could be exerted by activation of the CB1R.
http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0707584/full

Cannabidiol and Other Cannabinoids Reduce Microglial Activation in Vitro and in Vivo: Relevance to Alzheimer’s Disease
Microglial activation is an invariant feature of Alzheimer’s disease (AD). It is noteworthy that cannabinoids are neuroprotective by preventing β-amyloid (Aβ)-induced microglial activation both in vitro and in vivo. CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD. Given that CBD lacks psychoactivity, it may represent a novel therapeutic approach for this neurological disease.
http://www.ncbi.nlm.nih.gov/pubmed/21350020

Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation
Cannabinoids prevent Alzheimer’s Disease: Cannabis protects the brain by blocking microglial activation. “Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease. Because cannabinoids combine both anti-inflammatory and neuroprotective actions, our findings may set the basis for the use of these compounds as a therapeutic approach for AD.
http://www.jneurosci.org/content/25/8/1904.long

A Natural Choice For Pain Management

Most people do not know what it is like to be in pain every day but for the millions of Americans that do it can be difficult to live with.  When you wake up and go to sleep in pain it wears on you.  It can cause depression to set in.  When the pain is constant people seek out relief but sometimes find there is no easy answer.

Many seek help from traditional medicine only to find that it is costly, makes symptoms worse or causes unwanted side effects.   Pain management is a booming industry.  America is addicted to pain medications.  15,000 people in 2008 died from overdoses of legal prescription painkillers — more than died from heroin and cocaine overdoses combined.

But there is a natural way to relieve pain and modern science is slowly figuring out what millions already know.  Cannabis is not a new designer drug but has been around for thousands of years.  It was once used medicinally for a myriad of reasons.  With prohibitions for the last 75 years it has been difficult for science to unravel the mysteries.  Below you will see studies that show how cannabis can help with pain management.  Please Share with truth about the CURE!

Cannabinoid Receptors and Pain
The discovery of this ‘endocannabinoid system’ has prompted the development of a range of novel cannabinoid receptor agonists and antagonists, including several that show marked selectivity for CB(1) or CB(2) receptors. The endocannabinoid system has physiological and/or pathophysiological roles in the modulation of pain.”
Cannabinoid receptors and pain.
Pertwee RG. SourceDepartment of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Scotland, Aberdeen, UK. rgp@aberdeen.ac.uk

Abstract
Mammalian tissues contain at least two types of cannabinoid receptor, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB(2) receptors occur centrally and peripherally in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. The discovery of this ‘endocannabinoid system’ has prompted the development of a range of novel cannabinoid receptor agonists and antagonists, including several that show marked selectivity for CB(1) or CB(2) receptors. It has also been paralleled by a renewed interest in cannabinoid-induced antinociception. This review summarizes current knowledge about the ability of cannabinoids to produce antinociception in animal models of acute pain as well as about the ability of these drugs to suppress signs of tonic pain induced in animals by nerve damage or by the injection of an inflammatory agent. Particular attention is paid to the types of pain against which cannabinoids may be effective, the distribution pattern of cannabinoid receptors in central and peripheral pain pathways and the part that these receptors play in cannabinoid-induced antinociception. The possibility that antinociception can be mediated by cannabinoid receptors other than CB(1) and CB(2) receptors, for example CB(2)-like receptors, is also discussed as is the evidence firstly that one endogenous cannabinoid, anandamide, produces antinociception through mechanisms that differ from those of other types of cannabinoid, for example by acting on vanilloid receptors, and secondly that the endocannabinoid system has physiological and/or pathophysiological roles in the modulation of pain.
http://www.ncbi.nlm.nih.gov/pubmed/11164622 

The Future of Cannabinoids As Analgesic Agents: A Pharmacologic, Pharmacokinetic, and Pharmacodynamic Overview
Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders.”— So, in the future, cannabis will be an “extremely valuable tool for treating a number of currently intractable disorders.
The future of cannabinoids as analgesic agents: a pharmacologic, pharmacokinetic, and pharmacodynamic overview. McCarberg BH, Barkin RL. SourceFamily Medicine Kaiser Permanente, Escondido, California, USA. Bill.H.Mccarberg@kp.org

Abstract
For thousands of years, physicians and their patients employed cannabis as a therapeutic agent. Despite this extensive historical usage, in the Western world, cannabis fell into disfavor among medical professionals because the technology available in the 1800s and early 1900s did not permit reliable, standardized preparations to be developed. However, since the discovery and cloning of cannabinoid receptors (CB1 and CB2) in the 1990s, scientific interest in the area has burgeoned, and the complexities of this fascinating receptor system, and its endogenous ligands, have been actively explored. Recent studies reveal that cannabinoids have a rich pharmacology and may interact with a number of other receptor systems-as well as with other cannabinoids-to produce potential synergies. Cannabinoids-endocannabinoids, phytocannabinoids, and synthetic cannabinoids-affect numerous bodily functions and have indicated efficacy of varying degrees in a number of serious medical conditions. Nevertheless, despite promising preclinical and early clinical data, particularly in the areas of inflammation and nociception, development challenges abound. Tetrahydrocannabinol (THC) and other CB1 receptor agonists can have an undesirable CNS impact, and, in many cases, dose optimization may not be realizable before onset of excessive side effects. In addition, complex botanically derived cannabinoid products must satisfy the demanding criteria of the U.S. Food and Drug Association’s approval process. Recent agency guidance suggests that these obstacles are not insurmountable, although cannabis herbal material (“medical marijuana”) may present fatal uncertainties of quality control and dosage standardization. Therefore, formulation, composition, and delivery system issues will affect the extent to which a particular cannabinoid product may have a desirable risk-benefit profile and acceptable abuse liability potential. Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders. Further research is warranted to explore the therapeutic potential of this area.
http://www.ncbi.nlm.nih.gov/pubmed/17890938

Role of Cannabinoids in the Treatment of Pain and (Painful) Spasticity
In chronic pain and (painful) spasticity, an increasing number of randomized, double-blind, placebo-controlled studies have shown the efficacy of cannabinoids. Patients with unsatisfactory response to other methods of pain therapy and who were characterized by failed stress adaptation particularly benefited from treatment with cannabinoids. Different methods of administration and other types of cannabinoids, such as endocannabinoid modulators, should be tested in future trials.
Role of cannabinoids in the treatment of pain and (painful) spasticity.
Karst M, Wippermann S, Ahrens J. SourceDepartment of Anaesthesiology, Pain Clinic, Hannover Medical School, Hannover, Germany. karst.matthias@mh-hannover.de

Abstract
Both the discovery of the endocannabinoid system (ECS) and its role in the control of pain and habituation to stress, as well as the significant analgesic and antihyperalgesic effects in animal studies, suggest the usefulness of cannabinoids in pain conditions. However, in human experimental or clinical trials, no convincing reduction of acute pain, which may be caused by a pronociceptive, ECS-triggered mechanism on the level of the spinal cord, has been demonstrated. In contrast, in chronic pain and (painful) spasticity, an increasing number of randomized, double-blind, placebo-controlled studies have shown the efficacy of cannabinoids, which is combined with a narrow therapeutic index. Patients with unsatisfactory response to other methods of pain therapy and who were characterized by failed stress adaptation particularly benefited from treatment with cannabinoids. None of the attempts to overcome the disadvantage of the narrow therapeutic index, either by changing the route of application or by formulating balanced cannabinoid preparations, have resulted in a major breakthrough. Therefore, different methods of administration and other types of cannabinoids, such as endocannabinoid modulators, should be tested in future trials.
http://www.ncbi.nlm.nih.gov/pubmed/21142261

The Role of Endocannabinoids in Pain Modulation and the Therapeutic Potential of Inhibiting Their Enzymatic Degradation
The EndoCANNABINOID SYSTEM modulates pain. Cannabinoids inhibit FAAH and MAGL.
The Role of Endocannabinoids in Pain Modulation and the Therapeutic Potential of Inhibiting their Enzymatic Degradation. Alvarez-Jaimes LJ, Palmer JA. SourceJohnson and Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row,San Diego, CA 92121, USA. jpalmer9@its.jnj.co.

Abstract
The need for new pain therapies that provide greater relief without unwanted side-effects drives the search for new drug targets. The identification of endogenous lipid ligands for the two known cannabinoid receptors (CB(1) and CB(2)) has led to numerous studies investigating the role of these endocannabinoids in pain processes. The two most widely studied endocannabinoids are anandamide (AEA; arachidonoyl ethanolamide) and 2-arachidonoylglycerol (2 AG), but there are also a number of structurally related endogenous lipid signaling molecules that are agonists at cannabinoid and non-cannabinoid receptors. These lipid signaling molecules are not stored in synaptic vesicles, but are synthesized and released on-demand and act locally, as they are rapidly inactivated. This suggests that there may be therapeutic potential in modulating levels of these ligands to only have effects in active neural pathways, thereby reducing the potential for side-effects that result from widespread systemic cannabinoid receptor activation. One approach to modulate the levels and duration of action of these lipid signaling molecules is to target the enzymes responsible for their hydrolysis. The two main enzymes responsible for hydrolysis of these lipid signaling molecules are fatty acid amide hydrolase (FAAH) and monoacylglyceride lipase (MGL). This article will discuss the role of the endocannabinoid system in the modulation of pain and will review the current understanding of the properties of the hydrolytic enzymes and the recent advances in developing inhibitors for these targets, with particular relevance to the treatment of pain.”
http://www.ncbi.nlm.nih.gov/pubmed/21466449

Cannabinoids For Pain Management
Cannabinoids have been used for thousands of years to provide relief from suffering. Adverse effects are not uncommon with cannabinoids, though most are not serious and self-limiting. In view of the limited effect size and low but not inconsequential risk of serious adverse events, cannabinoids should be employed as analgesics only when safer and more effective medication trials have failed, or as part of a multimodal treatment regimen-In other words: Cannabinoids, which are safe and effective for pain, should only be used after you’ve tried all of Big Phama’s failed drugs, or in combination with Big Pharma.
Cannabinoids for pain management. Thaler A, Gupta A, Cohen SP.
SourcePain Management Division, Department of Anesthesiology, University of Pennsylvania School of Medicine, Philadelphia, PA 21029, USA.

Abstract
Cannabinoids have been used for thousands of years to provide relief from suffering, but only recently have they been critically evaluated in clinical trials. This review provides an in-depth examination of the evidence supporting cannabinoids in various pain states, along with an overview of potential adverse effects. In summary, there is strong evidence for a moderate analgesic effect in peripheral neuropathic and central pain conditions, and conflicting evidence for their use in nociceptive pain. For spasticity, most controlled studies demonstrate significant improvement. Adverse effects are not uncommon with cannabinoids, though most are not serious and self-limiting. In view of the limited effect size and low but not inconsequential risk of serious adverse events, cannabinoids should be employed as analgesics only when safer and more effective medication trials have failed, or as part of a multimodal treatment regimen.
http://www.ncbi.nlm.nih.gov/pubmed/21508629

The Role of Central and Peripheral Cannabinoid1 Receptors In the Antihyperalgesic Activity of Cannabinoids In A Model of Neuropathic Pain 
These data show that cannabinoids are highly potent and efficacious antihyperalgesic agents in a model of neuropathic pain. This activity is likely to be mediated via an action in both the CNS and in the periphery.
The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain.
Fox A, Kesingland A, Gentry C, McNair K, Patel S, Urban L, James I.
SourceNovartis Institute for Medical Sciences, 5 Gower Place, WC1E 6BN, London, UK. alyson.fox@pharma.novartis.com

Abstract
We have examined the effects of cannabinoid agonists on hyperalgesia in a model of neuropathic pain in the rat and investigated the possible sites of action. The antihyperalgesic activity of the cannabinoids was compared with their ability to elicit behavioural effects characteristic of central cannabinoid activity. WIN55,212-2 (0.3-10 mg kg(-1)), CP-55,940 (0.03-1 mg kg(-1)) and HU-210 (0.001-0.03 mg kg(-1)) were all active in a ‘tetrad’ of tests consisting of tail-flick, catalepsy, rotarod and hypothermia following subcutaneous administration, with a rank order of potency in each of HU-210 > CP-55,940 > WIN55,212-2. The effects of WIN55,212-2 in each assay were blocked by the Cannabinoid1 (CB1) antagonist SR141716A. In the partial sciatic ligation model of neuropathic pain WIN55,212-2, CP-55,940 and HU-210 produced complete reversal of mechanical hyperalgesia within 3 h of subcutaneous administration with D50 values of 0.52, 0.08 and 0.005 mg kg(-1), respectively. In this model WIN55,212-2 was also effective against thermal hyperalgesia and mechanical allodynia. WIN55,212-2 produced pronounced reversal of mechanical hyperalgesia following intrathecal administration that was blocked by the CB1 antagonist SR141716A. Following intraplantar administration into the ipsilateral hindpaw, WIN55,212-2 produced up to 70% reversal of mechanical hyperalgesia, although activity was also observed at high doses following injection into the contralateral paw. The antihyperalgesic effect of WIN55,212-2 injected into the ipsilateral paw was blocked by subcutaneously administered SR141716A, but was not affected by intrathecally administered SR141716A. These data show that cannabinoids are highly potent and efficacious antihyperalgesic agents in a model of neuropathic pain. This activity is likely to be mediated via an action in both the CNS and in the periphery.
http://www.ncbi.nlm.nih.gov/pubmed/11323130

 

Therapeutic Potential of Cannabinoid Receptor Agonists As Analgesic Agents
Increasing data emerging from controlled clinical trials support an analgesic activity of cannabinoids. However, the psychotropic side effects associated with tetrahydrocannabinol or synthetic derivatives essentially puts a brake on their use.”– In other words: Cannabinoids CURE pain, but we cannot have THe Cure because of the side-effects of THC, such as euphoria (feeling good), increased appetite, and temporary memory loss.
Therapeutic potential of cannabinoid receptor agonists as analgesic agents.
Fox A, Bevan S. SourceNovartis Institutes for Biomedical Research, Chronic Pain Unit, 5 Gower Place, London WC1E 6BS, UK. alyson.fox@.novartis.com

Abstract
Increasing data emerging from controlled clinical trials support an analgesic activity of cannabinoids. However, the psychotropic side effects associated with tetrahydrocannabinol or synthetic derivatives essentially puts a brake on their use, possibly limiting the degree of analgesia that can be achieved as well as providing regulatory hurdles. Animal studies show that although these side effects are mediated via central cannabinoid type 1 (CB(1)) receptors, the analgesic activity in chronic pain states may be mediated via spinal CB(1) and potentially CB(2) receptors, as well as peripheral CB(1) and CB2 receptors on sensory nerves or immune cells. The design of novel compounds that either specifically target peripheral CB(1) receptors or display high selectivity for CB(2) receptors may offer avenues for harnessing the analgesic effect of CB receptor agonists while avoiding the central adverse events seen with cannabinoid structures. Clinical trials with such compounds are required to determine whether either approach can provide the level of analgesia required to fulfil the unmet medical need left by current therapies for chronic pain.
http://www.ncbi.nlm.nih.gov/pubmed/16004597


Regenerative Medicine:Cannabis and Stem Cells

Although sometimes controversial, Regenerative Medicine does hold a key in our search for the cure to many diseases.  Regenerative Medicine, in a basic sense, is the “process of replacing or regenerating human cells, tissues or organs to restore or establish normal function. This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the body’s own repair mechanisms to heal previously irreparable tissues or organs.  Below you will see how Cannabis plays a role in stem cell science.

Embryonic Stem Cell Proteomics
Human embryonic stem cells potentially represent an unlimited source of cells and tissues for regenerative medicine. Understanding signaling events that drive proliferation and specialization of these cells into various differentiated derivatives is of utmost importance for controlling their behavior”
Embryonic stem cell proteomics. Van Hoof D, Mummery CL, Heck AJ, Krijgsveld J. SourceNetherlands Institute of Developmental Biology, Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. d.vanhoof@niob.knaw.nl

Abstract
Human embryonic stem cells potentially represent an unlimited source of cells and tissues for regenerative medicine. Understanding signaling events that drive proliferation and specialization of these cells into various differentiated derivatives is of utmost importance for controlling their behavior in vitro. Major progress has been made in unraveling these signaling events with large-scale studies at the transcriptional level, but analysis of protein expression, interaction and modification has been more limited, since it requires different strategies. Recent advances in mass spectrometry-based proteomics indicate that proteome characterization can contribute significantly to our understanding of embryonic stem cell biology. In this article, we review mass spectrometry-based studies of human and mouse embryonic stem cells and their differentiated progeny, as well as studies of conditioned media that have been reported to support self-renewal of the undifferentiated cells in the absence of the more commonly used feeder cells. In addition, we make concise comparisons with related transcriptome profiling reports.
http://www.ncbi.nlm.nih.gov/pubmed/16901201
Expression and Function of Cannabinoid Receptors CB1 and CB2 and Their Cognate Cannabinoid Ligands in Murine Embryonic Stem Cells
This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine Embryonic Stem cell differentiation. This study provides insights into cannabinoid system involvement in Embryonic Stem cell survival and hematopoietic differentiation.
Expression and Function of Cannabinoid Receptors CB1 and CB2 and Their Cognate Cannabinoid Ligands in Murine Embryonic Stem Cells
Shuxian Jiang,1 Yigong Fu,1 John Williams,2 JodiAnne Wood,2 Lakshmipathi Pandarinathan,2 Shiri Avraham,1 Alexandros Makriyannis,2 Shalom Avraham,#1 and Hava Karsenty Avraham#1* 1Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America 2Center for Drug Discovery, Northeastern University, Boston, Massachusetts, United States of America Thomas Zwaka, Academic Editor Baylor College of Medicine, United States of America

Background
Characterization of intrinsic and extrinsic factors regulating the self-renewal/division and differentiation of stem cells is crucial in determining embryonic stem (ES) cell fate. ES cells differentiate into multiple hematopoietic lineages during embryoid body (EB) formation in vitro, which provides an experimental platform to define the molecular mechanisms controlling germ layer fate determination and tissue formation.
Methods and Findings
The cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) are members of the G-protein coupled receptor (GPCR) family, that are activated by endogenous ligands, the endocannabinoids. CB1 receptor expression is abundant in brain while CB2 receptors are mostly expressed in hematopoietic cells. However, the expression and the precise roles of CB1 and CB2 and their cognate ligands in ES cells are not known. We observed significant induction of CB1 and CB2 cannabinoid receptors during the hematopoietic differentiation of murine ES (mES)-derived embryoid bodies. Furthermore, mES cells as well as ES-derived embryoid bodies at days 7 and 14, expressed endocannabinoids, the ligands for both CB1 and CB2. The CB1 and CB2 antagonists (AM251 and AM630, respectively) induced mES cell death, strongly suggesting that endocannabinoids are involved in the survival of mES cells. Treatment of mES cells with the exogenous cannabinoid ligand Δ9-THC resulted in the increased hematopoietic differentiation of mES cells, while addition of AM251 or AM630 blocked embryoid body formation derived from the mES cells. In addition, cannabinoid agonists induced the chemotaxis of ES-derived embryoid bodies, which was specifically inhibited by the CB1 and CB2 antagonists.
Conclusions
This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine ES cell differentiation. This study provides insights into cannabinoid system involvement in ES cell survival and hematopoietic differentiation.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1919431/?tool=pubmed
Cannabinoids Modulate Cell Survival In Embryoid Bodies
This study indicates that cannabinoid signalling is functionally implicated in the biology of differentiating ESCs (embryonic stem cells), being the first to show that activation of cannabinoid receptors is able to increase cell viability via reduction of cell death rate in EBs (embryoid bodies)
Cannabinoids modulate cell survival in embryoid bodies. Nones J, Spohr TC, Furtado DR, Sartore RC, Paulsen BS, Guimarães MZ, Rehen SK. Source Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941590, Rio de Janeiro, RJ, Brazil.

Abstract
ESCs (embryonic stem cells) are potentially able to replace damaged cells in animal models of neural pathologies such as Parkinson’s disease, stroke and spinal cord lesions. Nevertheless, many issues remain unsolved regarding optimal culturing procedures for these cells. For instance, on their path to differentiation in vitro, which usually involves the formation of EBs (embryoid bodies), they may present chromosomal instability, loss of pluripotency or simply die. Therefore, finding strategies to increase the survival of cells within EBs is of great interest. Cannabinoid receptors have many roles in the physiology of the adult body, but little is known about their role in the biology of ESCs. Herein, we investigated how two cannabinoid receptors, CB1 and CB2, may affect the outcome of ESCs aggregated as EBs. RT-PCR (reverse transcriptase-PCR) revealed that EBs expressed both CB1 and CB2 receptors. Aggregation of ESCs into EBs followed by 2-day incubation with a CB1/CB2 agonist reduced cell death by approximately 45%, which was reversed by a CB1 antagonist. A specific CB2 agonist also reduced cell death by approximately 20%. These data indicate that both cannabinoid receptors, CB1 and CB2, are involved in reducing cell death in EBs mediated by exogenous cannabinoids. No increase in proliferation, neural differentiation or changes in chromosomal stability was observed. This study indicates that cannabinoid signalling is functionally implicated in the biology of differentiating ESCs, being the first to show that activation of cannabinoid receptors is able to increase cell viability via reduction of cell death rate in EBs.
http://www.ncbi.nlm.nih.gov/pubmed/19947926

Cash “Cashy” Hyde: Children’s Cancer and Cannabis

Hearing your child has cancer is one of the worst things a parent can be faced with.  Watching your child go through chemo can be a horrifying experience in itself.  When news broke that a father was treating his son’s cancer with cannabis people were shocked.  There was reactions all over the board but we watched as the oil worked.  Cashy, as he is known has been diagnosed with Malignant and Aggressive Cancer classified as a PNET Brain Tumor.  He was able to replace the toxic drugs he was on with cannabis oil instead.  Below are studies that show how cannabis treats Brain Tumors.  With more research we can prove that cannabis does have medicinal value and can greatly aid or cure many ailments.  These are published medical studies that I encourage you to research and share your findings with everyone.  Spread the truth!
Information gathered by David Worrell edited by Cherry Girl
Please visit the Cashy Hyde Foundation Website for more on this amazing little boy!   

Hypothesis: Cannabinoid Therapy For the Treatment of Gliomas?
‎”Cannabinoids induce apoptosis of glioma cells in culture… In addition, cannabinoid treatment inhibits angiogenesis of gliomas in vivo. Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death. These and other findings reviewed here might set the basis for a potential use of cannabinoids in the management of gliomas.”
“Hypothesis: cannabinoid therapy for the treatment of gliomas?”
Velasco G, Galve-Roperh I, Sánchez C, Blázquez C, Guzmán M.
SourceDepartment of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Avenida Complutense, sn, 28040 Madrid, Spain.

Abstract
Gliomas, in particular glioblastoma multiforme or grade IV astrocytoma, are the most frequent class of malignant primary brain tumours and one of the most aggressive forms of cancer. Current therapeutic strategies for the treatment of glioblastoma multiforme are usually ineffective or just palliative. During the last few years, several studies have shown that cannabinoids-the active components of the plant Cannabis sativa and their derivatives–slow the growth of different types of tumours, including gliomas, in laboratory animals. Cannabinoids induce apoptosis of glioma cells in culture via sustained ceramide accumulation, extracellular signal-regulated kinase activation and Akt inhibition. In addition, cannabinoid treatment inhibits angiogenesis of gliomas in vivo. Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death. These and other findings reviewed here might set the basis for a potential use of cannabinoids in the management of gliomas.”
http://www.ncbi.nlm.nih.gov/pubmed/15275820

A Pilot Clinical Study of Delta9-tetrahydrocannabinol In Patients With Recurrent Glioblastoma Multiforme
‎”Delta(9)-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis.The primary end point of the study was to determine the safety of intracranial THC administration.Cannabinoid delivery was safe and could be achieved without overt psychoactive effects.The fair safety profile of THC, together with its antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”
‎A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Guzmán M, Duarte MJ, Blázquez C, Ravina J, Rosa MC, Galve-Roperh I, Sánchez C, Velasco G, González-Feria L. Source Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid 28040, Spain. mgp@bbm1.ucm.es

Abstract
Delta(9)-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans. Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration. We also evaluated THC action on the length of survival and various tumour-cell parameters. A dose escalation regimen for THC administration was assessed. Cannabinoid delivery was safe and could be achieved without overt psychoactive effects. Median survival of the cohort from the beginning of cannabinoid administration was 24 weeks (95% confidence interval: 15-33). Delta(9)-Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro and decreased tumour-cell Ki67 immunostaining when administered to two patients. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360617/?tool=pubmed

Cannabinoids and Gliomas
“Cannabinoids, the active components of Cannabis sativa L., inhibit the growth of different types of tumor cells, including glioma cells. Cannabinoids seem to be selective antitumoral compounds, as they kill glioma cells, but not their non-transformed astroglial counterparts. On the basis of these preclinical findings, a pilot clinical study of Delta(9)-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has been recently run. The good safety profile of THC, together with its growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed at evaluating the antitumoral activity of cannabinoids.”
Cannabinoids and gliomas. Velasco G, Carracedo A, Blázquez C, Lorente M, Aguado T, Haro A, Sánchez C, Galve-Roperh I, Guzmán M.
Source Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain.

Abstract
Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances–the endocannabinoids–that activate specific cell surface receptors. Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds, as they kill glioma cells, but not their non-transformed astroglial counterparts. On the basis of these preclinical findings, a pilot clinical study of Delta(9)-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has been recently run. The good safety profile of THC, together with its possible growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”
http://www.ncbi.nlm.nih.gov/pubmed/17952650

Cannabinoids As Potential New Therapy For the Treatment of Gliomas
“Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics) for their treatment are only palliative and survival diagnosis is normally 6-12 months. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of nontransformed counterparts. A pilot clinical trial on patients with glioblastoma multiforme demonstrated their good safety profile together and remarkable antitumor effects, and may set the basis for further studies aimed at better evaluating the potential anticancer activity of cannabinoids.”
Cannabinoids as potential new therapy for the treatment of gliomas.
Parolaro D, Massi P. Source Department of Structural & Functional Biology, Pharmacology Section, Center of Neuroscience, University of Insubria, Via A da Giussano 10, Busto Arsizio (VA), Italy. daniela.parolaro@uninsubria.it

Abstract
Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin) for their treatment are only palliative and survival diagnosis is normally 6-12 months. The development of new therapeutic strategies for the management of gliomas is therefore essential. Interestingly, cannabinoids have been shown to exert antiproliferative effects on a wide spectrum of cells in culture. Of interest, cannabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models, curbing the growth of xenografts generated by subcutaneous or intratecal injection of glioma cells in immune-deficient mice. Moreover, cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of nontransformed counterparts. A pilot clinical trial on patients with glioblastoma multiforme demonstrated their good safety profile together and remarkable antitumor effects, and may set the basis for further studies aimed at better evaluating the potential anticancer activity of cannabinoids.”
http://www.ncbi.nlm.nih.gov/pubmed/18088200

The Stress-Regulated Protein P8 Mediates Cannabinoid-Induced Apoptosis of Tumor Cells
‎”One of the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells.We identify the stress-regulated protein p8 as an essential mediator of cannabinoid antitumoral action. Activation of this pathway may constitute a potential therapeutic strategy for inhibiting tumor growth.”
The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Carracedo A, Lorente M, Egia A, Blázquez C, García S, Giroux V, Malicet C, Villuendas R, Gironella M, González-Feria L, Piris MA, Iovanna JL, Guzmán M, Velasco G. Source Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain.

Abstract
One of the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells. By using a wide array of experimental approaches, we identify the stress-regulated protein p8 (also designated as candidate of metastasis 1) as an essential mediator of cannabinoid antitumoral action and show that p8 upregulation is dependent on de novo-synthesized ceramide. We also observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway may constitute a potential therapeutic strategy for inhibiting tumor growth.”
http://www.ncbi.nlm.nih.gov/pubmed/16616335

Down-Regulation of Tissue Inhibitor of Metalloproteinases-1 in Gliomas: A New Marker of Cannabinoid Antitumoral Activity?
“Cannabinoids, the active components of Cannabis sativa L., inhibit tumor growth by inducing apoptosis of tumor cells and inhibiting tumor angiogenesis. We evaluated the effects of cannabinoids on the expression of tissue inhibitors of metalloproteinases (TIMPs), which play critical roles in the acquisition of migrating and invasive capacities by tumor cells. Delta(9)-tetrahydrocannabinol (THC) down-regulated TIMP-1. As TIMP-1 up-regulation is associated with high malignancy and negative prognosis of numerous cancers, TIMP-1 down-regulation may be a hallmark of cannabinoid-induced inhibition of glioma progression.”
Down-regulation of tissue inhibitor of metalloproteinases-1 in gliomas: a new marker of cannabinoid antitumoral activity? Blázquez C, Carracedo A, Salazar M, Lorente M, Egia A, González-Feria L, Haro A, Velasco G, Guzmán M. Source Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain.

Abstract
Cannabinoids, the active components of Cannabis sativa L. and their derivatives, inhibit tumor growth in laboratory animals by inducing apoptosis of tumor cells and inhibiting tumor angiogenesis. It has also been reported that cannabinoids inhibit tumor cell invasiveness, but the molecular targets of this cannabinoid action remain elusive. Here we evaluated the effects of cannabinoids on the expression of tissue inhibitors of metalloproteinases (TIMPs), which play critical roles in the acquisition of migrating and invasive capacities by tumor cells. Local administration of Delta(9)-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated TIMP-1 expression in mice bearing subcutaneous gliomas, as determined by Western blot and immunofluorescence analyses. This cannabinoid-induced inhibition of TIMP-1 expression in gliomas (i) was mimicked by JWH-133, a selective CB(2) cannabinoid receptor agonist that is devoid of psychoactive side effects, (ii) was abrogated by fumonisin B1, a selective inhibitor of ceramide synthesis de novo, and (iii) was also evident in two patients with recurrent glioblastoma multiforme (grade IV astrocytoma). THC also depressed TIMP-1 expression in cultures of various human glioma cell lines as well as in primary tumor cells obtained from a glioblastoma multiforme patient. This action was prevented by pharmacological blockade of ceramide biosynthesis and by knocking-down the expression of the stress protein p8. As TIMP-1 up-regulation is associated with high malignancy and negative prognosis of numerous cancers, TIMP-1 down-regulation may be a hallmark of cannabinoid-induced inhibition of glioma progression.”
http://www.ncbi.nlm.nih.gov/pubmed/17675107

Inhibition of Cancer Cell Invasion By Cannabinoids Via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1
‎”Cannabinoids, in addition to having palliative benefits in cancer therapy, have been associated with anticarcinogenic effects. Increased expression of TIMP-1 mediates an anti-invasive effect of cannabinoids. Cannabinoids may therefore offer a therapeutic option in the treatment of highly invasive cancers.”
Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1.
Ramer R, Hinz B. Source Institute of Toxicology and Pharmacology, University of Rostock, Schillingallee 70, Rostock D-18057, Germany.

Abstract
BACKGROUND: Cannabinoids, in addition to having palliative benefits in cancer therapy, have been associated with anticarcinogenic effects. Although the antiproliferative activities of cannabinoids have been intensively investigated, little is known about their effects on tumor invasion.

METHODS: Matrigel-coated and uncoated Boyden chambers were used to quantify invasiveness and migration, respectively, of human cervical cancer (HeLa) cells that had been treated with cannabinoids (the stable anandamide analog R(+)-methanandamide [MA] and the phytocannabinoid delta9-tetrahydrocannabinol [THC]) in the presence or absence of antagonists of the CB1 or CB2 cannabinoid receptors or of transient receptor potential vanilloid 1 (TRPV1) or inhibitors of p38 or p42/44 mitogen-activated protein kinase (MAPK) pathways. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting were used to assess the influence of cannabinoids on the expression of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMPs (TIMPs). The role of TIMP-1 in the anti-invasive action of cannabinoids was analyzed by transfecting HeLa, human cervical carcinoma (C33A), or human lung carcinoma cells (A549) cells with siRNA targeting TIMP-1. All statistical tests were two-sided.

RESULTS: Without modifying migration, MA and THC caused a time- and concentration-dependent suppression of HeLa cell invasion through Matrigel that was accompanied by increased expression of TIMP-1. At the lowest concentrations tested, MA (0.1 microM) and THC (0.01 microM) led to a decrease in invasion (normalized to that observed with vehicle-treated cells) of 61.5% (95% CI = 38.7% to 84.3%, P < .001) and 68.1% (95% CI = 31.5% to 104.8%, P = .0039), respectively. The stimulation of TIMP-1 expression and suppression of cell invasion were reversed by pretreatment of cells with antagonists to CB1 or CB2 receptors, with inhibitors of MAPKs, or, in the case of MA, with an antagonist to TRPV1. Knockdown of cannabinoid-induced TIMP-1 expression by siRNA led to a reversal of the cannabinoid-elicited decrease in tumor cell invasiveness in HeLa, A549, and C33A cells.

CONCLUSION: Increased expression of TIMP-1 mediates an anti-invasive effect of cannabinoids. Cannabinoids may therefore offer a therapeutic option in the treatment of highly invasive cancers.”
http://jnci.oxfordjournals.org/content/100/1/59.long

Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression
‎”Local administration of Δ9-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated MMP-2 expression in gliomas. As MMP-2 up-regulation is associated with high progression and poor prognosis of gliomas and many other tumors, MMP-2 down-regulation constitutes a new hallmark of cannabinoid antitumoral activity.”
Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression Cristina Blázquez1, María Salazar1, Arkaitz Carracedo1, Mar Lorente1, Ainara Egia1, Luis González-Feria2, Amador Haro1, Guillermo Velasco1, and Manuel Guzmán1 
+ Author Affiliations 1Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain and 2Department of Neurosurgery, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain  

Abstract
Cannabinoids, the active components of Cannabis sativa L. and their derivatives, inhibit tumor growth in laboratory animals by inducing apoptosis of tumor cells and impairing tumor angiogenesis. It has also been reported that these compounds inhibit tumor cell spreading, but the molecular targets of this cannabinoid action remain elusive. Here, we evaluated the effect of cannabinoids on matrix metalloproteinase (MMP) expression and its effect on tumor cell invasion. Local administration of Δ9-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated MMP-2 expression in gliomas generated in mice, as determined by Western blot, immunofluorescence, and real-time quantitative PCR analyses. This cannabinoid-induced inhibition of MMP-2 expression in gliomas (a) was MMP-2–selective, as levels of other MMP family members were unaffected; (b) was mimicked by JWH-133, a CB2 cannabinoid receptor–selective agonist that is devoid of psychoactive side effects; (c) was abrogated by fumonisin B1, a selective inhibitor of ceramide biosynthesis; and (d) was also evident in two patients with recurrent glioblastoma multiforme. THC inhibited MMP-2 expression and cell invasion in cultured glioma cells. Manipulation of MMP-2 expression by RNA interference and cDNA overexpression experiments proved that down-regulation of this MMP plays a critical role in THC-mediated inhibition of cell invasion. Cannabinoid-induced inhibition of MMP-2 expression and cell invasion was prevented by blocking ceramide biosynthesis and by knocking-down the expression of the stress protein p8. As MMP-2 up-regulation is associated with high progression and poor prognosis of gliomas and many other tumors, MMP-2 down-regulation constitutes a new hallmark of cannabinoid antitumoral activity.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116828/?tool=pubmed

How To Save Yourself From Cancer and Many Other Illnesses With Cannabis

People know of the big C word…Cancer.  When faced with the diagnosis of cancer what do you do, how do you react?  There are conventional treatments for cancer ranging from drugs to radiation to chemotherapy.  Most of the conventional therapies nearly destroy your body along with the cancer. There are some people who have decide to treat cancer in a natural way. When faced with the harsh reality of death as a possibility it can be hard to decide.

Rick Simpson has been providing people with instructions on how to make Hemp Oil medicines for about 8 years.  He has shown how you can treat ailments that are minor to curing cancer.  Below is his presentation RUN FROM THE CURE and other survivor stories that have used the Rick Simpson Oil.  After watching this ask yourself if its time to legalize Cannabis.

RUN FROM THE CURE – Full Version

Grandmother Cancer Survivor Using Rick Simpson Oil

Various Newscasts Pieced Together To Prove Cannabis Cures

You can also read more testimonials Here.  Spread the Truth about the CURE!!
http://phoenixtears.ca/testimonials/

Prostate Cancer and Cannabis:Cause and CURE

Cannabis has been used for thousands of years as a natural remedy for many ailments but only recently has modern science began to recognize the curing power of cannabis.  In 2011 alone there were about 240,890 new cases and about 33,720 deaths from prostate cancer.  Below are studies that show how cannabis can be an effective therapy for prostate cancer.   With more research we can prove that cannabis does have medicinal value and can greatly aid or cure many ailments.  These are published medical studies that I encourage you to research and share your findings with everyone.  Spread the truth!
Information gathered by David Worrell edited by Cherry Girl

Cause:

CXCL12 / CXCR4 / CXCR7 Chemokine Axis And Cancer Progression
‎”CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression.” Sun X, Cheng G, Hao M, Zheng J, Zhou X, Zhang J, Taichman RS, Pienta KJ, Wang J. SourceDepartment of Biochemistry and Molecular & Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China. Erratum in Cancer Metastasis Rev. 2011 Jun;30(2):269-70.

Chemokine Family and Their Cognate Receptors

Abstract
Chemokines, small pro-inflammatory chemoattractant cytokines that bind to specific G-protein-coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. The chemokine CXCL12 (also called stromal-derived factor-1) is an important α-chemokine that binds primarily to its cognate receptor CXCR4 and thus regulates the trafficking of normal and malignant cells. For many years, it was believed that CXCR4 was the only receptor for CXCL12. Yet, recent work has demonstrated that CXCL12 also binds to another seven-transmembrane span receptor called CXCR7. Our group and others have established critical roles for CXCR4 and CXCR7 on mediating tumor metastasis in several types of cancers, in addition to their contributions as biomarkers of tumor behavior as well as potential therapeutic targets. Here, we review the current concepts regarding the role of CXCL12 / CXCR4 / CXCR7 axis activation, which regulates the pattern of tumor growth and metastatic spread to organs expressing high levels of CXCL12 to develop secondary tumors. We also summarize recent therapeutic approaches to target these receptors and/or their ligands.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175097/?tool=pubmed 

Schematic representation showing the role of microenvironment in tumor cell CXCR4 receptor activation in both the primary and metastatic sites.

CURE:

Cannabinoid Receptor CB2 Modulates the CXCL12/CXCR4-Mediated Chemotaxis of T Lymphocytes
‎”Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes.
Ghosh S, Preet A, Groopman JE, Ganju RK.
SourceDivision of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.

Abstract
Cannabinoids have been shown to influence the immune system. However, their immunomodulatory effects have not been extensively studied. In this investigation, we have observed that both primary and Jurkat T cells express a functional cannabinoid receptor 2 (CB(2)). Furthermore, both the synthetic cannabinoids CP55,940 and WIN55,212-2, as well as the CB(2)-selective agonist JWH-015, caused a significant inhibition of the chemokine CXCL12-induced and CXCR4-mediated chemotaxis of Jurkat T cells, as well as their transendothelial migration. Involvement of the CB(2) receptor was further confirmed by partial reversal of the inhibition using the CB(2)-specific antagonist, AM630. Similarly, CP55,940 and JWH-015 inhibited the CXCL12-induced chemotaxis of primary CD4(+) and CD8(+) T lymphocytes. Further investigation of signaling studies to delineate the mechanism of inhibition revealed that cannabinoids enhance CXCL12-induced p44/42 MAP kinase activity. However, enhanced MAP kinase activity was not responsible for the inhibition of chemotaxis. This suggests that cannabinoids differentially regulate CXCR4-mediated migration and MAP kinase activation in T cells. Cannabinoids were also found to downregulate the PMA-enhanced enzyme activity of matrix metalloproteinase-9, which is known to play an important role in transendothelial migration. This study provides novel information regarding cannabinoid modulation of functional effects in T cells.”
http://www.ncbi.nlm.nih.gov/pubmed/16503355

The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis
“These results suggest prostate cancers may be influenced by the CXCL12:CXCR4 pathway during metastasis. This pathway would provide a novel target for therapeutic intervention.”
‎”The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis.  Arya M, Patel HR, McGurk C, Tatoud R, Klocker H, Masters J, Williamson M.  Source Prostate Cancer Research Centre, Institute of Urology,University College London, UK. manit_arya@hotmail.com

Abstract
AIM: Chemokines or chemotactic cytokines are known to be important in the directional migration or chemotaxis of leucocytes in conditions of homeostasis and in inflammatory or immunological responses. However, the role of chemokines is extending beyond their involvement in mediating leucocyte trafficking with an increasing body of evidence suggesting these proteins are intimately involved in many stages of tumour development and progression. Our aim was to study the role of the CXCL12:CXCR4 chemokine ligand:receptor complex in determining the organ-specific metastasis of prostate cancer. MATERIALS and

METHODS: CXCR4 mRNA expression was determined by RT-PCR in 3 metastatic prostate cancer cell lines DU145, LNCaP and PC3, the primary prostate cancer cell line 1542 CPT3X and the normal prostate epithelial cell lines 1542 NPTX and Pre 2.8. This was followed by Taqman quantitative PCR analysis of CXCR4 mRNA in these cell lines. Flow cytometry analysis was then used to measure the expression of the CXCR4 receptor protein on the cell surface. The influence of the receptor on cell migration was studied using Transwell, Migration Assays. Finally, Taqman quantitative PCR was performed on RNA obtained from laser microdissected fresh primary prostate tumour and benign tissue samples from patients.

RESULTS: In DU145, LNCaP and PC3 CXCR4 mRNA expression was approximately 1000, 400 and 21 times respectively that of 1542 NPTX, Pre 2.8 and 1542 CPT3X. In patient primary tumour samples and patient benign tissue specimens CXCR4 mRNA expression was similar to that of the metastatic cell line DU145. Flow cytometry analysis showed that significantly higher levels of the CXCR4 receptor were present on the cell surface of the 3 metastatic cell lines. Migration studies revealed that chemotaxis of the metastatic cell lines PC3 and DU145 was enhanced by CXCL12 ligand and inhibited by antibody to CXCR4. CXCL12 did not influence the migration of the normal prostate epithelial cell line 1542 NPTX.

CONCLUSIONS: We have demonstrated that human prostate cell lines derived from metastases express functional CXCR4 receptor and that CXCL12 ligand enhances their migratory capabilities. Also, laser microdissected primary patient tumours and patient benign tissue specimens express CXCR4 mRNA at high levels (it is suggested that post-transcriptional modification of the CXCR4 receptor plays a major role in regulating protein expression). These results suggest prostate cancers may be influenced by the CXCL12:CXCR4 pathway during metastasis. This pathway would provide a novel target for therapeutic intervention.”
http://www.ncbi.nlm.nih.gov/pubmed/15844659