Children’s Cancer and Cannabis

The words children and cannabis sound very uncomfortable to many but to parents who want to see their child thrive, for some, it sounds like a prayer answered.  It is a very controversial subject but a very important one to discuss.  In the United States over 10,000 children under the age of 15 are diagnosed with cancer each year.  One of the most famous cases of a child with cancer being treated with cannabis is Cashy Hyde.  Many know the story of how the frail little boy bounced back with the help of Rick Simpson Oil.  Below you will see studies on how cannabis has been looked at for childhood cancers.  I encourage all to do their own research and seek out the truth! ~ Cherry Girl

An Efficient New Cannabinoid Antiemetic in Pediatric Oncology
An efficient new cannabinoid antiemetic in pediatric oncology…Delta-8-tetrahydrocannabinol (delta-8-THC), a cannabinoid with lower psychotropic potency than the main Cannabis constituent, delta-9-tetrahydrocannabinol (delta-9-THC), was administered to eight children, aged 3-13 years with various hematologic cancers, treated with different antineoplastic drugs… The THC treatment started two hours before each antineoplastic treatment… Vomiting was completely prevented.

Cannabis-Induced Cytotoxicity in Leukemic Cell Lines: The Role of the Cannabinoid Receptors and the MAPK Pathway
Delta9-Tetrahydrocannabinol (THC) is the active metabolite of cannabis… We investigated the role of the CB-Rs (cannabinoid receptors) in mediating apoptosis (cell death) in 3 leukemic cell lines… We have shown that THC is a potent inducer of apoptosis (cell death/cell suicide)…Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway.

Cannabidiol-Induced Apoptosis in Human Leukemia Cells: A Novel Role of Cannabidiol in the Regulation of P22phox and Nox4 Expression
2006: “Cannabidiol-induced apoptosis (cell death) in human leukemia cells… results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22(phox) expression, may be a novel and highly selective treatment for leukemia.”— I believe cannabidiol is a non-psychoactive cannabinoid from cannabis.

The CB2 Cannabinoid Receptor Signals Apoptosis Via Ceramide-Dependent Activation of the Mitochondrial Intrinsic Pathway
2006: “Delta9-tetrahydrocannabinol and other cannabinoids exert pro-apoptotic actions in tumor cells via the CB2 cannabinoid receptor… the molecular mechanism involved in this effect has remained elusive. Here we used the human leukemia cell line Jurkat-that expresses CB2 as the unique CB receptor-to investigate this mechanism…results presented here show that CB2 receptor activation signals apoptosis (cell death).

Medical Marijuana: Should Minors Have the Same Rights As Adults?
“Failure to give an effective therapy to seriously ill patients, either adults or children, violates the core principles of both medicine and ethics. Medically, to deny physicians the right to prescribe to their patients a therapy that relieves pain and suffering violates the physician-patient relationship. Ethically, failure to offer an available therapy that has proven to be effective violates the basic ethical principle of nonmaleficence, which prohibits the infliction of harm, injury, or death and is related to the maxim primum non nocere (‘above all, or first, do no harm’)… Therefore, in the patient’s best interest, patients and parents/surrogates, have the right to request medical marijuana under certain circumstances and physicians have the duty to disclose medical marijuana as an option and prescribe it when appropriate. The right to an effective medical therapy, whose benefits clearly outweigh the burdens, must be available to all patients including children. To deny children the use of medical marijuana when appropriate is a grave injustice which violates the basic foundational beliefs of both medicine and… ” — ethics?

Human Endocannabinoid System: Science’s Target For New Therapies

Since the discovery of the human endocannabinoid system science has had it in its cross hairs for many potential therapies as well as a better understanding of how our body works within systems.  We have found that the endocannabinoid system has a role in many functions throughout the body.  Below you will see studies where the endocannabinoid system was targeted for therapies with promising outcomes.  Please feel free to share this information with others and your doctor when deciding which treatment options are best for you.  Keep in mind that cannabis is all natural and is used in its natural form.  There are many options when choosing cannabis for a treatment option and goes beyond just smoked cannabis.  I encourage all to do their own research and seek out the truth about cannabis ~ Cherry Girl

Possible Endocannabinoid Control of Colorectal Cancer Growth (2003)
Possible endocannabinoid control of colorectal cancer growth…Anandamide, 2-AG, and… CBR agonist… potently inhibit cell proliferation. This effect is blocked by the CB(1) antagonist, but not by the CB(2) antagonist, and is mimicked by CB(1)-selective, but not CB(2)-selective, agonists… both CB(1) and CB(2) receptors mediate inhibition of proliferation. Inhibitors of endocannabinoid inactivation enhance endocannabinoid levels and block cell proliferation.

The Endocannabinoid System In Amyotrophic Lateral Sclerosis (2008)
The endocannabinoid system in amyotrophic lateral sclerosis…Currently the only licensed therapy available for the treatment of ALS is the anti-glutamatergic agent Riluzole, which has limited therapeutic effects. However, there is increasing evidence that cannabinoids and manipulation of the endocannabinoid system may have therapeutic value in ALS, in addition to other neurodegenerative conditions. Cannabinoids exert anti-glutamatergic and anti-inflammatory actions through activation of the CB(1) and CB(2) receptors, respectively. Activation of CB(1) receptors therefore inhibit glutamate release… Meanwhile, CB(2) receptors influence inflammation, whereby receptor activation reduces microglial activation, resulting in a decrease in neurotoxic mediators. Finally, cannabinoid agents may also exert anti-oxidant actions by a receptor-independent mechanism. Therefore the ability of cannabinoids to target multiple neurotoxic pathways in different cell populations increase their therapeutic potential in the treatment of ALS. Recent studies investigating this potential in models of ALS, in particular those that focus on strategies that activate CB(2) receptors, are discussed.

Interaction of Endocannabinoid System and Steroid Hormones In the Control of Colon Cancer Cell Growth (2012)
Interaction of endocannabinoid system and steroid hormones in the control of colon cancer cell growth…Our results partially elucidated the role of EC system in the molecular mechanisms enrolled by steroids in the inhibition of colon cancer cell growth and strongly suggested that targeting the EC system represent a promising tool to improve the efficacy of CRC (colorectal cancer cell) treatments.

The Endocannabinoid System and Plant-Derived Cannabinoids in Diabetes and Diabetic Complications (2011)
The Endocannabinoid System and Plant-Derived Cannabinoids in Diabetes and Diabetic Complications…The modulation of the activity of this system holds tremendous therapeutic potential in a wide range of diseases, ranging from cancer, pain, neurodegenerative, and cardiovascular diseases to obesity and metabolic syndrome, diabetes, and diabetic complications… the role of the endocannabinoid system in primary diabetes…therapeutic potential of targeting the endocannabinoid system… certain plant-derived cannabinoids… possess potent anti-inflammatory and/or antioxidant properties.

The Endocannabinoid System In Ageing: A New Target For Drug Development (2006)
The endocannabinoid system in ageing: a new target for drug development…. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol are the main endogenous agonists of cannabinoid receptors able to mimic several pharmacological effects of Delta(9)-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana. AEA is released “on demand”…. Together with AEA and congeners, the proteins which bind, synthesize, transport and hydrolyze AEA form the “endocannabinoid system”. Endogenous cannabinoids are present in the central nervous system and in peripheral tissues, suggesting… therapeutic potential… drugs able to modulate the endocannabinoid tone for the treatment of ageing and age-related human pathologies.

Endocannabinoid System In Cardiovascular Disorders – New Pharmacotherapeutic Opportunities (2011)
Endocannabinoid system in cardiovascular disorders – new pharmacotherapeutic opportunities.The long history of Cannabis sativa had its development oriented for medicine after the discovery and chemical characterization of its main active ingredient, the 9-tetrahydrocannabinol (9-THC). Consequently, a binding site for 9-THC was identified in and the first cannabinoid receptor (CB1) was cloned, followed by the CB2 and by the discover of two endogenous agonists: anandamide and 2-arachidonoyl glycerol. Cannabinoid receptors, endocannabinoids and the enzymes that catalyze its synthesis and degradation constitute the endocannabinoid system (ECS), which plays an important role in the cardiovascular system…The evidence so far gathered shows that the modulation of ECS (as agonism or antagonism of its receptors) is an enormous potential field for research and intervention in multiple areas of human pathophysiology. The development of selective drugs for the CB1 and CB2 receptors may open a door to new therapeutic regimens.

The Endogenous Cannabinoid System. Therapeutic Implications For Neurologic and Psychiatric Disorders (2005)
The endogenous cannabinoid system. Therapeutic implications for neurologic and psychiatric disorders. For about 5,000 years, cannabis has been used as a therapeutic agent. There has been growing interest in the medical use of cannabinoids. This is based on the discovery that cannabinoids act with specific receptors (CB1 and CB2). CB1 receptors are located in specific brain areas and CB2 receptors on cells of the immune system… findings could possibly lead to the use of synthetic and natural cannabinoids as therapeutic agents in various areas.

Targeted Modulators of the Endogenous Cannabinoid System: Future Medications to Treat Addiction Disorders and Obesity (2007)
Targeted modulators of the endogenous cannabinoid system: future medications to treat addiction disorders and obesity…Pressing health care needs have made the rational design of targeted CB1 cannabinoid-receptor modulators a promising route to future medications with significant therapeutic impact.

The Importance of the Endogenous Cannabinoid System In Various Neuropsychiatric Disorders (2007)
The importance of the endogenous cannabinoid system in various neuropsychiatric disorders…The endogenous cannabinoid system was first described in 1988. There are two specific receptors, the CB2-receptor, located in the lymphatic system and the CB1-receptor occurring predominantly in the central nervous system…In 1992 endogenous ligands of the cannabinoid system were discovered for the first time (e.g. anandamide and 2-arachidonylglycerol)…A dysregulation in the endogenous cannabinoid/anandamide system could possibly play an import role in the etiology of Gilles de la Tourette syndrome and schizophrenic psychoses…administration of cannabinoids affects the symptoms of the Gilles de la Tourette syndrome positively… In ischaemic brain lesions cannabinoids seem to have a neuroprotective effect…interactions between the endogenous opioid system and the endogenous cannabainoid system are pointed out. This is of interest since it could be shown in experiments that the absence of CB1 receptors reduces the positive reinforcement of opiate administration.

Therapeutic Potential of the Endocannabinoid System in the Brain (2005)
Therapeutic potential of the endocannabinoid system in the brain. Cannabinoids… marijuana and other derivatives of Cannabis sativa… these compounds are now also considered for their therapeutic potential, since the term “cannabinoid” includes much more compounds than those present in Cannabis sativa derivatives… there are numerous synthetic cannabinoids obtained by modifications from plant-derived cannabinoids… All this boom of the cannabinoid pharmacology has an explanation in the discovery of the endocannabinoid signaling system, which plays a modulatory role… The objective of the article will be to review the advances in the study of the endocannabinoid system and their functions in the brain, as well as their alterations in a variety of pathologies and the proposed therapeutic benefits of novel cannabinoid-related compounds that improve the pharmacokinetic and pharmacodynamic properties of classic cannabinoids.

The Endocannabinoid Signaling System: A Marriage of PUFA and Musculoskeletal Health (2010)
The endocannabinoid signaling system: a marriage of PUFA and musculoskeletal health…The potential of dietary PUFA to regulate this signaling system to influence the metabolic and physiological outcomes favorable to musculoskeletal health is the purpose… we first introduce the EC agonists (ligands) and their receptors (CB1 and CB2) and the general actions of EC signaling in various organs and systems. Second, we describe EC signaling in bone and muscle and how dietary PUFA influence the levels of endogenous agonists. Third, we discuss the potential implications of how dietary PUFA impact this system to minimize muscle atrophy and osteopenia and support healthy muscle development and bone modeling.

The Endocannabinoid System: Physiology and Pharmacology (2005)
The endocannabinoid system: physiology and pharmacology…The endogenous cannabinoid system is an ubiquitous lipid signalling system that appeared early in evolution and which has important regulatory functions throughout the body in all vertebrates…Outside the brain, the endocannabinoid system is one of the crucial modulators of the autonomic nervous system, the immune system and microcirculation…Recent pharmacological advances have led to the synthesis of cannabinoid receptor agonists and antagonists, selective inhibitors of endocannabinoid degradation. These new tools have enabled the study of the physiological roles played by the endocannabinoids and have opened up new strategies in the treatment of pain, obesity, neurological diseases including multiple sclerosis, emotional disturbances such as anxiety and other psychiatric disorders including drug addiction. Recent advances have specifically linked the endogenous cannabinoid system to alcoholism, and cannabinoid receptor antagonism now emerges as a promising therapeutic alternative for alcohol dependence and relapse.”— I believe: since the endo-plant cannabinoid system can be the target for Big Pharma’s for-private-profit “treatments.

The Endocannabinoid System As An Emerging Target of Pharmacotherapy (2006)
The endocannabinoid system as an emerging target of pharmacotherapy. The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease…The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients’ need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

The Endocannabinoid System: An Osteopathic Perspective (2008)
The endocannabinoid system consists of cannabinoid receptors, endogenous ligands, and ligand-metabolizing enzymes. The system exemplifies the osteopathic principle that the body possesses self-regulatory mechanisms that are self-healing in nature…The endocannabinoid system is a homeostatic mechanism that exemplifies the key osteopathic concepts of mind-body unity on a molecular level… osteopathic physicians may enhance endocannabinoid function in their patients…The plant Cannabis sativa, the source of cannabis (ie, marijuana, hashish), is native to central Asia. Several indigenous “traditional medicine” systems (eg, Ayurvedic medicine, Tibetan medicine, traditional Chinese medicine) evolved and make use of this substance.

Our Endocannabinoid System: Key To Understanding The Human Body

Since discovering the endocannabinoid system scientists have been using it as a target to cure or help many ailments.  When looking through the myriad of published medical studies one will quickly see this trend.  This is just one more reason why understanding the human endocannabinoid system is crucial.  Below you will see studies where the endocannabinoid system was targeted for therapies with promising outcomes.  Please feel free to share this information with others and your doctor when deciding which treatment options are best for you.  Keep in mind that cannabis is all natural and is used in its natural form.  There are many options when choosing cannabis for a treatment option and goes beyond just smoked cannabis.  I encourage all to do their own research and seek out the truth about cannabis ~ Cherry Girl

The Endocannabinoid System: Role In Energy Regulation (2012)
The endocannabinoid system: role in energy regulation. Cannabis sativa has been used since antiquity to treat many ailments… The primary psychoactive constituent of this plant, Δ(9) -tetrahydrocannabinol (THC) is an FDA approved medication… The effects of THC are mediated through the endocannabinoid system (ECS), which promotes a positive energy balance through stimulation of appetite as well as shifting homeostatic mechanisms toward energy storage… we discuss… the therapeutic potential of targeting this system.

Cannabis Sativa and the Endogenous Cannabinoid System: Therapeutic Potential For Appetite Regulation (2011)
Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation. The herb Cannabis sativa (C. sativa) has been used for thousands of years as a medicine…only recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components… we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects… we also critically consider the mounting evidence which suggests non-Δ(9) tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa-induced feeding pattern changes… given the wide range of phytocannabinoids present in Cannabis sativa… we demonstrate non-Δ(9) tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.

The Endocannabinoid System and Prospects Her Stimulation In Clinical Medicine (2007)
The endocannabinoid system and prospects her stimulation in clinical medicine… The history of use by the man of plants of a sort Cannabis totals more than 4000 years… Cannabis sowing, named also “Indian” – cultural plant, which has set of applications. From it received fibres for hemp of ropes and make a fabric similar on linen. Its stalks went on manufacture glossy of a paper and building of plates… as fuel instead of diesel… The greatest popularity Cannabis has received as raw material for reception of products (marijuana, hashish etc) …Cannabis in the medical purposes: at migraine, spasmes, vomiting, pains of a different origin etc.

Cannabinoid System In the Skin – A Possible Target For future Therapies In Dermatology (2009)
Cannabinoid system in the skin -a possible target for future therapies in dermatology.Cannabinoids and their derivatives are group of more than 60 biologically active chemical agents, which have been used in natural medicine for centuries. The major agent of exogenous cannabinoids is Delta(9)-tetrahydrocannabinol (Delta(9)-THC), natural psychoactive ingredient of marijuana. However, psychoactive properties of these substances limited their use as approved medicines…cannabinoids are important mediators in the skin… we summarized the significant role of the cannabinoid system in the cutaneous physiology and pathology, pointing out possible future therapeutic targets.

Therapeutic Potential of the Endocannabinoid System In Perinatal Asphyxia (2011)
Therapeutic potential of the endocannabinoid system in perinatal asphyxia… Perinatal asphyxia is the most frequent cause of neonatal brain injury and, despite advances in neonatology, it has not been possible to reduce its incidence..it is necessary to find out new and more effective therapeutic strategies, appearing the use of cannabinoids as a promising one…The endocannabinoid system modulates a wide range of physiological processes in mammals… it has been considered as an endogenous neuroprotective system… modulation of the endocannabinoid system through the administration of cannabinoids and endocannabinoids has demonstrated neuroprotective effects both in vitro and in vivo… it seems to play an important role in the development of the central nervous system, as it appears in the fetal period since the beginning.
CONCLUSION: Modulation of the endocannabinoid system appears as a novel therapeutic strategy against neonatal hypoxic-ischemic brain injury.

The Role of the Endocannabinoid System In Islet Biology (2011)
The role of the endocannabinoid system in islet biology…It is now established that there is a functional endocannabinoid system in the pancreatic islet of Langerhans and that endocannabinoids are released concurrently with glucose-induced insulin secretion. The majority of the published papers show evidence of negative effects of the endocannabinoids on insulin secretion with antagonism of the cannabinoid 1 receptor improving beta cell function.

The Endocannabinoid System: A Promising Target For the Management of Type 2 Diabetes (2009)
The endocannabinoid system: a promising target for the management of type 2 diabetes…human observations suggest that the endocannabinoid (EC) system is overactivated in presence of abdominal obesity and/or diabetes, and contributes to disturbances of energy balance and metabolism… ECS regulates the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, but also intervenes in transport, metabolism and deposit of the nutrients in the digestive tract, liver, adipose tissue, skeletal muscle, and pancreas. Activation of both central and peripheral CB1 receptors promotes weight gain… Conversely, selective CB(1) receptor antagonist in clinical use, has shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and to increase HDL cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients.

The Endocannabinoid System As A Target For Obesity Treatment (2008)
The endocannabinoid system as a target for obesity treatment…Among the promising new agents are the CB(1) receptor antagonists. These agents target receptors of the endocannabinoid system, a neuromodulatory system found to influence energy balance, eating behavior, and metabolic homeostasis via central and peripheral mechanisms…antagonism of CB(1) receptors has resulted in meaningful weight loss and improvement of lipid and glycemic profiles. Thus, these agents provide a rational and effective approach for the management of not only overweight and obesity but also their metabolic and cardiovascular sequelae.

Pharmacotherapeutic Targeting of the Endocannabinoid Signaling System: Drugs For Obesity and the Metabolic Syndrome (2008)
Pharmacotherapeutic targeting of the endocannabinoid signaling system: drugs for obesity and the metabolic syndrome…Endogenous signaling lipids (“endocannabinoids”) functionally related to Delta(9)-tetrahydrocannabinol, the psychoactive ingredient of marijuana (Cannabis), are important biomediators and metabolic regulators critical to mammalian (patho)physiology…The ubiquitous and diverse regulatory actions of the endocannabinoid system in health and disease have supported the regulatory approval of natural products and synthetic agents as drugs that alter endocannabinoid-system activity. More recent data support the concept that the endocananbinoid system may be modulated for therapeutic gain at discrete pharmacological targets with safety and efficacy. Potential medications based on the endocannabinoid system have thus become a central focus of contemporary translational research for varied indications with important unmet medical needs…selective CB1 cannabinoid receptor ligands to attenuate endocannabinoid signaling represents a state-of-the-art approach. 

 

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.

 

 

Breaking News: Louisiana’s Neti Pot Brain-Eating Amoeba and Cannabis

This week Louisiana issued a warning about using tap water and neti pots.  The amoeba, formally known as the Naegleria fowleri, can be fatal when it is introduced into the body through the nasal cavity.  It must enter the body through the nasal cavity; it cannot be ingested through drinking water.  It is recommended that neti pot users strictly use sterile water and not tap water.

Susceptibility of Naegleria fowleri to A9-Tetrahydrocannabinol
Nature holds many mysteries and one is how this brain eating amoeba is susceptible to THC.  Although it does not stop their movement it does inhibit growth of the pathogenic amoeboflagellate Naegleria fowleri. THC is amoebostatic at 5 to 50 micrograms/ml. delta 9-THC prevents enflagellation and encystment.  When there are concentrations of A9-THC. N. fowleri will not grow in standard mammalian cell cultures.

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

Treating Obesity and Diabetes With Cannabis

It is estimated that about one-third of Americans are clinically obese, with 25.8 million diagnosed with diabetes.  It is no secret that the American culture has encouraged obesity and as a result reported cases of diabetes is on the rise.

Scientists are still hard at work looking for a cure to both epidemics.  One therapy looked at is using cannabinoids.  Below you will see studies that back up the strongly held belief that cannabis is a natural cure to many illnesses that should be legalized for all.  Please feel free to spread the truth ~ Cherry Girl

The Endocannabinoid System As A Target For Obesity Treatment 
Overweight and obesity are major factors contributing to the development of type 2 diabetes mellitus (DM) and cardiovascular disease (CVD)… researchers and clinicians continue to explore pharmacotherapy, with intense efforts being directed toward the development of agents that will reduce weight and simultaneously reduce or eliminate modifiable cardiovascular and metabolic risk factors. Amongthe promising new agents are the CB(1) receptor antagonists. These agents target receptors of the endocannabinoid system, a neuromodulatory system recently found to influence energy balance, eating behavior, and metabolic homeostasis via central and peripheral mechanisms. In animal and clinical studies, antagonism of CB(1) receptors has resulted in meaningful weight loss and improvement of lipid and glycemic profiles.

ANTIOBESITY EFFICACY OF LH-21, A CANNABINOID CB(1) RECEPTOR ANTAGONIST WITH POOR BRAIN PENETRATION, IN DIET-INDUCED OBESE RATS
The peripheral blockade of cannabinoid CB(1) receptors has been proposed as a safe and effective therapy against obesity, putatively devoid of the adverse psychiatric side effects…Conclusions and implications: These results support the hypothesis that the treatment with the peripherally neutral acting cannabinoid CB(1) receptor antagonist, LH-21, may promote weight loss through modulation of visceral adipose tissue.

The Endocannabinoid System: A Promising Target For The Management Of Type 2 Diabetes
The endoCANNABINOID system “regulates the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, but also intervenes in transport, metabolism and deposit of the nutrients in the digestive tract, liver, adipose tissue, skeletal muscle, and possibly pancreas. Activation of both central and peripheral CB1 receptors promotes weight gain and associated metabolicchanges. Conversely, selective CB(1) receptor antagonists, have been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and to increase HDL cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients.

The Implication of CNR1 Gene’s Polymorphisms In The Modulation Of Endocannabinoid System Effects
The endocannabinoid system (ECS) represents one of the most important physiologic systems involved in organism homeostasis…The discovery of ECS and its signaling pathways opens a door towards the understanding of several important physiologic processes regarding appetite, food intake, metabolism, weight gain, motor control, memory, learning, drug addiction and nociception. The detailed analysis and validation of the ECS functioning can bring us very close to the discovery of new diagnosis and treatment methods for obesity, drugs abuse and numerous psychic diseases.

Rehashing Endocannabinoid Antagonists: Can We Selectively Target The Periphery To Safely Treat Obesity And Type 2 Diabetes?
A growing body of evidence supports an important role for the endocannabinoid system as a regulator of appetite, body weight, and systemic metabolism, which is overactive in obesity and type 2 diabetes. While initial attempts to target this system using rimonabant were successful in producing weight loss and improving obesity-related metabolic complications in humans, adverse central nervous system side effects precluded introduction of this drug into clinical practice. However, new data, presented by Tam and colleagues, demonstrate that selective blockade of peripheral cannabinoid receptors may be a novel successful therapeutic approach.

Pharmacotherapeutic Targeting Of The Endocannabinoid Signaling System: Drugs For Obesity And The Metabolic Syndrome.
Endogenous signaling lipids (“endocannabinoids”) functionally related to Delta(9)-tetrahydrocannabinol, the psychoactive ingredient of marijuana (Cannabis), are important biomediators and metabolic regulators critical to mammalian (patho)physiology.More recent data support the concept that the endocananbinoid system may be modulated for therapeutic gain at discrete pharmacological targets with safety and efficacy.Pressing worldwide healthcare needs and increasing appreciation of endocannabinoid biology make the rational design and refinement of targeted CB1 receptor modulators a promising route to future medications with significant therapeutic impact against overweight, obesity, obesity-related cardiometabolic dysregulation, and, more generally, maladies having a reward-supported appetitive component.

Cannabis As A Treatment Option and Cure For Epilepsy and Seizures

3 Million Americans suffer each year from seizures.  One disorder that causes seizures is Epilepsy.  Epilepsy produces seizures affecting a variety of mental and physical functions. It is also called a seizure disorder. Seizures happen when clusters of nerve cells in the brain signal abnormally, which may briefly alter a person’s consciousness, movements or actions.

Epilepsy is the third most common neurological disorder in the U.S. after Alzheimer’s disease and stroke. Its prevalence is greater than cerebral palsy, multiple sclerosis and Parkinson’s disease combined. Despite how common it is and major advances in diagnosis and treatment, epilepsy is among the least understood of major chronic medical conditions.

While medications and other treatments help many people of all ages who live with epilepsy, more than a million people continue to have seizures that can severely limit their school achievements, employment prospects and participation in all of life’s experiences.

Below you will see studies that show cannabis as a treatment option as well as a possible cure.  Please share the truth about the cure ~ Cherry Girl

The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy
Several lines of evidence suggest that cannabinoid compounds are anticonvulsant. Here we show that the marijuana extract Delta9-tetrahydrocannabinol completely abolished spontaneous epileptic seizures. These data indicate not only anticonvulsant activity of exogenously applied cannabinoids but also suggest that endogenous cannabinoid tone modulates seizure termination and duration through activation of the CB1 receptor.
http://www.ncbi.nlm.nih.gov/pubmed/12954810

Changes in the Cannabinoid (CB1) Receptor Expression Level and G-protein Activation in Kainic Acid Induced Seizures 2011
It has been known for centuries that exogenous cannabinoids, such as tetrahydrocannabinol have anticonvulsant activity. Recent studies have advanced our understanding of the endogenous cannabinoid system and renewed the interest in cannabinoids as a potential treatment for epilepsy.
http://www.ncbi.nlm.nih.gov/pubmed/22079489

Endocannabinoids and Their Implications For Epilepsy
Activation of cannabinoid receptors has been implicated in neuroprotection against excitotoxicity and can help explain the anticonvulsant properties of cannabinoids that have been known since antiquity.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1176361/?tool=pubmed

Activation of the Cannabinoid Type-1 Receptor Mediates the Anticonvulsant Properties of Cannabinoids in the Hippocampal Neuronal Culture Models of Acquired Epilepsy and Status Epilepticus
Cannabinoids have been shown to have anticonvulsant properties, but no studies have evaluated the effects of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy (AE) and status epilepticus (SE).The results from this study show CB1 receptor-mediated anticonvulsant effects of the cannabimimetic WIN 55,212-2 (THC) against both SRED and low Mg2+-induced SE in primary hippocampal neuronal cultures and show that these in vitro models of AE and SE may represent powerful tools to investigate the molecular mechanisms mediating the effects of cannabinoids on neuronal excitability.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2617751/?tool=pubmed

Assessment of the Role of CB1 Receptors in Cannabinoid Anticonvulsant Effects 
Cannabinoid compounds like delta9-tetrahydrocannabinol and cannabidiol have been shown to be anticonvulsant in maximal electroshock…This study establishes a role for the cannabinoid CB1 receptor in modulating seizure activity in a whole animal model.
http://www.ncbi.nlm.nih.gov/pubmed/11779037

Biomedical Benefits of Cannabinoids? 
Cannabinoids appear to be of therapeutic value as antiemetics, antispasmodics, analgesics and appetite stimulants and may have potential uses in epilepsy, glaucoma and asthma.The place of cannabinoids in modern medicine remains to be properly evaluated, but present evidence suggests that they could be valuable, particularly as adjuvants, for symptom control in a range of conditions for which standard drugs are not fully satisfactory.
http://www.ncbi.nlm.nih.gov/pubmed/20575778

On the application of Cannabis in Paediatrics and Epileptology
In the US over 300,000 children are affected with epilepsy.
An initial report on the therapeutic application of delta 9-THC (THC) (Dronabinol, Marinol) in 8 children suffering from the following conditions, is given: neurodegenerative disease, mitochondriopathy, posthypoxic state, epilepsy, posttraumatic reaction. THC effected reduced spasticity, improved dystonia, increased initiative (with low dose), increased interest in the surroundings, and anticonvulsive action. In several cases treatment was discontinued and in none of them discontinuing resulted in any problems. The possibility that THC-induced effects on ion channels and transmitters may explain its therapeutic activity seen in epileptic patients is discussed.
http://www.ncbi.nlm.nih.gov/pubmed/15159680

Brain Cannabinoid Systems As Targets For the Therapy of Neurological Disorders 
Unprecedented developments in cannabinoid research within the past decade include discovery of a brain (CB1) and peripheral (CB2) receptor; endogenous ligands, anandamide, and 2-arachidonylglycerol; cannabinoid drug-induced partial and inverse agonism at CB1 receptors, antagonism of NMDA receptors and glutamate, and antioxidant activity; and preferential CB1 receptor localization in areas subserving spasticity, pain, abnormal involuntary movements, seizures, and amnesia. These endogenous structures and chemicals and mechanisms are potentially new pathophysiologic substrates, and targets for novel cannabinoid treatments, of several neurological disorders.
http://www.ncbi.nlm.nih.gov/pubmed/9974182

Downregulation of the CB1 Cannabinoid Receptor and Related Molecular Elements of the Endocannabinoid System in Epileptic Human Hippocampus 
These findings show that a neuroprotective machinery involving endocannabinoids is impaired in epileptic human hippocampus and imply that downregulation of CB(1) receptors and related molecular components of the endocannabinoid system may facilitate the deleterious effects of increased network excitability.
http://www.ncbi.nlm.nih.gov/pubmed/18354002

Cannabidiol Displays Antiepileptiform and Antiseizure Properties in Vitro and in Vivo
These findings suggest that CBD acts, potentially in a CB(1) receptor-independent manner, to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel antiepileptic drug in the unmet clinical need associated with generalized seizures.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819831/?tool=pubmed

Cannabinoid Receptor Activation Reverses Kainate-Induced Synchronized Population Burst Firing in Rat
Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present results indicate that cannabinoids exert their antiepileptic effects by impeding pathological synchronization of neuronal networks in the hippocampus.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701678/?tool=pubmed

Chronic Headaches and Cannabis: Finding A Natural Relief

It is estimated that there are over 45 million Americans that suffer from chronic headaches.  This can include tension, migraine and cluster headaches.  Most of the population knows what its like to have a headache once in awhile but millions of Americans face severe pain on a regular basis which can be difficult.  The other problem that chronic pain suffers face is that the medication they are prescribed stops working after building up a tolerance.

Many of the choices for headaches can have scary side effects.  Many patients seek a natural option.  It is important to look at all your treatment options as well as thoroughly knowing your illness.  Please feel free to share the truth with not only your friends but your doctor as well.  Many are not trained in the science of cannabis and do not realize what studies have already been conducted.  ~ Cherry Girl

Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?
Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging.
CONCLUSION:
Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.
http://www.ncbi.nlm.nih.gov/pubmed/18404144

Degradation of Endocannabinoids in Chronic Migraine and Medication Overuse Headache
Chronic migraine (CM) is frequently associated with medication overuse headache (MOH). The endocannabinoid system plays a role in modulating pain including headache and is involved in the common neurobiological mechanism underlying drug addiction and reward system. Anandamide (AEA) and 2-arachidonoylglycerol are the most biologically active endocannabinoids, which bind to both central and peripheral cannabinoid receptors. The level of AEA in the extracellular space is controlled by cellular uptake via a specific AEA membrane transporter (AMT), followed by intracellular degradation by the enzyme AEA hydrolase (fatty acid amide hydrolase, FAAH). AMT and FAAH have also been characterized in human platelets. We assayed the activity of AMT and of FAAH in platelets isolated from four groups of subjects: MOH, CM without MOH, episodic migraine and controls. AMT and FAAH were significantly reduced in CM and MOH, compared to either controls or episodic migraine group. This latter finding was observed in both males and females with CM and MOH. Changes observed in the biochemical mechanisms degrading endogenous cannabinoids may reflect an adaptative behaviour induced by chronic headache and/or drug overuse.
http://www.ncbi.nlm.nih.gov/pubmed/18358734

Endocannabinoids in Chronic Migraine: CSF Findings Suggest A System Failure 
Based on experimental evidence of the antinociceptive action of endocannabinoids and their role in the modulation of trigeminovascular system activation, we hypothesized that the endocannabinoid system may be dysfunctional in chronic migraine (CM). We examined whether the concentrations of N-arachidonoylethanolamide (anandamide, AEA), palmitoylethanolamide (PEA), and 2-arachidonoylglycerol (2-AG) in the CSF of patients with CM and with probable CM and probable analgesic-overuse headache (PCM+PAOH) are altered compared with control subjects. The above endocannabinoids were measured by high-performance liquid chromatography (HPLC), and quantified by isotope dilution gas-chromatography/mass-spectrometry. Calcitonin gene-related peptide (CGRP) levels were also determined by RIA method and the end products of nitric oxide (NO), the nitrites, by HPLC. CSF concentrations of AEA were significantly lower and those of PEA slightly but significantly higher both in patients with CM and PCM+PAOH than in nonmigraineur controls (p<0.01 and p<0.02, respectively). A negative correlation was found between AEA and CGRP levels in CM and PCM+PAOH patients (r=0.59, p<0.01 and r=-0.65, p<0.007; respectively). A similar trend was observed between this endocannabinoid and nitrite levels. Reduced levels of AEA in the CSF of CM and PCM+PAOH patients may reflect an impairment of the endocannabinoid system in these patients, which may contribute to chronic head pain and seem to be related to increased CGRP and NO production. These findings support the potential role of the cannabinoid (CB)1 receptor as a possible therapeutic target in CM.
http://www.ncbi.nlm.nih.gov/pubmed/17119542 

The Endocannabinoid System and Migraine
In this review we shall describe experimental and clinical data that, intriguingly, demonstrate the link between endocannabinoids and migraine, a neurovascular disorder characterized by recurrent episodic headaches and caused by abnormal processing of sensory information due to peripheral and/or central sensitization. Although the exact ECS-dependent mechanisms underlying migraine are not fully understood, the available results strongly suggest that activation of ECS could represent a promising therapeutical tool for reducing both the physiological and inflammatory components of pain that are likely involved in migraine attacks.
http://www.ncbi.nlm.nih.gov/pubmed/20353780

Cannabinoid (CB1) Receptor Activation Inhibits Trigeminovascular Neurons
Migraine is a common and disabling neurological disorder that involves activation or the perception of activation of the trigeminovascular system.  The data suggest that Cannabinoid receptors may have therapeutic potential in migraine, cluster headache, or other primary headaches, although the potential hazards of psychoactive side effects that accompany cannabinoid treatments may be complex to overcome.
http://www.ncbi.nlm.nih.gov/pubmed/17018694

Interictal Type 1 Cannabinoid Receptor Binding is Increased in Female Migraine Patients
It has been suggested that endocannabinoid deficiency may play a role in the pathophysiology of migraine. Conclusion: The increased interictal CB1R binding, especially in brain regions that exert top-down influences to modulate pain, supports the idea that endocannibinoid deficiency is present in female patients suffering from episodic migraine.
http://www.ncbi.nlm.nih.gov/pubmed/22077199

Cluster Attacks Responsive to Recreational Cannabis and Dronabinol
Pharmacological preparations of cannabinoid compounds have a variety of therapeutic uses in medicine, including different pain syndromes…We present a patient with cluster headache who was refractory to multiple acute and preventive medications but successfully aborted his attacks with recreational marijuana use. The beneficial effect may be related to the high concentration of cannabinoid receptors in the hypothalamus, which has been implicated as a site of dysfunction in neuroimaging studies of patients with cluster headache.
http://www.ncbi.nlm.nih.gov/pubmed/19220500

Cannabinoid Deficiency: Is It the Source of Your Illness?

Millions of Americans suffer from chronic illnesses many of those with painful side effects.  Drugs that are prescribed to patients can compound this with their side effects to the body.  Many seek a treatment option that is natural.   It is important to know your illness and all your treatment options.  Below you will see studies on cannabis as a treatment option for several illnesses as well as cannabinoid deficiency as a cause.  Please feel free to share the truth with not only your friends but your doctor as well.  Many are not trained in the science of cannabis and do not realize what studies have already been conducted.  ~ Cherry Girl

Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?
Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging.
CONCLUSION:
Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.
http://www.ncbi.nlm.nih.gov/pubmed/18404144

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.

Multiple Sclerosis and Cannabis: Finding a Natural Treatment Option

It is estimated that over 400,000 Americans suffer from Multiple sclerosis or MS.  MS is a chronic, often disabling disease that attacks the central nervous system (CNS), which is made up of the brain, spinal cord, and optic nerves. Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.

The body’s own defense system attacks myelin, the fatty substance that surrounds and protects the nerve fibers in the central nervous system. The nerve fibers themselves can also be damaged. The damaged myelin forms scar tissue (sclerosis), which gives the disease its name. When any part of the myelin sheath or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing the variety of symptoms that can occur.

Below you will see a study relating to cannabis as a therapeutic option for MS.  Please share the truth about the cure ~ Cherry Girl

Cannabinoids For Symptomatic Therapy of Multiple Sclerosis 2011
Treatment of spasticity remains difficult, which has prompted some patients to self-medicate with and perceive benefits from cannabis. Advances in the understanding of cannabinoid biology support these anecdotal observations. Various clinical reports as well as randomized, double-blind, placebo-controlled studies have now demonstrated clinical efficacy of cannabinoids for the treatment of spasticity in MS patients.

Breaking News

The FDA revoked approval of the use of a popular breast cancer drug Avastin.  It was found that Avastin exposed users to potentially harmful side effects such as severe high blood pressure and hemorrhaging.  Even with this news Avastin will remain on the market where Doctors can still prescribe it to breast cancer patients but with the revoking of FDA approval it will likely cost breast cancer patients $88,000 a year which would be too costly for most.
http://www.nytimes.com/2011/11/19/business/fda-revokes-approval-of-avastin-as-breast-cancer-drug.html?_r=1

Shocking news that scientists have caught up with the public they have found merit to medical marijuana.   The Institute of Medicine has published a study stating that they found merit to cannabis.  Just had to share please pass along.  The study is from 1999 so it is curious why the government still claims no medicinal value to cannabis.
IOM finds scientific merit to medical marijuana. Institute of Medicine

New Study Finds Cannabinoids Could Be A Beneficial Treatment Option For Parkinson’s Disease

Brand new science on Parkinson’s Disease Published 2011:

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation
The present in vivo and in vitro findings clearly indicate that the CB(1) receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.
Chung YC, Bok E, Huh SH, Park JY, Yoon SH, Kim SR, Kim YS, Maeng S, Hyun Park S, Jin BK.
SourceDepartment of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Korea;

Abstract
This study examined whether the cannabinoid receptor type 1 (CB(1)) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB(1) receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB(1) receptor. The present in vivo and in vitro findings clearly indicate that the CB(1) receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.
http://www.ncbi.nlm.nih.gov/pubmed/22079984

Neurodegeneration and Cannabis

Neurodegeneration effects millions of Americans.  Neurodegeneration is a broad term used for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s,Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes.

The Endocannabinoid System in Neuropathological States
Among the group of brain disorders that have been associated with the endocannabinoid system, a special interest in various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and ischemia. These three disorders will be reviewed here from the perspective of the types of changes experienced by the cannabinoid signalling in humans and cellular or animal models, and from a possible usefulness of certain cannabinoid compounds to alleviate symptoms and/or to delay their progression.”—In other words: Because of the endocannabinoid system and cannabinoid receptors, cannabinoids could cure neurodegenerative diseases.
http://www.ncbi.nlm.nih.gov/pubmed/19367511

The Endocannabinoid System in Targeting Inflammatory Neurodegenerative Diseases 
Past posts have shown that there are functional cannabinoid receptors in the CNS and that Cannabinoids modulate the endocannabinoid system. This science says: “An early combination of neuroprotective and anti-inflammatory approaches to these disorders seems particularly desirable… We discuss the apparently unique opportunity to modify neurodegeneration and neuroinflammation simultaneously by pharmacological manipulation of the endocannabinoid system in the CNS and in peripheral immune cells.
http://www.ncbi.nlm.nih.gov/pubmed/17350694

Cannabinoid Receptors and Endocannabinoids: Role in Neuroinflammatory and Neurodegenerative Disorders
The receptors for Δ9-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB1) and 2 (CB2) and play important functions in degenerative and inflammatory disorders of the central nervous system. We discuss plasticity of the endocannabinoid system during central nervous system disorders, as well as its dysregulation, both of which have opened the way to the use of either direct and indirect activators or blockers of CB1 and CB2 receptors for the treatment of the symptoms or progression of these diseases.”—Cannabinoids are direct activators and/or blockers of CB1 and CB2.
http://www.ncbi.nlm.nih.gov/pubmed/20632970

The Endocannabinoid System in Neurodegeneration
Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the best studied endocannabinoids, and act as agonists of cannabinoid receptors. AEA and 2-AG mimic pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol, the psychoactive principle of marijuana. Together with AEA, 2-AG and congeners, the proteins that bind, transport and metabolize these lipids form the “endocannabinoid system”. This new system will be presented in this review, in order to put in a better perspective the role of the endocannabinoid pathway in neurodegenerative disorders, like Parkinson’s disease, etc… In addition, the exploitation of antagonists of endocannabinoid receptors, or of inhibitors of endocannabinoid metabolism, as next-generation therapeutics will be discussed.
http://www.ncbi.nlm.nih.gov/pubmed/17274532

Cannabinoid Receptor Signalling in Neurodegenerative Diseases: A Potential Role For Membrane Fluidity Disturbance
Endocannabinoids (eCBs)’, belong to an ancient neurosignalling system that plays important functions in neurodegenerative and neuroinflammatory disorders like Alzheimer’s disease, Parkinson’s disease, etc…The results of these investigations might be exploited for the development of novel therapeutics able to combat disorders associated with abnormal activity of CB(1).
http://www.ncbi.nlm.nih.gov/pubmed/21323908

Cannabinoids and Neuroprotection in Motor-Related Disorders 
Neuroprotective properties of cannabinoids have been extensively studied in the last years in different neurodegenerative pathologies.This potential is based on the antioxidant, anti-inflammatory and anti-excitotoxic properties exhibited by these compounds that allow them to afford neuroprotection in different neurodegenerative disorders. In the review, we collect the latest advances in the knowledge of the cellular and molecular mechanisms through which cannabinoids arrest/delay the degeneration of specific neuronal subpopulations in these motor-related disorders. This should serve to encourage that the present promising evidence obtained mainly at the preclinical level might progress to a real exploitation of neuroprotective benefits of cannabinoid-based medicines.
http://www.ncbi.nlm.nih.gov/pubmed/18220777

Medicinal Use of Cannabis in the United States: Historical Perspectives, Current Trends, and Future Directions

Medical study conducted and published 2009 please share ~ Cherry Girl

Medicinal Use of Cannabis in the United States: Historical Perspectives, Current Trends, and Future Directions
Aggarwal SK, Carter GT, Sullivan MD, ZumBrunnen C, Morrill R, Mayer JD. Source: Medical Scientist Training Program, University of Washington, Seattle, WA, USA.

Abstract
Cannabis (marijuana) has been used for medicinal purposes for millennia, said to be first noted by the Chinese in c. 2737 BCE. Medicinal cannabis arrived in the United States much later, burdened with a remarkably checkered, yet colorful, history. Despite early robust use, after the advent of opioids and aspirin, medicinal cannabis use faded. Cannabis was criminalized in the United States in 1937, against the advice of the American Medical Association submitted on record to Congress. The past few decades have seen renewed interest in medicinal cannabis, with the National Institutes of Health, the Institute of Medicine, and the American College of Physicians, all issuing statements of support for further research and development. The recently discovered endocannabinoid system has greatly increased our understanding of the actions of exogenous cannabis. Endocannabinoids appear to control pain, muscle tone, mood state, appetite, and inflammation, among other effects. Cannabis contains more than 100 different cannabinoids and has the capacity for analgesia through neuromodulation in ascending and descending pain pathways, neuroprotection, and anti-inflammatory mechanisms. This article reviews the current and emerging research on the physiological mechanisms of cannabinoids and their applications in managing chronic pain, muscle spasticity, cachexia, and other debilitating problems.
http://www.ncbi.nlm.nih.gov/pubmed/19662925

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


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

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