Ganja For Your Guts: How Cannabis Can Help IBS

No one likes dealing with an upset stomach from taco night.  Those with Irritable Bowel Syndrome or IBS deal with those symptoms and more on a frequent basis.  It is estimated that 20% of the U.S. population has IBS.  It is no wonder then why scientists would be hard at work looking for a cure.  We are seeing more and more research targeting the human Endocannabinoid system to treat illnesses.  IBS is no exception.  Below you will see studies where science has researched the role of the Endocannabinoid system with IBS and how cannabis therapy could help patients.  As always I encourage all to do their own research and please feel free to share ~ Cherry Girl

The Role of the Endocannabinoid System in the Pathophysiology and Treatment of Irritable Bowel Syndrome
Activation of cannabinoid (CB)(1) and CB(2) receptors under various circumstances reduces motility, limits secretion and decreases hypersensitivity in the gut. Drugs that alter the levels of endocannabinoids in the gut also reduce motility and attenuate inflammation. In this review, we discuss the role of the endocannabinoid system in gastrointestinal physiology. We go on to consider the involvement of the endocannabinoid system in the context of symptoms associated with IBS and a possible role of this system in the pathophysiology and treatment of IBS.

Clinical Endocannabinoid Deficiency (CECD): Can This Concept Explain Therapeutic Benefits of Cannabis In Migraine, Fibromyalgia, Irritable Bowel Syndrome and Other Treatment-Resistant Conditions?
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.

Cannabinoids For Gastrointestinal Diseases: Potential Therapeutic Applications
A pharmacological modulation of the endogenous cannabinoid system could provide new therapeutics for the treatment of a number of gastrointestinal diseases, including nausea and vomiting, gastric ulcers, irritable bowel syndrome, Crohn’s disease, secretory diarrhoea, paralytic ileus and gastroesophageal reflux disease. Some cannabinoids are already in use clinically, for example, nabilone and delta(9)-tetrahydrocannabinol are used as antiemetics.

Cannabinoids and Gastrointestinal Motility: Animal and Human Studies
Activation of prejunctional CB1 receptors reduces excitatory enteric transmission (mainly cholinergic transmission) in different regions of the gastrointestinal tract. Consistently, in vivo studies have shown that cannabinoids reduce gastrointestinal transit in rodents through activation of CB1, but not CB2, receptors. However, in pathophysiological states, both CB1 and CB2 receptors could reduce the increase of intestinal motility induced by inflammatory stimuli. Cannabinoids also reduce gastrointestinal motility in randomized clinical trials. Overall, modulation of the gut endogenous cannabinoid system may provide a useful therapeutic target for disorders of gastrointestinal motility.

Alternative Targets Within the Endocannabinoid System for Future Treatment of Gastrointestinal Diseases
Of major therapeutic interest are nonpsychoactive cannabinoids or compounds that do not directly target cannabinoid receptors but still possess cannabinoid-like properties. Drugs that inhibit endocannabinoid degradation and raise the level of endocannabinoids are becoming increasingly promising alternative therapeutic tools to manipulate the ECS.

Irritable Bowel Syndrome: A Dysfunction of the Endocannabinoid System?

Cannabis, Cancer And Children:Why We Must Give Parents A Choice

There is something special about children that brings a smile.  Some parents wait a long time to be able to have that special time to cradle their child, gazing into their eyes.  Imagine being the parents faced with the reality that your child has cancer.  For over 10,000 parents each year that is the case.  Vigilantly staying by their child’s side through countless shots, painful procedures, body wrenching medications and worst of all watching as their child withers away before their eyes.  The spark slowly going out leaving behind a weak body.  Most would try anything to save their baby.  

Current therapies  such as chemotherapy are not precise measures.  Rates of success in comparisson with side effects make some wonder why alternatives are being stifled.    In contrast there is mounting evidence of the anti-tumor effects of cannabis compounds.  Cannabis has been praised for its large window of error since cannabis does not cause death.

Most in the cannabis community know who Cashy Hyde is.  He is the little boy who’s father treated him with cannabis oil and who today is cancer free.  Cashy has undergone extensive treatments that ravaged his tiny body.  His father watched as the light faded and decided to save his son.  He fed Cashy Rick Simpson Method Cannabis Oil through his feeding tube and miraculously watched his son bounce back to life.  Within days they noticed a difference.

Cashy is not alone.  There are millions of others that have been helped and cured with cannabis.  The discussion of cannabis is beyond smoke.  Cannabis research has shown that by targeting the Endocannabinoid system with the right combinations of compounds you will receive the desired effects including inducing cell death in cancer.

With so much more scientific medical research as proof the majority of the country is asking why we still pursue prohibition with a vengeance.  California has been helping patients since 1996.  Last year we saw a flood of stories where federal agencies terrorized local communities with their SWAT style raids.  In doing so they cut off supply of much needed medicine for patients just like Cashy.

We must do something to give parents an option to save their children.  When parents are told there is nothing more that can be done should we really take away hope.  Should we incarcerate parents for possessing a plant, one that science proves is lifesaving?  We need to bring sanity back into the equation.  We must change the laws.  Me must challenge the “way its always been”.  It is time to allow parents the right to decide for their children.  Several states have proposed or pending legislation.  Contact your state representatives and urge them to help change the future for our children.

Newly Released Studies Show Protection and Regeneration of Brain Cells with Cannabis Therapies

There are over 1.7 million cases of severe brain injury that are reported each year.  These injuries can be life altering for many but thanks to the hard work from the science and medical communities we are learning more about new treatment options.  Cannabis has been discovered to help with cell regeneration and repair in the brain.  Below you will see newly published studies where  cannabis has been applied to help with brain injuries. Truly exciting!!   As always I encourage all to do their own research as well and please feel free to share ~ Cherry Girl

Early Survival of Comatose Patients After Severe Traumatic Brain Injury With the Dual Cannabinoid CB1/CB2 Receptor Agonist KN38-7271
Despite many drug trials, no substance has yet been identified that improves the outcome of severe head injury. The dual cannabinoid CB1/CB2 receptor agonist KN38-7271 mediates potent neuroprotection in animal models. We describe here the first randomized, double-blind, prospective, placebo-controlled clinical phase IIa proof-of-concept trial to investigate the safety, pharmacokinetics, and potential efficacy of a cannabinoid receptor agonist in humans.  Conclusions KN38-7271 appeared beneficial in the acute early phase of the comatose patient after a head injury. Its use was safe and well tolerated by patients.

Cannabinoids As Neuroprotective Agents In Traumatic Brain Injury
Cannabinoids of all classes have the ability to protect neurons from a variety of insults that are believed to underlie delayed neuronal death after traumatic brain injury (TBI), including excitotoxicity, calcium influx, free radical formation and neuroinflammation.

Cannabidiol Administration After Hypoxia-Ischemia To Newborn Rats Reduces Long-Term Brain Injury and Restores Neurobehavioral Function 2012
Cannabidiol (CBD) demonstrated short-term neuroprotective effects in the immature brain following hypoxia-ischemia (HI).   In conclusion, CBD administration after HI injury to newborn rats led to long-lasting neuroprotection, with the overall effect of promoting greater functional rather than histological recovery.

Cannabidiol Reduces Brain Damage and Improves Functional Recovery After Acute Hypoxia-Ischemia In Newborn Pigs 2011
Newborn piglets exposed to acute hypoxia-ischemia (HI) received i.v. cannabidiol (HI + CBD) or vehicle (HI + VEH). In HI + VEH, 72 h post-HI brain activity as assessed by amplitude-integrated EEG (aEEG) had only recovered to 42 ± 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 ± 2.3 points, normal 36).   In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements.
 

Cannabis Has Cancer In The Cross-Hairs. Utilizing The Endocannabinoid System To Kill Cancer

It seems that these days the word cancer is everywhere.  From billboards encouraging donations to charities to news headlines to loved one effected by cancer most people are familiar.  There are more than 200 different types of cancer that can develop in over 60 different organs in the body.  Current therapies include poisoning the body in hopes that it will also kill the cancer.  Cannabis is used to help counteract the side effects of these therapies.  However new research points to cannabis as the compounds that can actually cause cancer cell death, essentially curing cancer.  There are countless studies that have been published showing the benefits of using the endocannabinoid system to target cancer cells with cannabinoids.  From that research we have found where using the endocannabinoid system has proven vital in fighting cancer.  Below you will see several studies that show how using the endocannabinoid system can be used in targeting cancer.  Please feel free to share and help others see that using cannabis is beyond the smoke.  I encourage all to do their own research as well ~ Cherry Girl

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.    Remarkably, these effects may be selective for the cancer cells, while normal cells and tissues are spared. Such apparent tumor cell selectivity makes the endocannabinoid system an attractive potential target for cancer therapy.

Targeting the Endocannabinoid System For the Treatment of Cancer–A Practical View
In recent years, considerable interest has been generated by findings that cannabinoids not only have useful palliative effects, but also can affect the viability and invasivity of a variety of different cancer cells.   It is concluded that cannabinoids (or agents modulating the endogenous cannabinoid system) are an attractive target for drug development in the cancer area….

The Endocannabinoid System As A Target For the Development of New Drugs For Cancer Therapy
Studies on the main bioactive components of Cannabis sativa, the cannabinoids, and particularly (THC), led to the discovery of a new endogenous signalling system that controls several physiological and pathological conditions: the endocannabinoid system. Recently, evidence has accumulated indicating that stimulation of cannabinoid receptors by either THC or the endocannabinoids influence the intracellular events controlling the proliferation and apoptosis(cell death) of numerous types of cancer cells, thereby leading to anti-tumour effects both in vitro and in vivo. This evidence is reviewed here and suggests that future anti-cancer therapy might be developed from our knowledge of how the endocannabinoid system controls the growth and metastasis of malignant cells.

Endocannabinoid System Modulation In Cancer Biology and Therapy
Endocannabinoid system modulation in cancer biology and therapy. The discovery of the endocannabinoid system… led to the development of therapeutic agents related to either the stimulation or antagonism of CB1 and CB2 cannabinoid receptors… evidence suggests that agonists of cannabinoid receptors, which share the useful property to discern between tumor cells and their non-transformed counterparts, could represent novel tumor-selective tools to treat cancer in addition to their already exploited use as palliative drugs.

Use of Cannabinoid Receptor Agonists In Cancer Therapy As Palliative and Curative Agents
“Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents… Cannabinoids (the active components of Cannabis sativa)… development, exploration and use of cannabinoid agonists for cancer therapy, not only as palliative but also as curative drugs.

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… cannabinoids might be effective anti-tumoral agents because of their ability to inhibit the growth of various types of cancer… Evidence suggests that the endocannabinoid system may be dysregulated in a number of cancers… 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.

Save Your Ass, Smoke Some Grass

When people think of grass, weed, pot or cannabis they think of hippies and parties.  What most people don’t think about is that cannabis is showing real promise, on the molecular level, in fighting cancers.  People of all walks have been touched by cancer.  Most people know of someone, has had a loved one go through it or they themselves have experienced cancer.  It is no wonder then that science and medicine have been working hard to find a cure.  Cannabis research has been taking notice especially for its anti-cancer discoveries.   Over 140,000 new cases were reported for colon and rectal cancers with 51,000 reported deaths.  Below you will see studies where cannabis has been examined in the context of colorectal cancers.  As always please feel free to share and I encourage all to do their own research as well ~ Cherry Girl

Single Nucleotide Change in the Cannabinoid Receptor-1 (CNR1) Gene in Colorectal Cancer Outcome
The cannabinoid receptor-1 (CNR-1) and endogenous agonists of this receptor are present in the central and peripheral nervous systems including the gastrointestinal nervous system.Indeed nontumor paired colorectal tissues showed nucleotide change. A large number of patients with mutation in the CNR1 gene were observed. These preliminary findings highlight the importance of further studies in the use of cannabinoid analogs as receptor ligands to analyze potential therapeutic effects.

Cannabinoid Receptor Activation Induces Apoptosis(programmed cell death) through Tumor Necrosis Factor α–Mediated Ceramide De novo Synthesis in Colon Cancer Cells
We show that the CB1 receptor was mainly expressed in human normal colonic epithelium whereas tumor tissue was strongly positive for the CB2 receptor.  The present study shows that either CB1 or CB2 receptor activation induces apoptosis through ceramide de novo synthesis in colon cancer cells. Our data unveiled, for the first time, that TNF-α acts as a link between cannabinoid receptor activation and ceramide production.

Apoptosis: Programmed Cell Death At A Molecular Level
Balanced apoptosis is crucial in development and homeostasis, and all multicellular organisms have a physiologically programmed continuum of pathways to apoptotic cell death. Further studies of the control at the molecular level of key components and promoters/suppressors of apoptosis may provide better approaches to treatment of autoimmune diseases, malignancies, and neurodegenerative disorders. Many important questions remain regarding the advantages of modifying apoptotic programs in clinical situations.

Cannabis: Your Heart Hero

More and more Americans are being classified as obese.  With obesity comes other complications such as cardiovascular disease.  Cardiovascular disease refers to any disease that affects the cardiovascular system, principally cardiac disease, vascular diseases of the brain and kidney, and peripheral arterial disease.  The causes of cardiovascular disease are diverse but atherosclerosis and/or hypertension are the most common.  It is estimated that one-third of Americans die from cardiovascular disease so it is no wonder that scientists have been hard at work trying to find a cure.   Below you will see studies where science has looked at cannabis compounds when applied to CVD.  Please feel free to share and I encourage all do their own research as well ~ Cherry Girl

Targeting Cannabinoid Receptor CB(2 ) in Cardiovascular Disorders: Promises and Controversies
“Cardiovascular disease is the leading cause of death and disability worldwide, which can be largely attributed to atherosclerosis, a chronic inflammation of the arteries… the lipid endocannabinoid system has emerged as a new therapeutic target in variety of disorders associated with inflammation and tissue injury, including those of the cardiovascular system. The discovery that delta-9-tetrahydrocannabinol (Δ9-THC), the main active constituent of marijuana, inhibited atherosclerotic plaque progression via a cannabinoid 2 (CB(2) ) receptor-dependent anti-inflammatory mechanism.

Endocannabinoid System in Cardiovascular Disorders – New Pharmacotherapeutic Opportunities
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.

Never Fear Cannabis Is Here! How Cannabis Can Help With Fear, Anxiety, and Other Psychiatric Disorders

Nearly 19 million Americans suffer from a  psychiatric disorder which could include disorders such as specific phobias, generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, obsessive-compulsive disorder and post-traumatic stress disorder.  Many veterans returning from war have found cannabis to be a relief from PTSD.  Below you will studies where science has studied the effects of cannabis compounds when applied to psychiatric disorders.  Please feel free to share and I encourage all to do their own research as well ~ Cherry Girl

The Endocannabinoid System in the Processing of Anxiety and Fear and How CB1 Receptors May Modulate Fear Extinction 
The endocannabinoid system recently emerged as an important modulator of many neuronal functions. Among them, the control of anxiety and acquired fear represents nowadays one of the most interesting fields of research.  Finally, a neurobiological model possibly able to implement the role of the endocannabinoid system in these processes will be proposed.

CB1 Cannabinoid Receptors Modulate Kinase and Phosphatase Activity During Extinction of Conditioned Fear in Mice
Cannabinoid receptors type 1 (CB1) play a central role in both short-term and long-term extinction of auditory-cued fear memory.  We propose that the endogenous cannabinoid system modulates extinction of aversive memories, at least in part via regulation of the activity of kinases and phosphatases in a brain structure-dependent manner.

Extinction of Emotional Response As A Novel Approach of Pharmacotherapy of Anxiety Disorders 
The patogenesis of anxiety may be related to the process of an extinction of aversive memories… Studies on molecular and cellular mechanisms responsible for individual fear extinction may serve as the basis of search for more effective forms of clinical treatment… ligands stimulating endogenous cannabinoid system… these substances stimulate different central mechanisms, they appear to act synergistically, to improve the behavioural therapy.

Enhancing Cannabinoid Neurotransmission Augments the Extinction of Conditioned Fear
the findings in the present study suggest that augmenting eCB-mediated neurotransmission by inhibition of eCB transport or breakdown may provide a novel mechanism for enhancing the extinction of fear. As such, eCB reuptake inhibitors may serve as useful adjuncts in the treatment of anxiety disorders (such as PTSD, panic disorder, and OCD) as well as drug addiction and other disorders that respond to behavioral treatments utilizing extinction processes.

The Endogenous Cannabinoid System Controls Extinction of Aversive Memories
Acquisition and storage of aversive memories is one of the basic principles of central nervous systems throughout the animal kingdom. In the absence of reinforcement, the resulting behavioural response will gradually diminish to be finally extinct.  We propose that endocannabinoids facilitate extinction of aversive memories through their selective inhibitory effects on local inhibitory networks in the amygdala.

The Endocannabinoid system and Extinction Learning
As several human psychiatric disorders, such as phobia, generalized anxiety disorders, and posttraumatic stress disorder (PTSD) appear to involve aberrant memory processing and impaired adaptation to changed environmental conditions, the hope has been fuelled that the endocannabinoid system might be a valuable therapeutic target for the treatment of these disorders.

Bringing the War Back Home: Mental Health Disorders Among 103,788 US Veterans Returning From Iraq and Afghanistan Seen at Department of Veterans Affairs Facilities
Co-occurring mental health diagnoses and psychosocial problems were detected early and in primary care medical settings in a substantial proportion of OEF/OIF veterans seen at VA facilities. Targeted early detection and intervention beginning in primary care settings are needed to prevent chronic mental illness and disability.

Psychosis and Trauma. Theorical Links Between Post-Traumatic and Psychotic Symptoms
The links between psychotic and psycho-traumatic symptoms are complex and multidirectional; this co-occurrence is a factor of seriousness. The clinician, while paying attention to these symptoms, has to distinguish the structure of the personality of the subject to articulate the psychotherapy and the pharmacological treatment. Further investigational studies may determine whether antipsychotics will enhance treatment response in PTSD patients with psychotic features.

Cannabis and Liver Disease

The human liver is the largest organ in the body.  It has many functions as well as afflictions.  Some are inherited and others are through abuse or viruses.  There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, hepatitis B and hepatitis C. Others can be the result of drugs, poisons or drinking too much alcohol. If the liver forms scar tissue because of an illness, it’s called cirrhosis.  Jaundice, or yellowing of the skin, can be one sign of liver disease.  Like other parts of your body, cancer can affect the liver. You could also inherit a liver disease such as hemochromatosis.  Below are studies that show the interaction of cannabis compounds and the liver.  Please feel free to share ~ Cherry Girl

The Endocannabinoid System As A Novel Target For the Treatment of Liver Fibrosis
We have recently demonstrated that CB1 and CB2 receptors display opposite effects in the regulation of liver fibrogenesis during chronic liver injury. Indeed, both receptors are up-regulated in the liver of cirrhotic patients, and expressed in liver fibrogenic cells. Moreover, CB1 receptors are profibrogenic and accordingly, the CB1 antagonist rimonabant reduces fibrosis progression in three experimental models. In keeping with these results, daily cannabis smoking is a risk factor for fibrosis progression in patients with chronic hepatitis C. In contrast, CB2 display antifibrogenic effects, by a mechanism involving reduction of liver fibrogenic cell accumulation. These results may offer new perspectives for the treatment of liver fibrosis, combining CB2 agonist and CB1 antagonist therapy.

The Endocannabinoid System and Liver Diseases
The endocannabinoid system and liver diseases… molecules targeting the CB(1) and CB(2) receptors may represent potential therapeutic agents for the treatment of liver diseases. At present, the CB(1) antagonists represent the most attractive pharmaceutical tool to resolve fat accumulation in patients with non-alcoholic fatty liver disease and to treat patients with cirrhosis, as they may slow the progression of fibrosis and attenuate the cardiovascular alterations associated with the advanced stage of the disease.

Endocannabinoids in Liver Disease
Marijuana has been used for its psychoactive and medicinal properties for millennia. As other plant-derived substances, marijuana has been slow to yield its secrets, with insights into its mechanism of action beginning to emerge only during the last decades… Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana… Although the documented therapeutic potential of CB(1) blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB(1) antagonists.

Endogenous Cannabinoids in Liver Disease: Many Darts For A Single Target
Endogenous cannabinoids are ubiquitous lipid-signaling molecules able to partially mimic the actions produced by Delta(9)-tetrahydrocannabinol, the compound responsible for most of the effects of marijuana… The endocannabinoid system is involved in the pathogenesis of the cardiovascular dysfunction occurring in advanced liver disease and also plays a role in the pathogenesis of portal hypertension and liver fibrosis… These findings indicate that the endocannabinoid system may open new avenues for the therapeutic regulation of fibrosis and portal hypertension in advanced liver disease.

Cannabinoid Receptors As New Targets of Antifibrosing Strategies During Chronic Liver Diseases
Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases… Chronic liver injury exposes the patient to liver fibrosis and its end stage, cirrhosis, is a major public health problem worldwide… prevailing causes of cirrhosis include chronic alcohol consumption, hepatitis C virus infection and non-alcoholic steatohepatitis…. the authors recently demonstrated that the endocannabinoid system shows promise as a novel target for antifibrotic therapy during chronic liver injury. Indeed, cannabinoid receptors CB1 and CB2 promote dual pro- and antifibrogenic effects, respectively. Therefore, endocannabinoid-based therapies, combining CB2 agonists and CB1 antagonists may open novel therapeutic perspectives for the treatment of chronic liver diseases.

CB1 Cannabinoid Receptor Antagonism: A New Strategy For the Treatment of Liver Fibrosis
Hepatic fibrosis, the common response associated with chronic liver diseases, ultimately leads to cirrhosis, a major public health problem worldwide.  Genetic or pharmacological inactivation of CB1 receptors decreased fibrogenesis by lowering hepatic transforming growth factor (TGF)-beta1 and reducing accumulation of fibrogenic cells in the liver after apoptosis and growth inhibition of hepatic myofibroblasts. In conclusion, our study shows that CB1 receptor antagonists hold promise for the treatment of liver fibrosis.

Role of Cannabinoids in Chronic Liver Diseases
The role of the endocannabinoid system in hepatic physiology and pathologic conditions has been studied recently. Unquestionably, influencing endocannabinoid signaling may have a beneficial effect on delaying or even reversing hepatic fibrosis.

CB2 Receptors As New Therapeutic Targets For Liver Diseases
phytocannabinoids have long been used for recreational and therapeutic purposes… studies have unravelled pleiotropic functions of CB2 receptors under physiological and pathological conditions, including acute and chronic liver diseases. Additional functions may soon arise… These findings may open novel therapeutic avenues, upon clinical development of CB2-specific molecules.

Beneficial Paracrine Effects of Cannabinoid Receptor 2 on Liver Injury and Regeneration
CONCLUSION: CB2 receptors reduce liver injury and promote liver regeneration following acute insult, via distinct paracrine mechanisms involving hepatic myofibroblasts. These results suggest that CB2 agonists display potent hepatoprotective (ability to prevent damage to the liver) properties, in addition to their antifibrogenic effects.

Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis
CB1 expression is upregulated in human ALF (alcoholic liver fibrosis ) which is at least in part triggered by acetaldehyde (AA) and oxidative stress. Inhibition of CB1… or via genetic knock-out protects against alcoholic-induced fibrosis in vitro and in vivo….CB1 antagonists have been used in treating alcohol dependence without causing significant depression.

The Endocannabinoid System As A Key Mediator During Liver Diseases: New Insights and Therapeutic Openings
“The endocannabinoid system as a key mediator during liver diseases: new insights and therapeutic openings… hepatic cannabinoid receptor 2 (CB(2)) receptors display beneficial effects on alcoholic fatty liver, hepatic inflammation, liver injury, regeneration and fibrosis. Cannabinoid receptor 1 (CB(1)) receptors have been implicated in the pathogenesis of several lesions such as alcoholic and metabolic steatosis, liver fibrogenesis, or circulatory failure associated with cirrhosis… data obtained with peripherally restricted CB(1) antagonists give real hopes in the development of active CB(1) molecules devoid of central adverse effects.

Pathogenesis of Alcohol-Induced Liver Disease: Classical Concepts and Recent Advances
Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking.  The observation that ALD and non-alcoholic steatohepatitis share common pathways and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non-coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy.

The Role of the Cannabinoid System in the Pathogenesis and Treatment of Alcohol Dependence
The lack of satisfactory results of alcohol dependence treatment force us to search for new directions of research.  SR141716 (rimonabant), a CB1 receptor antagonist, significantly lowers voluntary alcohol intake and motivation for its consumption in various experimental studies. Very encouraging results of preclinical studies were not completely confirmed in the clinical studies. However, further clinical studies are still necessary.

 

The Human Prenatal Endocannabinoid System

Since the discovery of the human endocannabinoid system science has been busy trying to unlock the mysteries of this complex system.  Science has uncovered many interesting features of this system.  This includes the presence of this multi-function system in fetuses.   Below you will see studies on how science has uncovered in-dept knowledge of the endocannabinoid system in pre and post natal subjects.  I encourage all to do their own research and please feel free to share the TRUTH ~ Cherry Girl

Multiple Roles For the Endocannabinoid System During the Earliest Stages Of Life: Pre- and Postnatal Development
The endocannabinoid system, including its receptors (CB(1) and CB(2)), endogenous ligands (‘endocannabinoids’), synthesising and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development.  Multiple roles for the endocannabinoid system during the earliest stages of life: pre- and postnatal development…the endocannabinoid system appears to play an essential role for development and survival… the endocannabinoid system plays several key roles in pre- and postnatal development. Future studies should further clarify the mechanisms involved… in order to design strategies for the treatment of conditions such as infertility, mental retardation and failure-to-thrive.

The Endocannabinoid-CB Receptor System: Importance For Development and In Pediatric Disease
The endocannabinoid-CB receptor system: Importance for development and in pediatric disease… it is suggested that children may respond positively to medicinal applications of cannabinoids without undesirable central effects. Excellent clinical results have previously been reported in pediatric oncology and in case studies of children with severe neurological disease or brain trauma. We suggest cannabinoid treatment for children or young adults with cystic fibrosis in order to achieve an improvement of their health condition including improved food intake and reduced inflammatory exacerbations.

On the Application of Cannabis In Paediatrics and Epileptology
An initial report on the therapeutic application of delta 9-THC (THC) (Dronabinol, Marinol) in 8 children resp. adolescents suffering from the following conditions, is given: neurodegenerative disease, mitochondriopathy, posthypoxic state, epilepsy, posttraumatic reaction. THC effected reduced spasticity, improved dystonia, increased initiative, increased interest in the surroundings, and anticonvulsive action…possibility that THC-induced effects on ion channels and transmitters may explain its therapeutic activity seen in epileptic patients.

The Endocannabinoid-CB(1) Receptor System In Pre- and Postnatal Life
The endocannabinoid-CB(1) receptor system in pre- and postnatal life.. CB(1) receptors display a transient presence in white matter areas of the pre- and postnatal nervous system, suggesting a role for CB(1) receptors in brain development…Further observations suggest that children may be less prone to psychoactive side effects of Delta(9)-tetrahydrocannabinol or endocannabinoids than adults. The medical implications of these novel developments are far reaching and suggest a promising future for cannabinoids in pediatric medicine for conditions including “non-organic failure-to-thrive” and cystic fibrosis.

Endocannabinoids and Food Intake: Newborn Suckling and Appetite Regulation In Adulthood
The appetite-stimulating effects of the cannabis plant (Cannabis sativa) have been known since ancient times, and appear to be effected through the incentive and rewarding properties of foods. Investigations into the biological basis of the multiple effects of cannabis have yielded important breakthroughs in recent years… exciting progress in the understanding of how the endocannabinoid CB receptor systems influence appetite and body weight is stimulating the development of therapeutic orexigenic and anorectic agents. Furthermore, the role of cannabinoid CB1 receptor activation for milk suckling in newborns may open new doors toward understanding nonorganic failure-to-thrive in infants, who display growth failure without known organic cause.

Ontogenetic Development of Cannabinoid Receptor Expression and Signal Transduction Functionality in the Human Brain
Previous evidence suggests that the endogenous cannabinoid system emerges relatively early during brain development in the rat. However, the pre- and postnatal pattern of appearance of CB1 cannabinoid receptors in humans has not been analysed in detail.   This early pattern of expression of functionally active cannabinoid receptors, along with the transient and atypical localization of these proteins in white matter areas during the prenatal stages, suggest an specific role of the endocannabinoid system in the events related to human neural development.

 

Cannabis And The Human Immune System

For over 50 years science has been trying to unravel the questions that surround our endocannabinoid system.  Science has discovered many exciting breakthroughs including how cannabis, our endocannabinoid stem and our immune system work together.  below you will see studies on how this has been studied.  Please feel free to do your own research, seek out and share the truth ~ Cherry Girl

Immune Control By Endocannabinoids – New Mechanisms of Neuroprotection?
The endocannabinoid system consists of cannabinoid receptors, their endogenous ligands and enzymes for synthesis and degradation of endocannabinoids and represents a local messenger system within and between the nervous and immune system. Apparently, the endocannabinoid system is involved in immune control and neuroprotection.

Cannabinoid Treatment Suppresses the T-helper Cell-Polarizing Function of Mouse Dendritic Cells Stimulated With Legionella Pneumophila Infection
“In conclusion, our results show that a major cellular target of THC-induced immune suppression of Th1 immunity is the dendritic cell and that the drug attenuates polarizing function… THC… might be of use in the treatment of chronic inflammatory diseases, such as celiac disease and Crohn’s disease, rheumatoid arthritis, and systemic lupus, and therefore might be in the class of anti-inflammatory drugs recognized to interfere with earlier stages of immunity by suppressing DC activation.

Role of Cannabinoid Receptors In Delta-9-Tetrahydrocannabinol Suppression of IL-12p40 In Mouse Bone Marrow-Derived Dendritic Cells Infected With Legionella Pneumophila
These results suggest that THC-induced suppression of serum IL-12 is partly due to a suppression of IL-12 production by dendritic cells and that G(i) signaling and cannabinoid receptors, but not TRPV1, are involved in this suppressive effect.

The Endogenous Cannabinoid 2-Arachidonoyl Glycerol As In Vivo Chemoattractant For Dendritic Cells and Adjuvant For Th1 Response To A Soluble Protein
The decision-making mechanisms that determine the choice of the appropriate effector immune response to a microbial challenge are poorly understood. The endocannabinoid 2-arachidonoylglycerol (2-AG), injected intradermally in mice together with a soluble protein and a T helper-2 (Th2) priming Toll-like receptors (TLRs) agonist during primary immunization, shifts the memory response to the Th1 type. As 2-AG may be induced in tissues by various stimuli at concentrations similar to that used in our study, this evidence might be of a wide-ranging pathophysiological relevance.

Presence and Regulation of the Endocannabinoid System In Human Dendritic Cells
Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been detected in several blood immune cells, including monocytes/macrophages, basophils and lymphocytes. However, their presence in dendritic cells, which play a key role in the initiation and development of the immune response, has never been investigated.  These findings demonstrate for the first time that the endogenous cannabinoid system is present in human dendritic cells and can be regulated by cell activation.

The Endocannabinoid System: Mechanisms Behind Metabolic Homeostasis and Imbalance
The endocannabinoid system: mechanisms behind metabolic homeostasis and imbalance…EC agonists and receptors have been identified in the brain, liver, and peripheral adipose tissue, and the EC system is known to affect metabolism in these areas and others through neuromodulatory signals. Meal size, body weight, and numerous metabolic factors such as triglyceride and cholesterol levels, insulin resistance, and glucose intolerance can be affected via the EC system.

Delta 9-Tetrahydrocannabinol Modulates Antigen Processing By Macrophages
THC differentially modulates the capacity of macrophages to process antigens that is necessary for the activation of CD4+ T cells… delta 9-Tetrahydrocannabinol modulates antigen processing by macrophages.

Cannabinoid Receptors: Key To Cannabis’ Healing Success

Since the discovery of the endocannabinoid system in the 60′s science has been hard at work trying to unlock the mysteries surrounding cannabis and the interaction of the human body.  For thousands of years cannabis has been used for medicinal, religious and recreation purposes.  Below you will see studies that explain a little as to why cannabis works the way it does within our system.  You will see how CB1 and   CB2 receptors interact with cannabis and how they play a key role in its therapeutic properties.   I encourage all to do their own research and seek out the truth please feel free to share ~ Cherry Girl

The CB(2) Cannabinoid Receptor Controls Myeloid Progenitor Trafficking: Involvement In the Pathogenesis of An Animal Model of Multiple Sclerosis
These findings demonstrate the protective role of CB(2) receptors in experimental autoimmune encephalomyelitis EAE pathology; provide evidence for a new site of CB(2) receptor action, namely the targeting of myeloid progenitor trafficking and its contribution to microglial activation; and support the potential use of non-psychoactive CB(2) agonists in therapeutic strategies for multiple sclerosis and other neuroinflammatory disorders.

Transcriptional Regulation of the Cannabinoid Receptor Type 1 Gene In T Cells By Cannabinoids
Effects of cannabinoids (CBs) are mediated by two types of receptors, CB1 and CB2. In this report, we investigated whether CBs regulate gene expression of their cognate receptors in T cells and studied underlying mechanisms in CD4+ Jurkat T cells.  In summary, up-regulation of CB1 in T lymphocytes in response to CBs themselves may facilitate or enhance the various immunomodulatory effects related to CBs.

Therapeutic Action of Cannabinoids In A Murine Model of Multiple Sclerosis
Cannabinoids may act as immunosuppressive compounds that have shown therapeutic potential in chronic inflammatory disorders… Overall, the data presented may have potential therapeutic implications in demyelinating pathologies such as MS; in particular, the involvement of cannabinoid receptor CB2 would enable nonpsychoactive therapy suitable for long-term use.

The Human Eye Expresses High Levels of CB1 Cannabinoid Receptor mRNA and Protein
These results further support the proposed role of the CB1 receptor in controlling intraocular pressure, helping to explain the antiglaucoma properties of marijuana.

CB1 and CB2 Receptor mRNA Expression In Human Peripheral Blood Mononuclear Cells (PBMC) From Various Donor Types
Marijuana cannabinoid receptors (CBR), CB1 and CB2, are G protein-coupled receptors… expressed in brain as well as cells of the periphery…results suggest that CBR expression is relatively constant across the human population.

Cannabinoid-receptor 1 Null Mice Are Susceptible To Neurofilament Damage and Caspase 3 Activation
Administered cannabinoids have been shown to ameliorate signs of CNS inflammatory disease in a number of animal models, including allergic encephalomyelitis. More recently, neuroprotective actions have been attributed to activation of the cannabinoid 1 receptor in a number of in vitro and in vivo models…The data presented further strengthen the hypothesis of neuroprotection elicited via cannabinoid receptor 1 signaling.

Detailed Characterization of CB2 Receptor Protein Expression In Peripheral Blood Immune Cells From Healthy Human Volunteers Using Flow Cytometry
These data provide the first detailed analysis of CB2 protein levels in blood leukocyte subsets from healthy donors and identifies the cell types which could be targeted with CB-mimetic drugs in humans.

Cannabinoid-Induced Immune Suppression and Modulation of Antigen-Presenting Cells
The study of marijuana cannabinoid biology has led to many important discoveries in neuroscience and immunology. These studies have uncovered a new physiological system, the endocannabinoid system, which operates in the regulation of not only brain function but also the regulation of the immune system. Studies examining the effect of cannabinoid-based drugs on immunity have shown that many cellular and cytokine mechanisms are suppressed by these agents leading to the hypothesis that these drugs may be of value in the management of chronic inflammatory diseases. In this report, we review current information on cannabinoid ligand and receptor biology, mechanisms involved in immune suppression by cannabinoids with emphasis on antigen-presenting cells, and preclinical and clinical models analyzing the therapeutic potential of cannabinoid-based drugs.

Immunoregulation of A CB2 Receptor Agonist In A Murine Model of NeuroAIDS
Chronic HIV-1 infection commonly affects behavioral, cognitive, and motor functions in the infected human host and is commonly referred to as HIV-1-associated neurocognitive disorders (HAND)…Our results support the notion that CB2 receptor agonists may be a viable therapeutic candidate for HAND.

Anandamide Prior To Sensitization Increases Cell-Mediated Immunity In Mice
The endocannabinoid system has become a topic of great interest in pharmacology due to its remarkable distribution in mammal organisms and capacity to play a modulatory role on several physiological systems, including modulation of immunity. Many studies have shown that administration of cannabinoids causes inhibitory effects on immune cells, including decreased proliferation and antigen-presenting cell (APC) co-stimulatory activity. In contrast, other groups have shown that some cannabinoids might present stimulatory actions on macrophage activity and T cell activation…Anandamide prior to sensitization increases cell-mediated immunity in mice.

Endogenous Modulators of Synaptic Transmission: Cannabinoid Regulation In the Supraoptic Nucleus
The magnocellular neurons of the hypothalamic supraoptic nucleus (SON) are a major source of both systemic and central release of the neurohypophyseal peptides, oxytocin (OXT) and arginine-vasopressin (AVP).  Further study of eCB signalling in the SON, including its interaction with AVP neurons, promises to extend our understanding of the synaptic regulation of SON physiological function.

 

 

Newly Released Studies That Show Medical Value Of Cannabis 2011

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

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

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

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

Prevention and Treatment of Alzheimer’s Disease With Cannabis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A Natural Choice For Pain Management

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

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

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


Cannabis: Inflammation and Pain Reliever

Cannabis has been used for thousands of years as a natural remedy for many things.  In modern times and especially now when medical marijuana has come more to the forefront we are seeing that it does in fact posses medicinal properties.  CBD (Cannabidiol) has recently been discussed more since discovering that it relieves pain, nausea, spasms, anxiety as well as its sedative and anti-inflammatory properties without the psychoactive response.
Below are studies that show how cannabis has properties that effect inflammation and pain.   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

Targeting Cannabinoid Agonists For Inflammatory and Neuropathic Pain.
“It is well known that cannabinoid receptor agonists produce relief of pain in a variety of animal models by interacting with cannabinoid receptors.A large body of preclinical data supports the hypothesis that either CB(2)-selective agonists or CB(1) agonists acting at peripheral sites, or with limited CNS exposure, will inhibit pain and neuroinflammation without side effects within the CNS.”
‎”Targeting cannabinoid agonists for inflammatory and neuropathic pain.
Cheng Y, Hitchcock SA.
 Source Amgen, Inc., Chemistry Research and Development, MS 29-2-C, Thousand Oaks, CA 91320, USA. yuanc@amgen.com 

Abstract
The cannabinoid receptors CB(1) and CB(2) are class A G-protein-coupled receptors. It is well known that cannabinoid receptor agonists produce relief of pain in a variety of animal models by interacting with cannabinoid receptors. CB(1) receptors are located centrally and peripherally, whereas CB(2) receptors are expressed primarily on immune cells and tissues. A large body of preclinical data supports the hypothesis that either CB(2)-selective agonists or CB(1) agonists acting at peripheral sites, or with limited CNS exposure, will inhibit pain and neuroinflammation without side effects within the CNS. There has been a growing interest in developing cannabinoid agonists. Many new cannabinoid ligands have been synthesized and studied covering a wide variety of novel structural scaffolds. This review focuses on the present development of cannabinoid agonists with an emphasis on selective CB(2) agonists and peripherally restricted CB(1) or CB(1)/CB(2) dual agonists for treatment of inflammatory and neuropathic pain.”
http://www.ncbi.nlm.nih.gov/pubmed/17594182

Antinociceptive Effects Induced Through the Stimulation of Spinal Cannabinoid Type 2 Receptors In Chronically Inflamed Mice
“The stimulation of spinal cannabinoid type 2 (CB(2)) receptors is a suitable strategy for the alleviation of experimental pain symptoms.These results demonstrate that effective analgesia can be achieved in chronic inflammatory settings through the stimulation of spinal cannabinoid CB(2) receptors even if this receptor population is not up-regulated.”
‎”Antinociceptive effects induced through the stimulation of spinal cannabinoid type 2 receptors in chronically inflamed mice. Curto-Reyes V, Boto T, Hidalgo A, Menéndez L, Baamonde A. Source Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Facultad de Medicina C/ Julián Clavería, 6. 33006 Oviedo, Asturias, Spain. 

Abstract
The stimulation of spinal cannabinoid type 2 (CB(2)) receptors is a suitable strategy for the alleviation of experimental pain symptoms. Several reports have described the up-regulation of spinal cannabinoid CB(2) receptors in neuropathic settings together with the analgesic effects derived from their activation. Besides, we have recently reported in two murine bone cancer models that the intrathecal administration of cannabinoid CB(2) receptor agonists completely abolishes hyperalgesia and allodynia, whereas spinal cannabinoid CB(2) receptor expression remains unaltered. The present experiments were designed to measure the expression of spinal cannabinoid CB(2) receptors as well as the analgesic efficacy derived from their stimulation in mice chronically inflamed by the intraplantar injection of complete Freund’s adjuvant 1week before. Both spinal cannabinoid CB(2) receptors mRNA measured by real-time PCR and cannabinoid CB(2) receptor protein levels measured by western blot remained unaltered in inflamed mice. Besides, the intrathecal (i.t.) administration of the cannabinoid CB(2) receptor agonists AM1241, (R,S)-3-(2-Iodo-5-nitrobenzoyl)-1-(1-methyl-2-piperidinylmethyl)-1H-indole, (0.03-1μg) and JWH 133, (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran, (3-30μg) dose-dependently blocked inflammatory thermal hyperalgesia and mechanical allodynia. The analgesic effects induced by both agonists were counteracted by the coadministration of the selective cannabinoid CB(2) receptor antagonist SR144528, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide, (5μg) but not by the cannabinoid CB(1) receptor antagonist AM251, N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, (10μg). The effects induced by AM1241 were also inhibited by the coadministration of the opioid receptor antagonist, naloxone (1μg). These results demonstrate that effective analgesia can be achieved in chronic inflammatory settings through the stimulation of spinal cannabinoid CB(2) receptors even if this receptor population is not up-regulated.”
http://www.ncbi.nlm.nih.gov/pubmed/21771590

Inhibition of Inflammatory Hyperalgesia By Activation of Peripheral CB2 Cannabinoid Receptors
‎”CONCLUSIONS: Local, peripheral CB2 receptor activation inhibits inflammation and inflammatory hyperalgesia. These results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.”
‎”Inhibition of inflammatory hyperalgesia by activation of peripheral CB2 cannabinoid receptors.  Quartilho A, Mata HP, Ibrahim MM, Vanderah TW, Porreca F, Makriyannis A, Malan TP Jr.  Source Department of Anesthesiology, The University of Arizona, Tucson, USA.

Abstract
BACKGROUND: Cannabinoid receptor agonists inhibit inflammatory hyperalgesia in animal models. Nonselective cannabinoid receptor agonists also produce central nervous system (CNS) side effects. Agonists selective for CB2 cannabinoid receptors, which are not found in the CNS, do not produce the CNS effects typical of nonselective cannabinoid receptor agonists but do inhibit acute nociception. The authors used the CB2 receptor-selective agonist AM1241 to test the hypothesis that selective activation of peripheral CB2 receptors inhibits inflammatory hyperalgesia.

METHODS: Rats were injected in the hind paw with carrageenan or capsaicin. Paw withdrawal latencies were measured using a focused thermal stimulus. The effects of peripheral CB2 receptor activation were determined by using local injection of AM1241. CB2 receptor mediation of the actions of AM1241 was shown by using the CB2 receptor-selective antagonist AM630 and the CB1 receptor-selective antagonist AM251.

RESULTS: AM1241 fully reversed carrageenan-induced inflammatory thermal hyperalgesia when injected into the inflamed paw. In contrast, AM1241 injected into the contralateral paw had no effect, showing that its effects were local. AM1241 also reversed the local edema produced by hind paw carrageenan injection. The effects of AM1241 were reversed by the CB2 receptor-selective antagonist AM630, but not by the CB1 receptor-selective antagonist AM251. AM1241 also inhibited flinching and thermal hyperalgesia produced by hind paw capsaicin injection.

CONCLUSIONS: Local, peripheral CB2 receptor activation inhibits inflammation and inflammatory hyperalgesia. These results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.”
http://www.ncbi.nlm.nih.gov/pubmed/14508331

Cannabidiol As An Emergent Therapeutic Strategy For Lessening the Impact of Inflammation on Oxidative Stress
‎”This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.”
 ‎”Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress.  Booz GW.

Abstract
Oxidative stress with reactive oxygen species generation is a key weapon in the arsenal of the immune system for fighting invading pathogens and initiating tissue repair. If excessive or unresolved, however, immune-related oxidative stress can initiate further increasing levels of oxidative stress that cause organ damage and dysfunction. Targeting oxidative stress in various diseases therapeutically has proven more problematic than first anticipated given the complexities and perversity of both the underlying disease and the immune response. However, growing evidence suggests that the endocannabinoid system, which includes the CB(1) and CB(2) G-protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development. This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.”
http://www.ncbi.nlm.nih.gov/pubmed/21238581

Inhibition of Pain Responses By Activation of CB(2) Cannabinoid Receptors
‎”Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence demonstrates that CB(1) cannabinoid receptor activation inhibits pain responses.CB(2) receptor agonists may have promise for the treatment of pain and inflammation without CNS side effects.”
‎”Inhibition of pain responses by activation of CB(2) cannabinoid receptors.
Malan TP Jr, Ibrahim MM, Vanderah TW, Makriyannis A, Porreca F.
SourceDepartment of Anesthesiology, The University of Arizona, PO Box 245114, Tucson, AZ 85724-5114, USA. malan@u.arizona.edu

Abstract
Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence demonstrates that CB(1) cannabinoid receptor activation inhibits pain responses. Recently, the synthesis of CB(2) cannabinoid receptor-selective agonists has allowed testing whether CB(2) receptor activation inhibits pain. CB(2) receptor activation is sufficient to inhibit acute nociception, inflammatory hyperalgesia, and the allodynia and hyperalgesia produced in a neuropathic pain model. Studies using site-specific administration of agonist and antagonist have suggested that CB(2) receptor agonists inhibit pain responses by acting at peripheral sites. CB(2) receptor activation also inhibits edema and plasma extravasation produced by inflammation. CB(2) receptor-selective agonists do not produce central nervous system (CNS) effects typical of cannabinoids retaining agonist activity at the CB(1) receptor. Peripheral antinociception without CNS effects is consistent with the peripheral distribution of CB(2) receptors. CB(2) receptor agonists may have promise for the treatment of pain and inflammation without CNS side effects.”
http://www.ncbi.nlm.nih.gov/pubmed/12505700

Activation of Peripheral Cannabinoid CB1 and CB2 Receptors Suppresses the Maintenance of Inflammatory Nociception: A Comparative Analysis
‎”Conclusions and Implications: Cannabinoids act locally through distinct CB1 and CB2 mechanisms to suppress mechanical hypersensitivity after the establishment of chronic inflammation, at doses that produced modest changes in thermal hyperalgesia. Additive antihyperalgesic effects were observed following prophylactic co-administration of the CB1- and CB2-selective agonists. Our results suggest that peripheral cannabinoid antihyperalgesic actions may be exploited for treatment of inflammatory pain states.”
“Activation of peripheral cannabinoid CB1 and CB2 receptors suppresses the maintenance of inflammatory nociception: a comparative analysis”
T Gutierrez,1 J N Farthing,1 A M Zvonok,2 A Makriyannis,2 and A G Hohmann1*
1Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA, USA 2Center for Drug Discovery, Northeastern University, Boston, MA, USA 

Summary
“In summary, our results demonstrate that selective activation of CB1 or CB2 receptors in the inflamed paw is sufficient to suppress tactile allodynia and mechanical hyperalgesia. This suppression is observed under conditions in which only a partial suppression of thermal hyperalgesia was observed. Collectively, our data suggest that peripheral cannabinoid analgesic mechanisms may be exploited to suppress the tactile hypersensitivity observed in chronic inflammatory pain states.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042894/?tool=pubmed

Combined cannabinoid therapy via an oromucosal spray.
“Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). Clinical assessment of combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.”
‎”Combined cannabinoid therapy via an oromucosal spray.
Perez J.
 Source Department of Anesthesia, Chronic Pain Unit, Hospital Clinic de Barcelona, Barcelona, Spain. jperez@clinic.ub.es

Abstract
Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.”