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


A Call To Action:Your Local Government

In California medical cannabis patients are under attack from not only the federal government but local governments as well.  City after city has pushed for ordinances against medical marijuana.  Some baring dispensaries and some banning growing.  Some do this out of ignorance of medical cannabis and the industry and others in fear of repercussions from the federal government.   At the local level we need to work together to create a system that will regulate medical marijuana in a fair safe manner. Below is a letter to our local city council.  I share it in hopes to spark conversations in other cities where patients are being oppressed.

To Our Local Government:

We are standing at a unique point in time.  When you look back which side will you be on?  Will it be the ignorant, stubborn side that wishes to cling to yesteryear where fear and misinformation oppressed citizens or will it be on the side that is enlightened and will one day be vindicated?  We can no longer ignore science.  We can no longer let this be a political game with innocent patients as the chips.

It is time that you step up and start fighting FOR the patient instead of against.  It is time that you team up with the patients and create a peaceful business environment.  You were elected to SERVE the people not rule.  Minority groups need to be heard too. There is too much proof out there, both in personal stories and medical science to say medical marijuana doesn’t have medicinal purposes.

We can no longer allow the federal government to dictate how the state, county or city conducts business with medical cannabis with bullying tatics.  We can no longer allow the federal government to ignore science.  We can no longer allow government, instead of science, medicine and our own judgment, to dictate what we put in our bodies and how we treat our illnesses.

These laws are turning innocent patients into criminals.  The actions taken in the form of raids, arrests, threats, monetarily and in court have destroyed lives and caused many to be condemned to a life of lower standards.  These laws and by extension all of you enforcing these laws are oppressing people.

There needs to be regulation.  There needs to be a partnership between law enforcement, the City and patients.  We need sanity back in government.  People need to be educated before swinging the mighty gavel. As a patient I want to be able to walk into a dispensary and know I am safe from criminals and the government.  I want to know that if I grow a few plants my family wont have their door knocked down and have a gun in their face.  I want to know that the officials that we elect are held to the standard of being level headed, fair and just.  I want to know that they would give consideration to 1 person the same as they would 10,000.

Prohibition and reefer madness has been going on for over 74 years.  People have been hearing lies for a long time and that has bred a lot of misconceptions, greed, violent black markets and many other things that scare people.  What they don’t realize is that prohibition has caused this.  Its going to take all of us to fix this.  Its going to take all of us taking a fair balanced look at cannabis and seeing how we can improve things.  We need to be the ones changing it together.  We will never have progress if there is fighting. It is ridiculous for innocent, lawful patients and caregivers to be punished because of misuse of federal power and the actions of criminals.  We should be allowed safe access to our voter and Dr approved medicine.

Corruption Through the Ages

It is said that if history is not learned it is doomed to repeat itself.  It is important to look back and know how we got here today.  We have looked at how Prohibition of Alcohol can be applied to today’s War on Drugs.  We have also looked at the current Drug War in terms of stats on arrests and how much money is wasted.  Now we will take a look at how the Banking System has played a role in the drug trade and the War on Drugs. If you study the timeline below you will see how corruption has a firm grip where ever there is money. In the past 10 years there has been major corruption linking the banking system and drug cartels.  This is just one key point in the War on Drugs and our fight for legalization.  Money does have control and it is vital to know all aspects when fighting for legalization.  In the timeline you will notice underline text.  These are areas that I encourage to be further researched as there is a lot of interesting history to be discovered.  Please Share: just click on the image below to read~ Cherry Girl

Also available in High Resolution

Adapted from “Banking Laid Bare” Steven Hager ~ High Times Dec 2011

Wachovia and J.P. Morgan connection to Slave Trade: http://www.ushistory.org/presidentshouse/news/ww061005.htm 

Why More Americans Support Legalization of Marijuana

Gallup Poll released yesterday showed American support for the legalization of marijuana has risen to 50%. What might have caused this surge in support and made Americans take a second look at cannabis? Have Americans finally seen what a waste the War on Drugs is? Media coverage has become more common and less taboo enabling more people to become enlightened to the many benefits of cannabis as well as the corruption and lies surrounding it. There are 16 states that have set up some sort of medical marijuana program. More doctors and medical studies have emerged that support the medical benefits of cannabis.  There is also anger in the nation at corruption and Big Pharma is one target.

We have seen several reports lately that have showed medical advancements and new knowledge of the powers of cannabis.  We have seen them not only in expected media like High Times but also on news channels ranging from local to MSNBC.  We have seen many reports of patients that cannabis has helped or cured them as well as scientists discovering why cannabis works.

16 states enacted some sort of medical marijuana program. California was the first to enact legislation and has run a medical marijuana program for 15 years.  Colorado is one state that is allowing for-profit dispensaries to operate.  Reports have shown how revenue from taxes and fees as well as the residual business that benefits are seen throughout the community.  In a time when the economy is slow its hard to ignore the fact that cannabis is a booming industry.  With more states challenging the federal government’s stand on cannabis we have this industry brought to the forefront.

Politics has affected this issue extensively.  Many times politicians are focused on their career and not on the issues that need to be addressed.  Instead they continue to follow the failed policies of the Drug War that has been failing for the last 70 plus years.  The current Obama administration has promised one thing while doing a completely opposite action.  Recently attacks from the federal government against California patients has become severe.  With many more urgent issues that need to be addressed many Americans see this use of government spending wasteful.

 

People have seen the costs associated with processing criminals for small amounts of marijuana as well as the search for marijuana grows.  In a time where everyone is scrutinizing government spending people have turned their attention to the money wasted on the War on Drugs.  The recent attacks on medical marijuana dispensaries in California have put federal government spending in the spotlight.

Although Occupy Wall St is disorganized one thing you can glean from the people is the frustration over corruption.  We have seen how Big Pharma has control over the industry.  People want affordable, quality medicine, and with more information emerging on the health risks of prescription medications as well as the up rise in addiction rates more people are looking for a natural solution.

Some other points that might explain the increase in support is the spotlight that has been shown on NYC and the racially profiled marijuana arrests, that are prevalent not only in NYC but all over the country.  In 2010 NYC spent $75 million arresting and jailing 50,000 people for possessing small amounts of marijuana.  Most of them were in their late teens or early twenties and nearly 90% of them were of color.  This is something that has caught the attention of the NAACP who has spoke out in support of legalization of marijuana.

 

With so many factors working for us there are just as many if not more working against the legalization for marijuana. There is legislation currently being processed  HR 2306: The Ending Federal Marijuana Prohibition Act of 2011 which you can request your representative to support.  There is also a proposed ballot that has support of private citizens, celebrities, law enforcement and judges.  Its called the Regulate Marijuana Like Wine Act of 2012.  Now is our opportunity to change history and right a wrong.  Reefer madness and all the ridiculous claims against cannabis have had their claim on Americans for far too long.  Now is the time to take a second look at cannabis.  Now is the time to act and help legalize a natural safe alternative!

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Prostate Cancer and Cannabis:Cause and CURE

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

Cause:

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

Chemokine Family and Their Cognate Receptors

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

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

CURE:

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

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

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

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

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

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

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

Toke and Poke:Cannabis and Breast Cancer

October is Breast Cancer Awareness month and its in full swing.  To help celebrate the lives lost as well as saved, we have gathered research that shows cannabis to be a useful treatment option not only for symptoms but for cancer itself.  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
Self examination is still a great way for early detection so don’t for get to toke and poke at least once a month.  (Video at bottom or page)

Cause:

Activation of Multiple Cancer-Associated Genes At the ERBB2 Amplicon in Breast Cancer
The ERBB2 (neu/HER2) oncogene, located at chromosome 17q12, is one of the most intensively studied genes in cancer, especially in breast cancer.
Kauraniemi P, Kallioniemi A. SourceLaboratory of Cancer Biology, University of Tampere and Tampere University Hospital, 33014 Tampere, Finland. paivikki.kauraniemi@uta.fi

Abstract
During the past decade the role of the ERBB2 (neu/HER2) oncogene as an important predictor of patient outcome and response to various therapies in breast cancer has been clearly established. This association of ERBB2 aberrations with more aggressive disease and poor clinical outcome, together with the high prevalence of such alterations in breast cancer, has also made ERBB2 an attractive target for therapy. A specific antibody-based therapy, Herceptin, directed against the extracellular domain of the ERBB2 receptor tyrosine kinase, was recently developed and several clinical trials have shown the therapeutic efficacy of this drug against ERBB2-positive breast cancer. However, a relatively large fraction of patients does not benefit from Herceptin treatment, indicating that other factors beyond ERBB2 itself must influence therapy response in ERBB2-positive tumors. It is well known that amplification of the 17q12-q21 region is the most common mechanism for ERBB2 activation in breast cancer and that it leads to simultaneous activation of several other genes. These co-amplified and co-activated genes may have an impact on disease progression and the clinical behavior of ERBB2-positive tumors and thus represent important targets of research. In this paper we discuss the current knowledge on the structure of the ERBB2 amplicon, the genes involved, and their possible contribution to breast cancer pathogenesis.”
http://erc.endocrinology-journals.org/content/13/1/39.long

CURE:

Cannabinoids Reduce ErbB2-Driven Breast Cancer Progression Through Akt Inhibition
“Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.”
‎”Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition.  Caffarel MM, Andradas C, Mira E, Pérez-Gómez E, Cerutti C, Moreno-Bueno G, Flores JM, García-Real I, Palacios J, Mañes S, Guzmán M, Sánchez C.
SourceDept, Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.

Abstract
BACKGROUND: ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors.

RESULTS: Our results show that both Delta9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2.

CONCLUSIONS: Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.”

The Expression Level of CB1 and CB2 Receptors Determines Their Efficacy at Inducing Apoptosis in Ast

‎”The high expression level of CB1 and CB2 receptors commonly found in malignant astrocytomas precludes the use of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or cannabinoids are applied at concentrations that bypass CB1 and CB2 receptors, yet still activate ERK1/2.” So, for astrocytomas, cannabinoids can only be used if they inhibit AKT and activate ERK1/2.
“The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas. Cudaback E, Marrs W, Moeller T, Stella N.
SourceDepartment of Pharmacology, University of Washington, Seattle, Washington, United States of America.

Abstract
BACKGROUND: Cannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB(1) and CB(2) receptors mediate this therapeutic effect is unclear.

PRINCIPAL FINDINGS: We generated astrocytoma subclones that express set levels of CB(1) and CB(2), and found that cannabinoids induce apoptosis only in cells expressing low levels of receptors that couple to ERK1/2. In contrast, cannabinoids do not induce apoptosis in cells expressing high levels of receptors because these now also couple to the prosurvival signal AKT. Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB(1), CB(2) and AKT, but still through a mechanism involving ERK1/2.

SIGNIFICANCE: The high expression level of CB(1) and CB(2) receptors commonly found in malignant astrocytomas precludes the use of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or cannabinoids are applied at concentrations that bypass CB(1) and CB(2) receptors, yet still activate ERK1/2.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806825/?tool=pubmed

Cannabidiol Induces Programmed Cell Death In Breast Cancer Cells By Coordinating the Cross-Talk Between Apoptosis and Autophagy
‎”Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Cannabidiol (CBD), a major nonpsychoactive constituent of cannabis, is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells.”
“Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy.
Shrivastava A, Kuzontkoski PM, Groopman JE, Prasad A. Source Division of Experimental Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. abailugu@bidmc.harvard.edu

Abstract
Cannabidiol (CBD), a major nonpsychoactive constituent of cannabis, is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells. However, the exact molecular mechanism through which CBD mediates this activity is yet to be elucidated. Here, we have shown CBD-induced cell death of breast cancer cells, independent of cannabinoid and vallinoid receptor activation. Electron microscopy revealed morphologies consistent with the coexistence of autophagy and apoptosis. Western blot analysis confirmed these findings. We showed that CBD induces endoplasmic reticulum stress and, subsequently, inhibits AKT and mTOR signaling as shown by decreased levels of phosphorylated mTOR and 4EBP1, and cyclin D1. Analyzing further the cross-talk between the autophagic and apoptotic signaling pathways, we found that beclin1 plays a central role in the induction of CBD-mediated apoptosis in MDA-MB-231 breast cancer cells. Although CBD enhances the interaction between beclin1 and Vps34, it inhibits the association between beclin1 and Bcl-2. In addition, we showed that CBD reduces mitochondrial membrane potential, triggers the translocation of BID to the mitochondria, the release of cytochrome c to the cytosol, and, ultimately, the activation of the intrinsic apoptotic pathway in breast cancer cells. CBD increased the generation of reactive oxygen species (ROS), and ROS inhibition blocked the induction of apoptosis and autophagy. Our study revealed an intricate interplay between apoptosis and autophagy in CBD-treated breast cancer cells and highlighted the value of continued investigation into the potential use of CBD as an antineoplastic agent.”
http://www.ncbi.nlm.nih.gov/pubmed/21566064

Medical Marijuana Stops Spread of Breast Cancer – NBC NEWS




Prohibition: Then and Now, History Repeating Itself?

We see Hollywood glamorizing the roaring 20’s, Prohibition Era, with the speakeasies and flapper girls. Then there was Al Capone and the mob’s criminal activities. Today, with the Drug Prohibition, we have stories of bodies being dumped in the streets and heads being found on school playgrounds. Can we not learn from history?

During the Prohibition Era which lasted from 1920 to 1933, people truly thought that passing more laws would make things safer and better.  They felt that alcohol was the cause of many social issues and if it were illegal things would improve.  Unfortunately it had the opposite affect.

Suddenly with liquor being available only through the black markets, criminals organized and gangs were created.  What were once legally run production, importation and distribution businesses were now taken over by gangs.

As a result of the prohibition prices went up further fueling more attraction to gangs who became rich.  Once gangs took hold of the industry fights broke out over territory and connections, spilling crime into the streets including mass murder.


A Bill was created in Congress that celebrated the Repeal day which notes that “throughout American history, alcohol has been consumed by its citizens”;that prohibition resulted in “abuses” and the “irresponsible over consumption of alcohol”; and that the ban on “‘intoxicating liquors’ in the United States, resulted in a dramatic increase in illegal activity, including unsafe black market alcohol production, organized crime, and noncompliance with alcohol laws…”

While prohibition was a complete failure one thing we can learn from them is that they did go through the proper processes.  With prohibition activists worked their way from the local level to the federal level eventually amending the constitution. When America repealed prohibition with a constitutional amendment it explicitly gave the power to regulate alcohol to the states.

In contrast to the drug prohibition, Congress as well as the Supreme court, was not Constitutional when it passed the Controlled Substances Act of 1970 which started the modern day Drug War.

Crime was not the only factor in the failure of prohibition.  The lack of regulation was also a problem.  Unlike the regulated liquor, black market liquor was more potent and more harmful.  Today we have unregulated marijuana that is available to the public causing concerns.  Harmful chemicals, mold and many other issues can have serious effects on the end user as well as the enviroment. Without proper regulation patients can find it hard to get safe, quality marijuana.

During the Prohibition Era doctors were still able to prescribe it to their patients unlike today where dispensaries, doctors and patients  are being terrorized by raids. After almost 40 years since the Controlled Substance Act passed there are hundreds of thousands of people in prison for nonviolent drug crimes. We have federal and local  police forces that all too often acts like an military force with nearly a trillion dollars spent on enforcement. All the while the street prices of drugs like cocaine and marijuana has dramatically dropped since the government began keeping track in the early 1980s.

H.R. 2306, entitled the ‘Ending Federal Marijuana Prohibition Act of 2011,’ prohibits the federal government from prosecuting adults who use or possess marijuana by removing the plant, and its primary psychoactive constituent, THC, from the five schedules of the federal Controlled Substances Act of 1970.  It is currently being cosponsored by 16 Congresspeople.

There are plenty of lessons to learn from the Prohibition Era as well as the Drug War thus far.  As they always say history will repeat itself if you never learn from it.  Prohibition does not work, as proven, it has the opposite effect. Now is the time to stop the corruption and end Prohibition against marijuana.