Cannabinoids may be therapeutic in breast c... [Oncol Nurs Forum. 2013] - PubMed - NCBI

I know it is hard for some of you to believe, but marijuana is the anti-cancer plant, science has spoken! Oncol Nurs Forum. 2013 Mar 1;402:191-2. doi: 10.1188/13.ONF.191-192

Cannabinoids may be therapeutic in breast cancer                .Behrend SW.SourceDepartment of Nursing, Fox Chase Cancer Center, Philadelphia, PA.                                                           Abstract:Cannabinoids are a group of compounds synthesized exclusively by the Cannabis sativa plant, commonly known as marijuana. In 1990, the first cannabinoid-specific membrane CB1 was characterized and cloned Matsuda, Lolait, Brownstein, Young, & Bonner, 1990, which catapulted biomedical research on these unique compounds. Cannabinoids refer to both marijuana-derived compounds with the active ingredient of 9-tetrahydrocannabinol THC and also the synthetic molecules that activate the same primary targets as THC. Therapeutic properties of marijuana have been well established; however, the clinical use of either plant-sourced or pure cannabinoids remains limited. The anticachexia properties of cannabinoids are found in tetrahydrocannabinol oral capsules of synthetically generated THC and are used to manage weight loss, wasting syndrome, and nausea and vomiting associated with cancer treatment.PMID: 23448745 [PubMed - in process]

via Cannabinoids may be therapeutic in breast c... [Oncol Nurs Forum. 2013] - PubMed - NCBI.

Cannabinoids selectively inhibit proliferation ... [J Neurooncol. 2005] - PubMed - NCBI

This is an important study because it shows that the naturally-occurring cannabinoid molecule THC was safer, and more effective against cancer cells than was a synthetic cannabinoid, WIN 55,212-2. Yet researchers are discouraged from using cannabinoids from marijuana in lieu of the synthetic ones, because good findings about THC might "send the wrong message to young people." So now young people are getting a hold of far more dangerous synthetic cannabinoids and using them recreationally...the Law of Unintended Consequences. Neurooncol. 2005 Aug;741:31-40.Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells.McAllister SD, Chan C, Taft RJ, Luu T, Abood ME, Moore DH, Aldape K, Yount G.  Abstract: Normal tissue toxicity limits the efficacy of current treatment modalities for glioblastoma multiforme GBM. We evaluated the influence of cannabinoids on cell proliferation, death, and morphology of human GBM cell lines and in primary human glial cultures, the normal cells from which GBM tumors arise. The influence of a plant derived cannabinoid agonist, Delta9-tetrahydrocannabinol Delta9-THC, and a potent synthetic cannabinoid agonist, WIN 55,212-2, were compared using time lapse microscopy. We discovered that Delta9-THC decreases cell proliferation and increases cell death of human GBM cells more rapidly than WIN 55,212-2. Delta9-THC was also more potent at inhibiting the proliferation of GBM cells compared to WIN 55,212-2. The effects of Delta9-THC and WIN 55,212-2 on the GBM cells were partially the result of cannabinoid receptor activation. The same concentration of Delta9-THC that significantly inhibits proliferation and increases death of human GBM cells has no significant impact on human primary glial cultures. Evidence of selective efficacy with WIN 55,212-2 was also observed but the selectivity was less profound, and the synthetic agonist produced a greater disruption of normal cell morphology compared to Delta9-THC.PMID: 16078104 [PubMed - indexed for MEDLINE]

via Cannabinoids selectively inhibit proliferation ... [J Neurooncol. 2005] - PubMed - NCBI.

Use of cannabinoid rece... [Best Pract Res Clin Endocrinol Metab. 2009] - PubMed - NCBI

THC from marijuana is a safe, effective and thoroughly enjoyable cannabinoid receptor agonist. Best Pract Res Clin Endocrinol Metab. 2009 Feb;                                                                                                      Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents.                                            Pisanti S, Malfitano AM, Grimaldi C, Santoro A, Gazzerro P, Laezza C, Bifulco M.Source Department of Pharmaceutical Sciences, University of Salerno, Italy.                                                                                           Abstract: Cannabinoids the active components of Cannabis sativa and their derivatives have received renewed interest in recent years due to their diverse pharmacological activities. In particular, cannabinoids offer potential applications as anti-tumour drugs, based on the ability of some members of this class of compounds to limit cell proliferation and to induce tumour-selective cell death. Although synthetic cannabinoids may have pro-tumour effects in vivo due to their immunosuppressive properties, predominantly inhibitory effects on tumour growth and migration, angiogenesis, metastasis, and also inflammation have been described. Emerging evidence suggests that agonists of cannabinoid receptors expressed by tumour cells may offer a novel strategy to treat cancer. In this chapter we review the more recent results generating interest in the field of cannabinoids and cancer, and provide novel suggestions for the development, exploration and use of cannabinoid agonists for cancer therapy, not only as palliative but also as curative drugs.PMID: 19285265 [PubMed - indexed for MEDLINE]

via Use of cannabinoid rece... [Best Pract Res Clin Endocrinol Metab. 2009] - PubMed - NCBI.

Marijuana Use Reduces Obesity

Marijuana use is significantly protective against obesity as well as the harmful illnesses that accompany the syndrome. This is because THC and other cannabinoids work as systemic biological health regulators, the are key to our ability to survive and thrive. We really do need to encourage more adults to use marijuana in some form to improve their health and guard against degenerative illnesses. Science continues to affirm this position. Med Hypotheses. 2013 Feb 11.                                               Cannabis and Δ9-tetrahydrocannabinol THC for weight loss?Le Foll B, Trigo JM, et al.

Abstract: Obesity is one of the highest preventable causes of morbidity and mortality in the developed world [1]. It has been well known for a long time that exposure to cannabis produces an increase of appetite a phenomenon referred to as the 'munchies'. This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome. This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile [2]. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market. We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age. Here, we propose that this effect is directly related to exposure to the Δ9-tetrahydrocannabinol THC present in cannabis smoke. We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.

via Cannabis and Δ9-tetrahydrocannabinol THC ... [Med Hypotheses. 2013] - PubMed - NCBI.

Cannabinoids: a new hope for breast cancer ... [Cancer Treat Rev. 2012] - PubMed - NCBI

Marijuana fights beast cancer, why wait for "officials" to approve it? Use it now! Family history of breast cancer? Use it now! History of poor diet and alcohol consumption? Use it now! Cancer Treat Rev. 2012 Nov;10. 2012

Cannabinoids: a new hope for breast cancer therapy?               Caffarel MM, et al., Dept. Biochemistry and Molecular Biology I, School of Biology, Complutense University-CIBERNED-IRYCIS, Madrid, Spain.                                                                                          Abstract: Breast cancer is a very common disease that affects approximately 1 in 10 women at some point in their lives. Importantly, breast cancer cannot be considered a single disease as it is characterized by distinct pathological and molecular subtypes that are treated with different therapies and have diverse clinical outcomes. Although some highly successful treatments have been developed, certain breast tumors are resistant to conventional therapies and a considerable number of them relapse. Therefore, new strategies are urgently needed, and the challenge for the future will most likely be the development of individualized therapies that specifically target each patient's tumor. Experimental evidence accumulated during the last decade supports that cannabinoids, the active components of Cannabis sativa and their derivatives, possess anticancer activity. Thus, these compounds exert anti-proliferative, pro-apoptotic, anti-migratory and anti-invasive actions in a wide spectrum of cancer cells in culture. Moreover, tumor growth, angiogenesis and metastasis are hampered by cannabinoids in xenograft-based and genetically-engineered mouse models of cancer. This review summarizes our current knowledge on the anti-tumor potential of cannabinoids in breast cancer, which suggests that cannabinoid-based medicines may be useful for the treatment of most breast tumor subtypes.Copyright © 2012 Elsevier Ltd. All rights reserved.

via Cannabinoids: a new hope for breast cancer ... [Cancer Treat Rev. 2012] - PubMed - NCBI.

Alzheimer’s Drug Failure: Implications for Future R&D in Neuroscience

Why do they bother to develop and test these drugs when it is well-established that the phytocannabinoids generated by the cannabis plant--especially THC and CBD--have unique and unequaled anti-Alzheimer's activities? It is quite clear that these cannabinoids work on several levels to protect the brain from changes that lead to various forms of dementia. THC and CBD work against inflammation and oxidation while neutralizing toxic compounds such as TNF--tumor necrosis factor and cannabinoids dissolve the beta-amyloid plaque while reducing the production of tau scar tissue and triggering the production of healthy replacement neurons. Big pharma just needs to acknowledge that nature does it better. Alzheimer’s Drug Failure: Implications for Future R&D in Neuroscience

Alzheimer’s disease is a debilitating neurodegenerative disease characterized by dementia and memory loss. It is the sixth leading cause of death in the United States, where more than 5 million people are affected. There is clearly a need for more effective therapies that address this and other neurodegenerative diseases; however, the research and development (R&D) efforts put forth by pharmaceutical companies have rarely been successful, as illustrated by the recent failure of the Alzheimer’s drug bapineuzumab in clinical trials.

Johnson & Johnson and Pfizer in separate press releases on August 6, 2012, announced the discontinuation of their joint Phase III clinical development of intravenous (IV) bapineuzumab in mild-to-moderate cases of Alzheimer’s disease. This comes on the heels of disappointing results from the clinical trial Study 301, in which bapineuzumab was being tested in patients who are non-carriers of the ApoE4 (Apolipoprotein E epsilon 4) gene. Results indicated that bapineuzumab did not satisfy either cognitive or functional performance endpoints. These disappointing study results follow similar results announced on July 23 from Study 302, in which bapineuzumab also failed to meet clinical endpoints in ApoE4 carrier patients.

Bapineuzumab IV is an antibody that targets the beta-amyloid protein (A), which is believed to cause brain toxicity and is implicated in the pathology of Alzheimer’s disease.

via Alzheimer’s Drug Failure: Implications for Future R&D in Neuroscience.

Alzheimer’s Drug Failure: Implications for Future R&D in Neuroscience

Why do they bother to develop and test these drugs when it is well-established that the phytocannabinoids generated by the cannabis plant--especially THC and CBD--have unique and unequaled anti-Alzheimer's activities? It is quite clear that these cannabinoids work on several levels to protect the brain from changes that lead to various forms of dementia. THC and CBD work against inflammation and oxidation while neutralizing toxic compounds such as TNF--tumor necrosis factor and cannabinoids dissolve the beta-amyloid plaque while reducing the production of tau scar tissue and triggering the production of healthy replacement neurons. Big pharma just needs to acknowledge that nature does it better. Alzheimer’s Drug Failure: Implications for Future R&D in Neuroscience

Alzheimer’s disease is a debilitating neurodegenerative disease characterized by dementia and memory loss. It is the sixth leading cause of death in the United States, where more than 5 million people are affected. There is clearly a need for more effective therapies that address this and other neurodegenerative diseases; however, the research and development (R&D) efforts put forth by pharmaceutical companies have rarely been successful, as illustrated by the recent failure of the Alzheimer’s drug bapineuzumab in clinical trials.

Johnson & Johnson and Pfizer in separate press releases on August 6, 2012, announced the discontinuation of their joint Phase III clinical development of intravenous (IV) bapineuzumab in mild-to-moderate cases of Alzheimer’s disease. This comes on the heels of disappointing results from the clinical trial Study 301, in which bapineuzumab was being tested in patients who are non-carriers of the ApoE4 (Apolipoprotein E epsilon 4) gene. Results indicated that bapineuzumab did not satisfy either cognitive or functional performance endpoints. These disappointing study results follow similar results announced on July 23 from Study 302, in which bapineuzumab also failed to meet clinical endpoints in ApoE4 carrier patients.

Bapineuzumab IV is an antibody that targets the beta-amyloid protein (A), which is believed to cause brain toxicity and is implicated in the pathology of Alzheimer’s disease.

via Alzheimer’s Drug Failure: Implications for Future R&D in Neuroscience.

Cannabis chemical combats chief genetic cause of autism - Health, News - Belfasttelegraph.co.uk

Once again we see the stunning scope of therapeutic applications for cannabis/marijuana and we have to ask; when will the politicians learn some science and defend the peoples' right to use this nearly free remedy that has fewer side effects and better outcomes than standard pharmaceutical remedies? Politicians like Senators Dianne Feinstein and Barbara Boxer are pathetic, failed leaders who care nothing about the suffering or healing of average people with cancer, AIDS, pain syndromes but spend their time grubbing more and more money to bulk up their already enormous fortunes. What filth and scum they are. Learn the science, confront the enemies of humanity and publicly humiliate them. Here's the latest: Cannabis chemical combats chief genetic cause of autism

Natural cannabis-like chemicals in the brain may help combat the leading genetic cause of autism, research has shown.Scientists linked blockages in a signalling pathway dependent on the compounds, called 2-AG endocannabinoid transmitters, with symptoms of Fragile X syndrome.Correcting the fault with drugs led to dramatic behavioural improvements in mice with a version of the condition.Fragile X syndrome is the most common known genetic cause of autism.It results from a mutation in the FMR1 gene on the female X chromosome. Men possess one copy of the chromosome, paired with a male Y chromosome, and women two.Boys are much more likely to be born with Fragile X than girls. This is thought to be because with two X chromosomes, a defect in one may be compensated for by the other.People with the syndrome suffer mental impairment, learning difficulties, and may be hyperactive or impulsive. They also possess notable physical characteristics such as an elongated face, flat feet and large ears.The scientists, writing in the journal Nature Communications, stress that while their discovery may help people with Fragile X syndrome it will not provide a cure."What we hope is to one day increase the ability of people with Fragile X syndrome to socialise and engage in normal cognitive functions," said lead researcher Professor Daniele Piomelli, from the University of California at Irvine in the United States.The study was the first to identify the role of endocannabinoids in the neurobiology of Fragile X, she said.About endocannabinoidsEndocannabinoid compounds are created naturally in the body and share a similar chemical structure with THC, the primary psychoactive component of the marijuana plant, Cannabis.Endocannabinoids are distinctive because they link with protein molecule receptors -- called cannabinoid receptors -- on the surface of cells. For instance, when a person smokes marijuana, the cannabinoid THC activates these receptors. And because the body's natural cannabinoids control a variety of factors -- such as pain, mood and appetite -- they're attractive targets for drug discovery and development.Piomelli is one of the world's leading endocannabinoid researchers. His groundbreaking work is showing that this system can be exploited by new treatments to combat anxiety, pain, depression and obesity.

via Cannabis chemical combats chief genetic cause of autism - Health, News - Belfasttelegraph.co.uk.

How stress and depression can shrink the brain | Mail Online

In a recent report on research into cannabis' effects on the brain, it was discovered that cannabinoids actually increase and improve functional connectivity in the brain. Chronic, long-term marijuana smokers had improved nerve connectivity in the brain compared with nonusers of cannabis. The following report indicates that stress and depression inhibit the formation of nerve connections in the brain so it is logical to conclude that using marijuana is not only a remedy for the discomfort caused by stress, but that it can actually prevent and repair the damage resulting from stress and depressive states. Now we need research to confirm that THC and other cannabinoids suppress the formation of, or block the activation of GATA1, the protein identified as the primary culprit responsible for the loss of functional connectivity and brain shrinkage. Cannabis remedies brain shrinkage and deterioration, so Grace Slick was correct when, during the Summer of Love she sang "Feed your head." How stress and depression can shrink the brain

Depression blocks the formation of new nerve connections in the brain

By Daily Mail Reporter

PUBLISHED: 03:31 EST, 13 August 2012 | UPDATED: 03:39 EST, 13 August 2012

Common symptoms of depressive disorder are memory loss and blunted emotional responses

Severe depression and chronic stress can shrink the brain by blocking the formation of new nerve connections, a study has shown.

The effect disrupts circuits associated with mental functioning and emotion.

It could explain why people with major depressive disorder (MDD) suffer from concentration and memory loss, as well as blunted emotional responses.

Several genes involved in building synapses, the connection points between brain cells, were suppressed in people with MDD, scientists found.

This was thought to contribute to shrinkage of the brain's prefrontal cortex, which is known to occur in MDD sufferers.

Researchers in the US analysed brain tissue from patients who had died after being diagnosed with MDD.

They found molecular signs of reduced activity in genes necessary for the function and structure of brain synapses.

Evidence pointed to the involvement of a single genetic "switch", or transcription factor - a protein called GATA1.

Turning on GATA1 reduced activity of the genes and triggered the loss of brain connections.

 

Study leader Professor Ronald Duman, from Yale University, said: 'We wanted to test the idea that stress causes a loss of brain synapses in humans.

'We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated.'

The research is published in the latest issue of the journal Nature Medicine.

Further studies on rats showed that when GATA1 was switched on, the rodents showed signs of depression. This suggests that loss of brain synapses may be linked to depressive symptoms as well as mental impairment.

'We hope that by enhancing synaptic connections, either with novel medications or behavioural therapy, we can develop more effective antidepressant therapies,' Prof Duman added. (Professor, we have the "novel medication," it is cannabis. And it is cheap, safe and very effective.)

 

Neuropsychopharmacology - Abstract of article: Functional Connectivity in Brain Networks Underlying Cognitive Control in Chronic Cannabis Users

Once again we see no harm to the brain from regular marijuana use, in fact this study presents evidence that connectivity in the brain is enhanced by long-term, chronic marijuana smoking. Unfortunately, hobbled by euphoranoia and marijuanaphobia, the authors speculate that these improvements in brain structure result from compensatory actions resulting from impairment by euphoria when in reality the improvement in brain structure is more likely the result of direct actions triggered by cannabinoids, especially THC. We know that THC has the amazing ability to stimulate the production of healthy new brain cells, a process known as neurogenesis, therefore it is not unreasonable to speculate that the improved connections in the brain result from the positive biochemical effects of this neuroprotective, neuroreparative cannabinoid. The powerful stigma associated with marijuana that was brainwashed into two generations with reefer madness campaigns supported by reams of pseudo-scientific data continues to blind researchers to the reality that cannabinoids are health-building and health-regulating compounds and that supplementing our naturally-produced supply of these vital compounds with cannabis or cannabis products vastly improves all aspects of human health. Functional Connectivity in Brain Networks Underlying Cognitive Control in Chronic Cannabis Users

Ian H Harding1, Nadia Solowij2,3, Ben J Harrison1, Michael Takagi1, Valentina Lorenzetti1, Dan I Lubman4, Marc L Seal5,6, Christos Pantelis1 and Murat Yücel1

1Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, VIC, Australia

2School of Psychology, University of Wollongong, Wollongong, NSW, Australia

3Schizophrenia Research Institute, Sydney, NSW, Australia

4Turning Point Alcohol and Drug Centre, Eastern Health and Monash University, Melbourne, VIC, Australia

5Murdoch Childrens Research Institute, Melbourne, VIC, Australia

6Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia

Correspondence: Dr IH Harding and Professor M Yücel, Department of Psychiatry, Melbourne Neuropsychiatry Centre, Alan Gilbert Building, University of Melbourne, 3/161 Barry Street, Carlton, Melbourne, VIC 3053, Australia, Tel: (+61 3) 8344 1861, Fax: (+61 3) 9348 0469, E-mail: hardingi@unimelb.edu.au and murat@unimelb.edu.au

Received 21 September 2011; Revised 13 February 2012; Accepted 1 March 2012

Advance online publication 25 April 2012

Top of page

Abstract

The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes.

Keywords:

attention; brain; cannabis; cognitive control; functional connectivity

via Neuropsychopharmacology - Abstract of article: Functional Connectivity in Brain Networks Underlying Cognitive Control in Chronic Cannabis Users.

Acute Stress Increases Circulating A... [Neuropsychopharmacology. 2012] - PubMed - NCBI

Detractors of the medical marijuana movement mock the access to cannabis dispensaries by patients due to "stress" ailments but as we once again see, science has proven them wrong. There is a growing body of evidence to prove that using marijuana not only relieves the feelings of stress that we often endure, it actually neutralizes or inhibits the production of damaging chemicals the result from stress. This study found that stress causes a rise in the blood levels of endocannabinoids in order to protect the body from the harm caused by stress-related compounds. So it logically follows that supplementing the activity of the endocannabinoids with phytocannabinoids from marijuana can increase this type of biochemical protection. But those of us who use it have known this for years and regret deeply that the stigma associated with marijuana has deprived millions of people from this safe, inexpensive and enjoyable stress-relieving remedy. Acute Stress Increases Circulating Anandamide and Other N-Acylethanolamines in Healthy Humans.

Dlugos A, Childs E, Stuhr KL, Hillard CJ, de Wit H.

Source

1] Department of Psychiatry, University of Muenster, Muenster, Germany [2] Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.

Abstract

Stress plays an important role in psychiatric disorders, and preclinical evidence indicates that the central endocannabinoid system modulates endocrine and neuronal responses to stress. This study aimed to investigate the effect of acute stress on circulating concentrations of endocannabinoids (eCBs) in healthy humans. A total of 71 adults participated in two sessions in which they were exposed to either a standardized psychosocial stress procedure (Trier Social Stress Test) or a control task. Blood samples for eCB and cortisol assays and cardiovascular and subjective measures were obtained before and at regular intervals after the tasks. Serum concentrations of the eCBs, N-arachidonylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), as well as of the N-acylethanolamides (NAEs), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), and of the O-acylglycerol, 2-oleoylglycerol (2-OG), were determined. Compared with the control condition, stress increased serum concentrations of AEA and the other NAEs immediately after the stress period. Increases in PEA were positively correlated with increases in serum cortisol after stress. Furthermore, anxiety ratings at baseline were negatively correlated with baseline concentrations of AEA. The sex and menstrual cycle status of the subject affected the NAE responses to stress. Interestingly, subjects of Asian and African-American races exhibited different patterns of stress responses compared with the Caucasian subjects. These results indicate that stress increases circulating NAEs in healthy human volunteers. This finding supports a protective role for eCBs in anxiety. Further research is needed to elucidate the function of these lipid mediators, and to determine the mechanisms that regulate their appearance in the circulation.Neuropsychopharmacology advance online publication, 4 July 2012; doi:10.1038/npp.2012.100.

via Acute Stress Increases Circulating A... [Neuropsychopharmacology. 2012] - PubMed - NCBI.

Acute Stress Increases Circulating A... [Neuropsychopharmacology. 2012] - PubMed - NCBI

Detractors of the medical marijuana movement mock the access to cannabis dispensaries by patients due to "stress" ailments but as we once again see, science has proven them wrong. There is a growing body of evidence to prove that using marijuana not only relieves the feelings of stress that we often endure, it actually neutralizes or inhibits the production of damaging chemicals the result from stress. This study found that stress causes a rise in the blood levels of endocannabinoids in order to protect the body from the harm caused by stress-related compounds. So it logically follows that supplementing the activity of the endocannabinoids with phytocannabinoids from marijuana can increase this type of biochemical protection. But those of us who use it have known this for years and regret deeply that the stigma associated with marijuana has deprived millions of people from this safe, inexpensive and enjoyable stress-relieving remedy. Acute Stress Increases Circulating Anandamide and Other N-Acylethanolamines in Healthy Humans.

Dlugos A, Childs E, Stuhr KL, Hillard CJ, de Wit H.

Source

1] Department of Psychiatry, University of Muenster, Muenster, Germany [2] Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.

Abstract

Stress plays an important role in psychiatric disorders, and preclinical evidence indicates that the central endocannabinoid system modulates endocrine and neuronal responses to stress. This study aimed to investigate the effect of acute stress on circulating concentrations of endocannabinoids (eCBs) in healthy humans. A total of 71 adults participated in two sessions in which they were exposed to either a standardized psychosocial stress procedure (Trier Social Stress Test) or a control task. Blood samples for eCB and cortisol assays and cardiovascular and subjective measures were obtained before and at regular intervals after the tasks. Serum concentrations of the eCBs, N-arachidonylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), as well as of the N-acylethanolamides (NAEs), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), and of the O-acylglycerol, 2-oleoylglycerol (2-OG), were determined. Compared with the control condition, stress increased serum concentrations of AEA and the other NAEs immediately after the stress period. Increases in PEA were positively correlated with increases in serum cortisol after stress. Furthermore, anxiety ratings at baseline were negatively correlated with baseline concentrations of AEA. The sex and menstrual cycle status of the subject affected the NAE responses to stress. Interestingly, subjects of Asian and African-American races exhibited different patterns of stress responses compared with the Caucasian subjects. These results indicate that stress increases circulating NAEs in healthy human volunteers. This finding supports a protective role for eCBs in anxiety. Further research is needed to elucidate the function of these lipid mediators, and to determine the mechanisms that regulate their appearance in the circulation.Neuropsychopharmacology advance online publication, 4 July 2012; doi:10.1038/npp.2012.100.

via Acute Stress Increases Circulating A... [Neuropsychopharmacology. 2012] - PubMed - NCBI.

Unbound MEDLINE | Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. PubMed Journal article abstract

This explains one way in which cannabis is effective against such a wide variety of illnesses, it reduces the level of tumor necrosis factor in the body. Rogers RC, Hermann GE

Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. [Journal Article, Research Support, N.I.H., Extramural]

J Neurosci 2012 Apr 11; 32(15):5237-41.

The early proinflammatory cytokine tumor necrosis factor (TNF) is released in significant quantities by the activated immune system in response to infection, leukemia, autoimmune disorders, and radiation sickness. Nausea, emesis, and anorexia are common features of these disorders. TNF action on vagal afferent terminals in the brainstem is a likely cause of the malaise associated with these disorders. Our previous work has shown that TNF action to excite vagal afferents occurs as a result of sensitization of ryanodine channels in afferent nerve terminals. For millennia, cannabinoids (CB) have been used to combat the visceral malaise associated with chronic disease, although the mechanism of action has not been clear. Previous work in culture systems suggests that CB1 agonists can suppress neurotransmission by downregulating ryanodine channels through a protein kinase A (PKA)-dependent mechanism. Laser confocal calcium imaging methods were used to directly examine effects of CB1 cannabinoid agonists and TNF on visceral afferent signaling in the rat hindbrain. CB1 agonists blocked the effects of TNF to amplify vagal afferent responsiveness; blockade of PKA with H89 also eliminated the TNF amplification effect. These results help to explain the effectiveness of cannabinoids in blocking the malaise generated by TNF-releasing disease processes by opposing effects on ryanodine channels.

via Unbound MEDLINE | Tumor necrosis factor activation of vagal afferent terminal calcium is blocked by cannabinoids. PubMed Journal article abstract.