The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

The CS World Cup: Goaltender Edition

Today, tending to the goals of mediating Alzheimer’s and preventing carcinogenesis, Publius spotlights two June abstracts from PubMed on the homeostatic cannabinoid system (CS). For Alzheimer’s disease it is CS modulation of cognitive decline; for preventing carcinogenesis the findings unveil a previously unknown CS signaling platform: CB2-GPR55 receptor heteromers.



I. CS Mediates Cognitive Decline In Alzheimer's Disease

Set: “It has been widely reported that β-amyloid peptide (Aβ) blocks long-term potentiation (LTP) of hippocampal synapses. Here, we show evidence that Aβ more potently blocks the potentiation of excitatory postsynaptic potential (EPSP)-spike coupling (E-S potentiation). This occurs, not by direct effect on excitatory synapses or postsynaptic neurons, but rather through an indirect mechanism: reduction of endocannabinoid-mediated peritetanic disinhibition.”

Setting: “During high-frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation.”

Science: “This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer's disease.”
β-Amyloid Inhibits E-S Potentiation through Suppression of Cannabinoid Receptor 1-Dependent Synaptic Disinhibition.
Orr AL, Hanson JE, Li D, Klotz A, Wright S, Schenk D, Seubert P, Madison DV.
Neuron. 2014 Jun 18;82(6):1334-45. doi: 10.1016/j.neuron.2014.04.039.
PMID: 24945775 [PubMed - in process]
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II. CS Oncology Signaling Unveiled: Evidence of Previously Unknown Platforms

Set: “The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. As a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells.”

Setting: “Here, we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo.”

Science: “These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology.”
Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling.
Moreno E, Andradas C, Medrano M, Caffarel MM, Pérez-Gómez E, Blasco-Benito S, Gómez-Cañas M, Pazos MR, Irving AJ, Lluís C, Canela EI, Fernández-Ruiz J, Guzmán M, McCormick PJ, Sánchez C.
J Biol Chem. 2014 Jun 18. pii: jbc.M114.561761. [Epub ahead of print]
PMID: 24942731 [PubMed - as supplied by publisher] Free Article
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Video: Homeostasis 1, Physiological Principles ~ Dr. John Campbell

Posted by Bryan W. Brickner

The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Here are seven new 2014 findings on how the cannabinoid system (CS) modulates homeostasis and other systems in our bodies: the roundup links to recent PubMed articles on the urinary, neuroendocrine, digestive, central nervous and serotonin systems.

I. Urinary System (Kidney / Diabetes) and CS
“A functionally active endocannabinoid system is present within the kidney. The cannabinoid receptor type 2 (CB2) is expressed by both inflammatory cells and podocytes, and its activation has beneficial effects in experimental diabetic nephropathy. … Thus, CB2 deletion worsens diabetic nephropathy, independent of bone marrow-derived cells.”
Deficiency of cannabinoid receptor of type 2 worsens renal functional and structural abnormalities in streptozotocin-induced diabetic mice.
Barutta F, Grimaldi S, Franco I, Bellini S, Gambino R, Pinach S, Corbelli A, Bruno G, Rastaldi MP, Aveta T, Hirsch E, Di Marzo V, Gruden G.
Kidney Int. 2014 May 14. doi: 10.1038/ki.2014.165. [Epub ahead of print]
PMID: 24827776 [PubMed - as supplied by publisher]
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II. Neuroendocrine System (Skin) and CS
“Recent evidence has shown that the neuroendocrine regulation of human skin biology also extends to keratins, the major structural components of epithelial cells. For example, thyrotropin-releasing hormone, thyrotropin, opioids, prolactin, and cannabinoid receptor 1-ligands profoundly modulate human keratin gene and protein expression in human epidermis and/or hair follicle epithelium in situ.”
Harnessing neuroendocrine controls of keratin expression: A new therapeutic strategy for skin diseases?
Ramot Y, Paus R.
Bioessays. 2014 May 13. doi: 10.1002/bies.201400006. [Epub ahead of print]
PMID: 24823963 [PubMed - as supplied by publisher]
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III. Digestive System and CS
“Palmitoylethanolamide (PEA), a naturally-occurring acylethanolamide chemically related to the endocannabinoid anandamide, interacts with targets that have been identified in peripheral nerves controlling gastrointestinal motility, i.e. cannabinoid (CB1 and CB2 ) receptors, transient receptor potential vanilloid type-1 (TRPV1), and peroxisomal proliferator activated receptor α (PPARα).”
Ultramicronized palmitoylethanolamide normalizes intestinal motility in a murine model of post-inflammatory accelerated transit: involvement of CB1 receptors and TRPV1.
Capasso R, Orlando P, Pagano E, Aveta T, Buono L, Borrelli F, Di Marzo V, Izzo AA.
Br J Pharmacol. 2014 May 12. doi: 10.1111/bph.12759. [Epub ahead of print]
PMID: 24818658 [PubMed - as supplied by publisher]
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IV. Central Nervous System and CS
“G-protein-coupled receptors (GPCRs) constitute an example of proteins that are the key factors in the framework needed to sustain brain and nerve structure and function. The versatility underlying nervous system anatomy takes advantage of a recently discovered feature of GPCRs, the possibility to form heteromers that, placed at specific neuronal subsets and at specific locations (pre-, post-, or peri-synaptic), contribute to attain unique neural functions.”
G-Protein-Coupled Receptor Heteromers as Key Players in the Molecular Architecture of the Central Nervous System.
Brugarolas M, Navarro G, Martínez-Pinilla E, Angelats E, Casadó V, Lanciego JL, Franco R.
CNS Neurosci Ther. 2014 May 9. doi: 10.1111/cns.12277. [Epub ahead of print]
PMID: 24809909 [PubMed - as supplied by publisher]
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V. Serotonin System and the CS
“Serotonin (5-HT) plays pivotal roles in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS), and luminal 5-HT time-dependently modulates visceral nociception. We found that duodenal biopsies from PI-IBS patients exhibited increased 5-HT and decreased anandamide levels and that decreased anandamide was associated with abdominal pain severity, indicating a link between 5- HT and endocannabinoid signaling pathways in PI-IBS.”
Vagal anandamide signaling via cannabinoid receptor 1 contributes to luminal 5-HT modulation of visceral nociception in rats.
Feng CC, Yan XJ, Chen X, Wang EM, Liu Q, Zhang LY, Chen J, Fang JY, Chen SL.
Pain. 2014 May 8. pii: S0304-3959(14)00225-5. doi: 10.1016/j.pain.2014.05.005. [Epub ahead of print]
PMID: 24813296 [PubMed - as supplied by publisher]
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VI. Central Nervous System (Blood-Brain Barrier) and CS
“Early brain injury (EBI), following subarachnoid hemorrhage (SAH), comprises blood-brain barrier (BBB) disruption and consequent edema formation. … We suggest that CB2R stimulation attenuates neurological outcome and brain edema, by suppressing leukocyte infiltration into the brain through TGF-β1 up-regulation and E-selectin reduction, resulting in protection of the BBB after SAH.”
Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats.
Fujii M, Sherchan P, Krafft PR, Rolland WB, Soejima Y, Zhang JH.
J Neurol Sci. 2014 Apr 30. pii: S0022-510X(14)00270-6. doi: 10.1016/j.jns.2014.04.034. [Epub ahead of print]
PMID: 24819918 [PubMed - as supplied by publisher]
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VII. Central Nervous System (Memory) and CS
“The reactivation of a memory can result in its destabilization, necessitating a process of memory reconsolidation to maintain its persistence. Here we show that the destabilization of a contextual fear memory is potentiated by the cannabinoid CB1 receptor agonist Arachidonyl-2-chloroethylamide (ACEA). … These results indicate that memory expression and destabilization, while being independent from one another, are both dependent upon memory reactivation. Moreover, memory destabilization can be enhanced pharmacologically, which may be of therapeutic potential.”
Inhibition and enhancement of contextual fear memory destabilization.
Lee JL, Flavell CR.
Front Behav Neurosci. 2014 Apr 28;8:144. doi: 10.3389/fnbeh.2014.00144. eCollection 2014.
PMID: 24808841 [PubMed] Free PMC Article
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Bonus Video:

Posted by Bryan W. Brickner

In March we noted the relentless strength of Alzheimer’s disease ~ and it’s still going strong. Good thing so is the science. Here are five more 2014 National Institutes of Health (PubMed) research updates on Alzheimer’s disease and cannabinoids.

The researchers in the third piece below make an interesting point concerning time; seems there haven’t been enough “adequately powered trials” on the safety of cannabinoids in older test subjects. That is harmful and a symptom of our polity.

Talk cannabinoids please … waiting another generation is not acceptable.

I.
Cannabinoid receptor-dependent metabolism of 2-arachidonoylglycerol during aging.
Pascual AC, Gaveglio VL, Giusto NM, Pasquaré SJ.
Exp Gerontol. 2014 Jul;55:134-42. doi: 10.1016/j.exger.2014.04.008. Epub 2014 Apr 24.
PMID: 24768821 [PubMed - in process]
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II.
Cannabinoids for pain in dementia: the good, the bad, and the ugly.
Ahmed AI, van den Elsen GA, van der Marck MA, Olde Rikkert MG.
J Am Geriatr Soc. 2014 May;62(5):1001-2. doi: 10.1111/jgs.12817. No abstract available.
PMID: 24828945 [PubMed - in process]
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III.
Efficacy and safety of medical cannabinoids in older subjects: a systematic review.
van den Elsen GA, Ahmed AI, Lammers M, Kramers C, Verkes RJ, van der Marck MA, Rikkert MG.
Ageing Res Rev. 2014 Mar;14:56-64. doi: 10.1016/j.arr.2014.01.007. Epub 2014 Feb 5.
PMID: 24509411 [PubMed - in process]
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IV.
Parsing the players: 2-arachidonoylglycerol synthesis and degradation in the CNS.
Murataeva N, Straiker A, Mackie K.
Br J Pharmacol. 2014 Mar;171(6):1379-91. doi: 10.1111/bph.12411.
PMID: 24102242 [PubMed - in process]
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V.
Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease.
González-Naranjo P, Pérez-Macias N, Campillo NE, Pérez C, Arán VJ, Girón R, Sánchez-Robles E, Martín MI, Gómez-Cañas M, García-Arencibia M, Fernández-Ruiz J, Páez JA.
Eur J Med Chem. 2014 Feb 12;73:56-72. doi: 10.1016/j.ejmech.2013.11.026. Epub 2013 Dec 7.
PMID: 24378710 [PubMed - in process]
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VI.
Video ~ Holistic Alzheimer’s Video: Cannabis Oil and Medical Marijuana

Posted by Bryan W. Brickner

Just as America plants new seeds for a new harvest, we need some new words for understanding all the kinds of cannabinoid businesses forming. It’s already clear the cannabinoid system (CS) is fundamental to health: now CS economics are taking place.

One key to understanding this new economy: synthetic cannabinoids are simply misplaced pharmaceutical cannabinoids and they work great in one place: research laboratories.

Cannabinoids are in our research labs, sold in white powders by pharmaceutical companies, and now there are pharmaceutical companies placing “green” cannabinoids in pills and sprays and ointments. Suddenly, even for those of us somewhat familiar with the terrain, all the words started blending together like a smoothie.

Publius of The Cannabis Papers found these distinctions useful:

Three Types of Cannabinoid Businesses
I.
Pharmaceutical cannabinoids
These businesses use synthetic cannabinoid in research and in products like Marinol, a synthetic-THC available as a prescription pharmaceutical.

II.
Herbiceutical cannabinoids
These are new businesses like GW Pharmaceutical; their product Nabiximols (Sativex) is made from plant cannabinoids-yet-pharmaceutical-grade.

III.
Herbaceutical cannabinoids
This would be perhaps the most varied business group; it would include hemp foods, such businesses as Dr. Bronner's hemp oil soaps, herbal (raw, phyto-) cannabinoid medical dispensaries, as well as all collective and individual home-grow businesses.

Standardization is the next issue for green cannabinoids, and it’s trifold: the plant varies as well as one’s CS (biology) and the human condition (physiology and psychology). As herbaceutical companies grow and prosper, the listing of the cannabinoids in the product implies (and requires) a basic knowledge of one’s CS; that’s when cannabinoids will not only be a source of bodily health – they’ll also become a source of economic health.

Tomorrow: An update on Cannabinoids and Passing the Alzheimer’s Test.
Posted by Bryan W. Brickner

The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Cancer research awareness and the cannabinoid system (CS) are the focus of May’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed CS science on preventing skin and colon carcinogenesis, phototherapy, melanomas, eicosands, gliomas, mitochondria and the omega-3 fatty acids DHA and EPA.

2014 ~ Skin Carcinogenesis, Inflammation and the CS
“Cancer is an environmental disease and skin cancer (melanoma and non-melanoma) is the most common of all cancers.”
The role of inflammation in skin cancer.
Maru GB, Gandhi K, Ramchandani A, Kumar G.
Adv Exp Med Biol. 2014;816:437-69. doi: 10.1007/978-3-0348-0837-8_17.
PMID: 24818733 [PubMed - in process]
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2014 ~ CB2 and Antitumor (Phototherapy)
“Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.”
Cannabinoid CB2 Receptor as a New Phototherapy Target for the Inhibition of Tumor Growth.
Jia N, Zhang S, Shao P, Bagia C, Janjic JM, Ding Y, Bai M.
Mol Pharm. 2014 May 8. [Epub ahead of print]
PMID: 24779700 [PubMed - as supplied by publisher]
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2014 ~ CB2 Receptor and Melanoma
“Extravasation of leukocytes through the BBB [blood-brain barrier] is decreased by the activation of type 2 cannabinoid receptors (CB2); therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. … Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.”
CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier.
Haskó J, Fazakas C, Molnár J, Nyúl-Tóth A, Herman H, Hermenean A, Wilhelm I, Persidsky Y, Krizbai IA.
Int J Mol Sci. 2014 May 8;15(5):8063-74. doi: 10.3390/ijms15058063.
PMID: 24815068 [PubMed - in process] Free Article
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2014 ~ Colon Carcinogenesis and CBD ~ Botanical Drug Substance
“CBD BDS [botanical drug substance] attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation.”
Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.
Romano B, Borrelli F, Pagano E, Cascio MG, Pertwee RG, Izzo AA.
Phytomedicine. 2014 Apr 15;21(5):631-9. doi: 10.1016/j.phymed.2013.11.006. Epub 2013 Dec 25.
PMID: 24373545 [PubMed - in process]
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2014 ~ Eicosands, 2-AG and Cancer
“While THC and its derivatives have garnered notoriety in the eyes of the public, the endocannabinoid system consists of two endogenous signaling lipids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide), which activate cannabinoid receptors CB1 and CB2 in the nervous system and peripheral tissues.”
Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids.
Kohnz RA, Nomura DK.
Chem Soc Rev. 2014 Mar 28. [Epub ahead of print]
PMID: 24676249 [PubMed - as supplied by publisher]
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2014 ~ Antitumor (Gliomas) and the CS
“These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.”
Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas.
Rocha FC, Dos Santos Júnior JG, Stefano SC, da Silveira DX.
J Neurooncol. 2014 Jan;116(1):11-24. doi: 10.1007/s11060-013-1277-1. Epub 2013 Oct 20.
PMID: 24142199 [PubMed - in process]
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2013 ~ Anticancer Effects of CBD
“Thus, VDAC1 [voltage-dependent anion channel 1] seems to serve as a novel mitochondrial target for CBD. The inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD.”
Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death.
Rimmerman N, Ben-Hail D, Porat Z, Juknat A, Kozela E, Daniels MP, Connelly PS, Leishman E, Bradshaw HB, Shoshan-Barmatz V, Vogel Z.
Cell Death Dis. 2013 Dec 5;4:e949. doi: 10.1038/cddis.2013.471.
PMID: 24309936 [PubMed - in process] Free PMC Article
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2010 ~ Preventing Carcinogenesis and the CS
“Our findings suggest that the expression of cannabinoid receptors and of FAAH in some tumour cells could well influence the effectiveness of DHA and EPA or their ethanolamide derivatives as anticancer agents.”
Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines.
Brown I, Cascio MG, Wahle KW, Smoum R, Mechoulam R, Ross RA, Pertwee RG, Heys SD.
Carcinogenesis. 2010 Sep;31(9):1584-91. doi: 10.1093/carcin/bgq151. Epub 2010 Jul 25.
PMID: 20660502 [PubMed - indexed for MEDLINE] Free PMC Article
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Posted by Bryan W. Brickner

The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Here are seven 2014 findings on how the cannabinoid system (CS) modulates homeostasis and other systems in our bodies: the roundup links to recent PubMed articles on the physiology, digestive, hypothalamic neurohypophyseal, vanilloid, dopamine, reproductive, and nervous systems.

I. Physiology System (Aging) and the CS
“2-arachidonoylglycerol (2-AG) is one of the principal endocannabinoids involved in the protection against neurodegenerative processes. … Taken together, the results of the present study show that CB1 and/or CB2 receptor antagonists trigger a significant modulation of 2-AG metabolism, underlining their relevance as therapeutic strategy for controling endocannabinoid levels in physiological aging.”

Cannabinoid receptor-dependent metabolism of 2-arachidonoylglycerol during aging.
Pascual AC, Gaveglio VL, Giusto NM, Pasquaré SJ.
Exp Gerontol. 2014 Apr 24. pii: S0531-5565(14)00129-6. doi: 10.1016/j.exger.2014.04.008. [Epub ahead of print]
PMID: 24768821 [PubMed - as supplied by publisher]
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II. Digestive System (Arachidonic Acid) and the CS
“The endogenous ligands of type-1 and type-2 cannabinoid receptors, N-arachidonoyl-ethanolamine and 2-arachidonoylglycerol, are arachidonic acid (AA) derivatives whose levels are regulated by the activity of metabolic enzymes, as well as by AA availability. Since the only sources of AA in mammals are diet and the enzymatic production in the liver from shorter-chain essential fatty acids like linoleic acid, it is realistic to hypothesize that endocannabinoid levels might be modulated by fatty acid composition of food.”

Endocannabinoid signaling and its regulation by nutrients.
Bisogno T, Maccarrone M.
Biofactors. 2014 Apr 21. doi: 10.1002/biof.1167. [Epub ahead of print]
PMID: 24753395 [PubMed - as supplied by publisher]
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III. Hypothalamic Neurohypophyseal System (Pituitary Stalk) and the CS
“Endocannabinoids (ECBs) are considered ubiquitous lipophilic agents, and this is a characteristic that is consistent with the wide range of homeostatic functions attributed to the ECB system. There is an increasing number of reports showing that the ECB system affects neurotransmission within the hypothalamic neurohypophyseal system.”

The endocannabinoid system and the neuroendocrine control of hydromineral balance.
Ruginsk SG, Vechiato FM, Elias LL, Antunes-Rodrigues J.
J Neuroendocrinol. 2014 Apr 17. doi: 10.1111/jne.12158. [Epub ahead of print]
PMID: 24750469 [PubMed - as supplied by publisher]
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IV. Vanilloid System (Retrograde Signaling) and the CS
“One of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), serves as a retrograde messenger at various types of synapses throughout the brain. … Whereas 2-AG primarily transmits a rapid, transient, point-to-point retrograde signal, the other major endocannabinoid, anandamide, may function as a relatively slow retrograde or non-retrograde signal or as an agonist of the vanilloid receptor.”

Endocannabinoid-mediated retrograde modulation of synaptic transmission.
Ohno-Shosaku T, Kano M.
Curr Opin Neurobiol. 2014 Apr 16;29C:1-8. doi: 10.1016/j.conb.2014.03.017. [Epub ahead of print] Review.
PMID: 24747340 [PubMed - as supplied by publisher]
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V. Dopamine System (Hedonistic Aspects) and the CS
“The endocannabinoid (ECB) system has emerged recently as a key mediator for reward processing. … Our data further indicate that the ECB system, and in particular CB1 receptor signaling, appear to be highly important for the mediation of hedonic aspects of reward processing.”

The CB1 Receptor as an Important Mediator of Hedonic Reward Processing.
Friemel CM, Zimmer A, Schneider M.
Neuropsychopharmacology. 2014 Apr 10. doi: 10.1038/npp.2014.86. [Epub ahead of print]
PMID: 24718372 [PubMed - as supplied by publisher]
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VI. Reproductive System (Sperm) and the CS
“In human spermatozoa, which exhibit a completely functional endocannabinoid system, the activation of cannabinoid receptor-1 (CB1) inhibited sperm mitochondrial membrane potential (ΔΨm). … In conclusion, E. coli LPS inhibited sperm ΔΨm through the activation of CB1, but this effect was not accompanied to the activation of mitochondrial dysfunction-related apoptotic/oxidative mechanisms, which could affect sperm motility and genomic integrity.”

Involvement of cannabinoid receptor-1 activation in mitochondrial depolarizing effect of lipopolysaccharide in human spermatozoa.
Barbonetti A, Vassallo MR, Costanzo M, Battista N, Maccarrone M, Francavilla S, Francavilla F.
Andrology. 2014 Apr 1. doi: 10.1111/j.2047-2927.2014.00210.x. [Epub ahead of print]
PMID: 24692267 [PubMed - as supplied by publisher]
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VII. Nervous System (Pain) and the CS
“We investigated the effects of anandamide on 4 neuronal sodium channel α subunits, Nav1.2, Nav1.6, Nav1.7, and Nav1.8, to explore the mechanisms underlying the antinociceptive effects of anandamide. … Anandamide inhibited the function of α subunits in neuronal sodium channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8. These results help clarify the mechanisms of the analgesic effects of anandamide.”

The endocannabinoid anandamide inhibits voltage-gated sodium channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8 in Xenopus oocytes.
Okura D, Horishita T, Ueno S, Yanagihara N, Sudo Y, Uezono Y, Sata T.
Anesth Analg. 2014 Mar;118(3):554-62. doi: 10.1213/ANE.0000000000000070.
PMID: 24557103 [PubMed - indexed for MEDLINE]
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~'~

Posted by Bryan W. Brickner

As a member of the 502nd Infantry, US Army 101st Airborne, my unit was deployed to the kingdom of Jordan in the late 1980s. Soon after, I found myself diagnosed with MS (multiple sclerosis) awaiting a medical discharge instead of starting my second enlistment.

I’ve presently had MS for over 25 years. Each time I went to the doctor with spasms or atrophy that was bending my body into painful and unnatural positions, I’d walk out with a new muscle relaxer or pain pill. By 2003 I found myself taking a cocktail of approximately 59 pills a day which did little for the pain and spasms, and instead turned me into what felt like a sleeping zombie. I’d literally fall asleep in the middle of a conversation! I was a prisoner in my own body.

Later that year I had a muscle spasm that lasted for days. Nothing I did or took would stop it. My cousin came over and convinced me to try cannabis. By the time we finished, my body had stopped twitching and I felt relaxed for the first time in a long time! I was also experiencing another strange sensation: I was hungry! At first, my wife was worried about my smoking on top of all the pills I was taking, but cannabis was providing unparalleled relief from the spasms and atrophy. No spasms or atrophy, no pain! After discussing it with her, we took inventory of my pills and began tapering down the ones I no longer needed thanks to the relief provided by one cannabis cigarette a day! We not only reduced the overall number of pills to just 24 per day, we were able to eliminate some intoxicating medicines all together. By the time we were finished I no longer took Valium, Xanax for tremors, Gabapentin, morphine and Vicodin for breakthrough pain, and several others. Also I reduced the methadone I take every day.

Since that time I have literally been a new man! I used to lay in bed for weeks at a time. I neither had the energy nor desire to ever leave my house. The pills had been making me sicker and weaker. Now I only stay in bed at night and go outside often (when it’s warm outside) and do the things I love – attending Bears, Blackhawks, Bulls, and Cubs games when I choose.

While the Medical Cannabis bill had passed in the Illinois legislature we had all been waiting for the Governor to sign it. My wife saw Governor Quinn at the Lincoln Hotel in Springfield and wanted him to meet me. He had to leave the Lincoln but told her he’d meet me in his office the next morning! He was on time and very nice. He was concerned with what I had to say. I told him about our Medical Cannabis bill and he said he would seriously consider it. When the signing came about I was asked to not only attend but to speak and I received the first pen he signed the bill with. Along with Governor Quinn, Senator William Haine was instrumental in getting Representative Lou Lang’s bill passed and signed. All of us patients who need this medicine are now waiting for the particulars such as dispensary locations, ID registration, and other necessary components of this newly legalized medicine to take effect so we can avail ourselves access.

We now know that this medicine may come in edibles, in vaporizers, tinctures and other ways of dispensing the product that we so seriously need; this personal journey, from Airborne to MS to Activism, has taught me much – mostly, how to think through stress, prepare for contingencies, and deal with life’s obstacle course.

Jim Champion

Edited by William Abens
Posted by bwb     

Cannabinoid System Video:
Three Veterans with PTS: Cannabis Therapy 2013   

The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Here are seven 2014 findings on how the cannabinoid system (CS) modulates homeostasis and other systems in our bodies: the roundup links to recent PubMed articles on the vanilloid, neurological, dopamine, visual, skeletal, and endocrine systems.

I. Vanilloid System and the CS
“These data indicate that the eCB system can modulate inflammatory activation of the endothelium and may have important implications for a variety of acute inflammatory disorders that are characterized by EC [Endothelial Cell] activation.”
The endocannabinoid/endovanilloid N-arachidonoyl dopamine (NADA) and synthetic cannabinoid WIN55,212-2 abate the inflammatory activation of human endothelial cells.
Wilhelmsen K, Khakpour S, Tran A, Sheehan K, Schumacher M, Xu F, Hellman J.
J Biol Chem. 2014 Mar 18. [Epub ahead of print]
PMID: 24644287 [PubMed - as supplied by publisher] Free Article
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II. Neurological System (Migraines) and the CS
“These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”
Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.
Greco R, Mangione AS, Sandrini G, Nappi G, Tassorelli C.
J Headache Pain. 2014 Mar 17;15(1):14. doi: 10.1186/1129-2377-15-14.
PMID: 24636539 [PubMed - in process] Free Article
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III. Dopamine System and the CS
“The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system.”
Involvement of the Cannabinoid CB1 Receptor in Modulation of Dopamine Output in the Prefrontal Cortex Associated with Food Restriction in Rats.
Dazzi L, Talani G, Biggio F, Utzeri C, Lallai V, Licheri V, Lutzu S, Mostallino MC, Secci PP, Biggio G, Sanna E.
PLoS One. 2014 Mar 14;9(3):e92224. doi: 10.1371/journal.pone.0092224. eCollection 2014.
PMID: 24632810 [PubMed - in process] Free PMC Article
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IV. Neurological System (Alzheimer’s disease) and the CS
“Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress.”
Cannabinoids for treatment of Alzheimer's disease: moving toward the clinic.
Aso E, Ferrer I.
Front Pharmacol. 2014 Mar 5;5:37. eCollection 2014. Review.
PMID: 24634659 [PubMed - as supplied by publisher] Free PMC Article
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V. Visual System and the CS
“Our findings provide neurophysiologic evidence for a link between cannabinoid-signaling, network dynamics and the function of a canonical cortical circuit.”
Cannabinoid neuromodulation in the adult early visual cortex.
Ohiorhenuan IE, Mechler F, Purpura KP, Schmid AM, Hu Q, Victor JD.
PLoS One. 2014 Feb 19;9(2):e87362. doi: 10.1371/journal.pone.0087362. eCollection 2014.
PMID: 24586271 [PubMed - in process] Free PMC Article
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VI. Skeletal System (Osteoarthritis) and the CS
“The ubiquitous distribution of cannabinoid receptors, together with the physiological role of the endocannabinoid system in the regulation of pain, inflammation and even joint function further support the therapeutic interest of cannabinoids for osteoarthritis.”
Involvement of the endocannabinoid system in osteoarthritis pain.
La Porta C, Bura SA, Negrete R, Maldonado R.
Eur J Neurosci. 2014 Feb;39(3):485-500. doi: 10.1111/ejn.12468.
PMID: 24494687 [PubMed - in process]
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VII. Endocrine System (HP-axis) and the CS
“Since the endocannabinoid system components are present at sites involved in the hypothalamic-pituitary axis regulation, several studies were performed in order to investigate the endocannabinoid-mediated neurotransmitters and hormones secretion under physiological and pathological conditions.”
Role of the Endocannabinoid System in the Neuroendocrine Responses to Inflammation.
De Laurentiis A, Araujo HA, Rettori V.
Curr Pharm Des. 2014 Jan 30. [Epub ahead of print]
PMID: 24588819 [PubMed - as supplied by publisher]
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~’~
posted by bwb

The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
By Publius

Colorectal (colon) cancer awareness and the cannabinoid system (CS) are the focus of March’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed CS science on preventing carcinogenesis, inducing apoptosis, attenuating cancer’s damage, and an estrogen-responsive connection to controlling colon cancer proliferation.

2013 ~ Attenuating Damage and the CS
“These findings support a discrete role for CB2 receptors in the attenuation of detrimental pro-inflammatory cytokine-mediated mucosal damage in the human colon without directly affecting mucosal epithelial barrier function.”
Cannabinoid CB2 receptor activation attenuates cytokine-evoked mucosal damage in a human colonic explant model without changing epithelial permeability.
Harvey BS, Nicotra LL, Vu M, Smid SD.
Cytokine. 2013 Aug;63(2):209-17. doi: 10.1016/j.cyto.2013.04.032. Epub 2013 May 22.
PMID: 23706402 [PubMed - indexed for MEDLINE]
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2013 ~ Immunoreactivity (Immune Reaction) and the CS
“The high immunoreactivity of the cannabinoid type 1 receptor is a significant prognostic factor following surgery in stage IV CRC [colorectal cancer].”
Expression of the cannabinoid type I receptor and prognosis following surgery in colorectal cancer.
Jung CK, Kang WK, Park JM, Ahn HJ, Kim SW, Taek Oh S, Choi KY.
Oncol Lett. 2013 Mar;5(3):870-876. Epub 2012 Dec 18.
PMID: 23426698 [PubMed] Free PMC Article
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2012 ~ Preventing Carcinogenesis and the CS
“Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis.”
Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.
Aviello G, Romano B, Borrelli F, Capasso R, Gallo L, Piscitelli F, Di Marzo V, Izzo AA.
J Mol Med (Berl). 2012 Aug;90(8):925-34. doi: 10.1007/s00109-011-0856-x. Epub 2012 Jan 10.
PMID: 22231745 [PubMed - indexed for MEDLINE]
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2011 ~ Inducing Apoptosis and the CS
“Cannabinoid receptor agonists induce phosphatases and phosphatase-dependent apoptosis in cancer cell lines; however, the role of the CB receptor in mediating this response is ligand-dependent.”
Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent.
Sreevalsan S, Joseph S, Jutooru I, Chadalapaka G, Safe SH.
Anticancer Res. 2011 Nov;31(11):3799-807.
PMID: 22110202 [PubMed - indexed for MEDLINE] Free PMC Article
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2008 ~ Silencing Cancer and the CS
“Here we show that CB1 expression was silenced in human colorectal cancer due to methylation of the CB1 promoter.”
Loss of cannabinoid receptor 1 accelerates intestinal tumor growth.
Wang D, Wang H, Ning W, Backlund MG, Dey SK, DuBois RN.
Cancer Res. 2008 Aug 1;68(15):6468-76. doi: 10.1158/0008-5472.CAN-08-0896.
PMID: 18676872 [PubMed - indexed for MEDLINE] Free PMC Article
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2008 ~ Estrogen-Responsive Genes and the CS
“The CB1 receptor can be considered an estrogen-responsive gene in DLD-1, HT-29 and SW620 cells. Up-regulation of CB1 expression by 17beta-estradiol is a further mechanism of estrogens to control colon cancer proliferation.”
Estrogenic induction of cannabinoid CB1 receptor in human colon cancer cell lines.
Notarnicola M, Messa C, Orlando A, Bifulco M, Laezza C, Gazzerro P, Caruso MG.
Scand J Gastroenterol. 2008 Jan;43(1):66-72.
PMID: 18938775 [PubMed - indexed for MEDLINE]
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2004 ~ Preventing Metastasis and the CS
“Therefore, specific inhibition of tumor cell migration via CB1-R engagement might be a selective tool to prevent metastasis formation without depreciatory effects on the immune system of cancer patients.”
Anandamide is an endogenous inhibitor for the migration of tumor cells and T lymphocytes.
Joseph J, Niggemann B, Zaenker KS, Entschladen F.
Cancer Immunol Immunother. 2004 Aug;53(8):723-8. Epub 2004 Mar 18.
PMID: 15034673 [PubMed - indexed for MEDLINE]
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2003 ~ Inhibiting Cancer and the CS
“The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) inhibit cancer cell proliferation by acting at cannabinoid receptors (CBRs).”
Possible endocannabinoid control of colorectal cancer growth.
Ligresti A, Bisogno T, Matias I, De Petrocellis L, Cascio MG, Cosenza V, D'argenio G, Scaglione G, Bifulco M, Sorrentini I, Di Marzo V.
Gastroenterology. 2003 Sep;125(3):677-87.
PMID: 12949714 [PubMed - indexed for MEDLINE]
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~ posted by bryan w. brickner

Here are five “more” 2014 National Institutes of Health (PubMed) research updates on Alzheimer’s disease and cannabinoids. I mention “more” because of the widely reported research this month, Plasma Phospholipids Identify Antecedent Memory Impairment in Older Adults.

CNN noted the plasma science as Blood test predicts Alzheimer’s disease.

Forbes saw the ability to identify memory impairment before its onset (by measuring various lipids/fats in blood) as double-edged: How A New Alzheimer’s Test Could Kill Long-Term Care Insurance – Or Make It Cheaper.

I also say “more” because this isn’t new news. The sixth item included is a video of CNN Int., reported in March 2008, on how cannabis may be “a boon to Alzheimer’s patients.”

While we wait for the boon (and it has to be a political boon now), the progression of the disease doesn’t. We’d be wise to mimic the strength of Alzheimer’s disease in our resolve to understand its causes and to offer relief: the disease is relentless … we aught to be as well.

I.
The influence of cannabinoids on generic traits of neurodegeneration.
Fagan SG, Campbell VA.
Br J Pharmacol. 2014 Mar;171(6):1347-60. doi: 10.1111/bph.12492.
PMID: 24172185 [PubMed - in process]
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II.
Cannabinoids for treatment of Alzheimer's disease: moving toward the clinic.
Aso E, Ferrer I.
Front Pharmacol. 2014 Mar 5;5:37. eCollection 2014. Review.
PMID: 24634659 [PubMed - as supplied by publisher] Free PMC Article
Related citations

III.
In vivo type 1 cannabinoid receptor availability in Alzheimer's disease.
Ahmad R, Goffin K, Van den Stock J, De Winter FL, Cleeren E, Bormans G, Tournoy J, Persoons P, Van Laere K, Vandenbulcke M.
Eur Neuropsychopharmacol. 2014 Feb;24(2):242-50. doi: 10.1016/j.euroneuro.2013.10.002. Epub 2013 Oct 17.
PMID: 24189376 [PubMed - in process]
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IV.
Altered Expression of the CB1 Cannabinoid Receptor in the Triple Transgenic Mouse Model of Alzheimer's Disease.
Bedse G, Romano A, Cianci S, Lavecchia AM, Lorenzo P, Elphick MR, Laferla FM, Vendemiale G, Grillo C, Altieri F, Cassano T, Gaetani S.
J Alzheimers Dis. 2014 Feb 4. [Epub ahead of print]
PMID: 24496074 [PubMed - as supplied by publisher]
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V.
Brain Innate Immunity In The Regulation Of Neuroinflammation: Therapeutic Strategies By Modulating Cd200-Cd200r Interaction Involve The Cannabinoid System.
Hernangomez M, Carrillo-Salinas FJ, Mecha M, Correa F, Mestre L, Loria F, Feliu A, Docagne F, Guaza C.
Curr Pharm Des. 2014 Jan 30. [Epub ahead of print]
PMID: 24588829 [PubMed - as supplied by publisher]
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VI.
Video Archives ~ CNN Int. March 2008 (B4-Obama)
Medical Marijuana Alzheimer, CNN Int. 11 Mar 2008
“Drug could be a boon to Alzheimer’s patients.”

Bryan W. Brickner