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Homeostatic Cannabinoid Science ~ Publius’ May Roundup

5/30/2014

Astrocyte / Blood-Brain Barrier by Ben Brahim Mohammed

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

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Passing the Alzheimer’s Test and One’s Cannabinoid System ~ An Update

5/29/2014

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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

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Business of Cannabinoids: Pharm Pills and Farm Herbs

5/28/2014

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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

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War Cry Heal Union and Civil War Unknowns ~ Memorial Day 2014

5/25/2014

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That’s Augustus Kotka from Indiana – his headstone I mean – acting as flag-bearer in the background. The foreground is the headstone for 9163, Unknown U.S. Soldier, Marietta National Cemetery.

This final resting place for northern citizen-soldiers caught-up in the War Between the States ~ the US Civil War 1861-65, might be considered a long way from home. Not necessarily though, as the flag they carried into battle had the Georgia star (and all other states in rebellion) still on it.

Not far away from Kotka and 9163, maybe a mile or so, is Marietta Confederate Cemetery. Here unknown citizen-soldiers dominate. The Union cemetery feels as if ten percent of the burials are unknown; this one feels like ninety percent.

The above headstone is for five unknown citizen-soldiers caught-up in the same debacle, our uncivil war. Two unknown citizens from Missouri and three fellows from Maryland interned far from what they might have considered home.

The war itself isn’t over if the wounds haven’t healed. We still have some healing to do in order to make a more perfect Union ~ one for all the people of We the People.

War Cry Heal Union
The Series
EwPublishing Summer 2014

Landings
Augustus Kotka gave a war cry on 11 August 1864; he was killed during the siege of Atlanta. It wasn’t a battle day. His death is noted in a diary from his unit, the 99th Indiana Regiment: it parenthetically states, “Augustus Kotka, Company C, killed.”

I found Kotka’s federal marker headstone in Pulaski County, IN; I then went to visit his burial headstone in Marietta National Cemetery.

This series began with the question, “Who killed Kotka?”

To get to that answer we’ll take a look at citizenship and representation; here I mean all citizens, future slaves to be citizens and also the southern citizens. In the series War Cry Heal Union, all the people of We the People are grouped together ~ northern and southern, for example, in the term “The Unrepresented.”

The series is outlined below and runs from 19 June to Constitution Day on 17 September. The ten postings vary in topics (ranging from war to peace to free speech) and build on James Madison’s idea that representing We the People according to our numbers is not only the American way ~ it’s our constitutional way.

This August is the 150th anniversary of Kotka’s final day in Georgia. Here is the opening to the August posting, “Johnny Reb and Gus Kotka Have a Talk” ~ and the full schedule for the series follows:

Johnny Reb: Whatcha’ wanna know Yank?

Augustus Kotka: Who killed me?

Johnny: That’s the same question for 150 years ~ with the same answer ~ you did.

Augustus: No, really, who got me shot?

Johnny: I did then.

Augustus: You always say that ~ this year things are different though …

~
War Cry Heal Union ~ The Series
JUNE
19 June 2014
Slavery is usurpation: usurpation is slavery.

27 June 2014
150th: War cry ~ 27 June 1864.

28 June 2014
100th: Empires crumble and Others build.

JULY
19 July 2014
Willy-Nicky and willy-nilly Emperors.

20 July 2014
150th: A Private, an Officer and a battle flag in Georgia, 20 July 1864.

27 July 2014
Factions heard not silenced: Henry Lee III, the Unrepresented and the First Amendment.

AUGUST
11 August 2014
150th: Johnny Reb and Gus Kotka ~ Georgia, 11 August 1864.

26 August 2014
Silent words: Napoleon, Johann Philipp Palm and 26 August 1806.

SEPTEMBER
16 September 2014
Virginian slavers at Harlem Heights NY: sacrifice and 16 September 1776.

17 September 2014
Constitution Day, Antietam and Heal Union ~ Sharpsburg MD: 17 September 1787, 1862 and 2014.

Happy Memorial Day All!
Bryan W. Brickner

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Preventing Carcinogenesis via One’s Cannabinoid System ~ Publius’ May 2014 Cancer Research Awareness

5/18/2014

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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]
Related citations

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

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Homeostatic Cannabinoid Science ~ Publius’ May Roundup

Passing the Alzheimer’s Test and One’s Cannabinoid System ~ An Update

Business of Cannabinoids: Pharm Pills and Farm Herbs

War Cry Heal Union and Civil War Unknowns ~ Memorial Day 2014

Preventing Carcinogenesis via One’s Cannabinoid System ~ Publius’ May 2014 Cancer Research Awareness

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