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

War Cry Heal Union: The series (3rd of 10)

The United States is the Other today: Hannah Arendt cast in lead.

The painting of the assassination on June 28th 1914 portrays the heir to the Austrian-Hungarian Empire, Archduke Franz Ferdinand, and his wife Sophie being shot by 19 year-old Gavrilo Princip on a Sarajevo street corner.

The painting encapsulates an era of endemic militancy that fueled 1914 Europe and the catastrophe called World War I: fired shots, stunned chauffer, blank-wall, sabered rider, plumed officer, soldiers sashed, lurched and rifled, and a grounded headless hat.

Those times and today’s circumstances are nicely summed in the Wall Street Journal article, Scars of World War I Linger in Europe on Eve of Centennial. The author notes war’s carnage is never simple (or just) and 15 million dead also means 15 million destroyed homes, families and relationships. Lyrically apropos war is not: it thrives and embellishes disharmonies in order to live off the discord. War needs Others, that is clear. One take home lesson for today is that Peace needs Others just as much (maybe more).

Hannah Arendt, who found citizenship in America, is today’s representative example of the Other. Born in 1906 in one of the Empires about to fall (the German one), Arendt “moved” to the United States running from the Nazis and their ideas of Otherness: Arendt became a US citizen.

Representative Arendt? ~ Yes, it has a nice sound to it.

Citizens like Hannah Arendt in Congress representing a district of thirty thousand as our constitution commands? That too sounds nice. Geez ~ she wrote The Origins of Totalitarianism (1951) and The Human Condition (1958), and would have added much to any mid-century policy debate.

Maybe that’s one of our political bad habits we can grow away from, this always thinking it can’t matter who’s representing us.

We will learn the constitutional lessons of representing We the People, or, like the generations before us, some will survive the carnage and do what the Others always do – start building again.

Peace Others.

Bryan W. Brickner
Ew Publishing

War Cry Heal Union: The series (2 of 10)

I came upon today’s story by happenstance ~ much like the citizens who fought and died there.

In 2011 I visited Marietta Georgia and its National Cemetery. Most of the federal soldiers interned there are from 1864 and Sherman’s campaign to capture Atlanta; many fought in the Kennesaw Mountain battle and, specifically, at Cheatham Hill, also known as “Dead Angle,” and the map indicated a monument to Illinois ~ my home state.

The above photo’s perspective is from the top of Cheatham Hill; on the morning of battle, 27 June 1864, this would have been the Tennessee/Confederate line (the sun is to the northwest ~ an afternoon photo). The Federals were in the forest background with the hill to their front. They were mostly citizen-soldiers from Illinois, Indiana and Ohio in infantry regiments; they would soon rush across that field and up the hill to assault the Tennesseans.

What are a citizen-soldier’s sentiments at such moments? Prayer for sure … and probably shouts of ~ “There’s Hell boys!” or “Here comes Hell boys!” ~ depending on one’s perspective.

At 9:00 a.m. Federal skirmishers and a human wave of blue moved out of the forest and up the hill to assault the Confederate breastworks …

Because we can, let’s pause the assault for a moment and give some thought to the carnage that is about to take place; let’s even ponder such things as: why are citizens from Illinois, Indiana and Ohio assaulting Tennesseans on a Georgia hilltop? Or, more clearly, what part of our Constitution failed: Madison’s theory of representing We the People according to our numbers or the lack thereof?

Since we just paused war for a moment, we might as well keep going and call in a couple of founding spirits ~ Benjamin Franklin (anti-slaver) and James Madison (slaver) ~ for an imagined-yet-real constitutional dialogue:

Ben Franklin: James, they didn’t use the blueprint and representing We the People at the ratio of one Representative for every thirty Thousand.

James Madison: I know Benjamin ~ they got caught-up in slavery and the three-fifths clause.

Franklin: By 1860, the last Census before the Civil War, the representation ratio had risen to 119,000 citizens per Representative [Brickner: Article the First page 100]. Obviously, that is un-representation and not our design for We the people of the United States Republic.

Madison: I know ~ it’s Plato’s Republic …

Franklin: … Which doesn’t work.

Madison: They’ll learn ~ we had too as well.

Yes, We the People still hold the Unrepresented “not yet” card. It’s the Constitution’s Article 1 Section 2 Clause 3: “The Number of Representatives shall not exceed one for every thirty Thousand, but each State shall have at Least one Representative.”

Okay, back to the assault. If the Illinois, Indiana and Ohio citizens have to charge (orders you know) and the Tennesseans, under the command of Benjamin Franklin Cheatham and Patrick R. Cleburne, have to obey orders and hold the line … you can see what’s about to happen. There’s no room for maneuver ~ nowhere to go. The Illinois citizens want the hill so they can take Atlanta (only 20 miles away) and go back home; the Tennesseans want the hill to save Atlanta and go back to a home.

So the assault happens … now the photo looks different; suddenly it’s a nice picture of a citizen-killing zone. Soldiers often say similar things ~ how peaceful Nature can be and feel … and then Hell breaks out.

On 27 June 1914, the 50th anniversary of the battle, the Illinois Monument was dedicated on Cheatham Hill; it’s on the spot where 15 Illinois Infantry Regiments fought and dug in: they couldn’t dislodge the Tennesseans and they couldn’t retreat down the hill without suffering terrible casualties; “Dig-in” was the command and dig they did. The Battle of Kennesaw Mountain 150th Anniversary group recently highlighted a 100 year-old article from The Marietta Journal and Courier written in preparation for the monument’s unveiling a century ago; the events at Dead Angle are honored:

“Cheatham’s Hill was one of the memorable battles of the war. The Federals and Confederates faced each other there for six days and six nights, their lines being so close that the soldiers were in ordinary speaking distance. They fought from the 27th of June to the 3rd of July, 1864 and on the last day the Confederates withdrew because of a flank movement. It was well they did so, as the Federals had constructed a tunnel far into the hill, had placed explosives under the Confederate position and intended to touch off the mine on the 4th of July.”

The tunnel is still visible today … and war continues its flanking movement.

The day after the monument's dedication, 28 June 1914, the heir to the Austrian throne is assassinated by an “unrepresented” subject of the empire (an anarchist); this singular event, seemingly a world away from Marietta and Cheatham Hill, would lead the European Empires into World War I ~ a war that would soon touch Georgia and all the other states in the Union.

Perhaps stated in terms of We the People of Europe, WW I (like our Civil War) was caused by a failure to represent ~ account for ~ The Unrepresented.

We’ll pick-up there tomorrow with Empires Crumble and Others Build, part 3 in the War Cry Heal Union series.

Video:
Cheatham Hill

Bryan W. Brickner
Ew Publishing

Serotonin activation was our topic on 19 April 2014; it’s serotonin life sciences today with the precursor 5-HTP (5-hydroxytryptophan) in highlight. 

Below are four (brief) science stories from the National Institutes of Health (PubMed). Shortened titles should suffice to suggest the main themes: Therapeutic 5-HTP, Hot Flash and Breast Cancer Reduction, Irritable Bowels, and Morphine’s Efficacy. The links and quotes are from PubMed (1998-2014).

Healthy Solstice Everyone!
~.~
Therapeutic 5-HTP Has Been Shown … (1998)
“5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. … Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.”
5-Hydroxytryptophan: a clinically-effective serotonin precursor.
Birdsall TC.
Altern Med Rev. 1998 Aug;3(4):271-80. Review.
PMID: 9727088 [PubMed - indexed for MEDLINE] Free Article
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Hot Flash (and Breast Cancer) Reduction: a hypothesis (2005)
“This would be particularly desirable for menopausal women with breast cancer or with risks of breast cancer. This article discusses the background information on hot flashes, SSRIs, tryptophan, and 5HTP, and possible clinical application of 5HTP for menopausal women with breast cancer risk.”
The potential of 5-hydryoxytryptophan for hot flash reduction: a hypothesis.
Curcio JJ, Kim LS, Wollner D, Pockaj BA.
Altern Med Rev. 2005 Sep;10(3):216-21.
PMID: 16164376 [PubMed - indexed for MEDLINE] Free Article
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A Serotonin-mediated Mechanism in Bowels (2014)
“Oral 5-HTP induced alterations in mucosal 5-HT metabolism. In healthy controls, a reinforcement of the intestinal barrier was seen whereas such reaction was absent in IBS [irritable bowel syndrome] patients. This could indicate the presence of a serotonin-mediated mechanism aimed to reinforce intestinal barrier function, which seems to dysfunction in IBS patients.”
Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome.
Keszthelyi D, Troost FJ, Jonkers DM, van Eijk HM, Lindsey PJ, Dekker J, Buurman WA, Masclee AA.
Aliment Pharmacol Ther. 2014 Jun 18. doi: 10.1111/apt.12842. [Epub ahead of print]
PMID: 24943480 [PubMed - as supplied by publisher]
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Serotonin and Morphine’s Efficacy (2014)
“Systemic administration of morphine increases 5-HT levels in the spinal cord, and the increase in 5-HT contributes to morphine-induced analgesia in the normal state but attenuates that in neuropathic pain through spinal 5-HT3 receptors. The plasticity of the descending serotonergic system may contribute to the reduced efficacy of systemic morphine in neuropathic pain.”
Peripheral Nerve Injury Reduces Analgesic Effects of Systemic Morphine via Spinal 5-Hydroxytryptamine 3 Receptors.
Kimura M, Obata H, Saito S.
Anesthesiology. 2014 Jun 2. [Epub ahead of print]
PMID: 24887968 [PubMed - as supplied by publisher]
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VIDEO:
5HTP benefit and side effects of 5htp, dosage, anxiety, weight loss, sleep

BONUS VIDEO: Serotonin/Binaural Beats
5-HTP secretion for happiness binaural beats, intensity WARNING

~ Posted by Bryan W. Brickner ~

War Cry Heal Union: The series (1 of 10)

Aesop ~ of Aesop’s Fables fame ~ was a slave.

Like the last slaves freed in the United States on 19 June 1865, Juneteenth, Aesop too had his freedom day. In his life he passed from owner to owner as a slave until his intellect won his freedom. Plutarch, a priest at Delphi, reports that after gaining his freedom Aesop was employed by King Croesus of Lydia. The king sent Aesop to Delphi to negotiate terms regarding Apollo’s oracle. The people of Delphi didn’t like Aesop’s talk ~ his logic ~ and took matters into their own hands. Plutarch reports the people of Delphi killed the famed-fabalist by forcing him over a cliff … more on Aesop in a moment.

A fable is a story with animals talking; civilization is a story with the animal human talking. The civilization story always begins with the same premise: things were once bad and then changed and people (tribes, clans, and nations) called it good; and always within the story of civilization, providing a seemingly visceral and vital role, is the slave. Essentially, civilization was designed by many and built by slaves.

Slavery is usurpation and usurpation is slavery. A citizen without rights is a slave; similar to a subject, they lack agency power to appeal to a higher law than the current sovereign. A (rightful) citizen, however, has agency to appeal to power in the form of written constitutions.

On April 9th, Usurpation Day 2014, it was noted that slavery is the shadow of usurpation (rights taken without right) and couldn’t be dismissed from Greek or American history. Simply, slavery cannot be edited out of the fable known as the United States of America: as part of our heritage it is part of us. To wit: in telling America’s story of slavery, let’s tell it through symbols. There is a version of the Greek Athena atop our acropolis, the US Capitol; her name is Freedom and she was designed with America in mind. That being so, it’s not ironic she was born in 1863 in the middle of our Civil War and great citizenship debacle. It’s also not ironic the foreman (wage-earner) went on strike while building Freedom and would not complete the bronze statue: slaves completed Freedom.

Oh yeah ~ back to Aesop the slave. There are lots of thoughts on where he came from; some say a northern Dorian settlement on the Black Sea, some Phrygia in modern-day Turkey, and even others Ethiopia; most likely it looks like he hailed from the Samos and Miletus area on the Mediterranean coast of Turkey. This eternal debate is easily solved by genetic fiat: according to DNA, we’re all out of Africa.

Ah, there we are ~ Aesop the human.

Bonus Video
Aesop’s The Lion & The Mouse

Next up in the series War Cry Heal Union:
27 June 2014: War Cry ~ Cheatham’s Hill, 27 June 1864.

Posted by Bryan W. Brickner