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   

In attending a hemp film showing, I got surprised.

I hadn’t read anything about the movie and didn’t even look up the title; you know, I thought I was just going to see a hemp film (and I’ve seen lots).

It was March, near Chicago’s Wicker Park neighborhood, and I knew it wouldn’t be a bunch of farmers; I knew it would be city folk in a collective space with walls of art and a view of Chicago.

Jack Herer was the surprise; he wasn’t there of course (1939-2010), yet the night was his. Bringing it Home: industrial hemp, healthy houses and a greener future for America (2013), a documentary by Linda Booker and Blaire Johnson, would have inspired an activist like Herer – also known as The Hemperor.

Herer authored The Emperor Wears No Clothes (1985), the best hemp book ever: it tells the political economic story of America’s hemp war and argues (shows really) that hemp can save our home – planet earth.

The Wicker Park crowd though was different than the one Herer wrote for; his audience didn’t know hemp was great. This group, about 25 people, all activists really, in one way or another, arrived already knowing hemp is great; most seemed to be there in support of hemp ~ you know, to show support and see a new show.

Then the movie started … sort of.

What began was a few seconds about a father discussing his ill daughter and her special health needs. The person monitoring said something like, “Oops ~ wrong spot.” I thought that meant we’d see the hemp film now …

The movie started and again it was about a father’s efforts to help his ill child, and it wasn’t about eating hemp: it was about living inside of hemp – in a hemp house – and the environmental (and economic) protection and benefits for individual and community.

Bringing It Home is not an individual health care story: the film is about the revolution that Herer talked about ~ the one with hemp saving the planet ~ and the documentary shows a Herer-like reality.

Here’s a Hemperor inspired Bringing it Home synopsis:

Seed ~
A father in search for the safest and cleanest building material for his environmentally sensitive child: he finds hemp.

Generation ~
No hemp in America to show so the movie goes to Europe. Here we find British farmers (not hippies mind you) working with the government to monitor the fields and the 16 types of industrial hemp that can be grown for seed and fiber.

Pollination ~
Hemp’s not just for breakfast anymore; the 21st century hempvolution is in housing: specifically, building materials.

Flower ~
Food, jobs, clothing, environmentally sound, and now eco-friendly housing … in Europe and the rest of the world. The movie notes the lack of American hemp and highlights the need to grow our own.

Harvest ~
Bringing It Home makes the point that hemp is too expensive to ship to America; not growing our own looks like an economic and environmental failure. From a business and government angle, the film shows America needs hemp investment for infrastructure; most notably, networks of fiber processing plants near the hemp fields in order to turn the green plant into the other green (cash).

Hemp and Earth Day go together, each one for the other one. Hemp offers us an earth gift: an economically environmental revolution that can help the earth get ready for what’s coming … and that’s the 22nd Century. So, like Bringing It Home teaches, let’s begin (and finish) the building with hemp.

Happy Earth Day 2014 Everyone!

Bonus Video:
HempCrete: Strongest & Greenest Building material in Nature

Posted by Bryan W. Brickner

Albert Hoffman 1993 (by Philip H. Bailey)

Bicycle Day is the day scientist Albert Hoffman took an intentional dose of lysergic acid diethylamide (LSD) and then rode his bike home.

Hoffman’s intentional dose on 19 April 1943 was actually his second “contact” with LSD. The macro dose day is the memorable bicycle ride home; the unintentional first dose was at a micro level absorbed through his skin (or somehow). Hoffman wasn’t ever very clear on how that happened; he did note a slight modulation from the micro experience … enough to convince him to try the macro.

LSD works because it modulates one’s serotonin system and its plethora of receptors (15 last time I checked). Hoffman was the first to experience the synaptic serotonin effects LSD yields – yet we all modulate our bodies via serotonin … we just do it daily in a micro way (it’s in us).

Below is a four-part science story from the National Institutes of Health (PubMed): it includes a dialogue between our immune and serotonin systems, an early microbiota life tale, a circadian clocks discussion, and talk of bowels (irritable and otherwise) and the brain-gut axis. The links and quotes are from PubMed.

Think of cannabinoids as the wheel’s hub and serotonin as the transmission: for certain, as Albert Hoffman attested, it’s a neurotransmission without equal.

Happy Bicycle Day 2014 Everyone!

~
I. A Dialogue (immune and serotonin systems)
“Neuropsychiatric disorders have long been linked to both immune system activation and alterations in serotonin (5-HT) signaling. In the CNS, the contributions of 5-HT modulate a broad range of targets, most notably, hypothalamic, limbic and cortical circuits linked to the control of mood and mood disorders. In the periphery, many are aware of the production and actions of 5-HT in the gut but are unaware that the molecule and its receptors are also present in the immune system where evidence suggests they contribute to the both innate and adaptive responses. In addition, there is clear evidence that the immune system communicates to the brain via both humoral and neuronal mechanisms, and that CNS 5-HT neurons are a direct or indirect target for these actions.”

A dialogue between the immune system and brain, spoken in the language of serotonin.
Baganz NL, Blakely RD.
ACS Chem Neurosci. 2013 Jan 16;4(1):48-63. doi: 10.1021/cn300186b. Epub 2012 Dec 7. Review.
PMID: 23336044 [PubMed - indexed for MEDLINE] Free PMC Article
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II. Early Life (immune, endocrine and serotonin systems)
“Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. … Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. … However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. … Moreover, this alteration is sex specific in contrast with the immunological and neuroendocrine effects which are evident in both sexes. Concentrations of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission.”

The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner.
Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, Dinan TG, Cryan JF.
Mol Psychiatry. 2013 Jun;18(6):666-73. doi: 10.1038/mp.2012.77. Epub 2012 Jun 12.
PMID: 22688187 [PubMed - indexed for MEDLINE]
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III. Circadian Clock (chickens and serotonin biosynthesis)
“Serotonin in blood plasma is primarily synthesized in the duodenum [first section of the small intestine], as brain derived serotonin does not cross the blood-brain barrier. Because serotonin in the brain and retina is synthesized under the control of a circadian clock, we sought to determine if a circadian clock in the duodenum regulates serotonin synthesis and release in blood. We examined gene expression in the duodenum of chickens at different times of the day and found that the duodenum rhythmically expresses molecular circadian clock genes and genes controlling serotonin biosynthesis, specifically tryptophan hydroxylase, in a light dark cycle (LD). … Because serotonin in the gut affects duodenal nutrient absorption and gut motility, the control of serotonin production in the duodenum by LD cycles could provide an additional mechanism by which the external environment controls nutrient uptake and digestive function.”

Biological clocks in the duodenum and the diurnal regulation of duodenal and plasma serotonin.
Ebert-Zavos E, Horvat-Gordon M, Taylor A, Bartell PA.
PLoS One. 2013 May 30;8(5):e58477. doi: 10.1371/journal.pone.0058477. Print 2013.
PMID: 23737937 [PubMed - indexed for MEDLINE] Free PMC Article
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IV. Bowels (irritable and otherwise: brain-gut axis)
“Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal discomfort, pain and changes in bowel habits, often associated with psychological/psychiatric disorders. It has been suggested that the development of IBS may be related to the body’s response to stress, which is one of the main factors that can modulate motility and visceral perception through the interaction between brain and gut (brain-gut axis). … Several lines of evidence indicate that 5-HT and its receptor subtypes are likely to have a central role in the pathophysiology of IBS. 5-HT released from enterochromaffin cells regulates sensory, motor and secretory functions of the digestive system through the interaction with different receptor subtypes. It has been suggested that pain signals originate in intrinsic primary afferent neurons and are transmitted by extrinsic primary afferent neurons. Moreover, IBS is associated with abnormal activation of central stress circuits, which results in altered perception during visceral stimulation.”

Serotonin receptors and their role in the pathophysiology and therapy of irritable bowel syndrome.
Stasi C, Bellini M, Bassotti G, Blandizzi C, Milani S.
Tech Coloproctol. 2014 Jan 15. [Epub ahead of print]
PMID: 24425100 [PubMed - as supplied by publisher]
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Plus ~ Today's Video ~
Serotonin and the Gut Brain Connection
http://www.youtube.com/watch?v=KYT5syDMsTQ

Posted by Bryan W. Brickner

Slavery is the shadow of usurpation (rights taken without right) the way mythology frames America’s beginning: it’s foundational.

Slavery has been edited out of Usurpation Day 2014; it will be duly accorded its role in both Athens and America in June (on the 19th).

Usurpation Day is not a time to be sad; it’s a celebratory day. The usurpation of the representation ratio on 9 April 1792 is our history … it’s not our heritage.

Heritage is ahistorical (timeless) and it is our focus today: specifically, ascending Athenian American heritage. Six greats ~ three from each polis: Plato and Madison, Pericles and Washington, and Athena and Freedom:

Plato
Plato’s contribution to our heritage is The Republic. In the book he outlines the just society and details three groups (factions/divisions) in his republican form of government: rulers, guardians and craftspeople (producers).

Madison
Madison’s contribution to our heritage is the addition of the representation ratio to Plato’s republican ideas. Whereas Plato’s republic has three factions, Madison’s republic has a fourth ~ We the People ~ and utilizes the decennial Census to augment representation in accordance with population growth (something Plato’s republican ideas lack).

Pericles
His era built the Parthenon. He was an Athenian leader during the Peloponnesian War and his Funeral Oration (speech) is noted in Thucydides’ work. 

Washington
His era built the District of Columbia. Washington was hailed as the first in war and the first in peace. His most famous speech is his Farewell Address. Washington’s library included the Greeks: Homer’s Iliad and Odyssey and Ovid’s Metamorphoses ~ which makes mention of 30,000 spirits who watch over the deeds of humans and bring agricultural bounty.

Athena
The Athenian’s had a statue of Athena inside the Parthenon. She is noted for many things to the Greeks; in particular, the victory at Troy and the homecoming of Odysseus. She was referred to as Promachus: first (foremost) fighter and one who leads in battle. Also, parthenongenesis is asexual reproduction without fertilization  ~ noting Athena’s birth from the head of Zeus.

Freedom
We the People have our own Athena: her name is Freedom and she watches over America from atop our acropolis, the US Capitol. There were three versions of Freedom’s statue. The first looked too much like Athena; the second, too much like Minerva (Rome’s Athena); the third they thought looked just about right I guess … you know, for being born in 1863 in the middle of the US Civil War.

Heritage (not history) is the key to Usurpation Day ~ and keep this in mind: America’s best days are ahead of US.

Let us pick-up there on 19 June … Juneteenth.

Bryan W. Brickner