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

Welcome Homeostasis!
Burning Man Edition

Today’s science roundup looks at four 2014 articles on how the cannabinoid system (CS) modulates our health through homeostasis. The line-up links to CS PubMed articles discussing: hippocampus inhibition and excitation, pain relief from a Chinese herb (thunder God vine), GABA pain dis-inhibition, and brain protection from a single ultralow dose of tetrahydrocannabinol (THC).

The annual Burning Man festival in Black Rock City (NV) was last week; participants test their CS by enduring two Black Rock extremes ~ art and nature ~ which create space for mind and body to catch a glimpse of … spirit.

I. Hippocampus Homeostasis (Inhibition and Excitation) and the CS (Endos)
“Endocannabinoids (eCBs) modulate both excitatory and inhibitory neurotransmission in hippocampus via activation of pre-synaptic cannabinoid receptors. Here, we present a model for cannabinoid mediated short-term depression of excitation (DSE) based on our recently developed model for the equivalent phenomenon of suppressing inhibition (DSI). … Finally, we explore under which conditions the combination of DSI and DSE can temporarily shift the fine balance between excitation and inhibition. This highlights a mechanism by which eCBs might act in a neuro-protective manner during high neural activity.”
Cannabinoid-mediated short-term plasticity in hippocampus.
Zachariou M, Thul R.
J Comput Neurosci. 2014 Aug 16. [Epub ahead of print]
PMID: 25123173 [PubMed - as supplied by publisher]
Related citations

II. Homeostasis (Pain Relief) and CS CB2 Signaling
“Celastrol, a major active ingredient of Chinese herb Tripterygium wilfordii Hook. f. (thunder god vine), has exhibited a broad spectrum of pharmacological activities, including anti-inflammation, anti-cancer and immunosuppression. … Taken together, our results demonstrate the analgesia effects of celastrol through CB2 signaling and propose the potential of exploiting celastrol as a novel candidate for pain relief.”
Celastrol attenuates inflammatory and neuropathic pain mediated by cannabinoid receptor type 2.
Yang L, Li Y, Ren J, Zhu C, Fu J, Lin D, Qiu Y.
Int J Mol Sci. 2014 Aug 6;15(8):13637-48. doi: 10.3390/ijms150813637.
PMID: 25101848 [PubMed - in process] Free Article
Related citations

III. Homeostasis (GABA Pain Dis-inhibition) and the CS
“At the cellular level, opioids and cannabinoids are hypothesised to activate descending analgesia through an indirect process of 'GABA disinhibition'-suppression of inhibitory GABAergic inputs onto output neurons which constitute the descending analgesic pathway.”
Descending modulation of pain: the GABA disinhibition hypothesis of analgesia.
Lau BK, Vaughan CW.
Curr Opin Neurobiol. 2014 Jul 24;29C:159-164. doi: 10.1016/j.conb.2014.07.010. [Epub ahead of print] Review.
PMID: 25064178 [PubMed - as supplied by publisher]
Related citations

IV. Homeostasis (CS CNS Protection) from a Single Ultralow Dose of THC
“In our previous studies, we found that a single ultralow dose of tetrahydrocannabinol (THC; 0.002 mg/kg, three to four orders of magnitude lower than the conventional doses) protects the brain from different insults that cause cognitive deficits. … Our results suggest that an ultralow dose of THC that lacks any psychotrophic activity protects the brain from neuroinflammation-induced cognitive damage and might be used as an effective drug for the treatment of neuroinflammatory conditions, including neurodegenerative diseases.”
Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation-induced cognitive damage.
Fishbein-Kaminietsky M, Gafni M, Sarne Y.
J Neurosci Res. 2014 Jul 16. doi: 10.1002/jnr.23452. [Epub ahead of print]
PMID: 25042014 [PubMed - as supplied by publisher]
Related citations

Video: Cannabinoid Profiles - THC, THCA, THCV, CBD, CBG, CBN, CBC & Terpenes    

“Hey Yank,” Johnny Reb said.
“Hey Reb,” answered Augustus Kotka [1833 to 11 August 1864: KIA US Army, Siege of Atlanta].
“Gus, this ain’t Georgia: where we at?”
“This is Nowhere,” Gus replied; “I didn’t feel like meeting there this time.”
“Nowhere’s nice,” Reb noted. “What’s up though? ~ Whatcha’ wanna know?”
“Who got me killed?”
“That’s the same question for 150 years Yank ~ with the same answer ~ you did.”
“No, really, who got me killed?”
“I did then.”
“You always say that ~ this year things are different though.”

“How so?”
“The Constitution … it should have worked by now.”
“You’re saying it ain’t working Yank?”
“I got killed fighting ‘For’ something, not ‘Against’ you.”
“Fair enough.”
“Right ~ ‘cept fair means both sides think it’s fair: I don’t think a civil war was fair in 1861.”
“You talking Representation?” asked Reb.
“I think so; what do you know?”
“Lots being a Spirit and all.”
“So how’s that make you feel?" asked Gus; "You know, not having Constitutional Representation and having a civil war over slavery and the three fifths clause and not George Washington’s thirty Thousand?”
“George was a Reb," answered Johnny, "and so was Henry “Light-Horse” Lee and his son Robert E. Lee; Virginia produced lots of rebels.”
“Yup ~ and lots of presidents too.”
“Four of the first five,” Reb added, “hey ~ maybe this Nowhere landscape can help us.”
“Okay.”
“Take this thistle here.”
“Ouch.”
“Right Gus ~ the thorns protect flowers so seeds can be made.”
“Okay.”
“And then look at these flowers …”

“… Look like weeds to me.”
“Flowering weeds then ~ yet they do it differently; they share space by numbers …”
“… And not thorns.”
“Right.”
“That’s our civil war,” followed Gus, “seems the founders intended something other than thorns; then what happened with Robert E. Lee?”
“Lee missed a great strategic opportunity,” said Reb.
“1862 Antietam? 1863 Gettysburg? Petersburg 1864?”
“No,” Reb assured, “Blair 1861.”
“Right. US General Winfield Scott, his mentor and fellow Virginian, had asked him to help the Union; and then President Abraham Lincoln, through his intermediary, Mr. Blair, offered US Colonel Robert E. Lee a promotion to Major General and command of an army to quell the rebellion.”
“That is so,” added Reb, “April 1861 was Lee’s moment for Civil Greatness.”
“How so?”    
“Try this on and see if it fits; if US Colonel Lee accepts President Lincoln’s offer, he buys the Union, Confederacy and Virginia a much valued commodity: Time. Lee had lots to work with: the prestige of his family, three decades of Union service, and was friends with Confederate President Jefferson Davis.”
“That makes sense.”
“If Lee takes command,” continued Reb, “he could have dawdled, played the newspaper game, or made a move ~ that would have been Civil and Strategic.”
“I see it Reb; it’s like he could have slowed things down, waited … and then what?”
“That is it ain’t it: then what?” pondered Johnny. “The way things were, with the slave states uniting and the non-slave states in turmoil, it’s not clear what would have happened.”
“Okay …”
“Though with his great abilities,” Reb imagined, “perhaps some big meeting with him and Jeff Davis in Fredericksburg Virginia.”
“Nice imagination Reb.”
“Thanks ~ it’s a fun thought that might have saved your life Gus.”
“And lots of Johnnies.”
“For sure ~ Lee would have had the loyalty of the Union and kinship with the rebellion at his hands; Lincoln would have looked like he needed Lee to make peace, and he probably did.”
“Interesting theory Reb …”
“Then see, Lee is a national hero,” Reb mused, “and he becomes President in 1864 ~ elected by the Union he saved.”
“You’re out there now Reb …”
“Not too far though,” continued Reb, “as no one expected a Nobody like Grant to become president.”
“Lee wasn’t into politics,” noted Gus.
“War is politics,” Reb clarified; “I’m just saying with his family name, being a Virginian that saved the Union … well, who knows how Great that might have been."
“Thanks for the line of thinking Reb ~ nice Ponderances.”
“Ponderances ~ I like that ...”

Johnny Reb then gave Gus Yank a Spirit speech: “You know Gus, the year 2020, with the decennial Enumeration (census), is a Time for We the People to build the United States of America the founders’ intended ~ and it’ll be even better than theirs because it fulfills their Spirit in a way they couldn’t …”
“… Representing the Unrepresented.”
“Right Gus; if we Represent in 2020, we’d be honoring our Republic by fulfilling the founders’ Constitutional Rebel vision: a House for We the People and a Senate for We the States.”
“Agreed.”
“Sun’s up Gus.”
“Sounds like ‘Sons Up’ Reb.”
“Sure does ~ Whatcha’ say we meet again?”
“Great.”
“Hey,” smarted Reb, “let’s meet ‘Somewhere’ next time.”
“Got a place in mind?” Gus chuckled.
“I do.”
“That’ll be fun ~ peace Reb.”
“Peace Yank ~ and see you again soon … ”
~
Video Adaptation:
Robert E Lee refuses command of the Union Army

*Extra/New WCHU series announcement from Ew Publishing: we’re adding one to the ten in the War Cry Heal Union series (see our 26 May 2014 release). The addition looks at Representing the Unrepresented “Stock of Abraham” via George Washington and the Hebrew Congregation of Rhode Island; it’ll be number 7.5 of 10 in one week, Monday 18 August 2014.
~
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

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

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
Related citations

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
Related citations

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
Related citations

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
Related citations

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
Related citations

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]
Related citations

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]
Related citations

~’~
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]
Related citations

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
Related citations

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]
Related citations

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
Related citations

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
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

~ 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]
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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

March Madness induces coaches, players and fans to intensity. A first sign of intensity, one in every ballgame played during this madness, is traditional and time-tested: the warm-up. This pre-game activity, designed with the players in mind, is really for the body: one has to wake the body up (stress it a bit) to make it intense – to raise consciousness.

One’s heart pumps more, legs stretch, breathing calms, and soon the first drops of intensity … sweat.

Sweat is also a sign of the cannabinoid system (CS). The CS modulates exercise by priming our other systems for activity: the research is exciting (maybe even more than a few of the games) and The National Institutes of Health (PubMed) provides the quotes and play-by-play.

Reward and Warm-up
Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'. (2012)

“Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise. Endocannabinoids (eCBs) are endogenous neurotransmitters that appear to play a major role in generating these rewards by activating cannabinoid receptors in brain reward regions during and after exercise.”

“This study provides the first evidence that inter-specific variation in neurotransmitter signaling may explain differences in locomotor behavior among mammals.”

Reward and Intensity
Exercise-induced endocannabinoid signaling is modulated by intensity. (2013)

“Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are densely expressed in brain networks responsible for reward.”

“Our results are consistent with intensity-dependent psychological state changes with exercise and therefore support the hypothesis that eCB activity is related to neurobiological effects of exercise. Thus, future studies examining the role of exercise-induced eCB signaling on neurobiology or physiology must take exercise intensity into account.”

Reward and Depression
Intense exercise increases circulating endocannabinoid and BDNF levels in humans – possible implications for reward and depression. (2012)

“The endocannabinoid system is known to have positive effects on depression partly through its actions on neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF). As BDNF is also considered the major candidate molecule for exercise-induced brain plasticity, we hypothesized that the endocannabinoid system represents a crucial signaling system mediating the beneficial antidepressant effects of exercise.”

“These findings provide evidence in humans that acute exercise represents a physiological stressor able to increase peripheral levels of AEA [anandamide] and that BDNF might be a mechanism by which AEA influences the neuroplastic and antidepressant effects of exercise.”

The CS handles intensities like a play-making point-guard; these ballgames and our enthusiasm involve an ancient biological process genetically developed for millions of years. You’ll recognize its presence in the cards of victory and the flush of defeat.

Oh yeah … the refs. Human too you know ~ meaning CS modulation is involved. So let’em warm-up proper and get prepared, as it’s that time: tip-off!

March Madness Modulation Everyone!

Bryan W. Brickner

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

Cancer prevention awareness and the cannabinoid system are the focus of February’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed science on inflammation, a unique receptor, GPR55, and the ability of one’s cannabinoid system to induce apoptosis, programmed cancer cell death.

2014 ~ Inflammation (HIV-1) and CS/GPR55
“Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection.”

Δ9-Tetrahydrocannabinol Treatment During Human Monocyte Differentiation Reduces Macrophage Susceptibility to HIV-1 Infection.
Williams JC, Appelberg S, Goldberger BA, Klein TW, Sleasman JW, Goodenow MM.
J Neuroimmune Pharmacol. 2014 Feb 23. [Epub ahead of print]
PMID: 24562630 [PubMed - as supplied by publisher]


2013 ~ Alcohol, Dentric Cells and CS/GPR55
"Our results provide insights into alcohol mechanisms of DC [dentric cell] regulation and show, for the first time, that alcohol is inducing CNR2 [CB2] and GPR55 in human DCs."

Differential expression and functional role of cannabinoid genes in alcohol users.
Agudelo M, Yndart A, Morrison M, Figueroa G, Muñoz K, Samikkannu T, Nair MP.
Drug Alcohol Depend. 2013 Dec 1;133(2):789-93. doi: 10.1016/j.drugalcdep.2013.08.023. Epub 2013 Sep 5.
PMID: 24060590 [PubMed - in process]


2013 ~ Inflammation (Cancer) and CS/GPR55
“GPR55 has been shown to have a role in cancer and gastrointestinal inflammation, as well as in obesity and type 2 diabetes mellitus (T2DM).”

A potential role for GPR55 in the regulation of energy homeostasis.
Simcocks AC, O'Keefe L, Jenkin KA, Mathai ML, Hryciw DH, McAinch AJ.
Drug Discov Today. 2013 Dec 24. pii: S1359-6446(13)00423-6. doi: 10.1016/j.drudis.2013.12.005. [Epub ahead of print] Review.
PMID: 24370891 [PubMed - as supplied by publisher]


2013 ~ CS Synergistic Against Cancer
“The observed synergistic effect with cannabinoid agonists implicates an involvement of the cannabinoid system.”

Cytotoxic effect of efavirenz is selective against cancer cells and associated with the cannabinoid system.
Hecht M, Harrer T, Büttner M, Schwegler M, Erber S, Fietkau R, Distel LV.
AIDS. 2013 Aug 24;27(13):2031-40. doi: 10.1097/QAD.0b013e3283625444.
PMID: 23612009 [PubMed - in process]


2011 ~ GPR55 Driving Cancer Cell Migration
“It has now been revealed that LPI [L-α-lysophosphatidylinositol] activates GPR55, a G protein-coupled receptor that couples to G(12/13) and G(q) proteins, which direct oncogenic signalling. New evidence indicates that LPI and GPR55 are key partners in driving cancer cell proliferation and migration.”

L-α-lysophosphatidylinositol meets GPR55: a deadly relationship.
Ross RA.
Trends Pharmacol Sci. 2011 May;32(5):265-9. doi: 10.1016/j.tips.2011.01.005. Epub 2011 Mar 1.
PMID: 21367464 [PubMed - indexed for MEDLINE]


2010 ~ Breast Cancer and CS/GPR55
“LPI and GPR55 play a role in the modulation of migration, orientation and polarization of breast cancer cells in response to the tumour microenvironment.”

A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells.
Ford LA, Roelofs AJ, Anavi-Goffer S, Mowat L, Simpson DG, Irving AJ, Rogers MJ, Rajnicek AM, Ross RA.
Br J Pharmacol. 2010 Jun;160(3):762-71. doi: 10.1111/j.1476-5381.2010.00743.x.
PMID: 20590578 [PubMed - indexed for MEDLINE] Free PMC Article


2006 ~ Evolution and CS/GPR55
“Within this limited number of twelve organisms, the endocannabinoid genes exhibited heterogeneous evolutionary trajectories, with functional orthologs limited to mammals (TRPV1 and GPR55), or vertebrates (CB2 and DAGLbeta), or chordates (MAGL and COX2), or animals (DAGLalpha and CB1-like receptors), or opisthokonta (animals and fungi, NAPE-PLD), or eukaryotes (FAAH).”

Evolutionary origins of the endocannabinoid system.
McPartland JM, Matias I, Di Marzo V, Glass M.
Gene. 2006 Mar 29;370:64-74. Epub 2006 Jan 23.
PMID: 16434153 [PubMed - indexed for MEDLINE]

~ posted by bwb

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

Here are a few recent 2013-14 findings on how cannabinoids modulate homeostasis and other systems in our bodies: the roundup links to seven recent PubMed articles on the central nervous, reproductive, neuromodulatory, limbic and opioid systems.

I. Nervous System (Alzheimer’s/Dementia) and CS
“The results confirm the constitutive role of the CB2 receptor system both in reducing amyloid plaque pathology in AD [Alzheimer’s disease] and also support the potential of cannabinoid therapies targeting CB2 to reduce Aβ; however, the results suggest that interventions may have a divergent effect on tau pathology.”

CB2 Receptor Deficiency Increases Amyloid Pathology and Alters Tau Processing in a Transgenic Mouse Model of Alzheimer's Disease.
  Koppel J, Vingtdeux V, Marambaud P, D'abramo C, Jimenez H, Stauber M, Friedman R, Davies P.
  Mol Med. 2013 Nov 8;19:357-64. doi: 10.2119/molmed.2013.00140.
  PMID: 24408112 [PubMed - in process] Free PMC Article

II. Reproductive System (Male) and CS
“Together with their receptors and metabolic enzymes, they form the "endocannabinoid system" (ECS). In male reproductive tracts, they affect Sertoli cell activities, Leydig cell proliferation, germ cell differentiation, sperm motility, capacitation, and acrosome reaction.”

The Endocannabinoid System and Spermatogenesis.
  Grimaldi P, Di Giacomo D, Geremia R.
  Front Endocrinol (Lausanne). 2013 Dec 16;4:192. eCollection 2013. Review.
  PMID: 24379805 [PubMed - as supplied by publisher] Free PMC Article

III. Neuromodulatory System and CS
“Emerging findings suggest the existence of a cross-talk between hypocretinergic and endocannabinoid systems. Although few studies have examined this relationship, the apparent overlap observed in the neuroanatomical distribution of both systems as well as their putative functions strongly point to the existence of such cross-modulation.”

Cannabinoid-hypocretin cross-talk in the central nervous system : what we know so far.
  Flores A, Maldonado R, Berrendero F.
  Front Neurosci. 2013 Dec 20;7:256. eCollection 2013. Review.
  PMID: 24391536 [PubMed - as supplied by publisher] Free PMC Article

IV. Limbic System (Emotions) and CS
"Based on the evidence reviewed here, we propose that the endocannabinoid system is an emotional buffer that moderates the effects of environmental context and stress on cognitive processes."

The endocannabinoid system: An emotional buffer in the modulation of memory function.
  Morena M, Campolongo P.
  Neurobiol Learn Mem. 2013 Dec 29. pii: S1074-7427(13)00266-9. doi: 10.1016/j.nlm.2013.12.010. [Epub ahead of print]
  PMID: 24382324 [PubMed - as supplied by publisher]

V. Central Nervous System (Nicotine/Acetylcholine) and CS
“Furthermore, it seems that there is a functional interaction between the BLA cannabinoid receptors and nicotine in producing the rewarding effects.”

Basolateral amygdala CB1cannabinoid receptors mediate nicotine-induced place preference.
  Hashemizadeh S, Sardari M, Rezayof A.
  Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 24. pii: S0278-5846(14)00011-6. doi: 10.1016/j.pnpbp.2014.01.010. [Epub ahead of print]
  PMID: 24468643 [PubMed - as supplied by publisher]

VI. Homeostasis and the CS
“The endocannabinoid system is present in stress-responsive neural circuits and it is emerging as a homeostatic system.”

Regulatory role of the Cannabinoid-2  receptor in stress-induced neuroinflammation in mice.
  Zoppi S, Madrigal JL, Caso JR, García-Gutiérrez MS, Manzanares J, Leza JC, García-Bueno B.
  Br J Pharmacol. 2014 Jan 28. doi: 10.1111/bph.12607. [Epub ahead of print]
  PMID: 24467609 [PubMed - as supplied by publisher]

VII. Opioid System and CS
“These results enhance our understanding of the mechanisms involved in the peripheral effect of crotalphine an antinociceptive peptide, as well as the interaction between the opioid and cannabinoid systems.”

Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine.
  Machado FC, Zambelli VO, Fernandes AC, Heimann AS, Cury Y, Picolo G.
  Br J Pharmacol. 2014 Feb;171(4):961-72. doi: 10.1111/bph.12488.
  PMID: 24460677 [PubMed - in process]

~
Bryan w. Brickner