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Peppered Cannabinoids: Caryophyllene

12/30/2017

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​Pass the pepper please!


You might have experienced something like this: you eat a pepper and it makes you sweat.
 
If you haven’t had that experience, try a habanero pepper (just a little) to play along.
 
Sweating is dependent on our cannabinoid system (CS): for example, CB2 skin receptors modulate/maintain mammalian body temperature.
 
And it’s not just a reaction to the pepper: the pepper is modulating cannabinoid receptors – especially forehead ones for habanero-eaters – and it seems the hotter the pepper equals more CB2 response.
 
This happens because of the ubiquitous essential oil caryophyllene.
 
Here’s a sales site with caryophyllene and black pepper oil information.
 
And here’s a 2008 NIH article, Beta-caryophyllene is a dietary cannabinoid, which confirms the caryophyllene found in black pepper is “dietary” and states the oil is also found in such things as oregano, cinnamon and cannabis. 
 
Of course, a re-examination of the world spice trade is needed: looks like early cannabinoid trafficking now – who knew?
 
*Next Up: NYE 2017 and an abstract serotonin poem, A Microbiota Ode to the Brain-Gut Axis.
 
Posted by Bryan W. Brickner
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Toast Them Hemp Seeds For Hempoween

10/31/2017

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PictureToasted Hemp Seeds for Hempoween




Two hundred and fifty-two years ago today, on 31 October 1765, George Hempington celebrated the first documented Hempoween. The farmer and his slaves had harvested 152 bushel of hemp seed; after milling the seed to collect the oil, George writes of his celebratory actions in his farm journal:
 
“31 October: Finished sowing Wheat in Hemp Ground at Rivr. Plantn. & plowed in a good deal of shattered Hemp Seed – 27 Bushls. in all 152.”
 
That, my friends, is a traditional Hempoween celebration: the scattering of shattered hemp seeds on your field (or garden) as a fertilizer for the next season.
 
There are also many more modern ways to enjoy your hemp products this Hempoween: one that was new to me is toasted hemp seeds. I purchased the little delicacies (see picture above) at a regular grocery store in the Midwest – nothing fancy, and no special license or doctor’s note was needed.
 
I did leave the original bag of toasted seeds with some hippies (burners really), and I don’t expect to see the treats again; you see, they are quite yummy toasted and I know what to expect when one leaves a bag of hemp products around burners.
 
So toast them hemp seeds this year while you are celebrating Hempoween, and perhaps even give a shout out of remembrance to George, his wife Artha, and the slaves who made it all possible.
 
Here’s to a happy – and toasted – Hempoween for all!
 
*Next Up: Sunday 5 November and a pamphlet release, Three Liminal Dialogues on Serotonin, Mosby and Luther.

Posted by Bryan W. Brickner

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Homeostasis: If Not Cannabinoid Receptor Three, then Cannabinoid Receptor Third

6/7/2017

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PictureThe Cannabis Papers by Publius








​In The Cannabis Papers: A citizen’s guide to cannabinoids (2011), we noted evidence for a CB3 receptor in addition to CB1 and CB2. The research suggested that there was more happening (things to be accounted for, scientifically) and another receptor was proposed. In 2017 it looks like the best answer is a third category of activity and not a specific receptor; notably, this third activity involves many other kinds of receptors.
 
The Guide to Pharmacology website has an introduction page for cannabinoid receptors; at the bottom of the page there is a section on this third activity (non-CB1 and non-CB2 modulation). The site notes it is “generally accepted” that other receptor types, and thus other systems, are modulated by cannabinoids; this is true for endo, plant and pharmaceutical cannabinoids.
 
This third signaling effect connects progesterone and nuclear receptors to cannabinoids; it also suggests modulating endometriosis is similar to homeostasis: both depend on cannabinoids for healing and health.
 
*Next Up: Wednesday 21 June and a 2020: Virtual Representation and We the People.
 
Posted by Bryan W. Brickner

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Homeostasis: Cannabinoid, Progesterone and Nuclear Receptors

5/31/2017

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PictureNuclear Receptor In Action


​Think of a cell as a hub: a center of communication.
 
This hub has gates and points of entry: for our example, think of cannabinoid and progesterone receptors. These receptors facilitate communication with other hubs and inside a hub (with other cells and inside a cell).
 
There are nuclear receptors in all hubs/cells; these receptors regulate our genes (by transcribing DNA) and control our development, homeostasis and metabolism.
 
Recall that endometriosis is a disruption of a hub and its network: the cells grow (generate) as they are designed to do, just in the wrong spot.
 
An obvious point of disruption and research is the communication between progesterone and nuclear receptors; another is anandamide and all the other cannabinoids (endo, plant and pharmaceutical), as they too can modulate nuclear receptors.
 
We’ll begin with that homeostatic science next week: cannabinoids modulating nuclear receptors - and thus our every day.
 
*Next Up: Wednesday 7 June and a Homeostasis: If Not CB Three, then CB Third.
 
Posted by Bryan W. Brickner

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Homeostasis: Endometriosis, Progesterone and Cannabinoid Systems

5/24/2017

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PictureProgesterone






​Progesterone-dependent regulation of endometrial cannabinoid receptor type 1 (CB1-R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
 
The above title was published in Fertility and Sterility in 2012 and can be found on PubMed.
 
The research finds that endometriosis, where cells grow outside instead of inside the uterus (endometrium), is caused by a failure to communicate between progesterone and the cannabinoid system; this failure is painful and contributes to infertility. Summary quote from the research: “Our studies reveal a role for the anti-inflammatory actions of progesterone in regulating endometrial cannabinoid signaling, which is disrupted in women with endometriosis.”
 
How does that work though? What is disrupted? If communication between progesterone and the CB1 receptor is disrupted (as cells grow, just in the wrong place), how do cells normally communicate in a healthy, undisrupted homeostatic way?
 
The answer involves cannabinoid and progesterone nuclear receptor signaling: let’s just begin there next week.
 
*Next Up: 31 May and a homeostatic view of Progesterone Nuclear Receptors and Cannabinoid Systems.
 
Posted by Bryan W. Brickner

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2020: Smells Like Umami – Cannabinoid Heteronomy Hubbub

8/20/2016

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PictureTomatoes are rich in umami components


 
Umami Hets
 
Umami is one of five basic tastes along with sweetness, sourness, bitterness and saltiness. We can taste umami because of heteronomy (Hets): specifically, the combination of two receptors to form one action. Today’s heteronomy update explained the umami Hets like this:
 
"Taste T1 receptors are obligate Hets: ‘T1R3 acts as an obligate partner in T1R1/T1R3 and T1R2/T1R3 heterodimers, which sense umami or sweet, respectively.’"
 
Pharmaceutical cannabinoid research has regressed on the subject of Hets; they see evidence of cannabinoid Hets yet can’t synthetically reproduce them. The update warns: “in a sense, the field is going backward instead of forward.”
​

Basic Pharmacological and Structural Evidence for Class A G-Protein-Coupled Receptor Heteromerization
Frontiers in Pharmacology ~ 31 March 2016
Abstract
Cell membrane receptors rarely work on isolation, often they form oligomeric complexes with other receptor molecules and they may directly interact with different proteins of the signal transduction machinery. For a variety of reasons, rhodopsin-like class A G-protein-coupled receptors (GPCRs) [Cannabinoids] seem an exception to the general rule of receptor–receptor direct interaction. In fact, controversy surrounds their potential to form homo- hetero-dimers/oligomers with other class A GPCRs; in a sense, the field is going backward instead of forward. This review focuses on the convergent, complementary and telling evidence showing that homo- and heteromers of class A GPCRs exist in transfected cells and, more importantly, in natural sources. It is time to decide between questioning the occurrence of heteromers or, alternatively, facing the vast scientific and technical challenges that class A receptor-dimer/oligomer existence pose to Pharmacology and to Drug Discovery.
​
*Next Up: The Union 2016 summer series continues on Saturday 27 August with part 9, Johnny Reb and Gus Kotka Nowhere Nobody Home.
 
Posted by Bryan W. Brickner

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2020: Bivalent Ligands Targeting Cannabinoid Receptors? Longer Linkers May Not Be The Solution

7/9/2016

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PictureCNR1 is CB1 genetics



CB1 pharmacophore
 
Today’s cannabinoid system science update looks at a piece of pharmaceutical research on bivalency and our CB1 receptors. Pharmaceutical researchers are trying to duplicate the cannabinoid bivalency trait found in our bodies, which is the ability to simultaneously influence two different kinds of receptors.
 
They understand what our bodies do (“evidence suggests that ligands enter CB1 through the lipid bilayer”) yet don’t know how to copy it (“linkers are unlikely to exit the receptor through its external face”). They conclude: “the entire premise of designing bivalent ligands targeting CB1 must be revisited.”
 
Our bodies keep doing the bivalency shuffle, all the time and every day, while the pharmaceutical researchers revisit the drawing board, and maybe (perhaps) take Nixon’s scheduling law with them.
 
Trends in Pharmacological Sciences
PubMed 2016
One for the Price of Two…Are Bivalent Ligands Targeting Cannabinoid Receptor Dimers Capable of Simultaneously Binding to both Receptors?
 
Abstract:
​Bivalent ligands bridging two G-protein-coupled receptors (GPCRs) provide valuable pharmacological tools to target oligomers. The success of therapeutically targeting the cannabinoid CB1 receptor has been limited, in part due to its widespread neuronal distribution. Therefore, CB1 ligands targeting oligomers that exhibit restricted distribution or altered pharmacology are highly desirable, and several bivalent ligands containing a CB1 pharmacophore have been reported. Bivalent ligand action presumes that the ligand simultaneously binds to both receptors within the dimeric complex. However, based on the current understanding of CB1 ligand binding, existing bivalent ligands are too short to bind both receptors simultaneously. However, ligands with longer linkers may not be the solution, because evidence suggests that ligands enter CB1 through the lipid bilayer and, thus, linkers are unlikely to exit the receptor through its external face. Thus, the entire premise of designing bivalent ligands targeting CB1 must be revisited.

 
Next Up: The Union 2016 summer series continues on Sunday 10 July with part 4, Johnny Reb and Gus Kotka Nowhere Enemy Is Time.
 
Posted by Bryan W. Brickner

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2020: Putamen Cannabinoids and Opioids Control Our Brains (Even the brains of presidential candidates)

6/12/2016

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PicturePurple is Caudate Nucleus and Putamen / Orange is Thalamus







​
Brains presidential
 
There are cannabinoid (pot) receptors and precursors all over our brains; there are also opioid (heroin, morphine, oxycodone) receptors and precursors there too.
 
“If you were” to click on the publication image below you’d find a schematic representation of our brain’s cannabinoid and opioid receptors. The “If you were” is because there is some caution involved; seems that after looking at the image for a bit (twenty seconds or so) one might see the image looking back at you: I’m just saying it might happen.
 
I looked at the image for a bit and can report it shows three levels of receptor density for both cannabinoids and opioids: low, moderate and high. Some parts of our brains are high in both; one such spot is the caudate putamen.
 
The caudate putamen, located at the center of our brains (and the brains of all presidential candidates, it should be said), is fundamental to movement and learning; basically, we wouldn’t be bipedal or remember much without it. Adding science to our sense of ourselves, and the discussion known as the 2016 presidential election, will help us get through the next big thing: the 2020 Enumeration, i.e., the census and the “thirty Thousand.”
 
Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies
Frontiers in Pharmacology
Pubmed: 5 FEB 2015


From the abstract: The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins). The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2. These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction. Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry. 
​
*Images from this publication
See all images (1)Free text 

Next Up: Announcing the release of an Ew Publishing research pamphlet, Aspasia of Miletus: Socrates’ Didaskalos, on Wednesday 15 June.

 Posted by Bryan W. Brickner

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Translated Publius: The Cannabis Papers in Estonian is Kodaniku Kanepilugemik

1/15/2016

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PictureKodaniku Kanepilugemik by Publius (2015)


Cannabinoider News
 
The Cannabis Papers by Publius (2011) was translated into Estonian and published by Mondegreen.
 
Kodaniku Kanepilugemik by Publius (2015)
ISBN: 978-9949-38-757-1

Mondegreen Print Facebook
 
Thanks All!
 
*Next Up: Johnny Reb, Gus Kotka and Free Blacks, Sunday 17 January, part 4 of the Union 2016 winter series.

Posted by Bryan W. Brickner

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Jonathan Magbie Remembrance: Endocannabinoid Pregnancy Science at 20 Years

9/24/2015

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PictureJonathan Magbie Remembrance




















Jonathan Magbie died eleven years ago today, 24 September 2004; in remembrance, this PubMed update spans 20 years of endocannabinoid pregnancy science, with an emphasis on preimplantation and implantation of a blastocyst.

Like all of us, Magbie was born (1977 for him) via a mother's cannabinoid system.

1995
The preimplantation mouse embryo is a target for cannabinoid ligand-receptor signaling.    
Paria BC, Das SK, Dey SK.
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9460-4.
PMID: 7568154 Free PMC Article
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1998
Effects of cannabinoids on preimplantation mouse embryo development and implantation are mediated by brain-type cannabinoid receptors.
Paria BC, Ma W, Andrenyak DM, Schmid PC, Schmid HH, Moody DE, Deng H, Makriyannis A, Dey SK.
Biol Reprod. 1998 Jun;58(6):1490-5.
PMID: 9623610 Free Article
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2000
Ligand-receptor signaling with endocannabinoids in preimplantation embryo development and implantation.
Paria BC, Dey SK.
Chem Phys Lipids. 2000 Nov;108(1-2):211-20. Review.
PMID: 11106792
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2002
Endocannabinoid signaling in synchronizing embryo development and uterine receptivity for implantation.
Paria BC, Wang H, Dey SK.
Chem Phys Lipids. 2002 Dec 31;121(1-2):201-10. Review.
PMID: 12505701
Similar articles

2006
Endocannabinoid signaling directs periimplantation events.
Wang H, Xie H, Dey SK.
AAPS J. 2006;8(2):E425-32.
PMID: 16808046 Free PMC Article
Similar articles

2008
Aspects of endocannabinoid signaling in periimplantation biology.
Sun X, Dey SK.
Mol Cell Endocrinol. 2008 Apr 16;286(1-2 Suppl 1):S3-11. doi: 10.1016/j.mce.2008.01.002. Epub 2008 Jan 18. Review.
PMID: 18294762 Free PMC Article
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2009
Endocannabinoids, sperm biology and human fertility.
Lewis SE, Maccarrone M.
Pharmacol Res. 2009 Aug;60(2):126-31. doi: 10.1016/j.phrs.2009.02.009. Epub 2009 Mar 4. Review.
PMID: 19559363
Similar articles

2010
Endocannabinoids and pregnancy.
Taylor AH, Amoako AA, Bambang K, Karasu T, Gebeh A, Lam PM, Marzcylo TH, Konje JC.
Clin Chim Acta. 2010 Jul 4;411(13-14):921-30. doi: 10.1016/j.cca.2010.03.012. Epub 2010 Mar 17. Review.
PMID: 20302856
Similar articles

2011
The manifold actions of endocannabinoids on female and male reproductive events.
Bari M, Battista N, Pirazzi V, Maccarrone M.
Front Biosci (Landmark Ed). 2011 Jan 1;16:498-516. Review.
PMID: 21196184
Similar articles

2012
Silencing or amplification of endocannabinoid signaling in blastocysts via CB1 compromises trophoblast cell migration.
Xie H, Sun X, Piao Y, Jegga AG, Handwerger S, Ko MS, Dey SK.
J Biol Chem. 2012 Sep 14;287(38):32288-97. doi: 10.1074/jbc.M112.381145. Epub 2012 Jul 24.
PMID: 22833670 Free PMC Article
Similar articles

2013
The endocannabinoid pathway and the female reproductive organs.
Di Blasio AM, Vignali M, Gentilini D.
J Mol Endocrinol. 2013 Jan 11;50(1):R1-9. doi: 10.1530/JME-12-0182. Print 2013 Feb. Review.
PMID: 23178290 Free Article
Similar articles

2014
Endocannabinoid signaling in mammalian ovary.
Cecconi S, Rossi G, Castellucci A, D'Andrea G, Maccarrone M.
Eur J Obstet Gynecol Reprod Biol. 2014 Jul;178:6-11. doi: 10.1016/j.ejogrb.2014.04.011. Epub 2014 Apr 18. Review.
PMID: 24948047
Similar articles

2015
Endocannabinoid signaling in female reproductive events: a potential therapeutic target?
Maccarrone M.
Expert Opin Ther Targets. 2015 Jun 30:1-5. [Epub ahead of print]
PMID: 26126134
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Peace.

*Next Up: Saturday 10 October and the first round of Whiskey221, a continuation of last year’s series Whiskey220 (it’s about George Washington, our Republic and whiskey rebels).

Posted by Bryan W. Brickner

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    Brickner has a 1997 political science doctorate from Purdue University, cofounded Illinois NORML in 2001, and was a 2007 National NORML Cannabis Advocate Awardee. He is also publisher and coauthor of the 2011 book banned by the Illinois Department of Corrections – The Cannabis Papers: A Citizen’s Guide to Cannabinoids.

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