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Teamwork: Publius’ Super Bowl of Cannabinoid Science

1/30/2015

CB1 and CB2 Receptor Genetics

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

A Super Bowl of Cannabinoids

In sports as in life, teamwork creates homeostasis. Sure there will be big plays and impressive moves in Sunday’s Super Bowl, yet all fans and players know it’s the little things that count – that create the conditions for that game-winning moment. It’s the same in our bodies as homeostatic processes – teamwork – function without notice or acclaim (even while we sleep). In celebration of game-winning moments, here are four new PubMed articles discussing our CS and homeostatic teamwork: management of neuroinflammatory (brain) disorders, CB1 anti-aversive panic properties, obesity and the therapeutic agents THCV and CBD, and cannabinoids as a tool in modern cancer pharmacotherapy.

Happy CS Super Bowl All!

I. Neuroinflammatory: Cannabinoids as Immunoregulatory and Immunomodulatory
“A growing body of evidence suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory properties, both in peripheral tissues and in the CNS, through the activation of cannabinoid receptors. In this review, the immunomodulatory effects of cannabinoid signaling on the most relevant brain immune cells will be discussed. In addition, the impact of cannabinoid regulation on the overall integration of the manifold brain immune responses will also be highlighted, along with the implication of these compounds as potential agents for the management of neuroinflammatory disorders.”
Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses.
Chiurchiù V, Leuti A, Maccarrone M.
J Neuroimmune Pharmacol. 2015 Jan 20. [Epub ahead of print]
PMID: 25601726 [PubMed - as supplied by publisher]
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II. Brain: Panic, Dorsolateral Periaqueductal Grey and CS CB1 Receptors
“Since the cannabinoid CB1 receptor modulates various types of aversive responses, this study tested the hypothesis that enhancement of endocannabinoid signalling in the dorsolateral periaqueductal grey inhibits panic-like reactions in rats. … The present results confirm the anti-aversive property of direct CB1 receptor activation in the dorsolateral periaqueductal grey.”
Role of endocannabinoid signalling in the dorsolateral periaqueductal grey in the modulation of distinct panic-like responses.
Batista LA, Bastos JR, Moreira FA.
J Psychopharmacol. 2015 Jan 19. pii: 0269881114566259. [Epub ahead of print]
PMID: 25601395 [PubMed - as supplied by publisher]
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III. Obesity: Liver Metabolism, Hepatosteatosis and the Cannabinoids THCV and CBD
“Obesity and associated metabolic syndrome have quickly become a pandemic and a major detriment to human health globally. The presence of non-alcoholic fatty liver disease (NAFLD; hepatosteatosis) in obesity has been linked to the worsening of the metabolic syndrome, including the development of insulin resistance and cardiovascular disease. Currently, there are few options to treat NAFLD, including life style changes and insulin sensitizers. Recent evidence suggests that the cannabinoids Δ9-tetrahydrocannabivarin (THCV) and cannabidiol (CBD) improve insulin sensitivity; we aimed at studying their effects on lipid levels. … Our results suggest that THCV and CBD might be used as new therapeutic agents for the pharmacological treatment of obesity- and metabolic syndrome-related NAFLD/hepatosteatosis.”
Two non-psychoactive cannabinoids reduce intra-cellular lipid levels and inhibit hepatosteatosis.
Silvestri C, Paris D, Martella A, Melck D, Guadagnino I, Cawthorne M, Motta A, Marzo VD.
J Hepatol. 2015 Jan 13. pii: S0168-8278(15)00003-3. doi: 10.1016/j.jhep.2015.01.001. [Epub ahead of print]
PMID: 25595882 [PubMed - as supplied by publisher]
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IV. Cancer: Cannabinoids and Antimetastatic and Antiangiogenesis
“Regarding the underlying antimetastatic mechanism, several studies revealed cannabinoids to alter the gene expression of cancer cells toward a less-aggressive phenotype and to modulate their secretomic profile. Cannabinoids likewise modulate the release of factors from tumor cells that subsequently suppress the chemoattraction of vessel cells thereby conferring antiangiogenesis. … In addition, beneficial interactions of cannabinoids with currently used chemotherapeutics as well as the influence of cannabinoids on tumor-immune surveillance are addressed. Collectively, the currently available data suggest cannabinoids as a potential tool in modern cancer pharmacotherapy.”
New insights into antimetastatic and antiangiogenic effects of cannabinoids.
Ramer R, Hinz B.
Int Rev Cell Mol Biol. 2015;314:43-116. doi: 10.1016/bs.ircmb.2014.10.005. Epub 2014 Dec 18.
PMID: 25619715 [PubMed - in process]
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Posted by Bryan W. Brickner

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Synaptic Super Bowl: A Touching Serotonin (5HT) Update

1/29/2015

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5HT Serotonin Receptor ~ Ribbon by S. Jahnichen

Super Touching Serotonin Edition

Fans and athletes alike produce serotonin (5HT) for game day; 80-90% of it is made by our stomach’s enterochromaffin cells (the rest is made in our brains) and then transported and distributed throughout our bodies.

Touch, or “good hands,” is a Super Bowl fundamental, as any big play – made or broken – is sparked by a finger’s give-and-take. Today’s serotonin system focus is on touch, in particular, serotonergic and dopaminergic activity. From the National Institutes of Health (PubMed), our Super Bowl line-up includes three 2015 articles and one from the archives (2005). The serotonin touch-tales include: brain trauma (blast) and the serotonin N-acetyltransferase gene (Aanat), food metabolism (tryptophan) and the kynurenine pathway, ADHD changes with age, and, the one from the archives, touch/massage therapy decreases cortisol and increases dopamine and serotonin.

Have a Serotonergic Super Bowl All!

I. Blast-related Brain Injury and the Serotonin N-Acetyltransferase Gene (Aanat)
“Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes like DNA methylation that regulate gene expression. … Functional validation via gene expression analysis of 30 differentially methylated neuronal and glial genes showed a 1.2 fold change in gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast animals (p < .05). These data provide the first genome-based evidence for changes in DNA methylation induced in response to multiple blast overpressure exposures. In particular, increased methylation and decreased gene expression were observed in the Aanat gene, which is involved in converting serotonin to the circadian hormone melatonin and is implicated in sleep disturbance and depression associated with TBI.”
Neuronal DNA Methylation Profiling of Blast-related Traumatic Brain Injury (TBI).
Haghighi F, Ge Y, Chen S, Xin Y, Umali MU, De Gasperi R, Gama Sosa MA, Ahlers ST, Elder GA.
J Neurotrauma. 2015 Jan 16. [Epub ahead of print]
PMID: 25594545 [PubMed - as supplied by publisher]
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II. Kynurenine Pathway (Food/Tryptophan Metabolism) and Serotonin Circuits
“The kynurenine pathway of tryptophan metabolism is involved in the pathogenesis of several brain diseases, but its physiological functions remain unclear. We report that kynurenic acid, a metabolite in this pathway, functions as a regulator of food-dependent behavioral plasticity in C. elegans. The experience of fasting in C. elegans alters a variety of behaviors, including feeding rate, when food is encountered post-fast. Levels of neurally produced kynurenic acid are depleted by fasting, leading to activation of NMDA-receptor-expressing interneurons and initiation of a neuropeptide-y-like signaling axis that promotes elevated feeding through enhanced serotonin release when animals re-encounter food. Upon reseeding, kynurenic acid levels are eventually replenished, ending the elevated feeding period. Because tryptophan is an essential amino acid, these findings suggest that a physiological role of kynurenic acid is in directly linking metabolism to activity of NMDA and serotonergic circuits, which regulate a broad range of behaviors and physiologies.”
Kynurenic Acid Is a Nutritional Cue that Enables Behavioral Plasticity.
Lemieux GA, Cunningham KA, Lin L, Mayer F, Werb Z, Ashrafi K.
Cell. 2015 Jan 15;160(1-2):119-31. doi: 10.1016/j.cell.2014.12.028.
PMID: 25594177 [PubMed - in process]
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III. Age, ADHD and Dopaminergic and Serotonergic Genes
“Elucidating genetic mechanisms involved in Attention-Deficit/Hyperactivity Disorder (ADHD) has been challenging. Relatively unexplored is the fact that genetic mechanisms can differ with age. The current study explored the association between dopaminergic and serotonergic genes, ADHD symptoms, and neurocognitive functioning in relation to age. … Our results are preliminary, but may point to differential genotype-phenotype associations at different ages. This can be seen as a proof of concept for the importance of age in dopaminergic and serotonergic genetic association analyses. Our findings are consistent with the idea that genetic and neurocognitive mechanisms underlying ADHD may change throughout life.”
The role of age in association analyses of ADHD and related neurocognitive functioning: A proof of concept for dopaminergic and serotonergic genes.
Thissen AJ, Bralten J, Rommelse NN, Arias-Vasquez A, Greven CU, Heslenfeld D, Luman M, Oosterlaan J, Hoekstra PJ, Hartman C, Franke B, Buitelaar JK.
Am J Med Genet B Neuropsychiatr Genet. 2015 Jan 14. doi: 10.1002/ajmg.b.32290. [Epub ahead of print]
PMID: 25586935 [PubMed - as supplied by publisher]
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IV. Massage (Touch) Decreases Cortisol and Increases Dopamine and Serotonin
“In this article the positive effects of massage therapy on biochemistry are reviewed including decreased levels of cortisol and increased levels of serotonin and dopamine. The research reviewed includes studies on depression (including sex abuse and eating disorder studies), pain syndrome studies, research on auto-immune conditions (including asthma and chronic fatigue), immune studies (including HIV and breast cancer), and studies on the reduction of stress on the job, the stress of aging, and pregnancy stress. … These studies combined suggest the stress-alleviating effects (decreased cortisol) and the activating effects (increased serotonin and dopamine) of massage therapy on a variety of medical conditions and stressful experiences.”
Cortisol decreases and serotonin and dopamine increase following massage therapy.
Field T, Hernandez-Reif M, Diego M, Schanberg S, Kuhn C.
Int J Neurosci. 2005 Oct;115(10):1397-413.
PMID: 16162447 [PubMed - indexed for MEDLINE]
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Video: The most important lesson from 83,000 brain scans, Daniel Amen, TEDxOrangeCoast

*Tomorrow: New Homeostasis with Publius’ Super Bowl of Cannabinoid Science.
~
Posted by Bryan W. Brickner

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New Book: Announcing Shivitti: A Review of Ka-Tzetnik 135633’s Vision

1/24/2015

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Yehiel De-Nur (KZ) testifying at the trial of Adolf Eichmann, Israel 1961

In memory and honor of the Liberation of Auschwitz, 27 January 1945

Our reviewed author, Yehiel De-Nur, wrote more than 20 books, many using the identity KZ for Ka-Tzetnik 135633, the concentration camp number branded on his arm.

The picture shows De-Nur testifying in Israel at the trial of Adolf Eichmann; the year is 1961 – sixteen years after Auschwitz and fifteen years before his LSD-serotonin therapy and healing. In the photo, the guard is showing De-Nur prisoner garb that would have reminded him of Auschwitz; if it looks like he’s about to gag, you’re correct; in a few moments he basically loses it and can’t continue with his testimony.

De-Nur “lived” through two years at Auschwitz; he was sent to his death, to be gassed and burned, and found a way to survive. His survival came with a burden: he worked in the crematorium and gave witness to the ashed dead of Auschwitz.

In 1976, with his sleep marred by three decades of Auschwitz nightmares, De-Nur left Israel and went to the Netherlands, Leiden University, in search of relief; he had heard stories of other concentration camp survivors using a new therapy at Leiden, a treatment involving LSD and his serotonin system.

Dr. Jan C. Bastiaans, Leiden University

SHIVITTI (the reminder of the presence of God): A Vision by Ka-Tzetnik 135633 is an LSD-serotonin therapy story. KZ (De-Nur) went to the Netherlands after 30 years of Auschwitz nightmares; locked away in his mind, in five LSD-serotonin therapy sessions, he was enabled to heal via his own body and its serotonin system.

The doctor who helped De-Nur, Jan C. Bastiaans, professor of psychiatry at Leiden University, treated over 300 people with LSD-serotonin therapy. Two resources from the Multidisciplinary Association for Psychedelic Studies give background and political context to his work: The LSD Therapy Career of Jan Bastiaans, M.D. (1998) and The Bastiaans Method of Drug-Therapy (1999).

Of course, this is very political. LSD, since 1970 in the US, has been a Schedule I drug: this means no medical value and high abuse. De-Nur’s book shows medical value (an N of 1) and he has only five sessions and stops; he then returns to Israel, waits ten years, then uses the tape recordings from the 1976 sessions to write his book. Hakibbutz Hameuchad published Shivitti: A Vision in Hebrew in 1987. Harper & Row published an English version in 1989; the book was published again in 1998 in the First Gateways Edition, the one used in the review.

We’ll stop for now and continue this journey next month with the addition of Hannah Arendt: specifically, her footnotes … from her book, The Human Condition.

Title: Shivitti: A Review of Ka-Tzetnik 135633’s Vision
Publisher: Bryan W. Brickner
Publication date: 23 January 2015
Price: $5.55 print and $2.99 Kindle

The booklet is available on CreateSpace, Kindle, Amazon and other online retailers.

Next: on Friday 30 January, a touching serotonin (5HT) update for the synaptic Super Bowl.

Posted by Bryan W. Brickner

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Put Women in Their (Rightful) Place: the House ~ A US Republic Update

1/23/2015

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US Constitution Preamble

A citizen ponders page turning and The State of the Union

Hmmm … The State of the Union, and there’s talk of page turning: turning what page? Must be the US Constitution, as they gather because it says so.

Yes, the Preamble is nice. States the goals and objectives, with John Bunyan-like capitalization. We the People, in Order to form a more perfect Union (sounds like marriage), establish Justice (nice), insure domestic Tranquility … Well, that’s a 2016 political, being domestic and all; let’s turn the page and see what it says about representing We the People in Congress …

one for every thirty Thousand

Hmmm … something underlined: “The number of Representatives shall not exceed one for every thirty Thousand.”

Well, that explains it, this must be the page they’re turning to; the founder Madison’s way, the way of Enumerated Representation, is America’s constitutional blueprint. Looks like we are to build America a new home, founded on the ratio “thirty Thousand,” a House where We the People are legally counted and represented.

How’s this story end? Let’s turn to the last page …

Women, see Persons ... a Republic

Well, what do we have here? A quote from Ben Franklin and – oh, an index line showing “Women, see Persons” – that’s good to know.

What’s Ben up to? When asked what kind of government they had “wrought,” he provided an eternal answer: “ … a Republic, if you can keep it.”

Hmmm … yes, a Republic, one built on small districts and represented in a large House, like Madison and the founders intended; sounds like a home for We the People (all Persons, Women included) is an American birthright.

Thanks for the page turning all ~ and thanks for the US Republic.

Today's video: Our American Republic, Episode 5: Republic

Next up: Tomorrow, in honor and memory of the Holocaust and the Liberation of Auschwitz on 27 January 1945, Ew Publishing will announce the release of a new booklet, Shivitti: A Review of Ka-Tzetnik 135633’s Vision, a prisoner’s story of LSD-serotonin therapy and healing from Auschwitz nightmares.

Posted by Bryan W. Brickner

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Teamwork: Publius’ Super Bowl of Cannabinoid Science

Synaptic Super Bowl: A Touching Serotonin (5HT) Update

New Book: Announcing Shivitti: A Review of Ka-Tzetnik 135633’s Vision

Put Women in Their (Rightful) Place: the House ~ A US Republic Update

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