Category: Anandamide

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

6/7/2017

The 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.

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Homeostasis: Endometriosis, Progesterone and Cannabinoid Systems

5/24/2017

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Progesterone

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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Homeostasis: Publius’ (Ultralow) THC Political Cannabinoid Science

9/5/2014

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The Cannabis Papers by Publius

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

Once Upon A Time ...

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Homeostasis: Publius’ Alcohol Political Cannabinoid Science

8/30/2014

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The Cannabis Papers by Publius (2011)

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

By Publius

Today’s science roundup looks at four articles on how the cannabinoid system (CS) modulates our health through homeostasis ~ including one on the de-homeostatic (harmful) effects caused by chronic alcohol use on one’s CS. The line-up links to 2014 PubMed articles discussing: heteromerization, chronic alcohol harms, sensory information salience and stress response attenuation.

I. Heteromerization (GPR55 and CB2) and the CS
“In HEK293 cells expressing GPR55 and cannabinoid CB2 R receptors, heteromers that are unique signaling units are formed. The signaling by agonists of either receptor is governed i) by the presence or absence of the partner receptors (with the consequent formation of heteromers) and ii) by the activation state of the partner receptor.”
Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signaling.
Balenga NA, Martínez-Pinilla E, Kargl J, Schröder R, Peinhaupt M, Platzer W, Bálint Z, Zamarbide M, Dopeso-Reyes I, Ricobaraza A, Pérez-Ortiz JM, Kostenis E, Waldhoer M, Heinemann A, Franco R.
Br J Pharmacol. 2014 Jul 22. doi: 10.1111/bph.12850. [Epub ahead of print]
PMID: 25048571 [PubMed - as supplied by publisher]
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II. De-Homeostasis (Chronic Alcohol Use) and the CS
“Chronic use of alcohol is associated with structural and functional alterations in brain areas that subserve cognitive processes. Of particular importance is the prefrontal cortex (PFC) that is involved in higher order behaviors such as decision making, risk assessment and judgment. … Overall, these results suggest that ethanol's down-regulation of cannabinoid signaling results in altered network activity in the prefrontal cortex.”
Chronic ethanol alters network activity and endocannabinoid signaling in the prefrontal cortex.
Pava MJ, Woodward JJ.
Front Integr Neurosci. 2014 Jul 18;8:58. doi: 10.3389/fnint.2014.00058. eCollection 2014.
PMID: 25100953 [PubMed] Free Article
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III. Homeostasis (Sensory Information) and the CS
“Emerging evidence from both basic and clinical research demonstrates an important role for endocannabinoid (ECB) signaling in the processing of emotionally salient information, learning, and memory. Cannabinoid transmission within neural circuits involved in emotional processing has been shown to modulate the acquisition, recall, and extinction of emotionally salient memories and importantly, can strongly modulate the emotional salience of incoming sensory information.”
The role of cannabinoid transmission in emotional memory formation: implications for addiction and schizophrenia.
Tan H, Ahmad T, Loureiro M, Zunder J, Laviolette SR.
Front Psychiatry. 2014 Jun 30;5:73. doi: 10.3389/fpsyt.2014.00073. eCollection 2014. Review.
PMID: 25071606 [PubMed] Free PMC Article
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IV. Homeostasis (Stress Response) and the CS
“Endocannabinoids are produced on demand and function to attenuate many of the physiological effects of the stress response. The endocannabinoid system is made up of cannabinoid receptors, the fatty acid signaling molecules that bind to and activate these receptors, and the enzymes that synthesize and catabolize these endocannabinoid signaling molecules.”
The endocannabinoid system modulates stress, emotionality, and inflammation.
Crowe MS, Nass SR, Gabella KM, Kinsey SG.
Brain Behav Immun. 2014 Jun 19. pii: S0889-1591(14)00172-X. doi: 10.1016/j.bbi.2014.06.007. [Epub ahead of print] Review.
PMID: 24953427 [PubMed - as supplied by publisher]
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Brain Video:
Why Do Some People Become Alcoholics?

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Homeostatic Cannabinoid Science ~ Publius’ May Roundup

5/30/2014

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Astrocyte / Blood-Brain Barrier by Ben Brahim Mohammed

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

Here are seven new 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 urinary, neuroendocrine, digestive, central nervous and serotonin systems.

I. Urinary System (Kidney / Diabetes) and CS
“A functionally active endocannabinoid system is present within the kidney. The cannabinoid receptor type 2 (CB2) is expressed by both inflammatory cells and podocytes, and its activation has beneficial effects in experimental diabetic nephropathy. … Thus, CB2 deletion worsens diabetic nephropathy, independent of bone marrow-derived cells.”
Deficiency of cannabinoid receptor of type 2 worsens renal functional and structural abnormalities in streptozotocin-induced diabetic mice.
Barutta F, Grimaldi S, Franco I, Bellini S, Gambino R, Pinach S, Corbelli A, Bruno G, Rastaldi MP, Aveta T, Hirsch E, Di Marzo V, Gruden G.
Kidney Int. 2014 May 14. doi: 10.1038/ki.2014.165. [Epub ahead of print]
PMID: 24827776 [PubMed - as supplied by publisher]
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II. Neuroendocrine System (Skin) and CS
“Recent evidence has shown that the neuroendocrine regulation of human skin biology also extends to keratins, the major structural components of epithelial cells. For example, thyrotropin-releasing hormone, thyrotropin, opioids, prolactin, and cannabinoid receptor 1-ligands profoundly modulate human keratin gene and protein expression in human epidermis and/or hair follicle epithelium in situ.”
Harnessing neuroendocrine controls of keratin expression: A new therapeutic strategy for skin diseases?
Ramot Y, Paus R.
Bioessays. 2014 May 13. doi: 10.1002/bies.201400006. [Epub ahead of print]
PMID: 24823963 [PubMed - as supplied by publisher]
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III. Digestive System and CS
“Palmitoylethanolamide (PEA), a naturally-occurring acylethanolamide chemically related to the endocannabinoid anandamide, interacts with targets that have been identified in peripheral nerves controlling gastrointestinal motility, i.e. cannabinoid (CB1 and CB2 ) receptors, transient receptor potential vanilloid type-1 (TRPV1), and peroxisomal proliferator activated receptor α (PPARα).”
Ultramicronized palmitoylethanolamide normalizes intestinal motility in a murine model of post-inflammatory accelerated transit: involvement of CB1 receptors and TRPV1.
Capasso R, Orlando P, Pagano E, Aveta T, Buono L, Borrelli F, Di Marzo V, Izzo AA.
Br J Pharmacol. 2014 May 12. doi: 10.1111/bph.12759. [Epub ahead of print]
PMID: 24818658 [PubMed - as supplied by publisher]
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IV. Central Nervous System and CS
“G-protein-coupled receptors (GPCRs) constitute an example of proteins that are the key factors in the framework needed to sustain brain and nerve structure and function. The versatility underlying nervous system anatomy takes advantage of a recently discovered feature of GPCRs, the possibility to form heteromers that, placed at specific neuronal subsets and at specific locations (pre-, post-, or peri-synaptic), contribute to attain unique neural functions.”
G-Protein-Coupled Receptor Heteromers as Key Players in the Molecular Architecture of the Central Nervous System.
Brugarolas M, Navarro G, Martínez-Pinilla E, Angelats E, Casadó V, Lanciego JL, Franco R.
CNS Neurosci Ther. 2014 May 9. doi: 10.1111/cns.12277. [Epub ahead of print]
PMID: 24809909 [PubMed - as supplied by publisher]
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V. Serotonin System and the CS
“Serotonin (5-HT) plays pivotal roles in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS), and luminal 5-HT time-dependently modulates visceral nociception. We found that duodenal biopsies from PI-IBS patients exhibited increased 5-HT and decreased anandamide levels and that decreased anandamide was associated with abdominal pain severity, indicating a link between 5- HT and endocannabinoid signaling pathways in PI-IBS.”
Vagal anandamide signaling via cannabinoid receptor 1 contributes to luminal 5-HT modulation of visceral nociception in rats.
Feng CC, Yan XJ, Chen X, Wang EM, Liu Q, Zhang LY, Chen J, Fang JY, Chen SL.
Pain. 2014 May 8. pii: S0304-3959(14)00225-5. doi: 10.1016/j.pain.2014.05.005. [Epub ahead of print]
PMID: 24813296 [PubMed - as supplied by publisher]
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VI. Central Nervous System (Blood-Brain Barrier) and CS
“Early brain injury (EBI), following subarachnoid hemorrhage (SAH), comprises blood-brain barrier (BBB) disruption and consequent edema formation. … We suggest that CB2R stimulation attenuates neurological outcome and brain edema, by suppressing leukocyte infiltration into the brain through TGF-β1 up-regulation and E-selectin reduction, resulting in protection of the BBB after SAH.”
Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats.
Fujii M, Sherchan P, Krafft PR, Rolland WB, Soejima Y, Zhang JH.
J Neurol Sci. 2014 Apr 30. pii: S0022-510X(14)00270-6. doi: 10.1016/j.jns.2014.04.034. [Epub ahead of print]
PMID: 24819918 [PubMed - as supplied by publisher]
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VII. Central Nervous System (Memory) and CS
“The reactivation of a memory can result in its destabilization, necessitating a process of memory reconsolidation to maintain its persistence. Here we show that the destabilization of a contextual fear memory is potentiated by the cannabinoid CB1 receptor agonist Arachidonyl-2-chloroethylamide (ACEA). … These results indicate that memory expression and destabilization, while being independent from one another, are both dependent upon memory reactivation. Moreover, memory destabilization can be enhanced pharmacologically, which may be of therapeutic potential.”
Inhibition and enhancement of contextual fear memory destabilization.
Lee JL, Flavell CR.
Front Behav Neurosci. 2014 Apr 28;8:144. doi: 10.3389/fnbeh.2014.00144. eCollection 2014.
PMID: 24808841 [PubMed] Free PMC Article
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Bonus Video:

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Preventing Carcinogenesis via One’s Cannabinoid System ~ Publius’ May 2014 Cancer Research Awareness

5/18/2014

1 Comment

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

Cancer research awareness and the cannabinoid system (CS) are the focus of May’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed CS science on preventing skin and colon carcinogenesis, phototherapy, melanomas, eicosands, gliomas, mitochondria and the omega-3 fatty acids DHA and EPA.

2014 ~ Skin Carcinogenesis, Inflammation and the CS
“Cancer is an environmental disease and skin cancer (melanoma and non-melanoma) is the most common of all cancers.”
The role of inflammation in skin cancer.
Maru GB, Gandhi K, Ramchandani A, Kumar G.
Adv Exp Med Biol. 2014;816:437-69. doi: 10.1007/978-3-0348-0837-8_17.
PMID: 24818733 [PubMed - in process]
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2014 ~ CB2 and Antitumor (Phototherapy)
“Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.”
Cannabinoid CB2 Receptor as a New Phototherapy Target for the Inhibition of Tumor Growth.
Jia N, Zhang S, Shao P, Bagia C, Janjic JM, Ding Y, Bai M.
Mol Pharm. 2014 May 8. [Epub ahead of print]
PMID: 24779700 [PubMed - as supplied by publisher]
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2014 ~ CB2 Receptor and Melanoma
“Extravasation of leukocytes through the BBB [blood-brain barrier] is decreased by the activation of type 2 cannabinoid receptors (CB2); therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. … Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.”
CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier.
Haskó J, Fazakas C, Molnár J, Nyúl-Tóth A, Herman H, Hermenean A, Wilhelm I, Persidsky Y, Krizbai IA.
Int J Mol Sci. 2014 May 8;15(5):8063-74. doi: 10.3390/ijms15058063.
PMID: 24815068 [PubMed - in process] Free Article
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2014 ~ Colon Carcinogenesis and CBD ~ Botanical Drug Substance
“CBD BDS [botanical drug substance] attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation.”
Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.
Romano B, Borrelli F, Pagano E, Cascio MG, Pertwee RG, Izzo AA.
Phytomedicine. 2014 Apr 15;21(5):631-9. doi: 10.1016/j.phymed.2013.11.006. Epub 2013 Dec 25.
PMID: 24373545 [PubMed - in process]
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2014 ~ Eicosands, 2-AG and Cancer
“While THC and its derivatives have garnered notoriety in the eyes of the public, the endocannabinoid system consists of two endogenous signaling lipids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide), which activate cannabinoid receptors CB1 and CB2 in the nervous system and peripheral tissues.”
Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids.
Kohnz RA, Nomura DK.
Chem Soc Rev. 2014 Mar 28. [Epub ahead of print]
PMID: 24676249 [PubMed - as supplied by publisher]
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2014 ~ Antitumor (Gliomas) and the CS
“These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.”
Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas.
Rocha FC, Dos Santos Júnior JG, Stefano SC, da Silveira DX.
J Neurooncol. 2014 Jan;116(1):11-24. doi: 10.1007/s11060-013-1277-1. Epub 2013 Oct 20.
PMID: 24142199 [PubMed - in process]
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2013 ~ Anticancer Effects of CBD
“Thus, VDAC1 [voltage-dependent anion channel 1] seems to serve as a novel mitochondrial target for CBD. The inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD.”
Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death.
Rimmerman N, Ben-Hail D, Porat Z, Juknat A, Kozela E, Daniels MP, Connelly PS, Leishman E, Bradshaw HB, Shoshan-Barmatz V, Vogel Z.
Cell Death Dis. 2013 Dec 5;4:e949. doi: 10.1038/cddis.2013.471.
PMID: 24309936 [PubMed - in process] Free PMC Article
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2010 ~ Preventing Carcinogenesis and the CS
“Our findings suggest that the expression of cannabinoid receptors and of FAAH in some tumour cells could well influence the effectiveness of DHA and EPA or their ethanolamide derivatives as anticancer agents.”
Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines.
Brown I, Cascio MG, Wahle KW, Smoum R, Mechoulam R, Ross RA, Pertwee RG, Heys SD.
Carcinogenesis. 2010 Sep;31(9):1584-91. doi: 10.1093/carcin/bgq151. Epub 2010 Jul 25.
PMID: 20660502 [PubMed - indexed for MEDLINE] Free PMC Article
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Indiscernible Cannabinoid Science ~ Publius’ April 2014 Roundup

4/29/2014

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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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Indiscernible Cannabinoid Science ~ Publius’ March 2014 Roundup

3/30/2014

1 Comment

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
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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
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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
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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
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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
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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]
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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]
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~’~
posted by bwb

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Preventing Carcinogenesis Via One’s Cannabinoid System ~ Publius’ March 2014 Colorectal Cancer Awareness

3/29/2014

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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]
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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
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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]
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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
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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
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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]
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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]
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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]
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~ posted by bryan w. brickner

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March Madness Modulation: Sports, Sweat and Cannabinoid Rewards

3/17/2014

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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

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

Homeostasis: Endometriosis, Progesterone and Cannabinoid Systems

Homeostasis: Publius’ (Ultralow) THC Political Cannabinoid Science

Homeostasis: Publius’ Alcohol Political Cannabinoid Science

Homeostatic Cannabinoid Science ~ Publius’ May Roundup

Preventing Carcinogenesis via One’s Cannabinoid System ~ Publius’ May 2014 Cancer Research Awareness

Indiscernible Cannabinoid Science ~ Publius’ April 2014 Roundup

Indiscernible Cannabinoid Science ~ Publius’ March 2014 Roundup

Preventing Carcinogenesis Via One’s Cannabinoid System ~ Publius’ March 2014 Colorectal Cancer Awareness

March Madness Modulation: Sports, Sweat and Cannabinoid Rewards

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