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Homeostatic Cannabinoid Science ~ Publius’ World Cup Edition

7/6/2014

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PictureThe Cannabis Papers by Publius (2011)






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


A World (Cup) of Cannabinoids: Fielders Edition

Today’s science roundup looks at ten articles on how the cannabinoid system (CS) modulates our health and homeostasis; the line-up links to 2014 CS PubMed articles: four directly on homeostasis, two on the circulatory system, two on the central nervous system, and one each on our digestive and respiratory systems.

I. CNS (Pediatric Brain Injury) and the CS
“Paediatric traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies showed neuroprotection after TBI by (endo)cannabinoid mechanisms, suggesting involvement of cannabinoid receptors (CBR). … The results may provide explanation for the neuroprotective properties of cannabinoid ligands and future therapeutic strategies of TBI.”
Early increase of cannabinoid receptor density after experimental traumatic brain injury in the newborn piglet.
Donat CK, Fischer F, Walter B, Deuther-Conrad W, Brodhun M, Bauer R, Brust P.
Acta Neurobiol Exp (Wars). 2014;74(2):197-210.
PMID: 24993629 [PubMed - in process]
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II. Digestive System (Irritable Bowel Syndrome) and the CS
“The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS.”
Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome.
de Carvalho Rocha HA, Dantas BP, Rolim TL, Costa BA, de Medeiros AC.
Ann Gastroenterol. 2014;27(3):200-206. Review.
PMID: 24976114 [PubMed - as supplied by publisher] Free PMC Article
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III. Respiratory System (Paraquat and Acute Lung Injury) and the CS
“Paraquat [PQ], a widely used herbicide, is well known to exhibit oxidative stress and lung injury. … The results suggested that activating CB2 receptor exerted protective activity against PQ-induced ALI [Acute Lung Injury], and it potentially contributed to the suppression of the activation of MAPKs and NF- κ B pathways.”
CB2 Receptor Activation Ameliorates the Proinflammatory Activity in Acute Lung Injury Induced by Paraquat.
Liu Z, Wang Y, Zhao H, Zheng Q, Xiao L, Zhao M.
Biomed Res Int. 2014;2014:971750. doi: 10.1155/2014/971750. Epub 2014 May 22.
PMID: 24963491 [PubMed - in process] Free PMC Article
Related citations

IV. Homeostasis (Indole Quinuclidine Analogs) and the CS
“Therefore, indole quinuclidines are a novel structural class of compounds exhibiting high affinity and a range of intrinsic activity at cannabinoid type-1 and type-2 receptors.”
Characterization of the intrinsic activity for a novel class of cannabinoid receptor ligands: Indole quinuclidine analogs.
Franks LN, Ford BM, Madadi NR, Penthala NR, Crooks PA, Prather PL.
Eur J Pharmacol. 2014 Aug 15;737:140-8. doi: 10.1016/j.ejphar.2014.05.007. Epub 2014 May 20.
PMID: 24858620 [PubMed - in process]
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V. Circulatory System (Ischemic Heart Disease) and the CS
“Ischemic heart disease is associated with inflammation, interstitial fibrosis and ventricular dysfunction prior to the development of heart failure. … Therefore, the endocannabinoid-CB2 receptor axis plays a key role in cardioprotection during the initial phase of ischemic cardiomyopathy development.”
The endocannabinoid-CB2 receptor axis protects the ischemic heart at the early stage of cardiomyopathy.
Duerr GD, Heinemann JC, Suchan G, Kolobara E, Wenzel D, Geisen C, Matthey M, Passe-Tietjen K, Mahmud W, Ghanem A, Tiemann K, Alferink J, Burgdorf S, Buchalla R, Zimmer A, Lutz B, Welz A, Fleischmann BK, Dewald O.
Basic Res Cardiol. 2014 Jul;109(4):425. doi: 10.1007/s00395-014-0425-x. Epub 2014 Jul 1.
PMID: 24980781 [PubMed - in process]
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VI. Homeostasis, Endocannabinoid Deficiencies and the CS
“Subsequent research has confirmed that underlying endocannabinoid deficiencies indeed play a role in migraine, fibromyalgia, irritable bowel syndrome and a growing list of other medical conditions. Clinical experience is bearing this out. Further research and especially, clinical trials will further demonstrate the usefulness of medical cannabis. As legal barriers fall and scientific bias fades this will become more apparent.”
Clinical endocannabinoid deficiency (CECD) revisited: Can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?
Smith SC, Wagner MS.
Neuro Endocrinol Lett. 2014 Jun 30;35(3):198-201. [Epub ahead of print]
PMID: 24977967 [PubMed - as supplied by publisher]
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VII. Homeostasis (Epilepsy, Neuronal Plasticity) and the CS
“Synaptic communication requires constant adjustments of pre- and postsynaptic efficacies. In addition to synaptic long-term plasticity, the presynaptic machinery underlies homeostatic regulations which prevent out of range transmitter release. In this mini-review we will discuss the relevance of selected presynaptic mechanisms to epilepsy including voltage- and ligand-gated ion channels as well as cannabinoid and adenosine receptor signaling.”
Presynaptic mechanisms of neuronal plasticity and their role in epilepsy.
Meier J, Semtner M, Winkelmann A, Wolfart J.
Front Cell Neurosci. 2014 Jun 17;8:164. doi: 10.3389/fncel.2014.00164. eCollection 2014. Review.
PMID: 24987332 [PubMed]
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VIII. Homeostasis (Turning Agonists into Antagonists) and the CS
“However, we discovered that bivalency has an influence on the effect at both cannabinoid receptors. Moreover, we found out that the spacer length and the attachment position altered the efficacy of the bivalent ligands at the receptors by turning agonists into antagonists and inverse agonists.”
Synthesis and biological evaluation of bivalent cannabinoid receptor ligands based on hCB2R selective benzimidazoles reveal unexpected intrinsic properties.
Nimczick M, Pemp D, Darras FH, Chen X, Heilmann J, Decker M.
Bioorg Med Chem. 2014 Jun 13. pii: S0968-0896(14)00454-4. doi: 10.1016/j.bmc.2014.06.008. [Epub ahead of print]
PMID: 24984935 [PubMed - as supplied by publisher]
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IX. Circulatory System (Blood Vessels-Heart) and the CS
“2-Arachidonoylglycerol [2-AG] plays an important role in the regulation of the circulatory system via direct and/or indirect, through their metabolites, effects on blood vessels and/or heart. Accumulating evidence reveals that 2-AG is involved in the pathogenesis of various shocks and atherosclerosis.”
Role of endocannabinoid 2-arachidonoylglycerol in the physiology and pathophysiology of the cardiovascular system.
Karabowicz P, Grzęda E, Baranowska-Kuczko M, Malinowska B.
Postepy Hig Med Dosw (Online). 2014 Jun 12;68(0):814-27.
PMID: 24934539 [PubMed - in process]
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X. CNS (Brain Mitochondria) and the CS
“Our results show that the use of appropriate controls and quantifications allows detecting mtCB1 receptor with CB1 receptor antibodies, and that, if mitochondrial fractions are enriched and purified, CB1 receptor agonists reliably decrease respiration in brain mitochondria.”
Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor.
Hebert-Chatelain E, Reguero L, Puente N, Lutz B, Chaouloff F, Rossignol R, Piazza PV, Benard G, Grandes P, Marsicano G.
Mol Metab. 2014 Apr 2;3(4):495-504. doi: 10.1016/j.molmet.2014.03.007. eCollection 2014 Jul.
PMID: 24944910 [PubMed] Free PMC Article
Related citations

See also: Alzheimer’s, Cancer and Homeostatic Cannabinoid Science

Bonus Video: Homeostasis

Posted by Bryan W. Brickner


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Indiscernible Cannabinoid Science ~ Publius’ April 2014 Roundup

4/29/2014

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Picture
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]
Related citations


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]
Related citations


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]
Related citations

~'~

Posted by Bryan W. Brickner
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Indiscernible Cannabinoid Science ~ Publius’ March 2014 Roundup

3/30/2014

1 Comment

 
Picture

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
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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
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

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    Author

    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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