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

Bonus Video: Homeostasis

Posted by Bryan W. Brickner


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Alzheimer’s, Cancer and Homeostatic Cannabinoid Science

6/29/2014

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PictureThe Cannabis Papers by Publius (2011)








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

The CS World Cup: Goaltender Edition

Today, tending to the goals of mediating Alzheimer’s and preventing carcinogenesis, Publius spotlights two June abstracts from PubMed on the homeostatic cannabinoid system (CS). For Alzheimer’s disease it is CS
modulation of cognitive decline; for preventing carcinogenesis the findings unveil a previously unknown CS signaling platform: CB2-GPR55 receptor heteromers.



I. CS Mediates Cognitive Decline In Alzheimer's Disease

Set: “It has been widely reported that β-amyloid peptide (Aβ) blocks long-term potentiation (LTP) of hippocampal synapses. Here, we show evidence that Aβ more potently blocks the potentiation of excitatory postsynaptic potential (EPSP)-spike coupling (E-S potentiation). This occurs, not by direct effect on excitatory synapses or postsynaptic neurons, but rather through an indirect mechanism: reduction of endocannabinoid-mediated peritetanic disinhibition.”

Setting: “During high-frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation.”

Science: “This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer's disease.”
β-Amyloid Inhibits E-S Potentiation through Suppression of Cannabinoid Receptor 1-Dependent Synaptic Disinhibition.
Orr AL, Hanson JE, Li D, Klotz A, Wright S, Schenk D, Seubert P, Madison DV.
Neuron. 2014 Jun 18;82(6):1334-45. doi: 10.1016/j.neuron.2014.04.039.
PMID: 24945775 [PubMed - in process]
Related citations


II. CS Oncology Signaling Unveiled: Evidence of Previously Unknown Platforms

Set: “The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. As a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells.”

Setting: “Here, we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo.”

Science: “These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology.”
Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling.
Moreno E, Andradas C, Medrano M, Caffarel MM, Pérez-Gómez E, Blasco-Benito S, Gómez-Cañas M, Pazos MR, Irving AJ, Lluís C, Canela EI, Fernández-Ruiz J, Guzmán M, McCormick PJ, Sánchez C.
J Biol Chem. 2014 Jun 18. pii: jbc.M114.561761. [Epub ahead of print]
PMID: 24942731 [PubMed - as supplied by publisher] Free Article
Related citations

Video: Homeostasis 1, Physiological Principles ~ Dr. John Campbell

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Passing the Alzheimer’s Test and One’s Cannabinoid System ~ An Update

5/29/2014

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Picture
In March we noted the relentless strength of Alzheimer’s disease ~ and it’s still going strong. Good thing so is the science. Here are five more 2014 National Institutes of Health (PubMed) research updates on Alzheimer’s disease and cannabinoids.

The researchers in the third piece below make an interesting point concerning time; seems there haven’t been enough “adequately powered trials” on the safety of cannabinoids in older test subjects. That is harmful and a symptom of our polity.

Talk cannabinoids please … waiting another generation is not acceptable.

I.
Cannabinoid receptor-dependent metabolism of 2-arachidonoylglycerol during aging.
Pascual AC, Gaveglio VL, Giusto NM, Pasquaré SJ.
Exp Gerontol. 2014 Jul;55:134-42. doi: 10.1016/j.exger.2014.04.008. Epub 2014 Apr 24.
PMID: 24768821 [PubMed - in process]
Related citations

II.
Cannabinoids for pain in dementia: the good, the bad, and the ugly.
Ahmed AI, van den Elsen GA, van der Marck MA, Olde Rikkert MG.
J Am Geriatr Soc. 2014 May;62(5):1001-2. doi: 10.1111/jgs.12817. No abstract available.
PMID: 24828945 [PubMed - in process]
Related citations

III.
Efficacy and safety of medical cannabinoids in older subjects: a systematic review.
van den Elsen GA, Ahmed AI, Lammers M, Kramers C, Verkes RJ, van der Marck MA, Rikkert MG.
Ageing Res Rev. 2014 Mar;14:56-64. doi: 10.1016/j.arr.2014.01.007. Epub 2014 Feb 5.
PMID: 24509411 [PubMed - in process]
Related citations

IV.
Parsing the players: 2-arachidonoylglycerol synthesis and degradation in the CNS.
Murataeva N, Straiker A, Mackie K.
Br J Pharmacol. 2014 Mar;171(6):1379-91. doi: 10.1111/bph.12411.
PMID: 24102242 [PubMed - in process]
Related citations

V.
Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease.
González-Naranjo P, Pérez-Macias N, Campillo NE, Pérez C, Arán VJ, Girón R, Sánchez-Robles E, Martín MI, Gómez-Cañas M, García-Arencibia M, Fernández-Ruiz J, Páez JA.
Eur J Med Chem. 2014 Feb 12;73:56-72. doi: 10.1016/j.ejmech.2013.11.026. Epub 2013 Dec 7.
PMID: 24378710 [PubMed - in process]
Related citations

VI.
Video ~ Holistic Alzheimer’s Video: Cannabis Oil and Medical Marijuana

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]
Related citations


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]
Related citations


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]
Related citations


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]
Related citations


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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Passing the Alzheimer’s Test Involves One’s Cannabinoid System

3/28/2014

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Picture
Here are five “more” 2014 National Institutes of Health (PubMed) research updates on Alzheimer’s disease and cannabinoids. I mention “more” because of the widely reported research this month, Plasma Phospholipids Identify Antecedent Memory Impairment in Older Adults.

CNN noted the plasma science as Blood test predicts Alzheimer’s disease.

Forbes saw the ability to identify memory impairment before its onset (by measuring various lipids/fats in blood) as double-edged: How A New Alzheimer’s Test Could Kill Long-Term Care Insurance – Or Make It Cheaper.

I also say “more” because this isn’t new news. The sixth item included is a video of CNN Int., reported in March 2008, on how cannabis may be “a boon to Alzheimer’s patients.”

While we wait for the boon (and it has to be a political boon now), the progression of the disease doesn’t. We’d be wise to mimic the strength of Alzheimer’s disease in our resolve to understand its causes and to offer relief: the disease is relentless … we aught to be as well.

I.
The influence of cannabinoids on generic traits of neurodegeneration.
Fagan SG, Campbell VA.
Br J Pharmacol. 2014 Mar;171(6):1347-60. doi: 10.1111/bph.12492.
PMID: 24172185 [PubMed - in process]
Related citations

II.
Cannabinoids for treatment of Alzheimer's disease: moving toward the clinic.
Aso E, Ferrer I.
Front Pharmacol. 2014 Mar 5;5:37. eCollection 2014. Review.
PMID: 24634659 [PubMed - as supplied by publisher] Free PMC Article
Related citations

III.
In vivo type 1 cannabinoid receptor availability in Alzheimer's disease.
Ahmad R, Goffin K, Van den Stock J, De Winter FL, Cleeren E, Bormans G, Tournoy J, Persoons P, Van Laere K, Vandenbulcke M.
Eur Neuropsychopharmacol. 2014 Feb;24(2):242-50. doi: 10.1016/j.euroneuro.2013.10.002. Epub 2013 Oct 17.
PMID: 24189376 [PubMed - in process]
Related citations

IV.
Altered Expression of the CB1 Cannabinoid Receptor in the Triple Transgenic Mouse Model of Alzheimer's Disease.
Bedse G, Romano A, Cianci S, Lavecchia AM, Lorenzo P, Elphick MR, Laferla FM, Vendemiale G, Grillo C, Altieri F, Cassano T, Gaetani S.
J Alzheimers Dis. 2014 Feb 4. [Epub ahead of print]
PMID: 24496074 [PubMed - as supplied by publisher]
Related citations

V.
Brain Innate Immunity In The Regulation Of Neuroinflammation: Therapeutic Strategies By Modulating Cd200-Cd200r Interaction Involve The Cannabinoid System.
Hernangomez M, Carrillo-Salinas FJ, Mecha M, Correa F, Mestre L, Loria F, Feliu A, Docagne F, Guaza C.
Curr Pharm Des. 2014 Jan 30. [Epub ahead of print]
PMID: 24588829 [PubMed - as supplied by publisher]
Related citations

VI.
Video Archives ~ CNN Int. March 2008 (B4-Obama)
Medical Marijuana Alzheimer, CNN Int. 11 Mar 2008
“Drug could be a boon to Alzheimer’s patients.”

Bryan W. Brickner

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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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