Bryan William Brickner
  • Blog
  • Interviews
  • Articles
  • Books
  • Photos and Video
  • Links

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

6/7/2017

1 Comment

 
PictureThe Cannabis Papers by Publius








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

1 Comment

Homeostasis: Endometriosis, Progesterone and Cannabinoid Systems

5/24/2017

0 Comments

 
PictureProgesterone






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

0 Comments

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

7/9/2016

0 Comments

 
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

0 Comments

Homeostasis: Publius’ Sleep Political Cannabinoid Science

9/29/2014

0 Comments

 
PictureThe Cannabis Papers by Publius (2011)





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

By Publius


Sleep Edition

Today’s political cannabinoid science looks at five 2014 PubMed articles on how the cannabinoid system (CS) modulates homeostasis and sleep; of political note, there’s one on CS deficiency disguised as “cannabis withdrawal” (i.e., the pharmaceutical cannabinoid Nabilone). The line-up links to CS PubMed articles discussing: de-homeostatic sleep disturbances, REM transitions, aging with THC, the wake-inducing effects of CBD, and arousal sleep regulation.

Some (Sleepy) Shakespeare ~ Sonnet 27
   “Weary with toil, I haste to my bed,
   The dear repose for limbs with travel tired;
   But then begins a journey in my head,
   To work my mind when body’s work’s expired.”

I. De-Homeostasis (Sleep Disturbances) and CS Withdrawal
“Chronic cannabis use has been associated with the development of a withdrawal syndrome on abrupt discontinuation. Withdrawal symptoms typically begin within 24 h of abstinence and manifest as irritability, nervousness, sleep disturbances and decreased appetite. There is growing evidence that supports the use of plant-derived and synthetic cannabinoids for the treatment of cannabis withdrawal. In this case report, we present 20-year-old woman who developed protracted nausea and vomiting secondary to cannabis withdrawal and was successfully treated with nabilone. Nausea and vomiting is not listed in the Diagnostic and Statistical Manual-5 diagnostic criteria for cannabis withdrawal syndrome and is an uncommon symptom presentation.”
Nabilone therapy for cannabis withdrawal presenting as protracted nausea and vomiting.
Lam PW, Frost DW.
BMJ Case Rep. 2014 Sep 22;2014. pii: bcr2014205287. doi: 10.1136/bcr-2014-205287.
PMID: 25246463 [PubMed - in process]
Related citations

II. Homeostasis (Astrocytes and the Reticular Activating System) and the CS/CB1
“The pedunculopontine nucleus (PPN) is known as the cholinergic part of the reticular activating system (RAS) and it plays an important role in transitions of slow-wave sleep to REM sleep and wakefulness. … Taken together, we propose that cannabinoid receptor stimulation modulates PPN neuronal activity in the following manner: active neurons may elicit calcium waves in astrocytes via endogenous CB1 receptor agonists. Astrocytes in turn release glutamate that activates different metabotropic glutamate receptors of neurons and modulate PPN neuronal activity.”
Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes.
Kőszeghy A, Kovács A, Bíró T, Szücs P, Vincze J, Hegyi Z, Antal M, Pál B.
Brain Struct Funct. 2014 Jul 10. [Epub ahead of print]
PMID: 25009314 [PubMed - as supplied by publisher]
Related citations

III. Homeostasis (Aging and the Effectiveness of THC) and the CS
“Overall, the pharmacodynamic effects of THC were smaller than effects previously reported in young adults. In conclusion, THC appeared to be safe and well tolerated by healthy older individuals. Data on safety and effectiveness of THC in frail older persons are urgently required, as this population could benefit from the therapeutic applications of THC.”
Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older subjects: A randomized controlled trial.
Ahmed AI, van den Elsen GA, Colbers A, van der Marck MA, Burger DM, Feuth TB, Rikkert MG, Kramers C.
Eur Neuropsychopharmacol. 2014 Jun 28. pii: S0924-977X(14)00175-8. doi: 10.1016/j.euroneuro.2014.06.007. [Epub ahead of print]
PMID: 25035121 [PubMed - as supplied by publisher]
Related citations

IV. Homeostasis (CBD as a Wake-Inducing Agent) and the CS
“Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on ∆(9)-tetrahydrocannabinol (∆(9)-THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant constituent with non-psychotropic properties, cannabidiol (CBD) has been enhanced. Recently, several groups have investigated the pharmacological properties of CBD with significant findings; furthermore, this compound has raised promising pharmacological properties as a wake-inducing drug. In the current review, we will provide experimental evidence regarding the potential role of CBD as a wake-inducing drug.”
Potential effects of cannabidiol as a wake-promoting agent.
Murillo-Rodríguez E, Sarro-Ramírez A, Sánchez D, Mijangos-Moreno S, Tejeda-Padrón A, Poot-Aké A, Guzmán K, Pacheco-Pantoja E, Arias-Carrión O.
Curr Neuropharmacol. 2014 May;12(3):269-72. doi: 10.2174/1570159X11666131204235805.
PMID: 24851090 [PubMed]
Related citations

V. Homeostasis (Arousal and Sleep) and the CS/CB1
"Cannabinoid type 1 (CB1) receptors are highly expressed in the brain and play a role in behavior control. ... The occurrence of multiple sleep alterations in KO [knock-out] indicates important roles of CB1 receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice."
Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.
Silvani A, Berteotti C, Bastianini S, Lo Martire V, Mazza R, Pagotta U, Quarta C, Zoccoli G.
PLoS One. 2014 Feb 20;9(2):e89432. doi: 10.1371/journal.pone.0089432.
eCollection2014.
PMID: 24586778 [PubMed - in process] Free PMC Article


Video: Density of Cannabinoid Receptors in the Brain and Human Body
~
Posted by Bryan W. Brickner


0 Comments

Homeostasis: Publius’ (Ultralow) THC Political Cannabinoid Science

9/5/2014

1 Comment

 
PictureThe 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]
Related citations

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
Related citations

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]
Related citations

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]
Related citations

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

PictureOnce Upon A Time ...



Posted by Bryan W. Brickner






1 Comment

Homeostasis: Publius’ Alcohol Political Cannabinoid Science

8/30/2014

3 Comments

 
PictureThe 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]
Related citations

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
Related citations

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
Related citations

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]
Related citations

Brain Video:
Why Do Some People Become Alcoholics?

Posted by Bryan W. Brickner


3 Comments

Homeostatic Cannabinoid Science ~ Publius’ World Cup Edition

7/6/2014

2 Comments

 
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]
Related citations

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
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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


2 Comments

Homeostatic Cannabinoid Science ~ Publius’ May Roundup

5/30/2014

0 Comments

 
Picture
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]
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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
Related citations

Bonus Video:

Posted by Bryan W. Brickner

0 Comments

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

5/29/2014

0 Comments

 
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

0 Comments

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

5/18/2014

1 Comment

 
Picture
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]
Related citations

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]
Related citations

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
Related citations

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]
Related citations

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]
Related citations

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]
Related citations

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
Related citations

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
Related citations

Posted by Bryan W. Brickner

1 Comment
<<Previous

    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.

    Archives

    November 2019
    October 2019
    September 2019
    July 2019
    June 2019
    May 2019
    April 2019
    March 2019
    February 2019
    January 2019
    December 2018
    November 2018
    October 2018
    September 2018
    August 2018
    July 2018
    June 2018
    April 2018
    March 2018
    February 2018
    December 2017
    November 2017
    October 2017
    September 2017
    August 2017
    July 2017
    June 2017
    May 2017
    April 2017
    March 2017
    February 2017
    January 2017
    December 2016
    November 2016
    October 2016
    September 2016
    August 2016
    July 2016
    June 2016
    May 2016
    April 2016
    March 2016
    February 2016
    January 2016
    December 2015
    November 2015
    October 2015
    September 2015
    August 2015
    June 2015
    May 2015
    April 2015
    March 2015
    February 2015
    January 2015
    December 2014
    November 2014
    October 2014
    September 2014
    August 2014
    July 2014
    June 2014
    May 2014
    April 2014
    March 2014
    February 2014
    January 2014
    December 2013
    November 2013
    October 2013
    September 2013
    July 2013
    June 2013
    April 2013
    January 2013
    October 2012

    Categories

    All
    17 September
    22nd Amendment
    2 AG
    2-AG
    435
    502nd Infantry
    5 HT
    5-HT
    5-HT
    5 HTP
    5-HTP
    7th Amendment
    9 April 1792
    Aborigine
    A Cabal
    Acetylcholine
    Adam Smith
    Aesop
    Aging
    Akhil Reed Amar
    Albert Hoffman
    Alcohol
    Alexander Hamilton
    Alexander R. Boteler
    Alice In Wonderland
    Alzheimer's/Dementia
    Ambrose Burnside
    American Revolution
    Anandamide
    Andrew Leitch
    Antietam/Sharpsburg
    Anti Republic
    Anti-Republic
    Anti-Semitism
    Archie Lieberman
    Art
    Artemis
    Article The First
    Aspasia Of Miletus
    Athena
    Augustus Kotka
    Bastogne
    Benjamin F. Cheatham
    Benjamin Franklin
    Bivalency
    Black Hawk War 1832
    Brain Gut Axis
    Brain-gut Axis
    Bringing It Home
    Burning Man
    California
    Cancer
    Candide
    Cannabinoids
    Cannabinoid System
    Cannabis
    Carcinogenesis
    Caryophyllene
    Caudate Putamen
    Cb1
    Cb2
    CB2 GPR55 Heteromers
    CB2-GPR55 Heteromers
    CBD
    Cheatham Hill
    Chicago
    Circulatory System
    Cluster Headache
    CNS
    Colitis
    Comrades
    Confederate
    Conservative-Liberal (CL)
    Constitutio Libertatis
    Constitution
    Daimon
    Daniel Morgan
    David Bradford
    David Redick
    Depression
    Despotism
    DHA
    Didaskalos
    Digestive System
    Domestic Tranquility
    Donald Trump
    Dopamine System
    Douglas Southall Freeman
    Dubuque
    Earth Day
    Eisenhower
    Elbridge Gerry
    Electoral College
    Emperor Napoleon
    Endocrine System
    Enumeration
    EPA
    Epilepsy
    Er
    Estrogen
    Exercise
    Ex Falso Quodlibet
    FAKE News
    Federalist 57
    Florida
    Fort Sumter
    Founders
    Francis P. Blair
    Freedom
    Free Markets Cannabis Act (FMCA)
    French Revolution
    GABA
    Gallant Fourteenth
    Georges Danton
    George Thomas
    George Washington
    Georg Groddeck
    Gettysburg
    Gideon
    Gliomas
    Glutamate
    Goddesses
    Government Grown
    Gpr55
    Graham Greene
    Hannah Arendt
    Harlem Heights
    Headache
    Hedonism
    Hemp
    Henry Knox
    Henry Kyd Douglas
    Henry Lee III
    Herbaceutical
    Herbiceutical
    Heteromers
    Hillary Clinton
    Homeostasis
    Horatio Gates
    Hot-flash-reduction
    Hypothalamic-neurohypophyseal
    Ice
    Illinois
    Immigrants
    Immune System
    Indiana
    Indiana 99th Regiment
    Indole-quinuclidine-analogs
    Inflammation
    Irritable Bowel Syndrome Ibs
    It
    Jack-herer
    James Monroe
    James Rumsey
    James W. Foley
    James Wilkinson
    Jean Baudrillard
    Jefferson Davis
    Jesus
    Jim-champion
    Joe
    Johann Palm
    John Adams
    John Bunyan
    John Finley Pettigrew
    John F Kennedy
    John-jay
    John Locke
    John Mosby
    Johnny Reb
    John Roberts
    Jonathan Magbie
    Kaiser Wilhelm
    Keith Marker
    Knowbody
    Kynurenine
    Lil Man
    Liminal
    Lincoln
    Lipids
    Louis Armstrong
    LSS
    Lt
    Lysergic Acid Diethylamide Lsd
    Madison
    March-madness
    Marijuana
    Martin Luther
    Maximilien Robespierre
    Melanocortin Circuit
    'Mericans
    Michigan
    Microbiota
    Migraine
    Mitochondria
    Molly Role
    Monroe Doctrine
    Montesquieu
    Morphine
    Mt-vernon
    Muggles
    Multiple-sclerosis
    Nabiximols-sativex
    Nazis
    Nemesis
    New York
    Nietzsche
    North Carolina
    Nowhere
    Nuclear Receptors
    Obama
    Obesity
    Ohio
    Once Upon A Time
    Opioid
    Otto Snow
    Pain Relief
    Paraquat
    Parmenides
    Parthenongenesis
    Patrick-henry
    Paula Lind Ayers
    Peace Terms
    Pediatric
    Pericles
    Philadelphia
    Phototherapy
    Physiodelia
    Physiology System
    Pituitary-stalk
    Plato
    Pot
    Pregnancy
    President Taylor
    Psilocybin
    PTSD
    Publius
    Puritans
    Putin
    Quakers
    Race
    Ra Chaka
    Ralph Waldo Emerson
    R. Bruce Dold
    Representation
    Reproductive System
    Republic
    Respiratory-system
    Richard Lee I
    Rick Simpson
    Robert Dahl
    Robert E. Lee
    Roman Republic
    Sarah Tonin
    Sarajevo
    Secession
    Serotonin System
    Shall
    Shivitti
    Silent Night
    Skeletal System
    Slavery
    Sleep
    Snake And Turkey
    Socrates
    Sophie Scholl
    Sophocles
    South Carolina
    Sperm
    Spermatogenesis
    Spermatozoa
    Sport
    Star Of David
    Stephen Young
    Suicidal
    Sun Tzu
    Sweat
    Tell Lie Vision
    Tell-Lie-Vision
    Texas
    THC
    The Boys
    The Cannabis Papers
    The Federalist Papers
    The-federalist-papers
    The Few
    The Lost Special Orders #191
    The Many
    The Quiet American (1955)
    The Unrepresented
    Thirty Thousand
    Thirty-thousand
    Thomas-jefferson
    Thomas Knowlton
    Thomas Sumpter (Sumter)
    Three Fifths Representation
    Three-fifths Representation
    Tom Paine
    Tory Crown
    Traumatic Brain Injury
    Trenton
    Truck Drivers
    Tryptophan
    Tsar Nicholas
    Tuscarora / Hemp Gatherers
    US Grant
    Us Supreme Court
    Usurpation
    Usurpecans
    Valkyrie
    Vanilloid-system
    Veritas
    Veterans
    Vietnam
    Virginia
    Visual-system
    Walter-benjamin
    Weed
    West Virginia
    We The People
    We-the-people
    Whiskey Rebellion
    White Rose
    William-abens
    William Findley
    William Washington
    Wine
    Winfield Scott
    Women
    Yale
    Yankee Doodle Dandy
    Zarathustra

    RSS Feed

Powered by Create your own unique website with customizable templates.