Albert Hoffman 1993 (by Philip H. Bailey)

Bicycle Day is the day scientist Albert Hoffman took an intentional dose of lysergic acid diethylamide (LSD) and then rode his bike home.

Hoffman’s intentional dose on 19 April 1943 was actually his second “contact” with LSD. The macro dose day is the memorable bicycle ride home; the unintentional first dose was at a micro level absorbed through his skin (or somehow). Hoffman wasn’t ever very clear on how that happened; he did note a slight modulation from the micro experience … enough to convince him to try the macro.

LSD works because it modulates one’s serotonin system and its plethora of receptors (15 last time I checked). Hoffman was the first to experience the synaptic serotonin effects LSD yields – yet we all modulate our bodies via serotonin … we just do it daily in a micro way (it’s in us).

Below is a four-part science story from the National Institutes of Health (PubMed): it includes a dialogue between our immune and serotonin systems, an early microbiota life tale, a circadian clocks discussion, and talk of bowels (irritable and otherwise) and the brain-gut axis. The links and quotes are from PubMed.

Think of cannabinoids as the wheel’s hub and serotonin as the transmission: for certain, as Albert Hoffman attested, it’s a neurotransmission without equal.

Happy Bicycle Day 2014 Everyone!

~
I. A Dialogue (immune and serotonin systems)
“Neuropsychiatric disorders have long been linked to both immune system activation and alterations in serotonin (5-HT) signaling. In the CNS, the contributions of 5-HT modulate a broad range of targets, most notably, hypothalamic, limbic and cortical circuits linked to the control of mood and mood disorders. In the periphery, many are aware of the production and actions of 5-HT in the gut but are unaware that the molecule and its receptors are also present in the immune system where evidence suggests they contribute to the both innate and adaptive responses. In addition, there is clear evidence that the immune system communicates to the brain via both humoral and neuronal mechanisms, and that CNS 5-HT neurons are a direct or indirect target for these actions.”

A dialogue between the immune system and brain, spoken in the language of serotonin.
Baganz NL, Blakely RD.
ACS Chem Neurosci. 2013 Jan 16;4(1):48-63. doi: 10.1021/cn300186b. Epub 2012 Dec 7. Review.
PMID: 23336044 [PubMed - indexed for MEDLINE] Free PMC Article
Related citations

II. Early Life (immune, endocrine and serotonin systems)
“Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. … Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. … However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. … Moreover, this alteration is sex specific in contrast with the immunological and neuroendocrine effects which are evident in both sexes. Concentrations of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission.”

The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner.
Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, Dinan TG, Cryan JF.
Mol Psychiatry. 2013 Jun;18(6):666-73. doi: 10.1038/mp.2012.77. Epub 2012 Jun 12.
PMID: 22688187 [PubMed - indexed for MEDLINE]
Related citations

III. Circadian Clock (chickens and serotonin biosynthesis)
“Serotonin in blood plasma is primarily synthesized in the duodenum [first section of the small intestine], as brain derived serotonin does not cross the blood-brain barrier. Because serotonin in the brain and retina is synthesized under the control of a circadian clock, we sought to determine if a circadian clock in the duodenum regulates serotonin synthesis and release in blood. We examined gene expression in the duodenum of chickens at different times of the day and found that the duodenum rhythmically expresses molecular circadian clock genes and genes controlling serotonin biosynthesis, specifically tryptophan hydroxylase, in a light dark cycle (LD). … Because serotonin in the gut affects duodenal nutrient absorption and gut motility, the control of serotonin production in the duodenum by LD cycles could provide an additional mechanism by which the external environment controls nutrient uptake and digestive function.”

Biological clocks in the duodenum and the diurnal regulation of duodenal and plasma serotonin.
Ebert-Zavos E, Horvat-Gordon M, Taylor A, Bartell PA.
PLoS One. 2013 May 30;8(5):e58477. doi: 10.1371/journal.pone.0058477. Print 2013.
PMID: 23737937 [PubMed - indexed for MEDLINE] Free PMC Article
Related citations

IV. Bowels (irritable and otherwise: brain-gut axis)
“Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal discomfort, pain and changes in bowel habits, often associated with psychological/psychiatric disorders. It has been suggested that the development of IBS may be related to the body’s response to stress, which is one of the main factors that can modulate motility and visceral perception through the interaction between brain and gut (brain-gut axis). … Several lines of evidence indicate that 5-HT and its receptor subtypes are likely to have a central role in the pathophysiology of IBS. 5-HT released from enterochromaffin cells regulates sensory, motor and secretory functions of the digestive system through the interaction with different receptor subtypes. It has been suggested that pain signals originate in intrinsic primary afferent neurons and are transmitted by extrinsic primary afferent neurons. Moreover, IBS is associated with abnormal activation of central stress circuits, which results in altered perception during visceral stimulation.”

Serotonin receptors and their role in the pathophysiology and therapy of irritable bowel syndrome.
Stasi C, Bellini M, Bassotti G, Blandizzi C, Milani S.
Tech Coloproctol. 2014 Jan 15. [Epub ahead of print]
PMID: 24425100 [PubMed - as supplied by publisher]
Related citations

Plus ~ Today's Video ~
Serotonin and the Gut Brain Connection
http://www.youtube.com/watch?v=KYT5syDMsTQ

Posted by Bryan W. Brickner

Slavery is the shadow of usurpation (rights taken without right) the way mythology frames America’s beginning: it’s foundational.

Slavery has been edited out of Usurpation Day 2014; it will be duly accorded its role in both Athens and America in June (on the 19th).

Usurpation Day is not a time to be sad; it’s a celebratory day. The usurpation of the representation ratio on 9 April 1792 is our history … it’s not our heritage.

Heritage is ahistorical (timeless) and it is our focus today: specifically, ascending Athenian American heritage. Six greats ~ three from each polis: Plato and Madison, Pericles and Washington, and Athena and Freedom:

Plato
Plato’s contribution to our heritage is The Republic. In the book he outlines the just society and details three groups (factions/divisions) in his republican form of government: rulers, guardians and craftspeople (producers).

Madison
Madison’s contribution to our heritage is the addition of the representation ratio to Plato’s republican ideas. Whereas Plato’s republic has three factions, Madison’s republic has a fourth ~ We the People ~ and utilizes the decennial Census to augment representation in accordance with population growth (something Plato’s republican ideas lack).

Pericles
His era built the Parthenon. He was an Athenian leader during the Peloponnesian War and his Funeral Oration (speech) is noted in Thucydides’ work. 

Washington
His era built the District of Columbia. Washington was hailed as the first in war and the first in peace. His most famous speech is his Farewell Address. Washington’s library included the Greeks: Homer’s Iliad and Odyssey and Ovid’s Metamorphoses ~ which makes mention of 30,000 spirits who watch over the deeds of humans and bring agricultural bounty.

Athena
The Athenian’s had a statue of Athena inside the Parthenon. She is noted for many things to the Greeks; in particular, the victory at Troy and the homecoming of Odysseus. She was referred to as Promachus: first (foremost) fighter and one who leads in battle. Also, parthenongenesis is asexual reproduction without fertilization  ~ noting Athena’s birth from the head of Zeus.

Freedom
We the People have our own Athena: her name is Freedom and she watches over America from atop our acropolis, the US Capitol. There were three versions of Freedom’s statue. The first looked too much like Athena; the second, too much like Minerva (Rome’s Athena); the third they thought looked just about right I guess … you know, for being born in 1863 in the middle of the US Civil War.

Heritage (not history) is the key to Usurpation Day ~ and keep this in mind: America’s best days are ahead of US.

Let us pick-up there on 19 June … Juneteenth.

Bryan W. Brickner    

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
Related citations

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
Related citations

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
Related citations

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

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

Colorectal (colon) cancer awareness and the cannabinoid system (CS) are the focus of March’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed CS science on preventing carcinogenesis, inducing apoptosis, attenuating cancer’s damage, and an estrogen-responsive connection to controlling colon cancer proliferation.

2013 ~ Attenuating Damage and the CS
“These findings support a discrete role for CB2 receptors in the attenuation of detrimental pro-inflammatory cytokine-mediated mucosal damage in the human colon without directly affecting mucosal epithelial barrier function.”
Cannabinoid CB2 receptor activation attenuates cytokine-evoked mucosal damage in a human colonic explant model without changing epithelial permeability.
Harvey BS, Nicotra LL, Vu M, Smid SD.
Cytokine. 2013 Aug;63(2):209-17. doi: 10.1016/j.cyto.2013.04.032. Epub 2013 May 22.
PMID: 23706402 [PubMed - indexed for MEDLINE]
Related citations

2013 ~ Immunoreactivity (Immune Reaction) and the CS
“The high immunoreactivity of the cannabinoid type 1 receptor is a significant prognostic factor following surgery in stage IV CRC [colorectal cancer].”
Expression of the cannabinoid type I receptor and prognosis following surgery in colorectal cancer.
Jung CK, Kang WK, Park JM, Ahn HJ, Kim SW, Taek Oh S, Choi KY.
Oncol Lett. 2013 Mar;5(3):870-876. Epub 2012 Dec 18.
PMID: 23426698 [PubMed] Free PMC Article
Related citations

2012 ~ Preventing Carcinogenesis and the CS
“Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis.”
Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.
Aviello G, Romano B, Borrelli F, Capasso R, Gallo L, Piscitelli F, Di Marzo V, Izzo AA.
J Mol Med (Berl). 2012 Aug;90(8):925-34. doi: 10.1007/s00109-011-0856-x. Epub 2012 Jan 10.
PMID: 22231745 [PubMed - indexed for MEDLINE]
Related citations

2011 ~ Inducing Apoptosis and the CS
“Cannabinoid receptor agonists induce phosphatases and phosphatase-dependent apoptosis in cancer cell lines; however, the role of the CB receptor in mediating this response is ligand-dependent.”
Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent.
Sreevalsan S, Joseph S, Jutooru I, Chadalapaka G, Safe SH.
Anticancer Res. 2011 Nov;31(11):3799-807.
PMID: 22110202 [PubMed - indexed for MEDLINE] Free PMC Article
Related citations

2008 ~ Silencing Cancer and the CS
“Here we show that CB1 expression was silenced in human colorectal cancer due to methylation of the CB1 promoter.”
Loss of cannabinoid receptor 1 accelerates intestinal tumor growth.
Wang D, Wang H, Ning W, Backlund MG, Dey SK, DuBois RN.
Cancer Res. 2008 Aug 1;68(15):6468-76. doi: 10.1158/0008-5472.CAN-08-0896.
PMID: 18676872 [PubMed - indexed for MEDLINE] Free PMC Article
Related citations

2008 ~ Estrogen-Responsive Genes and the CS
“The CB1 receptor can be considered an estrogen-responsive gene in DLD-1, HT-29 and SW620 cells. Up-regulation of CB1 expression by 17beta-estradiol is a further mechanism of estrogens to control colon cancer proliferation.”
Estrogenic induction of cannabinoid CB1 receptor in human colon cancer cell lines.
Notarnicola M, Messa C, Orlando A, Bifulco M, Laezza C, Gazzerro P, Caruso MG.
Scand J Gastroenterol. 2008 Jan;43(1):66-72.
PMID: 18938775 [PubMed - indexed for MEDLINE]
Related citations

2004 ~ Preventing Metastasis and the CS
“Therefore, specific inhibition of tumor cell migration via CB1-R engagement might be a selective tool to prevent metastasis formation without depreciatory effects on the immune system of cancer patients.”
Anandamide is an endogenous inhibitor for the migration of tumor cells and T lymphocytes.
Joseph J, Niggemann B, Zaenker KS, Entschladen F.
Cancer Immunol Immunother. 2004 Aug;53(8):723-8. Epub 2004 Mar 18.
PMID: 15034673 [PubMed - indexed for MEDLINE]
Related citations

2003 ~ Inhibiting Cancer and the CS
“The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) inhibit cancer cell proliferation by acting at cannabinoid receptors (CBRs).”
Possible endocannabinoid control of colorectal cancer growth.
Ligresti A, Bisogno T, Matias I, De Petrocellis L, Cascio MG, Cosenza V, D'argenio G, Scaglione G, Bifulco M, Sorrentini I, Di Marzo V.
Gastroenterology. 2003 Sep;125(3):677-87.
PMID: 12949714 [PubMed - indexed for MEDLINE]
Related citations

~ posted by bryan w. brickner

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

March Madness induces coaches, players and fans to intensity. A first sign of intensity, one in every ballgame played during this madness, is traditional and time-tested: the warm-up. This pre-game activity, designed with the players in mind, is really for the body: one has to wake the body up (stress it a bit) to make it intense – to raise consciousness.

One’s heart pumps more, legs stretch, breathing calms, and soon the first drops of intensity … sweat.

Sweat is also a sign of the cannabinoid system (CS). The CS modulates exercise by priming our other systems for activity: the research is exciting (maybe even more than a few of the games) and The National Institutes of Health (PubMed) provides the quotes and play-by-play.

Reward and Warm-up
Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'. (2012)

“Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise. Endocannabinoids (eCBs) are endogenous neurotransmitters that appear to play a major role in generating these rewards by activating cannabinoid receptors in brain reward regions during and after exercise.”

“This study provides the first evidence that inter-specific variation in neurotransmitter signaling may explain differences in locomotor behavior among mammals.”

Reward and Intensity
Exercise-induced endocannabinoid signaling is modulated by intensity. (2013)

“Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are densely expressed in brain networks responsible for reward.”

“Our results are consistent with intensity-dependent psychological state changes with exercise and therefore support the hypothesis that eCB activity is related to neurobiological effects of exercise. Thus, future studies examining the role of exercise-induced eCB signaling on neurobiology or physiology must take exercise intensity into account.”

Reward and Depression
Intense exercise increases circulating endocannabinoid and BDNF levels in humans – possible implications for reward and depression. (2012)

“The endocannabinoid system is known to have positive effects on depression partly through its actions on neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF). As BDNF is also considered the major candidate molecule for exercise-induced brain plasticity, we hypothesized that the endocannabinoid system represents a crucial signaling system mediating the beneficial antidepressant effects of exercise.”

“These findings provide evidence in humans that acute exercise represents a physiological stressor able to increase peripheral levels of AEA [anandamide] and that BDNF might be a mechanism by which AEA influences the neuroplastic and antidepressant effects of exercise.”

The CS handles intensities like a play-making point-guard; these ballgames and our enthusiasm involve an ancient biological process genetically developed for millions of years. You’ll recognize its presence in the cards of victory and the flush of defeat.

Oh yeah … the refs. Human too you know ~ meaning CS modulation is involved. So let’em warm-up proper and get prepared, as it’s that time: tip-off!

March Madness Modulation Everyone!

Bryan W. Brickner

We shall dream again.

The “we” is We the People. Women are more than half of We the People yet have only 18% representation in the US House.

The “shall” is constitutional. Counting the people is the purpose of the decennial Census; lawmakers are then to divide by the representation ratio in Article I, Section 2, Clause 3 of the US Constitution: “The Number of Representatives shall not exceed one for every thirty Thousand, but each State shall have at Least one Representative.”

The “dream” is foundational. The representation ratio is the constitutional definition of We the People.

The “again” is time. 2016’s presidential election is not about a woman in the White House: it’s about women in the US House of Representatives. Congress always added seats (representatives) to the US House after each Census: in 1920, they suddenly stopped.

We shall dream again America ~ as it’s a heritage dream ~ one that represents all of US.

Bryan W. Brickner

Women’s Suffrage Documentary

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

This roundup links to seven 2014 PubMed articles on cannabinoids modulating other systems in our bodies, such as: the olfactory, endocrine, vanilloid, serotonin, opioid, dopamine, and nervous systems. There’s also a bit of systemic science ~ getting a good night’s sleep.


I. Olfactory System and CS
“Thus, CB1 receptor-dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior.”

The endocannabinoid system controls food intake via olfactory processes.
  Soria-Gómez E, Bellocchio L, Reguero L, Lepousez G, Martin C, Bendahmane M, Ruehle S, Remmers F, Desprez T, Matias I,
  Wiesner T, Cannich A, Nissant A, Wadleigh A, Pape HC, Chiarlone AP, Quarta C, Verrier D, Vincent P, Massa F, Lutz B,
  Guzmán M, Gurden H, Ferreira G, Lledo PM, Grandes P, Marsicano G.
  Nat Neurosci. 2014 Mar;17(3):407-15. doi: 10.1038/nn.3647. Epub 2014 Feb 9.
  PMID: 24509429 [PubMed - in process]

II. Endocrine System (Hypothalamus-pituitary axis) and CS
“Whereas the effect on 3β-HSD was counteracted by SR141716A (Rimonabant) - a selective antagonist of CB1, thus indicating a CB1 dependent modulation - the effect on cyp17 was not, suggesting a possible involvement of receptors other than CB1, probably the type-1 vanilloid receptor (TRPV1), since AEA works as an endocannabinoid and an endovanilloid as well.”

Hypothalamus-pituitary axis: an obligatory target for endocannabinoids to inhibit steroidogenesis in frog testis.
  Chianese R, Ciaramella V, Fasano S, Pierantoni R, Meccariello R.
  Gen Comp Endocrinol. 2014 Feb 21. pii: S0016-6480(14)00053-7. doi: 10.1016/j.ygcen.2014.02.010. [Epub ahead of print]
  PMID: 24566122 [PubMed - as supplied by publisher]

III. Vanilloid System (Schizophrenia) and CS
“Our results indicate that the schizophrenia-like behaviors displayed by SHR [Spontaneously Hypertensive Rats]  are differently altered by cannabinoid and vanilloid drugs when compared to control animals and suggest the endocannabinoid and the vanilloid systems as a potential target for the treatment of schizophrenia.”

Effects of cannabinoid and vanilloid drugs on positive and negative-like symptoms on an animal model of schizophrenia: The SHR strain.
  Almeida V, Peres FF, Levin R, Suiama MA, Calzavara MB, Zuardi AW, Hallak JE, Crippa JA, Abílio VC.
  Schizophr Res. 2014 Feb 17. pii: S0920-9964(14)00062-0. doi: 10.1016/j.schres.2014.01.039. [Epub ahead of print]
  PMID: 24556469 [PubMed - as supplied by publisher]

IV. Serotonin, Opioid, and Dopamine Systems and CS
“In this review we highlight the evidence for the physiological role of such constitutive GPCR [G protein-coupled receptor]   activity (in particular for cannabinoid 1, serotonin 2C and mu-opioid receptors) in the ventral tegmental area and in its output regions like the nucleus accumbens. We also address the behavioral relevance of constitutive GPCR signaling and discuss the repercussions of its abolition in dopamine-related psychiatric diseases.”

The vital role of constitutive GPCR activity in the mesolimbic dopamine system.
  Meye FJ, Ramakers GM, Adan RA.
  Transl Psychiatry. 2014 Feb 11;4:e361. doi: 10.1038/tp.2013.130.
  PMID: 24518399 [PubMed - in process]

V. Sleep, Systems and CS
“Overall, these findings demonstrate that the EC [Endo-Cannabinoid] system actively regulates cortical up-states and important features of NREM sleep such as its duration and low frequency cortical oscillations.”

Endocannabinoid Modulation of Cortical Up-States and NREM Sleep.
  Pava MJ, den Hartog CR, Blanco-Centurion C, Shiromani PJ, Woodward JJ.
  PLoS One. 2014 Feb 10;9(2):e88672. doi: 10.1371/journal.pone.0088672. eCollection 2014.
  PMID: 24520411 [PubMed - in process] Free PMC Article

VI. Central Nervous System and CS
“In the present study, we discovered that 2-AG significantly protects CN neurons in culture against lipopolysaccharide (LPS)-induced inflammatory response.”

Endocannabinoid 2-Arachidonylglycerol Protects Primary Cultured Neurons Against LPS-Induced Impairments in Rat Caudate Nucleus.
  Lu Y, Peng F, Dong M, Yang H.
  J Mol Neurosci. 2014 Feb 9. [Epub ahead of print]
  PMID: 24510751 [PubMed - as supplied by publisher]

VII. Nervous System (Alzheimer’s/Dementia) and CS
“The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD.”

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]

~.~
February's Video
What if Cannabinoids in Cannabis Cured Cancer & Other Diseases?

  Posted by bwb.

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

Cancer prevention awareness and the cannabinoid system are the focus of February’s health update from Publius and The Cannabis Papers: A citizen’s guide to cannabinoids (2011). This month: PubMed science on inflammation, a unique receptor, GPR55, and the ability of one’s cannabinoid system to induce apoptosis, programmed cancer cell death.

2014 ~ Inflammation (HIV-1) and CS/GPR55
“Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection.”

Δ9-Tetrahydrocannabinol Treatment During Human Monocyte Differentiation Reduces Macrophage Susceptibility to HIV-1 Infection.
Williams JC, Appelberg S, Goldberger BA, Klein TW, Sleasman JW, Goodenow MM.
J Neuroimmune Pharmacol. 2014 Feb 23. [Epub ahead of print]
PMID: 24562630 [PubMed - as supplied by publisher]


2013 ~ Alcohol, Dentric Cells and CS/GPR55
"Our results provide insights into alcohol mechanisms of DC [dentric cell] regulation and show, for the first time, that alcohol is inducing CNR2 [CB2] and GPR55 in human DCs."

Differential expression and functional role of cannabinoid genes in alcohol users.
Agudelo M, Yndart A, Morrison M, Figueroa G, Muñoz K, Samikkannu T, Nair MP.
Drug Alcohol Depend. 2013 Dec 1;133(2):789-93. doi: 10.1016/j.drugalcdep.2013.08.023. Epub 2013 Sep 5.
PMID: 24060590 [PubMed - in process]


2013 ~ Inflammation (Cancer) and CS/GPR55
“GPR55 has been shown to have a role in cancer and gastrointestinal inflammation, as well as in obesity and type 2 diabetes mellitus (T2DM).”

A potential role for GPR55 in the regulation of energy homeostasis.
Simcocks AC, O'Keefe L, Jenkin KA, Mathai ML, Hryciw DH, McAinch AJ.
Drug Discov Today. 2013 Dec 24. pii: S1359-6446(13)00423-6. doi: 10.1016/j.drudis.2013.12.005. [Epub ahead of print] Review.
PMID: 24370891 [PubMed - as supplied by publisher]


2013 ~ CS Synergistic Against Cancer
“The observed synergistic effect with cannabinoid agonists implicates an involvement of the cannabinoid system.”

Cytotoxic effect of efavirenz is selective against cancer cells and associated with the cannabinoid system.
Hecht M, Harrer T, Büttner M, Schwegler M, Erber S, Fietkau R, Distel LV.
AIDS. 2013 Aug 24;27(13):2031-40. doi: 10.1097/QAD.0b013e3283625444.
PMID: 23612009 [PubMed - in process]


2011 ~ GPR55 Driving Cancer Cell Migration
“It has now been revealed that LPI [L-α-lysophosphatidylinositol] activates GPR55, a G protein-coupled receptor that couples to G(12/13) and G(q) proteins, which direct oncogenic signalling. New evidence indicates that LPI and GPR55 are key partners in driving cancer cell proliferation and migration.”

L-α-lysophosphatidylinositol meets GPR55: a deadly relationship.
Ross RA.
Trends Pharmacol Sci. 2011 May;32(5):265-9. doi: 10.1016/j.tips.2011.01.005. Epub 2011 Mar 1.
PMID: 21367464 [PubMed - indexed for MEDLINE]


2010 ~ Breast Cancer and CS/GPR55
“LPI and GPR55 play a role in the modulation of migration, orientation and polarization of breast cancer cells in response to the tumour microenvironment.”

A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells.
Ford LA, Roelofs AJ, Anavi-Goffer S, Mowat L, Simpson DG, Irving AJ, Rogers MJ, Rajnicek AM, Ross RA.
Br J Pharmacol. 2010 Jun;160(3):762-71. doi: 10.1111/j.1476-5381.2010.00743.x.
PMID: 20590578 [PubMed - indexed for MEDLINE] Free PMC Article


2006 ~ Evolution and CS/GPR55
“Within this limited number of twelve organisms, the endocannabinoid genes exhibited heterogeneous evolutionary trajectories, with functional orthologs limited to mammals (TRPV1 and GPR55), or vertebrates (CB2 and DAGLbeta), or chordates (MAGL and COX2), or animals (DAGLalpha and CB1-like receptors), or opisthokonta (animals and fungi, NAPE-PLD), or eukaryotes (FAAH).”

Evolutionary origins of the endocannabinoid system.
McPartland JM, Matias I, Di Marzo V, Glass M.
Gene. 2006 Mar 29;370:64-74. Epub 2006 Jan 23.
PMID: 16434153 [PubMed - indexed for MEDLINE]

~ posted by bwb

By Stephen Young

Distillers continue their work at Mt. Vernon, the home of George Washington, trying to make whiskey like the first US President used to make it.

As initially reported by Reason a couple years ago (and recently updated as, Celebrate George Washington’s Birthday, Drink Some Whiskey), a group using historical recipes and methods have been patiently testing ways to accurately recreate the drink that helped fuel a revolution.

I appreciate efforts to preserve history in a way that is interesting, so cheers to anyone who attempts to make history literally intoxicating.

But I propose a more family-oriented way to relive the past that gives a different sense of Washington’s entrepreneurial spirit: bring back hemp to Mt. Vernon.

As noted in The Cannabis Papers, a book I helped to write, Washington succeeded at his hemp business, and he expressed interest in it that seemed to go beyond mere profit. In his journals Washington described visiting the hemp plots regularly and seemed disappointed when he missed certain aspects of the crop’s growth.

That interest is easy to understand today: hemp was crucial to the colonies just as it was very important to a young nation. And hemp could be crucial now to the current American economy, if only it were allowed to be grown by American farmers. What better place to start a new tradition than at Mt. Vernon? Sure, the crop could be restarted at other estates of founding fathers, say Thomas Jefferson’s Monticello for example, but the first should be the first.

In the wake of discoveries about cannabinoids, hemp has even more potential uses than in the late 18th Century. Even uncultivated wild hemp, once derisively referred to as ditch weed, is now seen as life-saving medicine packed with therapeutic CBD that can stop maladies from epilepsy to cancer.

Washington played many roles with great success, such great success that he must be considered visionary. His revolutionary tactics baffled his enemies in battle. His understanding of representation aimed to ensure a continuing Republic. He put his efforts into businesses he knew would succeed. It’s clear Washington recognized the practical applications of hemp in his time, but I wouldn't be surprised if also he had some sense how important hemp would be in the future.

More Hemp from Mr. Young:

Part I ~ Government Grown: How Polo Illinois Helped Win the War

Part II ~ Government Grown: How Polo Illinois Helped Win the War

posted by bwb