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Homeostatic Cannabinoid Science ~ Publius’ May Roundup

5/30/2014

Astrocyte / Blood-Brain Barrier by Ben Brahim Mohammed

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

Here are seven new 2014 findings on how the cannabinoid system (CS) modulates homeostasis and other systems in our bodies: the roundup links to recent PubMed articles on the urinary, neuroendocrine, digestive, central nervous and serotonin systems.

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

Posted by Bryan W. Brickner

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Synaptic Serotonin’s Bicycle Day 2014: A (Short) Science Story

4/18/2014

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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
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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
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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

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Indiscernible Cannabinoid Science ~ Publius’ March 2014 Roundup

3/30/2014

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

Here are seven 2014 findings on how the cannabinoid system (CS) modulates homeostasis and other systems in our bodies: the roundup links to recent PubMed articles on the vanilloid, neurological, dopamine, visual, skeletal, and endocrine systems.

I. Vanilloid System and the CS
“These data indicate that the eCB system can modulate inflammatory activation of the endothelium and may have important implications for a variety of acute inflammatory disorders that are characterized by EC [Endothelial Cell] activation.”
The endocannabinoid/endovanilloid N-arachidonoyl dopamine (NADA) and synthetic cannabinoid WIN55,212-2 abate the inflammatory activation of human endothelial cells.
Wilhelmsen K, Khakpour S, Tran A, Sheehan K, Schumacher M, Xu F, Hellman J.
J Biol Chem. 2014 Mar 18. [Epub ahead of print]
PMID: 24644287 [PubMed - as supplied by publisher] Free Article
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II. Neurological System (Migraines) and the CS
“These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”
Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.
Greco R, Mangione AS, Sandrini G, Nappi G, Tassorelli C.
J Headache Pain. 2014 Mar 17;15(1):14. doi: 10.1186/1129-2377-15-14.
PMID: 24636539 [PubMed - in process] Free Article
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III. Dopamine System and the CS
“The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system.”
Involvement of the Cannabinoid CB1 Receptor in Modulation of Dopamine Output in the Prefrontal Cortex Associated with Food Restriction in Rats.
Dazzi L, Talani G, Biggio F, Utzeri C, Lallai V, Licheri V, Lutzu S, Mostallino MC, Secci PP, Biggio G, Sanna E.
PLoS One. 2014 Mar 14;9(3):e92224. doi: 10.1371/journal.pone.0092224. eCollection 2014.
PMID: 24632810 [PubMed - in process] Free PMC Article
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IV. Neurological System (Alzheimer’s disease) and the CS
“Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress.”
Cannabinoids for treatment of Alzheimer's disease: moving toward the clinic.
Aso E, Ferrer I.
Front Pharmacol. 2014 Mar 5;5:37. eCollection 2014. Review.
PMID: 24634659 [PubMed - as supplied by publisher] Free PMC Article
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V. Visual System and the CS
“Our findings provide neurophysiologic evidence for a link between cannabinoid-signaling, network dynamics and the function of a canonical cortical circuit.”
Cannabinoid neuromodulation in the adult early visual cortex.
Ohiorhenuan IE, Mechler F, Purpura KP, Schmid AM, Hu Q, Victor JD.
PLoS One. 2014 Feb 19;9(2):e87362. doi: 10.1371/journal.pone.0087362. eCollection 2014.
PMID: 24586271 [PubMed - in process] Free PMC Article
Related citations

VI. Skeletal System (Osteoarthritis) and the CS
“The ubiquitous distribution of cannabinoid receptors, together with the physiological role of the endocannabinoid system in the regulation of pain, inflammation and even joint function further support the therapeutic interest of cannabinoids for osteoarthritis.”
Involvement of the endocannabinoid system in osteoarthritis pain.
La Porta C, Bura SA, Negrete R, Maldonado R.
Eur J Neurosci. 2014 Feb;39(3):485-500. doi: 10.1111/ejn.12468.
PMID: 24494687 [PubMed - in process]
Related citations

VII. Endocrine System (HP-axis) and the CS
“Since the endocannabinoid system components are present at sites involved in the hypothalamic-pituitary axis regulation, several studies were performed in order to investigate the endocannabinoid-mediated neurotransmitters and hormones secretion under physiological and pathological conditions.”
Role of the Endocannabinoid System in the Neuroendocrine Responses to Inflammation.
De Laurentiis A, Araujo HA, Rettori V.
Curr Pharm Des. 2014 Jan 30. [Epub ahead of print]
PMID: 24588819 [PubMed - as supplied by publisher]
Related citations

~’~
posted by bwb

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Indiscernible Cannabinoid System Science ~ Publius’ February 2014 Roundup

2/27/2014

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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.

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Homeostatic Cannabinoid Science ~ Publius’ May Roundup

Synaptic Serotonin’s Bicycle Day 2014: A (Short) Science Story

Indiscernible Cannabinoid Science ~ Publius’ March 2014 Roundup

Indiscernible Cannabinoid System Science ~ Publius’ February 2014 Roundup

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