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Homeostasis: Publius’ Sleep Political Cannabinoid Science

9/29/2014

The 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

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Homeostasis: Equinox Serotonin (5HT) Headache Stories

9/20/2014

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Homeostatic Life Light (2014)

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

Headache Edition ~ Autumnal Equinox

Equinox and Homeostasis are mid-point extremes and today’s serotonin system science looks at 5-HT (5-hydroxytryptamine) and its role in modulating another extreme, the brain: specifically, headaches. Below are five (brief) science stories from the National Institutes of Health (PubMed). The serotonin brain tales include: pro-cognitive 5-HT4 receptors, mitigating medication overuse, abnormal headache chronicity, (red) wine interference mechanisms, and new cluster headache horizons.

Autumnal Equinox Health Everyone!

1. Serotonin 5-HT4 Receptors ~ Pro-Cognitive Hippocampal Effects
“Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. … These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.”
Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.
Peñas-Cazorla R, Vilaró MT.
Brain Struct Funct. 2014 Sep 3. [Epub ahead of print]
PMID: 25183542 [PubMed - as supplied by publisher]
Related citations

2. Serotonin Metabolism ~ Reversing Anxiety and Depression
“Medication overuse headache (MOH) affects between 1% and 2% of the general population but is present in up to 50% of patients seen in headache centers. … We conclude that headache frequency can be reduced to episodic headache in more than 50% of the patients by simple detoxification and information. Approximately half the patients will not have need for prophylactic medication after withdrawal. Pain perception is altered in patients with MOH but can be restored to a baseline pattern, indicating a reversible mechanism in the central sensitization leading to chronic pain. The great comorbidity with depression and anxiety could be a consequence of the altered serotonin metabolism indicating a reversible and potentially treatable condition.”
Medication overuse headache.
Munksgaard SB, Jensen RH.
Headache. 2014 Jul-Aug;54(7):1251-7. doi: 10.1111/head.12408. Epub 2014 Jul 2.
PMID: 24990298 [PubMed - in process]
Related citations

3. Serotonergic Homeostasis ~ Chronic Migraine and Tension-Type Headaches
“The primary aim of this study (TA-CH, Tryptophan Amine in Chronic Headache) was to investigate a possible role of tryptophan (TRP) metabolism in chronic migraine (CM) and chronic tension-type headache (CTTH). … Our results support the hypothesis that TRP metabolism is altered in CM and CTTH patients, leading to a reduction in plasma TRY. As TRY modulates the function of pain matrix serotonergic system, this may affect modulation of incoming nociceptive inputs from the trigeminal endings and posterior horns of the spinal cord. We suggest that these biochemical abnormalities play a role in the chronicity of CM and CTTH.”
Tryptamine levels are low in plasma of chronic migraine and chronic tension-type headache.
D'Andrea G, D'Amico D, Bussone G, Bolner A, Aguggia M, Saracco MG, Galloni E, De Riva V, D'Arrigo A, Colavito D, Leon A, Perini F.
Neurol Sci. 2014 Jul 14. [Epub ahead of print]
PMID: 25016960 [PubMed - as supplied by publisher]
Related citations

4. Serotonin Metabolism / Migraines ~ Wine Interference Mechanisms
“Wine, and specifically red wine, is a migraine trigger. Non-migraineurs may have headache attacks with wine ingestion as well. The reasons for that triggering potential are uncertain, but the presence of phenolic flavonoid radicals and the potential for interfering with the central serotonin metabolism are probably the underlying mechanisms of the relationship between wine and headache. Further controlled studies are necessary to enlighten this traditional belief.”
Wine and headache.
Krymchantowski AV, da Cunha Jevoux C.
Headache. 2014 Jun;54(6):967-75. doi: 10.1111/head.12365. Epub 2014 May 6.
PMID: 24801068 [PubMed - in process]
Related citations

5. Serotonin Homeostasis ~ New Migraine and Cluster Headache Horizons
“Migraine and cluster headache are primary headache disorders commonly encountered in clinical practice. … This article will highlight several of the new treatments that are currently under investigation including novel delivery mechanisms of already existing medications, calcitonin gene-related peptide (CGRP) receptor antagonists, antibodies to CGRP and its receptor, serotonin receptor agonists, transient receptor potential vanilloid receptor modulators, orexin receptor antagonists, glial cell modulators, and neuromodulation.”
New treatments for headache.
Vollbracht S, Rapoport AM.
Neurol Sci. 2014 May;35 Suppl 1:89-97. doi: 10.1007/s10072-014-1747-z.
PMID: 24867844 [PubMed - in process]
Related citations

Serotonin Video: The Truth about Depression BBC Full Documentary 2013
~
Posted by Bryan W. Brickner

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Constitution Day: Gus Kotka, Johnny Reb and Antietam 1862

9/16/2014

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Antietam Somewhere

War Cry Heal Union
The summer series finale (10 of 10)

Honoring Constitution Day 2014 and 1862

“Hey Gus.”
“Hey Reb.”
“Our Once Upon A Time chat got interrupted yesterday …”
“Darn Squeak.”
“… Right,” continued Reb, “and welcome to Somewhere.”
“I’d say it’s nice like Nowhere,” Gus observed, “– and thistles too.”
“It wasn’t always this nice.”
“So where is Somewhere Reb?”
“Antietam.”
“No shi-kiddding?”
“No kidding.”
“So, the Dandies of Harlem Heights.”
“Yeah.”
“I figure,” Gus began, “you wanted me to see the problem.”
“What problem is that?”
“The problem of who got me shot,” Gus stated, “so you brought me the story of the battle through the eyes of the Yankee Doodle Dandies.”
“American Rebels.”
“And to show me the similarities between Leitch and the other soldier, the one killed on the field.”
“Thomas Knowlton.
“Yeah him: I remember Leitch died thirteen days later ~ sort of one day for each Stripe.”
“Nice reckoning.”
“So where we at on Antietam?”
“An orientation perhaps?”
“Great ... and is it Constitution Day in Somewhere, I mean Antietam, too?”
“Eternally Gus …”

Sharpsburg Somewhere

“You were here Johnny.”
“Yeah,” Reb panned, “the question is where were you in September 1862?”
“South Bend Indiana.”
“Indiana ‘eh.”
“Right, the 99th Volunteers were mustered into the US Army …” Gus paused: “I volunteered after …”
“After what?” Reb asked.
“… Antietam is the culmination of Robert E. Lee’s Maryland Campaign.”
“You volunteered in August 1862, right?”
“Did: the 99th was mustered into service 21 August 1862,” affirmed Gus and added, “- I see your suggestion Johnny.”
“Still need that orientation Yank?”
“Not really.”
“Whatcha’ thinking?”
“All these citizens Reb … their lives for what?”
“The bloodiest day in our heritage.”
“There’s something else, isn’t there?”
“Generally …”
“The Potomac’s near.”
“Yes.”
“Can we go there?” asked Gus.
“For a moment …”

Potomac Somewhere

“… Here it is.”
“Big.”
“Not so big …”
“No, the thing across it?”
“Bridge Yank.”
“Monster of a Bridge.”
“Yeah.”
“Is that Virginia?” wondered Gus.
"It is."
“So much talk about it ~ seems like a place to go.”
“Say more ..."
“Crossing a river is symbolic.”
“It’s been said so.”
“Can we …”
“Visit Virginia,” Reb pondered, “like maybe next year?”
“I’m available ~ you?”
“Think so.”
“Summer again Reb?”
“Feels like Spring.”
“Great.”
“It's Time to go Gus.”
“You hear something?”
“No ... just Time.”
“Thanks Reb.”
“Thanks Gus.”

Gus and Reb Somewhere Sunset

*In October, look for Ew Publishing’s mini-series, Whiskey 220: The Rebellion. Hosted on the BWB Blog, Whiskey 220 honors the successful conclusion to a domestic insurrection 220 years ago; it does so by highlighting President George Washington’s personal notes while traveling to inspect the State militias: the series includes a meeting with Virginia’s Governor Henry Lee III. Whiskey 220 begins Saturday, 11 October.

Thanks All!
~
Posted by Bryan W. Brickner

Video:
Johnny Cash sings Civil War songs

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1776: Gus Kotka, Johnny Reb and the Dandies of Harlem Heights

9/15/2014

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War Cry Heal Union: The series (9 of 10)

Once upon a time …

“Hey Gus.”
“Hey Reb ~ Where we at?”
“Once Upon A Time.”
“Once Upon A Time?” Gus quizzed, “you said we’d meet Somewhere next time.”
“I did,” Reb confirmed, “and tomorrow's Somewhere …”

Once Upon A Time Green Bean

“Great … then what’s with the green bean?”
“It’s a kitchen Gus.”
“Okay …”
“There’s a Dandy story here,” assured Reb, “and it’ll make our Somewhere time better.”
“A dandy one ‘eh?”
“The Dandies of Harlem Heights.”
“No kidding?” crafted Gus, “… then what goes with Once Upon A Time?”
“Burners …” offered Reb.”
“Burners?”
“… They like art.”
“Who’s Art?”
“… C’mon Gus ~ this way.”
“Sure thing Reb ~ though who’s Art? …”

Once Upon A Time Do Not Stop

“… Hey Reb ~ wait-a-Sec.”
“What now Yank?”
“Are we in Art's dream?”
“You can say that.”
“Then how come you and I are different?”
“Whatcha’ mean Yank?”
“Once Upon A Time? …” thought Gus, “How’d you do this?”
“I’m a composite Spirit,” answered Johnny Reb, “and you’re an individual Spirit Gus.”
“Okay …”
“You get to do your Spirit thing, be that US Army Private, 99th Indiana Infantry Regiment - ”
“Volunteer.”
“Yes, Volunteer Augustus Kotka, killed skirmishing the siege of Atlanta, 11 August 1864.”
“And you Reb? … How’d you die?”
“All the Johnnies Gus.”
“All? … You mean all the deaths?”
“Yes ~ and all the lives too.”
“Which is why you can do more …”
“Right.”
“It’s like …” Gus reasoned, “you’re a Macro and I’m a Micro Spirit.”
“Right again.”
“One more thing … Is that a piñata?”
“… Gus ~ C’mon …”

Once Upon A Time 48 Stars

“… Gus ~ Here we are.”
“What kind of flag is that?”
“’Merican.”
“The stars Reb …”
“Forty-eight.”
“Lots ~ so where are the Dandies?”
“Here, in the map.” [Richard Hanser, The Glorious Hour of Lt. Monroe, 1976:87.]
“Map’s too small Reb.”
“I know … I just wanted to say something.”
“Good ~ I like listening.”
“Sure you do …”
“I do ~ speak your peace Johnny.”
“The Stripes,” started Reb, “they represent the 13 Colonies in Rebellion.”
“Yes ~ and the Spirit of ’76.”
“And that Spirit had bodies … you know, humans.”
“Of course.”
“In the map are four American Rebels: a General, Colonel, Major and Lieutenant.”
“Officers.”
“Yes: Washington, Knowlton, Leitch and Monroe.”
“George and James for Washington and Monroe: who’s Knowlton?”
“Thomas Knowlton, Connecticut.”
“Say more …”
“Bunker Hill, 1775.”
“With ya’ now.”
“In the map it’s more than a year later,” Reb continued, “16 September 1776 and the New York Battle of Harlem Heights.”
“Who’s Leitch?”
“Andrew Leitch, Virginia … he’d been in New York four days.”
“Had been … what happened?”
“Washington has Knowlton’s Rangers skirmishing –”
“I know Skirmish.”
“– Against some Brits. Knowlton then leads the Rangers and the Third Virginia Regiment on a flanking movement. Knowlton is shot scouting the Brits; Major Leitch, as second in command, steps into the spot Knowlton was just in to assess the situation …”
“That’s the right move.”
“… Right Yank ~ ‘cept the Brits had the range and put three shots into Leitch.”
“Did they die? ~ Then I mean?”
“Knowlton on the field and Leitch thirteen days later.”
“Yankee Doodle Dandy Rebels ~ Knowlton and Leitch.”
“Yes, a Stripe for Connecticut …”
“… And a Stripe for Virginia.”
“Soldiers like Washington and Monroe,” Reb continued, “who give witness to such moments, often feel they were fighting …”
“For something.”
“… And not Against something Gus: Yankee Doodle Dandies fought For Free Speech and Enumerated Representation, you know, like our Nowhere chat,” Reb flickered, “~ Oh’oh …”
“What?”
“Time to go.”
“Already?”
“Heard a Noise.”
“Whatcha’ hear?”
“Squeak.”
“Who’s Squeak?”
“… Gus ~ Tomorrow's Somewhere.”
“I’m with ya’ Reb …”

Video: Yankee Doodle: Music of the American Revolution
~
*Tomorrow ~ US Constitution Day, 17 September 2014, the War Cry Heal Union summer series finale: Gus Kotka, Johnny Reb and Antietam 17 September 1862.

Posted by Bryan W. Brickner

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Homeostasis: Publius’ (Ultralow) THC Political Cannabinoid Science

9/5/2014

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The 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

Once Upon A Time ...

Posted by Bryan W. Brickner

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Homeostasis: Publius’ Sleep Political Cannabinoid Science

Homeostasis: Equinox Serotonin (5HT) Headache Stories

Constitution Day: Gus Kotka, Johnny Reb and Antietam 1862

1776: Gus Kotka, Johnny Reb and the Dandies of Harlem Heights

Homeostasis: Publius’ (Ultralow) THC Political Cannabinoid Science

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