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March Homeostasis: Publius’ Go Endo-Cannabinoid Update

3/28/2015

The Cannabis Papers by Publius (2011)

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

Go Endo Health Edition

Health is an endo thing. As we learn more about our cannabinoid system (CS), we also learn more about health: in fact, the CS is where health begins. In celebration of CS homeostatic health, or endo-healing, here are four 2015 PubMed science stories discussing: cannabinoids in the treatment of late-onset Alzheimer’s disease (LOAD), an anti-epileptogenic approach based on the endo 2-AG, toll-like receptors mediating immune responses via the CS, and rheumatoid arthritis and the multiple regulatory functions of the CS – the endo 2-AG highlighted.

Go Endo All!

I. Late-Onset Alzheimer’s Disease (LOAD) and the CS
“Given the lack of effective treatments for late-onset Alzheimer's disease (LOAD) and the substantial burden on patients, families, healthcare systems, and economies, finding an effective therapy is one of the highest medical priorities. The past few years have seen a growing interest in the medicinal uses of cannabinoids, the bioactive components of the cannabis plant, including the treatment of LOAD and other physical conditions that are common in older people. Several in vitro and in vivo studies have demonstrated that cannabinoids can reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles, the key hallmarks of LOAD. Also, in population-based studies, cannabinoids reduced dementia-related symptoms (e.g., behavioral disturbances). The current article provides an overview of the potential of cannabinoids in the treatment of LOAD and related neuropsychiatric symptoms in older people. We also discuss the efficacy, safety and pharmacokinetics of cannabinoid-based drugs in older people with dementia.”
Cannabinoids in late-onset Alzheimer's disease.
Ahmed AI, van der Marck MA, van den Elsen GA, Olde Rikkert MG.
Clin Pharmacol Ther. 2015 Mar 18. doi: 10.1002/cpt.117. [Epub ahead of print]
PMID: 25788394 [PubMed - as supplied by publisher]
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II. Kindling Model of Temporal Lobe Epilepsy and the CS (2-AG)
“Endocannabinoids, including 2-arachidonoylglycerol (2-AG), activate presynaptic cannabinoid type 1 receptors (CB1R) on inhibitory and excitatory neurons, resulting in a decreased release of neurotransmitters. Event-specific activation of the endocannabinoid system by inhibition of the endocannabinoid degrading enzymes may offer a promising strategy to selectively activate CB1Rs at the site of excessive neuronal activation with the overall goal to prevent the development epilepsy. The aim of this study was to investigate the impact of monoacylglycerol lipase (MAGL) inhibition on the development and progression of epileptic seizures in the kindling model of temporal lobe epilepsy. … In conclusion, the data demonstrate that indirect CB1R agonism delays the development of generalized epileptic seizures, but has no relevant acute anticonvulsive effects. Furthermore, we confirmed that the effects of JZL184 on kindling progression are CB1R mediated. Thus, the data indicate that the endocannabinoid 2-AG might be a promising target for an anti-epileptogenic approach."
Inhibition of monoacylglycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice.
von Rüden EL, Bogdanovic RM, Wotjak CT, Potschka H.
Neurobiol Dis. 2015 Mar 18. pii: S0969-9961(15)00088-1. doi: 10.1016/j.nbd.2015.03.016. [Epub ahead of print]
PMID: 25796567 [PubMed - as supplied by publisher]
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III. Toll-Like Receptors (TLRs), Immune Responses and the CS
“Toll-like receptors (TLRs) mediate the innate immune response to pathogens and are critical in the host defence, homeostasis and response to injury. However, uncontrolled and aberrant TLR activation can elicit potent effects on neurotransmission and neurodegenerative cascades and has been proposed to trigger the onset of certain neurodegenerative disorders and elicit detrimental effects on the progression and outcome of established disease. Over the past decade, there has been increasing evidence demonstrating that the endocannabinoid system can elicit potent modulatory effects on inflammatory processes, with clinical and preclinical evidence demonstrating beneficial effects on disease severity and symptoms in several inflammatory conditions. This review examines the evidence supporting a modulatory effect of endocannabinoids on TLR-mediated immune responses both peripherally and centrally, and the implications for psychiatric disorders such as depression and schizophrenia.”
For whom the endocannabinoid tolls: Modulation of innate immune function and implications for psychiatric disorders.
Henry RJ, Kerr DM, Finn DP, Roche M.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 17. pii: S0278-5846(15)00055-X. doi: 10.1016/j.pnpbp.2015.03.006. [Epub ahead of print]
PMID: 25794989 [PubMed - as supplied by publisher]
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IV. Rheumatoid Arthritis and the CS
“Since the discovery of the endogenous receptor for Δ9-tetrahydrocannabinol, a main constituent of marijuana, the endocannabinoid system (comprising cannabinoid receptors and their endogenous ligands, as well as the enzymes involved in their metabolic processes) has been implicated as having multiple regulatory functions in many central and peripheral conditions, including rheumatoid arthritis (RA). RA is an immune-mediated inflammatory disease that is associated with the involvement of many kinds of cells (such as fibroblastlike synoviocytes [FLSs], osteoclasts, T cells, B cells, and macrophages) and molecules (such as interleukin-1β, tumor necrosis factor-α, interleukin-6, matrix metalloproteinases [MMPs], and chemokines). Increasing evidence suggests that the endocannabinoid system, especially cannabinoid receptor 2 (CB2), has an important role in the pathophysiology of RA. Many members of the endocannabinoid system are reported to inhibit synovial inflammation, hyperplasia, and cartilage destruction in RA. In particular, specific activation of CB2 may relieve RA by inhibiting not only the production of autoantibodies, proinflammatory cytokines, and MMPs, but also bone erosion, immune response mediated by T cells, and the proliferation of FLSs. In this review, we will discuss the possible functions of the endocannabinoid system in the modulation of RA, which may be a potential target for treatment.”
The endocannabinoid system and its therapeutic implications in rheumatoid arthritis.
Gui H, Tong Q, Qu W, Mao CM, Dai SM.
Int Immunopharmacol. 2015 Mar 16. pii: S1567-5769(15)00100-9. doi: 10.1016/j.intimp.2015.03.006. [Epub ahead of print] Review.
PMID: 25791728 [PubMed - as supplied by publisher]
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Today’s "Yes We Can" Video: Smoking Weed with the President of Uruguay: Full Length

Posted by Bryan W. Brickner

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Constitutional Love Fever: Gus Kotka, Johnny Reb and Heal Union 2015

3/20/2015

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Heal Union 1: The 2015 spring series begins

Light Lincoln Lee

"We in Virginia Reb?"
“Not today Yank.”
“Where we at?”
“Lee’s.”
“Robert E.’s?”
“No,” clarified Johnny Reb.
“Just a dude named Lee ...”
“Lee was a soldier,” added Reb, “US Army.”
“Lee around?”
“He’s a Spirit – like us.”
“I get it,” Gus noted.
“Let’s go inside – there’s something to show you.”
“Sounds fun.”
“You get to make a choice Yank.”
“Choice? – Spirits don’t get many choices Reb,” Gus paused, “that’s more of a human thing.”
“Different today.”
“A kind day, eh?”
“We’ll see …”

Johnny's Gus Choices

“Fancy pictures Reb.”
“They’re the choices Gus.”
“How so?”
“Pick one, you know.”
“Well, what’s an I-star?”
“Goddess.”
“Okay,” Gus smiled and continued, “and the 'Love Fever' gents in the middle …”
“The O’ Jays.”
“… Well, one’s gotta say love fever looks happy.”
“Agreed.”
“Pilgrim’s Progress,” observed Gus, “why that’s one we both know, eh’ Johnny?”
“True.”
“And another goddess.”
“Correct.”
“Choosing between goddesses,” Gus pondered, “there’s probably a fair amount of stories written on that.”
“Paris.”
“No Reb," Gus offered, "pretty sure that’s a city in France, yet what we have here is obvious.”
“It is.”
“Yeah – I figure you want me to pick the middle one, the one with those three rebels.”
“Rebels?”
“Yeah, they dress like rebels,” Gus followed, “you know, no uniforms and wear whatever.”
“Oh.”
“What army they in?”
“Arts.”
“Art’s got an army?”
“Sure.”
“Art’s Army,” Gus stated, “bunch of rebels, eh’?”
“Is that your choice Yank?”
“Sure is, the O’ Jays: now what?”
“Nothing.”

Reb Yank Fade

“Nothing?”
“Nothing today,” explained Reb, “yet a choice yields results.”
“Like volunteering.”
“Right Gus, like volunteering.”
“Reb, I can’t see anymore … can you?”
“Barely.”
“Time to fade, eh’ Johnny?”
“Time.”
“The O’ Jays,” Gus expressed, “their love fever looks constitutional.”
“You don’t say.”
“Yeah – and there was a doll at the beginning … did Lee have a …”
“Gladys.”
“Nice … Hey, is Virginia next?”
“We’re on our way.”
“Great.”
“Thanks Gus ~ you’re okay!”
“Thanks Johnny ~ you too!”

Today's Video: The O' Jays and I Love America.

*Next in the Heal Union series: Richmond Burns and A.P. Hill Dies, a 150th remembrance essay on Thursday, 2 April 2015.

Posted by Bryan W. Brickner

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Homeostasis: Spring Equinox Serotonin (5HT) Brain Stories

3/19/2015

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5HT Receptor Ribbon (by S. Jahnichen)

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

Spring Serotonergic Equinox

Equinox and homeostasis are mid-point extremes and today’s serotonin system science looks at 5HT (5-hydroxytryptamine) and its role in modulating another extreme, our brains. Below are three short science stories from the National Institutes of Health (PubMed). The serotonin equinox tales include: dopamine and serotonin neuronal interactions, maps of widespread 5HT receptor distribution in the prefrontal cortex, and impulsivity in binge drinkers (tryptophan metabolism).

Spring Equinox Health All!

I. Interactions Between Dopaminergic and Serotonergic Neuronal Systems
“The complex integration of neurotransmitter signals in the nervous system contributes to the shaping of behavioral and emotional constitutions throughout development. Imbalance among these signals may result in pathological behaviors and psychiatric illnesses. Therefore, a better understanding of the interplay between neurotransmitter systems holds potential to facilitate therapeutic development. Of particular clinical interest are the dopaminergic and serotonergic systems, as both modulate a wide array of behaviors and emotions and have been implicated in a wide range of affective disorders. Here we review evidence speaking to an interaction between the dopaminergic and serotonergic neuronal systems across development. We highlight data stemming from developmental, functional, and clinical studies, reflecting the importance of this transmonoaminergic interplay.”
Functional interplay between dopaminergic and serotonergic neuronal systems during development and adulthood.
Niederkofler V, Asher TE, Dymecki SM.
ACS Chem Neurosci. 2015 Mar 8. [Epub ahead of print]
PMID: 25747116 [PubMed - as supplied by publisher]
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II. Prefrontal Cortex Maps of Widespread Distribution of 5-HT Receptors
“Since the development of chemical neuroanatomical tools in the 1960's, a tremendous wealth of information has been generated on the anatomical components of the serotonergic system, at the microscopic level in the brain including the prefrontal cortex (PFC). The PFC receives a widespread distribution of serotonin (5-hydroxitryptamine, 5-HT) terminals from the median and dorsal raphe nuclei. 5-HT receptors were first visualized using radioligand autoradiography in the late 1980's and early 1990's and showed, in contrast to 5-HT innervation, a differential distribution of binding sites associated with different 5-HT receptor subtypes. … Tract tracing technology allowed a detailed cartography of the neuronal connections of PFC and other brain areas. Based on these data, maps have been constructed that reflect our current understanding of the different circuits where 5-HT receptors can modulate the electrophysiological, pharmacological and behavioral functions of the PFC.”
Cartography of 5-HT1A and 5-HT2A receptor subtypes in prefrontal cortex and its projections.
Mengod G, Palacios JM, Cortes R.
ACS Chem Neurosci. 2015 Mar 5. [Epub ahead of print]
PMID: 25739427 [PubMed - as supplied by publisher]
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III. Impulsivity, Binge Drinkers and Serotonergic Mechanisms (Tryptophan)
“Researchers have suggested binge drinkers experience disproportionate increases in impulsivity during the initial period of drinking, leading to a loss of control over further drinking, and that serotonergic mechanisms may underlie such effects. We examined the effects of a simulated alcohol binge and tryptophan depletion on 3 types of impulsivity-response initiation (immediate memory task [IMT]), response inhibition (GoStop task), and delay discounting (single key impulsivity paradigm [SKIP])-and tested whether observed effects were related to real-world binging. Adults (N = 179) with diverse drinking histories completed a within-subject crossover design over 4 experimental days. … Effects of alcohol and tryptophan manipulations on impulsivity were unrelated to patterns of binge drinking outside the laboratory. The effects of alcohol consumption on impulsivity depend on the component of impulsivity and the dose of alcohol consumed. Such effects do not appear to be a result of reduced serotonin synthesis.”
Effects of Tryptophan Depletion and a Simulated Alcohol Binge on Impulsivity.
Dougherty DM, Mullen J, Hill-Kapturczak N, Liang Y, Karns TE, Lake SL, Mathias CW, Roache JD.
Exp Clin Psychopharmacol. 2015 Mar 2. [Epub ahead of print]
PMID: 25730415 [PubMed - as supplied by publisher]
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Today’s Video: 5HTP benefit and side effects of 5htp, dosage, anxiety, weight loss, sleep

*Next: Saturday 21 March, the spring series Heal Union 2015 begins with Constitutional Love Fever: Gus Kotka, Johnny Reb and a few others.

Posted by Bryan W. Brickner

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Make Id Happen: International Women’s Day and Hannah Arendt Footnotes #2

3/6/2015

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Arendt Footnotes #2

(AF2 ~ second in a series)

Just Do Id

Jeremy Bentham (1748-1832) and utilitarianism as “universalized egoism” are the focus today with International (a word Bentham coined) Women’s Day as the lens. Let’s begin with the Footnote, #72, first this time, from Arendt’s The Human Condition (bold added):

“72. … His [Bentham] chief objection is that utility is not measurable and there fore does not ‘lead us to the consideration of the number,’ without which a ‘formation of the standard of right and wrong’ would not be possible. Bentham derives his happiness principle from the utility principle by divorcing the concept of utility from the notion of usage (see ch. 1, par. 3). This separation marks a turning point in the history of utilitarianism. For while it is true that the utility principle had been related primarily to the ego prior to Bentham, it is only Bentham who radically emptied the idea of utility of all reference to an independent world of use things and thus transformed utilitarianism into a truly ‘universalized egoism’ (Halevey).”

Hannah Arendt and Mother (1912)

Our beginning approach to Arendt’s work, called “love piracy,” is a metaphor. Our times our political and she lived and wrote political theory, so it’s like we can read her to see what concepts work fifty years on (her book was published in 1958).

Love piracy was something I learned in a political theory class at Purdue; it’s an open approach to knowledge (the text) while looking for things useful … oops, Arendt again. Today’s post is on utilitarianism, the famed theory of Jeremy Bentham that influenced world economics in the same way as Adam Smith and Karl Marx. Arendt is only footnoting this, speaking casually in a passing way, in regard to the utter vacuum within Bentham’s utilitarianism (where Nothing is ever useful).

Arendt notes that when Bentham derived “his happiness principle from the utility principle” he divorced it from usage; he had to in order to preserve a morality – a right and wrong. Yet there’s more; this divorce exposes (reveals) the culprit: the ego.

This too is Arendt as The Human Condition (THC) is a review of making; she focuses on the politics of making and ends up asking: is all of our making the problem?

She doesn’t stop there though; Arendt builds on the distinction between homo faber and animal rationale in THC; her work questions the making human (homo faber) as the future and suggests we take a clearer look (at ourselves) through the lens of animal rationale.

Id is Latin for “it.” Make It Happen, the theme for this year’s International Women’s Day, can also mean Make Id Happen – a focus on making things like water, food and shelter (animal basics) international priorities – for all of us.

Happy International Women’s Day All!

Today’s Video: First Lady Michelle Obama Honors International Women of Courage (8 March 2012)

Posted by Bryan W. Brickner

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March Homeostasis: Publius’ Go Endo-Cannabinoid Update

Constitutional Love Fever: Gus Kotka, Johnny Reb and Heal Union 2015

Homeostasis: Spring Equinox Serotonin (5HT) Brain Stories

Make Id Happen: International Women’s Day and Hannah Arendt Footnotes #2

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