Endocannabinoid System Thread

[ClearBlueLou]

Loving this thread, y’all...I only understand parts, but what I understand makes a ton of sense. Keep the party moving!

 

[C No Ego]

Loving this thread, y’all...I only understand parts, but what I understand makes a ton of sense. Keep the party moving!

going on 8 years now with spare time dedicated to this... really the last two years I have learned the most.

the most basic explanation is- cannabis' active compounds metabolize into the cell receptors and regulate / modulate the enzymes and hormones that drive cell metabolism = homeostasis... that is the main functioning of the ECS, to maintain cellular homeostasis of every bio-chemical signal and intracellular message that's formed from arachidonic acid. all oxidative reactions, cellular respiration and lipid metabolism is modulated by the cannabinoids in the ECS

 

[ClearBlueLou]

The big takeaway for me is that humans and cannabis have been actively interacting with each other for far longer than what we know as ‘civilization’ has existed, truly a botanical partner for our entire dirt-walk.

I’ve always been fascinated by biology, physiology, etc; I work with bodies and their issues professionally, and I study for fun...my knowledge of the ECS is rudimentary, but its significance isn’t lost on me.

 

[C No Ego]

The big takeaway for me is that humans and cannabis have been actively interacting with each other for far longer than what we know as ‘civilization’ has existed, truly a botanical partner for our entire dirt-walk.

exactly- the biomimicry of the phytocannabinoids in our ECS too relate to how carbon based life forms ( chordate life) use molecular structures to inform the cells of biological information that drives the metabolism of the life form.

the big question still= why did / does cannabis create phytocannabinoids that is such a great mimetic to our endogenous cannabinoids?

I've seen reports showing that the phytocannabinoids in the trichome serve as anti oxidants to protect the plant from UV rays. they also serve to look like spiders eyes and keep insects away... the cannabinoid crystals in the clear trichome refract like spider eyes! Also, another hypothesis is that the phytocannabinoids serve to inebriate the herbivore and keep it away from the plant, Except raw on the plant phytocannabinoids are non psychoactive and needs heating to become psychoactive so not sure on that one.

one thing is for sure... life moves in a certain way and all life will be reflective throughout the creation with all of the molecules created in nature to build solid mass and express life through that mass...

 

[C No Ego]

ECS research will surge when we can examine the carbon active forms (carboxyl group intact, non decarboxylated, acidic form ) of the cannabis cannabinoids...

new info is showing that the acidic cannabinoids can actually pass the blood brain barrier... we have not isolated the isoforms that show how yet though.

IMO, the carbon active enzymes still in tact on the phyto-molecule will provide a fresher type oxidant cannabimimetic reaction on our receptors. intracellular access is not as immediate with the acidic forms but just like CBD serves to modulate enzymes so too will the acidic cannabinoids...

when we heat the cannabinoids ,it is an oxidative reduction reaction that takes away the carboxyl chain grouping from the molecule and the molecule then compounds in upon itself to serve as an active molecular compound structure...

 

[C No Ego]

a Few more Reads ... enjoy

A Personal Retrospective: Elevating Anandamide (AEA) by Targeting Fatty Acid Amide Hydrolase (FAAH) and the Fatty Acid Binding Proteins (FABPs)
Dale G. Deutsch*

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062061/


Getting High on the Endocannabinoid System

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/

Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection

https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-015-0012-0

 

[ClearBlueLou]

You can burn fat quite efficiently without carbohydrates, in fact there is no actual biological "need" for carbohydrates in the human diet. Fat and Protein yes, carb no. Unfortunately there is still way too much dogma out there.

As for "normal" metabolic state.... "normal" actually these days is in fact "metabolically deranged", as most people are sugar burners as opposed to mainly fat burners.

The brain *REQUIRES* sugar. If your body doesn’t have enough glucose to fuel the brain, the the body will break down proteins and make sugar out of them. It’s called neoglucogenesis, and it happens. When you’re in fat-burning ‘ketotic’ mode, sugars are handled by the body very differently than the usual store-what-you-can’t-burn method.

I’ll add a search term: Dr. Robert Melemede. He’s a retired professor of biology who’s been working with the ECS for a long time. He has two videos on his YouTube channel, the longer one, with the podium, has better audio. They are largely the same speech, but as he says, he usually teaches this stuff in a classroom over the course of a year. VERY illuminating and thought-provoking stuff.

 

[florduh]

The brain *REQUIRES* sugar. If your body doesn’t have enough glucose to fuel the brain, the the body will break down proteins and make sugar out of them. It’s called neoglucogenesis, and it happens. When you’re in fat-burning ‘ketotic’ mode, sugars are handled by the body very differently than the usual store-what-you-can’t-burn method.

I’ll add a search term: Dr. Robert Melemede. He’s a retired professor of biology who’s been working with the ECS for a long time. He has two videos on his YouTube channel, the longer one, with the podium, has better audio. They are largely the same speech, but as he says, he usually teaches this stuff in a classroom over the course of a year. VERY illuminating and thought-provoking stuff.

The brain does require sugar. But when the body doesn't have enough sugar to process, the liver starts producing ketones to power the brain. Those ketones are produced from fatty acids. If ancient humans required a steady flow of carbs to power their brains, we wouldn't be here right now.

While the research isn't settled, it appears that a ketogenic diet has profound neuroprotective effects and at least one study showed marked improvement for Alzheimer's patients.

Source

 

[biohacker]

It’s called neoglucogenesis, and it happens.

I've only seen it referred to as gluconeogenesis.... and thank you @florduh for saving my keystrokes.

 

[C No Ego]

The brain does require sugar. But when the body doesn't have enough sugar to process, the liver starts producing ketones to power the brain. Those ketones are produced from fatty acids. If ancient humans required a steady flow of carbs to power their brains, we wouldn't be here right now.

While the research isn't settled, it appears that a ketogenic diet has profound neuroprotective effects and at least one study showed marked improvement for Alzheimer's patients.

Source

one of the reports I read showed that sugar as fuel provides about 4% sustained energy while lipid as fuel provides 35 to 40% sustained energy. I think it was the HUFAs /PUFAs reports on pro resolving lipid mediators

 

[ClearBlueLou]

I’ve heard it both ways, but you’re right, it’s usually rendered as gluconeogenesis.

 

[invertedisdead]

Also, another hypothesis is that the phytocannabinoids serve to inebriate the herbivore and keep it away from the plant, Except raw on the plant phytocannabinoids are non psychoactive and needs heating to become psychoactive so not sure on that one.

For example birds are not sensitive to capsaicin in chili peppers, thus they can feed on the hot seeds with no heat induced effects, where as other animalia would be turned off by the burning. Perhaps it is similar with cannabis, and there are a range of species that are directly affected by those acidic cannabinoids.

 

[ClearBlueLou]

Sticky, smelly terpene-laden resin could glue a critter’s eyes shut or otherwise interfere with vision, the sense of smell, might induce panic since it can’t be rubbed off...I imagine a lot of critters wouldn’t want to deal with a plant like that

 

[C No Ego]

For example birds are not sensitive to capsaicin in chili peppers, thus they can feed on the hot seeds with no heat induced effects, where as other animalia would be turned off by the burning. Perhaps it is similar with cannabis, and there are a range of species that are directly affected by those acidic cannabinoids.

WOW! do terpenes decarb cannabinoids??? Wow man I just had an AH HA moment there... thank you!

reading this one the last few days
Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943808/

seeing all kinds of referencing in there to cannabinoids yet they do not say it specifically...
like this- quote " Natural or pharmacological ligands (fatty acids and fibrates, respectively) primarily control the expression of genes involved in lipid metabolism "
Ligands are cannabinoids ETC

after learning ECS it is great to fill in the blanks on some of this bio-active lipid based research as they just do not have the canna lingo to explain the bio-chemical pathways...
I'm sure to there are some scientists who just refuse Canna knowledge too as their background is just to pompous to even go there LOL

 

[C No Ego]

Really enjoying this article relating the arachidonic acid pathways and plant evolution

Targeted metabolomics shows plasticity in the evolution of signaling lipids and uncovers old and new endocannabinoids in the plant kingdom

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264637/

and a list of articles from this author =
https://www.ncbi.nlm.nih.gov/pubmed/?term=Gertsch J[Author]&cauthor=true&cauthor_uid=28120902

 

[C No Ego]

interesting article about the history of identifying the active properties in cannabis

https://www.theroc.us/researchlibra... chemistry to endocannabinoids and beyond.pdf

found here= https://www.theroc.us/research

 

[ClearBlueLou]

One fact I learned early is that - at the time - we knew more about cannabis than we did about aspirin, in terms of how they do what they do and how they’re built.

Cannabis has an enormous number of chemicals, our cannabinoids, that occur in no other plant. The only other plant I know of that also has an enormous number of chemical components unique to it AND is credited with age old value in medicine is ginseng.

Interestingly, they are both adaptogens, and they may be tied for “most important medicinal plant on the planet”.
I find the idea of using ginseng with high-dose cannabis provokes my interest.

.

WOW! do terpenes decarb cannabinoids??? Wow man I just had an AH HA moment there... thank you!

reading this one the last few days
Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943808/

seeing all kinds of referencing in there to cannabinoids yet they do not say it specifically...
like this- quote " Natural or pharmacological ligands (fatty acids and fibrates, respectively) primarily control the expression of genes involved in lipid metabolism "
Ligands are cannabinoids ETC

after learning ECS it is great to fill in the blanks on some of this bio-active lipid based research as they just do not have the canna lingo to explain the bio-chemical pathways...
I'm sure to there are some scientists who just refuse Canna knowledge too as their background is just to pompous to even go there LOL

Well, no one likes to hear that their area of specialty is actually governed by something else they don’t know anything about. It’s predictable there’d be scoffing and ignoring, but that can’t last, the evidence is there, the research could be shuttered, but hopefully researchers would keep data from being lost.

 

[ClearBlueLou]

Did I’d again...

 

[C No Ego]

One fact I learned early is that - at the time - we knew more about cannabis than we did about aspirin, in terms of how they do what they do and how they’re built.

Cannabis has an enormous number of chemicals, our cannabinoids, that occur in no other plant. The only other plant I know of that also has an enormous number of chemical components unique to it AND is credited with age old value in medicine is ginseng.

Interestingly, they are both adaptogens, and they may be tied for “most important medicinal plant on the planet”.
I find the idea of using ginseng with high-dose cannabis provokes my interest.

.

Well, no one likes to hear that their area of specialty is actually governed by something else they don’t know anything about. It’s predictable there’d be scoffing and ignoring, but that can’t last, the evidence is there, the research could be shuttered, but hopefully researchers would keep data from being lost.

parts of the known wording describing the pathways was created by Weed scientists LOL
other scientists looking into it then need to use terms associated with Weed - oh the thought !
until this info is taught in medical schools scientists will be putting down weed science and missing out on new findings of bio-activity

 

[Tranquility]

the big question still= why did / does cannabis create phytocannabinoids that is such a great mimetic to our endogenous cannabinoids?

Roll of the dice. (Unless the Virus was of God or Aliens and intended for the effect.) Then, we tended to choose the plants infected.
https://www.sciencedaily.com/releases/2018/11/181126105506.htm

Summary: THC and CBD, bioactive substances produced by cannabis and sought by medical patients and recreational users, sprung to life thanks to ancient colonization of the plant's genome by viruses, researchers have found.
​

Now, for the reason I came here. No matter if the entourage effect is real or not, get ready to hear about it everywhere.
https://mjbizdaily.com/entourage-effect-marketing-by-cannabis-companies/

 

[invertedisdead]

Now, for the reason I came here. No matter if the entourage effect is real or not, get ready to hear about it everywhere.
https://mjbizdaily.com/entourage-effect-marketing-by-cannabis-companies/

While the "entourage effect" might be labeled as a cannabis term, the principal concept is already scientifically defined and studied under the biological term "synergism." In fact I would argue this concept of "whole plant healing" is the opposite of new marketing, and dates back thousands of years, at least as far back as ancient Chinese medicine and Ayurvedic teachings.

 

[Tranquility]

While the "entourage effect" might be labeled as a cannabis term, the principal concept is already scientifically defined and studied under the biological term "synergism." In fact I would argue this concept of "whole plant healing" is the opposite of new marketing, and dates back thousands of years, at least as far back as ancient Chinese medicine and Ayurvedic teachings.

I believe the cool kids would rather the term ensemble effect (As it is not a single driver being followed. https://hightimes.com/culture/the-ensemble-effect-not-the-entourage-effect-says-dr-grinspoon/ ); but, synergy is fine by me.

However, we are not going to be hearing it from the marketers just on whole plant healing, but on distilled chemicals from different sources and recombined in a way the recombiner feels is natural or works. It will not be used in some high thinking (heh) philosophy in regards to natural balance in regards to flower. You'll see the same natureific ad of evergreen trees and babbling brooks with healthy young beautiful people relaxing after a hard fought game of Ultimate while rubbing some of the full-spectrum cannabis ointment on each other's backs with nothing but "Naturally Healing" whispered in the clouds. For how far they will stretch the claims until they come up against the government for promising to treat or cure a disease no one can know.

 

[invertedisdead]

However, we are not going to be hearing it from the marketers just on whole plant healing, but on distilled chemicals from different sources and recombined in a way the recombiner feels is natural or works. It will not be used in some high thinking (heh) philosophy in regards to natural balance in regards to flower. You'll see the same natureific ad of evergreen trees and babbling brooks with healthy young beautiful people relaxing after a hard fought game of Ultimate while rubbing some of the full-spectrum cannabis ointment on each other's backs with nothing but "Naturally Healing" whispered in the clouds. For how far they will stretch the claims until they come up against the government for promising to treat or cure a disease no one can know.

Lmao! I agree 100%, they (big canna) will need to heavily market an entourage effect for all the fractionated and fragmented products that don't actually have one.

You already know how it goes in California with all the distillate pens and their "therapeutic organic plant derived strain specific terpenes" pieced together from various vegetables

 

[ClearBlueLou]

I confess, I’m just an old tree-hugging hippie freak, I don’t like a lot of what I see in the rise of industrial canna. Like other industrial cartels, extraction economics (if allowed to dig in) are the basis of business these days (and I *don’t* mean making extracts), so exploitation in all its horrific glories is preparing to drink deep of the plant and the users and the marketplace while providing as little as possible in return, just like Big Paper, Big Oil, Big Pharma, Big Chem, Wall Street....

I’ve spent the bulk of my life, more than 50 years, learning about and learning to appreciate cannabis. The potential for industrial cannabis in the present world is HUGE, and expanding as we learn to apply what we know, but Big Weed doesn’t care about that at all. Big Weed will cock-block true commercial-industrial development of the hemp side of cannabis in its monofocus on selling flowers and flower extracts. Big Weed will protect its Big brothers by sidelining everything but WEED.

This strikes me as a shocking waste of resources legal, economic, commercial, and constitutional.

It reinforces my sense that the biggest issue we’re struggling with is that the entire narrative is dominated by one class of cannabis products, the tonic/euphoric/medicinal class. We are not talking about THE PLANT, we’re arguing over every other red herring conceivable. We need THE PLANT to be legal, that conversation has to be based on sound common sense, of which shifting views on *weed* cannabis are only a part.

This isn’t a moral argument about whether hippies should get stoned, or about whether they’ll get kids high, or about whether they’ll go berserk. It’s a constitutional matter, as we have a clear 9th amendment right to grow plants, do things with them, make things out of them, and use them. It a legal matter, as hundreds of thousands languish in jail for cannabis-related infractions, millions carry prison records for cannabis-related infractions, and the plant itself is under attack from those who want to own cannabis genetics.

The commercial and economic importance of ensuring a return of cannabis to normal commerce can’t be overestimated, but it needs a strongly-established foundation, and the only way to do that is to sideline the question of ‘legal weed’ and deal with the legal status of the plant, cannabis, as an agricultural product.

 

[Tranquility]

It’s a constitutional matter, as we have a clear 9th amendment right to grow plants, do things with them, make things out of them, and use them.

While I liked and generally agree with your post, this sentence is not accurate. I would like it to be, but it is not. While a good libertarian interpretation of the Bill of Rights might agree, bazillions of cases at many levels that have addressed that argument have found differently. (Often with the additional constitutional claim the person was growing for his own intrastate use and, thus, the Commerce Clause would prevent federal regulation.)

The problem is, either we want more federal government or we want more limitations on federal government. The Constitution is the limiting document. Gonzales v. Raich was the case that gave the finger to the medical movement but was more in keeping with the theory of government power is always good thing as the government just represents all of us. Today's court make up might come to a different conclusion except, being conservative, assign a higher value to precedent than those on the left might like. That sets up the dichotomy if facts like Raich come up again as the assumed position of the justices are switched in this situation.

I prefer the dissent from O'connor that concludes (From Wikipedia):

Relying on Congress’ abstract assertions, the Court has endorsed making it a federal crime to grow small amounts of marijuana in one’s own home for one’s own medicinal use. This overreaching stifles an express choice by some States, concerned for the lives and liberties of their people, to regulate medical marijuana differently. If I were a California citizen, I would not have voted for the medical marijuana ballot initiative; if I were a California legislator I would not have supported the Compassionate Use Act. But whatever the wisdom of California’s experiment with medical marijuana, the federalism principles that have driven our Commerce Clause cases require that room for experiment be protected in this case.
​

As well as Thomas' dissent argument(From Wikipedia):

Respondents Diane Monson and Angel Raich use marijuana that has never been bought or sold, that has never crossed state lines, and that has had no demonstrable effect on the national market for marijuana. If Congress can regulate this under the Commerce Clause, then it can regulate virtually anything—and the Federal Government is no longer one of limited and enumerated powers.

Respondent's local cultivation and consumption of marijuana is not "Commerce ... among the several States."
[...]
Certainly no evidence from the founding suggests that "commerce" included the mere possession of a good or some personal activity that did not involve trade or exchange for value. In the early days of the Republic, it would have been unthinkable that Congress could prohibit the local cultivation, possession, and consumption of marijuana.
[...]
If the Federal Government can regulate growing a half-dozen cannabis plants for personal consumption (not because it is interstate commerce, but because it is inextricably bound up with interstate commerce), then Congress' Article I powers – as expanded by the Necessary and Proper Clause – have no meaningful limits. Whether Congress aims at the possession of drugs, guns, or any number of other items, it may continue to "appropria[te] state police powers under the guise of regulating commerce."
[...]
If the majority is to be taken seriously, the Federal Government may now regulate quilting bees, clothes drives, and potluck suppers throughout the 50 States. This makes a mockery of Madison's assurance to the people of New York that the "powers delegated" to the Federal Government are "few and defined", while those of the States are "numerous and indefinite."
​

Remember, though, those quotes were from the dissent. They were the losing argument.

Again.