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The Endocannabinoid System: Is It Really Millions of Years Old?

Recently discovered you have an endocannabinoid system, or ECS? Want to know how old it is? Check out this great post from Darby Hemp writers on the subject and find out.


We'll begin with something a bit more familiar to many of us, the poetic whit of Dr. Seuss:


“You'll get mixed up, of course, as you already know.

You'll get mixed up with many strange birds as you go.

So be sure when you step.

Step with care and great tact and remember that Life's a Great Balancing Act.

Just never forget to be dexterous and deft.

And never mix up your right foot with your left.”


An extraordinary well-suited quote for what follows...


Introduction

If you were ever to be tasked with researching or covering a complex and emergent topic like the Endocannabinoid System (ECS), local caffeine hubs have much to offer.


As an example, in the picture below is part of a large roasting operation in Bellingham Washington with a full seating area and fireplace. There you could sip/smell a cup of Joe derived from beans roasted mere feet from where you'd be busy reading with my earbuds in, listening to ambient soundtrack music and taking notes - it’s a loud process after all, roasting and bagging coffee.

Imagine as you're sitting within earshot of that contraption sipping and researching, a funny event unfolds we can use to begin our conversation about your ECS.


To the left in that picture is a public access door.


Let's say you're neck-deep in a PubMed article concerning the ECS and human energy balance and suddenly above the tranquil Jeremy Soule playing in your ears you hear an obvious hound dog barking a steady...roh roh roh…roh roh roh…roh...slight pause… then back into it tempo.


Roh roh roh...roh roh roh...roh...


Someone tied up their dog-duo outside to keep an eye on things while retrieving their mud.


They both look male, but let's say you're a horrible judge.


The hound's older, droopier, while the other dog is leaner, with a younger profile; almost a hound dog-sized lighter-coated wolf with much shorter hair. Anyway, the fascinating part (because of what you were just reading) is their divergent behavior.


Dog 1 - Even ECS Line: perfectly calm, sitting stoically, not so much as moving a muscle and glaring into the window with a half-bored half-annoyed look thanks to our good buddy the...


Hound Dog - ECS Deficiency: who's not only visibly bothered, constantly moving and changing positions, but barking as he nervously stares into the glass. His clearly much older body’s language is disturbed.


Such a dramatic difference in energy usage!


This is at the core of why hemp farming and extraction operations are springing up across America to supply both humans and their furry friends with plant extracts high in a phytochemical called cannabidiol (CBD).


But let's get back to our hound dog.


He's instinctively stressing you, even if ever so slightly, because he's distressed.


A dog’s bark alerting humans is at least 30,000 years old! The only spurring sound of similar kind stretching back further would be perhaps a woman’s scream or baby’s wail. He's panicking as only an old hound could though... so you dig'em instantly.


Picture folks going in and out and every time he's furiously wagging his tail, his attention on his human, not to be friendly but to exclaim,

“DUDE...let me inside, I’m dyin here!”

The other dog’s like,

“...”

Dog 1’s ECS is operating more optimally, keeping it in a far more relaxed and stabilized state, as impacted by his comrade’s stress as you or the other patrons guzzling seasonal blend.


Consider the roaster dulling the sound of barking in combination with music in your ears. Although just a large appliance, it too is operating optimally, pumping out cooked java beans thanks to all its hoses, drums, pressure gauges, moving parts, engines, controls, temperatures, etc., constantly being maintained by staff.


If any mechanism goes out of balance or stops functioning properly anywhere along the chain from raw bean to cold brew or a sack of coffee, the whole device shuts down or start acting like that trusty hound.


Thankfully evolution's done the work for us and we don’t have to micromanage our internal ECS machines - they’re autonomous and over 500-600 million years old.


Yes, present science puts it at roughly 600 million years which is far beyond human comprehension.


Might as well be a trillion.


How do we know? We’re about to get into it, but first let’s approach this from a big broad perspective.


Wagging Tails as Seen from Space

The moment-by-moment health of any living organism on earth, like our furry friends and their owners, is the result of an astoundingly complex balancing act of thousands of interconnected systems - biological, environmental, and cosmic.


Basically a never ending chain of linked systems coated in relativity.


These systems evolved over billions of years and continue to do so.


Arguably, the most important or foundational systems involve earth and its ability to sustain ‘conscious or sentient life’ in its endlessly variable and competing manifestations:

  • Our perfect distance from the sun, making it possible for liquid water.

  • Atmosphere so the environment stabilizes - not too warm or cold (ideally; variable).

  • The size of earth is just big enough to maintain atmosphere through gravitational pull.

  • And, we have a magnetic field to deflect solar wind that would otherwise strip away atmosphere and bombard life with deadly heated levels of radiation.

Those are the basics of the so-called Goldilocks Zone making it possible for life as we understand it to exist. A cosmic slacklining experiment; all systems a few planck lengths (smallest unit of measurement) from tipping out of balance, yet here we are, having a time-transcending digital conversation.


Now, let’s not forget each system is a universe of systems unto itself, like an atom or cell, but we’re not going to try and peel away layers of cosmic truth today... the point is…

All life is but a balancing act.

Until the genuine discovery of the ECS in 1988 through a government-funded study at the St. Louis University School of Medicine that identified and named the first cannabinoid receptor, humans were under the impression our bodies and minds were governed (to create and maintain sentience) by 11 systems:


Circulatory, digestive, endocrine, exocrine, lymphatic, muscular, nervous, renal, reproductive, respiratory and skeletal.


30 years later and we now understand the ECS as the project manager, overseer, or master controller if you will - present in all systems, especially the brain.


Based on current research, it seems the ECS is a primary means with which metazoan or multicellular animals/beings evolved a way to maintain internal equilibrium outside the awareness of the surface mind - so for example autonomous breathing. Put another way, the force of life couldn’t simply create a mind and body composed of these systems, there had to be a governing ruler to maintain overall system balance, to keep the orchestration in perfect working order.


A key master with a miraculous set of keys.


A conductor.


While there are many great ways to define the word or concept of homeostasis, the one from Britannica is among the best:

Homeostasis is any self-regulating process by which biological systems tend to maintain stability while adjusting to conditions that are optimal for survival. If homeostasis is successful, life continues; if unsuccessful, disaster or death ensues. The stability attained is actually a dynamic equilibrium, in which continuous change occurs yet relatively uniform conditions prevail.

A dynamic equilibrium we could apply to the biological, environmental, or cosmic individually, and all three simultaneously. One, big, balancing act.


A Goldilocks Compound & The Evolution of the ECS

Our dating of 500-600 million years comes primarily from Dr. John McPartland. Frankly, he’s the leader in this specific department.


Tip: If you’re that endo-nerdy dig into his powerful research on PubMed. We relied on some for this article, noted in references at the end.


Directly quoted from Martin A. Lee, co-founder of ProjectCBD and author of Smoke Signals: A Social History of Marijuana - Medical, Recreational and Scientific( love this book);

“As Dr. John McPartland has explained, this ancient, internal signal system started evolving over 600 million years ago (long before cannabis appeared) when the most complex life form was sponges.” [1]

We’ll get into a bit of their fascinating findings in a sec, but let’s assume the primary goal of the force of life in our universe is to create and evolve sentience.


Why? Who knows?


Can you conjure anything better for life to do with space, matter and time?


Sentience: you may be surprised but it’s difficult to find a concrete definition of this concept. You'll keep running into the animal sentience debate. How absurd! Who honestly believes animals aren’t conscious, aware of both themselves and the environment around them? Thus, for the purposes of how it’s being used in our discussion, we’ll draw from Webster’s New World College Dictionary, 5th Edition:

  1. a sentient state or quality; capacity for feeling or perceiving; consciousness

  2. mere awareness or sensation that does not involve thought or perception

With that, pause a moment and consider the triadic magnitude of systems required to create and sustain sentience in these respects - biological, environmental/ecological, and planetary, or cosmic in relation to what we discussed about little miss Goldilocks Zone.


For earth, in order for organisms to reach the stage of awareness our ancestors experienced after the planetary/environmental requirements were in place, it seems a cannabinoid-based retrograde neural messaging system is what evolved to manage, regulate, or modulate the supportive biological systems of sentience.


Let's take a leap through time...


Boom... our fossil record shows around this time (600-500 million years ago), diversity and the sheer amount of complex organisms exploded! And this all went down in a relatively short geological stretch of time. We call it the Cambrian Explosion, generally placed about 542 million years ago, with the event ending around 505 million years ago - recorded in Burgess Shale [2].

“As the number and variety of organisms increased, they occupied a variety of new marine environments and habitats. Cambrian seas teemed with animals of various sizes, shapes, and ecologies; some lived on or in the sea floor, while others actively swam in the water column. The fundamental ecological structure of modern marine communities was firmly established during the Cambrian. By the end of the period, some animals had also made the first temporary forays onto land, soon to be followed by plants.” [2]

The groundbreaking 2005 study Doctor McPartland was involved in, with another prolific name at this level of cannabinoid science Di Marzo, looked at the sea squirt. Intriguing because the earliest probable species of tunicate appears in the fossil record in the early Cambrian [3].

“A cannabinoid receptor orthologue (CiCBR) has been described in the sea squirt Ciona intestinalis. Here we report that CiCBR mRNA expression is highest in cerebral ganglion, branchial pharynx, heart and testis of C. intestinalis, and that this organism also contains cannabinoid receptor ligands and some of the enzymes for ligand biosynthesis and inactivation.” [4]

Mind-blowing, these ancient creatures were endowed with, evolved, or adapted the same cannabinoid receptors covering human (and puppy) brains today...hundreds of millions of years ago.


Wait, that’s not all these visionary doctors reveal.

“The endocannabinoid anandamide [AEA] was found in all tissues analyzed, with the highest concentrations being found in brain and heart. The endocannabinoid 2-AG was five-fold more abundant than anandamide, and was most abundant in stomach and intestine and least abundant in heart and ovaries.”

Wait a sec...your body make AEA and 2-AG!


Along with these revelations, they found the final piece of the ECS triad - receptors, cannabinoids, and enzymes the ECS uses to synthesize and breakdown or degrade endocannabinoids.

Using phylogenomic analysis, we identified orthologues of several endocannabinoid synthesizing and degrading enzymes. In particular, we identified and partly sequenced a fatty acid amide hydrolase (FAAH) orthologue, showing 44% identity with human FAAH and containing nearly all the amino acids necessary for a functional FAAH enzyme.

Your body also use FAAH. Is that it though, just us vertebrate mammals and some gooey marine life?


If we return to Martin Lee’s quote, the rest of McPartland’s analysis sums it up:

“Endocannabinoids and their receptors are present in fish, reptiles, earthworms, leeches, amphibians, birds and mammals —every animal except insects. Given its long evolutionary history, scientists surmised that the endocannabinoid system must serve an important and basic function in animal physiology.” [1]

Ya think?! Poor insects, still, that’s amazing!


Evolution brought about a governing system, but what’s its design?


When does it come about in the life cycle?


We know endocannabinoids AEA and 2-AG are concentrated in human breast milk [5], but how about other more ancient species?


Another tunicata called the Lamprey was studied by Dr. Maurice Elphick in 2012, because in many respects they reflect the brain structure of their earlier vertebrate ancestors. While looking into the evolution and comparative neurobiology of endocannabinoid signalling, he found:

“Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding.” [6]

Learning, motion control, and feeding are pretty important to maintain a homeostatic state.


The system wasn’t as advanced as yours yet, but it appears the function became dominant across the planet. The same ECS receptors in your body right now, CB1 and CB2, he claims were originated in this ancient marine life from a common ancestor to target axons, or “The long thread-like part of a nerve cell along which impulses are conducted from the cell body to other cells.


We don’t yet know the precise evolutionary origin of the ECS, but Dr. Maurice states these findings are,

“...indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB(1)/CB(2)-type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom.” [6]

Nine years earlier, in 2003, Dr. Elphick and his team declared,

“The ancestor of vertebrate CB(1) and CB(2) cannabinoid receptors originated in a deuterostomian invertebrate.” [7]

Note: A deuterostome is estimated to have genetically split lineages with protostomes about 17 million years before the Cambrian period. The oldest discovered lived approximately 540 million years ago.


As you look at the timeline of how multi-cellular intelligent life evolved to support and maintain sentience, the majority of lifeforms more complex than jellyfish came about at it seems the same time the ECS did. Without it, you and your levels of function and awareness simply wouldn’t be possible.


The ECS Triad

While new discoveries are being made and likely to uncover more, the three most basic components of your ECS are as follows.

  • Receptors: CB1 & CB2, located throughout the organ systems along with both central and peripheral nervous systems. Retrograde - meaning they function counter to more conventional pre-to-postsynaptic cellular communication.

  • Endocannabinoids: Produced by the body - AEA & 2-AG (more are being discovered) - used to perform the profound amount of homeostatic functions of the ECS.

  • Enzymes: To synthesize and breakdown endocannabinoids on demand by the ECS.

Your next question would might be, how did it unfold? Did receptors show up first or the endocannabinoids?


According to a 2007 study also published by McPartland, it was more of a co-evolution.

“Mirrored cladograms provided evidence of co-evolution (i.e., parallel cladogenesis). Therefore we propose that cannabinoid receptors initially co-evolved with a fatty acid ester ligand (akin to 2-AG) in ancestral metazoans, and affinity for fatty acid ethanolamide ligands (e.g., AEA) evolved thereafter.” [8]

Astonishing. Cannabinoid receptors began evolving initially with a 2-AG-like endocannabinoid, which led to the creation of AEA. First, in the marine life of the Cambrian Period, and then from there into vertebrates and plants. Arguably the ECS from the beginning over 500-600 million years ago, has been designed to make it possible for more complex life to survive long enough to procreate and then some.


To be prudent...


From Wikipedia:

Cladogenesis is an evolutionary splitting of a parent species into two distinct species, forming a clade. This event usually occurs when a few organisms end up in new, often distant areas or when environmental changes cause several extinctions...in contrast to anagenesis, in which an ancestral species gradually accumulates change, and eventually, when enough is accumulated, the species is sufficiently distinct and different enough from its original starting form that it can be labeled as a new species.” [9]

Quick Recap

Your endocannabinoid system is insanely old - receptors, endocannabinoids, and enzymes. In fact, it played a crucial role in the evolution of human beings. Without it, there would be no universal regulator system keeping all other core systems in balance. The ECS came about when environmental and planetary conditions were ripe and today cannabinoid receptors are likely the most abundant neurotransmitter receptors on earth!


Enter Cannabis - 30’ish Million Years Ago

Given the age of the ECS and the fact cannabis produces rough plant replicas of our endocannabinoids AEA and 2-AG (i.e. THC & CBD), we can assume it’s been around throughout a good portion of human evolution. Until recently, it was extremely hard to dig through centuries of varied taxonomic data to get a good idea of when cannabis appeared, but in October of 2018, McPartland again widened our perspective with these points from his published work in the area [10].

  • We have fossil leaves from Germany found in the late 19th century, but they weren’t dated. However, in the species epithet at the time it was referred to the Oligocene Epoch - 33.9 million to 23 million years ago (Friedrich).

  • A dated specimen from Bulgaria was dated to be from the Pontian age, some 7.3-5.3 million years ago (Palamarev) when the Miocene Epoch was ending.

  • We have a fossil seed also from the Miocene found in Siberia (Dorofeev).

  • Based on their findings and study of humulus (another ancient plant in the Cannabaceae family), “Humulus and Cannabis diverged from a common ancestor 27.8 mya. C. sativa and Cannabis indica diverged 1.05 million years ago.

That study is the most comprehensive we’ve come across so far digging into not only the age of cannabis and its ancient evolutionary relatives and divergences, but global origination, spread, the differences between Cannabis Sativa, Cannabis Indica, and Cannabis Ruderalis, as well as domestication data.


Speaking of which…


Early Cannabis Domestication

It’s widely accepted cannabis is one of the earliest known crops cultivated by humans (some claim directly responsible for the ancient agricultural revolution), but evidence gets murky past the 10,000-year mark.


In 2015 the Ohalo II site was discovered, a 23,000-year-old hunter-gatherers’ sedentary camp on the shore of the Sea of Galilee. They collected 150,000 samples of plant remains and declared,

“The archaeobotanically-rich plant assemblage demonstrates extensive human gathering of over 140 plant species and food preparation by grinding wild wheat and barley. This collection provides the earliest evidence of a human-disturbed environment—at least 11 millennia before the onset of agriculture—that provided the conditions for the development of "proto-weeds", a prerequisite for weed evolution. Finally, we suggest that their presence indicates the earliest, small-scale attempt to cultivate wild cereals seen in the archaeological record.” [11].

We saw no evidence in the literature to suggest cannabis was included in the samples, but to us, this shows incredible plant savvy. The idea they weren’t aware of cannabis is possible, but highly unlikely when it comes to all peoples in the more habitable zones on earth at the time.


Small bits of historical clues and evidence have been found the world over, however, we may never truly know how far back our relationship with cannabis goes...


In Conclusion

Hopefully, this helped you gain a better understanding of how old your endocannabinoid system is. And here’s to all the amazing information soon to be released thanks to the 2018 Farm Bill making hemp-cannabis farming once again legal and easier to research. We’ll leave you with this wonderful quote from a study published in the summer of 2018,

“The ECS may not only provide answers for diseases with no known cures, but it could change the way we approach medicine. This system would allow us to change our focus from invasive pharmacological interventions to uncovering the mystery of why the body is failing to maintain homeostasis.” [12]

Cheers!



References

[1] "The Discovery of the Endocannabinoid System" Martin A. Lee.

[2] "The Cambrian Explosion" The Burgess Shale, Royal Ontario Museum

[3] The Tunicate Wikipedia page.

[4] "Occurrence and possible biological role of the endocannabinoid system in the sea squirt Ciona intestinalis." NCBI, Matia, McPartland JM, Di Marzo V, 06/2005.

[5] "Cannabis and endocannabinoid modulators: Therapeutic promises and challenges" NCBI, Igor Grant, B Rael Cahn, 09/2008.

[6] "The evolution and comparative neurobiology of endocannabinoid signalling."NCBI, Elphick MR, 12/2012.

[7] "The invertebrate ancestry of endocannabinoid signalling: an orthologue of vertebrate cannabinoid receptors in the urochordate Ciona intestinalis." NCBI, Elphick MR, Satou Y, Satoh N, 01/2003.

[8] "Coevolution between cannabinoid receptors and endocannabinoid ligands." NCBI, McPartland JM, Norris RW, Kilpatrick CW, 08/2007.

[9] The Cladogenesis Wikipedia page.

[10] "Cannabis Systematics at the Levels of Family, Genus, and Species" John M. McPartland, NCBI 10/2018.

[11] "The Origin of Cultivation and Proto-Weeds, Long Before Neolithic Farming" Ainit Snir,

Dani Nadel, et al., Plos One Journals, 07/2015.

[12] "The Endocannabinoid System, Our Universal Regulator" Journal of Young Investigators, Chad A Sallaberry, Laurie Astern, 06/2018.