Science

GNUPHARMA'S

ENDOCANNABINOID
SCIENTIFIC PERSPECTIVE

How many people that you know have heard of the “endocannabinoid system”? How many of those people, that have heard about this system, think that is tied to cannabis? Surprisingly most do! In fact, most medical professionals, and even most PHD level researchers have very little knowledge of this CRITICAL system! We will examine why CRITICAL later, for now lets look at the history of the endocannabinoid system.

When did we develop this major and important system?

It is important, from an evolutionary standpoint, to determine common ancestors. This gives an indication of how important a physiological system is. For instance, when did we develop lungs? Or when did we develop legs? These are important questions as the older the system is, generally the more important it is to our function. Being of critical function makes sense as we drag these things up the evolutionary ladder. So when did we develop an endocannabinoid system? Before we developed lungs, or hands, or feet, or a brain…we developed an endocannabinoid system. In fact you have to go back to something called a sea squirt..which barely had a stomach or a central nervous system…but did have a fully functional endocannabinoid system. In fact from a sea squirt insects went one way and everything else went another. The endocannainoid system is SO important and SO ancient with share it with most life on the planet!

“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.”

- Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy.

The history & discovery of the Endocannabinoid System

A brief history of the endocannabinoid system: In 1988, the first cannabinoid receptor was found in the brain of a rat. Initially found by Allyn Howlett and William Devane these cannabinoid receptors turned out to be plentiful in the brain as well as thought the body. In 1990 Lisa Matsuda announced at the National Academy of Science’s Institute of Medicine that she and her colleagues at the National Institute of Mental Health had managed to pinpoint the DNA sequence that defines a THC-sensitive receptor in a rat’s brain. Not long after this announcement they were able to successfully clone that receptor, allowing them to create molecules that “fit” or “activate” the receptors. In 1992, the first endocannabinoid was discovered. Anandamide was the first, naturally occurring endogenous cannabinoid, or endocannabinoid. It was found by Raphael Mechoulam as well as NIMH researchers William Devane and Dr. Lumir Hanus. A second endocannabinoid was identified in 1995, discovered by none other than Mechoulam’s group yet again. This second major endocannabinoid was dubbed 2-arachidonoylglycerol or “2-AG” to keep it simple. This particular endocannabinoid attaches to both CB1 and CB2 receptors.

It was these discoveries, working backwards, tracing the metabolic pathways of THC, which allowed scientists to discover an entirely unknown molecular signaling system that resides within us as well as most other life on the planet. Due to the role cannabis played in discovering this system it was rightfully named the endocannabinoid system.

It was these discoveries, working backwards, tracing the metabolic pathways of THC, which allowed scientists to discover an entirely unknown molecular signaling system that resides within us as well as most other life on the planet. Due to the role cannabis played in discovering this system it was rightfully named the endocannabinoid system.

INSTITUTIONS

If the ECS is so important it is taught in every medical school right? WRONG. In fact only about 20 medical schools currently teach anything at all about the ECS. GnuPharma was recently asked to discuss its work on the endocannabinoid at a major University, during dialog the question was asked..”why isn’t a class taught on the endocannabinoid system?”. The answer was “no time”. While understandable, University’s are now turning out medical professionals who know nothing about this critical and important medical system.

“The discovery of the endocannabinoid system (ECS) is the single most important scientific medical discovery since the recognition of sterile surgical technique. As our knowledge expands, we are coming to realize that the ECS is a master control system of virtually all physiology. However, research and education of medical students involving the ECS is being intentionally restricted by politics. No justification can be made for the restriction of the scientific study of cannabis and the endocannabinoid system.” - David B. Allen, M.D.

YOUR MEDICAL PROFESSIONALS

If your state has a medical cannabis program, challenge your medical professionals on what they know about the ECS. They cannot treat your problems adequately without a full knowledge and understanding of the endocannabinoid system. Regrettably most medical professional know less that that kid selling cannabis down the block about the ECS. This is unfortunate because the ECS extends FAR beyond cannabis. Further, with a true understanding of what the ECS does, a medical professional is in a far better position to understand human physiology and function and how better to treat issues associated with dis-regulation.

“There was one professor who was an MD/Ph.D – a psychopharmacologist – who mentioned it. He was just talking about the usual marijuana abuse stuff and how it works through the CB1 receptors. But nobody was saying this is a widespread, homeostatic modulatory system which has the most prevalent neurotransmitter in the brain on a per second basis and regulates mood, appetite, memory, pain, inflammation, muscle relaxation, bone remodeling, reproduction, etc.” - Dr. Sunil Aggarwal

THE ENDOCANNABINOID SYSTEM

In our world, the ECS is your top umbrella.  It is your master regulatory system and operates under the control of the hypothalamus for the most part.  Why do we think this?  Well, mainly because EVERY single piece of cannabis research, cannabis anecdotal data, enodcannabinoid research, are indicating this very strongly.  A simple search of National Institute of Health  will yield over 50,000 studies and papers on the ECS.  As researchers are apt to do, alot of this researched is silo’ed.

So, what do we mean by “top umbrella”?  What we mean is that from current research it appears that our bodies are under intelligent control.  This intelligent control is, for the most part, governed by the hypothalamus [1] who’s primary job is to regulated homeostasis or overall body regulation.  How does the hypothalamus perform this wonderful feat?  By using the ECS as a modulator.  Although the mechanism are different in each major human physiological system, it is clear that that hypothalamic action thru the ECS, either directly or indirectly can cause changes in regulatory states regulatory state [2].  The relationship between the hypothalamus and the ECS is deep [3]!

Examples usually help, so lets consider some examples…

Feeding and Craving Behaviors

Humans, and all mammals, have a feeding and craving system. How do we get hungry? How much food should we eat? How do we know when we are nourished? All these questions are answered within the feeding and craving system. Further, many answers on addiction may also lay within this system as addiction craving are VERY similar to food cravings.

So, how does this system work? Well, we need a “traditional” explanation and then lets contrast that against an endocannabinoid explanation…

Plausible…but lets consider another explanation…

In the GnuPharma model, the hypothalamus is continuously watching ALL aspects of body regulation [5] .  Because it is monitoring resource levels, the hypothalamus can intelligently determine when resources are needed.  The mechanism of action of the hypothalamus is the ECS [6].  In this case, when resource need is identified by the hypothalamus, it initiates a process of releasing the hormone gherlin using the ECS [7] [8] [9]  Gherlin is the hormone that causes hunger pains [10].  As gherlin is released into the gut area, we becoming increasingly hungry.  Now the REALLY COOL stuff happens!  As you eat, your food is somewhat broken down in the stomach and sent to other gut organs for processing.  In our model, this is ALL under intelligent control of the hypothalamus which is also controlling what we absorb.  You have to have proper enzymes in your gut biome to break down food based pre-cursors, but, as you break down these pre-cursors into other pre-cursors, your body is absorbing them under the intelligent control of the hypothalamus [11] [12] [13] [14]  When the hypothalamus has determined we have adequate resources, another chemical mediator is release called leptin which shuts down the process [12].

Lets consider another example of a major human system…the immune response..

Again, for humans this is a critical system that is fundamental to our survival.  How do we repair physiological trauma?  How do we know when we are “hurt”?  What do our bodies need, in terms of resources, for repairs?

In traditional science, there is a hodge podge of explanations.  To simplify this, lets look at a traditional trauma and repair scenario under the immune.  Ask a neurologist, or even an immune PHD, how your body knows how much area to inflame under trauma and they will go white and stumble toward some cellular explanation.  Suffice to say, while a mind numbing array of detail can be provided here by traditional science, it again lacks logic and elegance.

In the GnuPharma model, again, the hypothalamus is constantly monitoring ALL aspects of the body and attempting to maximize homeostasis and regulation in each system.  The hypothalamus is queued into traumatic response actions by the pain response.  Depending on the severity, the ECS is then used by the hypothalamus to “fight or flight” or “remove the hand from the stove” [15].  The hypothalamus “evaluates” the damage and then begins to inflame the area of trauma.  Inflammation is under the intelligent control of the hypothalamus using the ECS [16].  Then the hypothalamus begins repair.  This is really cool as well…the hypothalamus uses endocannabinoids to determine what a stem cell will be [17].  So, stem cells are determined and queued for repair.  Providing the ECS has adequate resources, repair is completed and the area is deflammed.  Areas of lingering pain are generally areas where resources were lacking and repair could not be completed.

HOW GNUPHARMA NUTRITIONALLY FEEDS THIS SYSTEM

Perhaps first an example from another neurological channel most will understand.  We all know about serotonin and dopamine.  These two neurotransmitters or chemical mediators are critical in order for us to generate “mood” and “cognition”.  While not really taught or discussed, it should be obvious these are resources within the body and that they deplete.  We certainly are not born with a big bucket of serotonin/dopamin and die with the same amount.  These chemical mediators are CONSTANTLY being re-generated providing we are providing our bodies with the need resources.  What are these resources?  For serotonin and dopamine it is foods that contain tryptophan.  Tryptophan breaks down into L-Dopa which breaks down into serotonin and dopamine depending on the enzyme.  So by eating foods with tryptophan we give our bodies the resources they need to build chemical mediators responsible for our mood/cognition!  Guess what happens when we do NOT eat enough foods with tryptophan?  We suffer cognitively and mood wise [18] [19].

Dopamine_chemical_structure
Serotonin-2D-skeletal

So, we need nutrients to provide pre-cursors to our bodies to build chemical mediators! This should be obvious, but modern nutrition and medicine appear to have overlooked this vital fact. And what happens if we do not get the “pre-cursors”? Well we suffer! So, lets look more deeply at the ECS…

The ECS is a resources driven system.  We HAVE TO HAVE the pre-cursors in order to build the chemical mediators!  Further, it is our master regulatory system.  So guess what happens when we do not provide the ECS with the proper pre-cursors to build the chemical mediators? We do not regulate properly! We break! And we break statistically along the very lines we see health issues in society today.  In particular diseases of inflammation, pain issues, basically and disease of disregulation is, in actuality a disease of malnutrition.

Hopefully this satisfies that what GnuPharma has developed, is a way to nutritionally target these malnutrition deficiencies in the body.  Ideally, we would all just learn EXACTLY what we needed as pre-cursors for these critical system, but until then, GnuPharma seems to have developed a way to target nutrients at specific deficiencies.

INFLAMMATION

It is clearly established that the endocannabinoid system is directly responsible for inflammation.  In the GnuPharma model, a malnourished endocannabinoid system would not be able to properly manage this response.  By provided nutrients to the endocannabinoid system, we can ensure that the body has what it needs, the body will heal itself.  With proper nutrients the inflammation cycle will complete in a health human…without resources it will NOT.  The fact that we have diseases of inflammation is a clear indication we are woefully malnourished!

GNUPHARMA HAS DEVELOPED HERBAL FORMULATIONS WHICH HAVE
ACTIONS IN THE ENDOCANNABINOID SYSTEM!

This is a nutritional exercise in a similar way that you would build serotonin and dopamine from food that contain tryptophan.  For instance, as White Onion is broken down in the body, it expose a flavonoid called quercetin.  Quercetin is an ECS effector in that it causes cells to over-express CB1 neuro-receptor sites [20].  This has the the consequence of providing more CB1 surface area to deal with and ups effects associated with CB1 stimulation.  Granted, if you already have enough of this resources, your body will just eliminate it when you eat it as it is nutritional.  There certainly are herbs that contain flavonoids that provide direct stimulation at CB1 and CB2.  Again, your body will only use these if it “needs” them to build resources.  Echinacea has alkaloids that bind with the CB2 neuro-receptor.  Anthocyanins have components in them that bind to both CB1 and CB2 neuro-receptors [21].

GnuPharma’s patent (pending) describes how to take these non-cannabis plant components and build nutritionally targeted formulations.  GnuPharma has leaned heavily on the anecdotal evidence provided by the medical marijuana community.  For instance, in the medical marijuana world, pain can be addressed by consuming an indica strain of cannabis.  A sativa strain would not have the same pain relieving effects.  This indicated that the ratios of CBD’s:THC which are indicative of CB1/CB2 effects are critical.  Further, it also indicated cannabis turpenes also play a critical roll on its medical effects.  Again, in our world this is a resources exercise where medical cannabis is simply providing needed resources to the endocannabinoid system.  Point here is that pain lives in a “know” spectrum of CB1 to CB2 influence.  If that same influenced is mimicked, then similar results are achieved.

So what does all this mean?

  • We are woefully malnourished as to our endocannabinoid system.  This can be explained by our current diet
  • This malnourishment takes the form of diseases of the ability to manage pain, the ability to manage mood, diabetes, seizures, allergies, auto-immunes, and other diseases of inflammation.
  • While GnuPharma has yet to discover an overall nutrient package, nutrients can be intelligently provided to the body and the body will use those nutrients in a predictable and intelligent fashion.
  • GnuPharma has determined a potential nutritional package that will provide resources to assist the body with specific tasks.  In some cases these require different nutrients.
  • We badly need a new food “pyramid”..GnuPharma data and research is indicating we are all severely malnourished.