Best Summary ECS Cannabinoid Information

Best Summary _ ECS _ Cannabinoid _ Information

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THE ENDOCANNABINOID SYSTEM- ECS -

The Endocannabindoid System (ECS) is an ancient body system that is found in all animals with vertebrate, including humans.The function of the ECSis to maintain homeostasis throughout the animal’s body utilizing neuro-metabolic signaling and the CB1 and CB2 receptors. Within a cell, cannabinoids control basic metabolic processes such as glucose metabolism. Cannabinoids regulate intercellular communication, especially in the immune and nervous systems. In general, cannabinoids modulate and coordinate tissues, organ and body systems (including the cardiovascular, digestive, endocrine, excretory, immune, musculo- skeletal, nervous, reproductive, and respiratory systems). The effects of cannabinoids on consciousness are not well understood, but are well known. These effects also have therapeutic possibilities.

In September of 2005, Sanofi Aventis, the world’s 3rd largest pharmaceutical company, placed an advertisement in the Journal of the American Medical Association (JAMA) 09/21/05 issue and plainly stated the biological basis for how marijuana affects so many systems within the body.

Adipose tissue is defined as “a metabolically active endocrine organ -more than just a storage facility for fat, it has metabolic effects.” ECS over-activity in adipose tissue is associated with decreases in the hormone adiponectiun, which may be linked to dylipidemia, insulin resistance, and intra-abdominal adiposity.” CB1 receptors are “at the center of a cascade of events with potential impact on cardiometabolic risk.” And they “May assist in regulating physiologic processes, e.g., lipid and glucose metabolism.”

The Endocannabinoid system (ECS) is involved in regulating many physiological processes:

Nervous
Cardiovascular
Immune
Reproductive
Sleeping
Eating
Memory function
Relaxation

What are Cannabinoids?

Phytocannabinoids—Cannabinoids produced by the plant.

Phytocannabinoids are complex chemical compounds that are secreted by the cannabis plant through its flowers that mimic naturally occurring compounds produced by our bodies, called endocannabinoids (Anandamide and 2-AG).

Endocannabinoids—Cannabinoids produced by the body.

AEA (Anandamide)—An endogenous cannabinoid neurotransmitter found in organs in humans and most animals with an abundant amount located in the brain. While delta-9-tetrahydrocannabinol (THC) was first synthesized by Mechoulam in 1967, it was not until 1990 that the cannabinoid receptor was localized in the brain and cloned. Since then, discoveries in the field have proceeded at an ever-increasing pace.

Cannabinoid Receptor Sites

When cannabis is consumed, the cannabinoids bind to receptor sitesthroughout our brain and body (CB-1 and CB-2 respectively), with a wide variety of effects possible depending on the cannabinoid profile present in a given strain.

CB1 Receptor—Primarily found in the brain.

CB2 Receptor—Primarily found in the immune system.

How Do Cannabinoids Work in the Human Body?

THE FUNCTION OF THE ECS

The “simplest” description of the effects of marijuana in humans is that it modulates the regulation of homeostasis. Homeostasis is keeping the various systems in the body in relative balance. The balance between inhibition and excitation, bone formation and resorption, inflammatory/anti-inflammatory signaling, fat storage and release, blood sugar, blood pressure, hormone levels; all these systems are held in balance by the endocannabinoid system (ECS).

Though the ECSinvolved in maintaining nearly every biological process in all humans, this system wasn’t discovered until the late 1980’s. The human body contains not only contains receptors for cannabinoids, but an entire endocannabinoid system that processes cannabinoids. This system allows the body to benefit from the cannabinoids found in cannabis, some of which aren’t found anywhere else in nature.

Research revealed that the human body contains not only receptors for cannabinoids, but an entire endocannabinoid system (ECS) that processes cannabinoids. This system allows the body to benefit from the cannabinoids found in cannabis, some of which aren’t found anywhere else in nature. The endocannabinoid system regulates many of the functions of the human body: appetite, food intake, motor behavior, reproduction, and much more. That’s why the plant has such a wide therapeutic potential, and every day more are discovered.

Cannabinoids

Phytocannabinoids—Cannabinoids produced by the plant.

At least 85 different phytocannabinoids have been isolated from the cannabis plant. For years THC has been described as the primary compound in cannabis due to its famous psychoactive effects, but recent research has identified many other important cannabinoids, each linked with specific medicinal effects. During prohibition (the last 80 years), cannabis has been primarily bred to increase THC content to increase the altering effect of the plant, as demanded by the black market. Now that things are changing, other cannabinoids are reaching the medical spotlight and strains are being bred to increase their presence.

Common testing methods provide profiling for the three most prevalent cannabinoids – THC, CBD and CBN, but there are many others to be aware of, including the acid forms of each cannabinoid. There is still much to be studied about this plant and its many components, but with restrictions on scientific research of cannabis slowly relaxing, more information continues to come to light.

Here is an overview of the four (4) major cannabinoids that are supported by a solid body of research at this time:

1THC: Tetrahydrocannabinol

Effects:Responsible for the ‘’high’’ effect (psychotropic, euphoric), it amplifies all sensory functions such as sight, hearing, color sensitivity, and promotes a greater sense of well-being. THC produces strong feelings of euphoria. It sharpens the mind (cerebral) and promotes creativity. THC displays a wide range of properties, which can be expressed differently when accompanied by various other cannabinoids and terpenes.
Side effects vary from one person to another and include: dry mouth, dry eyes, disorientation, short-term memory malfunctions, increased heart-rate, anxiety, and paranoia. Most of these are a result of over-medication and are avoidable with low doses.

Medical Applications:

Neuroprotective – protects against nerve damage
Anxiolytic – reduces the symptoms of anxiety
Antispasmodic – relieves spasms and convulsions
Antiemetic – reduces vomiting and nausea
Analgesic – reduces pain
Appetite Stimulant – encourages eating and appetite
Antioxidant – fights free radicals in the bloodstream
Neuropathic analgesic – reduces pain from nerve damage
Bronchi-dilator -acts similarly to an inhaler to assist asthmatics with breathing
Anti-proliferative anticancer – reduces spread of certain cancers
Anti-inflammatory – reduces inflammation
Neurogenesis – promotes growth of new nerve tissue

2CBD: Cannabidiol

Effects: CBD has medical effects but does not make people feel “stoned” and actually counters some of the effects of THC. After decades in which only high-THC Cannabis was available, CBD-rich strains are now being grown by and for medical users. The reduced psychoactivity of CBD-rich Cannabis may make it an appealing treatment option for patients seeking anti-inflammatory, anti-pain, anti-anxiety and/or anti-spasm effects without euphoria or lethargy.

Medical Applications:

Rheumatoid arthritis
Diabetes
Alcoholism
PTSD
Epilepsy
AIDS
Anti-cancer/tumor
Arthritis
Depression
Crohn’s Disease
Eating Disorders
Glaucoma
Epilepsy/Seizure Disorders
Migraines
Multiple Sclerosis

3CBN: Cannabinol

Effects: Mildly psychoactive, sedative, analgesic. CBN is, just like aspirin, a non-narcotic type analgesic, but 3 times as strong. CBN is a breakdown product of THC. During storage (aging) CBN will slowly increase as THC deteriorates. CBN is effective at relieving tension headaches.

Medical Applications:

Antispasmodic – relieves spasms and convulsions
Analgesic – reduces pain
Anti-inflammatory – reduces inflammation
Antioxidant – fights free radicals in the bloodstream

4CBG: Cannabigerol**

CBG is perhaps the most under-studied of all cannabinoids, but holds promise of perhaps the most therapeutic properties.

**Cannabigerol (CBG) is the “stem cell” for many chemicals in marijuana, including THC and CBD. Scientists first discovered cannabigerol, or CBG, in 1964 as a constituent of hashish. In 1975, researchers found outthat CBGA (the acid form of CBG) is the first cannabinoid formed in the plant, essentially the first expression of cannabis’ unique class of constituents. From there, CBGA gets transformed into THCA, CBDA or CBCA by the action of enzymes. CBGA is the precursor for all the cannabinoids we know and love.

CBG also has a number of medicinal properties of its own. Cannabigerol (CBG) is non-psychoactive but still affects the overall effects of Cannabis. Many users find that strains with high CBG have less negative side effects of THC. CBG has been shown to promote apoptosis in cancer cells and inhibit tumor growth in mice.

Medical Applications:

Antioxidant – fights free radicals in the bloodstream
Anti-inflammatory – reduces inflammation
Anti-emetic (vomiting) and anti-nausea
Antibacterial
Eases Inflammatory Bowel Disease
Slows the proliferation of tumor cells
Pain relief
Eases effects of Psoriasis

Major Usefulness of the Major Cannabinoids

Cannabinoid / Therapeutic Effect
THC (9 Tetrahydrocannabinol) /

Anti cancer
Anti nauseant
Analgesic
Appetite stimulant
Antispasmodic
Muscle relaxant
Anti microbial
Neuroprotective
Helps with the symptoms of Crohn’s disease (anti-spasmodic, anti inflammatory)
Anti inflammatory
Antioxidant

CBD (Cannabidiol) /

Protects against cancer
Reduces nausea
Pain reliever
Sleep aid
Relieves spasms
Decreases seizures
Reduces anxiety
Muscle relaxant
Antibacterial
Protects nervous system
Anti diabetic
Improves circulation
Relieves psoriasis
Relieve Crohn’s Disease
Anti inflammatory
Bone stimulant
Relieves rheumatoid arthritis
Antioxidant

CBC (Cannabichromene) /

Anti cancer
Anti bacterial
Anti fungal
Anti inflammatory
Stimulates bone

CBG (Cannabigerol) /

Anti cancer
Anti inflammatory
Stimulates bone

CBN (Cannabichromene) /

Pain reliever
Sleep aid
Antispasmodic
Anti inflammatory
Antioxidant

THCV (Tetrahydrocannabivarin) /

Appetite suppressant
Anti seizure
Stimulates bone

The information in this chart was sent via email from Dr. David Bearman.

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October 15, 2005

Cannabinoids Arrive in Realm of Established Fact

Just as the marketing of Prozac by Eli Lilly familiarized the public with “clinical depression” and “selective serotonin reuptake inhibitors” (SSRIs), so

The marketing of Rimonabant as a weight-loss drug by Sanofi Aventis will educate millions about the endocannabinoid system (ECS). This was foreseen by Philip Denney, MD, who forwards, as part of the mounting evidence that he was right, a full-spread advertisement placed by Sanofi Aventis in the Sept. 21, 2005 issue of JAMA, the Journal of the American Medical Association. Denney and others remain skeptical about the longterm safety profile of a synthetic “cannabinoid-antagonist” drug that works by blocking the natural receptor system.

The JAMA ad touts:

“A NEWLY DISCOVERED PHYSIOLOGICAL SYSTEM…

The Endocannabinoid System (ECS).”

It succinctly explains the role the ECS appears to play in “metabolic syndrome,” the condition for which Sanofi Aventis hopes to get FDA approval to market Rimonabant. Footnotes direct interested physicians to papers from reputable sources. The significance of this carefully documented ad in such a prestigious journal is huge. It seems like only yesterday that the Drug Czar was ridiculing Tod Mikuriya as a practitioner of “Cheech and Chong medicine.” Now, plainly stated in JAMA by the world’s third-largest pharmaceutical company, is the biological basis for how marijuana affects so many systems within the body.

The left-hand page depicts an endocannabinoid floating like a stylized dolphin over a cell membrane from which cannabinoid receptors protrude like plugs in a distributor cap. Accompanying text asserts, “CB1-receptor activation triggers a cascade of intracellular events that impact cardiometabolic risk.” Metabolic syndrome is defined on the right-hand page as a cluster of risk factors: decreased “good” cholesterol; elevated blood pressure, trigycerides and glucose levels; and a widening waistline. Adipose tissue is defined as “a metabolically active endocrine organ -more than just a storage facility for fat, it has metabolic effects.”

The endocannabinoid system “impacts metabolic functions” and “consists of signaling molecules and their receptors, including the cannabinoid receptors (CB1 and CB2). The CB1 receptors “may impact lipid levels and insulin sensitivity.” They are “located centrally in the brain and peripherally in liver, muscle and adipose tissue. ECS over-activity in adipose tissue is associated with decreases in the hormone adiponectiun, which may be linked to dylipidemia, insulin resistance, and intra-abdominal adiposity.” CB1 receptors are “at the center of a cascade of events with potential impact on cardiometabolic risk.” And they “May assist in regulating physiologic processes, e.g., lipid and glucose metabolism.”

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Overview

Humans and animals alike naturally synthesize endocannabinoids, chemical compounds that activate the same receptors as delta-9-tetrahydrocannabinol (THC), the active component of marijuana (Cannabis sativa). Marijuana, as smoked in cigarettes, has many names both formal—cannabis, cannabis, hashish, hemp, sinsemilla—and informal—pot, dope, grass, weed, Mary Jane, bud, hash, bhang, kef, ganja, locoweed, reefer, doob, spliff, toke, roach.

Marijuana is famous for its significant psychoactive effects. Its ability to provide relief to chronic pain sufferers, to induce an increase in appetite, to alleviate nausea, and to ease anxiety are only some of the common uses for hemp. The interest in cannabis has risen in the United States since its medical and recreational use is now (2015) legal in 20 states.

Medical use of marijuana is allowed in the following 20 states (2015):

Washington
Oregon
California
Nevada
Arizona
New Mexico
Montana
Colorado
Illinois
Alaska
Hawaii
Michigan
Maine
Massachusetts
Rhode Island
Connecticut
New Jersey
Delaware
Maryland
Washington, DC

Recreational use of marijuana is allowed in the following two states (2015):

Colorado
Washington

Abbreviations

Abbreviations used in the discussion of cannabinoids and in this article are as follows:

THC: Δ9-Tetrahydrocannabinol
AEA: Anandamide
2-AG: 2-Arachidonoylglycerol
AA: Arachidonic acid
EC: Endocannabinoids
ECS: Endocannabinoid system
CB1-R: Cannabinoid binding receptor-1 (predominantly in brain)
CB2-R: Cannabinoid-binding receptor-2 (predominantly in immune system)
PE: Phosphatidylethanolamine
NAT: N -acyltransferase
NAPE: N -acyl-phosphatidylethanolamine
NAPE-PLD: NAPE-specific phospholipase D
MGL: Monoacylglycerol lipase
FAAH: Fatty acid amide hydrolase

Further investigation

Endocannabinoids are crucial to bioregulation. Their main role is in cell-signaling, and, because they are hydrophobic, their main actions are limited to paracrine (cell-to-cell) or autocrine (same cell), rather than systemic, effects. Unique characteristics of the ECS are as follows:

Lipid structure, making it lipophilic
Hydrophobic with limited mobility in an aqueous environment
Local cell-signaling (paracrine or autocrine)
Retrograde transmission in the brain; travels backward from postsynaptic to presynaptic cells
Formed from the internal lipid constituents of cellular membrane
Synthesized “on demand” and not stored
Very short half-life
Degradation by FAAH may regulate ECS bioactivity
Two G-protein–coupled receptors in the brain (CB1-R) and immune system (CB2-R)

With scientific evidence suggesting their role in inflammation, insulin sensitivity, and fat and energy metabolism, inhibition of endocannabinoids may be a tool in reducing the prevalence of metabolic syndrome and augmenting the benefits of physical exercise.[1, 2] Furthermore, modulation of the endocannabinoid system may be a cure for more chronic neurologic and immune conditions. Many questions are left unanswered about this relatively newly discovered regulatory system. Further investigation into this exciting field promises to shed insights into the mechanisms of health and disease and provide new therapeutic options.

History of endocannabinoid research

When Mechoulam and colleagues isolated THC in 1964, they made it possible to further understand the complex nature of the endocannabinoid system.[3] Other important events in endocannabinoid research are as follows:

2000-650 BCE: Cannabis (azaluu or gurgurru) mentioned in Assyrian pharmacopoeia at the library of Assurbanipal
1964: THC isolation and structure elucidation
1988: Cannabinoid-binding sites in rat brains identified
1991: Human CB1-R receptor successfully cloned
1992: Endogenous CB1-R ligand (EC), anandamide (based on Sanskrit for “supreme joy”), discovered in the brain
1993: CB2-R receptor found in the immune system successfully cloned
1995: Second EC, 2-AG discovered and more abundant in the brain than AEA

In the 21st century, new discoveries of other endocannabinoids, their site distributions, and roles are deepening our understanding of the endocannabinoid system.

Chemical Structure

Although the first EC to be identified was AEA, 2-AG is the most abundant in the brain.[4] Several other ECs have been identified, but their function and role in ECS physiology remains to be determined. Five of the best-known ECs are in the figure below. Note that all of them share the same 19-C backbone structure but differ in the R-group constituents.

The five best-known endocannabinoids showing the common 19-C backbone structure and specific R-group constituents.