Components of the ECS and Their Role in Health

 

The ECS consists of ligands, their metabolizers, and the receptors they bind to. Phyto-cannabinoids that are well known in the medical cannabis field have analogous compounds that the human body produces through various forms of exercise and proper diet

 

 

 

Cannabinoid Receptors

 

• THC, the active ingredient in marijuana, and the body’s own natural forms of THC, anandamide (AEA) and 2-AG produce effects by binding to and activating the CB1 receptor and the CB2 receptor.

• CB1 receptors are some of the most widely expressed receptors on cells throughout the body.

  • It is particularly abundant in the brain where it is responsible for mediating the well-known effects of the typical marijuana high (pain control, memory blocking, and increased appetite).

  • CB1 receptors are found on two broad classes of nerve terminals: excitatory, which increase the activity of target neurons, and inhibitory, which reduce activity.

  • Therefore, CB1 can either enhance or diminish synaptic signaling depending on which of these systems it modulates. This is an example of the ability of the ECS to be a homeostatic regulator by having the ability to increase or decrease message flow between cells.

• CB2 receptors are abundant in the immune system and appear to be involved in inflammation as well as pain responses.

  • CB2 receptors have been located in the central nervous system and have been shown to be active in the brain during certain kinds of inflammatory responses.

  • CB2 expression is highest in immune cells, where it seems to have several immunosuppressive effects, including inhibition of proinflammatory cytokine production.

    • Cytokines are molecules that may act systemically and are often responsible for many of the symptoms of infection (e.g., headache, fever, myalgia). In high concentrations, cytokines can be toxic, or even lethal.

• There is evidence that the CB1/CB2 receptors increase in density in the area affected by disease.

  • Basically, the body has a mechanism to increase the receptor sites for cannabinoids to bind to CB1/CB2 receptors in order to "catch" more cannabinoids.

  • As more cannabinoids bind to receptors in the area of disease, we see a decrease in disease symptoms and or inhibition of the progression of disease.

• Activation of central CB1 receptors promotes food intake and thereby weight gain

 

 

 

Phyto-cannabinoids

 

• THC from the cannabis plant mimics AEA and 2AG (cannabinoids produced by the body) much the same way that opioids from the poppy plant mimic endorphins produced by the body. It causes the psychoactive "high".

  • THC properties include it being a psychoactive agent, analgesic, muscle relaxant and antispasmodic,  bronchodilator, neuroprotective antioxidant, antipruritic agent in cholestatic jaundice, and has 20 times the anti-inflammatory power of aspirin and twice that of hydrocortisone .

• CBD has the potential to help a range of conditions including epilepsy, diabetes, rheumatoid arthritis, chronic pain, alcoholism, schizophrenia, PTSD, antibiotic-resistant infections, and various neurological disorders.

  • CBD, in clinical studies, exhibits Neurogenic and Neuroprotective effects and its anti-cancer properties.

  • CBD is an analgesic, a neuroprotective antioxidant more potent than ascorbate or tocopherol, anticonvulsant, anti-nausea, cytotoxic in breast cancer and many other cell lines while being a cytopreservative for normal cells, and prevents prion accumulation and neuronal toxicity.

  • CBD has also displayed powerful activity against methicillin-resistant Staphylococcus aureus (MRSA).

• CBG has been shown to stimulate bone and brain cell growth.

  • Older work on CBG suggests GABA uptake inhibition greater than THC or CBD, which could suggest muscle relaxant properties.

  • CBG has proved to be an effective cytotoxin in high dosage on human epithelioid carcinoma.

  • CBG has demonstrated modest antifungal effects.

  • CBG has analgesic, anti-erythemic effects, and the ability to block lipooxygenase were said to surpass those of THC.

  • CBG is the next most effective phytocannabinoid against breast cancer after CBD.

  • CBG inhibits keratinocyte proliferation, suggesting utility in psoriasis.

• CBN acts as a mild sedative and sleep aid.

  • CBN was judged inactive when tested alone in human volunteers, but produced greater sedation combined with THC.

  • CBN demonstrates anticonvulsant, anti-inflammatory and potent effects against MRSA.

  • CBN stimulates the recruitment of quiescent mesenchymal stem cells in marrow, suggesting promotion of bone formation.

  • CBN at high concentrations inhibits breast cancer resistance protein.

• THC-A is anti-inflammatory and can suppress muscle spasms.

  • THC-A turns into THC when the plant is vaporized, smoked, or cooked into edibles.

• CBC Acid is anti-inflammatory.

  • CBC has demonstrated analgesic activity, been shown to reduce THC intoxification in mice, demonstrated antibiotic and antifungal effects, and shown cytotoxicity in cancer cell lines.

  • CBC has recently been shown to increase the viability of adult neural stem progenitor cells essential for brain plasticity and suggestive of neurogenesis.

  • A CBC-extract displayed pronounced antidepressant effects in rodent models.

• CBC is anti-inflammatory, can reduce anxiety, and has been shown to stimulate bone growth.

• THCV can suppress appetite, help regulate blood sugar, and could potentially help with type 2 diabetes.

  • THCV produces weight loss, decreased body fat and serum leptin concentrations with increased energy expenditure in obese mice .

  • THCV also shows prominent anticonvulsant properties in rodent cerebellum and pyriform cortex.

  • THCV has demonstrated a CB2-based ability to suppress carageenan-induced hyperalgesia and inflammation, and both phases of formalin-induced pain behavior via CB1 and CB2 in mice.

• CBDV has been shown to be anticonvulsant in rodent hippocampal brain slices.

 

 

 

Endo-cannabinoids

 

• Endocannabinoids are products of dietary fatty acids.

• The ECS contains several endogenous lipid-based signaling molecules that bind to these receptors, known as endocannabinoids.

• The two best characterized endogenous ligands are 2-arachindonoylglycerol (2-AG) and anandamide (AEA) .

• 2-AG is an endocannabinoid, an endogenous agonist of the CB1 receptor. It is derived from the omega-6 fatty acid AA (acid arachidonic) and glycerol.

• AEA (Arachidonoylethanolamine), also referred to as anandamide, is an endogenous cannabinoid that acts as a “key” molecule fitting into the “locks” of the CB1 and CB2 receptors around the body.

  • THC is analogous to AEA and helps to stimulate production of AEA.

  • Anandamide may also be partly responsible for pain regulation and sleep patterns.

  • Anandamide has been shown to exert analgesic actions in different pain research models by binding strictly to peripheral CB1 receptors.

  • Anandamide plays an important role in the regulation of appetite, pleasure and reward.

 

 

 

Terpenes

 

• Terpenoids are essential oil components.

• Terpenoids, not cannabinoids, are responsible for the aroma of cannabis.

• BCP is a terpene that targets the body’s CB2 receptors.

  • BCP has also been shown to fight cancer, reduce anxiety and depression, and has even been found to be gastroprotective — meaning it can be used to treat ulcers.

  • BCP also is helpful for those suffering from atherosclerosis and osteoporosis and can even increase bone mass and blocks pain signals, all while avoiding any interference with the nervous system.

• Limonene is the second most widely distributed terpenoid in nature.

  • Limonene also produces apoptosis of breast cancer cells.

  • Citrus essential oils with terpenoid profiles resembling those in cannabis demonstrated strong radical scavenging properties.

  • Limonene is common to lemon and other citrus rinds as well.

• Myrcene is another common terpenoid in cannabis.

  • Myrcene diminishes inflammation via prostaglandin E-2.

  • Myrcene blocks hepatic carcinogenesis by aflatoxin.

  • Myrcene is a recognized sedative as part of hops preparations employed to aid sleep in Germany.

• Pinene is the most widely encountered terpenoid in nature.

  • Piene is anti-inflammatory and a bronchodilator in humans at low exposure levels.

  • Piene has shown activity as an inhibitor in aiding memory that could counteract short-term memory deficits induced by THC intoxication.

• Linalool is a terpenoid that has shown to have psychotropic anxiolytic activity.

  • Linalool has been shown to be sedating to mouse activity upon inhalation.

  • Linalool has demonstrated anticonvulsant and anti-glutamatergic activity.

• Nerolidol is a terpenoid alcohol with sedative properties.

  • Nerolidol has anti-protozoal parasite control benefits, as a potent antimalarial agent.

• Phytol is a terpenoid present in cannabis extracts.

  • Phytol was shown to prevent vitamin A-induced teratogenesis by inhibiting conversion of retinol to a harmful metabolite, all-trans-retinoic acid.

  • Phytol has have been shown to increase GABA expression.

 

 

Cannabinoid Degraders

 

• Cannabinoids are broken down by enzymes in the body. Once broken down, the cannabinoids no longer function as cannabinoids through degredation.

• FAAH is fatty acid amide hydrolase.

  • FAAH degrades AEA near the synapses it activates.

  • Blocking the enzyme FAAH has similar results as increasing the amount of AEA.

• 2-AG is degraded by monoacylglycerol lipase (MAGL); it is the main enzyme responsible for inactivating 2-AG.

• There are ways of blocking these above enzymes to increase the levels of AEA and 2-AG currently being worked on in labs.