The History of Cannabis

Cannabis is the world’s oldest pharmacopoeia. The earliest evidence of cannabis use dates back to 4000 BC in China and cannabis used as medicine dates back to 1000 BC in India, Syria and Tibet and 100 AD in China. Until the early 1900’s, cannabis was used for the skin, stomach, colds, urination, energy, epilepsy, anxiety, rheumatism, bronchitis, asthma, gout, edema, infectious wounds, headaches, pregnant women, a general tonic, and of course, to calm the mind.

In the early 1900’s cannabis started to lose popularity with the production of vaccines and analgesics such as aspirin, and then with the prohibition of cannabis in 1923. In 1940, a Harvard trained chemist Roger Adams successfully extracted CBD from cannabis, and despite the continued prohibition, cannabis started increasing in popularity again in the 1970’s due to the discovery of the isolation of Delta-9 Tetrahydrocannabinol (THC) by Dr. Mechoulam and Dr. Gaoni from the University of Jerusalem. And in the late 1980’s and early 1990’s the Endocannabinoid System (Dr. Hanus and Dr. Devane), CB1 receptor(Gerard and Colleagues from Brussels), CB2 receptor(Sean Munro from Cambridge), and the endocannabinoids Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) (Dr. Hanus and Dr. Devane) were discovered.

The Science of Cannabis

The ECS’s primary role is in maintaining homeostasis in the body, exists in all vertebrates and is active in our bodies even if we do not use cannabis. The endocannabinoids Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) are created and produced by the body’s endocannabinoid system in a very similar manner to how it produces endorphins, are similar to phyto-cannabinoids (cannabis plants), and help keep internal functions operating smoothly.

Interactions of AEA and 2-AG with the endocannabinoid receptors CB1 and CB2 affect biological functioning and health. The CB1 and CB2 receptors are found throughout the body and AEA and 2-AG bind to either of them in order to signal the Endocannabinoid System to take action. The effects that result depend on where the receptor is located and which endocannabinoid it binds to.

It has been scientifically shown that THC and CBD produce superior results when administered in combination with other chemical compounds found in phyto-cannabinoids (cannabis plants) like minor cannabinoids such as CBC, CBG, CBN and THCV and terpenes such as Myrcene, Limonene, Pinene, Linalool, Caryophyllene and Humulene, compared to pure THC and CBD extracts. And how the Entourage Effect can dramatically increase the medicinal utility of THC and CBD, either by magnifying their effects or increasing their therapeutic applications.

The therapeutic effects of cannabis compounds arise from their capacity to bind with naturally occurring endocannabinoid receptors found throughout the central nervous system (CB1 receptors) and especially in the immune cells of the peripheral nervous system (CB2 receptors). The endocannabinoids Anandamide (AEA) and 2- Arachidonoglycerol (2-AG) can bind to either receptor and the effects that result depend on where the receptor is located and which endocannabinoid it binds to.

However, compounds in phyto-cannabinoids can just as efficiently bind with these receptors. Phyto-cannabinoids will produce different effects on the body depending on which type of receptor site they bind to. For example, it is known that CBD interacts with the Endocannabinoid System (ECS) but it does not bind to CB1 or CB2 receptors the way that THC does, as CBD possibly works by preventing endocannabinoids from being broken down and allows them to have more effect on the body. Research has also shown that CBD has the capacity to either moderate or intensify the binding activity of THC with endocannabinoid receptors in the brain, and therefore new and unique properties may emerge from the interaction of various cannabis chemical compounds and that even tiny alterations in the formula may be enough to produce medically significant differences.

As there is a vast variety of cannabis cultivars available with a matching array of cannabinoids and terpenes, that when consumed, bind to these sites creating a multitude of different effects on the body and thus corresponding to a wide variety of healing properties, and therefore that is why the cannabis plant can treat so many different conditions (Ratcliff, S. (2020, June 18) The Science Behind the Entourage Effect. Retrieved from Cannabistech.com/articles/what-is-the-entourage-effect-in-cannabis)

Physiological issues may result when our bodies do not produce enough of the endocannabinoids Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) for the Endocannabinoid System (ECS) to function properly. The ECS is a biological grid of connectors with the largest network of neurotransmitters in the body, is present in every significant bodily structure, works towards maintaining homeostasis and is responsible for regulating many important functions. So when the signals from the ECS begin to transmit at improper levels, it can result in Endocannabinoid Deficiency Syndrome.

The CB1 and CB2 receptors react with the two primary endogenous cannabinoids AEA and 2-AG which the body produces as needed. These endocannabinoids can stimulate the cannabinoid receptors by binding to them and transmitting signals that create effects best suited to correct the physiological imbalances in the body. After the endocannabinoids finish their work, the ECS utilizes two types of metabolic enzymes – fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) that break down the endocannabinoids, and where FAAH breaks down AEA and MAGL typically breaks down 2-AG.

And because the ECS stretches through almost every substantial aspect of the human body, Endocannabinoid Deficiency Syndrome has the potential to have a wide range of effects. Any alterations that affect varying levels of endogenous cannabinoids, either through the destruction and failure in production of the weakening and strengthening of cannabinoid receptors can influence its regulatory capabilities for several functions. In addition, every individual has a certain cannabinoid baseline. This corresponds to the circulating levels of the primary endocannabinoids AEA and 2-AG, but also includes the rate of their synthesis and breakdown as well as the relative density of cannabinoid receptors in the brain.
Endocannabinoid deficiencies can occur in four ways:

  1. Not enough cannabinoid receptors – as there are not many connectors for the endocannabinoids to attach themselves to and without a connector, the signal cannot be transmitted to its designated area.
  2. An overabundance of metabolic enzymes – meaning the body is producing too many FAAH and MAGL enzymes that break down the endocannabinoid or they do so too soon before the endocannabinoid can bind to a receptor.
  3. Synthesizing insufficient endocannabinoids – the body is not making AEA and 2-AG correctly and so these deformed or incomplete molecules cannot make it to the receptors or cannot attach and transmit successfully if they do arrive.
  4. Not enough action between endocannabinoids and cannabinoid receptors – there is not adequate communication happening with the compounds and the connectors and this effect could be caused by anything from improper attachment to week signaling.

Finally, the signals transmitted by endocannabinoids can change in quantity, which means that the available cannabinoid receptors in the body would need to either increase or decrease too, and therefore it is this fluctuation that can restrict how your body reaches homeostasis leading to potential complications (Carter, W. (2020) 3 Signs of Endocannabinoid Deficiency Syndrome. Retrieved from cbdmd.com/blog/signs-of-endocannabinoid-deficiency).

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