Cannabinoid Receptors

Primary cannabinoid receptors are identified as Cannabinoid type 1 receptors (CB-R) and Cannabinoid type 2 receptors (CB2-R). These receptors can be “unlocked” by three kinds cannabinoids:

1. Endocannabinoids – endogenous-fatty-acid cannabinoids produced naturally in the body. (e.g., anadaminde and 2-AG)
2. Phytocannabinoids – concentrated in the oily resin of the buds and leaves of plants such as cannabis (e.g., THC and CBD)
3. Synthetic cannabinoids – manufactured by artificial means such as in a laboratory

CB1-R was first detected in the brain and studies now show that it is found many other organs, connective tissues, gonads and glands. CB1-R play an important role in the coordination of movements, spatial orientation, cognitive performance and motivation and sensory perceptions such as taste, touch, smell, and hearing.

The most important function of the CB1-R is the reduction of excessive or inadequate signaling by the neurotransmitters in the brain. When CB1-R is activated the hyperactivity of the messengers is regulated back into balance. Simply, when THC binds to BC1-R activity in the pain circuits in inhibited which results in a reduction of pain. Symptoms such as nausea, muscle spasticity and seizures can be either alleviated or diminished with cannabinoid therapy.

CB2-R are associated with the immune system and found outside of the brain in places such as the gut, spleen, liver, heart, kidneys, bones, blood vessels, lymph cells, endocrine glands and reproductive organs. Studies show that CB2-R plays an important role in the signal processing of the brain.

The TRPV1(transient receptor potential vanilloid-type one) is a receptor which detects and regulates body temperature. It also is responsible for the sensations of extreme external heat and pain and is subject to desensitization. If this receptor is continuously stimulated the pathway will eventually slow down or even stop. This stimulation raises therapeutic possibilities for agents to effectively treat certain kinds of neuropathic pain.

From 1992 to today research has shown that there are over 200 substances which resemble endocannabinoids and complement their function in what has been termed the “entourage effect.” Several endocannabinoids do not only bind to cannabinoid receptors, but also to a possible CB3 receptor (the GPR55 receptor) to vanilloid receptors and further receptors.

Aside from endocannabinoids, phytocannabinoids have been found in the cannabis plant and have been identified to work to mimic or counteract the effects of some endocannabinoids. Phytocannabinoids and terpenes are manufactured in resin glands (trichomes) present on the flowers and main fan leaves of late-stage cannabis plants. The amount of resin produced and its cannabinoid content varies by plant gender, growing conditions and harvesting time. A cannabinoids chemical stability is affected by temperature, moisture, light and storage, but they will eventually degrade over time in any storage conditions.

A cannabinoid is labeled as an “agonist” when is causes a receptor to act in the same way as it would to a naturally occurring hormone or neurotransmitter. Whereas when a cannabinoid is labeled as an “antagonist” the cannabinoid prevents a receptor from binding to the naturally occurring compound. When a cannabinoid is labeled as an “antagonist”, the resulting event is either altered or diminished. Research is still being conducted to better understand how specific cannabinoids can unlock or lock specific receptors.

Within the cannabis plant there have been over 100 phytocannabinoids that have been identified within the cannabis plant and many have documented medicinal values. Most are the same with just a slight chemical variation making them different from one another. The most commonly known and studied cannabinoids within the cannabis plant are THC which produces the feeling of being “high” and CBD for its healing properties.

Cannabinoids can be taken by a patient by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption or rectal suppository.

Entourage Effect

The entourage effect was introduced as a concept by Israeli scientists Shimon Ben-Shabat and Raphael Mechoulam in 1998. Their concept’s focus is that cannabinoids within the cannabis plant work together through a network of coincidental relationships as part of a greater organism and affect the body in a mechanism like the body’s own endocannabinoid system. In short, these compounds work better together than in isolation.

The medicinal superiority of cannabis in comparison to other products containing isolated, single components of the cannabis plant, or synthetic cannabinoids trying to replicate the natural components provokes more research to be conducted to fully understand the medicinal affects that can be found within the cannabis.

Research has shown that THC and CBD when combined give a patient better medicinal aid opposed to them being taken separately. When THC is taken separately and not in proper quantities, there have been reports of THC overdose. Good evidence shows that THC and CBD work together because CBD is known to lock out THC at the CB1-R. When applying the entourage effect, increasing the amount of CBD in the case of a THC overdose will lessen the effects caused by the overdose.

Synthetic cannabinoids have been created, such as Marinol, which are pure synthetic forms of THC. Marinol was introduced in the mid-80’s and it was designed to have the same effect as the cannabis plant as a whole. Upon usage from patients, it was found that patients were not receiving the same affects that came from naturally grown THC. This let researchers to realize that other compounds such as CBD and various terpenes play a larger role than previously realized.

New vs. Old Science

The discovery of the CB1 receptor was in 1988 by Allyn Howlett and Willian Devane. Upon their discovery, CB1 was recognized to have little binding affinity for the CB1 receptor. However, as of today research shows that CBD interacts directly with the CB1 receptor site in ways that are therapeutically relevant. CBD influences how a receptor responds to stimulation by THC and the endogenous cannabinoids. Allosteric modulation of CB1-R changes the conformation (shape) or the receptor, and this can have a dramatic impact on the efficiency of cell signaling.

A positive allosteric modulator that enhances CB1 receptor signaling indicates that CBD could be helpful treating diseases linked to endocannabinoid deficits such as anorexia, migraines, irritable bowel, fibromyalgia, and PTSD. It may also help in treating conditions associated with endocannabinoid excess or over activity, obesity, metabolic disorders, liver disease, cardiovascular issues.