Cannabinoid Science

The majority of pharmaceutical and academic research & development activities being performed with cannabis revolves around the understanding of its biologically active ingredients, the Cannabinoids

Currently there are 90+ cannabinoids that have been isolated from cannabis, each affecting the body’s cannabinoid receptors and responsible for unique pharmacological effects.

There are three general types of cannabinoids: herbal cannabinoids which occur uniquely in the cannabis, endogenous cannabinoids produced in the bodies of humans and animals and synthetic cannabinoids produced in the laboratory.

Cannabinoid Receptors

Before the 1980s, it was often speculated that cannabinoids produced their effects through nonspecific interaction with cell membranes, instead of interacting with specific receptors. The discovery of the first cannabinoid receptors in the 1980s helped to clarify their role. These receptors are common in animals, and have been found in mammals, birds, fish and reptiles. There are currently two known types of cannabinoid receptors, called CB1 and CB2.

CB1 receptors are found primarily in the brain, specifically in the basal ganglia and in the limbic system, including the hippocampus. They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are essentially absent in the medulla oblongata, the part of the brain that is responsible for respiratory and cardiovascular functions. Thus, there is not a risk of respiratory or cardiovascular failure as there is with many other drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis.

CB2 receptors are almost exclusively found in the immune system, with the greatest density in the spleen. CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis.

The protein sequences of these two receptors are about 45% similar. In addition, minor variations in each receptor have been identified. There is some indication that other receptors exist, but none have been confirmed. Cannabinoids bind reversibly and stereo-selectively to the cannabinoid receptors. The affinity of an individual cannabinoid to each receptor determines the effect of that cannabinoid. Cannabinoids that bind more selectively to certain receptors are more desirable for medical usage.

Herbal Cannabinoids

Herbal cannabinoids are nearly insoluble in water but soluble in lipids, alcohols and other non-polar organic solvents. All herbal cannabinoids are derived from their respective 2-carboxylic acids (2-COOH) by decarboxylation that is, catalyzed by heat, light, or alkaline conditions. Herbal cannabinoids occur naturally only in the cannabis plant, and are concentrated in a viscous resin that is produced in glandular structures known as trichomes. In addition to cannabinoids, the resin is rich in terpenes, which are largely responsible for the odor of the cannabis plant.

There are over ninety known herbal cannabinoids. Of these, tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prevalent and have received the most attemtion. Other common cannabinoids include:

CBG

Cannabigerol

CBC

Cannabichromene

CBL

Cannabicyclol

CBNCannabidiol

CBV

Cannabivarol

THCV

Tetrahydrocannabivarin

CBDV

Cannabidivarin

CBCV

Cannabichromevarin

CBGV

Cannabigerovarin

CBGM

Cannabigerol Monoethyl Ether

THC is the primary psychoactive component of the plant. Medically, it appears to mediate pain and to be neuroprotective. THC has a greater affinity for the CB1 receptor than for the CB2 receptors. Its effects are perceived to be more cerebral.

CBD is not psychoactive, and appears to mediate the euphoric effect of THC. It may decrease the rate of THC clearance from the body, perhaps by interfering with the metabolism of THC in the liver. Medically, it appears to relieve convulsion, inflammation, anxiety, and nausea. CBD has a greater affinity for the CB2 receptor than for the CB1 receptor. It is perceived to have more effect on the torso than on the brain or CNS.

Cannabinoids were first discovered in the 1940s. The structure of THC was first determined in 1964. Due to molecular similarity and ease of synthetic conversion, it was originally believed that CBD was a natural precursor to THC. However, it is now known that CBD and THC are produced independently in the cannabis plant.

Cannabis plants can exhibit wide variation in the quantity and type of cannabinoids they produce. The mixture of cannabinoids produced by a plant is known as the plant’s cannabinoid profile. Selective breeding has been used to control the genetics of plants and modify the cannabinoid profile. For example, strains of hemp, which are used as fiber, are bred such that they are low in psychoactive chemicals like THC. Strains used in medicine are often bred for high CBD content, and strains used for recreational purposes are usually bred for high THC content, or for a specific chemical balance. Some strains of more than 20% THC have been created.

Cannabinoids can be administered by: smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption, or rectal suppository. Once in the body, most cannabinoids are metabolized in the liver, although some is stored in fat.

Cannabinoids can be separated from the plant by extraction with organic solvents. However, to produce high purity, cannabinoid chemical synthesis or semisynthesis is generally required.

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