Cannabinoids refer to a group of chemical compounds which have a 21-carbon ring structure and activate the cannabinoid receptor sites in your body, and that produce effects similar to those seen from the Cannabis plant. Cannabinoids are found in all three species of cannabis – Cannabis Sativa, Cannabis Indica, and Cannabis Ruderalis (hemp). The receptor sites for cannabinoids are located on a wide variety of cells in your body including blood cells, nervous system cells, skin cells, etc. In fact, most of the major organ systems in the body have cannabinoid receptors. This widespread distribution of cannabinoid receptors throughout the body is responsible for the wide variety of effects and therapies that cannabis can be useful for. The cannabis plant also contains terpenes, flavonoids, plant sterols, polysaccharides, and other organic compounds that are not discussed in this article. These compounds act on other receptors than the cannabinoid receptors, which respond solely to the cannabinoids. However, it is felt that these other compounds may affect the cannabinoid receptors through indirect complex mechanisms.
Basically, there are currently three general classes of cannabinoids recognized. Phytocannabinoids are the type that are found in the natural cannabis plant species. Endocannabinoids are the type that are produced in the human body. Synthetic cannabinoids, also called ligands, are those that are chemically created for use as drugs or for research institutions. As you will see, there are some differences between and among these classes.
Phytocannabinoids are sourced directly from the plant. These are the types of cannabinoids you receive when you smoke, vape, eat, dab, or otherwise ingest the flowers, leaves, stems, seeds, or direct extracts unmodified from the plant. The roots do not seem to possess cannabinoids. The phytocannabinoids are the chemical compounds residing predominantly in the trichome glands of the plant, and the trichomes have the highest concentration of cannabinoids. There are perhaps between 100-150 known cannabinoids naturally occurring in the plant, including the well-known THC and CBD. These are chemically named Delta-9 Tetrahydrocannabinol and Cannabidiol respectively…
All of the phytocannabinoids originate from the mother molecule CBG or CBGV (cannabigerol or cannabigerivarin).
This cannabinoid (CBG) has no psychoactive properties but is useful in synergizing with the other cannabinoids, and may aid in the metabolism of CBD, as well as possess many other physiologic properties. Some of these properties of CBG and CBGV are not well established and are an area for future study and research.
In the evolution of the development of the cannabinoids in the plant, CBG and CBGV are converted to CBGA and CBGVA. These compounds then convert though three separate pathways to THCA, CBDA, and CBCA. These are the acid forms that are the carboxylated structures of THC, CBD, and CBC. The raw plant material contains the acidic carboxylated forms. The acidic forms – THCA CBDA and CBCA – breakdown when heated to THC CBD and CBC. These are the active forms for psychoactivity and produce the medicinal effect that you experience when you smoke cannabis. This decarboxylation removes a carboxyl group from the acid (THCA) to convert to the neutral form (THC). This can be accomplished by heat, light, or cooking in oil, or when smoking. To decarboxylate using your oven, please use 200 degrees for 20 minutes. When these cannabinoids age and breakdown due to oxidation, heat or light, then you have a few other cannabinoids created. These would include CBNA, CBN, Delta-8 THC, CBL, and CBLA. As you can see, the list of just some of these cannabinoids can be a bit confusing, and difficult to recite their proper pronunciation. For example, THCVA which is labeled Tetrahydrocannabivarinic acid. The list of phyto cannabinoids is extensive, with over 100 different ones including derivatives, isomers, and both acid and neutral forms. These require independent studies and research both as single agents, and also in combination with other cannabinoids.
Endocannabinoids are those which are produced by the human body. They are also produced by practically every living mammal, from the most primitive to the most advanced. It is safe to say that the vast majority of living animals has an endocannabinoid system and this system dates back many thousands of years. It is an evolutionary developmental system that is ingrained in our existence. It is responsible for homeostasis and to regulate all of our major bodily functions. The endocannabinoids are produced and degraded quickly in response to environmental needs and demands of your body. In general, it has been summarized that the endocannabinoid system (ECS) plays a role in eating, sleeping, protecting neurons, relaxing, and it can cause forgetfulness (this is not always a bad thing! – i.e. PTSD).
There are perhaps 5 major endocannabinoids that have been discovered so far. The first phytocannabinoid was discovered by the Israeli scientist Rafi Mechoulam in Tel Aviv in the nineties. He is responsible for identifying THC and later CBD in the plant. Also important is that he identified the endocannabinoid system in humans. Dr Mechoulam identified THC and CBD in the plant and then determined that they must also bind to a receptor somewhere in the body, and he identified the endocannabinoid system or ECS. This system is composed of the receptors cited above located throughout your body on the cell membranes of a wide variety of cells. These cannabinoid receptors (CB1 and CB2 among others...) respond to both phyto and endo cannabinoids to affect cellular function, by interacting through the cell membrane receptors thereby modifying cellular functions.
The two main endocannabinoids are Anandamide (arachidonylethanolamine) and 2-AG (arachidonylglycerol).
These are produced by the body and they activate the exact same receptors as the phytocannabinoids!! The mechanism, duration, mode of action, and physiologic effects of the endocannabinoids are similar to those produced by the phytocannabinoids, although some differences exist. These differences would include receptor binding strength, duration of action, mechanism of degradation, etc… But by and large the effects of endocannabinoids and phytocannabinoids can be seen as being similar. The endocannabinoid deficiency syndrome (ECDS) is a condition where your body is deficient or lacking in proper levels of endogenous cannabinoids. This causes an imbalance in function identified by digestive disorders, sleep or emotional disorders, neural malfunction, and increased anxiety and stress reactions, among other possible symptoms. The endocannabinoid deficiency syndrome, it should be noted, is not always the cause of these malfunctions. However, in cases where it is the cause of dysfunction, supplemental phytocannabinoids from the plant can be ingested to help alleviate symptoms caused by your lack of proper amounts of endocannabinoids. This makes up for a possible imbalance. The levels of Anandamide and other endocannabinoids can possibly be assessed though blood or serum testing in order to determine if there is a deficiency, so this disease could be chemically identified. Research in this area can be developed in the future, and patients with proven deficiencies can be treated using phytocannabinoids ingested from the plant.
Synthetic cannabinoids are those that are produced chemically and created in a lab or test tube. These are also called ligands. There are many companies producing synthetic cannabinoids predominantly to be used in research, and currently this research is being done mainly in mice. These synthetic ligands bind to the cannabinoid receptors and activate these receptors and initiate activity within the cell, thereby affecting the whole organism’s metabolism and bodily operations. They provide a similar effect as the two other classes of cannabinoids, but once again differences exist. Some of these compounds (i.e. JHW 073) are created to bind with more affinity and longevity to the receptors which allows longer study periods of researching their effect. Since they are not natural cannabinoids but man made, it is not always possible to assume they act in the exact same fashion. Nonetheless, they are very useful in research since the real plant material is still illegal to obtain for research in this country, and the same is true for many other countries. The International Cannabis Research Society, for example, uses synthetic ligands predominantly developed for research in mice, and studies their effects in a whole host of bodily systems, diseases, illnesses, and metabolic functions. In the future, research needs to be modified to use actual human subjects, and real-time cannabinoids that are available in the dispensary for real time results. This is coming…
The recent upsurge in the use of synthetic cannabis in “bath salts” and “spice” “K2” is one drawback to having created these synthetic cannabis ligands. These are dangerous, unregulated potentially harmful compounds. Bootleg or black-market individuals are marketing these chemicals for getting high, and they are available for ingestion illegally. Chemically produced in an underground lab, or hijacked from researchers, these are harmful, unregulated, and of unknown potency or purity. They are capable of causing harmful or extreme side effects not found with phytocannabinoids. They are not designed for safety in humans, and can cause extreme anxiety and severe unwanted effects. They should remain illegal and be confiscated by law enforcement so as not to give cannabis a “bad name”.
Cannabinoids as a group represent unique compounds found only in the cannabis plant or in the human body’s endocannabinoid system. Echinacea is the only other species of plant that holds a minor cannabinoid. Some cannabinoids are probably yet to be discovered. Most research is being done on THC and CBD, but the other hundred or so compounds require further investigation and research. Combining the cannabinoids generally produces a synergistic effect (entourage). A complex puzzle, but rest assured that researchers around the globe are studying the effects of all major cannabinoids and their effect on human health, disease, and biologic activity. These cannabinoids will become an accepted mode of therapy which can ultimately benefit all humankind.
Dr. Stanley R. Manstof
12201 Greenridge Drive
Boyds, Md. 20841
*MMCC Certified Provider
*American Academy of Cannabis Physicians
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*Technical Writer and Editor
*Member Society of Cannabis Clinicians
*International Cannabinoid Research Society
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