The term cannabinoids encompasses every chemical substance, natural or man-made, that binds to the body’s and brain’s cannabinoid receptors to produce effects similar to those produced by the plant Cannabis Sativa L. (Industrial Hemp). cannabinoids are a large and diverse group of substances that can be classified in various ways, but the most useful way to understand cannabinoid diversity is the following: endocannabinoids, phytocannabinoids and synthetic cannabinoids.
Endocannabinoids are a type of natural ligand that attaches to cannabinoid receptors. They are produced by most organisms in the animal kingdom, as noted in the article “The Endocannabinoid System of Animals” by Robert J. Silver. Both endocannabinoids and cannabinoid receptors make up the endocannabinoid system, which regulates a variety of physiological processes like neurotransmitter release, pain perception, and gastrointestinal, cardiovascular, and liver functions. The two most common endocannabinoids are anandamide and 2-arachidonoylglycerol. Endocannabinoids act as a natural key for the main cannabinoid receptors CB1 and CB2, causing their activation and subsequent action. CB1 receptors are mostly found in the central nervous system and are responsible for effects mediated by neuronal processes and psychoactive ‘secondary’ effects. CB2 receptors are mostly found in the immune system and regulate immunomodulatory effects. CB2 receptors have recently been discovered in the central nervous system and microglial cells, and they appear to be in certain neurons as well.
Phytocannabinoids are a class of compounds characterised by 21 carbon atoms which are only found in nature in the plant Cannabis Sativa L. Over 113 phytocannabinoids have already been discovered, including their acidic and neutral forms, and their transformation products. The plant is only able to synthesise the phytocannabinoids directly in their non-psychoactive forms. Therefore, the main phytocannabinoids present in fresh plant material are Δ9-THCA, CBDA, CBGA and CBCA. However, the carboxyl group is not very stable and it is easily lost as CO2 under the influence of heat or light, which causes the transformation into the active neutral forms. The acidic phytocannabinoids suffer partial decarboxylation in the drying and curing process of the biomass; subsequently, acidic phytocannabinoids and some of their active neutral forms (Δ9-THC, CBD, CBG and CBC) are mainly found in the plant dry material.
The main difference between phytocannabinoids, endocannabinoids and synthetic cannabinoids is that synthetic cannabinoids are completely man-made and created in a laboratory. An example of a synthetic cannabinoid would be dronabinol, which is the active compound of MARINOL®, a medicine that comes in capsules and has been consumed in the US since 1985 to prevent nausea, vomiting, loss of appetite and weight loss. Another example of a synthetic cannabinoid is nabilone, which is the active substance of CESAMET®, a medicine approved for the nausea and vomiting control caused by cancer chemotherapy. Both medicinal products have been approved for these purposes in the US, United Kingdom, Switzerland, Canada and Spain. Some selective cannabinoids for the CB1 receptor, such as JHW-018 and JHW-073, have been used as psychoactive components in so-called smart drugs that imitate the effects of Cannabis. These drugs go by the name “Spice.” There is not much information available about the effects of synthetic cannabinoids in humans, although some of them have already been shown to cause more distress and panic than phytocannabinoids. Synthetic cannabinoids were designed as research tools for cannabinoid scientific studies; however, they have never proven to be reliable for human consumption in clinical testing. In theory, they should never have left the laboratory where they were designed and synthesised.
The 2018 article “Synthetic cannabinoids severely elevate amino transferase levels. Natural cannabidiol does not” by Donish Cushing, Bomi Joseph published that the reason synthetic compounds are dangerous is because “The human body is not equipped with the tools needed to catabolize synthetic cannabinoids”. This is because novel cannabinoid molecules created through synthesis are chemically very different from their naturally derived counterparts. This means that the human body does not have the appropriate enzymes to break them down, which could be very dangerous.