What are Cannabinoids?

The word Cannabinoids refers to every chemical substance, regardless its origin or structure, that joins the cannabinoid receptors of the body and brain and that have similar effects to those produced by the plant Cannabis Sativa L. (Industrial Hemp). We know it is a large and varied group of substances that can be classified in several ways, but the most useful way to understand the cannabinoid diversity is the following:

PHYTOCANNABINOIDS

Phytocannabinoids make reference to the kinds of compounds characterised by 21 carbon atoms which only show in nature in the plant Cannabis Sativa L.. Over 80 phytocannabinoids have already been found, including their acidic and neutral forms, their analogous and other transformation products. The plant is just 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 in 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.

ENDOCANNABINOIDS

Endocannabinoids are produced by almost every organism in the animal kingdom. They are natural endogenous ligands produced by human and animal organisms that join the cannabinoid receptors. Both endocannabinoids and cannabinoid receptors form the endocannabinoid system, which is involved in a large variety of physiological processes, such as the control of the neurotransmitters release, the pain perception and the cardiovascular, gastrointestinal and liver functions. The two main endocannabinoids found are the anandamide and 2-arachidonoylglycerol. Endocannabinoids are the molecules that act as natural key for the main cannabinoid receptors CB1 and CB2 and cause their activation and subsequent action. CB1 is mainly located in the central nervous system and it is responsible for the effects mediated by neuronal processes and psychoactive 'secondary' effects. CB2 is mainly located in the immune system and it is responsible for the immunomodulatory effects. CB2 receptors have been recently discovered in the central nervous system, the microglial cells and they seem to be in certain neurons as well.

SYNTHETIC CANNABINOIDS

The main difference between phytocannabinoids, endocannabinoids and synthetic cannabinoids is that the latter are fully synthetic and created in the laboratory. An example of it 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 loss of weight. Another example would be nabilone, that 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. More recently, some selective cannabinoids for CB1 receptor, such as JHW-018 and JHW-073, have been used as psychoactive ingredients in smart drugs marketed as imitations of Cannabis effects. One of the names used for these drugs is “Spice”. There is not much information about the effects of synthetic cannabinoids in humans, although some of them have already shown to cause more distress and panic than phytocannabinoids. Synthetic cannabinoids have been designed as research tools for cannabinoid scientific studies, however, they have never shown to be reliable for human consumption in clinical testing. In theory, they should have never left the laboratory where they were designed and synthesised.

MAIN NON-PSYCHOACTIVE PHYTOCANNABINOIDS

The Industrial Hemp plant contains many phytocannabinoids with weak or null psychoactivity, which, from a therapeutic point of view, could be much more promising than Δ9-THC.

CBD is an important non-psychotropic phytocannabinoid that produces a large amount of pharmacological, anti-oxidant and anti-inflammatory effects, among others, transmitted by several mechanisms. It has been clinically proven in cases of anxiety, psychosis and movement disorders, as well as to alleviate neuropathic pain in individuals suffering from multiple sclerosis (it is sometimes combined with Δ9-THC in a 1:1 proportion, as happens in SATIVEX®).

CBDA does not join CB1 and CB2 cannabinoid receptors, although it is an inhibitor of selective COX-2 with anti-inflammatory effects. However, it can join certain vanilloids receptors, but its effects are not fully understood yet. In addition to this, it does act against proliferation.

CBG acts against proliferation and as an antibacterial. It is a ligand from CB2 cannabinoid receptor and an inhibitor of the re-absorption of anandamide. Furthermore, it is a vanilloids ligand.

CBC can cause hypothermia, sedation and hypoactivity in mice. It also acts as an anti-inflammatory, an antimicrobial and a soft analgesic. Moreover, it is a powerful antagonist of vanilloids and a weak inhibitor of the re-absorption of anandamide.