What are cannabinoids?

PHYTOCANNABINOIDS

Phytocannabinoids refer to the type of compounds characterized by 21 carbon atoms and found in nature only in the plant Cannabis Sativa L.. More than 80 phytocannabinoids have already been found, including their acidic and neutral forms, their analogues and other transformation products. The plant is only capable of synthesizing the phytocannabinoids directly in their non-psychoactive forms. Thus, the major phytocannabinoids in fresh plant material are Δ9-THCA, CBDA, CBGA, and CBCA. However, the carboxyl group is not very stable and is easily lost as CO2 when exposed to heat or light, causing conversion to the active neutral forms. The acidic phytocannabinoids are partially decarboxylated during biomass drying and curing; as a result, acidic phytocannabinoids and some of their active neutral forms (Δ9-THC, CBD, CBG, and CBC) are mainly present in the dry material of plants.

ENDOCANNABINOIDS

Endocannabinoids are produced by almost all organisms of the Animal Kingdom are produced. They are natural endogenous ligands produced by human and animal organisms that bind to cannabinoid receptors. Both the endocannabinoids and the cannabinoid receptors form the endocannabinoid system, which is involved in a variety of physiological processes such as controlling the release of neurotransmitters, pain perception and cardiovascular, gastrointestinal and liver functions. The two most important endocannabinoids are anandamide and 2-arachidonoylglycerol. Endocannabinoids are the molecules that act as a natural key to the main cannabinoid receptors CB1 and CB2, causing their activation and subsequent effects. CB1 is mainly located in the central nervous system and is responsible for the effects mediated by neuronal processes and psychoactive "secondary effects". CB2 is mainly located in the immune system and is responsible for the immunomodulatory effects. CB2 receptors have recently been discovered in the central nervous system, in microglial cells and apparently also in certain neurons.

SYNTHETIC CANNABINOIDS

The main difference between phytocannabinoids, endocannabinoids and synthetic cannabinoids is that the latter are completely synthetic and produced in a laboratory. An example of this would be dronabinol, the active ingredient in MARINOL®, a medicine in capsule form that has been used in the USA since 1985 to treat nausea, vomiting, loss of appetite and weight loss. Another example is nabilone, the active ingredient in CESAMET®, a drug approved to combat nausea and vomiting associated with cancer chemotherapy. Both drugs are approved for these purposes in the USA, the UK, Switzerland, Canada and Spain. More recently, some selective cannabinoids for the CB1 receptor, such as JHW-018 and JHW-073, have been used as psychoactive ingredients in smart drugs marketed as imitations of the effects of cannabis. One of the names used for these drugs is "spice". There is not much information on the effects of synthetic cannabinoids in humans, although some of them have already been shown to cause more stress and panic than phytocannabinoids. Synthetic cannabinoids were developed as research tools for scientific cannabinoid studies, but have never been shown to be reliable for human consumption in clinical trials. Theoretically, they should never have left the laboratory where they were developed and synthesized.

MAIN NON-PSYCHOACTIVE PHYTOCANNABINOIDS

The commercial hemp plant contains many phytocannabinoids with weak or no psychoactivity that may be more promising than Δ9-THC from a therapeutic perspective.

CBD is an important non-psychotropic phytocannabinoid that has a variety of pharmacological, antioxidant, and anti-inflammatory effects mediated by different mechanisms. It has been clinically proven to relieve anxiety, psychosis, and movement disorders, as well as neuropathic pain in individuals suffering from multiple sclerosis (sometimes combined with Δ9-THC in a 1:1 ratio, as in SATIVEX®).

CBDA does not act at the cannabinoid receptors CB1 and CB2, although it is a selective COX-2 inhibitor with anti-inflammatory activity. However, it can attach to certain vanilloid receptors, but its effects are not yet fully known. In addition, it has anti-proliferative effects.

CBG acts against proliferation and as an antibacterial agent. It is a ligand of the CB2 cannabinoid receptor and an inhibitor of anandamide reuptake. It is also a vanilloid ligand.

CBC can induce hypothermia, sedation and hypoactivity in mice. It also has anti-inflammatory, antimicrobial, and mild analgesic effects. It is also a potent antagonist of vanilloids and a weak inhibitor of anandamide reuptake.