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What are cannabinoids?

PHYTOCANNABINOIDS

Phytocannabinoids refer to the type of compounds characterised by 21 carbon atoms and found in nature only in the plant Cannabis Sativa L.. Over 80 phytocannabinoids have already been found, including their acidic and neutral forms, their analogues and other transformation products. The plant is only able to synthesise the phytocannabinoids directly in their non-psychoactive form. The most important phytocannabinoids in fresh plant material are therefore 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 drying and curing of the biomass; 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 the plants.

ENDOCANNABINOIDS

Endocannabinoids are produced by almost all organisms of the Animal Kingdom produced. They are natural endogenous ligands produced by human and animal organisms that bind to the cannabinoid receptors. Both endocannabinoids and 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 action. CB1 is mainly located in the central nervous system and is responsible for the effects and psychoactive "secondary effects" mediated by neuronal processes. 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 the laboratory. An example of this would be dronabinol, the active ingredient in MARINOL®, a drug 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 cannabis effects. 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 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 synthesised.

MAIN NON-PSYCHOACTIVE PHYTOCANNABINOIDS

The commercial hemp plant contains many phytocannabinoids with weak or no psychoactivity, which could be more promising from a therapeutic point of view than Δ9-THC.

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 people 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 effects. However, it can attach to certain vanilloid receptors, but its effects are not yet fully known. In addition, it acts against proliferation.

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.

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