Cannabinoïdes de synthèse : aspects pharmacologiques

The synthetic cannabinoids (SC) come from the pharmaceutical industry and were synthesized when the endocannabinoid system has been discovered in the 2000s. This system is mainly composed of the two subtypes of cannabinoid receptors 1 and 2 (RCB1 and RCB2) and their endogenous ligands anandamide and 2-arachidonoylglycerol (2-AG). These SC have been considered in many therapeutic applications, but the occurrence of many adverse effects (in particular psychotropic) in clinical trials led to the abortion of drug development, but their use as recreative drugs appeared simultaneously. RCB1 are essentially expressed in the brain, at presynaptic level on central neurons. Their stimulation results in a decrease of the release of neurotransmitters, leading to sedative and relaxing effects. Anandamide and 2-AG, released from the postsynaptic neuron after significant depolarization, allow, by acting on the RCB1 presynaptic receptors, to modulate the release of neurotransmitters and thus to oppose to the overstimulation of the postsynaptic neuron. Stimulation of RCB2 located in the immune system lead to anti-inflammatory effects. The SC has a greater affinity for these receptors than THC and is full agonist, unlike THC that is only a partial agonist, explaining the greater effects and toxicity observed for SC compared to THC. They are highly metabolized primarily by CYP2C9 and 1A2 and strongly glucuronized prior to urinary excretion.