Cannabinoids are transformation products and synthetic analogs of some terpene phenols (partially hydrogenated dibenzfuran derivatives), which are mainly found in the hemp plant(Cannabis sativa or Cannabis indica).
Phytocannabinoids: The hemp plant C. sativa contains > 110 natural phytocannabinoids from the group of terpene phenols , which have not yet been discovered in any other plant. The cannabinoids listed below are the best-studied phytocannabinoids:
Other phytocannabinoids (not derived from the cannabis plant):
- It has been shown that other plants also produce various phytocannabinoids. For example, N-isobutylamides, which are produced from echinacea , have been shown to be potent cannabinoid mimetics.
Endocannabinoids:
- These are endogenous substances with similar pharmacological properties to external cannabinoids (phytocannabinoids).
Synthetic cannabinoids:
- these have become an increasingly common drug of abuse, sold under various street names such as K2, Spice and Black Mamba.
The effects of cannabinoids come about through the binding and activation of cannabinoid receptors (CB receptors). THC, for example, is a potent agonist of the CB1 receptor, which mediates the psychotropic effects and the activation of the reward pathways. In addition, CBD and CBDV activate both TRPV1 and TRPV2 (so-called capsaicin receptors) and TRPA1 channels in a dose-dependent manner.
The following cannabinoid receptors are known to date:
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CB1 receptors: These are mainly found in the CNS, but also in the periphery such as the gastrointestinal tract, fat cells and postganglionic neurons of the autonomic nervous system. Their activation acts Gi/o-mediated inhibition of adenylcylcase, opening of K+ channels and closing of neuronal Ca2+ channels. CB1 receptors also appear to play a role in the regulation of food intake and energy metabolism.
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CB2 receptors: CB2 receptors are mainly found on immunocompetent cells of the hematopoietic system, in the intestine and on osteoblasts and osteoclasts. Their activation is also Gi/o-mediated.
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GPR18, GPR119 and GPR55 receptors: These G-protein-coupled receptors (GPR) act as cannabinoid receptors in the endocannabinoid system . They mediate a broad spectrum of biochemical reactions.
Endogenous ligands of the CB receptors(endocannabinoids) are the arachidonic acid derivatives anandamide and 2-arachidonylglacerol. Little is yet known about their physiological significance.
Other ligands of the CB receptors: A new class of potent cannabinoid mimetics are the N-isobutylamides, which are produced from echinacea. These bind to the peripheral CB2 cannabinoid receptors on immune cells, but not to the CB1 receptors in the central nervous system.
Yangonin from the kava plant (Piper methysticum) and various catechins from the tea plant (Camellia sinensis) also act on CB1 receptors.