Cannabinoids

Sticky, resinous substances secreted by the hemp plant(cannabis) as resin on the surface of the leaves. This film has an antimicrobial effect and offers the plant protection against microorganisms (bacteria and fungi). The most common cannabinoids are tetrahydrocannabinol and cannabidiol. Cannabis produces over 100 cannabinoids with very different pharmacological effects. The common precursor of these phytocannabinoids is cannabigerol.

In addition to the natural cannabinoids, there are synthetic cannabinoids such as nabilone, which is used as an antiemetic in oncology, and endocannabinoids produced by humans, in particular anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

The cannabinoid receptors CB1 and CB2 are the target structures of cannabinoids when absorbed into the human organism. The receptors bind N-palmitoylethanolamine (PEA) and mediate analgesic, sedative and antiemetic effects.

The expression of cannabinoid receptors in human skin is dermatologically relevant. This knowledge has already been used in studies for the treatment of chronic pruritus (available preparation = Physiogel AI cream).

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:

• Delta 9 -tetrahydrocannabinol: The best pharmacologically and clinically investigated, highly psychotropic main active ingredient of Cannabis sativa is delta 9 -tetrahydrocannabinol( THC=dronabinol ).
• Cannabidiol: Cannabidiol is in 2nd place in terms of quantity. Cannabidiol has antiphlogistic, anti-schizophrenic and anti-epileptic but not psychotropic effects.
• Cannabinol: A third well-studied substance is cannabinol.
• Cannabidivarin (CBDV): antiepileptic effect; ligand of TRPV1- as well as TRPV2

• Cannabigerol(CBGV): Affinity to CB1 receptors

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:

• 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.
• 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.
• 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.

The study of cannabinoids led to the discovery of the endocannabinoid system.

Cannabinoids act:

• Psychotropic (already in dosages of 5-10mg ^Delta9 -THC ).
• Euphoric (very strong effect when smoking hashish)
• Sedating
• Muscle relaxant (e.g. in MS patients)
• Spasmolytic
• Analgesic
• Antiemetic
• Appetite stimulant
• Immunomodulatory: Topically applied cannabinoids (CBD and THC) suppress proinflammatory cytokines, IL such as IL-6 and IL-17. Pretreatment with CBD leads to upregulation of IL-10.

Cannabinoids lead to

• Disturbances in visual/acoustic sensory perceptions.

In higher doses, they cause psychosis-like states (hallucinations, thought disorders, disturbances of time and space perception, impairment of cognitive functions).

Degradation: THC is metabolized mainly in the liver (HWZ=50h). This process also produces metabolites that are still active, such as 11-hydroxy-THC. THC and its metabolites are very lipophilic and have very large distribution areas, from which they are eliminated only very slowly via the stool (70%) and urine 30%. Therefore, they can be detected in the excrement even a very long time after their consumption, which can be of great importance forensically.

The doping list includes phytocannabioids with the active ingredient tetrahydrocannabinol (THC), e.g. hashish (approx. 5-15 % THC) and marijuana (approx. 5 % THC). In addition to these, also synthetic products such as "Spice", JWH01, JWH073 and HU-210.

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