Cannabinoids

Author:Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 16.06.2023

Dieser Artikel auf Deutsch

Requires free registration (medical professionals only)

Please login to access all articles, images, and functions.

Our content is available exclusively to medical professionals. If you have already registered, please login. If you haven't, you can register for free (medical professionals only).


Requires free registration (medical professionals only)

Please complete your registration to access all articles and images.

To gain access, you must complete your registration. You either haven't confirmed your e-mail address or we still need proof that you are a member of the medical profession.

Finish your registration now

DefinitionThis section has been translated automatically.

There are three main classes of cannabinoids:

Phytocannabinoids from the plant Cannabis sativa, consisting of 100 different compounds, of particular importance are D9, THC and Cannabidiol(CBD), see also under Cannabis.

Endocannabinoids produced by humans, mainly anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

Synthetic cannabinoids.

General informationThis section has been translated automatically.

Cannabinoids are transformation products and synthetic analogues of some terpene phenols (partially hydrogenated dibenzfuran derivatives) found mainly 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 studied, highly psychotropic main active ingredient of Cannabis sativa is Delta 9 -tetrahydrocannabinol (THC=dronabinol).
  • Cannabidiol: In terms of quantity, cannabidiol is in 2nd place. Cannabidiol has antiphlogistic, anti-schizophrenic and anti-epileptic effects but not psychotropic.
  • Cannabinol: A third well-studied substance is cannabinol.
  • Cannabidivarin (CBDV): antiepileptic effect; ligand of TRPV1- as well as TRPV2.
  • Cannabigerol(CBGV): affinity for CB1 receptors

Other phytocannabinoids (not derived from the cannabis plant):

  • Other plants were also shown to produce diverse phytocannabinoids. For example, N-isobutylamides prepared from Echinacea were found 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 comes from binding and activating cannabinoid receptors (CB receptors). For example, THC is a potent agonist of the CB1 receptor, which mediates the psychotropic effects and activation of the reward pathways. Furthermore, 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 occur mainly in the CNS, but also in the periphery such as gastrointestinal tract, fat cells, postganglionic neurons of the autonomic nervous system. Their activation acts Gi/o-mediated inhibition of adenylcylcase, opening of K+ channels and closure 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 found mainly 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 wide range of biochemical reactions.

Endogenous ligands of CB receptors(endocannabinoids) are the arachidonic acid derivatives anandamide and 2-arachidonylglacerol. Little is known about their physiological significance.

Other ligands of CB receptors: A new class of potent cannabinoid mimetics are the N-isobutylamides, which are prepared 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.

PathophysiologyThis section has been translated automatically.

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.

Note(s)This section has been translated automatically.

Cannabinoids are on the doping list!

Marijuna contains about 5% THC.

Hash contains 5-15% THC, depending on variety and origin.

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

LiteratureThis section has been translated automatically.

  1. Korte, G et al. (2010) Tea catechins' affinity for human cannabinoid receptors. Phytomedicine 17: 19-22
  2. Ständer S et al (2005) Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci 38: 177-188
  3. Sivesind TE et al (2022) Cannabinoids for the Treatment of Dermatologic Conditions. JID Innovations 2:100095 doi:10.1016/j.xjidi.2022.100095

Authors

Last updated on: 16.06.2023