Cannabidiol

from Wikipedia, the free encyclopedia
Structural formula
Structure of cannabidiol
General
Surname Cannabidiol (CBD)
other names
  • (-) - trans -Cannabidiol
  • (-) - trans -2- para- mentha-1,8-dien-3-yl-5-pentylresorcinol
  • 2 - [(1 R , 6 R ) -3-methyl-6-prop-1-en-2-yl-1-cyclohex-2-enyl] -5-pentylbenzo-1,3-diol ( IUPAC )
  • CANNABIDIOL - SYNTHETICALLY PRODUCED ( INCI )
Molecular formula C 21 H 30 O 2
External identifiers / databases
CAS number 13956-29-1
EC number 689-176-3
ECHA InfoCard 100.215.986
PubChem 644019
ChemSpider 559095
DrugBank DB09061
Wikidata Q422917
Drug information
ATC code

N03 AX24

properties
Molar mass 314.46 g · mol -1
Physical state

firmly

Melting point

66-67 ° C

solubility

practically insoluble in water, soluble in ethanol , methanol , diethyl ether , benzene , chloroform and petroleum ether

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning 08 - Dangerous to health

Caution

H and P phrases H: 302-361
P: ?
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Cannabidiol ( CBD ) is a non- psychoactive cannabinoid from female hemp (cannabis). There are antispasmodic , anti-inflammatory, anti-anxiety and anti-nausea described effects. Further pharmacological effects such as an antipsychotic effect are being researched.

chemistry

Like all cannabinoids, cannabidiol is mainly present in the plant as an acid (CBD carboxylic acid ).

Cannabidiol was first synthesized by Raphael Mechoulam . CBD cyclizes in the presence of Lewis acids (for example boron trifluoride diethyl etherate or proton donors such as p -toluenesulfonic acid ) to give Δ 8 - and Δ 9 - THC . Heating with water under reflux leads to cyclization. In a strongly basic environment under oxidative conditions, CBD is first hydroxylated on the aromatic and then oxidized to quinone . When stored for a long time in the presence of air, it is oxidized to cannabinol .

pharmacology

Cannabidiol binds to the cannabinoid receptors CB 1 and CB 2 agonistically, but it can also block their activity via an unexplained mechanism. It also acts as an antagonist at the G protein-coupled receptor GPR55 , the physiological role of which has not yet been clarified.

Cannabidiol has a pleiotropic effect, which means that effects as well as side effects can be triggered in different ways. For this reason, the mechanism of action is not yet exactly known. However, it is assumed that the voltage- controlled ion channel VDAC 1 ( voltage-dependent anion-selective channel protein 1 ) has an effect on the mitochondria . These channels play a role in calcium transport in the cells, which is important for the transmission of electrical signals in nerve cells ( calcium signaling ). In addition, there are pronounced pharmacokinetic interactions with other anti-epileptic drugs, especially clobazam . The immunosuppressive effect of cannabidiol is based on apoptosis of the T lymphocytes of the immune system. The CD4 + CD25 + FOXP3 + regulatory T cells are not affected by this .

Medical applications

Effects of cannabidiol

CBD is part of the medicinally used hemp extract nabiximols , as the spasmolytic in multiple sclerosis is used. It has been available as an oral spray for this indication since 2011. In addition, it has been on the market for rare forms of epilepsy (Epidyolex) since October 2019 . It is approved for the oral treatment of certain forms of epilepsy in children ( Lennox-Gastaut syndrome , Dravet syndrome ).

For other indications there is no or insufficient evidence of effectiveness. In 2019, the FDA issued several warnings against vendors who illegally advertised efficacy in cancer , Alzheimer's disease or autism .

CBD could be a candidate for the treatment of inflammatory bowel disease because of its immunosuppressive effects . Use in mood disorders is being investigated. To neuroprotective effects of Cannabidiols, whether through its antioxidant properties, effects on the CB 2 receptors or adenosine receptors , research is carried out.

Products containing cannabidiol

drug

Cannabidiol is approved under the name Epidiolex in the USA and Epidyolex in the EU as a prescription drug for the treatment of the above-mentioned forms of epilepsy in children. In Germany, too, cannabidiol requires a prescription for use as a medicinal product (e.g. "Oily Cannabidiol Solution NRF "). The standardized full extract from the cannabis plant, Nabiximols (trade name: Sativex Spray for use in the oral cavity ), approved in various countries , contains cannabidiol as well as THC and is therefore subject to narcotics regulations.

Transdermal forms of application are being investigated.

Dietary supplements and other foods

In Germany, foods with cannabidiol are offered in the dietary supplement sector without health-related claims, but with an explicit reference to the CBD they contain. The marketability of these products is sometimes called into question. In fact, other hemp- based foods (e.g. hemp oils or hemp seeds ) also contain significant amounts of CBD. The responsible state authorities in each case monitor the sale of products containing CBD. Some products have already been withdrawn from the market.

In response to a request from individual EU member states in 2019, the European Commission specified the entry for the hemp plant Cannabis sativa in the Novel Food catalog by adding the entries “cannabinoids” and “cannabidiol”. In contrast to the hemp plant, which was completely or partially consumed as food before May 15, 1997, this is denied for the substances CBD and other cannabinoids. The same should apply to extracts of the hemp plant. The German Federal Office for Consumer Protection and Food Safety (BVL) therefore regards all foods, especially food supplements, which contain CBD or other cannabinoids, as novel foods and therefore only marketable after prior approval (as of March 2019). Various administrative courts have denied the marketability of products containing CBD.

A legal opinion commissioned by the European Industrial Hemp Association by the Frankfurt attorney Thomas Büttner comes to the conclusion that extracts from the hemp plant are to be equated with the hemp plant, since on the one hand there are sufficient indications for a significant consumption as food before May 15, 1997 and On the other hand, there is also a systematic contradiction to the general classification paradigm, according to which traditional extraction processes do not change the food itself in a legally relevant manner. Accordingly, in addition to the hemp extracts produced in a completely new way, only foods to which pure CBD or other cannabinoids are added as an ingredient should be classified as novel foods. and not generally all foods that contain CBD in any form.

The consumer advice centers agree with the BVL's view. Since products containing CBD are neither approved nor examined with regard to dosage, safety and interactions, they should not be sold at all; the consumer advice centers advise against consumption. Controls have also shown that CBD oils are "harmful to health or unsuitable for human consumption" due to the increased levels of psychoactive THC. In Cologne, the sale of foods containing CBD was banned in June 2020.

The healing promises made with CBD oils (e.g. alleged healing or alleviation of pain, depression or insomnia) are considered advertising with disease-related statements and are generally prohibited due to the lack of proof of effectiveness and the lack of approval. This also applies to analogous statements for dietary supplements or foods containing CBD. Another problem with CBD oils is the usually very small and therefore pharmacologically insignificant amount of CBD they contain, which is sometimes far below the amounts tested in studies. As a result, it is completely unclear whether CBD oils can have an effect or whether it is more of an expensive lifestyle product.

In Switzerland, CBD products like oils are legal as long as they do not exceed the THC limit of 1%. In Austria the situation is not that clear. There, CBD products may not contain more than 0.3% THC. In addition, however, legal experts are of the opinion that it is inadmissible to advertise or sell the products as "dietary supplements" or as "medicines", since otherwise the products would give the false impression of having a beneficial effect on health.

In August 2020, the Ministry for Rural Areas and Consumer Protection of Baden-Württemberg published a study in its 2019 annual report in which 49 food samples of CBD products were examined. Almost half of the samples were judged to be unsafe due to excessively high THC levels. A similar result was found for cosmetic products. Parts of the hemp plant that are not approved for processing were found in 9 of 40 samples.

Further products

CBD oil is offered for cosmetic use. In Switzerland and Austria, so-called "industrial hemp" with a high CBD content and a low THC content is sold, which can also be smoked. In Germany, these products would fall under the Narcotics Act, unless one of the following conditions applies:

  1. The hemp used is listed in the EU variety catalog or
  2. the THC content of the hemp falls below 0.2% and it is only sold for commercial or scientific purposes.

In general, the pure substance cannabidiol, unlike THC, is not subject to any narcotics regulations.

Side effects

The following undesirable effects are known for CBD:

  • very common: drowsiness and drowsiness (10%)
  • common: malaise, diarrhea, loss of appetite, rashes
  • Insomnia, trouble sleeping, restlessness
  • possibly increased frequency of infections

See also

literature

Web links

Commons : Cannabidiol  - collection of images, videos and audio files

Individual evidence

  1. ↑ Entry on CANNABIDIOL - SYNTHETICALLY PRODUCED in the CosIng database of the EU Commission, accessed on May 13, 2020.
  2. ↑ a b The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , p. 282.
  3. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of [(1R, 6R) -3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl] -5-pentylbenzene-1,3 Template: Linktext-Check / Escaped is shown, which is derived from a self-classification by the distributor -diol in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 28, 2017.
  4. ↑ a b Entry on cannabidiol in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on December 19, 2016.
  5. ↑ S. Chayasirisobhon: Cannabis and Neuropsychiatric Disorders: An Updated Review. In: Acta neurologica Taiwanica. Volume 28 (2), June 2019, pp. 27-39, PMID 31867704 (review).
  6. ^ S. Atalay, I. Jarocka-Karpowicz, E. Skrzydlewska: Antioxidative and Anti-Inflammatory Properties of Cannabidiol. In: Antioxidants. Volume 9, Number 1, December 2019, p., Doi: 10.3390 / antiox9010021 , PMID 31881765 (Review).
  7. ^ R. Mechoulam et al .: Cannabidiol - recent advances. In: Chemistry & Biodiversity. 4, 8, 2007, pp. 1678-1692, doi: 10.1002 / cbdv.200790147 . PMID 17712814 .
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  9. ^ Y. Gaoni, R. Mechoulam: Hashish-VII The isomerization of cannabidiol to tetrahydrocannabinols. In: Tetrahedron . 22, 4, 1966, pp. 1481-1488, doi: 10.1016 / S0040-4020 (01) 99446-3 .
  10. ^ R. Mechoulam, Z. Ben-Zvi: Hashish-XIII On the nature of the beam test. In: Tetrahedron . 24, 15, 1968, pp. 5615-5624, doi: 10.1016 / 0040-4020 (68) 88159-1 .
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  13. ^ R. Schicho, M. Storr: A potential role for GPR55 in gastrointestinal functions. In: Current Opinion in Pharmacology . Volume 12, Number 6, December 2012, pp. 653-658, doi: 10.1016 / j.coph.2012.09.009 . PMID 23063456 . PMC 3660623 (free full text).
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  15. ↑ AL Geffrey et al .: Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. In: Epilepsia . tape 56 , 2015, p. 1246-1251 .
  16. ↑ Sadiye Amcaoglu Rieder et al .: Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression . In: Immunobiology . tape 215 , no. August 8 , 2010, PMID 19457575 .
  17. ↑ Saphala Dhital et al .: Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation . In: Cellular Immunology . tape 312 , 2017, PMID 27865421 .
  18. ↑ P. Flachenecker: A new multiple sclerosis spasticity treatment option: effect in everyday clinical practice and cost-effectiveness in Germany. In: Expert Review of Neurotherapeutics . Volume 13, Number 3 Suppl 1, February 2013, pp. 15–19, doi: 10.1586 / ern.13.1 . PMID 23369055 .
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  21. ↑ V. Micale et al .: endocannabinoid system and mood disorders: priming a target for new therapies. In: Pharmacology & therapeutics. Volume 138, number 1, April 2013, pp. 18-37, doi: 10.1016 / j.pharmthera.2012.12.002 . PMID 23261685 .
  22. ↑ D. Hermann and M. Schneider: Potential protective effects of cannabidiol on neuroanatomical alterations in cannabis users and psychosis: a critical review. In: Curr Pharm Des. 18 (32), 2012, pp. 4897-4905. Review. PMID 2276143 .
  23. ↑ Appendix 1 (to § 1 No. 1 and § 5) Substances and preparations according to § 1 No. 1 of the Ordinance on the Prescription of Medicinal Products
  24. ↑ Dixon H. Xu et al .: The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities . In: Current Pharmaceutical Biotechnology . December 1, 2019, doi : 10.2174 / 1389201020666191202111534 , PMID 31793418 .
  25. ↑ DC Hammell et al .: Transdermal cannabidiol reduces inflammation and pain-related behaviors in a rat model of arthritis . In: European journal of pain (London, England) . tape 20 , no. 6 , July 2016, p. 936-948 , doi : 10.1002 / ejp.818 , PMID 26517407 , PMC 4851925 (free full text) - (English).
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  28. ↑ Entry "cannabinoids" in the EU Commission's catalog of novel foods
  29. ↑ Updated EC ruling for CBD classes supplement ingredient as Novel Foo. Retrieved May 26, 2020 (English).
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  32. ↑ Legal opinion (PDF)
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  34. ↑ Cologne prohibits the sale of CBD products as food . In: Deutsche Apothekerzeitung . June 23, 2020.
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  38. ↑ Annual report 2019: Food, consumer goods, cosmetics, drinking water, animal feed. Ministry for Rural Areas and Consumer Protection Baden-Württemberg, August 2020, accessed on 6 August 2020 .
  39. ↑ Smoking weed for nerds. In: The time. May 22, 2019 ( zeit.de ).
  40. ↑ Products with cannabidiol (CBD) PDF, accessed on August 28, 2019.
  41. ↑ common catalog of varieties for agricultural plant species in accordance with Article 9 of Commission Delegated Regulation (EU) No. 639/2014 of March 11, 2014 to supplement Regulation (EU) No. 1307/2013 of the European Parliament and of the Council with provisions on direct payments to Owners of agricultural holdings within the framework of the support schemes of the Common Agricultural Policy and to amend Annex X of the aforementioned regulation (OJ L 181 of June 20, 2014, p. 1) with the reference date March 15 of the respective cultivation year
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