The most important cannabinoids (THC, CBD, CBC, CBG, CBN) and their therapeutic effects

cannabinoids

There are over 100 different phytocannabinoids in the cannabis plant that interact with the body’s endocannabinoid system (ECS). The best known is the psychotropic tetrahydrocannabinol (THC), while cannabidiol (CBD) is the most common non-intoxicating cannabinoid. In addition, among the numerous phytocannabinoids, cannabichromene (CBC), cannabigerol (CBG) and cannabinol (CBN) have important therapeutic effects.

The chemical structure of tetrahydrocannabinol (THC) was deciphered in 1964. About 30 years later, researchers discovered the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) [1]. These milestones led to the discovery of the endocannabinoid system (ECS), which has an important role in the regulation of physiological processes such as appetite, pain perception, mood and memory.

THC – Tetrahydrocannabinol

Tetrahydrocannabinol (THC), or more precisely delta-9-tetrahydrocannabinol, is primarily known for its psychotropic effect, which is mediated via CB1 receptors. The cannabinoid also has numerous medical effects. Indications with a good study record include, for example: Spasticity in multiple sclerosis, nausea and vomiting in cancer patients, neuropathic pain and loss of appetite in HIV and cancer patients. THC can also be effective in other diseases, for example Tourette’s syndrome [2].

When THC is combined with other cannabinoids, the effect can be enhanced: In a study by the University of London from 2017, THC and CBD in combination were shown to fight prepared human leukaemia cells more effectively than the individual substances. Leukaemia is cancer of the hematopoietic system [3]. THC lowers intraocular pressure and could therefore be an anti-glaucoma agent [14].

CBD – Cannabidiol

Cannabidiol (CBD), the best-known cannabinoid after THC, does not trigger psychotropic effects and also has many positive medical effects. CBD binds only weakly on CB1- and CB2-receptors of the encocannabinoid system. On CB1-receptors CBD acts as negativ allosteric modulator, making it more difficult for THC to bind to the receptor. In this way the psychotropic effect are modulated by CBD [18]. A finished drug containing CBD has already been approved for the treatment of rare forms of childhood epilepsy (Lennox-Gaustaut and Dravet syndromes), as well as seizures associated with tuberous sclerosis (TSC) [4].

Promising studies are also available for the treatment of anxiety and for antipsychotic effects in schizophrenia [5]. CBD has antidepressant properties [6]. Due to its antioxidant and anti-inflammatory effects, CBD can be helpful in diseases associated with oxidative stress, such as cancers, neurodegenerative diseases (e.g. Alzheimer’s disease) or metabolic diseases (e.g. diabetes mellitus) [7].

CBC – Cannabichromen

Cannabichromene (CBC) belongs to the non-psychotropic cannabinoids of the cannabis plant. Plants that produce a lot of CBD are bred by selective crossing. CBC acts on CB2 receptors, but not on CB1 receptors. It also affects TRP channels, which play a role in pain and inflammation. In studies on mice, CBC reduced pain and enhanced the analgesic effect of THC [8]. CBC also shows antidepressant [6], antibacterial and antifungal properties [9]. The anti-inflammatory effects of CBC were first described in 1980 in an animal model. CBC reduced the formation of oedema (water retention) in inflamed rat paws.

In experiments, CBC was also able to stabilise the cell membrane of red blood cells. The anti-inflammatory effect was compared with that of the non-steroidal anti-inflammatory drug phenylbutazone: At similar doses, CBC was more effective than phenylbutazone. In addition, CBC is better tolerated [10]. In 2013, an Italian research team showed that CBC can have a positive effect on the viability of isolated mouse stem cells by interacting with adenosine A1 receptors [11].

CBG – Cannabigerol

Cannabigerol (CBG) is the precursor substance from which the cannabis plant forms the cannabinoids THC, CBD and CBC. The non-psychotropic cannabinoid is a so-called partial agonist at CB1 and CB2 receptors, i.e. it binds to the receptors, but exerts only a weak effect. Therefore, CBG reduces the psychotropic effects of THC [12]. In addition, CBG also acts at alpha2-adrenoreceptors and 5-HT1A-receptors, a certain serotonin receptor. Research on CBG is still in its infancy, but recent studies show positive effects in various diseases. According to current studies, CBG can be effective in neurological diseases (e.g. Huntington’s disease, Parkinson’s disease, multiple sclerosis) and chronic inflammatory bowel diseases.

CBG has a blood pressure-lowering effect by binding to the alpha2-adrenoreceptor and could therefore be used in metabolic syndrome [13]. It has also been shown that CBG can lower intraocular pressure, which makes the substance interesting for the treatment of glaucoma [14]. CBG can also be effective in skin diseases such as psoriasis. CBG inhibits the pathologically increased formation of horn cells in psoriasis [15].

CBN – Cannabinol

Cannabinol (CBN) is an oxidation product of THC, i.e. it is formed by the influence of heat and oxygen and is mainly found in aged cannabis products. It was discovered as early as 1899 and is thus the first cannabinoid to be researched. Studies on humans have shown that CBN has a slightly psychotropic effect, which is intensified when combined with THC [16]. Medically, CBN can be used due to its sedative and anticonvulsant (antispasmodic) effects. In addition, studies indicate anti-inflammatory and antibiotic effects, which could also combat multi-resistant germs such as MRSA (methicillin-resistant Staphylococcus aureus).

CBN could also be an option for external applications in the future. By inhibiting the formation of horny cells, CBN could be helpful in psoriasis. Since CBN also acts on heat sensors (TRPV2), the cannabinoid can potentially be used for the local therapy of burns [8]. In 2019, a Canadian research team found in a study on rats that CBN alone or in combination can relieve chronic muscle pain, such as that experienced in fibromyalgia [17].

Researchers continue to work on gaining more knowledge about the effects of cannabinoids through scientific studies. Science will continue to answer questions about these and other phytocannabinoids in the coming years.

[1]          Trends in Pharmacological Sciences. Volume 36, Issue 5, Pages 277-296. Endocannabinoid signaling at the periphery: 50 years after THC.. M. Maccarrone, I. Bab, T. Bíró, Guy A. Cabral, Sudhansu K. Dey, V. Di Marzo, Justin C. Konje, G. Kunos, R. Mechoulam, P. Pacher, Keith A. Sharkey, A. Zimmer. (May 2015).

[2]          Fraguas-Sánchez, A.I., Torres-Suárez, A.I. Medical Use of Cannabinoids. Drugs 78, 1665–1703 (2018). https://doi.org/10.1007/s40265-018-0996-1

[3]          Scott KA, Dalgleish AG, Liu WM. Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration. Int J Oncol. 2017 Jul;51(1):369-377. doi: 10.3892/ijo.2017.4022. Epub 2017 May 29. PMID: 28560402.

[4]          https://www.ema.europa.eu/en/medicines/human/EPAR/epidyolex

[5]          White CM. A Review of Human Studies Assessing Cannabidiol’s (CBD) Therapeutic Actions and Potential. J Clin Pharmacol. 2019 Jul;59(7):923-934. doi: 10.1002/jcph.1387. Epub 2019 Feb 7. PMID: 30730563.

[6]          El-Alfy AT, Ivey K, Robinson K, Ahmed S, Radwan M, Slade D, Khan I, ElSohly M, Ross S. Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated    from Cannabis sativa L. Pharmacol Biochem Behav. 2010 Jun;95(4):434-42. doi: 10.1016/j.pbb.2010.03.004. Epub 2010 Mar 21. PMID: 20332000; PMCID: PMC2866040.

[7]          Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants (Basel). 2019 Dec 25;9(1):21. doi: 10.3390/antiox9010021. PMID: 31881765; PMCID: PMC7023045.

[8]          Ethan B. Russo, Jahan Marcu, Chapter Three – Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads, Editor(s): David Kendall, Stephen P.H. Alexander, Advances in Pharmacology, Academic Press, Volume 80, 2017, Pages 67- 134, ISSN 1054-3589, ISBN 9780128112328,                                                                                                     https://doi.org/10.1016/bs.apha.2017.03.004.                                                                                                 (https://www.sciencedirect.com/science/article/pii/S1054358917300273)

[9]          Turner CE, Elsohly MA. Biological activity of cannabichromene, its homologs and isomers. J Clin Pharmacol. 1981 Aug-Sep;21(S1):283S-291S. doi: 10.1002/j.1552-4604.1981.tb02606.x. PMID: 7298870.

[10]        Life Sciences. Volume 26, Issue 23, 9, Pages 1991-1995. Anti-inflammatory properties of cannabichromene – ScienceDirect. Philip W. Wirth, E. Sue Watson, Mahmoud ElSohly,   Carlton E. Turner, James C. Murphy. (1980).

[11]        Noriko Shinjyo, Vincenzo Di Marzo, The effect of cannabichromene on adult neural stem/progenitor cells, Neurochemistry International, Volume 63, Issue 5, 2013, Pages 432- 437, ISSN 0197-0186, https://doi.org/10.1016/j.neuint.2013.08.002.

[12]        Joshua A. Hartsel, Joshua Eades, Brian Hickory, Alexandros Makriyannis, Chapter 53 –   Cannabis sativa and Hemp, Editor(s): Ramesh C. Gupta, Nutraceuticals, Academic Press, 2016, Pages 735-754, ISBN 9780128021477, https://doi.org/10.1016/B978-0-12- 802147-7.00053-X.                                                                                                                                                       (https://www.sciencedirect.com/science/article/pii/B978012802147700053X)

[13]     Potential Clinical Uses of CBG Rahul Nachnani, Wesley M. Raup-        Konsavage and Kent E. Vrana Journal of Pharmacology and Experimental Therapeutics February 1, 2021, 376 (2) 204-212; DOI: https://doi.org/10.1124/jpet.120.000340

[14]        Colasanti BK. A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol. J Ocul Pharmacol. 1990 Winter;6(4):259-69. doi: 10.1089/jop.1990.6.259. PMID: 1965836.

[15]        Wilkinson JD, Williamson EM. Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J Dermatol Sci. 2007 Feb;45(2):87-92. doi: 10.1016/j.jdermsci.2006.10.009. Epub 2006 Dec 6. PMID: 17157480.

[16]     Effects of Δ9-Tetrahydrocannabinol and Cannabinol in Man

Karniol I.G. · Shirakawa I. · Takahashi R.N. · Knobel E. · Musty R.E. Pharmacology 1975;13:502–512 https://doi.org/10.1159/000136944

[17]        Wong H, Cairns BE. Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain. Arch Oral Biol. 2019 Aug;104:33-39. doi:                   10.1016/j.archoralbio.2019.05.028. Epub 2019 May 28. PMID: 31158702.

[18]        Chung H, Fierro A, Pessoa-Mahana CD (2019) Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study. PLoS ONE 14(7): e0220025. https://doi.org/10.1371/journal.pone.0220025

About Minyi Lü

Minyi Lü leidet an chronischen Schmerzen aufgrund ihrer Fingerarthrose. Ihre Beschwerden behandelt sie seit 2017 sehr erfolgreich mit medizinischem Cannabis. Als Pharmazeutin im Praktikum bringt sie nun ihr Know-how ein, um über die neuesten wissenschaftlichen Erkenntnisse rund um Medizinalcannabis zu berichten.

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