Cannabichromene

Cannabichromene
Names
IUPAC name
2-Methyl-2-(4-methylpent-3-enyl)-7-pentyl-5-chromenol
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.236.929 Edit this at Wikidata
UNII
  • InChI=1S/C21H30O2/c1-5-6-7-10-17-14-19(22)18-11-13-21(4,23-20(18)15-17)12-8-9-16(2)3/h9,11,13-15,22H,5-8,10,12H2,1-4H3 ☒N
    Key: UVOLYTDXHDXWJU-UHFFFAOYSA-N ☒N
  • InChI=1/C21H30O2/c1-5-6-7-10-17-14-19(22)18-11-13-21(4,23-20(18)15-17)12-8-9-16(2)3/h9,11,13-15,22H,5-8,10,12H2,1-4H3
    Key: UVOLYTDXHDXWJU-UHFFFAOYAG
  • CCCCCC1=CC2=C(C=CC(O2)(C)CCC=C(C)C)C(=C1)O
Properties
C21H30O2
Molar mass 314.469 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene,[1] exhibits anti-inflammatory properties in vitro, which may, theoretically, contribute to cannabis analgesic effects.[2] It is a phytocannabinoid, one of the hundreds of cannabinoids found in the Cannabis plant.[3] It bears structural similarity to the other natural cannabinoids, including tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabinol (CBN), among others.[3][4] CBC and cannabinols are present in cannabis.[3] It is not scheduled by the Convention on Psychotropic Substances.

Biosynthesis

Within the Cannabis plant, CBC occurs mainly as cannabichromenic acid (CBCA, 2-COOH-CBC, CBC-COOH). Geranyl pyrophosphate and olivetolic acid combine to produce cannabigerolic acid (CBGA; the sole intermediate for all other phytocannabinoids), which is cyclized by the enzyme CBCA synthase to form CBCA. Over time, or when heated above 93 °C, CBCA is decarboxylated, producing CBC. See also the biosynthetic scheme image below.[citation needed]

CBC biosynthetic scheme

Pharmacology

Cannabichromene has been hypothesized to affect THC psychoactivity, though in vivo effects have not been demonstrated.[5] CBC acts on the TRPV1 and TRPA1 receptors, interfering with their ability to break down endocannabinoids (chemicals such as anandamide and 2-AG that the body creates naturally).[6][unreliable source?] CBC has shown antitumor effects in breast cancer xenoplants in mice.[7] It also has anticonvulsant activity in a mouse model.[8]

In vitro, CBC binds weakly to CB1 and CB2 with binding affinities of 713 nM and 256 nM, respectively, which are significantly lower than that for THC with 35 nM at CB1.[9][10] acting as an agonist for cAMP stimulation and an antagonist at beta-arrestin.[9] Additionally, CBC is an agonist of TRPA1, and less potently TRPV3 and TRPV4.[3] CBC has two stereoisomers.

References

  1. ^ "Cannabichromene". PubChem. National Center for Biotechnology Information. 16 February 2019. Retrieved 12 February 2019.
  2. ^ Morales P, Hurst DP, Reggio PH (2017). "Molecular Targets of the Phytocannabinoids: A Complex Picture". Phytocannabinoids. Progress in the Chemistry of Organic Natural Products. Vol. 103. pp. 103–31. doi:10.1007/978-3-319-45541-9_4. ISBN 978-3-319-45539-6. PMC 5345356. PMID 28120232.
  3. ^ a b c d Turner, Sarah E.; Williams, Claire M.; Iversen, Leslie; Whalley, Benjamin J. (2017). "Molecular Pharmacology of Phytocannabinoids". In Kinghorn, A. Douglas; Falk, Heinz; Gibbons, Simon; Kobayashi, Jun'ichi (eds.). Phytocannabinoids: Unraveling the Complex Chemistry and Pharmacology of Cannabis sativa. Progress in the Chemistry of Organic Natural Products. Vol. 103. Springer International Publishing. pp. 61–101. doi:10.1007/978-3-319-45541-9_3. ISBN 978-3-319-45539-6. PMID 28120231.
  4. ^ Aizpurua-Olaizola, Oier; Soydaner, Umut; Öztürk, Ekin; Schibano, Daniele; Simsir, Yilmaz; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz (2016). "Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes". Journal of Natural Products. 79 (2): 324–331. doi:10.1021/acs.jnatprod.5b00949. PMID 26836472.
  5. ^ Ilan AB, Gevins A, Coleman M, ElSohly MA, de Wit H (September 2005). "Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids". Behavioural Pharmacology. 16 (5–6): 487–96. doi:10.1097/00008877-200509000-00023. PMID 16148455. S2CID 827221.
  6. ^ "What Is CBC (Cannabichromene)?". CNBS. Retrieved 2019-03-31.
  7. ^ Ligresti, A.; Moriello, A. S.; Starowicz, K.; Matias, I.; Pisanti, S.; De Petrocellis, L.; Laezza, C.; Portella, G.; Bifulco, M.; Di Marzo, V. (2006-09-01). "Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma | Journal of Pharmacology and Experimental Therapeutics". Journal of Pharmacology and Experimental Therapeutics. 318 (3): 1375–1387. doi:10.1124/jpet.106.105247. PMID 16728591. S2CID 1341744.
  8. ^ Anderson LL, Ametovski A, Lin Luo J, Everett-Morgan D, McGregor IS, Banister SD, Arnold JC. Cannabichromene, Related Phytocannabinoids, and 5-Fluoro-cannabichromene Have Anticonvulsant Properties in a Mouse Model of Dravet Syndrome. ACS Chem Neurosci. 2021 Jan 20;12(2):330-339. doi:10.1021/acschemneuro.0c00677 PMID 33395525
  9. ^ a b Zagzoog, Ayat; Mohamed, Kawthar A.; Kim, Hye Ji J.; Kim, Eunhyun D.; Frank, Connor S.; Black, Tallan; Jadhav, Pramodkumar D.; Holbrook, Larry A.; Laprairie, Robert B. (2020-11-23). "In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa". Scientific Reports. 10 (1): 20405. doi:10.1038/s41598-020-77175-y. ISSN 2045-2322. PMC 7684313. PMID 33230154.
  10. ^ Rosenthaler, Sarah; Pöhn, Birgit; Kolmanz, Caroline; Nguyen Huu, Chi; Krewenka, Christopher; Huber, Alexandra; Kranner, Barbara; Rausch, Wolf-Dieter; Moldzio, Rudolf (November 2014). "Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures". Neurotoxicology and Teratology. 46: 49–56. Bibcode:2014NTxT...46...49R. doi:10.1016/j.ntt.2014.09.003. PMID 25311884.