Chemistry:JWH-015

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Short description: Chemical compound
JWH-015
JWH-015.svg
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
Chemical and physical data
FormulaC23H21NO
Molar mass327.427 g·mol−1
3D model (JSmol)
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JWH-015 is a chemical from the naphthoylindole family that acts as a subtype-selective cannabinoid agonist. Its affinity for CB2 receptors is 13.8 nM, while its affinity for CB1 is 383 nM, meaning that it binds almost 28 times more strongly to CB2 than to CB1.[1] However, it still displays some CB1 activity, and in some model systems can be very potent and efficacious at activating CB1 receptors,[2] and therefore it is not as selective as newer drugs such as JWH-133.[3] It has been shown to possess immunomodulatory effects,[4][5] and CB2 agonists may be useful in the treatment of pain and inflammation.[6][7] It was discovered and named after John W. Huffman.

Metabolism

JWH-015 has been shown in vitro to be metabolized primarily by hydroxylation and N-dealkylation, and also by epoxidation of the naphthalene ring,[8] similar to the metabolic pathways seen for other aminoalkylindole cannabinoids such as WIN 55,212-2.[9] Epoxidation of polycyclic aromatic hydrocarbons (see for example benzo(a)pyrene toxicity) can produce carcinogenic metabolites, although there is no evidence to show that JWH-015 or other aminoalkylindole cannabinoids are actually carcinogenic in vivo. JWH-015 may signal certain cancers to shrink through a process called apoptosis.[10]

Legal status

In the United States, all CB1 receptor agonists of the 3-(1-naphthoyl)indole class such as JWH-015 are Schedule I Controlled Substances.[11]

As of October 2015 JWH-015 is a controlled substance in China.[12]

References

  1. ↑ "Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2)receptor binding". Drug and Alcohol Dependence 60 (2): 133–140. August 2000. doi:10.1016/S0376-8716(99)00152-0. PMID 10940540. 
  2. ↑ "The CB2-preferring agonist JWH015 also potently and efficaciously activates CB1 in autaptic hippocampal neurons". Pharmacological Research 66 (5): 437–442. November 2012. doi:10.1016/j.phrs.2012.08.002. PMID 22921769. 
  3. ↑ "Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor". Current Topics in Medicinal Chemistry 8 (3): 187–204. 2008. doi:10.2174/156802608783498014. PMID 18289088. 
  4. ↑ "Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes". Molecular Immunology 43 (14): 2169–2179. July 2006. doi:10.1016/j.molimm.2006.01.005. PMID 16503355. 
  5. ↑ "CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways". American Journal of Physiology. Heart and Circulatory Physiology 294 (3): H1145–H1155. March 2008. doi:10.1152/ajpheart.01328.2007. PMID 18178718. 
  6. ↑ "Prescribing and use of benzodiazepines: an epidemiologic perspective". Journal of Psychoactive Drugs 24 (1): 63–64. 1992. doi:10.1080/02791072.1992.10471620. PMID 1352348. 
  7. ↑ "Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision". Anesthesiology 106 (4): 787–794. April 2007. doi:10.1097/01.anes.0000264765.33673.6c. PMID 17413917. 
  8. ↑ "Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS". Analytical and Bioanalytical Chemistry 386 (5): 1345–1355. November 2006. doi:10.1007/s00216-006-0717-6. PMID 16955257. 
  9. ↑ "In vitro metabolism of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate, a cannabinoid receptor agonist". Drug Metabolism and Disposition 30 (10): 1077–1086. October 2002. doi:10.1124/dmd.30.10.1077. PMID 12228183. 
  10. ↑ "Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: involvement of CB2". British Journal of Cancer 101 (6): 940–950. September 2009. doi:10.1038/sj.bjc.6605248. PMID 19690545. 
  11. ↑ 21 U.S.C. § 812: Schedules of controlled substances
  12. ↑ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in zh). China Food and Drug Administration. 27 September 2015. http://www.sfda.gov.cn/WS01/CL0056/130753.html. 



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