JWH-015

JWH-015
Systematic (IUPAC) name
(2-Methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone
Clinical data
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Identifiers
155471-08-2 Yes
PubChem CID 4273754
ChemSpider 3480676
Chemical data
Formula C23H21NO
327.43 g/mol
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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 28x more strongly to CB2 than 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 Dr. John W. Huffman.

Metabolism

JWH-015 has been shown in vitro to be metabolised 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. A study published in the British Journal of Cancer shows that JWH-015 may signal certain cancers to shrink through a process called apoptosis.[10]

References

  1. ↑ Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR (August 2000). "Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2)receptor binding". Drug Alcohol Depend 60 (2): 133–40. doi:10.1016/S0376-8716(99)00152-0. PMID 10940540.
  2. ↑ Murataeva N, Mackie K, Straiker A (November 2012). "The CB2-preferring agonist JWH015 also potently and efficaciously activates CB1 in autaptic hippocampal neurons". Pharmacol. Res. 66 (5): 437–42. doi:10.1016/j.phrs.2012.08.002. PMC 3601544. PMID 22921769.
  3. ↑ Marriott KS, Huffman JW (2008). "Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor". Curr Top Med Chem 8 (3): 187–204. doi:10.2174/156802608783498014. PMID 18289088.
  4. ↑ Ghosh S, Preet A, Groopman JE, Ganju RK (July 2006). "Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes". Mol. Immunol. 43 (14): 2169–79. doi:10.1016/j.molimm.2006.01.005. PMID 16503355.
  5. ↑ Montecucco F, Burger F, Mach F, Steffens S (March 2008). "CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways". Am. J. Physiol. Heart Circ. Physiol. 294 (3): H1145–55. doi:10.1152/ajpheart.01328.2007. PMID 18178718.
  6. ↑ Balter MB, Uhlenhuth EH (1992). "Prescribing and use of benzodiazepines: an epidemiologic perspective". J Psychoactive Drugs 24 (1): 63–4. doi:10.1186/1742-2094-2-29. PMID 1352348.
  7. ↑ Romero-Sandoval A, Eisenach JC (April 2007). "Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision". Anesthesiology 106 (4): 787–94. doi:10.1097/01.anes.0000264765.33673.6c. PMID 17413917.
  8. ↑ Zhang Q, Ma P, Cole RB, Wang G. 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. 2006 Nov;386(5):1345-55. PMID 16955257
  9. ↑ Zhang Q, Ma P, Iszard M, Cole RB, Wang W, Wang G (October 2002). "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 Metab. Dispos. 30 (10): 1077–86. doi:10.1124/dmd.30.10.1077. PMID 12228183.
  10. ↑ N Olea-Herrero, D Vara, S Malagarie-Cazenave, Díaz-Laviada (18 August 2009). "Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: Involvement of CB2". British Journal of Cancer: 101, 940–950. doi:10.1038/sj.bjc.6605248. Retrieved 10 July 2014.