JWH-015

JWH-015
Legal status
Legal status
Identifiers
IUPAC name
  • (2-Methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.161.912
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Chemical and physical data
FormulaC23H21NO
Molar mass327.427 g·mol−1
3D model (JSmol)
SMILES
  • CCCN1C(=C(C2=CC=CC=C21)C(=O)C3=CC=CC4=CC=CC=C43)C
InChI
  • InChI=1S/C23H21NO/c1-3-15-24-16(2)22(20-12-6-7-14-21(20)24)23(25)19-13-8-10-17-9-4-5-11-18(17)19/h4-14H,3,15H2,1-2H3 ☒N
  • Key:LJSBBBWQTLXQEN-UHFFFAOYSA-N ☒N
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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 Dr. 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. 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]

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. ↑ 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. S2CID 5896815.
  6. ↑ Balter MB, Uhlenhuth EH (1992). "Prescribing and use of benzodiazepines: an epidemiologic perspective". J Psychoactive Drugs. 24 (1): 63–4. doi:10.1080/02791072.1992.10471620. 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 (Nov 2006). "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): 1345–55. doi:10.1007/s00216-006-0717-6. PMID 16955257. S2CID 9116612.
  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. S2CID 10848076.
  10. ↑ N Olea-Herrero; D Vara; S Malagarie-Cazenave; I 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 (6): 101, 940–950. doi:10.1038/sj.bjc.6605248. PMC 2743360. 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 Chinese). China Food and Drug Administration. 27 September 2015. Retrieved 1 October 2015.
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