JWH-015

Chemical compound

JWH-015
INN
Drug class
Routes of administration
Pregnancy category
Bioavailability
Metabolism
Elimination half-life
Excretion
Legal status
CAS Number	155471-08-2
PubChem	4273754
DrugBank
ChemSpider	3480676
KEGG

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.<ref name="pmid10940540">,

 Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2)receptor binding, 
 Drug and Alcohol Dependence, 
 
 Vol. 60(Issue: 2),
 pp. 133–140,
 DOI: 10.1016/S0376-8716(99)00152-0,
 PMID: 10940540,</ref> However, it still displays some CB1 activity, and in some model systems can be very potent and efficacious at activating CB1 receptors,<ref name="pmid22921769">, 
 The CB2-preferring agonist JWH015 also potently and efficaciously activates CB1 in autaptic hippocampal neurons, 
 Pharmacological Research, 
 
 Vol. 66(Issue: 5),
 pp. 437–442,
 DOI: 10.1016/j.phrs.2012.08.002,
 PMID: 22921769,
 PMC: 3601544,</ref> and therefore it is not as selective as newer drugs such as JWH-133.<ref name="pmid18289088">, 
 Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor, 
 Current Topics in Medicinal Chemistry, 
 2008,
 Vol. 8(Issue: 3),
 pp. 187–204,
 DOI: 10.2174/156802608783498014,
 PMID: 18289088,</ref> It has been shown to possess immunomodulatory effects,<ref name="pmid16503355">, 
 Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes, 
 Molecular Immunology, 
 
 Vol. 43(Issue: 14),
 pp. 2169–2179,
 DOI: 10.1016/j.molimm.2006.01.005,
 PMID: 16503355,</ref><ref name="pmid18178718">, 
 CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways, 
 American Journal of Physiology. Heart and Circulatory Physiology, 
 
 Vol. 294(Issue: 3),
 pp. H1145–H1155,
 DOI: 10.1152/ajpheart.01328.2007,
 PMID: 18178718,</ref> and CB2 agonists may be useful in the treatment of pain and inflammation.<ref name="pmid1352348">, 
 Prescribing and use of benzodiazepines: an epidemiologic perspective, 
 Journal of Psychoactive Drugs, 
 1992,
 Vol. 24(Issue: 1),
 pp. 63–64,
 DOI: 10.1080/02791072.1992.10471620,
 PMID: 1352348,</ref><ref name="pmid17413917">, 
 Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision, 
 Anesthesiology, 
 
 Vol. 106(Issue: 4),
 pp. 787–794,
 DOI: 10.1097/01.anes.0000264765.33673.6c,
 PMID: 17413917,</ref> 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,<ref>,

 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, 
 
 Vol. 386(Issue: 5),
 pp. 1345–1355,
 DOI: 10.1007/s00216-006-0717-6,
 PMID: 16955257,</ref> similar to the metabolic pathways seen for other aminoalkylindole cannabinoids such as WIN 55,212-2.<ref name="pmid12228183">, 
 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, 
 
 Vol. 30(Issue: 10),
 pp. 1077–1086,
 DOI: 10.1124/dmd.30.10.1077,
 PMID: 12228183,</ref> 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.<ref>, 
 Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: involvement of CB2, 
 British Journal of Cancer, 
 
 Vol. 101(Issue: 6),
 pp. 940–950,
 DOI: 10.1038/sj.bjc.6605248,
 PMID: 19690545,
 PMC: 2743360,</ref>

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.<ref>Template:UnitedStatesCode2</ref>

As of October 2015 JWH-015 is a controlled substance in China.<ref>

关于印发《非药用类麻醉药品和精神药品列管办法》的通知(link). {{{website}}}. China Food and Drug Administration. 27 September 2015.

Accessed 1 October 2015.

</ref>

JWH-015 has been classified under the German BtMG as Anlage II.<ref>

Stoffe gem. Anlagen zum BtMG(link). {{{website}}}.

Accessed 2024-11-23.

</ref>

References

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  JWH-015