JWH-015: Difference between revisions

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

Newer edit →

Revision as of 16:09, 24 November 2024

Chemical compound

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

@@ Line 1: / Line 1: @@
-[[File:JWH-015.svg|thumb|JWH-015.svg]] {{Short description|Synthetic cannabinoid}}
+{{Short description|Chemical compound}}
-{{Infobox drug
+{{Drugbox
-| image = JWH-015 structure.png
+| Verifiedfields = changed
-| width = 200
+| Watchedfields = changed
-| IUPAC name = (2-Methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone
+| verifiedrevid = 444488130
-| CAS number = 155471-08-2
+| IUPAC_name = (2-Methyl-1-propyl-1''H''-indol-3-yl)-1-naphthalenylmethanone
-| ATC prefix = none
+| image = JWH-015.svg
-| PubChem = 9866750
-| ChemSpiderID = 8041551
+<!--Clinical data-->
-| UNII = 0P6C6ZOP5U
+| tradename =
-| C=24
+| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
-| H=23
+| pregnancy_US = <!-- A / B            / C / D / X -->
-| N=1
+| pregnancy_category =
-| O=1
+| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
-| smiles = CCCn1cc(c2c1cccc2)C(=O)c3cccc4c3cccc4C
+| legal_CA = Schedule II
-| StdInChI = 1S/C24H23NO/c1-3-14-25-16-21(20-12-6-7-13-22(20)25)24(26)23-15-10-8-9-11-18(15)17-19(23)2/h6-13,16-17H,3-5,14H2,1-2H3
+| legal_UK = Class B
-| StdInChIKey = QXJYQXQKMLXGMW-UHFFFAOYSA-N
+| legal_US = Schedule I
+| legal_DE = Anlage II
+| routes_of_administration =
+<!--Pharmacokinetic data-->
+| bioavailability =
+| protein_bound =
+| metabolism =
+| elimination_half-life =
+| excretion =
+<!--Identifiers-->
+| IUPHAR_ligand = 5558
+| CAS_number_Ref = {{cascite|correct|??}}
+| CAS_number = 155471-08-2
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = W4FL204T10
+| ATC_prefix =
+| ATC_suffix =
+| PubChem = 4273754
+| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
+| DrugBank =
+| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
+| ChemSpiderID      = 3480676
+<!--Chemical data-->
+| C=23 | H=21 | N=1 | O=1
+| smiles            = CCCN1C(=C(C2=CC=CC=C21)C(=O)C3=CC=CC4=CC=CC=C43)C
+| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
+| StdInChI          = 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
+| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
+| StdInChIKey       = LJSBBBWQTLXQEN-UHFFFAOYSA-N
 }}
-'''JWH-015''' is a synthetic [[cannabinoid]] from the [[naphthoylindole]] family. It acts as a selective agonist for the [[cannabinoid receptor]] [[CB2 receptor|CB2]], with a Ki of 13.8 nM and selectivity of approximately 27.8 times over the [[CB1 receptor|CB1]] receptor.
+'''JWH-015''' is a chemical from the [[naphthoylindole]] family that acts as a subtype-selective [[cannabinoid]] [[agonist]]. Its affinity for [[Cannabinoid receptor type 2|CB<sub>2</sub> receptors]] is 13.8 nM, while its affinity for [[Cannabinoid receptor type 1|CB<sub>1</sub>]] is 383 nM, meaning that it binds almost 28 times more strongly to CB<sub>2</sub> than to CB<sub>1</sub>.<ref name="pmid10940540">{{cite journal | vauthors = Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR | display-authors = 6 | title = Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB<sub>1</sub> and CB<sub>2</sub>)receptor binding | journal = Drug and Alcohol Dependence | volume = 60 | issue = 2 | pages = 133–140 | date = August 2000 | pmid = 10940540 | doi = 10.1016/S0376-8716(99)00152-0 }}</ref> However, it still displays some CB<sub>1</sub> activity, and in some model systems can be very potent and efficacious at activating CB<sub>1</sub> receptors,<ref name="pmid22921769">{{cite journal | vauthors = Murataeva N, Mackie K, Straiker A | title = The CB2-preferring agonist JWH015 also potently and efficaciously activates CB1 in autaptic hippocampal neurons | journal = Pharmacological Research | volume = 66 | issue = 5 | pages = 437–442 | date = November 2012 | pmid = 22921769 | pmc = 3601544 | doi = 10.1016/j.phrs.2012.08.002 }}</ref> and therefore it is not as selective as newer drugs such as [[JWH-133]].<ref name="pmid18289088">{{cite journal | vauthors = Marriott KS, Huffman JW | title = Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor | journal = Current Topics in Medicinal Chemistry | volume = 8 | issue = 3 | pages = 187–204 | year = 2008 | pmid = 18289088 | doi = 10.2174/156802608783498014 }}</ref> It has been shown to possess [[immunomodulatory]] effects,<ref name="pmid16503355">{{cite journal | vauthors = Ghosh S, Preet A, Groopman JE, Ganju RK | title = Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes | journal = Molecular Immunology | volume = 43 | issue = 14 | pages = 2169–2179 | date = July 2006 | pmid = 16503355 | doi = 10.1016/j.molimm.2006.01.005 }}</ref><ref name="pmid18178718">{{cite journal | vauthors = Montecucco F, Burger F, Mach F, Steffens S | title = CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 294 | issue = 3 | pages = H1145–H1155 | date = March 2008 | pmid = 18178718 | doi = 10.1152/ajpheart.01328.2007 | s2cid = 5896815 }}</ref> and CB<sub>2</sub> agonists may be useful in the treatment of pain and inflammation.<ref name="pmid1352348">{{cite journal | vauthors = Balter MB, Uhlenhuth EH | title = Prescribing and use of benzodiazepines: an epidemiologic perspective | journal = Journal of Psychoactive Drugs | volume = 24 | issue = 1 | pages = 63–64 | year = 1992 | pmid = 1352348 | doi = 10.1080/02791072.1992.10471620 }}</ref><ref name="pmid17413917">{{cite journal | vauthors = Romero-Sandoval A, Eisenach JC | title = Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision | journal = Anesthesiology | volume = 106 | issue = 4 | pages = 787–794 | date = April 2007 | pmid = 17413917 | doi = 10.1097/01.anes.0000264765.33673.6c | author2-link = James C. Eisenach | doi-access = free }}</ref> It was discovered and named after [[John W. Huffman]].
-== Pharmacology ==
+==Metabolism==
-JWH-015 is known for its high affinity for the [[CB2 receptor]], which is primarily found in the [[immune system]]. This selectivity makes it a subject of interest for research into [[anti-inflammatory]] and [[immunomodulatory]] effects. Unlike many other synthetic cannabinoids, JWH-015 has a lower affinity for the [[CB1 receptor]], which is predominantly located in the [[central nervous system]].
+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>{{cite journal | vauthors = Zhang Q, Ma P, Cole RB, Wang G | title = Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS | journal = Analytical and Bioanalytical Chemistry | volume = 386 | issue = 5 | pages = 1345–1355 | date = November 2006 | pmid = 16955257 | doi = 10.1007/s00216-006-0717-6 | s2cid = 9116612 }}</ref> similar to the metabolic pathways seen for other [[aminoalkylindole]] [[cannabinoids]] such as [[WIN 55,212-2]].<ref name="pmid12228183">{{cite journal | vauthors = Zhang Q, Ma P, Iszard M, Cole RB, Wang W, Wang G | title = 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 | journal = Drug Metabolism and Disposition | volume = 30 | issue = 10 | pages = 1077–1086 | date = October 2002 | pmid = 12228183 | doi = 10.1124/dmd.30.10.1077 | s2cid = 10848076 }}</ref> [[Epoxidation]] of [[polycyclic aromatic hydrocarbon]]s (see for example  [[Benzo(a)pyrene#Toxicity|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>{{cite journal | vauthors = Olea-Herrero N, Vara D, Malagarie-Cazenave S, Díaz-Laviada I | title = Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: involvement of CB2 | journal = British Journal of Cancer | volume = 101 | issue = 6 | pages = 940–950 | date = September 2009 | pmid = 19690545 | pmc = 2743360 | doi = 10.1038/sj.bjc.6605248 }}</ref>
-== Chemical Structure ==
+==Legal status==
-The chemical structure of JWH-015 includes a [[naphthalene]] ring attached to a [[methanone]] group, which is further connected to a [[2-methyl-1-propylindole]] moiety. This structure is similar to other compounds in the [[naphthoylindole]] family, such as [[JWH-018]] and [[JWH-073]].
-== Legal Status ==
+In the United States, all CB<sub>1</sub> receptor agonists of the 3-(1-naphthoyl)indole class such as JWH-015 are [[Schedule I Controlled Substance]]s.<ref>{{UnitedStatesCode2|21|812|Schedules of controlled substances}}</ref>
-The legal status of JWH-015 varies by country. In some jurisdictions, it is classified as a controlled substance due to its potential for abuse and lack of accepted medical use. In others, it remains legal for research purposes.
-== Research Applications ==
+As of October 2015 JWH-015 is a controlled substance in China.<ref>{{cite web | url=http://www.sfda.gov.cn/WS01/CL0056/130753.html | title=关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | trans-title = Notice on Issuing the Measures for the Listing and Control of Non-Medicinal Narcotic Drugs and Psychotropic Substances | publisher=China Food and Drug Administration | date=27 September 2015 | language=zh | access-date=1 October 2015 | archive-date=1 October 2015 | archive-url=https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html | url-status=dead }}</ref>
-JWH-015 is primarily used in scientific research to study the effects of selective [[CB2 receptor]] activation. It has been investigated for its potential therapeutic applications in conditions such as [[autoimmune diseases]], [[inflammatory disorders]], and [[pain management]].
-== See Also ==
+JWH-015 has been classified under the German [[BtMG]] as Anlage II.<ref>{{cite web | title=Stoffe gem. Anlagen zum BtMG | url=https://www.bfarm.de/SharedDocs/Downloads/DE/Bundesopiumstelle/Betaeubungsmittel/BtM-Stoffe.xls?__blob=publicationFile | access-date=2024-11-23}}</ref>
-* [[Synthetic cannabinoids]]
-* [[Cannabinoid receptor]]
-* [[JWH-018]]
-* [[JWH-073]]
 == References ==
-{{Reflist}}
+{{reflist|35em}}
+{{Cannabinoids}}
-[[Category:Synthetic cannabinoids]]
+[[Category:Naphthoylindoles]]
+[[Category:JWH cannabinoids]]
+[[Category:Designer drugs]]
+[[Category:CB1 receptor agonists]]
 [[Category:CB2 receptor agonists]]
-[[Category:Naphthoylindoles]]
-[[Category:Research chemicals]]
-[[Category:Medicine-stub]]
-{{medicine-stub}}