'''''JWH-015''''' is a synthetic [[cannabinoid]] that acts as a selective agonist for the [[cannabinoid receptor]]s. It is part of the [[naphthoylindole]] family of compounds and is known for its potential therapeutic applications as well as its use in scientific research.
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==Chemical Properties==
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JWH-015 is chemically classified as a naphthoylindole, with the full chemical name ''(2-Methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone''. It has a molecular formula of C24H23NO and a molecular weight of 341.45 g/mol. The compound is characterized by its indole core structure, which is common among many synthetic cannabinoids.
JWH-015 acts as a selective agonist for the [[CB2 receptor]], with a moderate affinity for the [[CB1 receptor]]. This selectivity makes it of interest for research into the [[endocannabinoid system]] and its potential therapeutic applications, particularly in the modulation of immune responses and inflammation.
'''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]].
===Mechanism of Action===
The primary action of JWH-015 is through its interaction with the CB2 receptor, which is predominantly expressed in the [[immune system]]. Activation of this receptor by JWH-015 can lead to anti-inflammatory effects and modulation of immune cell activity. The compound's lower affinity for the CB1 receptor, which is primarily found in the [[central nervous system]], results in fewer psychoactive effects compared to other cannabinoids.
==Metabolism==
==Potential Applications==
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>
Research into JWH-015 has explored its potential use in treating conditions such as [[chronic pain]], [[inflammation]], and [[autoimmune diseases]]. Its selective action on the CB2 receptor makes it a candidate for therapies that aim to minimize psychoactive side effects while providing therapeutic benefits.
==Legal status==
==Legal Status==
The legal status of JWH-015 varies by country. In some jurisdictions, it is classified as a controlled substance due to its structural similarity to other synthetic cannabinoids that have been associated with recreational use and potential abuse.
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>
==Safety and Toxicology==
As with many synthetic cannabinoids, the safety profile of JWH-015 is not fully understood. Studies have indicated that it may have a lower risk of psychoactive effects compared to other cannabinoids, but its long-term effects and potential toxicity remain areas of active research.
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>
==Related Pages==
* [[Cannabinoid receptor]]
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 cannabinoid]]
* [[Endocannabinoid system]]
== References ==
* [[CB1 receptor]]
{{reflist|35em}}
* [[CB2 receptor]]
{{Cannabinoids}}
[[Category:Synthetic cannabinoids]]
[[Category:Indoles]]
[[Category:Naphthoylindoles]]
[[Category:Naphthoylindoles]]
[[Category:JWH cannabinoids]]
[[Category:Designer drugs]]
[[Category:CB1 receptor agonists]]
[[Category:CB2 receptor agonists]]
Latest revision as of 18:57, 23 March 2025
Synthetic cannabinoid
Chemical structure of JWH-015
JWH-015 is a synthetic cannabinoid that acts as a selective agonist for the cannabinoid receptors. It is part of the naphthoylindole family of compounds and is known for its potential therapeutic applications as well as its use in scientific research.
JWH-015 is chemically classified as a naphthoylindole, with the full chemical name (2-Methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone. It has a molecular formula of C24H23NO and a molecular weight of 341.45 g/mol. The compound is characterized by its indole core structure, which is common among many synthetic cannabinoids.
JWH-015 acts as a selective agonist for the CB2 receptor, with a moderate affinity for the CB1 receptor. This selectivity makes it of interest for research into the endocannabinoid system and its potential therapeutic applications, particularly in the modulation of immune responses and inflammation.
The primary action of JWH-015 is through its interaction with the CB2 receptor, which is predominantly expressed in the immune system. Activation of this receptor by JWH-015 can lead to anti-inflammatory effects and modulation of immune cell activity. The compound's lower affinity for the CB1 receptor, which is primarily found in the central nervous system, results in fewer psychoactive effects compared to other cannabinoids.
Research into JWH-015 has explored its potential use in treating conditions such as chronic pain, inflammation, and autoimmune diseases. Its selective action on the CB2 receptor makes it a candidate for therapies that aim to minimize psychoactive side effects while providing therapeutic benefits.
The legal status of JWH-015 varies by country. In some jurisdictions, it is classified as a controlled substance due to its structural similarity to other synthetic cannabinoids that have been associated with recreational use and potential abuse.
As with many synthetic cannabinoids, the safety profile of JWH-015 is not fully understood. Studies have indicated that it may have a lower risk of psychoactive effects compared to other cannabinoids, but its long-term effects and potential toxicity remain areas of active research.
