JWH-018

JWH-018

Systematic (IUPAC) name
Naphthalen-1-yl-(1-pentylindol-3-yl)methanone
Clinical data
Pregnancy cat.	?
Legal status	Schedule I (US)
Routes	Smoked, Oral
Identifiers
CAS number	209414-07-3 N
ATC code	?
PubChem	CID 10382701
ChemSpider	8558143 Y
ChEMBL	CHEMBL561013 Y
Chemical data
Formula	C24H23NO
Mol. mass	341.45 g/mol
InChI InChI=1S/C24H23NO/c1-2-3-8-16-25-17-22(20-13-6-7-15-23(20)25)24(26)21-14-9-11-18-10-4-5-12-19(18)21/h4-7,9-15,17H,2-3,8,16H2,1H3 Y Key:JDNLPKCAXICMBW-UHFFFAOYSA-N Y
Physical data
Solubility in water	hydrophobic, n/a mg/mL (20 °C)
N(what is this?)  (verify)

JWH-018 (1-pentyl-3-(1-naphthoyl)indole) or AM-678^[1] is an analgesic chemical from the naphthoylindole family, which acts as a full agonist at both the CB₁ and CB₂ cannabinoid receptors, with some selectivity for CB₂.^[2][3][4][5] It produces effects in animals similar to those of THC, a cannabinoid naturally present in cannabis, leading to its use in synthetic cannabis.

History

John W. Huffman, an organic chemist at Clemson University, synthesized analogues and metabolites of Δ⁹-tetrahydrocannabinol (THC), the principal active component of cannabis. JWH-018 is one of these analogues, with studies showing an affinity for the cannabinoid (CB₁) receptor five times greater than that of THC. Cannabinoid receptors are found in mammalian brain and spleen tissue; however, the structural details of the active sites are currently unknown.^[6][7]

On December 15, 2008, it was reported by the German pharmaceutical company THC Pharm that JWH-018 was found as one of the active components in at least three versions of the herbal blend Spice, which has been sold as an incense in a number of countries around the world since 2002.^[8][9][10] An analysis of samples acquired four weeks after the German prohibition of JWH-018 took place found that the compound had been replaced with JWH-073.^[11]

Pharmacology

JWH-018 is a full agonist of both the CB₁ and CB₂ cannabinoid receptors, with a reported binding affinity of 9.00±5.00 nM at CB₁ and 2.94±2.65 nM at CB₂.^[12]

JWH-018 administered to rats resulted in the excretion of an indole-N-desalkyl metabolite as well as several hydroxylated metabolites in urine. The highest signals were observed for the hydroxylated N-desalkyl metabolites. Hydroxylation took place on the side chain and in both aromatic systems, the naphthalene and the indole rings, as could be shown by mass shift of the corresponding fragments and by MS³ experiments.^[13] Human metabolites were similar although most metabolism took place on the indole ring and pentyl side chain, and the hydroxylated metabolites were extensively conjugated with glucuronide.^[14]

Usage

At least one case of JWH-018 dependence has been reported. On October 15, 2011, coroner reports released to the media reveal that the death of a South Carolina college basketball player was attributed to "drug toxicity and organ failure" caused by JWH-018. The user consumed JWH-018 daily for eight months. Withdrawal symptoms were similar to those experienced as a result of cannabis dependence.^[15] JWH-018 has been shown to cause profound changes in CB₁ receptor density following administration, causing desensitization to its effects more rapidly than related cannabinoids.^[5]

Compared to THC, which is a partial agonist at CB₁ receptors, JWH-018 (and many of its analogues) are full agonists. This means that users may experience far more intense effects compared to smoking cannabis. THC has been shown to inhibit GABA neurotransmission in the brain via several pathways.^[16][17] JWH-018 may cause intense anxiety, agitation, and, in rare cases (generally with non-regular JWH users), has been assumed to have been the cause of seizures and convulsions by inhibiting GABA neurotransmission more effectively than THC. Cannabinoid receptor full agonists may present serious dangers to the user when used to excess.^[18]

Various physical and psychological adverse effects have been reported from JWH-018 use. One study reported psychotic relapses and anxiety symptoms in well-treated patients with mental illness following JWH-018 inhalation.^[19] Due to concerns about the potential of JWH-018 and other synthetic cannabinoids to cause psychosis in vulnerable individuals, it has been recommended that people with risk factors for psychotic illnesses (like a past or family history of psychosis) not use these substances.^[20]

According to the writer Kevin Keck, who sampled various brands of herbal incense containing JWH-018 for research on the subject, "A small amount does produce visual distortions and a marijuana-like buzz. I can easily understand how individuals with little or no experience in navigating this psychic terrain could experience extreme panic attacks that prompt them to seek medical attention...It is not a problem that responsible people use [JWH-018], it is a serious problem that naïve and foolish people use [it]. It is the same problem that surrounds alcohol and any other number of legal prescription drugs."^[21]

Detection in biological fluids

JWH-018 usage is not detectable with the usual immunoassay screening methods employed for detecting cannabis use from urine specimens. Determination of the parent drug in serum or its metabolites in urine has been accomplished by GC-MS or LC-MS. Serum JWH-018 concentrations are generally in the 1-10 μg/L range during the first few hours after recreational usage. The major urinary metabolite is a compound that is monohydroxylated on the omega minus one carbon atom of the alkyl side chain. A lesser metabolite monohydroxylated on the omega (terminal) position was present in the urine of 6 users of the drug at concentrations of 6-50 μg/L, primarily as a glucuronide conjugate.^{[22][23][24][25][26][27][28][29][30]}

Legal status

JWH-018 powder as it was commonly sold online

Country	Date of Ban	Notes
Austria	The Austrian Ministry of Health announced on 18 December 2008 that Spice would be controlled under Paragraph 78 of their drug law on the grounds that it contains an active substance which affects the functions of the body, and the legality of JWH-018 is under review.
Belarus	1 January 2010
Canada	June 3, 2010	JWH-018 is not a controlled substance in Canada. Note: the most current CDSA can be found here[31]
France	February 24, 2009	[32][33]
Germany	22 January 2009	[34]
Ireland	11 May 2010	An immediate ban was announced on 11 May 2010 by Minister for Health Mary Harney.[35]
Italy	2 July 2010	[36]
Latvia	28 November 2009
Poland		[32]
South Korea	1 July 2009	[37]
Sweden	30 July 2009	A bill to ban JWH-018 was accepted on 30 July 2009 and was in effect on 15 September 2009.[38]
Estonia	24 July 2009
Romania	15 February 2010
Russia	22 January 2010
Ukraine	31 May 2010
United Kingdom	23 December 2009	[39]
United States	1 March 2011	JWH-018 and four similar cannabinoids were classified as Schedule I controlled substances by the Drug Enforcement Administration on March 1, 2011, making their possession and use illegal in all 50 states.[40] The law allows for a one-year DEA study of the effects of JWH-018 on the human body to determine and whether it should be permanently classified as Schedule I in the United States.[41]

See also

• JWH-073
• JWH-250
• JWH-200

References

1. ^ "Department of Justice :: Drug Enforcement Administration". 2011-03-01. http://www.scribd.com/doc/49741625/DEA-Rule-on-Synthetic-Cannabinoids. Retrieved 2011-03-02. 
2. ^ Aung, M. M.; et al. (2000). "Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB₁ and CB₂ receptor binding". Drug and Alcohol Dependence 60 (2): 133–140. doi:10.1016/S0376-8716(99)00152-0. PMID 10940540. 
3. ^ US patent 6900236, Alexandros Makriyannis, Hongfeng Deng, "Cannabimimetic indole derivatives", issued 2005-05-31 
4. ^ US patent 7241799, Alexandros Makriyannis, Hongfeng Deng, "Cannabimimetic indole derivatives", issued 2007-07-10 
5. ^ ^{a b} B.K. Atwood et. al., "JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB1 receptor agonist." British Journal of Pharmacology, Vol. 160, No. 3. 585-593. 2010.[1]
6. ^ "Clemson University :: Department of Chemistry". Clemson.edu. http://www.clemson.edu/chemistry/people/huffman.html. Retrieved 2010-08-23. 
7. ^ 11:10. "Drugs Forum". Drugs Forum. http://www.drugs-forum.com/forum/showthread.php?s=118de94c4da38df748848101980625d4&t=71910. Retrieved 2010-08-23. 
8. ^ Gefährlicher Kick mit Spice (German)
9. ^ Erstmals Bestandteile der Modedroge „Spice“ nachgewiesen (German)
10. ^ Spice enthält chemischen Wirkstoff (German)
11. ^ Lindigkeit, Rainer; Boehme, A; Eiserloh, I; Luebbecke, M; Wiggermann, M; Ernst, L; Beuerle, T (30 October 2009). "Spice: A never ending story?". Forensic science international (Forensic Science International) 191 (1): 58–63. doi:10.1016/j.forsciint.2009.06.008. PMID 19589652 
12. ^ Aung, M.M., Griffin, G., Huffman, J.W., et al. Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding. Drug and Alcohol Dependence 60 133-140 (2000)
13. ^ Studies on the metabolism of JWH-018 and of a homologue of CP 47,497, pharmacologically active ingredients of different misused incense (“Spice”) using GC-MS and LC-MSn techniques - T. Kraemer, K.Y. Rust, M.R. Meyer, D.K. Wissenbach, D. Bregel, M. Hopf, H.H. Maurer, J. Wilske (Institute of Legal Medicine, Saarland University, 66421 Homburg, Germany http://www.gtfch.org/cms/images/stories/media/tk/tk76_2/abstractsvortraege.pdf
14. ^ Sobolevsky T, Prasolov I, Rodchenkov G (July 2010). "Detection of JWH-018 metabolites in smoking mixture post-administration urine". Forensic Science International 200 (1-3): 141–7. doi:10.1016/j.forsciint.2010.04.003. PMID 20430547. 
15. ^ Zimmermann, US; Winkelmann, PR; Pilhatsch, M; Nees, JA; Spanagel, R; Schulz, K (2009). "Withdrawal Phenomena and Dependence Syndrome After the Consumption of "Spice Gold"". Dtsch Arztebl Int 106 (27): 464–467. doi:10.3238/arztebl.2009.0464. PMC 2719097. PMID 19652769. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2719097. 
16. ^ Laaris, Nora; Good, Cameron H.; Lupica, Carl R. (July – August 2010). "Δ⁹-tetrahydrocannabinol is a full agonist at CB1 receptors on GABA neuron axon terminals in the hippocampus". Neuropharmacology 59 (1–2): 121–127. doi:10.1016/j.neuropharm.2010.04.013. PMC 2882293. PMID 20417220. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2882293. Retrieved 2011-07-26. 
17. ^ Hoffman, Alexander F.; Lupica, Carl R. (2000-04-01). "Mechanisms of cannabinoid inhibition of GABA_A synaptic transmission in the hippocampus.". The Journal of Neuroscience 20 (7): 2470–2479. ISSN 0270-6474. PMID 10729327. http://www.jneurosci.org/content/20/7/2470.long. Retrieved 2011-07-26. 
18. ^ European Monitoring Centre for Drugs and Drug Addiction. "Understanding the Spice Phenomenon." 2009. ISBN 978-92-9168-411-3.[2]
19. ^ Every-Palmer, S. Synthetic cannabinoid use and psychosis: an explorative study. Journal of Drug and Alcohol Dependence 2011. [Epub ahead of print].
20. ^ Every-Palmer, S. (2010), WARNING: LEGAL SYNTHETIC CANNABINOID-RECEPTOR AGONISTS SUCH AS JWH-018 MAY PRECIPITATE PSYCHOSIS IN VULNERABLE INDIVIDUALS. Addiction, 105: 1859–1860. doi: 10.1111/j.1360-0443.2010.03119.x.
21. ^ . Creative Loafing. August 24, 2010. http://charlotte.creativeloafing.com/gyrobase/a_user_s_guide_to_legal_weed_/Content?oid=1028428 User's Guide to "Legal Weed" 
22. ^ Möller I, Wintermeyer A, Bender K, et al. Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. Drug Test. Anal. Sep 24, 2010. [Epub ahead of print]
23. ^ Teske J, Weller JP, Fieguth A, et al. Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography-tandem mass spectrometry. J Chrom. B 878: 2659-2663, 2010.
24. ^ Auwärter, V.; Dresen, S.; Weinmann, W.; Müller, M.; Pütz, M.; Ferreirós, N. (2009). "'Spice' and other herbal blends: harmless incense or cannabinoid designer drugs?". Journal of mass spectrometry : JMS 44 (5): 832–837. doi:10.1002/jms.1558. PMID 19189348.  edit Free version
25. ^ Zimmermann, U.; Winkelmann, P.; Pilhatsch, M.; Nees, J.; Spanagel, R.; Schulz, K. (2009). "Withdrawal phenomena and dependence syndrome after the consumption of "spice gold"". Deutsches Arzteblatt international 106 (27): 464–467. doi:10.3238/arztebl.2009.0464. PMC 2719097. PMID 19652769. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2719097.  edit
26. ^ Sobolevsky, T.; Prasolov, I.; Rodchenkov, G. (2010). "Detection of JWH-018 metabolites in smoking mixture post-administration urine". Forensic science international 200 (1–3): 141–147. doi:10.1016/j.forsciint.2010.04.003. PMID 20430547.  edit
27. ^ Beuck S, Möller I, Thomas A, et al. Structure characterisation of urinary metabolites of the cannabimimetic JWH-018 using chemically synthesised reference material for the support of LC-MS/MS-based drug testing. Anal. Bioanal. Chem. 2011 Apr 1 [Epub ahead of print] PMID:21455647
28. ^ Moran CL, Le VH, Chimalakonda KC, et al. Quantitative Measurement of JWH-018 and JWH-073 Metabolites Excreted in Human Urine. Anal. Chem. 2011 Apr 20 [Epub ahead of print] PMID:21506519
29. ^ Logan BK, Kacinko SL, McMullin MM, et al. Identification of primary JWH-018 and JWH-073 metabolites in human urine. NMS Labs Technical Bulletin, May 25, 2011. http://toxwiki.wikispaces.com/file/view/JWH_metabolites_Technical_Bulletin_Final_v1.1.pdf
30. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, CA, 2011, p. 1566. http://www.biomedicalpublications.com/spice.pdf
31. ^ "Controlled Drugs and Substances Act". Laws.justice.gc.ca. 2010-08-16. http://laws.justice.gc.ca/en/C-38.8/. Retrieved 2010-08-23. 
32. ^ ^{a b} "EMCDDA | Drug profile: Synthetic cannabinoids and 'Spice'". Emcdda.europa.eu. 2010-08-17. http://www.emcdda.europa.eu/publications/drug-profiles/synthetic-cannabinoids#control. Retrieved 2010-08-23. 
33. ^ http://www.afssaps.fr/var/afssaps_site/storage/original/application/d23d05edc58479d91c803b496017f073.pdf
34. ^ BGBl I Nr. 3 vom 21.01.2009, 22. BtMÄndV vom 19. Januar 2009, S. 49–50.
35. ^ Many head shop products banned - Irish Times.
36. ^ http://www.politicheantidroga.it/comunicazione/comunicati/2010/luglio/spice,-n-joy-e-mefedrone-da-oggi-stupefacenti.aspx (Italian)
37. ^ 최연희 (2 July 2009). "1일부터 ‘5-메오-밉트’ 등 향정신성의약품 지정". 헬스코리아뉴스. http://www.hkn24.com/news/articleView.html?idxno=28611. Retrieved 18 February 2010. 
38. ^ http://www.regeringen.se/sb/d/12102/a/130038 (Swedish)
39. ^ Ford, Richard (2009-12-23). "Three legal highs banned after deaths linked to the drugs". The Times (London). http://business.timesonline.co.uk/tol/business/law/article6965663.ece. Retrieved 2010-05-07. 
40. ^ Cook, Morgan (2011-02-28). "Synthetic marijuana illegal as of Tuesday". North County Times (San Diego). http://www.nctimes.com/news/local/sdcounty/article_d000d0ec-653e-51a8-bc3d-55e144f415c1.html. Retrieved 2011-02-28. 
41. ^ Meserve, Jeanne (2011-02-28). "DEA imposes "emergency" ban to control synthetic marijuana". CNN. http://www.cnn.com/2011/US/02/28/dea.synthetic.marijuana/index.html?iref=allsearch. Retrieved 2011-03-01. 

http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10716926

External links

• JWH-018 Report Psychonaut Web Mapping Research Project