As a full agonist at both the CB1 and CB2 cannabinoid receptors, this chemical compound is classified as an analgesic medication.[10] The analgesic effects of cannabinoid ligands, mediated by CB1 receptors are well established in treatment ofneuropathic pain, as well ascancer pain andarthritis.[10]
These compounds work by mimicking the body's naturally-produced endocannabinoid hormones such as2-AG andanandamide (AEA), which are biologically active and can exacerbate or inhibit nerve signaling.[10] As the cause is poorly understood inchronic pain states, more research and development must be done before the therapeutic potential of this class of biologic compounds can be realized.[10]
John W. Huffman, an organic chemist atClemson University, synthesized a variety of chemical compounds that affect theendocannabinoid system. JWH-018 is one of these compounds, with studies showing an affinity for the cannabinoid CB1 receptor five times greater than that of THC.[11]
On 15 December 2008, it was reported by German pharmaceutical companies that JWH-018 was found as one of the active components in at least three versions of thegrey market drugSpice, which has been sold as an incense in a number of countries around the world since 2006.[12][13][14] An analysis of samples acquired four weeks after the German prohibition of JWH-018 took place found that the manufacturers hadshortened the alkyl chain by one carbon to circumvent the ban.[15]
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.[6] JWH-018 has anEC50 of 102 nM for human CB1 receptors, and 133 nM for human CB2 receptors.[16] JWH-018 producesbradycardia andhypothermia in rats at doses of 0.3–3 mg/kg, suggesting potent cannabinoid-like activity.[16]In synthetic cannabinoids, the switch to being a full agonist, increases the activation towards extending its psychoactivity and not regulating but also extending central nervous-activity anymore, to be more selective (CB1). This is meaning an activation of the central nervous system. Therefore, indirectly activating dopaminerelease in the cortexareas of the frontal brain. This is meaning, that it is activating and so, is being dopaminerg. Therefore, it can induce potent dopaminergic and hypnotic states with JWH-018 being heavy sedative with a binding affinity of 9.0 KnM.
Metabolism of JWH-018 was assessed using Wistar rats which had been administered an ethanolic extract containing JWH-018. Urine was collected for 24 hours, followed by extraction of JWH-018 metabolites using both liquid-liquid extraction and solid-phase extraction.GC-MS was utilized to separate and identify the extracted compounds. JWH-018 and its N-dealkylated metabolite were only detected in small amounts, with hydroxylated N-dealkylated metabolites comprising the primary signal. The observed mass shift indicates that it is likely that hydroxylation occurs in both thenaphthalene andindole portions of the molecule.[17] Human metabolites were similar although most metabolism took place on the indole ring and pentyl side chain, and the hydroxylated metabolites were extensively conjugated withglucuronide.[18] Wheninhaled, the median half-life of JWH-018 is 1.69 hours.[19]
At least one case of JWH-018 dependence has been reported by the media.[5] The user consumed JWH-018 daily for eight months.Withdrawal symptoms were more severe than those experienced as a result ofcannabis dependence. 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.[9]
On 15 October 2011, Anderson County coroner Greg Shore attributed the death of a South Carolina college basketball player to "drug toxicity and organ failure" caused by JWH-018.[20] A November 2011 email concerning the case was released in December 2011 under the Freedom of Information Act after multiple requests to see the information had been denied.[21]
Compared to THC, which is apartial agonist at CB1 receptors, JWH-018, and many synthetic cannabinoids, arefull agonists. JWH-018 may cause intenseanxiety, agitation, and in rare cases, has been assumed to have been the cause ofseizures andconvulsions. JWH-018 and analogs of it may present serious dangers to the user when used to excess.[22]
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.[23] Due to concerns about the potential of JWH-018 and other synthetic cannabinoids to causepsychosis in vulnerable individuals, it has been recommended that people with risk factors for psychotic disorders, such as a past or family history of psychosis, not use these substances.[24]
JWH-018 usage is readily detected in urine using "spice" screening immunoassays from several manufacturers focused on both the parent drug and its omega-hydroxy and carboxyl metabolites.[25] JWH-018 will not be detected by older methods employed for detecting THC and other cannabis terpenoids. Determination of the parent drug in serum or itsmetabolites in urine has been accomplished byGC-MS orLC-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 six users of the drug at concentrations of 6–50 μg/L, primarily as a glucuronide conjugate.[26][27][28][29][30][31][32][33][34]
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 that affects the functions of the body, and the legality of JWH-018 is under review.
JWH-018 is considered a Schedule 9 prohibited substance in Australia under thePoisons Standard (October 2015).[35] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[35]
Despite the Canadian federal government having officially legalized the recreational use of cannabis on October17, 2018(seeCannabis Act), substances such as JWH-018 andJWH-073 are both on the most recently amended Schedule II of the Controlled Drugs and Substances Act.[36]
The Anti-narcotics department declared synthetic cannabinoids and their analogues illegal after an outbreak of JWH-018 containing product referred to as "Joker".[48]
Turkish authorities were first informed about JWH-018 through theEuropean Monitoring Centre for Drugs and Drug Addiction (EMCDDA). The seizure of 2C-B in blue pill form on 13 October 2010 and the seizure of 0.6 g JWH-018 on 16 April 2010 in Eskisehir was reported through the Early Warning System (EWS). Upon these reports the EWS committee initiated the regulation process by warning the Ministry of Health.[54] In response to the official letter #86106 issued by the Ministry of Health dated 22 December 2010, the Council of Ministers decided on 7 January 2011 to add 14cannabinoids; namely JWH-018,CP 47,497,JWH-073,HU-210,JWH-200,JWH-250,JWH-398,JWH-081,JWH-073,JWH-015,JWH-122,JWH-203,JWH-210,JWH-019;phenethylamines2C-B and2C-P as well asCatha edulis to the list of substances subject to the Law on Control of Narcotic Drugs. The regulation is in effect since 13 February 2011.[55] Upon letter #12099 issued by the Ministry of Health dated 6 February 2012, 4 more cannabinoids (AM-2201,RCS-4,JWH-201 andJWH-302),Salvia divinorum and several other chemicals (complete list here[56]) were added to the list of controlled substances on 17 February 2012 which is effective since 22 March 2012.[57]
^Pulver B, Fischmann S, Gallegos A, Christie R (March 2023). "EMCDDA framework and practical guidance for naming synthetic cannabinoids".Drug Testing and Analysis.15 (3):255–276.doi:10.1002/dta.3403.PMID36346325.
^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.PMID20430547.
^Toennes SW, Geraths A, Pogoda W, Paulke A, Wunder C, Theunissen EL, et al. (April 2018). "Pharmacokinetic properties of the synthetic cannabinoid JWH-018 in oral fluid after inhalation".Drug Testing and Analysis.10 (4):644–650.doi:10.1002/dta.2310.PMID28967189.
^Arntson A, Ofsa B, Lancaster D, Simon JR, McMullin M, Logan B (June 2013). "Validation of a novel immunoassay for the detection of synthetic cannabinoids and metabolites in urine specimens".Journal of Analytical Toxicology.37 (5):284–290.doi:10.1093/jat/bkt024.PMID23625703.
^Möller I,et al. Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. Drug Test. Anal. 24 Sep 2010. [Epub ahead of print]
^Teske J,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.
^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.PMID20430547.
^Beuck S, Möller I, Thomas A, Klose A, Schlörer N, Schänzer W, et al. (August 2011). "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.401 (2):493–505.doi:10.1007/s00216-011-4931-5.PMID21455647.S2CID33433526.
^Appendino G, Minassi A, Taglialatela-Scafati O (2014). "Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs".Natural Product Reports.31 (7):880–904.doi:10.1039/c4np00010b.PMID24823967.
De Luca MA, Bimpisidis Z, Melis M, Marti M, Caboni P, Valentini V, et al. (December 2015). "Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid".Neuropharmacology.99:705–14.doi:10.1016/j.neuropharm.2015.08.041.hdl:11392/2330864.PMID26327678.
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