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JWH-018 (1-pentyl-3-(1-naphthoyl)indole) or AM-678 is an analgesic chemical from the naphthoylindole family that acts as a full agonist at both the CB1 and CB2 cannabinoid receptors, with some selectivity for CB2. It produces effects in animals similar to those of tetrahydrocannabinol (THC), a cannabinoid naturally present in cannabis, leading to its use in synthetic cannabis products that in some countries are sold legally as “incense blends 

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As a full agonist at both the CB1 and CB2 cannabinoid receptors, this chemical compound is classified as an analgesic medication. The analgesic effects of cannabinoid ligands, mediated by CB1 receptors are well established in treatment of neuropathic pain, as well as cancer pain and arthritis. JWH-018 compounds work by mimicking the body’s naturally-produced endocannabinoid hormones such as 2-AG and anandamide (AEA), which are biologically active and can exacerbate or inhibit nerve signaling.  

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John W. Huffman, an organic chemist at Clemson University, synthesized a variety of chemical compounds that affect the endocannabinoid 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. Cannabinoid receptors are found in mammalian brain and spleen tissue; however, the structural details of the active sites are currently unknown.  

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On December 15, 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 the grey market drug Spice, which has been sold as an incense in a number of countries around the world since 2002. An analysis of samples acquired four weeks after the German prohibition of JWH-018 took place found that the manufacturers had shortened the alkyl chain by one carbon to circumvent the ban. 

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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. JWH-018 has an EC50 of 102 nM for human CB1 receptors, and 133 nM for human CB2 receptors. JWH-018 produces bradycardia and hypothermia in rats at doses of 0.3–3 mg/kg, suggesting potent cannabinoid–like activity. 

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At least one case of JWH-018 dependence has been reported by the media. The user consumed JWH-018 daily for eight months. Withdrawal symptoms were more severe than those experienced as a result of cannabis 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.

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Other Names; K2; SPICE; JWH-073; Legal Weed; ‘synthetic cannabis’, ‘herbal incense’, Synthetic cannabinoids, 1-Pentyl-3-(1-naphthoyl)indole, 1-pentyl-3-(1-naphthoyl)-indole, JWH 018, JWH018, AM 678

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