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JWH-018 Germany. JWH-018 (1-pentyl-3-(1-naphthoyl)indole) or AM-678^[1] 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”.^{[2][3][4][5][6]}

As a full agonist at both the CB₁ and CB₂ cannabinoid receptors, this chemical compound is classified as an analgesic medication.^[7] 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.^[7]

These 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.^[7] As the cause is poorly understood in chronic pain states, more research and development must be done before the therapeutic potential of this class of biologic compounds can be realized.

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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 the naphthalene and indole portions of the molecule.^[14] 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.^[15]