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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.
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.
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.
Compared to THC, which is a partial agonist at CB1 receptors, JWH-018, and many synthetic cannabinoids, are full agonists. THC has been shown to inhibit GABA receptor neurotransmission in the brain via several pathways. It inhibites GABA neurotransmission more effectively than THC.