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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”.
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.
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. 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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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.
On October 15, 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. An email dated Nov 4, 2011 concerning the case was finally released by the city of Anderson S.C. on Dec 16, 2011 under the Freedom of Information Act after multiple requests by media to see the information had been denied.
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. 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.
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. 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.