What is JWH 018 (1-pentyl-3-(1-naphthoyl)indole) ?
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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Fatalities associated with synthetic cannabinoids use
Fatalities associated with synthetic cannabinoid abuse have been reported. Shanks et al. reported three cases where fatalities were associated with synthetic cannabinoid use. In case one, a 57-year old man died due to the use of JWH-018. The cardiac blood showed 199 ng/mL of JWH-018 along with other prescription drugs. In the second case, a 52-year old year man died who showed 19.6 ng/mL of JWH-018 and 68.3 ng/mL of JWH-073 in cardiac blood. In the third case, a 29-year old man died who showed only the presence of JWH-018 (83.3 ng/mL) in the cardiac blood but no other drug. Labay et al. recently reviewed cases where death was related to the use of synthetic cannabinoids.
The authors identified six deaths related to abuse of JWH-018 (postmortem blood levels: 0.11–0.65 ng/mL), six deaths related to abuse of JWH-122, six deaths related to abuse of JWH-210, one each associated with abuse of JWH-175 and JWH-250, respectively. In addition, two fatalities associated with abuse of XLR-11 and nine fatalities associated with abuse of AM-2201 (postmortem blood levels: 0.13–17.0 ng/mL) were also reported. Patton et al. also reported the death of a 23-year old man due to AM-2201 overdose. The metabolite of AM-2201 was detected in the postmortem blood.
Death due to use of synthetic cannabinoids (S)-methyl-2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (5F-AMB), a new synthetic cannabinoid first reported in Japan in early 2014, has also been reported. The concentration of 5F-AMB was only 0.3 ng/mL. However, the authors concluded that the death was accidental. Shanks et al. described a death associated with use of a new synthetic cannabinoid ADB-4-fluorobenzyl-1H-indazole-3-carboxamide (FUBINACA). In this drug, 1-amino-3,3-dimethoxy-1-oxobutane-2yl (ABD) group is linked with the FUBINACA base at the amide group. The concentration of this relatively new synthetic cannabinoid in the postmortem blood was 7.3 ng/mL.
USES of JWH 018
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, and many synthetic cannabinoids, are full agonists. THC has been shown to inhibit GABA receptor neurotransmission in the brain via several pathways. It 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 the use. One study reported psychotic relapses and anxiety symptoms in well-treated patients with mental illness following this 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.
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