JWH-018indole) 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
THC, a cannabinoid naturally present in cannabis, leading to its use in
synthetic cannabis products such as "legal cannabis herbal incense blends"
which in some countries are sold legally as "incense", labeled "not for human
consumption". History
John W. Huffman, an organic chemist at Clemson University, synthesized
analogues and metabolites of Δ9-tetrahydrocannabinol, the principal
active component of cannabis. JWH-018 is one of these analogues, with studies
showing an affinity for the cannabinoid 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.
On December 15, 2008, it was reported by the German pharmaceutical company THC
Pharm that JWH-018 was found as one of the active components in at least three
versions of the herbal blend 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 compound had been replaced with JWH-073.
Pharmacology 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. = Pharmacokinetics =
JWH-018 administered to rats resulted in the excretion of an indole-N-desalkyl
metabolite as well as several hydroxylated metabolites in urine. The
highest signals were observed for the hydroxylated N-desalkyl metabolites.
Hydroxylation took place on the side chain and in both aromatic systems, the
naphthalene and the indole rings, as could be shown by mass shift of the
corresponding fragments and by MS3 experiments. 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. Usage
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 similar to
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 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, 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 not use these substances.
Detection in biological fluids JWH-018 usage is readily detected in
urine using "spice" screening immunoassays from several manufacturers
focused on both the parent drug and its omega-hydroxy and carboxyl metabolites.
JWH-018 will not be detected by older methods employed for detecting THC and
other cannabis terpenoids. Determination of the parent drug in serum or its
metabolites in urine has been accomplished by GC-MS or LC-MS. Serum
JWH-018 concentrations are generally in the 1–10 μg/L range during the first few
hours after recreational usage. The major urinary metabolite is a compound
that is monohydroxylated on the omega minus one carbon atom of the alkyl side
chain. A lesser metabolite monohydroxylated on the omega position
was present in the urine of 6 users of the drug at concentrations of 6–50 μg/L,
primarily as a glucuronide conjugate. Legal status
Synthesis See also
References External links
JWH-018 Report Psychonaut Web Mapping Research Project
User of legal high