JWH-018
Encyclopedia
JWH-018 or AM-678 is an analgesic
chemical from the naphthoylindole family, which 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", including Spice, Relaxinol, and Mr. Nice Guy, which are 'legally' sold as "incense" and labeled as "not for human consumption." The effects of JWH-018 are also seen in other drugs, such as Dissociatives, Hallucinogens and Psychedelics.
, an organic chemist at Clemson University
, synthesized analogues and metabolites of Δ9-tetrahydrocannabinol (THC), the principal active component of cannabis. JWH-018 is one of these analogues, 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.
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
.
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
.
. 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 of its analogues) are full agonists. This means that users may experience far more intense effects compared to smoking cannabis. 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.. Additionally, as a Dissociative drug
and Psychoactive Substance, JWH-018 has the ability to cause Dissociation
and temporary Substance-induced psychosis
in otherwise healthy individuals.
According to the writer Kevin Keck
, who sampled various brands of herbal incense containing JWH-018 for research on the subject, "A small amount does produce visual distortions and a marijuana-like buzz. I can easily understand how individuals with little or no experience in navigating this psychic terrain could experience extreme panic attacks that prompt them to seek medical attention...It is not a problem that responsible people use [JWH-018], it is a serious problem that naïve and foolish people use [it]. It is the same problem that surrounds alcohol and any other number of legal prescription drugs."
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 (terminal) position was present in the urine of 6 users of the drug at concentrations of 6-50 μg/L, primarily as a glucuronide conjugate.
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
chemical from the naphthoylindole family, which 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
Tetrahydrocannabinol
Tetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ1-THC , or dronabinol, is the main chemical psychoactive substance found in the cannabis plant. It was first isolated in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed...
, a cannabinoid naturally present in cannabis, leading to its use in synthetic cannabis products such as "legal cannabis herbal incense blends", including Spice, Relaxinol, and Mr. Nice Guy, which are 'legally' sold as "incense" and labeled as "not for human consumption." The effects of JWH-018 are also seen in other drugs, such as Dissociatives, Hallucinogens and Psychedelics.
History
John W. HuffmanJohn W. Huffman
John William Huffman is a professor emeritus of organic chemistry at Clemson University who first synthesised many novel cannabinoids, including JWH-007, JWH-015, JWH-018, JWH-019, JWH-030, JWH-051, JWH-073, JWH-081, JWH-122, JWH-133, JWH-147, JWH-171, JWH-182, JWH-203, JWH-210, JWH-250, JWH-307,...
, an organic chemist at Clemson University
Clemson University
Clemson University is an American public, coeducational, land-grant, sea-grant, research university located in Clemson, South Carolina, United States....
, synthesized analogues and metabolites of Δ9-tetrahydrocannabinol (THC), the principal active component of cannabis. JWH-018 is one of these analogues, 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.
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
Spice (drug)
Synthetic cannabis is a psychoactive herbal and chemical product which, when consumed, mimics the effects of cannabis. It is best known by the brand names K2 and Spice, both of which have largely become genericized trademarks used to refer to any synthetic cannabis product...
, 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
JWH-073
JWH-073 is an analgesic chemical from the naphthoylindole family, which acts as a partial agonist at both the CB1 and CB2 cannabinoid receptors. It is somewhat selective for the CB1 subtype, with affinity at this subtype approximately 5x the affinity at CB2. The abbreviation JWH stands for John W...
.
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 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
Glucuronide
A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond...
.
Usage
At least one case of JWH-018 dependence has been reported. On October 15, 2011, coroner reports released to the media reveal that the death of a South Carolina college basketball player was attributed to "drug toxicity and organ failure" caused by JWH-018. The user consumed JWH-018 daily for eight months. Withdrawal symptoms were similar to those experienced as a result of cannabis dependenceCannabis dependence
Cannabis dependence is a condition defined in DSM-IV applying the general concept of substance dependence to cannabis.Despite cannabis being one of the most widely used illicit drugs in the world, controlled trials for cannabis use disorder have only been reported in literature in the last 15 years...
. 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
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
at CB1 receptors, JWH-018 (and many of its analogues) are full agonists. This means that users may experience far more intense effects compared to smoking cannabis. THC has been shown to inhibit GABA receptor
GABA receptor
The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
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.. Additionally, as a Dissociative drug
Dissociative drug
Dissociatives are a class of psychoactive drugs which are said to reduce or block signals to the conscious mind from other parts of the brain...
and Psychoactive Substance, JWH-018 has the ability to cause Dissociation
Dissociation
Dissociation is an altered state of consciousness characterized by partial or complete disruption of the normal integration of a person’s normal conscious or psychological functioning. Dissociation is most commonly experienced as a subjective perception of one's consciousness being detached from...
and temporary Substance-induced psychosis
Substance-induced psychosis
Substance-induced psychosis is a form of substance-related disorder where psychosis can be attributed to substance use.Various psychoactive substances have been implicated in causing, exacerbating, and/or precipitating psychotic states and/or disorders in users...
in otherwise healthy individuals.
According to the writer Kevin Keck
Kevin Keck
Kevin Keck is an American essayist and poet. His writing is largely autobiographical. He is best known for his collection of personal essays Oedipus Wrecked , which chronicles his sexual coming-of-age in a humorous style that is often compared to David Sedaris and Sarah Vowell...
, who sampled various brands of herbal incense containing JWH-018 for research on the subject, "A small amount does produce visual distortions and a marijuana-like buzz. I can easily understand how individuals with little or no experience in navigating this psychic terrain could experience extreme panic attacks that prompt them to seek medical attention...It is not a problem that responsible people use [JWH-018], it is a serious problem that naïve and foolish people use [it]. It is the same problem that surrounds alcohol and any other number of legal prescription drugs."
Detection in biological fluids
JWH-018 usage is not detectable with the usual immunoassay screening methods employed for detecting cannabis use from urine specimens. Determination of the parent drug in serum or its metabolitesDrug metabolism
Drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
in urine has been accomplished by GC-MS or LC-MS
Liquid chromatography-mass spectrometry
Liquid chromatography–mass spectrometry is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry. LC-MS is a powerful technique used for many applications which has very high...
. 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 (terminal) 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
| Country | Date of Ban | Notes | |
|---|---|---|---|
| Austria | The Austrian Ministry of Health announced on 18 December 2008 that Spice would be controlled under Paragraph 78 of their drug law on the grounds that it contains an active substance which affects the functions of the body, and the legality of JWH-018 is under review. | ||
| Belarus | 1 January 2010 | ||
| Canada | June 3, 2010 | JWH-018 is a controlled substance in Canada listed under schedule 2 synthetic cannabinoids. Note: the most current CDSA can be found here | |
| France | February 24, 2009 | ||
| Germany | 22 January 2009 | ||
| Ireland | 11 May 2010 | An immediate ban was announced on 11 May 2010 by Minister for Health Mary Harney. | |
| Italy | 2 July 2010 | ||
| Latvia | 28 November 2009 | ||
| Poland | |||
| South Korea | 1 July 2009 | ||
| Sweden | 30 July 2009 | A bill to ban JWH-018 was accepted on 30 July 2009 and was in effect on 15 September 2009. | |
| Estonia | 24 July 2009 | ||
| Romania | 15 February 2010 | ||
| Russia | 22 January 2010 | ||
| Ukraine | 31 May 2010 | ||
| United Kingdom | 23 December 2009 | ||
| United States | 1 March 2011 | JWH-018 and four similar cannabinoids were classified as Schedule I controlled substances by the Drug Enforcement Administration Drug Enforcement Administration The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States... on March 1, 2011, making their possession and use illegal in all 50 states. The law allows for a one-year DEA study of the effects of JWH-018 on the human body to determine and whether it should be permanently classified as Schedule I in the United States. |
External links
- JWH-018 Report Psychonaut Web Mapping Research Project