Synthetic cannabinoids
Synthetic cannabinoids
are a class of chemicals that bind to cannabinoid receptors in the body, but that are different from the natural cannabinoids in cannabis plants. They are often marketed as designer drugs or sold in products with claims that they give the effects of cannabis. When these chemicals are sprayed or otherwise soaked into a plant or other base material the blend is sometimes misleadingly referred to as synthetic marijuana.[1] These "synthetic marijuana" products are sold for recreational drug use.[1] There are several psychoactive artificial cannabinoid families (e.g. AM-xxx, HU-xxx, JWH-xxx, CP xx) that are sprayed onto plant matter that is then sold under brand names like K2[2] and Spice,[3] both of which are now often used as generic terms for any synthetic cannabinoid product. When synthetic cannabinoid blends first went on sale in the early 2000s, it was thought that they achieved an effect through a mixture of natural herbs. Laboratory analysis in 2008 showed that this was not the case, and that many in fact contain synthetic cannabinoids that act on the body in a similar way to cannabinoids naturally found in cannabis, such as THC
or CBD. A large and complex variety of synthetic cannabinoids, most often cannabicyclohexanol, JWH-018, JWH-073, or HU-210, are used in an attempt to avoid the laws that make cannabis illegal, making synthetic cannabinoid a designer drug. They have been sold under various brand names, online, in head shops, and other stores. These blends are often marketed as herbal incense or "herbal smoking blends", and the products are usually consumed through smoking. Although synthetic cannabinoids may not produce positive results in drug tests for cannabis, it is possible to detect their metabolites in human urine. The synthetic cannabinoids contained in these products have been made illegal in many countries. A study has associated synthetic cannabinoid use with psychotic episodes and death.[4]


1 Uses 2 Adverse effects

2.1 Detection in body fluids

3 Pharmacology

3.1 Relationship to cannabis 3.2 List of synthetic cannabinoids 3.3 CBD analogs 3.4 Ingredients 3.5 Legal herbs 3.6 Pharmacodynamics

4 History 5 Society and culture

5.1 Other names 5.2 Legal issues and regional availability

5.2.1 Europe 5.2.2 South America 5.2.3 Asia 5.2.4 Australasia 5.2.5 North America

6 See also 7 References 8 External links

Uses[edit] Synthetic cannabinoids
Synthetic cannabinoids
are used for recreational drug use;[1] however many were designed for research purposes, in part due to legal restrictions on natural cannabinoids preventing research. Studies are ongoing to examine their therapeutic potential.[5][6][7] One study found that while mice developed withdrawal symptoms from THC, that was not the case with the synthetic cannabinoid AM-1710, which was able to relieve neuropathic pain, but without inducing either tolerance or withdrawal, suggesting that CB2 receptors could be a viable target for development of pain-management drugs that avoid adverse outcomes of cannabis use.[8] The drug is used in an attempt to get the effects of cannabis or similar effects.[9] Part of the appeal of the drug is that it is marketed as being like natural cannabis.[9] In comparison with cannabis, it is inexpensive and can be easy to obtain as a commercial product through convenience stores, tobacco shops, or head shops.[9] A standard drug test will not identify a user of synthetic cannabinoids whereas natural cannabis would be traced.[9] Synthetic cannabinoids have been legal in the past, or at least, not illegal to sell or possess.[9] There are many different chemicals which are called "synthetic cannabinoids" and many of them are regulated by different laws or not mentioned in laws,[9] Adverse effects[edit] Synthetic cannabinoids
Synthetic cannabinoids
frequently produce adverse effects which lead to hospitalization or referrals to poison control centers.[9][10] Synthetic cannabinoids
Synthetic cannabinoids
can be any of a number of different drugs, each with different effects.[9] There is no way to describe general effects among all the different chemicals because they all have different effects.[9] Also, each chemical will have different effects at different dosages, but because the drugs are crudely manufactured, it is not possible to know what chemicals the drugs contain or how much of any chemical a user is taking.[9][11] Synthetic cannabinoids
Synthetic cannabinoids
are potent drugs capable of causing clinical intoxication and death[11] (probably due to CNS depression and hypothermia) when used. Many compounds have been banned in the U.S. and numerous other countries, although loopholes remain and new examples continue to be encountered on a regular basis with changed chemical make-ups designed to get around bans.[12][13] No official studies have been conducted on the effects of synthetic cannabinoids on humans (as is often the case with illegal and potentially toxic compounds).[14] However, reports describing effects seen in patients seeking medical care after taking synthetic cannabinoids have been published. Compared to cannabis and its active cannabinoid THC, the adverse effects are often much more severe and can include hypertension, tachycardia, myocardial infarction,[15] agitation, vomiting, hallucinations, psychoses, seizures, convulsions[16] and panic attacks.[17][18][19][20][21] Among individuals who need emergency treatment after using synthetic cannabis, the most common symptoms are accelerated heartbeat, high blood pressure, nausea, blurred vision, hallucination and agitation.[22] Other symptoms included epileptic seizures, and acute psychosis.[22] At least one death has been linked to overdose of synthetic cannabinoids[23] and in Colorado three deaths in September 2013 have been investigated for being linked to synthetic cannabinoids.[24] These more severe adverse effects in contrast to use of marijuana are thought to stem from the fact that many of the synthetic cannabinoids are full agonists to the cannabinoid receptors, CB1R and CB2R, compared to THC
which is only a partial agonist and thus not able to saturate and activate all of the receptor population regardless of dose and resulting concentration.[25] It has also been seen that phase 1 metabolism of JWH-018
results in at least nine monohydroxylated metabolites and with at least three of the metabolites shown to have full agonistic effect on CB1R, which, compared to metabolism of THC, only results in one psychoactive monohydroxylated metabolite. This may further explain the increased toxicity of synthetic cannabinoids compared to THC.[23] Professor John W. Huffman, who first synthesised many of the cannabinoids used in synthetic cannabis mimics, is quoted as saying, "People who use it are idiots.[14] You don't know what it's going to do to you."[26] A user who consumed 3 g of Spice Gold every day for several months showed withdrawal symptoms, similar to those associated with withdrawing from the use of narcotics. Doctors treating the user also noted that his use of the product showed signs associated with addiction.[27] One case has been reported wherein a user, who had previously suffered from cannabis-induced recurrent psychotic episodes, suffered reactivation of his symptoms after using Spice. Psychiatrists treating him have suggested that the lack of an antipsychotic chemical, similar to cannabidiol found in natural cannabis, may make synthetic cannabinoid products more likely to induce psychosis than natural cannabis.[28] Studies are currently available which suggest an association between synthetic cannabinoids and psychosis.[29] The use of synthetic cannabinoids can be associated with psychosis and physicians are beginning to investigate possible use of synthetic cannabinoids in patients with inexplicable psychotic symptoms. In contrast to most other recreational drugs, the dramatic psychotic state induced by use of synthetic cannabinoids has been reported, in multiple cases, to persist for several weeks, and in one case for seven months, after complete cessation of drug use.[30] Individuals with risk factors for psychotic disorders are often counseled against using synthetic cannabinoids.[31] Detection in body fluids[edit] Synthetic cannabinoid consumption does not cause a positive urine drug test for THC, its metabolites, or other cannabinoids present in marijuana using standard immunological screening procedures, GC-MS-screening, or multi-target screening by LC-MS/MS.[27][32] Serum concentrations of synthetic cannabinoids are generally in the 1–10 μg/L range during the first few hours after recreational usage. The major urinary metabolites, in most cases formed by oxidation of the alkyl side-chain to an alcohol and carboxylic acid followed by glucuronide conjugation, but also by N-dealkylation and aromatic hydroxylation, are usually present in urine at similar concentrations. The presence of synthetic cannabinoids or their metabolites in biofluids may be determined using specifically-targeted commercially available immunoassay screening methods, while liquid chromatography-mass spectrometry is most often used for confirmation and quantitation.[33][34][35][36][37] Pharmacology[edit] Relationship to cannabis[edit] Main article: Cannabis
(drug) Use of the term "synthetic marijuana" to describe products containing synthetic cannabinoids is controversial and, according to Dr. Lewis Nelson, a medical toxicologist at the NYU School of Medicine, a misnomer. Nelson claims that relative to marijuana such products containing synthetic cannabinoids "are really quite different, and the effects are much more unpredictable. It's dangerous."[38] Since the term synthetic does not apply to the plant but rather to the chemical that the plant contains (tetrahydrocannabinol), the term synthetic cannabinoid itself is more appropriate.[39] Research on the safety of synthetic cannabinoids is now being conducted and its findings published. Initial studies have been largely concerned with the role of synthetic cannabinoids in psychosis. Synthetic cannabinoids
Synthetic cannabinoids
may precipitate psychosis and in some cases it may be protracted. Some studies suggest that synthetic cannabinoid intoxication is associated with acute psychosis, worsening of previously stable psychotic disorders, and may trigger a chronic (long-term) psychotic disorder among vulnerable individuals such as those with a family history of mental illness.[40][41] Synthetic cannabinoids
Synthetic cannabinoids
are stated to be toxic and addictive to the brain but include a broad class of compounds in which neurotoxicity may vary substantially.[42] List of synthetic cannabinoids[edit]

(= JWH-018), AM-679, AM-694, AM-1220, AM-1221, AM-1235, AM-1241, AM-1248, AM-2201, AM-2232, AM-2233, AM-2389 AMB-CHMINACA, AMB-FUBINACA APICA, APINACA APP-FUBINACA BAY 38-7271, BAY 59-3074 BB-22 BIM-018 BML-190 BRL-4664 Cannabicyclohexanol CB-13 CP-47497, CP-55940, CP-55244 CT-3 CUMYL-PICA, CUMYL-PINACA, CUMYL-THPINACA DMA (5'-dimethylammonium delta-8-tetrahydrocannabinol), TMA (5'-trimethylammonium delta-8-tetrahydrocannabinol) (water-soluble) DMHP EAM-2201 FAB-144 FDU-NNE1, FDU-PB-22 FUB-144, FUB-APINACA, FUB-JWH-018, FUB-PB-22, FUBIMINA GW-405,833 HHC HU-210, HU-211, HU-239, HU-243, HU-308 JWH-007, JWH-015, JWH-018, JWH-019, JWH-073, JWH-081, JWH-098, JWH-116, JWH-122, JWH-133, JWH-149, JWH-167, JWH-182, JWH-193, JWH-198, JWH-200, JWH-203, JWH-210, JWH-249, JWH-250, JWH-251, JWH-302, JWH-398, JWH-424 JTE-907, JTE 7-31 L-759,633, L-759,656 LY-2183240, LY-320135 MAM-2201 MDA-19 MDMB-CHMICA, MDMB-CHMINACA, MDMB-FUBICA, MDMB-FUBINACA MEPIRAPIM MN-18, MN-25 Nantradol Nabilone Nabitan NESS-0327, NESS-040C5 NM-2201 NNE1 O-774, O-1057, O-1812, O-2050, O-2694, O-6629 Org 28611 PB-22 PF-03550096 PTI-1, PTI-2 PX-1, PX-2, PX-3 RCS-4, RCS-8 SDB-005, SDB-006 SP-111 SR-141716A, SR-144528 STS-135 Synhexyl THJ-018, THJ-2201 UR-144 WIN-48098, WIN-54461, WIN-55212-2, WIN-55225, WIN-56098 XLR-11

CBD analogs[edit]

abn-CBD O-2654

Ingredients[edit] Synthetic cannabis
Synthetic cannabis
mimics are sometimes claimed by the manufacturers to contain a mixture of traditionally used medicinal herbs, each of which producing mild effects, with the overall blend resulting in the cannabis-like intoxication produced by the product. Herbs listed on the packaging of Spice include Canavalia maritima (coastal jack-bean), Nymphaea caerulea
Nymphaea caerulea
(blue Egyptian water lily), Scutellaria nana
Scutellaria nana
(dwarf skullcap), Pedicularis densiflora
Pedicularis densiflora
(Indian warrior), Leonotis leonurus (lion's tail), Zornia latifolia
Zornia latifolia
(maconha brava), Nelumbo nucifera (lotus), and Leonurus sibiricus
Leonurus sibiricus
(honeyweed). However, when the product was analyzed by laboratories in Germany and elsewhere, it was found that many of the characteristic "fingerprint" molecules expected to be present from the claimed plant ingredients were not present. There were also large amounts of synthetic tocopherol present. This suggested that the actual ingredients might not have been the same as those listed on the packet, and a German government risk assessment of the product conducted in November 2008 concluded that it was unclear as to what the actual plant ingredients were, where the synthetic tocopherol had come from, and whether the subjective cannabis-like effects were actually produced by any of the claimed plant ingredients or instead caused by a synthetic cannabinoid drug. Legal herbs[edit] Unlike herbal smoking blends, synthetic cannabis mimics may use chemicals on their herbs, but both can use legal psychotropic herbs.[43] Some herbs used may be salvia divinorum[citation needed], Turnera diffusa
Turnera diffusa
(damiana), Nymphaea caerulea
Nymphaea caerulea
(blue lotus), passion flower, or other mildly psychoactive herbs that can be sold legally. In many cases the herbs have no effect on humans or are overpowered by the chemicals on them. Pharmacodynamics[edit]

Binding affinity
Binding affinity
of some cannabinoids identified in synthetic cannabis mimics compared to THC

Name Structure Binding affinity
Binding affinity
for the CB1 receptor Binding affinity
Binding affinity
for the CB2 receptor


Ki = 40.7±1.7 nM[44] Ki = 36.4±10 nM[44]


Ki = 234 pM (100–800 times more potent than THC)[45]


Ki = unknown. Reported to be five times more potent than THC, based on physiological responses in rats.[46]


Ki = 8.90±1.80 nM[44] Ki = 38.0±24.0 nM[44]


Ki = 9.00±5.00 nM[44] Ki = 2.94±2.65 nM[44]


Ki = 1.0 nM[47] Ki = 2.6 nM[47]

History[edit] The first synthetic cannabinoids were synthesized by Roger Adams in the early 1940s. Early cannabinoid research concentrated on tetrahydrocannabinol or "THC" as the main psychoactive and analgesic compound found in the cannabis plant. Other natural cannabinoids such as cannabidiol or "CBD" are less well studied, and not illegal in most jurisdictions. Most synthetic cannabinoids are analogs of THC. The first generation of THC
analogs (synhexyl, nabilone, nabitan, nantradol) featured slight variations of the THC
molecule, such as esterifying the phenolic hydroxy group, extending and branching of the pentyl side chain, or substituting nitrogen for oxygen in the benzopyran ring.[48] These analogs can be grouped into classical (HU-210), bicyclic (CP-55,940), and tricyclic (CP-55,244). Tritium-labelled cannabinoids such as [³H] CP-55,940
were instrumental in discovering the cannabinoid receptors in the early 1990s.[49] Nabilone
entered the clinic in 1981 as an antiemetic. Synthetic THC (marinol, dronabinol) entered the clinic in 1985 as an antiemetic and again in 1991 as an appetite stimulant.[50] The second generation of THC
analogs features compounds derived from anandamide (metanandamide), aminoalkylindole (WIN 55,212-2), pyrrole, pyrazole (SR-141716A), and indene (BAY 38-7271).

Selective cannabinoid receptor ligands

  CB₁ CB₂

Agonist Noladin ether HU-308, JWH-133

Antagonist SR-141716A, LY-320135, AM-251 SR-144528, AM-630

is apparently the most active cannabinoid used at present. It is up to 800 times more active than THC
in mice. AM-404
(a paracetamol metabolite) is an inhibitor of endocannabinoid cellular uptake, prolonging their effects.[51] Nabitan, O-1057
and TMA are water-soluble. In January 2009, researchers at the University of Freiburg
University of Freiburg
in Germany announced that an active substance in Spice was an undisclosed analogue of the synthetic cannabinoid CP 47,497.[52] Later that month, CP 47,497
CP 47,497
along with its dimethylhexyl, dimethyloctyl and dimethylnonyl homologues, were added to the German controlled drug schedules.[53][54] In May, the analogue of CP 47,497
CP 47,497
was named "cannabicyclohexanol".[55] In July 2010, it was announced that JWH-018
is one of the active components in at least three versions of Spice, which had been sold in a number of countries around the world since 2002, often marketed as incense.[56][57][58][59] Another potent synthetic cannabinoid, HU-210, has been reported to have been found in Spice seized by U.S. Customs and Border Protection.[60] 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.[61] Different ratios of JWH-018
and CP 47,497
CP 47,497
and their analogues have been found in different brands of synthetic cannabis mimic products[32] and manufacturers constantly change the composition of their products.[62] The amount of JWH-018
in Spice has been found to vary from 0.2% to 3%.[63] Other non-cannabinoid ingredients have also been found in synthetic cannabis mimics around the world, but they do not produce classical cannabis intoxication effects. This includes substituted cathinone derived stimulant drugs such as 4-methylbuphedrone and 4-methyl-alpha-PPP, and psychedelic tryptamine derivatives such as 4-HO-DET.[64][65] In 2013, a designer opioid drug, AH-7921, was detected in smoking blends in Japan, along with several novel cannabinoids and a cathinone analogue.[66] According to the Psychonaut Web Mapping Research Project, synthetic cannabinoids, sold under the brand name Spice, first appeared in Europe in 2004.[67] The brand "Spice" was released in 2004 by the now-dormant company The Psyche Deli in London, UK. In 2006 the brand gained popularity. According to the Financial Times, the assets of The Psyche Deli rose from £65,000 in 2006 to £899,000 in 2007.[68] The EMCDDA[clarification needed] reported in 2009 that Spice products were identified in 21 of the 30 participating countries. Because Spice was the dominant brand until 2009, the competing brands that started to appear from 2008 on were also dubbed Spice. Spice can, therefore, refer to both the brand Spice, as to all herbal blends with synthetic cannabinoids added. In 2009 a survey of readers of a popular English magazine Mixmag
found that 12.5% had used synthetic cannabis mimics, compared to 85% who had used cannabis.[69] Society and culture[edit] Other names[edit] According to a 2012 US Federal Bureau of Investigation
Federal Bureau of Investigation
memo which mentions a group of five synthetic chemicals made temporarily illegal by the US Drug Enforcement Administration
Drug Enforcement Administration
the year before, the term for naming this compound is either herbal incense or synthetic marijuana. The memo suggests that Dr. John W. Huffman, an organic chemist at Clemson University, was responsible for the development of the first synthetic marijuana (JWH-018) created as a part of his groundbreaking research on cannabinoid receptors in the human brain. The FBI concludes that as a result of the publication of his research people searching for a "marijuana-like-high" would follow Dr Huffman's recipes and methods.[70] In addition to synthetic marijuana, K2 and Spice, other brand names include Black Mamba, Bombay Blue, Genie, and Zohai.[71] According to Partnership at, other names also include Bliss.[72] The drug is also known as "synthetic cannabinoid receptor agonists". Legal issues and regional availability[edit] Europe[edit]

Austria the Austrian Ministry of Health announced on December 18, 2008 that Spice would be controlled under Paragraph 78 of their drug law on the grounds that it contains an active substance that affects the functions of the body, and the legality of JWH-018
is under review.[73][74][75] Germany JWH-018, CP 47,497
CP 47,497
and the C6, C8 and C9 homologues of CP 47,497
CP 47,497
have been illegal in Germany since January 22, 2009.[54][76] Since November 26, 2016 all substances belonging to the group of synthetic cannabinoids are illegal in Germany.[77] Finland Spice blends are classified as a medicine in Finland, and, therefore, it is illegal to order them without a prescription. In practice, it is not possible to get a prescription.[citation needed] France JWH-018, CP 47,497
CP 47,497
(and its homologues) and HU-210
were all made illegal in France on February 24, 2009.[78] Ireland from June 2010, JWH-018, along with a variety of other designer drugs, has been illegal.[79] Latvia JWH-018, JWH-073, CP 47,497
CP 47,497
(and its homologues) and HU-210
as well as leonotis leonurus have been all banned in Latvia since 2005.[80] After the first confirmed lethal case from the use of legal drugs in late 2013, parliament significantly increased the number of temporarily banned substances used in Spice and similar preparations. On April 3, 2014, parliament made selling of the temporarily banned substances a criminal offence.[81] Poland JWH-018
and many of the herbs mentioned on the ingredient lists of Spice and similar preparations were made illegal in May 2009. The bill was passed by Polish Sejm,[82][83] Polish Senat[84] and was signed by the President.[85] Romania Spice was made illegal in Romania on February 15, 2010.[86] Russia on April 9, 2009, the Chief Medical Officer of the Russian Federation issued a resolution on reinforcing control over the sales of smoking blends. These blends, marketed under the trade names AM-HI-CO, Dream, Spice (Gold, Diamond), Zoom, Ex-ses, Yucatán Fire and others, have been declared to contain Salvia divinorum, Hawaiian wood rose, and blue lotus, and are prohibited to be sold. These substances have been found to have "psychotropic, narcotic effects, contain poisonous components and represent potential threat for humans". The resolution does not mention JWH-018
or other synthetic cannabinoids.[87] On January 14, 2010, the Russian government issued a statement including 23 synthetic cannabinoids found in smoking blends Hawaiian Rose and Blue Lotus on the list of prohibited narcotic and psychotropic substances.[88] About 780 new psychoactive substances were added to the list from 2011 to 2014. The drugmakers avoided all the bans by making slight changes to the drugs. In the autumn of 2014, more than two-thousand Spice consumers in Russia sought medical attention, one-thousand were admitted to hospitals, and 40 people died[89] On October 30, 2014, President Vladimir Putin
Vladimir Putin
brought in a bill that would ban the turnover of any type of smoking blends and introduce administrative sanctions and criminal responsibility for it.[90] Slovakia Spice is legal in Slovakia. The National Anti-Drug Unit is considering adding it to the list of controlled substances.[91] The latest anti-drug law version (468/2009) valid since January 2010 does not mention active compounds of Spice.[92] Spain Spice is unregulated in Spain. For this reason, Spice is available in grow shop stores or cannabis related stores, and it can be bought and shipped online without any legal impediment from those kind of stores.[93] However, as Spanish law permits growing up to two cannabis plants per household, and the possession and consumption of cannabis on private property is also legal, cannabis alternatives like Spice are largely redundant and thus remain relatively unknown in Spain.[94] Sweden CP 47,497-C6, CP 47,497-C7, CP 47,497-C8, CP 47,497-C9, JWH-018, JWH-073
and HU-210
were all made illegal in Sweden on September 15, 2009. The bill was accepted on July 30, 2009 and was put in effect on September 15, 2009.[95] Switzerland Spice has been banned in Switzerland.[96] Turkey Spice, which is colloquially called bonzai in Turkey, was added to the list of drugs and psychotropic substances in 07.01.2011 by the law which numbered as 2011/1310 B.K.K. (February 13, 2011 and the Official Gazette No. 27845)[97] United Kingdom Many cannabinoids were legal in the United Kingdom until December 2009, when they were classified as a Class B drugs.[98] The UK continued to ban new synthetic cannabinoids as they came to market but they were typically replaced instantly by novel alternatives. In May 2016 the Psychoactive
Substances Act[99] came into force, which intends to restrict the production, sale and supply of new psychoactive substances.

South America[edit]

Chile the Chilean Ministry of Health on April 24, 2009, declared the sale of synthetic cannabis mimics to be illegal.[100]


South Korea South Korea officially added JWH-018, CP 47,497
CP 47,497
and HU-210
to the controlled substance list on July 1, 2009, effectively making these chemicals illegal.[101] Japan Japan has banned JWH-018, CP 47, 497, and homologues, and HU-210
since October 2009.[citation needed] United Arab Emirates The United Arab Emirates had stated that Spice is an illegal substance and possession or intent to sell is a jailable offense.[102]


Australia on June 17, 2011, the Western Australian government banned all of the synthetic cannabinoids found in already existing products, including brands such as Kronic, Kalma, Voodoo, Kaos, and Mango Kush. Western Australia was the first state in Australia to prohibit the sale of certain synthetic cannabinoids.[103][104] On June 18, 2013, an interim ban made a large list of product brands and synthetic substances illegal to sell anywhere in Australia.[105] This ban lapsed on October 13, 2013, and a permanent ban has not been imposed.[106] Synthetic cannabinoids and related products remain illegal in NSW, where a bill was passed on September 18, 2013, that bans entire families of synthetic drugs instead of only banning existing compounds that have been identified.[107][108] The introduction of this law makes NSW the first state in Australia to completely ban substances with psychoactive properties.[108]

New Zealand Spice is illegal in New Zealand, it is classified as a Class C controlled drug.[109] The New Zealand
New Zealand
Parliament passed a law in July 2013 banning the sale of legal highs in dairies and supermarkets, but allowing some "low risk" drugs to continue to be sold through speciality licensed shops.[110] Synthetic cannabinoids, as well as all other legal highs were outlawed at midnight on 7 May 2014, after a law was passed a week prior by the New Zealand
New Zealand

An analysis of 41 different synthetic cannabis mimic blends sold commercially in New Zealand, conducted by the Institute of Environmental Science and Research and released in July 2011, found 11 different synthetic cannabinoid ingredients used, including JWH-018, JWH-073, AM-694, AM-2201, RCS-4, RCS-4
butyl homologue, JWH-210, JWH-081, JWH-250
(or possibly JWH-302, isomer not determined), JWH-203, and JWH-122—with between one and five different active ingredients, though JWH-018
was present in 37 of the 41 blends tested. In two brands, the benzodiazepine anxiolytic drug phenazepam was also found, which is classified as a prescription medicine in New Zealand, and these brands were ordered to be removed from the market by emergency recall.[112][113] Since this time, a further 15 cannabinoid compounds have been detected as ingredients of synthetic cannabis mimicking blends in New Zealand
New Zealand
and banned as temporary class drugs.[114] In 2013 another hypnotic medication, zaleplon, was found to have been used as an active ingredient in a blend that had been sold in New Zealand
New Zealand
during 2011 and 2012.[115] North America[edit]


Spice is not specifically prohibited in Canada, but synthetic cannabis mimics are listed as a schedule II drug. Schedule II to the Controlled Drugs and Substances Act makes reference to specific synthetic compounds JWH-XXX and AM-XXXX, although is not limiting to those identified.[116][117] Health Canada
Health Canada
is debating the subject.[118][119]

United States

See also: JWH-018
§ United States The case of David Mitchell Rozga, an American teenager from Indianola, Iowa, brought international attention to K2. Rozga shot himself in the head with a family owned hunting rifle in an apparent suicide in June 6, 2010. After news of Rozga's death, it was reported by friends that they had smoked K2 with Rozga approximately one hour before his death. The nature of his death and reports from numerous family members, had led investigators to suspect that it was likely Rozga was under the influence of a mind-altering substance, at the time of his death. The death of Rozga has been used as a face of political lobbying against the continuation of K2, and other legal synthetic drugs, such as bath salts. Following the incident, an act to ban the use and distribution of the drug was proposed by US Senator Chuck Grassley
Chuck Grassley
of Iowa
as the "David Mitchell Rozga Act". It was approved into legislation by the United States Congress in June 2011.[120] On July 10, 2012, President Barack Obama signed the Synthetic Drug Abuse Prevention Act of 2012
Synthetic Drug Abuse Prevention Act of 2012
into law. It banned synthetic compounds commonly found in synthetic marijuana, placing them under Schedule I of the Controlled Substances Act.[71] Prior to that, some compounds within synthetic cannabis mimics (HU-210) were scheduled in the US under federal law, while others (JWH-073) have been temporarily scheduled until final determination of their status can be made.[121][122][123][124] The Drug Enforcement Administration (DEA) considers it to be a "drug of concern",[125] citing "...a surge in emergency-room visits and calls to poison-control centers. Adverse health effects associated with its use include seizures, hallucinations, paranoid behavior, agitation, anxiety, nausea, vomiting, racing heartbeat, and elevated blood pressure."[126][127] Several states independently passed acts making it illegal under state law, including Kansas
in March 2010,[128] Georgia and Alabama
in May 2010,[129][130] Tennessee
and Missouri
in July 2010,[131][132] Louisiana
in August 2010,[citation needed] Mississippi
in September 2010,[citation needed] and Iowa.[133] An emergency order was passed in Arkansas
in July 2010 banning the sale of synthetic cannabis mimics.[134] In October 2010, the Oregon Board of Pharmacy listed synthetic cannabinoid chemicals on its Schedule 1 of controlled substance, which means that the sale and possession of these substances is illegal under the Oregon Uniform Controlled Substances Act.[135] According to the National Conference of State Legislatures, several other states are also considering legislation, including New Jersey, New York, Florida, and Ohio.[132] Illinois passed a law on July 27, 2010 banning all synthetic cannabinoids that goes into effect January 1, 2011.[136] Michigan banned synthetic cannabinoids in October 2010,[137] and the South Dakota
South Dakota
Legislature passed a ban on these products which was signed into law by Gov. Dennis Daugaard
Dennis Daugaard
on February 23, 2012 (and which took immediate effect under an emergency clause of the state constitution).[138] Indiana
banned synthetic cannabinoids in a law which became effective in March 2012.[139] North Carolina banned synthetic cannabis mimics by a unanimous vote of the state senate, due to concerns that its contents and effects are reasonably similar to cannabis, and may cause equal effects in terms of psychological dependency.[140][141] Following cases in Japan involving the use of synthetic cannabinoids by navy, army and marine corps personnel resulted in the official banning of it,[142] a punitive general order issued on January 4, 2010 by the Commander Marine Corps Forces, Pacific prohibits the actual or attempted possession, use, sale, distribution and manufacture of synthetic cannabis mimics as well as any derivative, analogue or variant of it.[143] On June 8, 2010, the US Air Force issued a memorandum that banned the possession and use of Spice, or any other mood-altering substance except alcohol or tobacco, among its service members.[144] On November 24, 2010, the DEA announced that it would make JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol, which are often found in synthetic cannabis mimics, illegal using emergency powers.[145] They will be placed in Schedule I of the Controlled Substances Act, within a month of the announcement, and the ban will last for at least a year.[146][147] The temporary ban, for at least a year, came into effect on March 1, 2011.[148] On October 20, 2011, the Louisiana
State University football program announced that it had suspended three players, including star cornerback Tyrann Mathieu, who tested positive for synthetic cannabinoids.[149] In July 2016, over 33 people were suspected to have overdosed on K2 and were rushed to the hospital. Police raided 5 Brooklyn bodegas in search of the synthetic cannabinoid.[150] See also[edit]

List of designer drugs § Synthetic cannabinoid Endocannabinoid enhancer Endocannabinoid system – cannabinoid receptors in the nervous system Phytocannabinoid Structural scheduling of synthetic cannabinoids


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External links[edit]

Erowid Synthetic cannabinoid profile European Monitoring Centre for Drugs and Drug Addiction

v t e



Alkylamides Caryophyllene CBC CBCV CBD CBDV CBG CBGM CBGV CBL CBDL CBN CBV Epigallocatechin gallate Gallocatechol Perrottetinene Serinolamide A THC THC-C4 THCA THCV Yangonin

Active metabolites: 8,11-DiOH-THC 11-COOH-THC 11-OH-THC


Arachidonoyl ethanolamide (AEA; anandamide) 2-Arachidonoylglycerol
(2-AG) 2-Arachidonyl glyceryl ether
2-Arachidonyl glyceryl ether
(2-AGE; noladin ether) 2-Oleoylglycerol
(2-OG) N-Arachidonoyl dopamine
N-Arachidonoyl dopamine
(NADA) N-Arachidonylglycine
(NAGly) 2-Arachidonoyl lysophosphatidylinositol (2-ALPI) N- Arachidonoyl serotonin
Arachidonoyl serotonin
(AA-5-HT) Docosatetraenoylethanolamide
(DEA) Lysophosphatidylinositol
(LPI) Oleamide Oleoylethanolamide
(OEA) Palmitoylethanolamide
(PEA) RVD-Hpα Stearoylethanolamide (SEA) O-Arachidonoyl ethanolamine (O-AEA; virodhamine)

Synthetic cannabinoids

Classical cannabinoids (dibenzopyrans)

A-40174 A-41988 A-42574 Ajulemic acid AM-087 AM-411 AM-855 AM-905 AM-906 AM-919 AM-926 AM-938 AM-2389 AM-4030 AMG-1 AMG-3 AMG-36 AMG-41 Dexanabinol
(HU-211) DMHP Dronabinol HHC HU-210 HU-243 JWH-051 JWH-133 JWH-139 JWH-161 JWH-229 JWH-359 KM-233 L-759,633 L-759,656 Levonantradol
(CP 50,5561) Menabitan Nabazenil Nabidrox (Canbisol) Nabilone Nabitan Naboctate O-224 O-581 O-774 O-806 O-823 O-1057 O-1125 O-1191 O-1238 O-2048 O-2113 O-2365 O-2372 O-2373 O-2383 O-2426 O-2484 O-2545 O-2694 O-2715 O-2716 O-3223 O-3226 Parahexyl Pirnabine THC-O-acetate THC-O-phosphate

Non-classical cannabinoids

Cannabicyclohexanol CBD-DMH CP 47,497 (C6)-CP 47,497 (C9)-CP 47,497 CP 55,244 CP 55,940 HU-308 HU-320 HU-331 HU-336 HU-345 HU-446 HU-465 HU-910 HUF-101 Nonabine O-1376 O-1422 O-1601 O-1656 O-1657 O-1660 O-1663 O-1871 SPA-229 Tinabinol


1-Butyl-3-(2-methoxybenzoyl)indole 1-Butyl-3-(4-methoxybenzoyl)indole 1-Pentyl-3-(2-methoxybenzoyl)indole AM-630 AM-679 AM-694 AM-1241 AM-2233 GW-405,833
(L-768,242) Pravadoline RCS-4 WIN 54,461


AM-1220 AM-1221 AM-1235 AM-2201 AM-2232 CHM-081 EAM-2201 FUB-JWH-018 JWH-007 JWH-015 JWH-018 JWH-019 JWH-073 JWH-081 JWH-098 JWH-116 JWH-122 JWH-149 JWH-164 JWH-182 JWH-193 JWH-198 JWH-200 JWH-210 JWH-398 JWH-424 MAM-1220 MAM-2201 NE-CHMIMO


THJ-018 THJ-2201


WIN 55,212-2


JWH-175 JWH-176 JWH-184 JWH-185 JWH-192 JWH-194 JWH-195 JWH-196 JWH-197 JWH-199


Cannabipiperidiethanone JWH-167 JWH-203 JWH-249 JWH-250 JWH-251 JWH-302 RCS-8


(UR-12) NNE1 PX-1 Org 28312 Org 28611 SDB-006 STS-135


(PB-22) NM-2201

Tetramethylcyclo- propanoylindoles

5Br-UR-144 5Cl-UR-144 A-796,260 A-834,735 FUB-144 UR-144 XLR-11 XLR-12

Indazole-3- carboxamides


Tetramethylcyclo- propanoylindazoles



JWH-030 JWH-147 JWH-307 JWH-369 JWH-370


AM-883 AM-1346 ACEA ACPA Methanandamide
(AM-356) O-585 O-689 O-1812 O-1860 O-1861




4-HTMPIPO 5F-PY-PICA 5F-PY-PINACA 5F-3-pyridinoylindole A-836,339 A-955,840 Abnormal cannabidiol AB-001 BzODZ-EPyr AM-1248 AM-1714 AZ-11713908 BAY 38-7271 BAY 59-3074 BIM-018 CB-13 CB-86 CBS-0550 CUMYL-4CN-B7AICA CUMYL-5F-P7AICA CUMYL-PEGACLONE FUBIMINA GSK-554,418A GW-842,166X JTE 7-31 LASSBio-881 LBP-1 Leelamine MDA-7 MDA-19 MEPIRAPIM NESS-040C5 NMP-7 O-889 O-1269 O-1270 O-1399 O-1602 O-2220 PF-03550096 PSB-SB-1202 PTI-1 PTI-2 QMPSB S-444,823 SER-601 Tedalinab URB-447 VSN-16 WIN 56,098

Allosteric CBR ligands

Org 27569 Org 27759 Org 29647 RTI-371 Pregnenolone

Endocannabinoid enhancers (inactivation inhibitors)

4-Nonylphenylboronic acid AM-404 Arachidonoyl serotonin Arvanil BIA 10-2474 Biochanin A CAY-10401 CAY-10429 Genistein Guineesine IDFP JNJ 1661010 JNJ-42165279 JZL184 JZL195 Kaempferol LY-2183240 MK-4409 O-1624 O-2093 Oleoylethanolamide
(OEA) Olvanil Palmitoylethanolamide
(PEA) PF-04457845 PF-622 PF-750 PF-3845 PHOP URB-447 URB-597 URB-602 URB-754 VDM-11

Anticannabinoids (antagonists/inverse agonists/antibodies)

AM-251 AM-281 AM-630 AM-1387 AM-4113 AM-6527 AM-6545 BML-190 Brizantin (Бризантин) CAY-10508 CB-25 CB-52 CB-86 Dietressa (Диетресса) Drinabant
(AVE1625) Hemopressin Ibipinabant
(SLV319) JTE-907 LH-21 LY-320,135 MDA-77 MJ-15 MK-9470 NESS-0327 NIDA-41020 O-606 O-1184 O-1248 O-1918 O-2050 O-2654 Otenabant
(CP-945,598) PF-514273 PipISB PSB-SB-487 Rimonabant
(SR141716) Rosonabant
(E-6776) SR-144,528 Surinabant
(SR147778) Taranabant
(MK-0364) TM-38837 VCHSR

See also: Cannabinoid receptor
Cannabinoid receptor
modulators (cannabinoids by pharmacology) List of: AM cannabinoids JWH cannabinoids Designer drugs § Synthetic cannabimimetics

v t e

Cannabinoid receptor
Cannabinoid receptor

Receptor (ligands)


Agonists (abridged; see here for more): 2-AG 2-AGE (noladin ether) 11-Hydroxy-THC α-Amyrin β-Amyrin AB-CHMINACA AM-1172 AM-1220 AM-1221 AM-1235 AM-2201 AM-2232 Anandamide Arvanil AZ-11713908 Cannabinol CB-13 CP 47,497 CP 55,940 Dimethylheptylpyran DEA ECG EGCG Epicatechin Gallocatechol
(gallocatechin) Honokiol HU-210 JWH-007 JWH-015 JWH-018 JWH-073 Kavain L-759,633 Levonantradol Menabitan Nabilone Nabitan NADA O-1812 Oleamide Pravadoline Serinolamide A THC
(dronabinol) UR-144 WIN 55,212-2 Yangonin

Antagonists: AM-251 AM-6545 Cannabidiol Cannabigerol Drinabant Falcarinol
(carotatoxin) Hemopressin Ibipinabant LY-320,135 MK-9470 NESS-0327 O-2050 Otenabant PF-514273 PipISB Rimonabant Rosonabant Surinabant Taranabant THCV TM-38837 VCHSR Virodhamine

Antibodies: Brizantin (Бризантин) Dietressa (Диетресса)

Unknown/unsorted: MAFP


Agonists: 2-AG 2-AGE (noladin ether) 3,3'-Diindolylmethane 4-O-Methylhonokiol α-Amyrin β-Amyrin A-796,260 A-834,735 A-836,339 AM-1172 AM-1221 AM-1235 AM-1241 AM-2232 Anandamide AZ-11713908 Cannabinol Caryophyllene CB-13 CBS-0550 CP-55,940 GW-405,833
(L-768,242) GW-842,166X HU-308 JTE 7-31 JWH-007 JWH-015 JWH-018 JWH-73 JWH-133 L-759,633 L-759,656 Magnolol MDA-19 Nabitan NADA PF-03550096 S-444,823 SER-601 Serinolamide A UR-144 Tedalinab THC
(dronabinol) THCV Tetrahydromagnolol Virodhamine

Antagonists: 4-O-Methylhonokiol AM-630 BML-190 Cannabidiol Honokiol JTE-907 SR-144,528 WIN 54,461 WIN 56,098

NAGly (GPR18)

Agonists: Abnormal cannabidiol ACPA AM251 Anandamide Cannabidiol NADGly THC
(dronabinol) O-1602

Antagonists: CID-85469571 O-1918


Agonists: 2-AGE (noladin ether) 2-ALPI Abnormal cannabidiol AM-251 CID1011163 CID1252842 CID1792579 CP 55,940 GSK-494581A Lysophosphatidylinositol ML-184 ML-185 ML-186 O-1602 Oleoylethanolamide Palmitoylethanolamide THC

Antagonists: Cannabidiol CID-16020046 ML-191 ML-192 ML-193 O-1918 PSB-SB-487 PSB-SB-1202 PSB-SB-1203 Tetrahydromagnolol


Agonists: 2-Oleoylglycerol Anandamide APD668 AR-231,453 AS-1269574 MBX-2982 N-Oleoyldopamine Oleoylethanolamide Olvanil PSN-375,963 PSN-632,408

Transporter (modulators)


Inhibitors: 5'-DMH-CBD AM-404 AM-1172 Arachidonoyl serotonin Arvanil Cannabidiol Guineensine LY-2183240 O-2093 OMDM-2 Paracetamol
(acetaminophen) SB-FI-26 UCM-707 URB-597 VDM-11 WOBE490 WOBE491 WOBE492

Enzyme (modulators)


Inhibitors: 4-Nonylphenylboronic acid AACOCF3 AM-404 Arachidonoyl serotonin BIA 10-2474 Biochanin A Genistein IDFP JNJ-1661010 JNJ-42165279 JZL-195 Kaempferol LY-2183240 MAFP Palmitoylisopropylamide Paracetamol
(acetaminophen) PF-3845 PF-04457845 PF-750 SA-47 SA-57 TAK 21d TC-F 2 UCM710 URB-597

Activators: PDP-EA


Inhibitors: ABX-1431 IDFP JJKK 048 JW 642 JZL-184 JZL-195 JZP-361 KML 29 MAFP MJN110 NAM Pristimerin URB-602


Inhibitors: JZP-169 JZP-430 KT182 KT185 KT195 KT203 LEI-106 ML294 ML295 ML296 UCM710 WWL-70


Inhibitors: Betulinic acid Maslinic acid MAFP Oleanolic acid Orlistat
(tetrahydrolipstatin) Ursolic acid


Precursors: Phosphatidylethanolamine NAPE Diacylglycerol

Others: 2-PG (directly potentiates activity of 2-AG at CB1 receptor) ARN-272 (FAAH-like anandamide transporter inhibitor)

See also Receptor/signaling modulators Cannabinoids (cannabinoids b