Synthetic cannabis

Synthetic cannabis is a psychoactive herbal and chemical product that, when consumed, mimics the effects of cannabis. It is best known by the brand names K2[1] and Spice,[2] both of which have largely become genericized trademarks used to refer to any synthetic cannabis product. (It is also for this reason that synthetic cannabis is often referred to as spice product, due to the latter.) A type of synthetic cannabis sold in Australasia is known as Kronic.

When synthetic cannabis blends first went on sale in the early 2000s, it was thought that they achieved an effect through a mixture of legal herbs. Laboratory analysis in 2008 showed that this is not the case, and that they in fact contain synthetic cannabinoids that act on the body in a similar way to cannabinoids naturally found in cannabis, such as THC. 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 cannabis a designer drug. It has been sold under various brand names, online, in head shops, and at some gas stations.

It is often marketed as "herbal incense"; however, some brands market their products as "herbal smoking blends". In either case, the products are usually smoked by users. Although synthetic cannabis does not produce positive results in drug tests for cannabis, it is possible to detect its metabolites in human urine. The synthetic cannabinoids contained in synthetic cannabis products have been made illegal in many European countries. On November 24, 2010, the U.S. Drug Enforcement Agency announced it would use emergency powers to ban many synthetic cannabinoids within a month.[3] Prior to the announcement, several US states had already made them illegal under state law. As of March 1, 2011, five cannabinoids, JWH-018, JWH-073, CP-47,497, JWH-200, and cannabicyclohexanol are now illegal in the US.[4]

Contents

History

According to the Psychonaut Web Mapping Research Project, synthetic cannabis products, sold under the brand name Spice, first appeared in Europe in 2004.[5] 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.[6] The EMCDDA 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, relate to both the brand 'Spice', as to all herbal blends with synthetic cannabinoids added.

A survey of readers of Mixmag in the UK in 2009 found that one in eight respondents had used synthetic cannabis, compared to 85% who had used cannabis.[7]

Ingredients

Synthetic cannabis is 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, Nymphaea caerulea, Scutellaria nana, Pedicularis densiflora, Leonotis leonurus, Zornia latifolia, Nelumbo nucifera, and Leonurus sibiricus. 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 be 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.

Synthetic cannabinoid ingredients

In January 2009, researchers at the University of Freiburg in Germany announced that an active substance in Spice was an undisclosed analogue of the synthetic cannabinoid CP 47,497.[8] Later that month, CP 47,497 along with its dimethylhexyl, dimethyloctyl and dimethylnonyl homologues, were added to the German controlled drug schedules.[9][10] In May the analogue of CP 47,497 was named cannabicyclohexanol.[11]

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.[12][13][14][15] Another potent synthetic cannabinoid, HU-210, has been reported to have been found in Spice seized by U.S. Customs and Border Protection.[16] 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.[17]

Different ratios of JWH-018 and CP 47,497 and their analogues have been found in different brands of synthetic cannabis[18] and manufacturers constantly change the composition of their products.[19] The amount of JWH-018 in Spice has been found to vary from 0.2% to 3%.[20]

An analysis of 41 different synthetic cannabis 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 so these brands were ordered to be removed from the market by emergency recall.[21][22]

Pharmacological properties of cannabinoids identified in synthetic cannabis, with THC for comparison
Name Structure Binding affinity for the CB1 receptor Binding affinity for the CB2 receptor
THC Ki = 40.7±1.7 nm[23] Ki = 36.4±10 nm[23]
Cannabicyclohexanol Ki = unknown. Reported to be 5 times more potent than THC, based on physiological responses in rats[24]
HU-210 Ki = 234 pM (100–800 times more potent)[25]
JWH-018 Ki = 9.00±5.00 nm[23] Ki = 2.94±2.65 nm[23]
JWH-073 Ki = 8.90±1.80 nm[23] Ki = 38.0±24.0 nm[23]
AM-2201 Ki = 1.0 nM[26] Ki = 2.6 nM[26]

Safety

No official studies have been conducted on its effects on humans.[27] Though its effects are not well-documented, extremely large doses may cause negative effects that are in general not noted in marijuana users, such as increased agitation and vomiting.[28] Professor John W. Huffman, who first synthesised many of the cannabinoids used in synthetic cannabis, is quoted as saying, "People who use it are idiots."[27] "You don't know what it's going to do to you."[29] 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.[30] 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 cannabis more likely to induce psychosis than natural cannabis.[31]

Drug testing

Spice does not cause a positive drug test for cannabis or other illegal drugs using GC-MS-screening with library search, multi-target screening by LC-MS/MS, or immunological screening procedures.[18][30] A study has been conducted into the detection of metabolites of JWH-018 in urine; the metabolites are mainly conjugates with glucuronic acid and can be reliably detected by GC–MS/MS and LC–MS/MS.[32]

Legal status

Europe

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.[33][34][35]
Germany
JWH-018, CP 47,497 and the C6, C8 and C9 homologues of CP 47,497 are illegal in Germany since January 22, 2009.[10][36]
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.
France
JWH-018, CP 47,497 (and its homologues) and HU-210 were all made illegal in France on February 24, 2009.[37]
Ireland
From June 2010, JWH-018, along with a variety of other designer drugs, is illegal.[38]
Latvia
JWH-018, JWH-073, CP 47,497 (and its homologues) and HU-210 are all banned in Latvia as well as leonotis leonurus.[39]
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,[40][41] Polish Senat[42] and was signed by the President.[43]
Romania
Spice was made illegal in Romania on February 15, 2010.[44]
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.[45] 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. Thus, all of these plants and compounds are now illegal in the Russian Federation.[46]
Slovakia
Spice is legal in Slovakia. The National Anti-Drug Unit is considering adding it to the list of controlled substances.[47] The latest anti-drug law version (468/2009) valid since January 2010 still does not mention active compounds of Spice.[48]
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.[49]
Switzerland
Spice has been banned in Switzerland.[50]
United Kingdom
Spice was legal in the United Kingdom until December 2009, when it was classified as a Class B drug.[51]

South America

Chile
The Chilean Ministry of Health on April 24, 2009 declared the sale of synthetic cannabis to be illegal.[52]

Asia

South Korea
South Korea officially added JWH-018, CP 47,497 and HU-210 to the controlled substance list on July 1, 2009, effectively making these chemicals illegal.[53]
Japan
Japan has banned JWH-018, CP 47, 497, and homologues, and HU-210 since Oct. 2009

Australasia

Australia
A variety of synthetic cannabis called Kronic[54] is available in Australia and, As of 15 June 2011 (2011 -06-15), is not illegal.[55] However, on June 13, 2011, the Western Australian state government made the decision to place a ban on any products containing synthetic cannabinoids, including brands such as Kronic, Kalma, Voodoo, Kaos, and Mango Kush, effective from Friday the June 17, 2011. This makes Western Australia the first state in Australia to make the synthetic cannabis-containing products illegal.[56] The sale of synthetic cannabis will be banned in the state of NSW from July 1, with retailers required to arrange for destruction of any unsold quantities after that date. A ban on the use of synthetic cannabis will come into effect on the July 8, 2011, under current legislation.[57]
New Zealand
Spice is illegal in New Zealand, it is classified as a Class C controlled drug.[58] Kronic is widely available in dairies and is not illegal.[59]

North America

Canada

Spice and specific forms of JWHxxx are not specifically prohibited in Canada, but synthetic cannabis is listed as a schedule II drug.[60][61] Health Canada is debating on the subject.[62][63]

United States

See also: JWH-018#United States

Some compounds within synthetic cannabis (HU-210) are currently scheduled in the USA under federal law, while others (JWH-073) have been temporarily scheduled until final determination of their status can be made.[64][65][66][67] The Drug Enforcement Administration (DEA) considers it to be a "drug of concern",[68] 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."[69] [70]

Several states independently passed acts making it illegal under state law, including Kansas in March 2010,[71] Georgia and Alabama in May 2010,[72][73] Tennessee and Missouri in July 2010,[74][75] Louisiana in August 2010, and Mississippi in September 2010. An emergency order was passed in Arkansas in July 2010 banning the sale of synthetic cannabis.[76] 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.[77] According to the National Conference of State Legislatures, several other states are also considering legislation, including Michigan, New Jersey, New York, Florida, Indiana, and Ohio.[75] Illinois passed a law on July 27, 2010 banning all synthetic cannabinoids that goes into effect January 1, 2011. Michigan banned synthetic cannabinoids in October 2010[78]

Following cases in Japan involving the use of synthetic cannabis by Navy, Army and Marine Corps personnel resulted in the official banning of it,[79] 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 or manufacture of synthetic cannabis as well as any derivative, analogue or variant of it.[80] On June 8, 2010, the U.S. 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.[81]

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, illegal using emergency powers.[82] 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.[83][84] The temporary ban, for at least a year, came in to effect on March 1, 2011.[85]

On October 20, 2011, the Louisiana State University football program announced that it had suspended three players who tested positive for synthetic cannabis.[86]

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