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. These "synthetic marijuana" products are sold for recreational drug use.
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 and Spice, both of which are now often used as generic terms used 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. Studies have associated synthetic cannabinoid use with psychotic episodes and death.
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.
Maps, Directions, and Place Reviews
Uses
Synthetic cannabinoids are used for recreational drug use; 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. 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.
The drug is used in an attempt to get the effects of cannabis or similar effects. Part of the appeal of the drug is that it is marketed as being like natural cannabis. 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. A standard drug test will not identify a user of synthetic cannabinoids whereas natural cannabis would be traced. Synthetic cannabinoids have been legal in the past, or at least, not illegal to sell or possess. There are many different chemicals which are called "synthetic cannabinoids" and many of them are regulated by different laws or not mentioned in laws,
Adverse effects
Synthetic cannabinoids frequently produce adverse effects which lead to hospitalization or referrals to poison control centers. Synthetic cannabinoids can be any of a number of different drugs, each with different effects. There is no way to describe general effects among all the different chemicals because they all have different effects. 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.
Synthetic cannabinoids are potent drugs capable of causing clinical intoxication and death (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.
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). 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, agitation, vomiting, hallucinations, psychoses, seizures, convulsions and panic attacks. 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. Other symptoms included epileptic seizures, and acute psychosis.
At least one death has been linked to overdose of synthetic cannabinoids and in Colorado three deaths in September 2013 have been investigated for being linked to synthetic cannabinoids.
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. 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.
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. You don't know what it's going to do to you." 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. 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.
Studies are currently available which suggest an association between synthetic cannabinoids and psychosis. 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. Individuals with risk factors for psychotic disorders are often counseled against using synthetic cannabinoids.
Detection in body fluids
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. Serum concentrations of synthetic cannabinoids are generally in the 1-10 ?g/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.
Pharmacology
Relationship to cannabis
There is controversy about calling this substance Spice or K2 or synthetic marijuana. "Synthetic marijuana" is a misnomer according to Dr. Lewis Nelson, a medical toxicologist at the NYU School of Medicine who states they are "really quite different, and the effects are much more unpredictable. It's dangerous". Since the term synthetic does not apply to the plant but rather to the chemical that the plant contains (tetrahydrocannabinol), the term synthetic cannabinoid is more appropriate. Research on the safety of synthetic cannabinoids is now being published. Initial studies have been largely concerned with the role of synthetic cannabinoids in psychosis. Synthetic cannabinoids may precipitate psychosis and in some cases it may be prolonged. 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. Synthetic cannabinoids are stated to be toxic and addictive to the brain but it is a wide class of compounds in which the toxicity varies wildly.
List of synthetic cannabinoids
- 4-HTMPIPO
- 5F-AB-FUPPYCA, 5F-AB-PINACA, 5F-ADB, 5F-ADBICA, 5F-ADB-PINACA, 5F-AMB, 5F-AMB-PICA, 5F-APINACA, 5F-CUMYL-PINACA, 5F-EMB-PINACA, 5F-NNE1, 5F-PB-22, 5F-PCN, 5F-SDB-006
- A-836339
- AB-001, AB-005, AB-CHFUPYCA, AB-CHMINACA, AB-FUBICA, AB-FUBINACA, AB-PICA, AB-PINACA
- ADB-CHMINACA, ADB-FUBICA, ADB-FUBINACA, ADB-PINACA, ADBICA
- ADAMANTYL-THPINACA
- ADBICA
- ADSB-FUB-187
- AM251, AM-404, AM-630, AM-678 (= 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
- abn-CBD
- O-2654
Ingredients
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 (blue Egyptian water lily), Scutellaria nana (dwarf skullcap), Pedicularis densiflora (Indian warrior), Leonotis leonurus (lion's tail), Zornia latifolia (maconha brava), Nelumbo nucifera (lotus), and 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
Unlike herbal smoking blends, synthetic cannabis mimics may use chemicals on their herbs, but both can use legal psychotropic herbs. Some herbs used may be salvia divinorum, Turnera diffusa (damiana), 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.
Pharmacokinetics
History
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. 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.
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.
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).
HU-210 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. Nabitan, O-1057 and TMA are water-soluble.
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. Later that month, CP 47,497 along with its dimethylhexyl, dimethyloctyl and dimethylnonyl homologues, were added to the German controlled drug schedules. In May, the analogue of CP 47,497 was named "cannabicyclohexanol".
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. Another potent synthetic cannabinoid, HU-210, has been reported to have been found in Spice seized by U.S. Customs and Border Protection. 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.
Different ratios of JWH-018 and CP 47,497 and their analogues have been found in different brands of synthetic cannabis mimic products and manufacturers constantly change the composition of their products. The amount of JWH-018 in Spice has been found to vary from 0.2% to 3%.
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. In 2013, a designer opioid drug, AH-7921, was detected in smoking blends in Japan, along with several novel cannabinoids and a cathinone analogue.
According to the Psychonaut Web Mapping Research Project, synthetic cannabinoids, sold under the brand name Spice, first appeared in Europe in 2004. 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. 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, 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.
Society and culture
Other names
According to a 2012 US Federal Bureau of Investigation memo which mentions a group of five synthetic chemicals made temporarily illegal by the US Drug enforcement Agency 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.
In addition to synthetic marijuana, K2 and Spice, other brand names include Black Mamba, Bombay Blue, Genie, and Zohai. According to Partnership at Drugfree.org, other names also include Bliss. The drug is also known as "synthetic cannabinoid receptor agonists".
Legal issues and regional availability
Europe
South America
Asia
Australasia
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. Since this time, a further 15 cannabinoid compounds have been detected as ingredients of synthetic cannabis mimicking blends in New Zealand and banned as temporary class drugs. 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 during 2011 and 2012.
North America
Spice and specific forms of JWHxxx are not specifically prohibited in Canada, but synthetic cannabis mimics are listed as a schedule II drug. Health Canada is debating the subject.
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 of Iowa as the "David Mitchell Rozga Act". It was approved into legislation by the United States Congress in June 2011. On July 10, 2012, President Barack Obama signed the 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.
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. The Drug Enforcement Administration (DEA) considers it to be a "drug of concern", 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."
Several states independently passed acts making it illegal under state law, including Kansas in March 2010, Georgia and Alabama in May 2010, Tennessee and Missouri in July 2010, Louisiana in August 2010, Mississippi in September 2010, and Iowa. An emergency order was passed in Arkansas in July 2010 banning the sale of synthetic cannabis mimics. 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. According to the National Conference of State Legislatures, several other states are also considering legislation, including New Jersey, New York, Florida, and Ohio. 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, and the South Dakota Legislature passed a ban on these products which was signed into law by Gov. Dennis Daugaard on February 23, 2012 (and which took immediate effect under an emergency clause of the state constitution). Indiana banned synthetic cannabinoids in a law which became effective in March 2012. 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.
Following cases in Japan involving the use of synthetic cannabinoids by navy, army and marine corps personnel resulted in the official banning of it, 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. 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.
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. 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. The temporary ban, for at least a year, came into effect on March 1, 2011.
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.
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.
Source of the article : Wikipedia
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