Synthetic weed

Synthetic cannabis
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Commercially known as Synthetic cannabis (synthetic marijuana), or technically cannabinoid research chemicals, is any designer drug that mimics the effects of cannabis.[1] There are several psychoactive artificial cannabinoid families (eg AM-xxx, HU-xxx, JWH-xxx, CP xx) that are used as designer drugs sprayed on herbs and sold as natural highs under brand names like K2[2] and Spice,[3] both of which are genericized trademarks used for any synthetic cannabis product. Synthetic cannabis is often termed spice product.

When synthetic cannabis 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 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 US Drug Enforcement Administration announced it would use emergency powers to ban many synthetic cannabinoids within a month.[4] Prior to the announcement, several US states had already made them illegal under state law. In the US, as of March 1, 2011, five cannabinoids, JWH-018, JWH-073, CP-47,497, JWH-200, and cannabicyclohexanol have been placed on Schedule I of the Controlled Substances Act (and are therefore illegal to possess or use in the US); the Drug Enforcement Administration claims that said action is "to avoid an imminent hazard to the public safety."[5][6] In July 2012, the Synthetic Drug Abuse Prevention Act of 2012 was signed into law. It banned synthetic compounds commonly found in synthetic cannabis, placing them under Schedule I of the Controlled Substances Act.[7]

Misnomer

There is controversy about calling Spice and K2 synthetic cannabis. Synthetic marijuana is a misnomer according to Lewis Nelson, MD, a medical toxicologist at the NYU School of Medicine. "It's really quite different, and the effects are much more unpredictable. It's dangerous, and there is no quality control in what you are getting."[8] 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.[9] Research on the safety of synthetic cannabinoids is now becoming available. Initial studies are focused on the role of synthetic cannabinoids in psychosis. Synthetic cannabis 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 it may trigger a chronic (long-term) psychotic disorder among vulnerable individuals such as those with a family history of mental illness.[10][11]
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 (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 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.
Artificial cannabinoids

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.[12] Later that month, CP 47,497 along with its dimethylhexyl, dimethyloctyl and dimethylnonyl homologues, were added to the German controlled drug schedules.[13][14] In May the analogue of CP 47,497 was named cannabicyclohexanol.[15]

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.[16][17][18][19] Another potent synthetic cannabinoid, HU-210, has been reported to have been found in Spice seized by U.S. Customs and Border Protection.[20] 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.[21]

Different ratios of JWH-018 and CP 47,497 and their analogues have been found in different brands of synthetic cannabis[22] and manufacturers constantly change the composition of their products.[23] The amount of JWH-018 in Spice has been found to vary from 0.2% to 3%.[24]

Other non-cannabinoid ingredients have also been found in synthetic cannabis blends 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.[25][26] In 2013 a designer opioid drug AH-7921 was detected in smoking blends in Japan, along with several novel cannabinoids and a cathinone analogue.[27]

New Zealand

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.[28][29] Since this time, a further 15 cannabinoid compounds have been detected as ingredients of synthetic cannabis blends in New Zealand and banned as temporary class drugs.[30] 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 2011-2012.[31]
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

No official studies have been conducted on the effects of synthetic cannabinoids on humans (as is usually the case with known toxic and/or illegal compounds).[36] 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,[37] agitation, vomiting, hallucinations, psychoses, seizures, convulsions[38] and panic attacks.[39][40][41][42][43] 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.[44] Other symptoms included epileptic seizures, acute psychosis, and heart attacks.[44]

At least one death has been linked to overdose of synthetic cannabinoids[45] and in Colorado three deaths in September 2013 have been investigated for being linked to synthetic cannabinoids.[46] In December 2012, after two weeks of daily synthetic cannabis use, a 17-year old girl suffered multiple strokes and subsequent brain damage, leaving her blind and paralyzed.[47]

These more severe adverse effects in contrast to use of marijuana are believed 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 no matter of dose and resulting concentration.[48] 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.[45]

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."[36] "You don't know what it's going to do to you."[49] 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.[50] 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.[51]

Studies are currently available which suggest an association between synthetic cannabinoids and psychosis. Physicians should be aware that the use of synthetic cannabinoids can be associated with psychosis and 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.[52] Individuals with risk factors for psychotic disorders should be counseled against using synthetic cannabinoids.[53]
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.[22][50] 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.[54]