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Synthetic cannabinoids are synthetic molecules that act in a way similar to that of plant cannabinoids, naturally present in cannabis (such as THC).

They are primarily cannabinoid receptor agonists. Most were developed for therapeutic purposes (analgesia), others were synthesized with the aim of creating legal alternatives to cannabis.

Synthetic cannabinoids are the most important class of new synthetic products . Of the 73 new synthetic substances reported by the EMCDDA in 2012, 30 were synthetic cannabinoids

The first "synthetic cannabis" was in the form of a mixture of various plants that had been impregnated with synthetic cannabinoids.

It appeared in the mid-2000s as Spice [3] ( Spice Gold , Spice Silver ...). Other brands then appeared ( K2 , Yucatan Fire , etc…). These products only really gained popularity from the second half of the 2000s.

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nb= For those who knew the saga of "Dune" by Franck Herbert, the name "Spice" was given in reference to the "Spice" of the science fiction novel, the spice produced by the planet Arrakis, which increased the psychic abilities and allowed interstellar travel, for example.

At the end of 2008, analyzes detected the presence of synthetic cannabinoids in these mixtures, in particular CP-47,497-C8 and JWH-018. Following measures to ban these compounds in several countries, manufacturers will then use new molecules. In 2009, other synthetic cannabinoids such as JWH-073, JWH-019, JWH-250, JWH-398 and HU-210 will be identified . Other new compounds will be regularly identified thereafter.

Most synthetic cannabinoid powders that are used in “legal highs” are manufactured in China and then shipped in bulk through legal transportation and distribution networks.

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Shipments of several kilos are often intercepted by European authorities, but purity is rarely determined. A study in South Korea reported purities between 75% and 90% on bulk powder samples. European seizures of bulk powders include 54 kilograms of JWH-018 in Denmark (2012), 21 kilograms of JWH-018 in Finland (2012) and 20 kilograms of AM-2201 in Spain (2013).

Once in Europe, the products are mixed with herbs. This form is primarily intended for smoking. Among the grasses used as a carrier, the following species can be mentioned: Canavalia maritima , Nymphaea caerulea , Scutellaria nana , Pedicularis densiflora , Leonotis leonurus , Zornia latifolia , Nelumbo nucifera or Leonurus sibiricus

Other types of research chemical substances have also been identified in some samples

fatty acid derivatives with effects similar to cannabinoids: oleamide, palmitamide, stearamide

MAOIs: harmine, harmaline

an opioid: O-desmethyltramadol

other molecules, some of which come from the plants used as a support and others which would have been added

Today, CS is no longer found only within herbal smoking blends but can be obtained as an isolated powder from some RC suppliers. They can also be found in resin form (like the Bang Solid or Afghan Insense brands) in response to the growing popularity of cannabis resin in many countries. It can also be found in some e-liquids for electronic cigarettes.

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Many of the synthetic cannabinoids have code names that relate to their discovery. In some cases, their code name comes from the initials of the name of the scientists who first synthesized them: the "JWH" compounds come from John W. Huffman, the "AM" compounds come from Alexandros Makriyannis. In other cases, they may come from the company where they were synthesized: the “HU” series comes from the Hebrew University of Jerusalem, the CP series was created by the Pfizer laboratory.

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Others may have codenames derived from their chemical name: APICA for N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide or APINACA for N-(1-adamantyl)-1-pentyl -1H-indazole-3-carboxamide

More recently, those involved in the "legal high" business have started using code names that were likely chosen to help market the products. For example, AKB-48 is another used name of APINACA. AKB-48 is the name of a popular Japanese girl group that has been compared to British pop group 'Spice Girls'. The synthetic cannabinoid APICA is also referred to by the alternate name of "2NE1", which is the name of a South Korean girl group that has also been compared to the Spice Girls.

Finally, the synthetic cannabinoid XLR-11, appears to have been named after the first liquid fuel developed in the United States for use in airplanes.

Synthetic cannabinoids have various structures. We can distinguish

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THC and some examples of CS

Naphthoylindoles:

JWH-007, JWH-015, JWH-018, JWH-019, JWH-073, JWH-081, JWH-098, JWH-116, JWH-122, JWH-149, JWH-182, JWH-193, JWH- 198, JWH-200, JWH-210, JWH-398, JWH-424, AM-1220, AM-1221, AM-1235, AM-2201, AM-2232, MAM-2201

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Dibutylone (bk-DMBDB is a stimulant drug of the amphetamine, phenethylamine, and cathinone drug classes. It is structurally related to butylone, a designer drug that has been detected in products marketed as bath salts or plant food.

In 2018, dibutylone was the third most common drug of the cathinone class to be identified in Drug Enforcement Administration seizures

Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body,] drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects.[ Stimulants are widely used throughout the world as prescription medicines as well as without a prescription (either legally or illicitly) as performance-enhancing or recreational drugs.

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Among narcotics, stimulants produce a noticeable crash or comedown at the end of their effects. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine (Vyvanse), methylphenidate (Ritalin), and amphetamine (Adderall). It was estimated in 2015 that the percentage of the world population that had used cocaine during a year was 0.4%. For the category "amphetamines and prescription stimulants" (with "amphetamines" including amphetamine and methamphetamine) the value was 0.7%, and for MDMA 0.4%

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Stimulants in therapeutic doses, such as those given to patients with ADHD, increases ability to focus, vigor, sociability, libido and may elevate mood. However, in higher doses stimulants may actually decrease the ability to focus, a principle of the Yerkes-Dodson Law. In higher doses stimulants may also produce euphoria, vigor, and decrease need for sleep.

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Many, but not all, stimulants have ergogenic effects. Drugs such as ephedrine, pseudoephedrine, amphetamine and methylphenidate have well documented ergogenic effects, while cocaine has the opposite effect.[5] Neurocognitive enhancing effects of stimulants, specifically modafinil, amphetamine and methylphenidate have been documented in healthy adolescents, and is a commonly cited reason among illicit drug users for use, particularly among college students in the context of studying.

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In some cases psychiatric phenomenon may emerge such as stimulant psychosis, paranoia, and suicidal ideation. Acute toxicity has been reportedly associated with a homicide, paranoia, aggressive behavior, motor dysfunction, and punding. The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia.[7] Most drugs classified as stimulants are sympathomimetics, that is they stimulate the sympathetic branch of the autonomic nervous system. This leads to effects such as mydriasis, increased heart rate, blood pressure, respiratory rate and body temperature.

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When these changes become pathological, they are called arrhythmia, hypertension, and hyperthermia, and may lead to rhabdomyolysis, stroke, cardiac arrest, or seizures. However, given the complexity of the mechanisms that underlie these potentially fatal outcomes of acute stimulant toxicity, it is impossible to determine what dose may be lethal

Assessment of the effects of stimulants is relevant given the large population currently taking stimulants. A systematic review of cardiovascular effects of prescription stimulants found no association in children, but found a correlation between prescription stimulant use and ischemic heart attacks.[10] A review over a four-year period found that there were few negative effects of stimulant treatment, but stressed the need for longer-term studies.

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A review of a year long period of prescription stimulant use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only.[12] Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning, and appears to be relatively safe.

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Abuse of prescription stimulants (not following physician instruction) or of illicit stimulants carries many negative health risks. Abuse of cocaine, depending upon route of administration, increases risk of cardiorespiratory disease, stroke, and sepsis.[14] Some effects are dependent upon the route of administration, with intravenous use associated with

the transmission of many disease such as Hepatitis C, HIV/AIDS and potential medical emergencies such as infection, thrombosis or pseudoaneurysm,while inhalation may be associated with increased lower respiratory tract infection, lung cancer, and pathological restricting of lung tissue.

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Cocaine may also increase risk for autoimmune disease[ and damage nasal cartilage. Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, resulting in an increased risk for Parkinson's disease

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HU-210 is a synthetic agonist analog of Δ9-THC, which is the primary psychoactive component of marijuana. HU-210 is a potent central cannabinoid (CB1)

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