Synthetic cannabinoids
Synthetic cannabinoids, or neocannabinoids, are a class of designer drug molecules that bind to the same receptors to which cannabinoids in cannabis plants attach. These novel psychoactive substances should not be confused with synthetic phytocannabinoids or synthetic endocannabinoids from which they are distinct in many aspects.
Typically, synthetic cannabinoids are sprayed onto plant matter and are usually smoked, although they have also been ingested as a concentrated liquid form in the United States and United Kingdom since 2016. They have been marketed as herbal incense, or "herbal smoking blends", and sold under common names such as K2, spice, and synthetic marijuana. They are often labeled "not for human consumption" for liability defense. A large and complex variety of synthetic cannabinoids are designed in an attempt to avoid legal restrictions on cannabis, making synthetic cannabinoids designer drugs.
Most synthetic cannabinoids are agonists of the cannabinoid receptors. They have been designed to be similar to THC, the natural cannabinoid with the strongest binding affinity to the CB1 receptor, which is linked to the psychoactive effects or "high" of marijuana. These synthetic analogs often have greater binding affinity and greater potency to the CB1 receptors. There are several synthetic cannabinoid families [|which are classified by the creator of the substance], which can include several substances with different base structures such as classical cannabinoids and unrelated naphthoylindoles.
Synthetic marijuana compounds began to be manufactured and sold in the early 2000s. From 2008 to 2014, 142 synthetic cannabinoid receptor agonists were reported to the European Monitoring-Center for Drugs and Drug Addiction.
Reported user negative effects include palpitations, paranoia, intense anxiety, nausea, vomiting, confusion, poor coordination, and seizures. There have also been reports of a strong compulsion to re-dose, withdrawal symptoms, and persistent cravings. There have been several deaths linked to synthetic cannabinoids. The Centers for Disease Control and Prevention found that the number of deaths from synthetic cannabinoid use tripled between 2014 and 2015. In 2018, the United States Food and Drug Administration warned of significant health risks from synthetic cannabinoid products that contain the rat poison brodifacoum, which is added because it is thought to extend the duration of the drugs' effects. Severe illnesses and death have resulted from this contamination.
Synthetic cannabinoid products
It is often difficult to determine what is in these products without reagent testing because masking agents, such as tocopherol, eugenol, and fatty acids, are added to confound identification. Just as the synthetic used differ between each synthetic cannabinoid product sold, so do the other contents of the counterfeit product.Counterfeit black market cannabis products
- Counterfeit cannabis-liquid for e-cigarettes: Synthetic cannabinoids are increasingly offered in e-cigarette form as "c-liquid". Several schoolchildren in Greater Manchester collapsed after vaping synthetic cannabinoids mis-sold as THC e-liquid.
- Counterfeit cannabis buds: Hemp buds laced with synthetic cannabinoids.
- Counterfeit cannabis edible: The Florida Poison Information Center in Jacksonville warned parents in September 2020 that the number of people poisoned by fake marijuana edibles and candies has tripled.
- Counterfeit hashish: From December 2018, different samples of hashish have been found to contain synthetic cannabinoids.
Counterfeit CBD products
"Herb/incense" blends
Synthetic cannabinoids found in herb blends
Synthetic cannabinoid components of 'Spice' :| Compound | Type |
| HU-210 | Classic cannabinoid |
| AM-694 | Benzoylindole |
| RCS-4 | Benzoylindole |
| WIN 48,098 | Benzoylindole |
| CP-47,497 | Cyclohexylphenol |
| JWH-018 | Naphthoylindole |
| JWH-019 | Naphthoylindole |
| JWH-073 | Naphthoylindole |
| JWH-081 | Naphthoylindole |
| JWH-122 | Naphthoylindole |
| JWH-210 | Naphthoylindole |
| AM-2201 | Naphthoylindole |
| JWH-203 | Phenylacetylindole |
| JWH-250 | Phenylacetylindole |
| RCS-8 | Phenylacetylindole |
Non-cannabinoid chemicals found in herb blends
Most blends consist of synthetic cannabinoids sprayed onto inert vegetable matter, but some contain other psychoactive substances, including psychoactive herbs, e.g., wild dagga and Indian warrior, and psychoactive alkaloids, e.g., betonicine, aporphine, leonurine, nuciferine, and nicotine.In 2013, AH-7921 was detected in smoking blends in Japan. In 2018, there was an outbreak of synthetic cannabinoids contaminated with anticoagulants, mainly brodifacoum, in at least 11 states in the US that caused coagulopathy and resulted in the treatment of over 300 people and at least eight deaths.
One of the most common non-cannabinoid ingredients in these products is oleamide, a fatty acid derivative that acts similarly to a cannabinoid and has hypnotic properties. Analysis of 44 products synthetic cannabinoid revealed oleamide in 7 of the products tested. Other non-cannabinoid ingredients that have been found in synthetic cannabinoid blends include harmine and harmaline, reversible monoamine oxidase inhibitors, which have been found with myristicin and asarone; substituted cathinone derived stimulant drugs such as 4-methylbuphedrone and 4'-methyl-alpha-PPP; and psychedelic tryptamine derivatives such as 4-HO-DET.
Herbs labeled on packages marketed as legal high
Packages of synthetic cannabinoid products can claim to contain a wide array of plants. However, oftentimes, none of the listed ingredients have been detectable.Herbal components of 'Spice' :
| Common name | Psychoactive alkaloids | Species | Family |
| Beach bean | Unknown | Canavalia maritima; syn. C. rosea | Fabaceae |
| Blue/Sacred lotus | Nuciferine and aporphine | Nelumbo nucifera | Nelumbonaceae |
| Dog rose/Rosehip | Unknown | Rosa canina | Roseceae |
| Dwarf skullcap | Unknown | Scutellaria nana | Lamiacae |
| Honeyweed/Siberian motherwort | Leonurine | Leonurus sibiricus | Lamiaceae |
| Indian warrior | Unknown | Pedicularis densiflora | Orobanchaceae |
| Lion's ear/tail, Wild dagga | Leonurine | Leonotis leonurus | Lamiacae |
| 'Maconha brava' | Genistein, apigenin | Zornia latifolia or Z. diphylla | Fabaceae |
| Marshmallow | Unknown | Althaea officinalis | Malvaceae |
| White and blue water lily | Nupharine, nymphaeine, aporphine and nuciferine | Nymphaea alba and N. caerulea | Nymphaeaceae |
Naming synthetic cannabinoids
Many of the early synthetic cannabinoids that were synthesized for use in research were named after either the scientist who first synthesized them or the institution or company where they originated.| Compounds | Inventor |
| AM | Alexandros Makriyannis |
| CP | Charles Pfizer |
| HU | Hebrew University |
| JWH | John W. Huffman |
Some of the names of synthetic cannabinoids synthesized for recreational use were given names to help market the products. For example, AKB-48 is also the name of a popular Japanese girl band; 2NE1 is also a South Korean girl band; and XLR-11 was named after the first US-developed liquid fuel rocket for aircraft. Now many synthetic cannabinoids are assigned names derived from their four main structural components, core, tail, linker, and linked group, where the name is formatted as LinkedGroup-TailCoreLinker. For example, in 5F-MDMB-PINACA, 5F stands for the terminal fluorine or "fluorine on carbon 5" of the pentyl chain; MDMB stands for "methyl-3,3-dimethyl butanoate", the linked group; and PINACA stands for "pentyl chain indazole carboxamide ".
Common names
Use of the term "synthetic marijuana" to describe products containing synthetic cannabinoids is controversial and, according to Lewis Nelson, a medical toxicologist at the NYU School of Medicine, a mistake. Nelson claims that relative to marijuana, products containing synthetic cannabinoids "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 cannabinoid that the plant contains, the term synthetic cannabinoid is more appropriate.Nearly 700 "herbal incense" blends exist. They are often called "synthetic marijuana", "natural herbs", "herbal incense", or "herbal smoking blends" and often labeled "not for human consumption". In some Spanish-speaking countries, such as Chile and Argentina, such preparations are often referred to as cripy.
According to the Psychonaut Web Mapping Research Project, synthetic cannabinoids, sold under the brand name Spice, were first released in 2005 by the now-dormant company the Psyche Deli in London. 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.