Synthetic cannabinoid

Overview

Synthetic cannabinoids (also known as synthetic marijuana, noids, herbal incense, K2, or spice) are a class of compounds that bind to cannabinoid receptors to produce cannabis-like subjective effects. Most synthetic cannabinoids are analogs of Δ9-tetrahydrocannabinol (THC), the main active compound of cannabis, while non-psychoactive cannabinoids such as CBD are less well studied. Like THC, most synthetic cannabinoids bind to the same cannabinoid receptors in the brain and are often sold as legal alternatives. PW

Synthetic cannabinoids, or neocannabinoids, are a class of designer drug molecules that bind to the same receptors to which cannabinoids (e.g THC, CBD and CBN) in cannabis plants attach. These novel psychoactive substances should not be confused with synthetic phytocannabinoids (obtained by chemical synthesis) or synthetic endocannabinoids from which they are distinct in many aspects.[1–4] WP

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, Five Spice, spice, and synthetic marijuana. They are often labeled "not for human consumption" to support a liability legal 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.[5–8] WP

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 (e.g., AM-xxx, CP-xx,xxx, HU-xx, JWH-xxx) which are classified by the creator of the substance (e.g., JWH stands for John W. Huffman), which can include several substances with different base structures such as classical cannabinoids and unrelated naphthoylindoles.[9][10][11] WP

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 (EMCDDA).[6][12] WP

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 (CDC) 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 reduce first pass metabolism. Severe illnesses and death have resulted from this practice.[12–15] WP

References

1. Harm reduction site UNODC, Laboratory & Scientific Service. Details for Synthetic cannabinoids
2. Journal / agency Mechoulam, R; Lander, N; Breuer, A; Zahalka, J. Synthesis of the individual, pharmacologically distinct, enantiomers of a tetrahydrocannabinol derivative. Tetrahedron: Asymmetry. 1990. doi:10.1016/S0957-4166(00)86322-3
3. Journal / agency Seely, Kathryn A.; Lapoint, Jeff; Moran, Jeffery H.; Fattore, Liana. Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2012-12-03. doi:10.1016/j.pnpbp.2012.04.017 · PMID 22561602 · PMC3936256
4. Journal / agency Riboulet-Zemouli, Kenzi. 'Cannabis' ontologies I: Conceptual issues with Cannabis and cannabinoids terminology. Drug Science, Policy and Law. 2020. doi:10.1177/2050324520945797
5. Other Macher, Roland; Burke, Tod W; Owen, Stephen S. Synthetic Marijuana. 2012-05-01
6. Other Science, Live. Synthetic Marijuana Linked To Seizures, Psychosis And Death. 2017-02-07
7. Journal / agency Diao X, Huestis MA. Approaches, Challenges, and Advances in Metabolism of New Synthetic Cannabinoids and Identification of Optimal Urinary Marker Metabolites. Clinical Pharmacology and Therapeutics. February 2017. doi:10.1002/cpt.534 · PMID 27727455
8. Journal / agency Banister SD, Stuart J, Kevin RC, Edington A, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Hibbs DE, Glass M, Connor M, McGregor IS, Kassiou M. Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135. ACS Chemical Neuroscience. August 2015. doi:10.1021/acschemneuro.5b00107 · PMID 25921407
9. Journal / agency Cannaert A, Storme J, Franz F, Auwärter V, Stove CP. Detection and Activity Profiling of Synthetic Cannabinoids and Their Metabolites with a Newly Developed Bioassay. Analytical Chemistry. December 2016. doi:10.1021/acs.analchem.6b02600 · PMID 27779402
10. Journal / agency Structure-Activity Relationships of the Cannabinoids. NIDA Research Monograph. 1987
11. Other K2: Scary Drug or Another Drug Scare?. 2010-03-03
12. Journal / agency Abouchedid R, Ho JH, Hudson S, Dines A, Archer JR, Wood DM, Dargan PI. Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation. Journal of Medical Toxicology. December 2016. doi:10.1007/s13181-016-0571-7 · PMID 27456262 · PMC5135680
13. Journal / agency Notes from the Field: Increase in Reported Adverse Health Effects Related to Synthetic Cannabinoid Use — United States, January–May 2015. June 12, 2015
14. Journal / agency Frequently Asked Questions | Marijuana | CDC. 2018-03-16
15. Journal / agency Statement from FDA warning about significant health risks of contaminated illegal synthetic cannabinoid products that are being encountered by FDA. July 19, 2018

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