Synthetic cannabinoids

"Spice (drug)" redirects here. For the fictional drug in Frank Herbert's Dune novels, see Melange (fictional drug).
Bag and contents of a well-known early brand of synthetic cannabinoids named Spice that contains herbs covered with synthetic cannabinoids, now illegal throughout much of the world

Synthetic cannabinoids are a class of designer drug molecules that bind to the same receptors to which cannabinoids (THC, CBD and many others) in cannabis plants attach.[1] These novel psychoactive substances should not be confused with synthetic phytocannabinoids (obtained by chemical synthesis) or synthetic endocannabinoids from which they are in many aspects distinct.[2][3][4]

Typically, synthetic cannabinoids are sprayed onto plant matter[5] and are usually smoked,[6] although they have also been ingested as a concentrated liquid form in the United States and United Kingdom since 2016.[7] They have been marketed as herbal incense, or "herbal smoking blends",[6] and sold under common names like K2, spice,[8] and synthetic marijuana.[5] They are often labeled "not for human consumption" for liability defense.[8] A large and complex variety of synthetic cannabinoids are designed in an attempt to avoid legal restrictions on cannabis, making synthetic cannabinoids designer drugs.[6]

Most synthetic cannabinoids are agonists of the cannabinoid receptors. They have been designed to be similar to THC,[9] the natural cannabinoid with the strongest binding affinity to the CB1 receptor, which is linked to the psychoactive effects or "high" of marijuana.[10] 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.[11]

Synthetic marijuana compounds began to be manufactured and sold in the early 2000s.[6] From 2008 to 2014, 142 synthetic cannabinoid receptor agonists were reported to the European Monitoring-Center for Drugs and Drug Addiction (EMCDDA).[12]

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.[12] 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.[13][14] 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.[15] Severe illnesses and death have resulted from this contamination.[15]

  1. ^ UNODC, Laboratory & Scientific Service. "Details for Synthetic cannabinoids". United Nations Office on Drugs and Crime. Retrieved 2021-10-17.
  2. ^ Mechoulam, R; Lander, N; Breuer, A; Zahalka, J (1990). "Synthesis of the individual, pharmacologically distinct, enantiomers of a tetrahydrocannabinol derivative". Tetrahedron: Asymmetry. 1 (5): 315–318. doi:10.1016/S0957-4166(00)86322-3.
  3. ^ Seely, Kathryn A.; Lapoint, Jeff; Moran, Jeffery H.; Fattore, Liana (2012-12-03). "Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 39 (2): 234–243. doi:10.1016/j.pnpbp.2012.04.017. ISSN 1878-4216. PMC 3936256. PMID 22561602.
  4. ^ Riboulet-Zemouli, Kenzi (2020). "'Cannabis' ontologies I: Conceptual issues with Cannabis and cannabinoids terminology". Drug Science, Policy and Law. 6: 12, 19. doi:10.1177/2050324520945797. ISSN 2050-3245. S2CID 234435350.
  5. ^ a b Macher R, Burke TW, Owen SS (2012-05-01). "Synthetic Marijuana". FBI: Law Enforcement Bulletin. Retrieved 2020-03-19.
  6. ^ a b c d Science, Live (2017-02-07). "Synthetic Marijuana Linked To Seizures, Psychosis And Death". Huffington Post. Retrieved 2018-05-04.
  7. ^ Diao X, Huestis MA (February 2017). "Approaches, Challenges, and Advances in Metabolism of New Synthetic Cannabinoids and Identification of Optimal Urinary Marker Metabolites". Clinical Pharmacology and Therapeutics. 101 (2): 239–253. doi:10.1002/cpt.534. PMID 27727455. S2CID 10910467.
  8. ^ a b Banister SD, Stuart J, Kevin RC, Edington A, Longworth M, Wilkinson SM, et al. (August 2015). "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. 6 (8): 1445–58. doi:10.1021/acschemneuro.5b00107. PMID 25921407.
  9. ^ Cannaert A, Storme J, Franz F, Auwärter V, Stove CP (December 2016). "Detection and Activity Profiling of Synthetic Cannabinoids and Their Metabolites with a Newly Developed Bioassay". Analytical Chemistry. 88 (23): 11476–11485. doi:10.1021/acs.analchem.6b02600. hdl:1854/LU-8506703. PMID 27779402.
  10. ^ Rapaka RS, Makriyannis A, eds. (1987). "Structure-Activity Relationships of the Cannabinoids" (PDF). NIDA Research Monograph. 79 – via U.S. Department of Health and Human Services.
  11. ^ "K2: Scary Drug or Another Drug Scare?". Newsweek. 2010-03-03. Retrieved 2018-05-04.
  12. ^ a b Abouchedid R, Ho JH, Hudson S, Dines A, Archer JR, Wood DM, Dargan PI (December 2016). "Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation". Journal of Medical Toxicology. 12 (4): 396–401. doi:10.1007/s13181-016-0571-7. PMC 5135680. PMID 27456262.
  13. ^ "Notes from the Field: Increase in Reported Adverse Health Effects Related to Synthetic Cannabinoid Use — United States, January–May 2015". www.cdc.gov. June 12, 2015. Retrieved 2018-11-01.
  14. ^ "Frequently Asked Questions | Marijuana | CDC". www.cdc.gov. 2018-03-16. Retrieved 2018-05-04. 10. How harmful is K2/Spice (synthetic marijuana or synthetic cannabinoids)?
  15. ^ a b "Statement from FDA warning about significant health risks of contaminated illegal synthetic cannabinoid products that are being encountered by FDA" (Press release). United States Food and Drug Administration. July 19, 2018.