DARK Classics in Chemical Neuroscience: Synthetic Cannabinoids (Spice/K2)

December 4, 2019

Abstract

This Review covers the background, pharmacology, adverse effects, synthesis, pharmacokinetics, metabolism, and history of synthetic cannabinoid compounds. Synthetic cannabinoids are a class of novel psychoactive substances that act as agonists at cannabinoid receptors. This class of compounds is structurally diverse and rapidly changing, with multiple generations of molecules having been developed in the past decade. The structural diversity of synthetic cannabinoids is supported by the breadth of chemical space available for exploitation by clandestine chemists and incentivized by attempts to remain ahead of legal pressures. As a class, synthetic cannabinoid products have a more serious adverse effect profile than that of traditional phytocannabinoids, including notable risks of lethality, as well as a history of dangerous adulteration. Most synthetic cannabinoids are rapidly metabolized to active species with prolonged residence times and peripheral tissue distribution, and analytical confirmation of use of these compounds remains challenging.

Overall, the emergence of synthetic cannabinoids serves as a noteworthy example of the pressing public health challenges associated with the increasing development of easily synthesized, structurally flexible, highly potent, psychoactive drugs.

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  1. Glatfelter, G. C., Partilla, J. S., & Baumann, M. H. (2022). Structure-activity relationships for 5F-MDMB-PICA and its 5F-pentylindole analogs to induce cannabinoid-like effects in mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(4), 924–932. https://doi.org/10.1038/s41386-021-01227-8
  2. Giorgetti, A., Pascali, J. P., Fais, P., Pelletti, G., Gabbin, A., Franchetti, G., Cecchetto, G., & Viel, G. (2021). Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications. Life (Basel, Switzerland), 11(5), 440. https://doi.org/10.3390/life11050440
  3. Lin, M., Lee, J. C., Blake, S., Ellis, B., Eubanks, L. M., & Janda, K. D. (2020). Broadly Neutralizing Synthetic Cannabinoid Vaccines. JACS Au, 1(1), 31–40. https://doi.org/10.1021/jacsau.0c00057
  4. Walsh, K. B., & Andersen, H. K. (2020). Molecular Pharmacology of Synthetic Cannabinoids: Delineating CB1 Receptor-Mediated Cell Signaling. International journal of molecular sciences, 21(17), 6115. https://doi.org/10.3390/ijms21176115