Pyrolysis of UR-144, a Synthetic Cannabinoid, Augments an Affinity to Human CB 1 Receptor and Cannabimimetic Effects in Mice

J Toxicol Sci. 2017;42(3):335-341. doi: 10.2131/jts.42.335.

Abstract

Drug abusers most often smoke 'herbal incense' as a cigarette or inhale it using a smoking tool. Smoking may cause pyrolysis of the drug and produce decomposed products of which biological effect has never been investigated. The synthetic cannabinoid UR-144 is known to undergo thermal degradation, giving a ring-opened isomer, so-called UR-144 degradant. The present study demonstrates by using UR-144 as a model drug that the smoke of burned UR-144 contains the UR-144 degradant. The UR-144 degradant showed approximately four fold higher agonist activity to human CB1 receptor and augmented hypothermic and akinetic actions in mice compared to UR-144. These results indicate that smoking behavior may increase psychological actions of the certain synthetic cannabinoids.

Keywords: CB1 receptor; Smoking; Synthetic cannabinoid; UR-144; UR-144 degradant.

MeSH terms

  • Animals
  • Hot Temperature / adverse effects*
  • Humans
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Male
  • Marijuana Smoking*
  • Mice, Inbred BALB C
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / metabolism*

Substances

  • (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone
  • Indoles
  • Receptor, Cannabinoid, CB1