The short-acting synthetic cannabinoid AB-FUBINACA induces physical dependence in mice

Drug Alcohol Depend. 2020 Sep 1:214:108179. doi: 10.1016/j.drugalcdep.2020.108179. Epub 2020 Jul 15.

Abstract

Background: Recent years have seen a rise in the diversity and use of synthetic cannabinoids. The present study evaluated the behavioral effects of the third-generation indazole-3-carboxamide-type synthetic cannabinoid, AB-FUBINACA.

Methods: Adult male and female C57BL/6J mice were treated with AB-FUBINACA (0-3 mg/kg, i.p.) and tested repeatedly in the tetrad battery measuring catalepsy, antinociception, hypothermia, and locomotor activity. Mice treated with AB-FUBINACA (≥2 mg/kg, i.p.) displayed classic cannabinoid effects in the tetrad that were blocked by the CB1 receptor selective antagonist rimonabant. To address tolerance and withdrawal effects, a second group of mice was injected with AB-FUBINACA (3 mg/kg, s.c.) or vehicle consisting of 5% ethanol, 5% Kolliphor EL, and 90 % saline every 12 h and tested daily in modified tetrad over the course of 5 days. On the 6th day, withdrawal was precipitated using rimonabant (3 mg/kg, s.c.), and somatic signs of withdrawal (i.e., head twitches and paw tremors) were quantified.

Results: Although mice did not develop tolerance to AB-FUBINACA or cross-tolerance to Δ9-tetrahydrocannabinol (THC; 50 mg/kg, i.p.), somatic precipitated withdrawal signs were observed. Repeated tetrad testing up to 48 h post injection indicated that AB-FUBINACA effects are relatively short-lived, as compared with THC. Brain levels of AB-FUBINACA, as quantified by UHPLC-MS/MS, were undetectable 4 h post injection.

Conclusions: These data indicate that the cannabinoid effects of AB-FUBINACA are relatively short-lived, yet sufficient to induce dependence in mice.

Keywords: Cannabis use disorder; Drug dependence; Substance use disorder; Synthetic marijuana.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cannabinoids / pharmacology
  • Dronabinol / pharmacology
  • Drug Tolerance
  • Indazoles / pharmacology*
  • Locomotion / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptor, Cannabinoid, CB1
  • Rimonabant / pharmacology
  • Substance-Related Disorders
  • Tandem Mass Spectrometry

Substances

  • Cannabinoids
  • Indazoles
  • Receptor, Cannabinoid, CB1
  • Dronabinol
  • AB-FUBINACA
  • Rimonabant