Cannabinergic aminoalkylindoles, including AM678=JWH018 found in 'Spice', examined using drug (Δ(9)-tetrahydrocannabinol) discrimination for rats

Behav Pharmacol. 2011 Sep;22(5-6):498-507. doi: 10.1097/FBP.0b013e328349fbd5.


We examined four different cannabinergic aminoalkylindole ligands, including one drug (AM678=JWH018) found in herbal 'Spice' concoctions, for their ability to substitute for Δ(9)-tetrahydrocannabinol (THC), and the ability of the cannabinoid receptor 1-selective antagonist/inverse agonist rimonabant to block the substitution, 30 and 90 min after intraperitoneal injection. Rats trained to discriminate the effects of vehicle from those produced by 3 mg/kg of THC were used. The order of potency was: AM5983≥AM678>AM2233>WIN55212-2 at both test intervals. AM5983 and AM678 appeared eight times more potent than THC, followed by AM2233 (about twice as potent as THC), and WIN55212-2 approximately THC at the 30-min test interval. The aminoalkylindoles showed reduced potency (i.e. an increased ED50 value) at the longer injection-to-test interval of 90 min compared with testing at 30 min. The rightward shifts by coadministration of rimonabant were approximately 8-fold to 12-fold for AM5983 and AM678, compared with an approximately 3-fold rightward shift for the WIN55212-2 curve. AM2233 (1.8 mg/kg) substitution was also blocked by 1 mg/kg of rimonabant. In conclusion, AM5983 and AM678=JWH018 are potent cannabimimetics derived from an aminoalkylindole template. WIN55212-2 seemed to interact differently with rimonabant, compared with either AM5983 or AM678, indicating potential differences in the mechanism(s) of action among cannabinergic aminoalkylindoles.

Publication types

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

MeSH terms

  • Animals
  • Discrimination Learning / drug effects*
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology*
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Injections, Intraperitoneal
  • Ligands
  • Male
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Rimonabant
  • Time Factors


  • Indoles
  • Ligands
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Dronabinol
  • Rimonabant