Cannabinergic aminoalkylindoles, including AM678=JWH018 found in 'Spice', examined using drug (Δ(9)-tetrahydrocannabinol) discrimination for rats.
Torbjörn U C Järbe, Hongfen Deng, Subramanian K Vadivel, Alexandros Makriyannis
Behavioural Pharmacology September 2011 DOI: 10.1097/fbp.0b013e328349fbd5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study in rats Peer reviewed |
|---|---|
| Population | Rats trained to discriminate vehicle from 3 mg/kg THC |
| Interventions | AM5983 AM2233 WIN55212-2 rimonabant Δ(9)-tetrahydrocannabinol (THC) |
| Dose | 3 mg/kg THC; 1.8 mg/kg AM2233; 1 mg/kg rimonabant |
| Duration | Testing at 30 and 90 min after intraperitoneal injection |
| Measures | ED50 values from drug discrimination substitution tests |
| Topics | Cannabis |
| Key points | AM5983 and AM678 (JWH018) are potent cannabimimetics, substituting for THC at roughly eight times THC's potency, while AM2233 was about twice as potent and WIN55212-2 approximately equal to THC. Rimonabant blocked substitution, shifting AM5983 and AM678 curves 8- to 12-fold but WIN55212-2 only about 3-fold, which the authors interpret as possible mechanistic differences among aminoalkylindoles. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 16
- Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines Journal of Neuroscience November 12, 2014
- Δ9-tetrahydrocannabinol: Drug discrimination abuse liability testing in female Lister Hooded rats: Trials, tribulations and triumphs. Journal of pharmacological and toxicological methods 2020
- Finding order in chemical chaos - Continuing characterization of synthetic cannabinoid receptor agonists. Neuropharmacology May 15, 2018
- Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of five novel synthetic cannabinoids in rats. Psychopharmacology March 2018
- Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. Current Topics in Behavioral Neurosciences 2018
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