Locomotor depression and THC-like discriminative stimulus effects of three novel synthetic cannabinoids: ADBICA, THJ-2201, and ADB-PINACA

Abstract

Aims: Synthetic cannabinoids have become increasingly popular as quasi-legal alternatives to marijuana in recent years. As is often the case with designer drugs, when one group of synthetic cannabinoids is scheduled, novel analogs are synthesized to replace them. Numerous adverse effects and incidences of overdose have been associated with newer synthetic cannabinoid analogs. The goal of the current studywas to characterize the locomotor anddiscriminative stimulus effects of three novel synthetic cannabinoid compounds: ADBICA, THJ-2201, and ADB-PINACA. Methods: The effects of these compounds on locomotor activity were tested in male Swiss-Webster (ND4) mice over an 8-hour period in an open field assay of locomotor activity (n=8 per dose). The discriminative stimulus effects of the compounds were tested in male Sprague-Dawley rats trained to discriminate 3mg/kg 9THC from vehicle in a drug-discrimination assay (n=6 per drug). Results: 9-THC (ID50 =13.2mg/kg), ADBICA (ID50 =1.0mg/kg), THJ-2201 (ID50 =0.8mg/kg), and ADB-PINACA (ID50 =0.28mg/kg) produced significant depression of locomotor activity compared to vehicle. Locomotor depression induced by the test compoundswas shorter acting (30–80min) compared to 9-THC (120–210min). ADBICA (ED50 =0.11mg/kg), THJ-2201 (ED50 =0.15), and ADBPINACA (ED50 =0.38) fully substituted for the discriminative stimulus effects of 9-THC. ADBICA and ADB-PINACA significantly attenuated response rate at the doses tested. Conclusions: Our results indicate that these novel synthetic cannabinoid compounds produce locomotor depression and discriminative stimulus effects similar to 9-THC, and may have potential for abuse as alternatives to 9-THC. The stimulus effects of each of the compounds were shorter acting and at least tenfold more potent than 9-THC. Future studies on the reinforcing properties of these compounds are necessary to fully elucidate their abuse liability. Financial support: NIH N01DA-13-8908.