INHIBITORY EFFECTS OF CERTAIN ENANTIOMERIC CANNABINOIDS IN THE MOUSE VAS-DEFERENS AND THE MYENTERIC PLEXUS PREPARATION OF GUINEA-PIG SMALL-INTESTINE

1 The psychoactive cannabinoids (-)-DELTA(9)-tetrahydrocannabinol ((-) -DELTA(9)-THC) and the 1,1-dimethylheptyl homologue of (-)-11-hydroxy- DELTA(8)-tetrahydrocannabinol ((-)-DMH) both inhibited electrically-ev oked contractions of the mouse isolated vas deferens and the myenteric plexus-longitudinal muscle preparation of the guinea-pig small intest ine. 2 Concentrations of (-)-DELTA(9)-THC and (-)-DMH that decreased t witch heights by 50% were 6.3 and 0.15 nM respectively in the mouse va s deferens and 60 nM and 1.4nM 0.15 nM respectively in the mouse vas d eferens and 60 nM and 1.4 nM respectively in the myenteric plexus prep aration. (-)-DMH was about 40 times more potent than (-)-DELTA(9)-THC in both preparations, supporting the notion that their mode of action in each tissue is the same. 3 The psychically inactive cannabinoid, ()-DMH, had no inhibitory effect in the mouse vas deferens at a concent ration of 30 nM, showing it to be at least 1000 times less potent than (-)-DMH. In the myenteric plexus preparation, (+)-DMH was about 500 t imes less potent than its (-)-enantiomer. 4 The inhibitory effects of sub-maximal concentrations of (-)-DELTA(9)-THC were not attenuated by 300 nM naloxone. 5 The findings that (-)-DELTA(9)-THC and (-)-DMH are highly potent as inhibitors of the twitch response of the mouse vas de ferens and guinea-pig myenteric plexus preparation and that DMH shows considerable stereoselectivity suggest that the inhibitory effects of cannabinoids in these preparations are mediated by cannabinoid recepto rs.