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-evoked contractions of the mouse isolated vas deferens and the myenteric plexus-longitudinal muscle preparation of the guinea-pig small intestine. 2 Concentrations of (-)-DELTA(9)-THC and (-)-DMH that decreased twitch heights by 50% were 6.3 and 0.15 nM respectively in the mouse vas deferens and 60 nM and 1.4nM 0.15 nM respectively in the mouse vas deferens and 60 nM and 1.4 nM respectively in the myenteric plexus preparation. (-)-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 concentration of 30 nM, showing it to be at least 1000 times less potent than (-)-DMH. In the myenteric plexus preparation, (+)-DMH was about 500 times 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 deferens 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 receptors.