Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and the myenteric plexus preparation of guinea‐pig small intestine

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Abstract
1 The psychoactive cannabinoids (−)-Δ9-tetrahydrocannabinol ((−)-Δ9-THC) and the 1,1-dimethylheptyl homologue of (−)-11-hydroxy-Δ8-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 (−)-Δ9-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 1.4 nm respectively in the myenteric plexus preparation. (−)-DMH was about 40 times more potent than (−)-Δ9-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 (−)-Δ9-THC were not attenuated by 300 nm naloxone. 5 The findings that (−)-Δ9-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.