Effects of delta-9-tetrahydrocannabinol, 11-hydroxy-delta-9-tetrahydrocannabinol and cannabidiol on neuromuscular transmission in the frog.

Intracellular recording techniques were used on neuromuscular junctions of the sartorius muscle of the frog, in vitro, to define the synaptic pharmacology of delta-9-tetrahydrocannabinol (THC), 11-hydroxy-THC and cannabidiol (CBD). The frequency of miniature endplate potentials was increased by THC, decreased by CBD and was unaffected by 11-hydroxy-THC, whereas the amplitude of the miniature endplate potentials was depressed by all three cannabinoids. In addition, the mean quantum content of the endplate potential (m) was first increased and then decreased by THC and 11-hydroxy-THC, but CBD produced only depression. Changes in m and the frequency of the miniature endplate potential indicated presynaptic sites of drug action and reduction of the amplitude of the miniature endplate potential suggested a postsynaptic site. The findings suggest possible mechanisms of action for the central excitatory and depressant properties of the cannabinoids.