The actions of in vivo and in vitro administration of Δ9-tetrahydrocannabinol on neuromuscular transmission were studied using the rat phrenic nerve-diaphragm preparation. Diaphragms obtained from animals treated acutely with intravenously administered Δ9-tetrahydrocannabinol (4 mgkg) showed an increase in both frequency and amplitude of miniature end-plate potentials as well as a prolonged duration of the end-plate potentials. Similar changes were observed when diaphragms were treated in vitro with 10−4 M Δ9-tetrahydrocannabinol. Δ9-Tetrahydrocannabinol administered either in vivo or in vitro had no significant effect on cholinesterase activity, and had no effect on the resting membrane potential of muscle fibres. [14C]-Δ9-Tetrahydrocannabinol was not specifically localized at the end-plate regions but was distributed equally throughout the muscle fibres. While the data suggest that Δ9-tetrahydrocannabinol acts mainly on the presynaptic site, an additional action on the postsynaptic membrane cannot be excluded.

Fibers of the cat soleus muscle had a mean resting potential of 87 millivolts as measured with an intracellular microelectrode. Miniature end plate potentials had a mean amplitude of 0.95 millivolt, a mean frequency of 1.01 per second, a mean duration of 4.44 milliseconds, and a mean rate of rise of 0.99 volt per second. Two populations of response could be discerned on the basis of rate of rise. Neither alpha-chloralose nor nerve section had any significant effect on the response pattern. The in vivo preparation appears to provide a superior representation of the physiology of the myoneural junction.