Molecular Pharmacology, Vol 17, 344-349, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Effects of ⁹-Tetrahydrocannabinol on Excitable Membranes and Neuromuscular Transmission

¹ Department of Physiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032

The effects of ⁹-tetrahydrocannabinol (THC) on excitable membranes and neuromuscular transmission were investigated utilizing the isolated sciatic nerve—sartorius muscle preparation of the frog. Neuromuscular transmission was depressed upon bath application of 30 x 10^-6 M THC. Records taken at junctional regions showed that upon nerve stimulation only 50% of the muscle fibers tested elicited a propagated action potential. These action potentials showed a reduction in the overshoot, the maximum rate of rise, and the maximum rate of fall. For the remainder of the muscle fibers, 10% showed no end-plate potentials and 40% gave subliminal end-plate potentials with amplitudes ranging from 5 to 30 mV. At blocked junctions the miniature end-plate potential amplitude was increased and the frequency was reduced. The resting potential of THC-treated fibers did not differ from that of controls. Muscle fiber action potentials recorded at nonjunctional regions showed a decrease in the overshoot, in the maximum rate of rise, and in the maximum rate of fall. The above changes persisted after THC was removed from the bathing solution. THC caused a small but significant increase in postjunctional membrane sensitivity to carbamylcholine. At junctional regions, the membrane input resistance and membrane time constant were unchanged. THC caused a decrease in the quantal content, and if drug application was prolonged, a complete blockade of quantal release was produced. Thus, THC blocks neuromuscular transmission by depressing the release of acetylcholine from presynaptic nerve terminals. In addition, THC depresses the ionic conductance mechanisms which underlie the propagation of action potentials in excitable membranes.

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ACKNOWLEDGMENT We thank Dr. W. D. Niemi for helpful discussions during the course of the experiments.

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