Influence of 11-hydroxy-delta-9-tetrahydrocannabinol on spinal motoneurons in cat

Intracellular recording techniques were used on spinal motoneurons in the cat in order to define the synaptic pharmacology of 11-hydroxy-delta-9-tetrahydrocannabinol (11-hydroxy-delta-9-THC), the principal metabolite of delta-9-tetrahydrocannabinol (delta-9-THC). The 11-hydroxy derivative increased the amplitude of excitatory postsynaptic potentials; such an excitatory response did not appear to be the result of changes in afferent input. The increase in excitatory postsynaptic potentials, however, may be accounted for by a rise in membrane resistance. The cannabinoid also concomitantly produced synaptic depression, as indicated by a rise in the firing threshold for the motoneuron action potential. The responses to 11-hydroxy derivative suggest synaptic sites and mechanisms of action; for instance, the data indicate that the cannabinoid affected postsynaptic conductance. Finally, the similarity between the synaptic effects of the 11-hydroxy derivative and those of delta-9-THC suggest that the metabolite may contribute to the pharmacological properties of its parent compound.