Science Cannabis

64 THE SCIENCE OF MARIJUANAsee Pertwee,1995; Piomelli et al., 1998; and Felder and Glass, 1998).Although CB1 receptors are often coupled to inhibition of cyclic AMPformation, this is not always the case. In some nerve cells, activation ofCB1 receptors inhibits the function of calcium ion channels, particularlythose of the N-subtype. This may help to explain how cannabinoids inhibitthe release of neurotransmitters, since these channels are essentialfor the release of these substances from nerve terminals. CB1 receptorsare not usually located on the cell body regions of nerve cells — wherethey might control the electrical firing of the cells — but are concentratedinstead on the terminals of the nerve fibers, at sites where they makecontacts (known as synapses) with other nerve cells. Here the CB1 receptorsare well placed to modify the amounts of chemical neurotransmitterreleased from nerve terminals, and thus to modulate the process of synaptictransmission by regulating the amounts of chemical messenger moleculesreleased when the nerve terminal is activated. Experiments withnerve cells in tissue culture, or with thin slices of brain tissue incubatedin the test tube have shown that the addition of THC or other cannabinoidscan inhibit the stimulation-evoked release of various neurotransmitters,including the inhibitory amino acid "y-aminobutyric acid(GABA), and the amines noradrenaline and acetylcholine. In the peripheralnervous system CB-1 receptors are also found on the terminals ofsome of the nerves that innervate various smooth muscle tissues. RogerPertwee and his colleagues in Aberdeen have made use of this in devisinga variety of organ bath assays, in which THC and other cannabinoidsinhibit the contractions of smooth muscle in the intestine, vas deferens,and urinary bladder, evoked by electrical stimulation. Such bioassayshave proved valuable in assessing the agonist/antagonist properties ofnovel cannabinoid drugs (Pertwee, 1995).Although the actions of cannabinoids appear generally to be to inhibitneurotransmitter release, this does not mean that their overall effectis always to dampen down activity in neural circuits. For example, reducingthe release of the powerful inhibitory chemical GABA might havethe opposite effect by reducing the level of inhibition. This may explaintwo important effects of cannabinoids that have been described in recentyears. These are that administration of THC leads to a selective increase