PROCEEDINGS OF THE BRITISH PHARMACOLOGICAL SOCIETY

s marked T are by title only. Some actions of A1 tetrahydrocannabinol and cannabidiol at cholinergic junctions J. M. LAYMAN* and A. S. MILTON, Department ofPharmacology, School ofPharmacy, University ofLondon, Brunswick Square, London, WCIN lAX The effects of Al-tetrahydrocannabinol (THC) and cannabidiol (CBD), two pharmacologically active constituents of cannabis resin, have been studied at several cholinergic sites. THC reduced the twitch response of the transmurally stimulated ileum of the guinea-pig. At a concentration ofTHC of 1 59 x 10-7M, a 50% reduction in response was observed after 25 min exposure to the drug, whilst at a concentration of 3X18 x 10-6M the onset of inhibition occurred within 45 s and was complete in 5 minutes. In some of the experiments the THC inhibition could be partially overcome by repeated tetani, otherwise complete inhibition persisted for several hours after the THC was removed. This inhibition of the transmurally stimulated ileum by THC was not affected by pretreatment of the tissue with phentolamine and propranolol. In contrast to THC, CBD was without effect on the transmurally stimulated ileum at concentrations as high as 318 x 10-6 M. In some experiments both THC and CBD reduced the response of the guinea-pig ileum to acetylcholine, both compounds being effective at a concentration of 3*18 x 10-7 M. These observations differ from the results reported by Gill, Paton & Pertwee (1970) who found that THC was either without effect, or potentiated the action of acetylcholine on the guinea-pig ileum. However this inhibitory action of both THC and CBD may be a general depressant one, as the response of the tissue to histamine was also reduced. The effects of THC and CBD on the spontaneous release of acetylcholine from the guinea-pig ileum was also investigated. Both compounds reduced the output of acetylcholine; on this preparation CBD was more active than THC, a 15 % reduction in acetylcholine output was produced by a concentration of CBD at 4 x 10-7M compared with THC at 1-75 x 10-6M, and a 35% reduction by CBD at 1 27x 10-6M, or THCat 159x 10-5M. 380P Proceedings of the Neither THC nor CBD in concentrations up to 1P59 x 10-5M had any effect on the rat phrenic nerve diaphragm preparation, or on acetylcholine induced contractions of the frog rectus abdominis muscle. THC (1-59 x 10-5mol/kg) was given intraperitoneally to the anaesthetized cat and had no effect on the preor post-ganglionically stimulated nictitating membrane. THC and CBD would therefore appear to be inactive at the cholinergic sites investigated other than at the postganglionic parasympathetic nerve ending. J.M.L. is the holder of a Merchant Taylors' Company Research Award. This work was supported by a grant from the Medical Research Council. REFERENCE GILL, E. W., PATON, W. D. M. & PERTWEE, R. G. (1970). Preliminary experiments on the chemistry and pharmacology of cannabis. Nature, Lond., 228, 134-136. An anticurare effect of hexamethonium at the mammalian neuromuscular junction C. B. FERRY* and A. R. MARSHALL, Departunenit of Pharmnacology, Univer-sit! of Newvcastle upon Tj'ne The effect of hexamethonium on blocked or partly blocked neuromuscular transmission has been investigated using the rat diaphragm-phrenic nerve preparation immersed in a saline medium (Liley, 1956) at 36' C. In preparations in which the contractile responses to nerve stimulation had been reduced to about 200% after the addition of (+)-tubocurarine chloride(8 x 10-7M) following the addition of hexamethonium (2.8 x 1O-4M) the contractions increased to about 40% of the unblocked control within 8 minutes. This partial reversal of the block due to (+)-tubocurarine was maintained until the hexamethonium was washed