Summary1. After oral administration to mice, pethidine, A8-tetrahydrocannabinol (THC), A9-THC, a cannabis extract and cannabinol had a dose-dependent antinociceptive effect when measured by the hot-plate method. Cannabidiol was inactive at 30 mg/kg. A8-THC, A9-THC and pethidine did not differ significantly in potency, but A9-THC was 6 5 times more active than cannabinol. 2. After oral administration, three different cannabis extracts, A8-THC, A9-THC and morphine produced dose-dependent depressions of the passage of a charcoal meal in mice. A8-THC and A9-THC were equipotent and were about five times less potent than morphine. Cannabidiol was inactive up to 30 mg/kg. The effect of the three cannabis extracts on intestinal motility could be accounted for by their A9-THC content.3. The antinociceptive effect of pethidine and the effect of morphine on intestinal motility were antagonized by nalorphine whilst the effects of the cannabis extracts and the pure cannabinoids were not. 4. From these results it is concluded that although cannabis and the narcotics share several common pharmacological properties, the mode of action of each is pharmacologically distinct.

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Performance on some complex and difficult tasks has been shown to be negatively affected for some time after an acute dose of alcohol has been cleared from the system. However, Dauncey reported impairment of a relatively simple reaction time task 3 hr after a dose of alcohol, when the blood alcohol concentration was at or near 0. This impairment was positively related to the subject's drinking history. A replication using the same task found a linear dose/impairment relationship during intoxication. A second simple reaction time task and a vigilance task showed a trend toward impairment, but only a divided attention task was significantly affected during intoxication. There was no significant effect of dose on any of these tests during a "morning after" session. The results are discussed in relation to the differences in method between Dauncey and this study.

Fifteen volunteers received cannabidiol (CBD) (320 microgram/kg) or placebo (both orally, T0), and 60 min later they consumed an ethanolic beverage (0.54 g/kg) or placebo. The effects were measured at T1 (100 min after CBD ingestion), T2 (160 min) and T3 (220 min) using cognitive, perceptual and motor function tests. Factorial analysis indicated that test procedures could be adequately expressed by three rotated factors: A reaction speed factor (I), a standing steadiness factor (II) and a psychomotor coordination/cognitive factor (III). Ethanol produced a significant decrement in factor III. There was no demonstrable effect of CBD, either alone or in combination with ethanol. Neither CBD nor ethanol produced any significant effect on pulse rate. Prior administration of CBD did not significantly affect the blood ethanol levels. Whilst the subjects were able to identify correctly when they were given ethanol, they did not report any subjective effects of CBD.

Emmelin and Feldberg (1947) showed that there were three smooth-muscle stimulating substances in the sting of the nettle: acetylcholine (ACh), histamine, and a third they did not identify. They described six properties of this unidentified third substance: constriction of the blood vessels of rabbit's ear; stimulation of in vitro preparations of rabbit's and guinea-pig's small intestine; lowering of rabbit's blood pressure; solubility in ether; and instability to boiling in alkaline solution. Since these properties coincided with those of 5-hydroxytryptamine (5-HT) subsequently described, we explored the possibility that the third substance of Emmelin and Feldberg might be 5-HT. Demonstration that this was so has already been briefly reported (Chesher and Collier, 1955) and the present paper sets out the detailed evidence on which identification rests and describes further investigations of nettle sting. MATERIALS AND METHODSFor ease of supply we used the dioecious nettle, Urtica dioica. Both sexes showed the characteristic activity; but in all except a very few experiments female plants were used. Twenty-five or more individual stings were removed with forceps from the stalk or leaf and suspended in 0.5 ml. of the Ringer solution appropriate to the preparation in use. Acetylcholine chloride, atropine sulphate, 5-hydroxytryptamine (serotonin) creatinine sulphate, lysergic acid diethylamide tartrate (LSD), mepyramine maleate, and tryptamine hydrochloride were used and weights given are those of the salts. Dried whole wasp venom apparatus was used for reference as a source of kinin (Jaques and Schachter, 1954).Preparations of rat's colon were suspended in a 25 ml. bath at 22-24°C. in an oxygenated Ringer solution containing: NaCl, 0.9%; KC1, 0.04%.; CaCl2, 0.003%; NaHCO3, 0.015%; glucose, 0.1%, as described by Gaddum, Peart, and Vogt (1949). For rat's uterus the temperature was adjusted to 290 C. and the concentration of calcium in the Ringer solution doubled. For guineapig's ileum a temperature of 35-370 C. was used and the Ringer adjusted to contain 0.024% CaC12, 0.05% NaHCO8 and 0.0005% MgCI2 (Feldberg, 1951). To antagonize ACh on all these preparations, 24 ng./ml. atropine, and to antagonize histamine on the guineapig's ileum, -80 ng./ml. mepyramine, were added to the Ringer solution. For most preparations of the uterus, young rats received on the previous day 20 pg. stilboestrol in oil by the intramuscular route. This pretreatment was omitted before experiments on a possible fourth substance in nettle sting.In preparing extracts for chromatography, leaf and stalk of nettle were extracted with acetone in a chill room at 4°C. and the extract concentrated by evaporation at this temperature for 3 days. Unidirectional descending paper chromatograms were run on Whatman No. 1 paper at 40 C. for 18 hr., using as solvent n-butanol-acetic acid (10 to 1) saturated with water. 1% p-Dimethylaminobenzaldehyde (Ehrlich's reagent) in aqueous n-butanol containing 0.5% HCO was used as developer. RESULTSComparison of Third Sub...