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Δ1-Tetrahydrocannabinol (Δ1-THC, Ia) was oxidized with selenium dioxide to yield 7-hydroxy-(VI), 6α-hydroxy-(VIIa), 6β-hydroxy-(VIIIa) and 6-oxo-Δ1-THC (IX) together with cannabinol (CBN, III), 7-hydroxy-(X), 6-hydroxy-(XI) and 7-oxo-CBN (XII). Δ6-THC (IIa) was transformed merely to 7-hydroxy-(IVa) and 7-oxo-Δ6-THC (Va) in a similar manner. Individual products isolated are well defined mainly on the spectroscopic evidences. The oxidation of Ia favors the endocyclic allyl methylene rather than the exocyclic allyl methyl while the reverse is the case with IIa. Such a sharp contrast shown in their reactivities as mentioned above must be interpreted in terms of the steric interference at the reactive center.

A rapid and sensitive method for determination of morphine in human urine using gas chromatography is described. The method involves charcoal absorption and solvent extraction of morphine followed by gas chromatographic analysis of the trimethylsilyl derivative. It is possible to detect morphine by this method more than 96 hrs after injection.

Using Yanagita's activity-level counter, effects of morphine administration upon the spontaneous activities of rats under various conditions were studied. And the following facts were elucidated;1. It was shown numerically that the more the size of the dose was large and the more the duration of morphine repetition was long, the faster and the stronger their spontaneous activities became.2. Such changes of the spontaneous activities of rats due to the repeated administration of morphine can be regarded as one the signs of tolerance.3. The changes of the spontaneous activities of rats or some sorts of tolerance occur as fast as the appearance of physical dependence.4. The mechanisms by which rats become hyperactive by the repeated administration of morphine may be explained chiefly by the development of tolerance to the sedative action of morphine and by the absence of tolerance to the excitatory action of the drug. However, the extraordinary increases recognized by the long term repetition of morphine request us further studies.5. As far as slow morphinization of rats is adopted, the abstinent phenomenon of the morphinized rats is sedation.6. The disappearance of tolerance after the cessation of morphine administration occurs very late, far later than the disappearance of abstinent phenomenon.7. Frequent administrations of nalorphine to the morphinized rats can not shorten the duration of tolerance retention after the cessation of the medication.

Increases both in spontaneous locomotor activity and in body weight were observed after the administration of morphine-HCl (100 mg/kg, i. p.) to tolerant rats. These signs were inhibited by pretreatment of the morphine-tolerant rats with cholinergic antagonists; the inhibition by scopolamine was greater than that by methscopolamine or atropine. These results suggest that both central and peripheral cholinergic mechanisms participate in the increases both in spontaneous locomotor activity and in body weight of tolerant rats after morphine administration.