Hashish VI1: Conversion of (-)-Δ 1(6)-Tetrahydrocannabinol to (-)-Δ 1(7)-Tetrahydrocannabinol. Stability of (-)-Δ 1 and (-)-Δ 1(6)-Tetrahydrocannabinols

Zusammenfassung Die Synthese von (—)-¹⁽⁷⁾-Tetrahydrocannabinol (THC) auf (—)-¹⁽⁶⁾ wird beschrieben. Das Hauptprodukt der oxidativen Zerstörung von (—)-¹-THC ist Cannabinol. Beschleunigte Versuche der Luftoxidation von (—)-¹-THC und (—)-¹⁽⁶⁾-THC haben gezeigt, dass das letztere beständiger ist. Dieser Unterschied kann mit der Reaktivität des C₃-benzylisch-allylischen Wasserstoffes in (—)-¹-THC erklärt werden.     

Hashish: Synthesis of Δ9-tetrahydrocannabinol (THC), a metabolite ofΔ 9-THC1

Summary The synthesis of (±)-211-dihydroxy- ⁹-THC, a difunctionalized metabolite of ⁹-THC, is presented.Acknowledgment. This work was carried out with the support of NIDA Grant No. DA 00574. We are grateful to Mr. J. Coe for assistance with some of the experiments.     

Δ6-Tetrahydrocannabinol-7-oic acid,a urinary Δ6-THC metabolite: Isolation and synthesis

Zusammenfassung 7-Hydroxy- ⁶-tetrahydrocannabinol (7-Hydroxy- ⁶-THC), ein psychotomimetisch aktiver Metabolit des ⁶-THC, wird von Kaninchen in inaktive ⁶-THC-7 Säure metabolisiert. Die Synthese dieser Säure wird beschrieben.

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The work in Jerusalem was supported by the US National Institute of Mental Health and in Stockholm by the Swedish Medical Research Council.     

Effect of acute administration of Δ1-tetrahydrocannabinol on β-endorphin levels in plasma and brain tissue of the rat

Summary Acute treatment with ¹-tetrahydrocannabinol (¹-THC) elevated the concentration of -endorphin-like immunoreactivity (-ELIR) in plasma and in the hypothalamus, but not in the hippocampus of rats habituated to the injection procedure. These effects were not obtained with the psychotropically inert analog of (¹-THC), cannabidiol. In animals that had not been habituated to the injection procedure, placebo treatment induced a decrease in hippocampal -ELIR.The authors acknowledge the skillful technical assistance of Mrs Willeke Logtenberg.     

The partitioning ofΔ 1-tetrahydrocannabinol into erythrocyte membranes in vivo and its effect on membrane fluidity1into erythrocyte membranes in vivo and its effect on membrane fluidity1

Summary ¹-Tetrahydrocannabinol ( ¹-THC) has been quantified directly in erythrocyte membranes from drug-treated mice using gas chromatography/mass spectrometry. Concentrations of approximately 6 ng ¹-THC/mg membrane protein (10^–5 M) were found when effects of the drug on behavior were prevalent. At these concentrations the drug produced a decrease in membrane order as measured by ESR.This work was supported by grants from the Medical Research Council, the Wellcome Trust and the E. P. Abraham Cephalosporin Trust     

Decrease of serum alpha-tocopherol levels in rabbits after acute treatment withΔ 9-tetrahydrocannabinol

Summary The i.v. administration of 10 mg of ⁹-THC in rabbits produced, after 24 h, a 50% reduction of the initial values of serum alpha-tocopherol.Grant of the Italian Ministry of Health, Service of Social Medicine; thanks are due to Dr O. J. Braenden, Director, UN Narcotics Laboratory at Geneva, for the gift of pure ⁹-THC.     

Isotope effect studies on the dehydrogenation of Δ1-tetrahydrocannabinol in the rat

Summary Isotope effect studies on the metabolic dehydrogenation of ¹-tetrahydrocannabinol in rats are described and its is shown that this process is confined to a very short period following i.v. administration. The implications of this finding are discussed.The authors are grateful for generous fifts of³H-¹-THC from Dr S. Burstein (Worcester Foundation for Experimental Biology, Massachusetts), and of¹⁴C-¹-THC from the National Institute on Drug Abuse. The authors thank the staff of the Small Animal Unit, Wallaceville Research Centre for their cooperation, and the U.S. National Institute on Drug Abuse for their support.     

A comparison of the pharmacological activity in man of intravenously administered 1368-11368-11368-1, cannabinol,and cannabidiol

Resumen Se hizo un estudio comparativo de la actividad del ⁹-tetrahidrocannabinol, cannabinol, y cannabidiol en producir efectos similares a la marihuana cuando son inyectados i.v. a humanos. Estas substancias son los componentes predominantes de la marihuana o del hashish. Se encontro que a las dosis inyectados cannabidiol no tiene ninguna potencia, y que cannabinol es capaz de producir efectos tipicos de la marihuana, aunque a dosis varias veces mas grandes que las del ⁹-tetrahidrocannabinol.     

416-1416-1416-1416-2416-2416-2

Summary (–)-8-Hydroxymethyl-¹-tetrahydrocannabinol (THC)1, a novel analog of ¹, is shown to be as active as ¹ and twice as active as ¹ in the dog ataxia test.Acknowledgment. This work was supported by NIDA (Grant Nos. DA-00574-01 and DA-00490).     

Development of tolerance toΔ 9-THC in the frog

Résumé Après injections bi-journalières de ⁹-THC à des grenouilles, nous avons calculé la durée de la perte du réflexe de redressement. La tolérance au ⁹-THC fut évidente après la seconde injection et, après la troisième, aucun effect ne fut visible. Ceci suggère que la tolérance se développe par le ⁹-THC, et non par ses métabolites, puisque les grenouilles n'ont pas de système enzymatique d'hydroxylation.     

Wirkung von 6β-Methoxy-9β,10α-pregna-4,6-dien-3,20-dion

Summary 6-Methoxy-9,10 -pregna-4,6-diene-3,20-dione inhibites the ⁴-3-oxosteroid-5-reduction in microsomes and the ⁴-3-oxosteroid-5-reduction in the soluble fraction of male rat liver. The 3- and 3-hydroxysteroid dehydrogenase are not inhibited by this substance.

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Diese Arbeit wurde von der Firma Hoffmann-La Roche, Basel, unterstützt.     

10-Hydroxy-Δ2-decenoic acid in the honeybee(Apis mellifera)

Zusammenfassung Die Mandibulardrüsen der Honigbienen-Arbeiterinnen enthalten 10-Hydroxy-²-decensäure. Es wird angenommen, dass diese Drüsen die Quelle der im Weisel- und Arbeiterinnenlarvenfutter vorkommenden 10-Hydroxy-²-decensäure sind.     

Interaction of chloramphenicol and 181-1181-1181-1in barbital-anesthetized mice

Résumé L'augmentation de l'anesthésie produite par le barbital chez la souris traitée au ¹-tétrahydrocannabinol ( ¹-THC) à 10 ou 20 mg/kg par voie i.p. est accentuée d'une manière significative par le traitement préalable au chloramphénicol (CHPC) à 100 mg/kg, mais non pas par 50 mg/kg de ce composé injecté par voie i.p. Le CHPC seul n'a aucun effet. Le CHPC étant un inhibiteur des systèmes enzymatiques des microsomes hépatiques, on en a conclu que l'effet du ¹-THC sur le prolongement de la durée du sommeil au barbital est dû au composé parent plutôt qu'à l'un des produits de transformation biologique.     

Regulation ofL-valine absorption by opioids interacting withμ-receptors in rabbit ileum

In intact tissue, [d-Ala²,MePhe⁴, Gly-ol⁵] enkephalin (10^–5 M;-ligand), diminsihed short-circuit current (I_sc) and increased water, Na⁺ and Cl^– net fluxes in vitro under open circuit conditions; it also inhibitedL-valine absorption andL-valine-dependent variations of short-circuit current (I_{sc, val}). Naloxone (10^–6 M) antagonized these effects. In the absence of the muscularis and myenteric plexus this enkephalin or morphine (-ligand) reduced I_sc and I_{sc, val}. These enkephalin effects occurred at different times. Different concentrations of enkephalin were tested for their effects on I_{sc, val}. [d-Ala²,d-Leu⁵] enkephalin (mainly a -ligand) significantly decreased I_sc but not I_{sc, val}. The reduction ofL-valine absorption does not depend on the effects on basal ion transport. Interaction of opioids with-receptors located in the submucosal plexus and/or in the epithelial cell accounts for this reduction. This enkephalin effect seems to be at least partially under the control of the myenteric plexus.     

Open-field behavior and acquisition of discriminative response control in Δ9-THC tolerant rats

Résumé La tolérance de l'effet du 1- ⁹-tétrahydrocannabinol ( ⁹-THC) a été examinée par une méthode nouvelle. Les résultats obtenus permettent une interprétation de tolérance pharmacologique pour ⁹-THC.

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Numbering system according to IUPAC rules. The drug was generously supplied by Dr.T. Petrzilka, University of Zürich.     

Ein neues Verfahren zur Herstellung von 19-Norsteroiden

Summary The new methods for the production of 19-norsteroids described involve the conversion of 5-halogen-6-hydroxy-steroids into the corresponding 5-halogen-6:19-ethers either with lead tetraacetate or by the hypoiodite reaction^8,10. The 6:19-oxygen bridge is then opened reductively either directly or after oxidation of the 6:19-ethers to lactones or preferably after introduction of a ^4,6-3-oxo grouping. Acylolytic cleavage of the ⁴-3-oxo-6:19-ethers followed by alkaline hydrolysis gives ^4,6-3-oxo-19-hydroxy-steroids. The 19-hydroxycompounds formed are easily converted into 19-norsteroids by known methods.

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Über Steroide, 189. (vorläufige) Mitteilung; 188. Mitt. vgl.J. Kalvoda, J. Schmidlin, G. Anner undA. Wettstein, Exper.18, 398 (1962).     

Inhibition of human testicular glucose-6-phosphate dehydrogenase by unsaturated C19-steroids

Zusammenfassung Die Bebrütung einer gereinigten G-6-PDH aus menschlichem Testisgewebe mit 3-substituierten ⁴- oder ⁵-C₁₉-Steroiden zeigte, dass 3-Hydroxy-⁴-oder ⁵-androsten-17-on auch wirksame Inhibitoren der testikulären G-6-PDH darstellen. Zur gleichen Zeit konnten die früher gefundenen Zusammenhänge zwischen chemischer Struktur eines Steroids und seiner biologischen Aktivität im G-6-PDH-Hemmtest uneingeschränkt bestätigt werden.     

The distribution of some enzymes involved in the steroidogenesis of hen's ovary

Riassunto È stata studiata con metodi istochimici la distribuzione della ⁵-3-idrossisteroide deidrogenasi ( ⁵-3-HSDH) e delle 17-idrossisteroide deidrogenasi (17-HSDH), DPN- e TPN-dipendenti, nell'ovario di gallina ovulante. Mentre la ⁵-3-HSDH è presente in tutti i tessuti a secrezione steroide dell'ovario, la 17-HSDH è localizzata solo nelle cellule della granulosa.     

Microbiological oxidation of the pentyl side chain of cannabinoids

Summary Syncephalastrum racemosum ATCC 18192 andMycobacterium rhodochrous ATCC 19067 partially degrade the n-pentyl side chain of cannabidiol, cannabinol, ⁸-tetrahydrocannabinol and ⁹-tetrahydrocannabinol. Carboxylic acid and alcohol side chain derivatives are major metabolites.Acknowledgment. The authors wish to express their gratitude to Dr E. H. Fairchild for pmr and mass spectra, Dr R. L. Foltz for gc-ms analysis and to the National Institute on Drug Abuse for financial assistance in the form of a research grant.     

Cytogenetic effects of delta-9-tetrahydrocannabinol (Δ 9-THC) on hamster bone marrow

Summary Single s.c. injections of 10 or 1000 mg/kg of ⁹-THC did not induce discernable chromosomal damage but caused significant mitotic inhibition in the bone marrow of Syrian hamsters.Acknowledgments. The authors which to thank Mr R.H. Graham, Department of National Health and Welfare, Health Protection Branch, for the generous supply of ⁹-THC. This research was supported by a grant to Dr M.G. Joneja from the Department of National Health and Welfare.