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.     

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.     

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.     

Transport of the synthetic peptide DSIP through the blood-brain barrier in rabbit

The synthetic delta sleep inducing peptide (DSIP) passes the blood-brain barrier, since i.v. injection in free moving rabbits (30 nmoles/kg) significantly increases the cortical delta activity and decreases the motor activity during 5 h.     

Transport of the synthetic peptide DSIP through the blood-brain barrier in rabbit

Summary The synthetic delta sleep inducing peptide (DSIP) passes the blood-brain barrier, since i.v. injection in free moving rabbits (30 nmoles/kg) significantly increases the cortical delta activity and decreases the motor activity during 5 h.Acknowledgment. This work was supported by grants from the Swiss National Science Foundation (Nos 3.871-72, 3.525.75, 3.443.074, 3.780.076), Fonds für Lehre und Forschung der Universität Basel, Merck Sharp and Dohme (USA), Ciba-Stiftung Basel.     

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     

Increased ALA dehydratase activity and spleen weight in lead-intoxicated rats. A consequence of increased blood cell destruction

Lead was given in the diet (1%) to rats from birth and at different times the animals were studies for delta amino levulinic acid dehydratase (ALAD) activity, spleen weight, 59Fe incorporation in erythrocytes and 51Cr-labeled erythrocytes survival. The increased ALAD and spleen weight found after lead treatment is explained as a consequence of a shortened survival, which results in a younger age of circulating erythrocytes with higher ALAD activity.     

The free radical oxidation of the tetrahydrocannabinols

Summary The free radical oxidation of ¹ and ⁶-tetrahydrocannabinol has been examined by spin trapping techniques and intermediates that would lead to cannabinol have been trapped. The 1st step in the oxidation of ¹-THC involves the removal of 3-H, while for ⁶-THC, either 2-H or 5-H. Intermediates were isolated which could be pyrolysed to the diene and cannabinol.     

The synthesis of a peptide having the structure attributed to a sound habituating material.

A peptide isolated from rats habituated to a sound stimulus has been given the structure (see article) Glu-Ala-Gly-Tyr-Ser-Lys-OH. A synthesis of this compound afforded a product that different from the natural material on the basis of chromatographic and physiological comparisons. The proposed sequence must therefore be in error.     

Human growth hormone in urine: development of an ultrasensitive radiometric assay

An immunoradiometric assay for human growth hormone (HGH) has been developed which has a detection limit of 1 ng/l and can measure HGH in unextracted urine from normal children and adults. The assay is based on a two-step procedure, using a solid-phase goat-anti-HGH immunosorbent for immunoextraction and [125I]-labeled monoclonal HGH-antibody for detection and quantification. The assay is not affected by urea, NaCl or changes of pH from 5-8. The mean urine HGH concentration in normal children is 6.78 +/- 7.6 (SD) pg/ml, in patients with HGH-deficiency 1.3 +/- 0.9 pg/ml which increases to 11.7 +/- 13.4 pg/ml on the day of growth hormone injection.     

Muscular dystrophy in adult mice chronically treated with Δ9- THC at behavioural doses

Summary After chronic treatment with ₉-THC at behavioural doses, a muscular dystrophy was demonstrated in adult mice, on the basis of histological and biochemical data and of functional tests on muscle.Grant of the Italian Ministry of Health, Service of Social Medicine, and of C. N. R.     

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.     

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.     

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.     

Characteristics of the partial derivative of hemoglobin saturation with respect ot oxygen pressure : delta S 02/delta P 02]

The first (delta S/delta P) and second (delta 2S/delta [H+] delta P) partial derivatives of hemoglobin saturation with respect to oxygen pressure and [H+] were numerically calculated for the blood of non-smoking young adult at different pH, PCO2 and [2.3-DPG]. Their functional value in respiratory physiology was stressed.     

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.     

Increased ALA dehydratase activity and spleen weight in lead-intoxicated rats. A consequence of increased blood cell destruction

Summary Lead was given in the diet (1%) to rats from birth and at different times the animals were studied for delta amino levulinic acid dehydratase (ALAD) activity, spleen weight,⁵⁹Fe incorporation in erythrocytes and⁵¹Cr-labeled erythrocytes survival. The increased ALAD and spleen weight found after lead treatment is explained as a consequence of a shortened survival, which results in a younger age of circulating erythrocytes with higher ALAD activity.Supported by Contract No. 140-76-12 ENV. B. of the E. C. Environmental Research Program.     

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.     

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.