Cannabidiol and its pharmacokinetic interaction with delta1-tetrahydrocannabinol.

Co-administration of cannabidiol with delta1-tetrahydrocannabinol was found to have no effect on the rate of disappearance of delta1-tetrahydrocannabinol from the blood of rats. The implications of this finding are discussed.     

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.     

Effect of acute administration of delta 1-tetrahydrocannabinol on beta-endorphin levels in plasma and brain tissue of the rat

Acute treatment with delta 1-tetrahydrocannabinol (delta 1-THC) elevated the concentration of beta-endorphin-like immunoreactivity (beta-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 delta 1-THC, cannabidiol. In animals that had not been habituated to the injection procedure, placebo treatment induced a decrease in hippocampal beta-ELIR.     

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.     

Interactions ofΔ 11-tetrahydrocannabinol with cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentographywith cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentography

Summary Oral administration to man of 20 mg ¹1-tetrahydrocannabinol (THC) together with placebo or 40 mg cannabinol (CBN) or 40 mg cannabidiol (CBD) gave evidence of a possible limited interaction of THC with CBN but not with CBD as indicated by average plasma THC levels. Peak CBD and CBN concentrations were similar to that of THC, viz. about 5–8 ng/ml.Supported by the Swedish Medical Research Council and grant MH-00424 from the Veterans Administration.     

A possible chemical basis for the higher mutagenicity of marijuana smoke as compared to tobacco smoke.

The results of comparative anslyses of polynuclear aromatic hydrocarbons in marijuana and tobacco smoke indicate a considerably higher content of potential carcinogens in the former. A model experiment involving delta9-tetrahydrocannabinol suggests that the pyrolysis products of cannabinoids are major contributors to the polynuclear aromatic hydrocarbons.     

Changes in rat erythrocyte membrane induced by delta 1-tetrahydrocannabinol, scanning electron microscope study.

Although some biochemical dose-dependent effects are revealed in erythrocytes exposed to delta 1-tetrahydrocannabinol (THC) already at concentrations well below 10 microM, marked morphological changes of the erythrocyte membrane become evident, by scanning electron microscopy, only at THC concentrations beyond 15 microM. These observations provide evidence additional to previous chemical and physical studies, in which 15 microM is found to be a critical concentration with respect to the effects of TCH on erythrocyte membrane.     

Different effects of synthetic delta 9-tetrahydrocannabinol and cannabis extract on steroid metabolism in male rats

Repeated oral administration of cannabis extract as well as synthetic delta9-tetrahydrocannabinol to male rats produced significant changes in excretion of androgenic steroids and their metabolites as detectable in blood and urine. Cannabis extracts were found to be significantly more active than the mixtures containing same amounts of synthetic cannabinoids.     

(±)9, 10-dihydroxy-Δ 6a(10a)-tetrahydrocanabinol and (±)8, 9-dihydroxy-Δ 6a(10a)-tetrahydrocannabinol: 2 new cannabinoids fromCannabis sativa L.

Summary The structures of 2 new polyhydroxylated cannabinoids, (±)9, 10-dihydroxy- ^6a(10a)-tetrahydorcannabinol and (±)8, 9-dihydroxy- ^6a(10a)-tetrahydrocannabinol, obtained from a hexane extract of an IndianCannabis variant were determined by spectral means and correlation with cannabinol.Acknowledgments. Supported by contract No. HSM-42-70-109 from the National Institute on Drug Abuse and the Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi. The authors are grateful to Mrs Glenda Lewis (Research Institute) for running the gas chromatographic analyses and to Mr C. Versluis (Analytical Chemistry Laboratory, University Of Utrecht, The Netherlands) for recording an element list of both compounds.Cannabis Herbarium specimens are stored in the herbarium, Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677, USA.     

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.     

Cannabidiol and cannabinol in man

Résumé Le cannabidiol administré à dose de 100 mg par os et de 30 mg par injection i.v. fut inactif dans les sujets d'étude. Le cannabinol, à dose orale de 400 mg, le fut aussi. Ces constituants du cannabis ne contribuent donc pas à l'effet pharmacologique.     

A novel cannabinoid containing a 1,8-cineol moiety

Summary The synthesis of a novel cannabinoid containing a 1,8-cineol moiety (1) is described. It is much less biologically active than ¹-tetrahydrocannabinol.Acknowledgment. This work was supported by NIDA (grant No. DA-00574-01).     

Tolerance to,and symmetrical cross-tolerance between,cannabionol and 295-1295-1295-1

Summary Tolerance to, and symmetrical cross-tolerance between, cannabinol and ⁹-tetrahydrocannabinnol (THC) occurs in rabbits which uniquely exhibit behavioral convulsions with THC.This research was supported by funds (grant No.DA01448) and cannabinoids from the National Institute on Drug Abuse.     

Interaction between delta-6-tetrahydrocannabinol (delta-6-THC) and lithium at the blood brain barrier in rats

Summary Neither the acute nor the chronic i.p. administration of delta-6-tetrahydrocannabinol affected the passage of lithium from blood to brain in normal rats.     

Infusion of a novel peptide, PHI, in man. Pharmacokinetics and effect on gastric secretion

PHI, infused in man, achieved plateau plasma levels of 297 pmoles/1. The plasma half life was 3.1 min, metabolic clearance rate was 16.4 ml/kg/min and estimated volume of distribution was 73.2 ml/kg. No subjective side effects were noted during the infusion and there was no significant alteration in submaximal pentagastrin stimulated gastric acid or pepsin secretion.     

Evolution of testosterone metabolism during neonatal life in the guinea pig]

The neonatal period is characterized in the male Guinea-Pig by a steady increase in the metabolic clearance rate of testosterone and by a decrease in the conversion rate of testosterone to androstenedione. The transient rise in testosterone production rate on day 3 is concomitant with the neonatal peak in plasma testosterone.     

Effect of transmembrane potential on noradrenaline transport in chromaffin granules]

Imposing a transmembrane potential positive with respect to the medium on chromaffin granule ghosts increased the initial rate of the delta pH-induced uptake of noradrenaline, whereas imposing a negative potential decreased this rate. The increase of the uptake rate was proportional to the potential. The ATP-induced uptake of noradrenaline was also sensitive to the potential since imposing a transient negative potential onto the positive potential generated by the membrane ATPase induced a latency in this transport.     

Sea urchin elongation factor 1δ (EF1δ) and evidence for cell cycle-directed localization changes of a sub-fraction of the protein at M phase

Eukaryotic elongation factor 1 (eEF1) is a translational multimolecular complex reported in higher eukaryotes to be a target of CDK1/cyclin B, the universal regulator of M phase, but whose role in the cell cycle remains to be determined. A specific polyclonal antibody was produced and used to characterize the delta subunit of sea urchin elongation factor 1 (SgEF1) in early embryos, a powerful model for investigating cell cycle regulation. The SgEF1 protein was present in unfertilized eggs as two isoforms of 35 and 37 kDa, issued from two different mRNAs. The two canonical eEF1 partners, eEF1 and eEF1, were shown to co-immunoprecipitate with the SgEF1 isoforms. Both isoforms were associated in a macromolecular complex, which resolved upon gel filtration chromatography at a molecular weight > 400 kDa, suggesting association with other yet unidentified partners. After fertilization, the amount as well as the ratio of both SgEF1 isoforms remained constant during the first cell division as judged by Western blotting. Immunofluorescence analysis showed that a pool of the protein concentrated as a ring at the embryo nuclear location around the period of nuclear envelope breakdown and was visualized later as two large spheres around the mitotic spindle poles. Thus, the eEF1 protein shows cell cycle-specific localization changes in sea urchin embryos.Received 27 May 2003; received after revision 1 July 2003; accepted 4 July 2003     

The toxicity of twoBacillus thuringiensis δ-endotoxins to gypsy moth larvae is inversely related to the affinity of binding sites on midgut brush border membranes for the toxins

Summary The-endotoxin fromBacillus thuringiensis subspecieskurstaki strain HD1-9 is almost 400 times more potent than the-endotoxin from strain HD-73 as a gypsy moth larvicide. The two-endotoxins compete for a high-affinity binding site on the brush border membrane of larval gypsy moth midguts. The affinity for the-endotoxin from strain HD-73 is much greater than the affinity for the-endotoxin from strain HD1-9.     

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.