J.J. Ghosh

Effect of treatment with cannabis extract on the water and glycogen contents of the uterus in normal and estradiol-treated prepubertal rats.

Abstract Studies were carried out on the effects of administering cannabis extract on the water and glycogen content of uterine tissues of prepubertal rats, pretreated (14 and 40 hr) with estradiol benzoate. Cannabis extract reduced the total water and glycogen content of the uterine tissues in control as well as in estradiol-treated rats. The decrease in water content caused by cannabis extract administration was more prominent in the 14-hr than in the 40-hr estradiol-treated group. In the case of glycogen content, however, cannabis extract inhibited the estradiol-induced increase both in the 14- and 40-hr hormone-treated groups. The results indicate that cannabis extract may exert some antiestrogenic effect.

In vivo and in vitro effects of Δ9-tetrahydrocannabinol on rat liver microsomal drug-metabolizing enzymes☆

Abstract The in vivo and in vitro effects of Δ9-tetrahydrocannabinol (Δ9-THC) on rat liver microsomal dimethylaniline-N-demethylase, p-nitroanisole-O-demethylase and aniline hydroxylase activities were studied. In vivo acute administration of Δ9-THC produced a marked inhibitory effect of these drug-metabolizing enzyme activities at the higher dose (50 mg/kg) after 6 hr of ip injection. The inhibition was of mixed type for the two demethylases and noncompetitive in case of aniline hydroxylase, whereas comparatively fewer inhibitory effects on these enzyme activities were observed at the lower dose (10 mg/kg). Chronic treatment with Δ9-THC for 21 days (10 mg/kg/day) competitively inhibited the N- and O-demethylase activities but had no inhibitory effect on aniline hydroxylase. Under in vitro conditions of drug treatment at doses of 2, 4, and 8 μg/mg of protein, two demethylase activities were found to be inhibited in a competitive manner whereas comparatively less and mixed type of inhibition was observed with aniline hydroxylase only at higher doses of the drug. These results suggest that Δ9-THC changes the conformation of the hepatic microsomal membrane in a characteristic way, and there exists a qualitative difference between the two substrate-binding sites of the microsomal membrane regarding their interaction with a highly lipophilic drug like Δ9-THC.

Delta-9-tetrahydrocannabinol: its effect on hypothalamo-pituitary system in male rats.

Subcutaneous administration of delta-9-tetrahydrocannabinol (delta 9-THC) in adult male rats caused a decrease in serum luteinizing hormone (LH) levels with unchanged serum prolactin, pituitary LH and pituitary prolactin content. Response of pituitary to in vitro gonadotropin releasing hormone (GnRH) remained unaltered while the response to in vivo GnRH treatment was markedly increased with the drug indicating the pituitary to be functionally normal. Differences in the in vitro and in vivo response could be due to the endogenous steroid levels. The hypothalamic LH-RH content concommitantly increased. Delta-9-tetrahydrocannabinol may inhibit the release of luteinizing hormone releasing hormone (LHRH).

Effect of citreoviridin, a toxin from Penicillium citreoviride NRRL 2579, on glycogen metabolism of rat brain

Effects of subcutaneous administration of 0·25, 0·50 and 0·75 ld50 doses of citreoviridin, isolated from Penicillium citreoviride NRRL 2579, on glycogen metabolism of rat brain are reported. Glycogen content and glycogen synthetase (EC 2.4.1.11) activity was reduced significantly (P < 0·001) in a dose-dependent manner in the tissues of intoxicated animals. On the other hand, the toxin produced no significant changes in glycogen phosphorylase (EC 2.4.1.1) and glucose-6-phosphatase (EC 3.1.3.9) activities of brain.

Action of Δ9-tetrahydrocannabinol on membrane-bound monoamine oxidase activity

Abstract In vivo administration (ip) of Δ 9 -tetrahydrocannabinol ( Δ 9 -THC) to adult rats under acute conditions (10 and 50 mg/kg) produced a dose-dependent stimulation of monoamine oxidase (MAO; monoamine: O 2 oxidoreductase (deaminating), EC 1.4.3.4) activity in blood platelets and in mitochondrial preparations of hypothalamus and heart. Chronic treatment (10 mg/kg/day for 15 consecutive days) produced a smaller stimulating effect on MAO activity of these tissues. In vitro treatment with Δ 9 -THC produced (1) a stimulatory effect in hypothalamic MAO up to a concentration of 4 μg/mg of protein, (2) an inhibitory effect on heart MAO, and (3) a slight though not insignificant inhibitory effect on platelet MAO. Kinetic studies of in vivo and in vitro Δ 9 -THC-treated enzyme (MAO) are discussed on the basis of K m and V max values obtained from Linewwaver-Burk plots. When KSCN, KNO 3 , and urea were used, they produced a significant inhibitory effect on MAO activity in all these tissues, even in the presence of Δ 9 -THC, indicating that a characteristic interaction between membrane-bound MAO and Δ 9 -THC can be disrupted by these chaotropic agents.

Interaction of Δ9-tetrahydrocannabinol with reserpine, phenobarbital, and LSD-25 on plasma and adrenal corticosterone

Δ 9 -Tetrahydrocannabinol ( Δ 9 -THC; 10 and 50 mg/kg) administered acutely produces significant hypersecretion of corticosterone. Phenobarbital (75 mg/kg) administration lowers the basal corticosterone concentrations and partially inhibits the corticosterone elevating effect of Δ 9 -THC (10 mg/kg). LSD-25 (50 μ g/kg) produces neither a stimulatory nor an inhibitory effect on Δ 9 -THC-induced changes and does not affect the corticosterone concentrations. Administration of reserpine (2.5 mg/kg) produces a significant elevation of corticosterone and an additive effect on the Δ 9 -THC (10 mg/kg)-induced changes upon simultaneous administration of the two drugs. No tolerance to the corticosterone elevating effect of Δ 9 -THC is obtained upon chronic administration (10 mg/kg/day for 21 days). Rats treated chronically with Δ 9 -THC respond to one single dose of the above drugs in a way similar to that observed in acute studies.

Influence of cannabis and delta-9-tetrahydrocannabinol on the biochemistry of the male reproductive organs

Abstract Studies have been made on the effect of repeated subcutaneous administration of cannabis extract and delta-9-tetrahydrocannabinol on the fructose and citric acid contents of male reproductive organs of prepubertal as well as adult albino rats. Results indicate that both the fructose and the citric acid contents of the male reproductive organs are reduced significantly by cannabis. The reduction further appears to be dose-related to the amount of THC being administered, in case of both young and adult rats. Thus the study corroborates the previously reported antitestosteronic action of the drug.

Δ9-Tetrahydrocannabinol-induced changes in brain ribosomes

Abstract The action of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) on the stability of rat brain cortex and hypothalamic ribosomes has been studied. Δ 9 -THC, both under in vivo and in vitro conditions, does not significantly affect the chemical composition and uv absorption characteristics of the brain cortex and hypothalamus. Studies with Δ 9 -THC reveal that: (a) at low doses (2 mg/kg under in vivo conditions; 0.2 and 0.5 mg/g of tissue slices under in vitro conditions) the ribosomal particles are less susceptible to breakdown and the ribosomal RNAs have a greater proportion of hydrogen-bonded structure than those of the corresponding control tissues; (b) at high doses (10 and 50 mg/kg under in vivo conditions; 1.0 and 5.0 mg/g of tissue slices under in vitro conditions) and under chronic treatment with Δ 9 -THC (10 mg/kg/day for 21 consecutive days) the ribosomal particles become more susceptible to breakdown with relcase of protein, RNA, and acid-soluble nuclcotides than do the ribosomes of the corresponding controls, and they have a smaller proportion of hydrogenbonded structure than the ribosomal RNAs of control brain cortex and hypothalamus. These differential effects of Δ 9 -THC, depending on the concentration and the condition of treatment of the brain ribosomes, may be ascribed to the difference in the degree and mode of hydrophobic interaction between the Δ 9 -THC molecule and the ribosomal components.

Effect of pre- and post-treatments with diazepam on the rat brain GABAergic system during anoxic stress and recovery

Anoxia induced by exposure to N(2) gas for 15, 30, 50 and 60 s showed appearance of varying degrees of restlessness, tremor and convulsive behaviour resulting in mortality of adult rats. Diazepam treatment in pre- and post-anoxic conditions (10 and 20 mg/kg, respectively) has been found to decrease the anoxia-induced mortality rate along with suppression of other abnormal behaviours. In anoxic rats an increase in glutamate (Glu) level was noted. There was no change in the activity of glutamic acid decarboxylase (GAD), but GABA-aminotransferase (GABA-T) activity decreased significantly. In diazepam-treated (pre- and post-anoxic) rats there was an increase in the GAD activity with concomitant increase in ?-aminobutyric acid (GABA) level. GABA-T activity as well as Glu level became normalized. Results indicate that diazepam treatment may have some protecting ability from anoxia-induced imbalance in rat brain glutamatergic and GABAergic functions.

Effect of cannabis extract on uterine glycogen metabolism in prepubertal rats under normal and estradiol-treated conditions.

Abstract Repeated administration of cannabis extract on two uterine glycogen metabolising enzymes, glycogen phosphorylase and glycogen synthetase in prepubertal rats, treated with or without estradiol benzoate reduces the glycogen content of uterus by increasing phosphorylase activity (both total and form a) and by decreasing glycogen synthetase activity. In estradiol treated rats, however, cannabis extract has been found to inhibit the estradiol-induced rise in type a phosphorylase activity, glycogen synthetase activity being inhibited as in the previous case. Hence reduction of glycogen content in uterus by cannabis extract in estradiol-treated rats appears to be primarily due to decreased synthesis. The results indicate the antiestrogenic effect of this drug at the level of uterine glycogen metabolizing enzymes.