Tetrahydrocannabinol Administration Research Articles

Time course of the effects of naturally occurring cannabinoids on morphine abstinence syndrome

The effects of a single intraperitoneal injection (10 mg/kg) of Δ 9-tetrahydrocannabinol, Δ 8-tetrahydrocannabinol and 11-hydroxy- Δ 8-tetrahydrocannabinol on abstinence syndrome were investigated in mice rendered dependent on morphine by pellet implantation. In morphine dependent mice from which the pellets had been removed, δ 9-tetrahydrocannabinol inhibited the naloxone-precipitated jumping response as evidenced by an increase in the ED 5 0 of naloxone. This inhibition was evident for 24 hr, the most pronounced effect being produced between two to four hr after Δ 9-tetrahydrocannabinol administration. Withdrawal defecation was also inhibited for two hours. Similarly, in mice from which pellets were not removed, Δ 9-tetrahydrocannabinol suppressed the jumping response; however, the intensity of effect was less than when the pellets were removed. Δ 8-Tetrahydrocannabinol and 11-hydroxy- Δ 8-tetrahydrocannabinol were not effective in suppressing morphine abstinence syndrome two hr following their administration. The suppression of jumping response was specific, since, the vertical jumping behavior induced by coadministration of amphetamine and ℓ-dopa was not affected by cannabinoids. These results demonstrate that single injection of Δ 9-tetrahydrocannabinol is effective in controlling morphine abstinence syndrome for 24 hr, and that the drugs related to cannabinoids may show promise in narcotic detoxification.

Effects of Δ 9-tetrahydrocannabinol administration on marker proteins of rat testicular cells

The effects of chronic administration of 2 mg Δ 9-tetrahydrocannabinol per kg body weight upon rat testicular cell function was examined by use of selected testicular cell marker proteins. γ-Glutamyl transpeptidase was used as a marker of Sertoli cell plasma membranes; sorbitol dehydrogenase was used as a marker of pachytene spermatocytes. The interstitial cells were marked by cytochrome P-450, a microsomal component, and β-glucuronidase, a lysosomal component. The results of this study show a rapid reduction in microsomal P-450 content following 2 days of tetrahydrocannabinol administration. In addition, γ-glutamyl transpeptidase was significantly reduced at 2 days and continued to decline to day 9. β-Glucuronidase and sorbitol dehydrogenase exhibited no significant change over the course of the experiment. It is suggested that the reduction of testosterone synthesis in testes of tetrahydrocannabinol treated rats may be the result of a reduction in P-450 content.

Effect of Δ 9-tetrahydrocannabinol administration on hepatic functions

The effects of single (10 and 50 mg/kg) and chronic (10 mg/kg/day for 21 days) i.p. administration of Δ 9-tetrahydrocannabinol (Δ 9-THC) on hepatic functions of rat were studied at cellular and subcellular levels. After chronic administration, (a) protein, RNA, phospholipid, cholesterol contents of liver microsomal fraction and microsomal Gl-6-Pase and Mg +2-ATPase activities increased significantly, (b) microsomal lipid peroxidation value decreased and (c) GOT and GPT activities of liver and serum and hepatic triglyceride contents remained unchanged. Most of the parameters studied were unaffected after single administration of the drug excepting a decrease in microsomal lipid peroxidation and increase in Mg +2-ATPase activity. No apparent harmful effect of the drug on hepatic functions is obvious from the present study.

Tetrahydrocannabinol (THC): Metabolism and subjective effects

C-14-labeled delta-9-tetrahydrocannabinol (delta-9-THC) was administered in spiked cigarettes to nine experienced marijuana smokers. Blood samples obtained by repeated venipuncture showed that the subjects' subjective estimates of being “high” appeared to parallel the blood concentration of THC metabolites at least as closely as the blood concentration of THC itself. After 30 minutes, subjective effects declined less rapidly than either THC or its metabolites. Substantial inter-individual consistency in THC concentrations was found, suggesting that administration of THC in cigarettes under standardized smoking conditions can produce reliable blood concentrations of THC. A second session was run with the same subjects, this time omitting venipuncture, and using unlabeled THC. Significant differences between the effects of initial doses of THC under stress and no-stress conditions appeared in the detailed subjective effects inventories provided by subjects.

Effects of high dosage delta‐9‐tetrahydrocannabinol on sleep patterns in man

Electroencephalographic readings and eye movement were recorded in experienced marijuana users under placebo and tetrahydrocannabinol (THC). Four subjects were studied for 3 baseline nights, 3 nights under initial dosage of 70 mg/day, the last 3 nights of a 2-wk period of 210 mg/day, and the first 3 nights of withdrawal. Three other subjects were studied only during the latter 2 conditions. Administration of THC significantly reduced eye movement activity during sleep with rapid eye movements (REM) and, to a lesser extent, the duration of REM itself. Withdrawal led to increases above baseline in both measures but the "rebound" effect was greater for eye movement. Stage 4 sleep tended to increase on drug, but this effect was not statistically significant. On withdrawal, stage 4 sleep decreased significantly; this change was marked only on the first withdrawal night. The functional or biological significance of these changes is unclear. Nevertheless, these are the most marked effects of THC on brain electrical activity demonstrated thus far. Since its pattern of effects on sleep appears unique to THC, this drug may prove to be a valuable tool in the elucidation of the pharmacology of sleep. Possible relations between effects on sleep pattern and on behavior are discussed.

Reduction in number of nuclear membrane-attached ribosomes in infant rat brain following acute Δ 9-tetrahydrocannabinol administration

Reduction in number of nuclear membrane-attached ribosomes in infant rat brain following acute Δ 9-tetrahydrocannabinol administration