Abstract
The effects of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) on the synthesis and degradation of hepatic microsomal cytochrome P-450 were studied in mice. Cannabinoids used (10, 50 and 100 mg/kg, i.p.) did not affect δ-aminolevulinic acid synthetase activity in the liver. Δ9-THC-treatment (10, 50 and 100 mg/kg, i.p.) markedly stimulated heme oxygenase activity in hepatic 18000 x g supernatant fractions in a dosedependent manner, whereas CBD-treatment was without effect. In vitro experiments, CBD and Δ9-THC (40 to 160 μM) markedly inhibited nicotinamide adenine dinucleotide phosphate (NADPH)-induced lipid peroxidation in hepatic microsomes. When CBD was incubated with the hepatic microsomes in the presence of an NADPH-generating system, cytochrome P-450 content decreased significantly. However, Δ9-THC showed no effects in similar experiments. The rate of decrease in the cytochrome P-450 content using CBD (160 μM) was 0.212 nmol/mg protein/20 min in microsomes from control mice. This value increased significantly in microsomes from phenobarbital-treated mice (0.792 nmol/mg protein/20 min) but not in those from 3-methylcholanthrene-treated mice (0.190 nmol/mg protein/20 min). The metabolic rate (per nmol cytochrome P-450) of CBD was also increased significantly by phenobarbital-treatment but not by 3-methylcholanthrene-treatment. These results suggest that CBD metabolites rather than CBD itself, play some role in the decreasing effect on cytochrome P-450 content in the hepatic microsomes in vitro, and that the microsomal formation of reactive metabolite of CBD is increased by phenobarbital-treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 39-45 |
| Number of pages | 7 |
| Journal | Journal of Pharmacobio-Dynamics |
| Volume | 9 |
| Issue number | 1 |
| Publication status | Published - 1986 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Effects of two cannabinoids on hepatic microsomal cytochrome P-450. / Watanabe, K.; Hamajima, K.; Narimatsu, S.; Yamamoto, I.; Yoshimura, H.
In: Journal of Pharmacobio-Dynamics, Vol. 9, No. 1, 1986, p. 39-45.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of two cannabinoids on hepatic microsomal cytochrome P-450
AU - Watanabe, K.
AU - Hamajima, K.
AU - Narimatsu, S.
AU - Yamamoto, I.
AU - Yoshimura, H.
PY - 1986
Y1 - 1986
N2 - The effects of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) on the synthesis and degradation of hepatic microsomal cytochrome P-450 were studied in mice. Cannabinoids used (10, 50 and 100 mg/kg, i.p.) did not affect δ-aminolevulinic acid synthetase activity in the liver. Δ9-THC-treatment (10, 50 and 100 mg/kg, i.p.) markedly stimulated heme oxygenase activity in hepatic 18000 x g supernatant fractions in a dosedependent manner, whereas CBD-treatment was without effect. In vitro experiments, CBD and Δ9-THC (40 to 160 μM) markedly inhibited nicotinamide adenine dinucleotide phosphate (NADPH)-induced lipid peroxidation in hepatic microsomes. When CBD was incubated with the hepatic microsomes in the presence of an NADPH-generating system, cytochrome P-450 content decreased significantly. However, Δ9-THC showed no effects in similar experiments. The rate of decrease in the cytochrome P-450 content using CBD (160 μM) was 0.212 nmol/mg protein/20 min in microsomes from control mice. This value increased significantly in microsomes from phenobarbital-treated mice (0.792 nmol/mg protein/20 min) but not in those from 3-methylcholanthrene-treated mice (0.190 nmol/mg protein/20 min). The metabolic rate (per nmol cytochrome P-450) of CBD was also increased significantly by phenobarbital-treatment but not by 3-methylcholanthrene-treatment. These results suggest that CBD metabolites rather than CBD itself, play some role in the decreasing effect on cytochrome P-450 content in the hepatic microsomes in vitro, and that the microsomal formation of reactive metabolite of CBD is increased by phenobarbital-treatment.
AB - The effects of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) on the synthesis and degradation of hepatic microsomal cytochrome P-450 were studied in mice. Cannabinoids used (10, 50 and 100 mg/kg, i.p.) did not affect δ-aminolevulinic acid synthetase activity in the liver. Δ9-THC-treatment (10, 50 and 100 mg/kg, i.p.) markedly stimulated heme oxygenase activity in hepatic 18000 x g supernatant fractions in a dosedependent manner, whereas CBD-treatment was without effect. In vitro experiments, CBD and Δ9-THC (40 to 160 μM) markedly inhibited nicotinamide adenine dinucleotide phosphate (NADPH)-induced lipid peroxidation in hepatic microsomes. When CBD was incubated with the hepatic microsomes in the presence of an NADPH-generating system, cytochrome P-450 content decreased significantly. However, Δ9-THC showed no effects in similar experiments. The rate of decrease in the cytochrome P-450 content using CBD (160 μM) was 0.212 nmol/mg protein/20 min in microsomes from control mice. This value increased significantly in microsomes from phenobarbital-treated mice (0.792 nmol/mg protein/20 min) but not in those from 3-methylcholanthrene-treated mice (0.190 nmol/mg protein/20 min). The metabolic rate (per nmol cytochrome P-450) of CBD was also increased significantly by phenobarbital-treatment but not by 3-methylcholanthrene-treatment. These results suggest that CBD metabolites rather than CBD itself, play some role in the decreasing effect on cytochrome P-450 content in the hepatic microsomes in vitro, and that the microsomal formation of reactive metabolite of CBD is increased by phenobarbital-treatment.
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M3 - Article
VL - 9
SP - 39
EP - 45
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 1
ER -