Effects of acute and subacute cannabidiol treatment on hepatic drug metabolism

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Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Ingall, Glynnis Beth
Title Effects of acute and subacute cannabidiol treatment on hepatic drug metabolism
Date 1978-06
Description Cannabidiol (CBD) was administered both acutely and sub-acutely to mice, and the resulting effects on hexobarbital sleep time and on the hepatic microsomal drug-metabolizing system were assessed. Acutely administered CBD significantly prolonged hexobarbital sleep time, an effect that persisted for as long as 24 hr; but following subacute treatment, tolerance rapidly developed to the CBD effect. Brain hexobarbital concentration upon awakening v/as unchanged by either acute or subacute CBD treatment, which suggests that neither the acute effect of CBD on sleep time nor the tolerance that develops in subacutely treated animals is the result of a central interaction of the drug with the barbiturate. Acute CBD treatment increased the half-time of hexobarbital in the brain, evidence that the drug decreased the rate of hexobarbital metabolism. Tolerance was accompanied by a decrease in the elevated half-time of brain hexobarbital, suggesting that tolerance was a consequence of a return toward the normal rate of hexobarbital metabolism. Acutely administered CBD caused a 30 per cent depression in cytochrome P-450 concentration; the duration of the decline approxiniated the duration of CBD's prolongation effect on sleep time. Following subacute treatment, cytochrome P-450, total liver protein and microsomal protein concentrations were the same as the controls, but NADPH-cytochrome c reductase activity and liver weight increased by about 20 per cent; the latter increases did not represent a functionally significant induction of hexobarbital metabolism. The evidence suggests that the CBD-caused prolongation of barbiturate sleep time is the result of a decrease in the rate of barbiturate metabolism related to a decrease in cytochrome P-450 concentration. Tolerance to the effect is associated with a return to a normal metabolic rate and to normal cytochrome P-450 values.
Type Text
Publisher University of Utah
Subject Metabolism; Brain Hexobarbital
Subject MESH Liver; Cannabinoids; Cytochromes
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Effects of acute and subacute cannabidiol treatment on hepatic drug metabolism". Spencer S. Eccles Health Sciences Library. Print version of "Effects of acute and subacute cannabidiol treatment on hepatic drug metabolism". available at J. Willard Marriott Library Special Collection. RM 31.5 1978 I53.
Rights Management © Glynnis Beth Ingall.
Format Medium application/pdf
Format Extent 624,043 bytes
Identifier undthes,4425
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 624,076 bytes
ARK ark:/87278/s6vd717m
Setname ir_etd
ID 190816
Reference URL https://collections.lib.utah.edu/ark:/87278/s6vd717m