Document Detail

Alteration of delta 9-tetrahydrocannabinol-induced teratogenicity by stimulation and inhibition of its metabolism.
MedLine Citation:
PMID:  886474     Owner:  NLM     Status:  MEDLINE    
Treatment of pregnant mice with delta 9-tetrahydrocannabinol (THC) significantly increased the incidence of in utero deaths. SKF-525A pretreatment increased the incidence of THC-induced in utero deaths. THC also significantly reduced the body weight of surviving fetuses. Phenobarbital treatment antagonized THC-induced reduction of fetal body weight, but did not reduce resorption rate. Administration of THC, 50 or 200 mg/kg, did not induce fetal anomalies. However, both SKF-525A and phenobarbital treatment potentiated THC-induced cleft palates. SKF-525A treatment plus THC produced 36% cleft palates. Phenobarbital treatment plus THC produced 77% cleft palates. Pretreatments altered the level of tetrahydrocannabinol plus metabolites found in plasma, placenta, fetus and amnionic fluid. In general, SKF-525A increased levels and phenobarbital decreased levels. Two chemically reactive metabolites of THC are proposed, 9,10-epoxyhexahydrocannabinol and an 11-oxo derivative. SKF-525A pretreatment increased the concentration of both of these metabolites. Phenobarbital treatment increased the levels of the proposed 9,10-epoxyhexahydrocannabinol. Possible covalent binding of THC was observed. An active metabolite theory may apply to the teratogenic properties of THC.
R D Harbison; B Mantilla-Plata; D J Lubin
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  202     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1977 Aug 
Date Detail:
Created Date:  1977-09-22     Completed Date:  1977-09-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  455-65     Citation Subset:  IM    
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MeSH Terms
Amniotic Fluid / metabolism
Body Weight / drug effects
Cleft Palate / chemically induced
Drug Interactions
Fetal Death / chemically induced
Fetus / drug effects,  metabolism
Gestational Age
Maternal-Fetal Exchange
Phenobarbital / pharmacology
Placenta / metabolism
Proadifen / pharmacology
Teratogens / metabolism*
Tetrahydrocannabinol / blood,  metabolism,  pharmacology*
Reg. No./Substance:
0/Teratogens; 1972-08-3/Tetrahydrocannabinol; 302-33-0/Proadifen; 50-06-6/Phenobarbital

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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