The long term objective of this consortium proposal is to provide a multi-disciplinary evaluation of the maternal and fetal effects of repetitive inhalation of marijuana smoke during the latter third of pregnancy. Results to date show that marijuana smoke exposure decreases the efficiency of gas exchange across the lung and placenta, shortens the duration of gestation, and drecreases the rate of fetal growth with accelerated functional maturation. We now propose to test the following hypotheses: First, that the magnitude of effect of marijuana smoke exposure is a function of the gestational age of the fetus at the time of first exposure; and second, that the magnitude of effect is a function of the dose and frequency of marijuana exposure.
The specific aim i s to comare the effects of continuous (daily) versus intermittent (every 3rd day) marijuana smoke exposure at two gestational ages on a variety of hemodynamic, metabolic, neurobehavioral and endocrine parameters. The proposed experiments can only be fulfilled with the use of the chronically-instrumented pregnant sheep model. The proposal's main strength lies in a uniform experimental design and dosing regimen, thus allowing simultaneous comparative data accrural in multiple areas for analysis. Maternal and fetal plasma THC levels and materal respiratory response will be used for standardizing the results from the different laboratories. In addition, the research plan employs an inhalational route of administration with a dosing regimen designed to mimic human patterns of abuse, and utilizes a well-accepted animal model which allows detailed evaluation of fetal effects by investigators thoroughly trained in its use. This consortium proposal should provide badly needed infomation in an area of societal concern.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003722-05
Application #
3208326
Study Section
Special Emphasis Panel (SRCD (12))
Project Start
1985-02-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1992-06-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Szeto, H H (1993) Kinetics of drug transfer to the fetus. Clin Obstet Gynecol 36:246-54
Szeto, H H; Cheng, P Y; Decena, J A et al. (1992) Developmental changes in continuity and stability of breathing in the fetal lamb. Am J Physiol 262:R452-8
Szeto, H H (1992) Behavioral states and their ontogeny: animal studies. Semin Perinatol 16:211-6
Szeto, H H; Wu, D L; Cheng, Y et al. (1992) Maternal marijuana smoking alters respiratory timing in the fetal lamb. Pharmacol Biochem Behav 43:1227-31
Szeto, H H; Cheng, P Y; Decena, J A et al. (1992) Fractal properties in fetal breathing dynamics. Am J Physiol 263:R141-7
Szeto, H H; Wu, D L; Decena, J A et al. (1991) Effects of single and repeated marijuana smoke exposure on fetal EEG. Pharmacol Biochem Behav 40:97-101
Szeto, H H (1990) Spectral edge frequency as a simple quantitative measure of the maturation of electrocortical activity. Pediatr Res 27:289-92
Clapp 3rd, J F; Keve, T M; Vial, C et al. (1988) Ovine placental perfusion balance: effect of marijuana smoke. Am J Obstet Gynecol 159:1430-4
Clapp 3rd, J F; Wesley, M; Cooke, R et al. (1987) The effects of marijuana smoke on gas exchange in ovine pregnancy. Alcohol Drug Res 7:85-92
Abrams, R M; Cook, C E; Davis, K H et al. (1985) Plasma delta-9-tetrahydrocannabinol in pregnant sheep and fetus after inhalation of smoke from a marijuana cigarette. Alcohol Drug Res 6:361-9