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.
