Fetal disposition of delta 9-tetrahydrocannabinol (THC) during late pregnancy in the rhesus monkey.
Three late-term (Gestational Days 146-151) rhesus monkeys were given 0.3 mg/kg delta 9-tetrahydrocannabinol (THC) intravenously via the maternal radial vein to quantify the placental transfer and fetal disposition of THC, the major psychoactive component of marijuana. Simultaneous blood samples were obtained from a maternal uterine vein and an intraplacental artery at 0, 3, 15, 30, 45, 60, 90, 120, and 180 min after dosing using an intraplacental cannulation technique. Samples of fetal plasma, spleen, testis, lung, brain, liver, bile, kidney, adrenals, thymus, and placenta were obtained at 180 min postdose. Samples were analyzed for THC and a major metabolite, 11-nor-9-carboxy-THC (11-nor), by radioimmunoassay (RIA). Peak plasma THC values were obtained 3 and 15 min after dosing in the mother (1419 ng/ml) and fetus (83 ng/ml), respectively. By 3 hr, maternal and fetal plasma THC levels were equal (37 ng/ml). Maternal plasma was sampled beyond 180 min at 24, 48, 72, and 96 hr postdose, times at which THC and 11-nor concentrations were either near or at the lower limit of sensitivity for the RIA (2 ng/ml). While maternal plasma 11-nor levels peaked at 1 hr (44 ng/ml), almost no 11-nor was detected in fetal plasma (less than 5 ng/ml). Fetal tissue concentrations of THC were 53 +/- 6 ng/g (SE) for brain and 114 +/- 10 ng/g for liver, while 11-nor was undetectable in placenta, fetal liver, and fetal brain. These data demonstrate that THC rapidly crosses the placenta and enters the fetus. The lack of 11-nor in fetal plasma and tissues suggests that this metabolite does not readily cross the placenta and that the fetus does not readily metabolize THC to 11-nor at this stage of development. A portion of this data was presented at the 1985 meeting of The American Society of Primatologists and at the 1986 meeting of The Teratology Society.
Bailey
J R
JR
Cunny
H C
HC
Paule
M G
MG
Slikker
W
W
D000818:Animals; D013759:Dronabinol / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008253:Macaca mulatta; D008431:Maternal-Fetal Exchange; D011247:Pregnancy
C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol