PROJECT SUMMARY
Cannabis use during pregnancy is increasing with its legalization in many states and the belief by many that it
is a safe and effective treatment for pregnancy-related nausea. This proposal investigates to what extent
prenatal maternal supplementation with phosphatidylcholine (PChol) mitigates the effects of prenatal cannabis
exposure on the fetus and subsequent child behavior. Higher maternal levels of choline have been shown to
improve brain development. Choline in the amniotic fluid activates fetal alpha7-nicotinic receptors, before
cerebral cholinergic innervation fully develops, late in gestation. Alpha7-nicotinic receptors and cannabinoid
CB1 receptors are expressed on the same cerebral interneurons. Choline activation promotes interneuron
development, whereas THC, by interfering with endogenous signaling, retards their development. Consistent
with this translational model, a preliminary clinical observational investigation found that mothers with higher
gestational choline levels have newborns with more normal fetal development of cerebral inhibition, even if
mothers continued moderate cannabis use during pregnancy despite clinical advice. The child’s subsequent
ability to pay attention is increased. We propose a randomized, double-blind, placebo-controlled trial of
phosphatidylcholine supplementation in 120 pregnant women who use cannabis during pregnancy. Pregnant
women will be randomly assigned to receive (1) 7200mg PChol, equivalent to 1028mg choline (Treatment
Group, n=60) or (2) corn oil placebo (Placebo Group, n=60). The first aim of this project tests the hypothesis
that maternal choline supplementation will interact with maternal cannabis use on the P50 auditory evoked
response inhibition, an electrophysiological marker of the development of inhibitory neurotransmission, one
month after birth. Aim 2 tests the hypothesis that maternal choline supplementation will interact with maternal
cannabis use to mitigate its adverse effects on offspring’s development of attention, temperament, and
cognitive behaviors. Prenatal cannabis use, assessed from mothers’ self-report and urine and serum
metabolite levels, returned pill count, estimates of choline intake from the mother’s recall of her diet, and
plasma levels of choline and its metabolites will be obtained at 14, 16, 22, 28, 34 and 40 weeks of gestation.
Cannabis use in the postnatal period and breast milk cannabinoid and choline levels will also be measured.
Neonate and infant hair will be analyzed for cannabinoids to detect 3rd trimester and postnatal exposure. The
two aims together will document the possible effectiveness of prenatal choline supplementation to protect the
fetus’s brain development from exposure to cannabis during gestation. The outcomes of this proposal could
have an innovative public health effect to protect the brain development of fetuses whose mothers continue to
use cannabis despite medical advice to abstain. These effects may result in decreased risk of mental problems
in the children.
