Abstract 1 in 5 women report cannabis use during pregnancy, with nausea cited as their primary motivation. Studies show that (-)-△9–tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis, causes fetal growth restriction, though the mechanisms are not well understood. Given the critical role of the placenta to transfer oxygen and nutrients from mother, to the fetus, any compromise in the development of fetal-placental circulation significantly affects maternal-fetal exchange and thereby, fetal growth. The goal of this study was to examine, in rats, the impact of maternal Δ9-THC exposure on fetal development, neonatal outcomes, and placental development. Dams received a daily intraperitoneal injection (i.p.) of vehicle control or Δ9-THC...

Abstract Cannabis consumption is increasing worldwide either for recreational or medical purposes. Its use during gestation is associated with negative pregnancy outcomes such as, intrauterine growth restriction, preterm birth, low birth weight, and increased risk of miscarriage, though the underlying molecular mechanisms are unknown. Cannabis sativa main psychoactive compound, Δ9-tetrahydrocannabinol (THC) is highly lipophilic, and as such, readily crosses the placenta. Consequently, THC may alter normal placental development and function. Here, we hypothesize alterations of placental steroidogenesis caused by THC exposure. The impact on placental estrogenic signaling was examined by studying THC effects upon the enzyme involved in estrogens production, aromatase and on estrogen receptor α...

Please use this link to access this publication. Abstract Objective To assess whether prenatal exposure to marijuana (THC) results in abnormal amplitude integrated encephalograms (aEEG). Design This was a (2018–2020) prospective cohort study of prenatally THC-exposed newborns. Maternal and Infant demographics, urine (UDS) and umbilical cord drug screening (UCDS) were recorded. A limited channel continuous aEEG was obtained within 48 h of birth. Statistical analysis included univariate, multivariate, and logistical regression. Results A total of 30 mother/infant dyads were enrolled. 60% (18/30) of neonates had abnormal aEEGs with sleep wake cycle (SWC) disturbances (p < 0.001). UCDS Carboxy-THC pg/g levels were similar in infants with abnormal [1758...

Abstract Elevated molecular stress in women is known to have negative impacts on the reproductive development of oocytes and the embryos prior to implantation. In recent years, the prevalence of cannabis use among women of reproductive age has risen due to its ability to relieve psychological stress and nausea, which are mediated by its psychoactive component, ∆-9-tetrahydrocannabinol (THC). Although cannabis is the most popular recreational drug of the 21st century, much is unknown about its influence on molecular stress in reproductive tissues. The current literature has demonstrated that THC causes dose- and time-dependent alterations in glucocorticoid signaling, which have the potential to compromise morphology,...

Abstract Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks (SD = 4.3)]. Voxelwise hippocampal...

Abstract Recent changes in legal status and public perception of cannabis have contributed to an increase use amongst women of reproductive age. Concurrently, there is inadequate evidence-based knowledge to guide clinical practice regarding cannabis and its effects on fertility and early embryonic development. This study aimed to evaluate the effects of the primary psychoactive component of cannabis, delta-9 tetrahydrocannabinol (THC), during oocyte maturation, and its impact on the developing embryo. Bovine oocytes were matured in vitro for 24 h under clinically relevant doses of THC mimicking plasma levels achieved after therapeutic (0.032 μM) and recreational (0.32 and 3.2 μM) cannabis use. THC-treated oocytes were assessed for...

Abstract Prenatal cannabis use is a significant problem and poses important health risks for the developing fetus. The molecular mechanisms underlying these changes are not fully elucidated but are thought to be attributed to delta-9-tetrahydrocannabinol (THC), the main bioactive constituent of cannabis. It has been reported that THC may target the mitochondria in several tissue types, including placental tissue and trophoblast cell lines, and alter their function. In the present study, in response to 48-h THC treatment of the human extravillous trophoblast cell line HTR8/SVneo, we demonstrate that cell proliferation and invasion are significantly reduced. We further demonstrate THC-treatment elevated levels of cellular reactive...

Abstract The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At...

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and...

Abstract Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of...