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  • Endocrine System, Pregnancy
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Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study

Abstract Objective To assess the impact of fetal exposure to cannabis on adiposity and glucose-insulin traits in early life. Research Design and Methods We leveraged a subsample of 103 mother-child pairs from Healthy Start, an ethnically diverse Colorado-based cohort. Twelve cannabinoids/metabolites of cannabis (including Δ9-tetrahydrocannabinol and cannabidiol) were measured in maternal urine collected at ~27 weeks’ gestation. Fetal exposure to cannabis was dichotomized as exposed (any cannabinoid > limit of detection [LOD]) and not exposed (all cannabinoids < LOD). Fat mass and fat-free mass were measured via air displacement plethysmography at follow-up (mean age: 4.7 years). Glucose and insulin were obtained after an overnight fast. Generalized...
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Maternal cannabis use during pregnancy and maternal and neonatal outcomes: A retrospective cohort study

Please use this link to access this publication. Abstract Objective To examine the relationship between reported prenatal cannabis use and neonatal and maternal outcomes and whether the legalisation of cannabis in Canada affected the rates of reported use or the association with maternal and neonatal outcomes. Design Population-based retrospective cohort study. Setting Routinely collected data in a real-world setting. Population All women in the Canadian province of Nova Scotia with singleton births between 1 January 2004 and 30 June 2021. Methods The association between cannabis use and maternal and neonatal outcomes was examined using generalised linear models with inverse probability weighting. Main outcome measures...
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Long-term effects of prenatal cannabis exposure: Pathways to adolescent and adult outcomes

Please use this link to access this publication. Abstract With the increased prevalence, potency, and acceptability of cannabis use during pregnancy, it is important to understand the developmental effects of prenatal cannabis exposure (PCE). This review discusses methodological considerations for studies of PCE, including the assessment of exposures, covariates, and outcomes, and reviews findings from prospective, longitudinal studies of PCE. There is some evidence for associations between PCE and restricted growth at birth, but not for long-term effects on growth. PCE appears to have subtle yet enduring effects on memory and achievement in children and adolescents. Despite differences in sample demographics and measurement, there are remarkably consistent effects...
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Cannabinoids accumulate in mouse breast milk and differentially regulate lipid composition and lipid signaling molecules involved in infant development

Abstract Maternal cannabis use during lactation may expose developing infants to cannabinoids (CBs) such as ∆-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBs modulate lipid signaling molecules in the central nervous system in age- and cell-dependent ways, but their influence on the lipid composition of breast milk has yet to be established. This study investigates the effects of THC, CBD, or their combination on milk lipids by analyzing the stomach contents of CD1 mouse pups that have been nursed by dams injected with CBs on postnatal days (PND) 1 -10. Stomach contents were collected 2 hours after the last injection on PND10 and HPLC/MS/MS was used to...
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Intrauterine cannabis exposure and fetal and maternal blood flow: a case–control study

Abstract Introduction Cannabis consumption during pregnancy increases the risk of pregnancy and neonatal complications. Since the underlying mechanism is unknown, the purpose of this study is to evaluate the changes in maternal and fetal blood flow in pregnancies exposed to cannabis, Δ9-tetrahydrocannabinol (THC). Material and methods A case–control study between 2013 and 2020, included women with continued cannabis exposure during the pregnancies, defined by qualitative detection of THC in urine (Cannabis Group), and low-risk pregnancy women divided into tobacco smokers (Tobacco Group), and non-tobacco smokers (Control Group). We evaluated the association between cannabis consumption and maternal and fetal blood flow parameters measured by Doppler...
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Association of Cannabis Use With Nausea and Vomiting of Pregnancy

Please use this link to access publication Abstract Our objective was to evaluate whether cannabis use was associated with nausea and vomiting in early pregnancy. Participants from nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be) enrolled from October 2010 through September 2013 with a PUQE (Pregnancy-Unique Quantification of Emesis) questionnaire and an available stored urine sample from the first study visit (median gestational age 12 weeks) were included. Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH); positive results were confirmed with liquid chromatography tandem mass spectrometry. The primary outcome was moderate-to-severe nausea by the PUQE score. Overall, 9,250 participants were included, and 5.8%...
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Sex-dependent Effect of In-utero Exposure to Δ9-Tetrahydrocannabinol on Glucagon and Stathmin-2 in Adult Rat Offspring

Please use this link to access publication Abstract Objectives Administration of Δ9-tetrahydrocannabinol (Δ9-THC) to pregnant rats results in glucose intolerance, insulin resistance and reduced islet mass in female, but not male, offspring. The effects of Δ9-THC on other islet hormones is not known. One downstream target of the cannabinoid receptor, stathmin-2 (Stmn2), has recently been shown to suppress glucagon secretion, thereby suggesting Δ9-THC may also affect alpha-cell function. The aim of the present study was to determine the effects of in-utero Δ9-THC exposure on the profile of glucagon, insulin and Stmn2 in the rat offspring islet and serum. Methods Pregnant Wistar rat dams were injected with Δ9-THC (3 mg/kg per...
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EVIDENCE FOR DIFFERENTIAL EFFECTS OF Δ9-THC (Δ9-TETRAHYDROCANNABINOL) ON PRE- VERSUS POST-IMPLANTATION EMBRYONIC STEM CELLS

Abstract Objective Recreational marijuana use is becoming increasingly widespread. With potential implications for fertility and embryonic development, we set out to evaluate the impact of THC exposure on the pre- and post-implantation embryo through embryonic stem cell proliferation, mitochondrial function and metabolism. Materials and Methods Mouse embryonic stem cells (ESCs) can be differentiated into epiblast-like cells (EpiLCs) using known in vitro methods via growth factors and cytokines. ESCs recapitulate important features of pre-implantation stem cells; EpiLCs model post-implantation features. ESCs and EpiLCs were exposed to a range of Δ9-THC concentrations: 0-100μM over 48 hours. Cell proliferation and viability were assessed via Trypan blue and...
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Animal evidence considered in determination of cannabis smoke and Δ9-tetrahydrocannabinol as causing reproductive toxicity (developmental endpoint): Part III. Proposed neurodevelopmental mechanisms of action

Please use this link to access publication Abstract This review summarizes the most common potential pathways of neurodevelopmental toxicity due to perinatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) that lead to behavioral and other adverse outcomes (AOs). This is Part III in a set of reviews highlighting the animal-derived data considered by California's Developmental and Reproductive Toxicant Identification Committee (DARTIC) in 2019. The Hazard Identification Document (HID) provided to the DARTIC included a summary of human, whole animal, and mechanistic data on the neurodevelopmental toxicity of cannabis smoke and Δ9-THC. The literature search for mechanistic data has been updated through 2020. We focus on mechanistic pathways...
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Chronic prenatal delta-9-tetrahydrocannabinol exposure adversely impacts placental function and development in a rhesus macaque model

Abstract Cannabis use in pregnancy is associated with adverse perinatal outcomes, which are likely mediated by the placenta. However, the underlying mechanisms and specific vasoactive effects of cannabis on the placenta are unknown. Our objective was to determine the impact of chronic prenatal delta-tetrahydrocannabinol (THC, main psychoactive component of cannabis) exposure on placental function and development in a rhesus macaque model using advanced imaging. Animals were divided into two groups, control (CON, n = 5) and THC-exposed (THC, n = 5). THC-exposed animals received a THC edible daily pre-conception and throughout pregnancy. Animals underwent serial ultrasound and MRI at gestational days 85 (G85), G110, G135 and G155 (full...
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