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...

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...

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%...

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...

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...

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...

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...

Abstract As cannabis use during pregnancy increases, it is important to understand its effects on the developing fetus. Particularly, the long-term effects of its psychoactive component, delta-9-tetrahydrocannabinol (THC), on the offspring’s reproductive health are not fully understood. This study examined the impact of gestational THC exposure on the miRNA profile in adult rat ovaries and the possible consequences on ovarian health. Prenatal THC exposure resulted in the differential expression of 12 out of 420 evaluated miRNAs. From the differentially expressed miRNAs, miR-122-5p, which is highly conserved among species, was the only upregulated target and had the greatest fold change. The upregulation of miR-122-5p and...

Please use this link to access this publication Abstract Background Cannabis remains one of the most widely abused drugs during pregnancy. In utero exposure to its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), can result in long-term neuropsychiatric risk for the progeny. This study investigated epigenetic signatures underlying these enduring consequences. Methods Rat dams were exposed daily to THC (0.15 mg/kg) during pregnancy, and adult male offspring were examined for reward and depressive-like behavioral endophenotypes. Using unbiased sequencing approaches, we explored transcriptional and epigenetic profiles in the nucleus accumbens (NAc), a brain area central to reward and emotional processing. An in vitro CRISPR (clustered regularly interspaced short palindromic repeats) activation model coupled with RNA sequencing was also applied...

Abstract Despite increased prevalence of maternal cannabis use, little is understood regarding potential long-term effects of prenatal cannabis exposure (PCE) on neurodevelopmental outcomes. While neurodevelopmental cannabis exposure increases the risk of developing affective/mood disorders in adulthood, the precise neuropathophysiological mechanisms in male and female offspring are largely unknown. Given the interconnectivity of the endocannabinoid (ECb) system and the brain’s fatty acid pathways, we hypothesized that prenatal exposure to Δ9-tetrahydrocannabinol (THC) may dysregulate fetal neurodevelopment through alterations of fatty-acid dependent synaptic and neuronal function in the mesolimbic system. To investigate this, pregnant Wistar rats were exposed to vehicle or THC (3 mg/kg) from gestational day (GD)7...