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Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp) for comparison). Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic...
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Cannabis and Breastfeeding

Cannabis is a drug derived from hemp plant, Cannabis sativa, used both as a recreational drug or as medicine. It is a widespreadvillegal substance, generally smoked for its hallucinogenic properties. Little is known about the adverse effects of postnatal cannabisvexposure throw breastfeeding because of a lack of studies in lactating women. The active substance of cannabis is the delta-9-TetraHydroCannabinol (THC). Some studies conclude that it could decrease motor development of the child at one year of age. Therefore, cannabis use and abuse of other drugs like alcohol, tobacco, or cocaine must be contraindicated during breastfeeding. Mothers who use cannabis must stop breastfeeding, or ask...
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Endocannabinoid System in First Trimester Placenta: Low FAAH and High CB1 Expression Characterize Spontaneous Miscarriage

Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were the first endocannabinoids to be characterized, that bind two G protein-coupled receptors, CB1 and CB2. AEA synthesized by multiple pathways, including NAPE-specific phospholipase D (NAPE-PLD) and degraded by the fatty acid amide hydrolase (FAAH). AEA levels are critical in regulating embryo development and the ‘‘window’’ of implantation. We examined the expression of nape-pld mRNA, CB1 and FAAH in human placenta hypothesizing that their altered signaling may contribute to spontaneous miscarriage. First trimester placentas from women with spontaneous miscarriage (group 1) were matched with placentas from women who underwent termination (group 2). Nape-pld expression was analyzed by RT-PCR; CB1...
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Fetal Alcohol Spectrum Disorder: Potential Role of Endocannabinoids Signaling

Abstract One of the unique features of prenatal alcohol exposure in humans is impaired cognitive and behavioral function resulting from damage to the central nervous system (CNS), which leads to a spectrum of impairments referred to as fetal alcohol spectrum disorder (FASD). Human FASD phenotypes can be reproduced in the rodent CNS following prenatal ethanol exposure. Several mechanisms are expected to contribute to the detrimental effects of prenatal alcohol exposure on the developing fetus, particularly in the developing CNS. These mechanisms may act simultaneously or consecutively and differ among a variety of cell types at specific developmental stages in particular brain regions. Studies have...
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Five-year Follow-up of Rural Jamaican Children whose Mothers used Marijuana during Pregnancy

This research provides data on the development of 59 Jamaican children, from birth to age 5 years, whose mothers used marijuana during pregnancy. Approximately one-half of the sample used marijuana during pregnancy and were matched with non-users according to age, parity, and socioeconomic status. Testing of the children was done at 1, 3, and 30 days of age with the Brazelton Neonatal Behavioral Assessment Scales and at ages 4 and 5 years with the McCarthy Scales of Children's Abilities. Data about the child's home environment and temperament were collected from direct observations as well as from standardized questionnaires. The results show no significant differences...
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Identifying Prenatal Cannabis Exposure and Effects of Concurrent Tobacco Exposure on Neonatal Growth

BACKGROUND: Cannabis is the most frequently used illicit drug among pregnant women, but data describing the effects of prenatal cannabis exposure and concurrent nicotine and cannabis exposures on neonatal growth are inconsistent. Testing of meconium, the first neonatal feces, offers objective evidence of prenatal cannabis exposure, but the relative ability of meconium testing and maternal self-report to identify affected neonates remains unclear. METHODS: Eighty-six pregnant women provided detailed self-reports of daily cannabis and tobacco consumption throughout pregnancy. Cannabinoids and tobacco biomarkers were identified in oral fluid samples collected each trimester and quantified in meconium at birth. RESULTS: Cannabis-using women were significantly more likely to...
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Lasting impacts of prenatal cannabis exposure and the role of endogenous cannabinoids in the developing brain

Cannabis is the most commonly used illicit substance among pregnant women. Human epidemiological and animal studies have found that prenatal cannabis exposure influences brain development and can have long-lasting impacts on cognitive functions. Exploration of the therapeutic potential of cannabis-based medicines and synthetic cannabinoid compounds has given us much insight into the physiological roles of endogenous ligands (endocannabinoids) and their receptors. In this article, we examine human longitudinal cohort studies that document the longterm influence of prenatal exposure to cannabis, followed by an overview of the molecular composition of the endocannabinoid system and the temporal and spatial changes in their expression during brain development....
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Ligand-receptor signaling with endocannabinoids in preimplantation embryo development and implantation

Although adverse effects of cannabinoids on pregnancy have been indicated for many years, the mechanisms by which they exert their actions were not clearly understood. Only recently, molecular and biochemical approaches have led to the identification of two types of cannabinoid receptors, brain-type receptors (CB1-R) and spleen-type receptors (CB2-R), which mediate cannabinoid effects. These findings were followed by the discovery of endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG). The natural cannabinoids and endocannabinoids exert their effects via cannabinoid receptors and share similar pharmacological and physiological properties. Recent demonstration of expression of functional CB1-R in the preimplantation embryo and synthesis of anandamide in the pregnant uterus of...
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Maternal Marijuana Use During Lactation and Infant Development at One Year

Prenatal marijuana exposure is associated with adverse perinatal effects. Very little is known about the effect of postnatal marijuana exposure on infant development. Postnatal exposure can result from maternal use of marijuana during lactation. Delta-9-tetrahydrocannabinol (THC) transfers and concentrates in the mother's milk and is absorbed and metabolized by the nursing infant. The present study investigated the relationship between infant exposure to marijuana via the mother's milk and infant motor and mental development at one year of age. One hundred and thirty-six breast-fed infants were assessed at one year of age for motor and mental development. Sixty-eight infants were exposed to marijuana via the...
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Multiple Roles for the Endocannabinoid System During the Earliest Stages of Life: Pre- and Postnatal Development

The endocannabinoid system, including its receptors (CB1 and CB2), endogenous ligands (‘endocannabinoids’), synthesising and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development. In addition, the endocannabinoids, notably 2-arachidonyl glycerol, are also present in maternal milk. During three distinct developmental stages (i.e. embryonic implantation, prenatal brain development and postnatal suckling), the endocannabinoid system appears to play an essential role for development and survival. Thus, during early pregnancy, successful embryonic passage through the oviduct and implantation into the uterus both require critical enzymatic control of optimal anandamide levels at the appropriate...
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