Cannabis in pregnancy

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Cannabis consumption in pregnancy may or may not be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits. [1] The American College of Obstetricians and Gynecologists recommended that cannabis use be stopped before and during pregnancy. There has not been any official link between birth defects and marijuana use. [2] Cannabis is the most commonly used illicit substance among pregnant women. [3]

Contents

Cannabis has an ancient tradition of usage as a medicine in obstetrics and gynecology, and a comprehensive historical review find that cannabis extracts, may represent an efficacious and safe alternative for treatment of a wide range of conditions in women including dysmenorrhea, dysuria, hyperemesis gravidarum, and menopausal symptoms. [4]

Endocannabinoid system

The role of the endocannabinoid system (ECS) in female fertility has long been suspected and studied. [5] Most studies through 2013 linking development of the fetus and cannabis show effects of consumption during the gestational period, but abnormalities in the endocannabinoid system during the phase of placental development are also linked with problems in pregnancy. [1] According to Sun and Dey (2012), endocannabinoid signaling plays a role in "female reproductive events, including preimplantation embryo development, oviductal embryo transport, embryo implantation, placentation, and parturition". [5] Karusu et al (2011) said that a "clear correlation ... in the actual reproductive tissues of miscarrying versus healthy women has yet to be established. However, the adverse effects of marijuana smoke and THC on reproductive functions point to processes that are modulated by ECS.". [6]

Recent data indicates that endometrial expression of cannabinoid receptors in marijuana smoking mothers is higher than non-smokers. [7] Keimpema and colleagues (2011) said, "Prenatal cannabis exposure can lead to growth defects during formation of the nervous system"; "[c]annabis impacts the formation and functions of neuronal circuitries by targeting cannabinoid receptors ... By indiscriminately prolonging the "switched-on" period of cannabinoid receptors, cannabis can hijack endocannabinoid signals to evoke molecular rearrangements, leading to the erroneous wiring of neuronal networks". [8] A report prepared for the Australian National Council on Drugs concluded cannabis and other cannabinoids are contraindicated in pregnancy as they may interact with the endocannabinoid system. [1] [9]

Research

Although conclusions cannot be drawn from existing data, there is some evidence that prenatal exposure to cannabis may be associated with deficits in language, attention, cognitive performance, and delinquent behaviors. [10] THC exposure in rats during the prenatal developmental phase may cause epigenetic changes in gene expression, but there is limited knowledge about the risk for psychiatric disorders because of ethical barriers to studying the developing human brain. [11] While animal studies cannot take into account factors that could influence the effects of cannabis on human maternal exposure, such as environmental and social factors, [12] a 2011 review of rodent studies by Campolongo et al. said there was "... increasing evidence from animal studies showing that cannabinoid drugs ... induce enduring neurobehavioral abnormalities in the exposed offspring ..." [12] Campolongo et al. added that "clinical studies report hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis". [12] Martin et al. investigated recent trends in substance abuse treatment admissions for cannabis use in pregnancy in the US, based on Treatment Episodes Data Set (TEDS) from 1992 to 2012, and discovered that, while the proportion of treatment admissions for pregnant women was stable (about 4%), the admissions for women who were pregnant and reported any marijuana use grew from 29% to 43%. [13] A 2015 review found that cannabis use by pregnant mothers corresponded to impaired brain maturation in their children, and that those children were more predisposed to neurodevelopmental disorders; these results do not demonstrate causality. [14]

The National Institute on Drug Abuse states that further research is required to "disentangle" effects of cannabis use from a mother's concomitant drug use and other environmental factors. [15] A 2016 meta-analysis showed that after accounting for confounding factors, cannabis alone was not responsible for adverse neonatal outcomes. [16]

Pregnancy and miscarriage by endocannabinoids

The endocannabinoid (EC), a N-acylethanolamine (NAE), Anandamide (AEA: C 22 H 37 NO 2; 20:4, ω-6), that is synthesized "on demand", [17] is the key to a successful pregnancy and outcome, by a temporary low amount, coursed by high FAAH activity, at the uterine lining. [18] The lower AEA content uses the CB1 receptors, that are at high levels on the blastocyst (fertilized egg), to make the attachment to the lining of the uterus. [19] Another study have also shown, that healthy women, with higher lymphocyte FAAH, have lower blood AEA compared to aborting women. [20]

As low level of AEA, called on and synthesized "on demand" if needed to activate related receptors, and broken down by FAAH, is necessary for attachment and prevention of miscarriage, and abortion, it is found that the phytocannabinoid Δ9-tetrahydrocannabinol (THC: C 21 H 30 O 2), that can mimic "the called" AEA activation at CB1 and CB2 receptors, [21] is able to lower blood AEA (and the demand for it) by a biphasic reaction. Anandamide (AEA) reach maximal values at 30 min., as it increase slightly from0.58 ± 0.21 ng/ml at baseline to 0.64 ± 0.24 ng/ml (p < 0.05). After reaching maximal concentrations, the EC plasma levels (also 2-Arachidonoylglycerol (2-AG: C23H38O4; 20:4, ω-6) decrease markedly to a nadir of 300 min after THC administration, to 0.32 ± 0.15 ng/ml for anandamide, and the plasma concentrations returned to near baseline levels until 48 hours after the experiment in 25 healthy volunteers, who received a large intravenous dose of THC (0.10 mg/kg). [22]

The endocannabinoid-CB1-receptor system is found unique in its absolute control over the initiation of the milk suckling response in new-borns, and it is further proposed that cannabis-based medicines should be developed to benefit infant failure to thrive. [23]

Developmental observations suggest that CB1 receptors develop only gradually during the postnatal period, which block for the psychoactive effects of cannabinoid treatment in the young organism. Therefore, it is suggested that children may respond positively to medicinal applications of cannabinoids without undesirable central effects. Clinical results have been reported in pediatric oncology and in case studies of children with severe neurological disease or brain trauma, and cystic fibrosis (CF) suggesting cannabinoid treatment for children or young adults, in order to achieve an improvement of their health condition including improved food intake and reduced inflammatory exacerbations. [24] In CF mice treated with THC in infancy show normal motor activity and anxiety levels in adulthood. [25] As the etiology of CF is associated with an imbalance of fatty acids ( n6 and n3 ), and therefore assumed, that endocannabinoid activity, which plays an important role in fertility, is disrupted and could be one of the causes of infertility, a study find CF males treated with THC fully fertile, producing offspring comparable by the number of litters and the number of pups with wild-type mice, and there counterparts, not treated, were completely infertile. Thereby, mild stimulation of the endocannabinoid system in infancy and adolescence appears to normalize many reproductive processes and prevent infertility in CF males. [26]

Morning sickness/hyperemesis gravidarum

Hyperemesis Gravidarum (HG), is a debilitating ailment characterized by severe nausea and vomiting, malnutrition, and weight loss during pregnancy, and occurs to 1-2% of pregnant women globally. It is a perplexing female mystery for the present-day medical establishment. The frustration is mostly felt by women who are survivors of HG, desperately searching for a cure and increased understanding of this disease. Several pregnant women have revealed their personal experience with cannabis, having used it to relieve symptoms of HG, who would otherwise have become severely emaciated, dehydrated, and malnourished due to persistent, uncontrollable vomiting and the inability to eat and drink in their pregnancy. [27] [28]

See also

Related Research Articles

<span class="mw-page-title-main">Tetrahydrocannabinol</span> Chemical compound

Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term THC usually refers to the Delta-9-THC isomer with chemical name (−)-trans-Δ9-tetrahydrocannabinol. THC is a terpenoid found in cannabis and, like many pharmacologically active phytochemicals, it is assumed to be involved in the plant's evolutionary adaptation against insect predation, ultraviolet light, and environmental stress. THC was first discovered and isolated by Israeli chemist Raphael Mechoulam in Israel in 1964. It was found that, when smoked, THC is absorbed into the bloodstream and travels to the brain, attaching itself to endocannabinoid receptors located in the cerebral cortex, cerebellum, and basal ganglia. These are the parts of the brain responsible for thinking, memory, pleasure, coordination and movement.

<span class="mw-page-title-main">Anandamide</span> Chemical compound (fatty acid neurotransmitter)

Anandamide (ANA), also known as N-arachidonoylethanolamine (AEA), an N-acylethanolamine (NAE), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid receptors, the same receptors that the psychoactive compound THC in cannabis acts on. Anandamide is found in nearly all tissues in a wide range of animals. Anandamide has also been found in plants, including small amounts in chocolate. The name 'anandamide' is taken from the Sanskrit word ananda, which means "joy, bliss, delight", plus amide.

<span class="mw-page-title-main">Effects of cannabis</span> Effects resulting from the use of cannabis

The effects of cannabis are caused by chemical compounds in the cannabis plant, including 113 different cannabinoids such as tetrahydrocannabinol (THC) and 120 terpenes, which allow its drug to have various psychological and physiological effects on the human body. Different plants of the genus Cannabis contain different and often unpredictable concentrations of THC and other cannabinoids and hundreds of other molecules that have a pharmacological effect, so the final net effect cannot reliably be foreseen.

<span class="mw-page-title-main">Cannabinoid</span> Compounds found in cannabis

Cannabinoids are several structural classes of compounds found in the cannabis plant primarily and most animal organisms or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is also a major constituent of temperate cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea.

<span class="mw-page-title-main">Cannabinoid receptor</span> Group of receptors to cannabinoid compounds

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates– a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains. Cannabinoid receptors are activated by three major groups of ligands: endocannabinoids; phytocannabinoids ; and synthetic cannabinoids. All endocannabinoids and phytocannabinoids are lipophilic.

<span class="mw-page-title-main">Cannabinol</span> Naturally-occurring cannabinoid

Cannabinol (CBN) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS).

<span class="mw-page-title-main">Tetrahydrocannabivarin</span> Homologue of tetrahydrocannabinol

Tetrahydrocannabivarin is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown to exhibit neuroprotective activity, appetite suppression, glycemic control and reduced side effects compared to THC, making it a potential treatment for management of obesity and diabetes.

The endocannabinoid system (ECS) is a biological system composed of endocannabinoids, which are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors (CBRs), and cannabinoid receptor proteins that are expressed throughout the vertebrate central nervous system and peripheral nervous system. The endocannabinoid system remains under preliminary research, but may be involved in regulating physiological and cognitive processes, including fertility, pregnancy, pre- and postnatal development, various activity of immune system, appetite, pain-sensation, mood, and memory, and in mediating the pharmacological effects of cannabis. The ECS plays an important role in multiple aspects of neural functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others.

<span class="mw-page-title-main">Fatty-acid amide hydrolase 1</span>

Fatty-acid amide hydrolase 1 or FAAH-1(EC 3.5.1.99, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide (AEA), an N-acylethanolamine (NAE) in 1993. In humans, it is encoded by the gene FAAH. FAAH also regulate the contents of NAE's in Dictyostelium discoideum, as they modulate their NAE levels in vivo through the use of a semispecific FAAH inhibitor.

<span class="mw-page-title-main">11-Hydroxy-THC</span> Chemical compound

11-Hydroxy-Δ9-tetrahydrocannabinol, usually referred to as 11-hydroxy-THC is the main active metabolite of tetrahydrocannabinol (THC), which is formed in the body after Δ9-THC is consumed.

<span class="mw-page-title-main">Cannabinoid receptor 1</span> Mammalian protein found in Homo sapiens

Cannabinoid receptor 1 (CB1), is a G protein-coupled cannabinoid receptor that in humans is encoded by the CNR1 gene. The human CB1 receptor is expressed in the peripheral nervous system and central nervous system. It is activated by endocannabinoids, a group of retrograde neurotransmitters that include anandamide and 2-arachidonoylglycerol (2-AG); plant phytocannabinoids, such as docosatetraenoylethanolamide found in wild daga, the compound THC which is an active constituent of the psychoactive drug cannabis; and synthetic analogs of THC. CB1 is antagonized by the phytocannabinoid tetrahydrocannabivarin (THCV).

<span class="mw-page-title-main">JWH-018</span> Chemical compound

JWH-018 (1-pentyl-3-(1-naphthoyl)indole, NA-PIMO or AM-678) is an analgesic chemical from the naphthoylindole family that acts as a full agonist at both the CB1 and CB2 cannabinoid receptors, with some selectivity for CB2. It produces effects in animals similar to those of tetrahydrocannabinol (THC), a cannabinoid naturally present in cannabis, leading to its use in synthetic cannabis products that in some countries are sold legally as "incense blends".

<span class="mw-page-title-main">Raphael Mechoulam</span> Israeli chemist (1930–2023)

Raphael Mechoulam was a Bulgarian-born Israeli organic chemist and a professor in the Department of Natural Materials at the School of Pharmacy in the Faculty of Medicine of the Hebrew University of Jerusalem. Mechoulam served as Rector of the university from 1979-1982. He was elected to the Israel Academy of Sciences and Humanities in 1994 and served as its scientific chair from 2007-2013. He was a recipient of the Israel Prize for Chemistry Research in 2000 and the Harvey Prize for 2019-2020.

A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include antagonists, inverse agonists, and antibodies of CBRs. The discovery of the endocannabinoid system led to the development of CB1 receptor antagonists. The first CBR inverse agonist, rimonabant, was described in 1994. Rimonabant blocks the CB1 receptor selectively and has been shown to decrease food intake and regulate body-weight gain. The prevalence of obesity worldwide is increasing dramatically and has a great impact on public health. The lack of efficient and well-tolerated drugs to cure obesity has led to an increased interest in research and development of CBR antagonists. Cannabidiol (CBD), a naturally occurring cannabinoid and a non-competitive CB1/CB2 receptor antagonist, as well as Δ9-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. CBD is a very low-affinity CB1 ligand, that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant.

<i>N</i>-Acylethanolamine Class of chemical compounds

An N-acylethanolamine (NAE) is a type of fatty acid amide where one of several types of acyl groups is linked to the nitrogen atom of ethanolamine, and highly metabolic formed by intake of essential fatty acids through diet by 20:4, n-6 and 22:6, n-3 fatty acids, and when the body is physically and psychologically active,. The endocannabinoid signaling system (ECS) is the major pathway by which NAEs exerts its physiological effects in animal cells with similarities in plants, and the metabolism of NAEs is an integral part of the ECS, a very ancient signaling system, being clearly present from the divergence of the protostomian/deuterostomian, and even further back in time, to the very beginning of bacteria, the oldest organisms on Earth known to express phosphatidylethanolamine, the precursor to endocannabinoids, in their cytoplasmic membranes. Fatty acid metabolites with affinity for CB receptors are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA), by brown algae which diverged about 1500 MYA, by sponges, which diverged from eumetazoans about 930 MYA, and a lineages that predate the evolution of CB receptors, as CB1 – CB2 duplication event may have occurred prior to the lophotrochozoan-deuterostome divergence 590 MYA. Fatty acid amide hydrolase (FAAH) evolved relatively recently, either after the evolution of fish 400 MYA, or after the appearance of mammals 300 MYA, but after the appearance of vertebrates. Linking FAAH, vanilloid receptors (VR1) and anandamide implies a coupling among the remaining ‘‘older’’ parts of the endocannabinoid system, monoglyceride lipase (MGL), CB receptors, that evolved prior to the metazoan-bilaterian divergence, but were secondarily lost in the Ecdysozoa, and 2-Arachidonoylglycerol (2-AG).

<span class="mw-page-title-main">Cannabis use disorder</span> Continued use of cannabis despite clinically significant impairment

Cannabis use disorder (CUD), also known as cannabis addiction or marijuana addiction, is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and ICD-10 as the continued use of cannabis despite clinically significant impairment.

<span class="mw-page-title-main">Tetrahydrocannabinolic acid</span> Chemical compound

Tetrahydrocannabinolic acid is a precursor of tetrahydrocannabinol (THC), an active component of cannabis.

The endocannabinoid transporters (eCBTs) are transport proteins for the endocannabinoids. Most neurotransmitters are water-soluble and require transmembrane proteins to transport them across the cell membrane. The endocannabinoids on the other hand, are non-charged lipids that readily cross lipid membranes. However, since the endocannabinoids are water immiscible, protein transporters have been described that act as carriers to solubilize and transport the endocannabinoids through the aqueous cytoplasm. These include the heat shock proteins (Hsp70s) and fatty acid-binding proteins for anandamide (FABPs). FABPs such as FABP1, FABP3, FABP5, and FABP7 have been shown to bind endocannabinoids. FABP inhibitors attenuate the breakdown of anandamide by the enzyme fatty acid amide hydrolase (FAAH) in cell culture. One of these inhibitors (SB-FI-26), isolated from a virtual library of a million compounds, belongs to a class of compounds that act as an anti-nociceptive agent with mild anti-inflammatory activity in mice. These truxillic acids and their derivatives have been known to have anti-inflammatory and anti-nociceptive effects in mice and are active components of a Chinese herbal medicine used to treat rheumatism and pain in human. The blockade of anandamide transport may, at least in part, be the mechanism through which these compounds exert their anti-nociceptive effects.

Cannabis use and trauma is the contribution that trauma plays in promoting the use and potential abuse of cannabis. Conversely, cannabis use has been associated with the intensity of trauma and PTSD symptoms. While evidence of efficacious use of cannabis is growing in novelty, it is not currently recommended.

<span class="mw-page-title-main">Δ-8-Tetrahydrocannabinol</span> Isomer of tetrahydrocannabinol

Δ-8-tetrahydrocannabinol is a psychoactive cannabinoid found in the Cannabis plant. It is an isomer of delta-9-tetrahydrocannabinol, the compound commonly known as THC.

References

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