Pregnancy, Breastfeeding & Cannabis
Daniel D Price MD
Medical Cannabis Consultant
When pregnancy causes nausea and vomiting, pain, anxiety, and poor sleep, due primarily to a tempest of hormones and profound changes in the human body, some women consider using cannabis (Cannabis sativa) that is known for easing these conditions. Since cannabis legalization, more and more women are continuing to use cannabis as they did before becoming pregnant, or may consider starting to use cannabis as a “natural” medicine (ref. Volkow 2019). In this article, we will explore the safety of cannabis use during pregnancy and breastfeeding.
If you are familiar with the endocannabinoid system, you can skip to SECTION 2, otherwise, it is important to understand how cannabis works in the body, which is described next in SECTION 1.
SECTION 1: The Endocannabinoid System
The human body is made up of multiple different physiological systems, such as the immune system, gastrointestinal system, and the focus of our discussion here: the reproductive system. The endocannabinoid system, discovered in the 1980s, is a master system that helps regulate the other physiological systems in the body to promote balance – the way a symphony conductor directs the instruments in an orchestra to produce beautiful music.
The endocannabinoid system is composed of cannabinoid receptors on cell walls and within mitochondria inside cells scattered throughout the body in various physiological systems. Two endocannabinoid receptors have been named so far: CB1 and CB2. CB1 receptors are widespread but more prominent in the brain and spinal cord (ref. Pertwee 1997). CB2 receptors tend to be peripheral and concentrate in organs of the immune system, such as the spleen, thymus and blood cells (ref. Pacher 2006). The endocannabinoid system has been identified in almost every brain structure and organ system in the human body (ref. Fride 2002, Fride 2006).
Endocannabinoids (endogenous cannabinoids) are compounds produced on demand by cells and released into the intercellular space, where they bind to endocannabinoid receptors on adjacent cells producing local effects specific to the physiologic system. Two endocannabinoids have been named: anandamide (from ananda the Sanskrit word for bliss) and 2-AG.
The endocannabinoid system is present throughout the animal kingdom and has even been observed in primitive organisms. Cannabinoid receptors and anandamide have been detected in sperm cells from sea urchins as well as humans and other species. It has been postulated that anandamide is released from sea urchin egg cells, where it modulates the rate of fertilization by sperm via inhibition of the acrosome reaction (ref. Schuel 2005).
The reason the cannabis plant produces so many different effects on the body is because compounds in the plant, known as phytocannabinoids (-phyto meaning plant in Greek), are able to bind to endocannabinoid receptors as well as to other receptor systems, such as the serotonin,
dopamine and opioid systems. Over 100 phytocannabinoids have been identified in the plant, but THC and CBD are by far the most abundant. Unlike endocannabinoids that are rapidly inactivated producing focused effects, phytocannabinoids, like THC, are sequestered in adipose tissue (fat) and released slowly over extended periods of time leading to longer-lasting stimulation of cannabinoid receptors (ref. Iversen 2003). This is concerning when considering negative side effects.
SECTION 2: The Endocannabinoid System in Pregnancy
The endocannabinoid system has been detected in virtually all components of the reproductive system and at virtually all stages of fertilization and fetal development (ref. Walker 2019). The endocannabinoid system has been shown to be important for fertility (ref. Beth 1990), successful implantation of the fertilized egg in the uterus (ref. Fride 2004), early fetal brain development, neural differentiation and axonal migration (ref. Wang 2008, Fernandez 2000), and the normal onset of labor (ref. Wang 2008). Postnatally, the endocannabinoid system plays a crucial role in breast feeding (ref. Fride 2008), as discussed in SECTION 6.
CB1 and CB2 receptors and other cannabinoid receptors are widespread throughout the bodies of the mother and developing fetus. In fact, the endocannabinoid system is regarded as one of the most important vehicles by which developing cell systems communicate. The endocannabinoid system fine tunes the other physiological systems and can even turn them off or on as needed to maintain balance and proper functioning (ref. Backes 2017). This includes hormone production, which is central to reproduction, fetal and newborn development.
SECTION 3: Is Cannabis Safe During Pregnancy?
In 2017, a committee of leading physicians and research scientists affiliated with the National Academy of Sciences, produced the most authoritative review of the cannabis literature since 1999 entitled: The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (ref. NAS 2017; link to download in SECTION 9: References). The inappropriate classification of cannabis as Schedule 1 (unsafe, with no accepted medical use, and high potential for abuse and dependency) by the US Food and Drug Administration has stifled research, so there is little information on the physiological effects of cannabis in pregnancy on the mother and the fetus. Human studies performed to date focus on THC-dominant strains of cannabis, so the studies referred to in this section did not evaluate the use of CBD in pregnancy. A discussion of CBD follows in SECTION 4. Moreover, most of the data reflect cannabis administered by smoking and not cannabis exposure through other, safer routes of administration.
Concern for the fetus and newborn stems from the fact that THC crosses the placenta (ref. Bailey 1987). In the chapter on cannabis and pregnancy, the committee identified only one recent good- to fair-quality systematic review (ref. Gunn 2016). This review sought information on a comprehensive set of complications of pregnancy and on fetal and neonatal outcomes up to 6 weeks postpartum. The committee also identified 30 primary articles in the scientific literature that best address the committee’s research questions of interest.
The committee began with the question: Is there an association between cannabis use and pregnancy complications for the mother? They looked at miscarriage rates, fetal distress, and other maternal complications, and concluded: “There is limited evidence of a statistical association between maternal cannabis smoking and pregnancy complications for the mother.”
The next question was: Is there an association between cannabis use and fetal growth and development? They examined for fetal birth weight, length, head circumference, intrauterine growth restriction and congenital malformations. They concluded that: “There is substantial evidence of a statistical association between maternal cannabis smoking and lower birth weight of the offspring.”
They asked: Is there an association between maternal cannabis use and neonatal conditions in the infant? They evaluated for prematurity, neonatal ICU admission, and other neonatal conditions. After reviewing all available data, they concluded: “There is limited evidence of a statistical association between maternal cannabis smoking and admission of the infant to the neonatal ICU.”
The final question asked was: Is there an association between maternal cannabis use and later outcomes for the offspring? They looked at incidences of sudden infant death syndrome, breastfeeding, physical growth, cognition and academic achievement, behavior, substance use and delinquency, and mental health and psychosis. Their conclusion was: “There is insufficient evidence to support or refute a statistical association between maternal cannabis smoking and later outcomes in the offspring (e.g., sudden infant death syndrome, cognition/academic achievement, and later substance use).”
SECTION 4: CBD Use During Pregnancy
Increased consumption of CBD and other cannabis products has been noted in pregnant women, particularly during the first trimester (ref. Volkow 2019). Maternal use of CBD is concerning because the potential adverse outcomes of in utero exposure to pharmaceutically relevant concentrations of cannabinoids, like CBD, are not well-characterized.
Research on zebrafish (Danio rerio), who exhibit cellular and molecular changes during aging similar to mammals (ref. Adams 2018), reported that embryonic exposure to high doses of CBD caused larval developmental teratogenicity and altered the expression of several genes (ref. Carty 2018). Teratogenicity refers to the ability of an agent, such as radiation, chemicals or medications, to disturb the development of an embryo or fetus causing termination of the pregnancy or producing a congenital malformation (birth defect). Importantly, lower doses of CBD that did not induce teratogenicity and fall within the lower end of the human therapeutic range resulted in long-term changes in fecundity (the ability to produce live offspring; ref. Carty 2019). Negative effects of high CBD exposure were also seen in mammalian models. For example, in utero exposure to high doses of CBD caused eye and brain dysmorphologies (birth defects) in mice as well as zebrafish (ref. Fish 2019; No kidding, the researcher’s last name is really Fish and his career has been devoted to studying… fish).
Decidualization is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy. Decidualization involves proliferation and differentiation of endometrial stromal cells lining the uterus and is essential for the establishment of a receptive
endometrium and for pregnancy to occur. Deregulation of decidualization has been associated with miscarriages, infertility and other pregnancy-related disorders. Research has elucidated the role of the hormone estradiol in decidualization, where it regulates proliferation of endometrial stromal cells and expression of receptors for the hormone progesterone, whose role is to stimulate the uterus to prepare for and maintain pregnancy. CBD, but not THC, was found to inhibit endometrial stromal cell differentiation. Researchers also observed that CBD prevents a normal increase in transcript levels of the CYP19A1 gene that is essential to the process, as well as preventing the typical elevation in estradiol levels seen in differentiating endometrial stromal cells. Moreover, the study demonstrated that CBD inhibits the activity of aromatase, an adrenal enzyme that converts androstenedione and estrone into estrogen, the hormone that regulates a woman’s menstrual cycle and affects her entire reproductive system. In summary, the researchers discovered a novel effect of CBD on human endometrial differentiation, which may lead to infertility problems (ref. Amada 2020).
These findings suggest that while CBD produces fewer negative effects than THC in general, there are reasons for concern regarding the use of CBD in pregnancy that should be respected. CBD, like THC, should be avoided during pregnancy. If after careful consideration with her obstetrician, a woman decides to try CBD, guidelines for minimizing the risks of using medical cannabis are listed below in SECTION 8.
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