Pregnancy, Breastfeeding & Cannabis
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.
SECTION 5: Effects of Second-hand Cannabis Smoke
There are currently no published studies evaluating the effects of second-hand cannabis smoke on developing human fetuses. However, exposure of non-smoking women to second-hand tobacco smoke during pregnancy has been shown to cause low birth weight, preterm delivery and sudden infant death syndrome (crib death) and is associated with intrauterine growth restriction and spontaneous miscarriage (ref. California EPA 2005). Second-hand tobacco smoke alone results in about 50,000 deaths each year in Americans of all ages (ref. California EPA 2005, Surgeon General 2006). Evidence suggests that the effects of child exposure to second-hand cannabis smoke are harmful as well (ref. Volkow 2014, Volkow 2016). Detectable levels of cannabis metabolites have been found in children exposed to second-hand cannabis smoke (ref. Wilson 2017, Cone 2015).
It is a common belief that, unlike tobacco smoke, cannabis smoke is benign (ref. Johnson 2002). The psychoactive substance in cannabis is THC rather than nicotine in tobacco, however, cannabis smoke is still the result of biomass combustion and contains many of the same toxins as tobacco smoke (ref. Moir 2008). Laboratory studies of the chemical composition of mainstream and side-stream smoke from cannabis cigarettes confirm the presence of known carcinogens (agents that cause cancer) and other chemicals linked to respiratory disease (ref. Moir 2008). Interestingly, some toxic chemicals found in both second-hand cannabis smoke and second-hand tobacco smoke, actually occur in higher concentrations in second-hand cannabis smoke (ref. Padilla 2015).
For these reasons, pregnant women and children should avoid second-hand cannabis smoke, and family and friends should not smoke around a pregnant woman. In my opinion, there is no good reason to ingest cannabis by smoking. If inhalation is a crucial mode of ingestion, as it might be in severe nausea and vomiting, vaping is safer than smoking, though there are many unknowns about vaping, including what chemicals make up the vapor and how they affect physical health over the
long term (ref. Blaha 2020). In vaporization, no combustion takes place, so many harmful chemicals are never formed. Another, safer alternative and my favorite, is to use a cannabis tincture placed under the tongue where it is rapidly absorbed directly into the bloodstream through the sublingual venous plexus. This avoids the need to swallow an edible that is likely to be vomited back out.
SECTION 6: Cannabis Use and Breastfeeding
Normally, endocannabinoids, particularly 2-AG, are naturally present in a mother’s milk. CB1 receptor blockade in animal experiments has been shown to interfere with milk suckling in mouse pups, possibly by interfering with innervation of the tongue muscles (ref. Fride 2008). The same is thought to be true in human neonates as well.
In addition to 2-AG from the mother’s milk, the normal mouse pup brain has been observed to contain high levels of CB1 receptors and 2‐AG on the first day of life in structures including the hypothalamus, which is associated with feeding behavior. This suggests that pup brain‐derived 2‐AG represents a major stimulus for the newborn to start drinking milk immediately after birth (ref. Berrendero 1999).
In animal models, THC crossed the placenta, producing fetal plasma levels that were approximately 10% of maternal levels after acute exposure. Significantly higher fetal concentrations were observed after repetitive exposures (ref. Mark 2017). Limited data suggest that THC also appears in human breast milk (ref. Perez-Reyes 1982).
Currently available data are insufficient to evaluate the effects of cannabis use on infants during breastfeeding. In the absence of such data, cannabis use is discouraged (ref. Reese-Stremtan 2015). As mentioned below, the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics advise doctors that: “Breastfeeding women should be informed that the potential risks of exposure to [cannabis] metabolites are unknown and should be encouraged to discontinue [cannabis] use” (ref. ACOG 2017, Ryan 2018).
SECTION 7: Recommendations of Physician Organizations
In 2017, the American College of Obstetricians and Gynecologists issued revised recommendations regarding cannabis use during pregnancy and lactation accompanied by an excellent review of the limited data available (ref. ACOG 2017; link in SECTION 9: References). Their recommendations include:
In 2018, the American Academy of Pediatrics’ Committee on Substance Abuse and Prevention and Section on Breastfeeding also provided a literature review supporting their recommendations for doctors entitled: “[Cannabis] use during pregnancy and breastfeeding: Implications for neonatal and childhood outcomes”. The recommendations are similar to those of the American College of Obstetricians and Gynecologists, though some are more austere (ref. Ryan 2018; link in SECTION 9: References).
In an editorial published in the journal Future Neurology, a group of neurologists expressed deep concern that: “a broad array of impairments can arise from disrupted endocannabinoid signaling caused by phytocannabinoid [i.e. cannabis] use during pregnancy” (ref. Harkany 2015).
SECTION 8: My Recommendations as a Doctor Specializing in Cannabis Medicine
In my opinion based on the available scientific evidence, women should avoid using cannabis during pregnancy and breastfeeding – hard stop. While the evidence is limited and sometimes conflicting, the potential risk to the developing fetus or newborn is significant and worthy of caution. Negative effects of cannabis can impact the baby for its entire life. One should always weigh the risks and benefits of any treatment, cannabis as well as prescription and over the counter medications. I strongly recommend that pregnant women include their obstetrician when considering the use of cannabis medically or otherwise.
A rare example of when a pregnant woman and her doctor might consider using medical cannabis as described below, is in a rare condition called hyperemesis gravidarum. Hyperemesis gravidarum is estimated to occur in about 2% of pregnancies in the USA (ref. Eliakim 2000). It is different from typical nausea and vomiting during pregnancy that has been reported to occur up to 80% of pregnant women (ref. Lacroix 2000). Hyperemesis gravidarum is characterized by almost constant, profuse, unrelenting, incapacitating nausea and vomiting that is often resistant to pharmaceutical antiemetics, which are generally classified as Category B at best by the US Food and Drug Administration, meaning that there are no adequate, well-controlled studies in pregnant women to prove a drug poses no risk to the fetus.
Hyperemesis gravidarum can result in extreme dehydration, electrolyte imbalances, malnutrition, severe weight loss, pregnancy induced hypertension, premature delivery and even fetal demise. Frequent visits to the emergency room and hospital admissions are the norm, and a diagnosis of hyperemesis gravidarum categorizes the woman as having a high-risk pregnancy. The effects can be so physically and psychologically devastating that some women have opted for termination, even in wanted pregnancies, because the symptoms are so severe. Additionally, 2 recent studies demonstrated that the odds of developing autism spectrum disorder may be significantly elevated for children of mothers who experience hyperemesis gravidarum (ref. Fejzo 2019, Getahun 2019).
If traditional pharmaceutical antiemetics have failed, a pregnant woman and her physician may decide that the risk of harm to the fetus from hyperemesis gravidarum outweighs the potential risk of limited cannabis use. An article in the online lay press describes one woman’s experience with this difficult, complex process (ref. Watts 2017; link in SECTION 9: References). In rare cases like these, in order to minimize the risk of cannabis exposure, I strongly recommend that patients:
With respect to item number 4 on the list, I strongly recommend that any pregnant mother who decides with her doctor to try using cannabis medicinally start by microdosing in order to minimize risk to the fetus and limit side effects. Research on cannabis in microdose form has shown it to be safer and usually more effective than higher doses for a wide variety of physical ailments, such as chronic pain (ref. Portenoy 2012), nausea, insomnia, and PTSD with associated night terrors (ref. Cameron 2014).
An excellent example of the power of microdosing was demonstrated in a 2012 randomized, placebo-controlled, graded-dose study of patients with advanced cancer and severe, uncontrolled pain unresponsive to traditional opioid painkillers. Patients were given nabiximols, a pharmaceutical form of CBD and THC in a sublingual spray, in low, medium, and high doses. Patients who received the lowest dosage of cannabinoids showed the greatest reduction in pain, while those receiving higher doses actually experienced more pain (ref. Portenoy 2012). The dose-dependent properties of cannabis can also explain the historical medical references to the use of low doses of cannabis to prevent miscarriages, while high doses of cannabis were used as an early abortifacent (ref. Blesching 2015).
In summary, based on the available scientific evidence, I recommend that women avoid the use of any amount of cannabis in any form at any time during pregnancy and breastfeeding. Of note, I work as a medical consultant for Tikun Olam, an international developer of cannabis medicines. Tikun Olam also advises against the use of cannabis, including their products, during pregnancy and breastfeeding.
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