Surgeon General Jerome Adams yesterday issued an advisory about the "health risks" posed by marijuana use during pregnancy. He considers it "alarming" that "many retail dispensaries recommend marijuana to pregnant women for morning sickness." During a press conference explaining the advisory, Secretary of Health and Human Services Alex Azar declared that "no amount of marijuana use during pregnancy or adolescence is safe."
Azar's formulation is weirdly categorical, since it's widely accepted that the use of potentially hazardous medications during pregnancy may be appropriate when the benefits outweigh the risks. And while there are legitimate reasons to be concerned about the danger that cannabis may pose to fetuses, the evidence is more ambiguous than Adams and Azaar imply. The relevant question is not whether marijuana use during pregnancy is completely "safe" but whether the evidence against it is strong enough to conclude that it should always be avoided, even when it provides relief to women who would otherwise be incapacitated by nausea.
Marinol, an anti-nausea medication that the Food and Drug Administration (FDA) approved in 1985, is an instructive example. The FDA has placed Marinol, a.k.a dronabinol, in Pregnancy Category C, which means "animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks." That category also includes commonly prescribed drugs such as the asthma medication albuterol and the antidepressants Prozac (fluoxetine) and Zoloft (sertraline). Marinol's classification is especially relevant in this context, since it is a capsule containing THC, the main active ingredient in marijuana and the cannabinoid that worries Adams in connection with developing fetuses.
While Marinol's manufacturer, AbbVie, says pregnant women should not take it, the advice from the companies that make Prozac, Zoloft, and Proventil (an albuterol inhaler) is notably different. Eli Lilly says Prozac "should be used during pregnancy only if the potential benefit justifies the potential risks to the fetus." Similarly, Pfizer says, "Women who are pregnant, plan to become pregnant, or who are breastfeeding should not take ZOLOFT without consulting their physician." Merck says, "If you are pregnant or nursing, contact your physician about use of PROVENTIL HFA Inhalation Aerosol."
Marinol, which contains only THC and is taken orally, is not quite the same as marijuana, which contains lots of other compounds and can be smoked, vaped, or absorbed in the mouth via sprays or drops as well as swallowed in the form of beverages or edibles. What does research show specifically about the effects of marijuana use during pregnancy?
Adams cites The Health Effects of Cannabis and Cannabinoids, a 2017 report from the National Academies of Sciences, Engineering, and Medicine, so let's start there. "There is limited evidence of a statistical association between maternal cannabis smoking and pregnancy complications for the mother," the report says. "There is substantial evidence of a statistical association between maternal cannabis smoking and lower birth weight of the offspring….There is limited evidence of a statistical association between maternal cannabis smoking and admission of the infant to the neonatal intensive care unit….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)."
The meaning of these "statistical association[s]" remains unclear, as a 2018 report from the American Academy of Pediatrics (AAP) explains. "The evidence for independent, adverse effects of marijuana on human neonatal outcomes and prenatal development is limited," the AAP notes, "and inconsistency in findings may be the result of the potential confounding caused by the high correlation between marijuana use and use of other substances such as cigarettes and alcohol, as well as sociodemographic risk factors. However, the evidence from the available research studies indicate reason for concern, particularly in fetal growth and early neonatal behaviors."
Given the uncertainty, the AAP, like the American College of Obstetricians and Gynecologists, recommends abstinence during pregnancy and breastfeeding. The American Medical Association, meanwhile, has proposed a milder warning for cannabis products: "Marijuana use during pregnancy and breastfeeding poses potential harms."
The AAP and the ob-gyn group prefer that pregnant women err on the side of abstinence, which also seems to be what Adams is recommending. But prospective mothers may reach different conclusions, especially if they suffer from severe nausea and find that marijuana relieves it more effectively than other medications.
The National Institute on Drug Abuse (NIDA) is sponsoring four studies aimed at more definitively measuring the risks of marijuana use during pregnancy. "I don't want us to cry wolf," NIDA Executive Director Nora Volkow told the Associated Press this month. "We have to do these studies in a way that can identify risks."
A NIDA-sponsored study by researchers at the University of Washington, for example, is enrolling pregnant women in their first trimester who are already using marijuana for morning sickness. "Infants will undergo brain scans at 6 months and will be compared with babies whose mothers didn't use marijuana while pregnant," A.P. reports. The researchers will not supply marijuana to the subjects, and the study is limited to women who have already decided that the benefits of using cannabis during pregnancy outweigh the risks.
"They're making a choice that people might not agree with," said the lead researcher, Natalia Kleinhans. "But it's not out of desperation. It's an informed choice."
The very attempt to verify marijuana's risks has aroused the ire of physicians who think the issue is already settled. "We should be encouraging women who are pregnant to not use marijuana instead of incentivizing them to continue," a critic of the study, Washington ob-gyn Pat Marmion, told A.P.
That position is hard to fathom given the unsettled state of the science and the fact that many women are already using marijuana to relieve pregnancy-related nausea. Virginia ob-gyn Mishka Terplan perceives a double standard, noting that drugs commonly prescribed for morning sickness may also have unknown risks. (My wife, for example, was prescribed compazine, a Pregnancy Category C drug, for morning sickness.) "We shouldn't assume that because we classify something as illegal that it is shameful," Terplan said, "and that because something is legal and prescribed, it's helpful."
Susan Weiss, who directs NIDA's Division of Extramural Research, firmly rejects the suggestion that the existing evidence is adequate. "One of the big arguments about why this is unethical is that we already know the answers," she told A.P. "That is not true….We're living in this very large social experiment and we need to learn from it."