By Rebecca B. Perkins, MD, MSc
Associate Professor, Department of Obstetrics and Gynecology, Boston University School of Medicine/Boston Medical Center, Boston
SYNOPSIS: This study examined associations between maternal cannabis use in pregnancy and neurobehavioral problems diagnosed in children between ages 3 and 6 years. Maternal cannabis use was associated with higher cortisol levels, as well as abnormal behaviors, including anxiety, aggression, and hyperactivity. Placental analyses for a subset of children indicate a potential mechanism for neurobehavioral disorders as the result of selective gene regulation.
SOURCE: Rompala G, Nomura Y, Hurd YL. Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring. Proc Natl Acad Sci U S A 2021;118:e2106115118.
Recreational cannabis use has increased significantly, and many states have passed laws allowing both medical and recreational use. The marketing of marijuana as both a “natural” remedy and a medical treatment for nausea has led to a widespread misperception that consumption is safe. Recent surveys indicate that 3% to 16% of pregnant women used marijuana in the past month.1,2 In addition, tetrahydrocannabinol (THC) concentrations in cannabis preparations have increased steadily over the past decade, exacerbating potential harms.3 THC passes freely from mother to fetus via the placenta. Prior studies have linked maternal cannabis use to fetal growth restriction, preterm birth, and low birth weight.4-6 In addition, associations have been found between maternal cannabis use and autism, depression, psychosis, and drug-seeking behavior in offspring, which are thought to be mediated by reduction in dopaminergic receptors in the fetal brain.7-10
The study by Rompala et al examines the effect of maternal cannabis use on the placental transcriptome and neurocognitive development of children at ages 3-6 years in a longitudinal cohort of 322 mother-child pairs from the greater New York metropolitan area. In this cohort, maternal cannabis use was associated with younger parental age, single-mother pregnancies, maternal anxiety, depression, cigarette smoking, and African American race; these variables were controlled for in statistical analyses. Investigators examined hair samples from children ages 3-6 years for cortisol levels (a biomarker of stress), and performed heart rate variability testing, which measures parasympathetic nervous system activation and is associated with anxiety-related disorders. They also performed neurobehavioral testing for anxiety-related abnormal behavior. Among children born to mothers who used cannabis during pregnancy, they found higher cortisol levels, reductions in heart rate variability, and higher levels of clinically significant aggression, anxiety, and hyperactivity. Placental biopsies revealed reduced immune-related gene expression, with changes in both pro-inflammatory cytokines and immune cell-type markers. The authors postulated that these findings indicate a potential mechanism for the observed negative neurobehavioral effects on offspring via placental dysregulation.
COMMENTARY
This study adds to the body of literature indicating the substantial, long-term, negative effects of maternal cannabis use on child development. The American College of Obstetricians and Gynecologists discourages marijuana use during pregnancy and lactation because of the potential negative effects on offspring.11 OB/GYNs should work actively to assess the use of marijuana during pregnancy and discuss its harmful effects with patients, including increased aggression, anxiety, and hyperactivity during childhood. Similar to alcohol, marijuana should be avoided to prevent damage to the developing fetal brain. Patients using marijuana for medicinal purposes should be transitioned to safer medications prior to pregnancy.
In the early 2000s, opioids were heavily marketed by the pharmaceutical industry to physicians as revolutionary, non-addictive painkillers, despite evidence to the contrary.12 This directly affected prescribing behavior.12 For several years, physicians were required to ask all patients about pain with hard-stop electronic medical record alerts, likely leading to countless unnecessary prescriptions for narcotics.13 Two decades later, the pharmaceutical companies are paying damages for opioid marketing practices as the nation grapples with an unprecedented toll of drug addiction, with more than 100,000 deaths in 2020.14,15 The cannabis industry is following the same tactics, increasing the potency of its product combined with aggressive marketing as a health and wellness product.3,15 The U.S. cannabis market is expected to reach $41.5 billion annually by 2025.16,17 Legalization of marijuana is associated with higher rates of driving fatalities, emergency room visits for intoxication in adults and children, and psychiatric hospitalizations.18
As physicians, it is crucial that we provide our patients with information about the harms of legal drugs during pregnancy. There are no data to support safe consumption levels for alcohol or marijuana.
REFERENCES
- Volkow ND, Han B, Compton WM, McCance-Katz E. Self-reported medical and nonmedical cannabis use among pregnant women in the United States. JAMA 2019;322:167-169.
- Brown QL, Sarvet AL, Shmulewitz D, et al. Trends in marijuana use among pregnant and nonpregnant reproductive-aged women, 2002-2014. JAMA 2017;317:207-209.
- Chandra S, Radwan MM, Majumdar CG, et al. New trends in cannabis potency in USA and Europe during the last decade (2008-2017). Eur Arch Psychiatry Clin Neurosci 2019;269:5-15.
- Hurd YL, Wang X, Anderson V, et al. Marijuana impairs growth in mid-gestation fetuses. Neurotoxicol Teratol 2005;27:221-229.
- Fried PA, Watkinson B, Gray R. Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana. Neurotoxicol Teratol 1999;21:513-525.
- Corsi DJ, Walsh L, Weiss D, et al. Association between self-reported prenatal cannabis use and maternal, perinatal, and neonatal outcomes. JAMA 2019;322:145-152.
- Wang X, Dow-Edwards D, Anderson V, et al. In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus. Biol Psychiatry 2004;56:909-915.
- Corsi DJ, Donelle J, Sucha E, et al. Maternal cannabis use in pregnancy and child neurodevelopmental outcomes. Nat Med 2020;26:1536-1540.
- Fine JD, Moreau AL, Karcher NR, et al. Association of prenatal cannabis exposure with psychosis proneness among children in the Adolescent Brain Cognitive Development (ABCD) study. JAMA Psychiatry 2019;76:762-764.
- Spano MS, Ellgren M, Wang X, Hurd YL. Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood. Biol Psychiatry 2007;61:554-563.
- [No authors listed]. Committee Opinion No. 722: Marijuana use during pregnancy and lactation. Obstet Gynecol 2017;130:e205-e209.
- Beilfuss S, Linde S. Pharmaceutical opioid marketing and physician prescribing behavior. Health Econ 2021;30:3159-3185.
- Saigh O, Triola MM, Link RN. Brief report: Failure of an electronic medical record tool to improve pain assessment documentation. J Gen Intern Med 2006;21:
185-188.
- Dyer O. Purdue Pharma to plead guilty and pay $8.3bn over opioid marketing. BMJ 2020;371:m4103,
- Centers for Disease Control and Prevention. Drug overdose deaths in the U.S. top 100,000 annually. Published Nov. 17, 2021. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2021/20211117.htm
- Sprinklr. How cannabis companies market themselves in the pot boom. Published Jan. 20, 2021. https://www.sprinklr.com/blog/cannabis-marketing-strategies/
- Harris N. The dos and don’ts of marketing for the cannabis industry. New Perspective. Published Feb. 25, 2021. https://www.npws.net/blog/marketing-cannabis-industry/
- Sabet K. Lessons learned in several states eight years after states legalized marijuana. Curr Opin Psychol 2021;38:25-30.
