Science Lagging Behind Rapid Cannabis Legalization and Commercialization

Torri D. Metz, MD, MSCannabis legalization has progressively increased across the United States. On many street corners, billboards tout the value of cannabis to assist with nearly every ailment. Dispensary business is booming. BDSA, a leading cannabis market research organization, estimated that the U.S. cannabis industry would reach $29.6 billion in legal sales in 2023.1 Similarly, there is an increasing perception of safety of cannabis products that extends across social strata and into pregnancy.2 Yet, the scientific understanding of cannabis and the health effects of cannabis remains in its infancy. This is, in part, due to regulatory hurdles, difficulty ascertaining use patterns, changing content and concentration of cannabis products, different modalities of cannabis use, and a strong societal push to conflate the benefits of use while minimizing any adverse effects. In the pregnant population, there are also ethical concerns with conducting randomized trials, which are the scientific gold standard on which we build the tenets of “evidence-based” medicine, and unique concerns about reliance on self-reported use given the stigma and legal ramifications of reporting use in pregnancy. In this month's issue of Obstetrics & Gynecology, Bhatia et al3 (see page 156) report on the prevalence of cannabidiol (CBD) product use in pregnant individuals compared with nonpregnant individuals using data from the International Cannabis Policy Study, which is a cross-sectional survey that recruited participants across the United States and Canada. In the study, the prevalence of past-month CBD use in the pregnant population was nearly double that of reproductive-aged females outside of pregnancy, and one in five pregnant individuals reported use of CBD-only products. There are limitations to this work, in that it is a cross-sectional, web-based sample that is unlikely to be representative of the general population. Nonetheless, it is critically important work, because it begins to provide some insight into use patterns of CBD-only products in pregnancy. The prevalence of use was very high among pregnant people, indicating that pregnant individuals may perceive that CBD is a safe drug to use in pregnancy, despite there being essentially no data examining whether or not this is the case. The majority of participants in the study by Bhatia et al reported using CBD oils, which may be perceived as safer or may simply be more available. Pregnant individuals had increased odds of having a prescription for CBD than those who were not pregnant, which is surprising because the reported indications for CBD use included mental health disorders, nausea, and seizures, which all have a number of other options for therapies that are likely to be safer and have demonstrated efficacy in pregnancy.4–6 The provision of a prescription for CBD likely signifies to a patient that CBD is safe in pregnancy. Similarly, in another cross-sectional study of more than 10,000 participants using PRAMS (Pregnancy Risk Assessment Monitoring System) data from 2017 to 2019, 63% of pregnant individuals reported that they were not told to avoid cannabis use in pregnancy, and 8% noted that they were advised to use cannabis by their prenatal care practitioner.7 The American College of Obstetricians and Gynecologists recommends against prescribing cannabis products for people who are pregnant or lactating.8 Moving forward, it will be valuable to address who is prescribing CBD products for common pregnancy ailments and health conditions for pregnant individuals and to study how best to provide education about the safety and efficacy of other available therapies. As the authors note, data are scant to nonexistent on the topic of CBD products in pregnancy. There certainly may be differential effects of different cannabis products on pregnancy outcomes. The literature related to delta-9-tetrahydrocannabinol (THC) and its metabolites demonstrates a consistent association between cannabis use and decreased fetal growth.9 There also remain persistent concerns about the long-term neurodevelopmental effects of maternal cannabis use on the fetus and, subsequently, the newborn.10 It is thought that these effects are likely through interaction with CBD receptors (CB1 and CB2), because endogenous cannabinoids are active in placentation and in fetal neurodevelopment.10 Because CBD has lower affinity for these receptors when compared with THC products, it is possible that CBD would have a less detrimental effect.11 However, CBD products are not federally regulated and have been found to also contain THC.12 Thus, the adverse effects noted with THC products may still apply, and there is some suggestion of a synergistic effect between THC and CBD in animal models.13 Development of urine and serum assays to help ascertain use of CBD products will be helpful in moving the field forward, given the inability to rely on self-reported use in pregnancy because of the drastic underestimation of use in self-reported data.14,15 This publication in Obstetrics & Gynecology represents an important initial step in investigating the use of CBD-only products in pregnancy. Based on published literature, the rate of cannabis use among pregnant individuals in the U.S. is likely in the range of 5–10%, with rates as high as 30% in some subsets of the population.10 Thus, a substantial number of mothers and fetuses are exposed to cannabis, and there should be an urgency to investigate the health effects in pregnancy for both mothers and their offspring. The lack of broad public health messaging for pregnant people to abstain from cannabis use likely stems from a lag in the science. It is difficult for clinicians at the bedside to convey a strong recommendation regarding abstinence of use in pregnancy when we continue to lack data related to pregnancy outcomes for modern cannabis products. Yet, evidence regarding potential harms of prenatal cannabis use continues to mount.16,17 Examination of the association between different cannabis product types and adverse outcomes will be a critical piece of this effort. Pregnant individuals deserve to be informed about cannabis use and the anticipated outcomes of use so that they can make educated decisions about their use in pregnancy. Whenever possible, evidence should drive counseling. We are failing pregnant people as the science continues to lag behind the legalization and commercialization of cannabis.

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