Motherisk Int J 2020;1:7
Rana Cohen BSc Pharm, Mati Berkovitch MD
Motherisk Israel Program and Ariel University Faculty of Medicine
I see increasing reports in the social media of American women with hyperemesis gravidarum reporting on beneficial effects of cannabis in hyperemesis. What about the fetal risks of cannabis?
Excellent question. There is new evidence of neurodevelopmental risks of hyperemesis gravidarum itself. In contrast, after 40 years and numerous studies, the fetal risks of cannabis have not been substantiated. This review tries to present a risk: benefit balance.
Hyperemesis Gravidarum (HG) affects up to 2% of pregnant women, with strong evidence of serious physical, emotional and behavioral adverse effects on the mother (1). Presently the effectiveness of existing anti-emetic medications on HG symptom relief is meagre. The antiemetic effects of cannabinoid have long been documented. In parallel there is growing evidence outside the realm of clinical studies suggesting efficacy of cannabis for HG symptoms. There are concerns regarding the potential effects of cannabis on fetal brain development, while new research suggests that HG itself may adversely affect cognitive development in exposed children.
Objectvies and Methods
To systematically review:
a) Peer and non- peer review data on the efficacy of cannabis in HG;
b) Published data on fetal safety/risk of cannabis on fetal brain development;
c) Published data on fetal neurodevelopmental risks of HG;
d) To balance these aspects and suggest a research agenda to move forward.
a) There are numerous peer review publications showing the antiemetic effects of cannabis in non- pregnant individuals, but not in pregnancy (2). In contrast, with the legalization of cannabis in the USA there is wide new evidence from social media and self-help women’s websites, describing favorable, and often dramatic effects in women with HG(3). In a proportion of these cases favorable child development is also described, with no reports of adverse fetal outcome. Several peer reviewed questionnaire studies from British Columbia and Hawaii describe high efficacy of cannabis on severe NVP, as reported by the women and physicians (4-5).
b) We describe 4 cases of HG who were treated with cannabis at concentrations of 18-22% and followed up by us. In all 4 there was a dramatic improvement in HG with doses of 2-3 puffs every 2-3 hours. Typical use was of 1 g/d. All 4 children have been described to develop normally (6).
c) Over the last 4 decades, a large number of studies have followed up children exposed in utero to cannabis, comparing them to non- exposed infants. Overall, there were no consistent cognitive deficits, ADHD or other adverse effects. A small number of studies claimed small effect size adverse effects, although there is potential confounding by concomitant maternal drinking, smoking and other lifestyle confounders (7-8).
d) Several longitudinal studies have documented loss of IQ and increased risk of conditions such as ADHD, among offspring exposed in utero to maternal HG. This evidence is consistent with famine studies documenting cognitive fetal effects in the Netherland and China after maternal starvation, and the known nutritional deficits of HG (9).
The balance of the above data suggests that the efficacy and safety of different cannabinoids in HG should be considered. Because of the ethical-medicolegal aspects of such research, it would make sense to study first some of the thousands of the pregnant women using cannabis medically or recreationally in states where cannabis use is legal.
Without well-designed, controlled studies, it would be difficult to address the potential efficacy and safety of cannabis for HG.
1) Clark SM, Costantine MM, Hankins GD. Review of NVP and HG and early pharmacotherapeutic intervention. Obstet Gynecol Int. 2012;252- 676(10):24
2) Mersiades AJ, Tognela A, Haber PS, et al. Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV). BMJ Open. 2018 Sep 12;8(9):e020745. doi: 10.1136/bmjopen-2017-020745.
3) https://www.facebook.com . Accessed June 24, 2019
4) Roberson EK1, Patrick WK1, Hurwitz EL1 Hawaii J Med Public Health. 2014 Sep;73(9):283-7.
5) Westfall RE1, Janssen PA, Lucas P, Capler R. Survey of medicinal cannabis use among childbearing women: patterns of its use in pregnancy and retroactive self-assessment of its efficacy against 'morning sickness'. Complement Ther Clin Pract. 2006 Feb;12(1):27-33. Epub 2005 Dec 22.]
6) Cohen R, Koren G: The use of cannabis for hyperemesis gravidarum-A report from Motherisk Israel. The Forth Coloqium on Hyperemesis Gravidarum. Amsterdam, Netherland, October10-11, 2019.
7) Sharapova SR, Phillips E, Sirocco K, Kaminski JWet al. Effects of prenatal marijuana exposure on neuropsychological outcomes in children aged 1-11 years: A systematic review. Paediatr Perinat Epidemiol. 2018 Nov;32(6):512-532.
8) El Marroun H, Bolhuis K, Franken IHA, et al. Preconception and prenatal cannabis use and the risk of behavioral and emotional problems in the offspring. IntJ Epidemiol 2019; 48: 287-296
9) Koren G, Ornoy A, Berkovitch M. Hyperemesis gravidarum-Is it a cause of abnormal fetal brain development? Reprod Toxicol. 2018 Aug;79:84-88