Underplaying the dangers of cannabis for women of childbearing age is sexist and pregnancy discrimination.
Dear Editor
Nutt overstated the case for medicinal cannabis and misrepresented the harms in pregnancy when dismissing Professor Chris Whitty’s rightful concerns as the Chief Scientific Adviser at the Department of Health and Social Care when informing MPs: “we have to conduct research in such a way that we avoid another thalidomide tragedy”.(1,2) Nutt plays straight into the hands of those interested businesses who chose Big Tobacco’s successful model of minimizing tobacco harms (3,4) by spreading “agnotology” (Greek agnōsis, "not knowing"). The neologism was coined by Robert Proctor, Professor in the history of science at Stanford University, who credited Big Tobacco for inducing ignorance and doubt.
Cannabis, a mixture of hundreds of cannabinoids, can cross the placental and blood–brain barriers and is excreted in breast milk. The fetal risks are serious, and the scope is wider than pregnancy alone as cannabis accumulates and has many weeks long duration of activity. Thus risks concern all women of child bearing age especially as many pregnancies are unplanned. This is a public health issue regarding societal wide levels of use; avoiding pregnancy exposure is not possible by women ceasing use just before becoming pregnant or in early pregnancy.
The teratogenic activity of cannabis was reported as early as 1968 and is robustly evidence based.(5,6) Professional associations warned about teratogenicity, including a risk of ventricular septal defect and Ebstein's syndrome, 15 years ago.(7,8) Malformations also include anencephaly, esophageal atresia, diaphragmatic hernia and gastroschisis.(9)
Cannabis is an independent factor increasing the likelihood of stillbirth, preterm birth, fetal growth restriction and low birth weight.(10-14) These adverse pregnancy outcomes remain significant after adjusting for race/ethnicity and tobacco.(15)
Cannabis use compromises offspring long-term neurobehavioral development, a very vulnerable period. Changes in brain microstructure and intellectual function, including decreases in intelligence quotient, have been noted in adult chronic cannabis users and appear permanent in early users.(16-18) So it should be no surprise that the stimulation of cannabinoid receptors during the perinatal period alters maturation in areas of the brain that subserve mood and cognitive function, therefore impacting neurodevelopmental outcomes (cognitive function, rewarding and emotional processes).(19-22)
Last, developmental cannabis exposure alters epigenetic processes. Epigenetic modifications involve chromatin histones methylations or acetylations. These changes can affect the immune system and brain maturation.(23,24) These gene alterations are potentially heritable. Findings also point to possible pre-conception paternal reproductive risk.(25)
Cannabis is already the most commonly used harmful substance during pregnancy, its use in the US rising from 3.4% (2002), to 7.0% (2017) and over 8% during the pandemic.(26) Research has indicated that pregnant women rarely report receiving helpful information about perinatal marijuana use from their healthcare providers.(27) Worse still, nearly 70% of Colorado cannabis dispensaries recommended cannabis products to treat nausea in the first trimester despite the US FDA issuing advice against cannabis during pregnancy and breastfeeding.(28,29) Nutt’s essay ostensibly deals with the medical indications for a drug which has not yet found its safe place in the medical armamentarium, but it gives women and the medical profession wrong information despite repeated warning against pre, ante and postnatal cannabis use from professional associations.(30,31) Alongside alcohol and tobacco, will another profitable, dependence-inducing product be commercialized despite causing harms to future children?
References
1 Nutt D. Why doctors have a moral imperative to prescribe and support medical cannabis—an essay by David Nutt. BMJ 2022;376:n3114. doi: https://doi.org/10.1136/bmj.n3114
3 Gornall J. Tobacco cash behind cannabis research in Oxford. BMJ. 2020;368:m1044. doi:10.1136/bmj.m1044
4 Gornall J. Big cannabis in the UK: is industry support for wider patient access motivated by promises of recreational market worth billions? BMJ 2020;368:m1002. doi:10.1136/bmj.m1002
6 Banerjee BN, Galbreath C, Sofia RD. Teratologic evaluation of synthetic delta-9-tetrahydrocannabinol in rats. Teratology 1975;11:99-101.
7 Jenkins KJ, Correa A, Feinstein JA, Botto L, Britt AE, Daniels SR et al. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 2007;115:2995-3014.
8 Reece AS, Hulse GK. Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends. Clin Pediatr (Phila) 2019;58:1085-1123. doi:10.1177/0009922819861281
9 van Gelder MM, Donders AR, Devine O, Roeleveld N, Reefhuis J; National Birth Defects Prevention Study. Using bayesian models to assess the effects of under-reporting of cannabis use on the association with birth defects, national birth defects prevention study, 1997-2005. Paediatr Perinat Epidemiol 2014;28:424-433. doi:10.1111/ppe.12140
10 Fergusson DM, Horwood LJ, Northstone K; ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Maternal use of cannabis and pregnancy outcome. BJOG 2002;109:21-27. doi:10.1111/j.1471-0528.2002.01020.x
11 Gunn JK, Rosales CB, Center KE, et al. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open. 2016;6:e009986. doi:10.1136/bmjopen-2015-009986
12 Crume TL, Juhl AL, Brooks-Russell A, Hall KE, Wymore E, Borgelt LM. Cannabis use during the perinatal period in a state with legalized recreational and medical marijuana: The association between maternal characteristics, breastfeeding patterns, and neonatal outcomes. J Pediatr 2018;197:90-96. doi: 10.1016/j.jpeds.2018.02.005
13 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. doi:10.1001/jama.2019.8734
14 Metz TD, Borgelt LM. Marijuana Use in Pregnancy and While Breastfeeding. Obstet Gynecol 2018;132:1198-1210. doi:10.1097/AOG.0000000000002878
15 Rodriguez CE, Sheeder J, Allshouse AA, et al. Marijuana use in young mothers and adverse pregnancy outcomes: a retrospective cohort study. BJOG 2019;126:1491-1497. doi:10.1111/1471-0528.15885
16 Bossong MG, Niesink RJ. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog Neurobiol 2010;92:370-385. doi:10.1016/j.pneurobio.2010.06.010
17 Filbey FM, Aslan S, Calhoun VD, et al. Long-term effects of marijuana use on the brain. Proc Natl Acad Sci U S A. 2014;111:16913-16918. doi:10.1073/pnas.1415297111
Rigucci S, Marques T, Di Forti M, et al. Effect of high potency cannabis on corpus callosum microstructure. Psychol Med 2016;46:841-854. doi:10.1017/S0033291715002342
18 deShazo RD, Parker SB, Williams D, et al. Marijuana's Effects on Brain Structure and Function: What Do We Know and What Should We Do? A Brief Review and Commentary. Am J Med 2019;132:281-285. doi:10.1016/j.amjmed.2018.09.006
19 DiNieri JA, Wang X, Szutorisz H, et al. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry. 2011;70:763-769. doi:10.1016/j.biopsych.2011.06.027
20 Higuera-Matas A, Ucha M, Ambrosio E. Long-term consequences of perinatal and adolescent cannabinoid exposure on neural and psychological processes. Neurosci Biobehav Rev 2015;55:119-46. doi: 10.1016/j.neubiorev.2015.04.020.
21 Jansson LM, Jordan CJ, Velez ML. Perinatal Marijuana Use and the Developing Child. JAMA. 2018;320(6):545-546. doi:10.1001/jama.2018.8401
22 Paul SE, Hatoum AS, Fine JD, et al. Associations Between Prenatal Cannabis Exposure and Childhood Outcomes: Results From the ABCD Study. JAMA Psychiatry. 2021;78(1):64-76. doi:10.1001/jamapsychiatry.2020.2902
23 Smith A, Kaufman F, Sandy MS, Cardenas A. Cannabis Exposure During Critical Windows of Development: Epigenetic and Molecular Pathways Implicated in Neuropsychiatric Disease. Curr Environ Health Rep 2020;7:325-342. doi:10.1007/s40572-020-00275-4
24 Reece AS, Hulse GK. Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. Mutat Res 2016;789:15-25. doi: 10.1016/j.mrfmmm.2016.05.002
25 Murphy SK, Itchon-Ramos N, Visco Z, Huang Z et coll. Cannabinoid exposure and altered DNA
methylation in rat and human sperm. Epigenetics 2018; 13:1208-21. doi:10.1080/15592294.2018.1554521
26 Young-Wolff KC, Ray GT, Alexeeff SE, et al. Rates of Prenatal Cannabis Use Among Pregnant Women Before and During the COVID-19 Pandemic. JAMA. 2021;326:1745-1747. doi:10.1001/jama.2021.16328
27 Jarlenski M, Tarr JA, Holland CL, Farrell D, Chang JC. Pregnant Women's Access to Information About Perinatal Marijuana Use: A Qualitative Study. Womens Health Issues. 2016;26(4):452-459. doi:10.1016/j.whi.2016.03.010
28 Dickson B, Mansfield C, Guiahi M, et al. Recommendations From Cannabis Dispensaries About First-Trimester Cannabis Use. Obstet Gynecol. 2018;131(6):1031-1038. doi:10.1097/AOG.0000000000002619
30 Committee on Obstetric Practice. Committee opinion no. 722: marijuana use during pregnancy and lactation. Obstet Gynecol 2017;130:e205-9. doi:10.1097/AOG.0000000000002354
31 Ryan SA, Ammerman SD, O’Connor ME; Committee on Substance Use and Prevention. Marijuana use during pregnancy and breastfeeding: implications for neonatal and childhood outcomes. Pediatrics 2018;e20181889A. doi:10.1542/peds.2018-1889A
Competing interests:
No competing interests
11 February 2022
Alain Braillon
Previously senior consultant.
Susan Bewley (Department of Women & Children's Health, King's College London, London, UK)
Rapid Response:
Underplaying the dangers of cannabis for women of childbearing age is sexist and pregnancy discrimination.
Dear Editor
Nutt overstated the case for medicinal cannabis and misrepresented the harms in pregnancy when dismissing Professor Chris Whitty’s rightful concerns as the Chief Scientific Adviser at the Department of Health and Social Care when informing MPs: “we have to conduct research in such a way that we avoid another thalidomide tragedy”.(1,2) Nutt plays straight into the hands of those interested businesses who chose Big Tobacco’s successful model of minimizing tobacco harms (3,4) by spreading “agnotology” (Greek agnōsis, "not knowing"). The neologism was coined by Robert Proctor, Professor in the history of science at Stanford University, who credited Big Tobacco for inducing ignorance and doubt.
Cannabis, a mixture of hundreds of cannabinoids, can cross the placental and blood–brain barriers and is excreted in breast milk. The fetal risks are serious, and the scope is wider than pregnancy alone as cannabis accumulates and has many weeks long duration of activity. Thus risks concern all women of child bearing age especially as many pregnancies are unplanned. This is a public health issue regarding societal wide levels of use; avoiding pregnancy exposure is not possible by women ceasing use just before becoming pregnant or in early pregnancy.
The teratogenic activity of cannabis was reported as early as 1968 and is robustly evidence based.(5,6) Professional associations warned about teratogenicity, including a risk of ventricular septal defect and Ebstein's syndrome, 15 years ago.(7,8) Malformations also include anencephaly, esophageal atresia, diaphragmatic hernia and gastroschisis.(9)
Cannabis is an independent factor increasing the likelihood of stillbirth, preterm birth, fetal growth restriction and low birth weight.(10-14) These adverse pregnancy outcomes remain significant after adjusting for race/ethnicity and tobacco.(15)
Cannabis use compromises offspring long-term neurobehavioral development, a very vulnerable period. Changes in brain microstructure and intellectual function, including decreases in intelligence quotient, have been noted in adult chronic cannabis users and appear permanent in early users.(16-18) So it should be no surprise that the stimulation of cannabinoid receptors during the perinatal period alters maturation in areas of the brain that subserve mood and cognitive function, therefore impacting neurodevelopmental outcomes (cognitive function, rewarding and emotional processes).(19-22)
Last, developmental cannabis exposure alters epigenetic processes. Epigenetic modifications involve chromatin histones methylations or acetylations. These changes can affect the immune system and brain maturation.(23,24) These gene alterations are potentially heritable. Findings also point to possible pre-conception paternal reproductive risk.(25)
Cannabis is already the most commonly used harmful substance during pregnancy, its use in the US rising from 3.4% (2002), to 7.0% (2017) and over 8% during the pandemic.(26) Research has indicated that pregnant women rarely report receiving helpful information about perinatal marijuana use from their healthcare providers.(27) Worse still, nearly 70% of Colorado cannabis dispensaries recommended cannabis products to treat nausea in the first trimester despite the US FDA issuing advice against cannabis during pregnancy and breastfeeding.(28,29) Nutt’s essay ostensibly deals with the medical indications for a drug which has not yet found its safe place in the medical armamentarium, but it gives women and the medical profession wrong information despite repeated warning against pre, ante and postnatal cannabis use from professional associations.(30,31) Alongside alcohol and tobacco, will another profitable, dependence-inducing product be commercialized despite causing harms to future children?
References
1 Nutt D. Why doctors have a moral imperative to prescribe and support medical cannabis—an essay by David Nutt. BMJ 2022;376:n3114. doi: https://doi.org/10.1136/bmj.n3114
2 PicklesK. Medical cannabis may be harmful, MPs are told: Experts warn that drug trials have shown only 'moderate benefits' for sufferers. Daily Mail 27 March 2019. Available at https://www.dailymail.co.uk/health/article-6854171/Medical-cannabis-harm... Acessed 9 February 2022
3 Gornall J. Tobacco cash behind cannabis research in Oxford. BMJ. 2020;368:m1044. doi:10.1136/bmj.m1044
4 Gornall J. Big cannabis in the UK: is industry support for wider patient access motivated by promises of recreational market worth billions? BMJ 2020;368:m1002. doi:10.1136/bmj.m1002
5 Persaud TV, Ellington AC. Teratogenic activity of cannabis resin. Lancet. 1968;2:406-407. doi:10.1016/s0140-6736(68)90626-0
6 Banerjee BN, Galbreath C, Sofia RD. Teratologic evaluation of synthetic delta-9-tetrahydrocannabinol in rats. Teratology 1975;11:99-101.
7 Jenkins KJ, Correa A, Feinstein JA, Botto L, Britt AE, Daniels SR et al. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 2007;115:2995-3014.
8 Reece AS, Hulse GK. Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends. Clin Pediatr (Phila) 2019;58:1085-1123. doi:10.1177/0009922819861281
9 van Gelder MM, Donders AR, Devine O, Roeleveld N, Reefhuis J; National Birth Defects Prevention Study. Using bayesian models to assess the effects of under-reporting of cannabis use on the association with birth defects, national birth defects prevention study, 1997-2005. Paediatr Perinat Epidemiol 2014;28:424-433. doi:10.1111/ppe.12140
10 Fergusson DM, Horwood LJ, Northstone K; ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Maternal use of cannabis and pregnancy outcome. BJOG 2002;109:21-27. doi:10.1111/j.1471-0528.2002.01020.x
11 Gunn JK, Rosales CB, Center KE, et al. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open. 2016;6:e009986. doi:10.1136/bmjopen-2015-009986
12 Crume TL, Juhl AL, Brooks-Russell A, Hall KE, Wymore E, Borgelt LM. Cannabis use during the perinatal period in a state with legalized recreational and medical marijuana: The association between maternal characteristics, breastfeeding patterns, and neonatal outcomes. J Pediatr 2018;197:90-96. doi: 10.1016/j.jpeds.2018.02.005
13 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. doi:10.1001/jama.2019.8734
14 Metz TD, Borgelt LM. Marijuana Use in Pregnancy and While Breastfeeding. Obstet Gynecol 2018;132:1198-1210. doi:10.1097/AOG.0000000000002878
15 Rodriguez CE, Sheeder J, Allshouse AA, et al. Marijuana use in young mothers and adverse pregnancy outcomes: a retrospective cohort study. BJOG 2019;126:1491-1497. doi:10.1111/1471-0528.15885
16 Bossong MG, Niesink RJ. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog Neurobiol 2010;92:370-385. doi:10.1016/j.pneurobio.2010.06.010
17 Filbey FM, Aslan S, Calhoun VD, et al. Long-term effects of marijuana use on the brain. Proc Natl Acad Sci U S A. 2014;111:16913-16918. doi:10.1073/pnas.1415297111
Rigucci S, Marques T, Di Forti M, et al. Effect of high potency cannabis on corpus callosum microstructure. Psychol Med 2016;46:841-854. doi:10.1017/S0033291715002342
18 deShazo RD, Parker SB, Williams D, et al. Marijuana's Effects on Brain Structure and Function: What Do We Know and What Should We Do? A Brief Review and Commentary. Am J Med 2019;132:281-285. doi:10.1016/j.amjmed.2018.09.006
19 DiNieri JA, Wang X, Szutorisz H, et al. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry. 2011;70:763-769. doi:10.1016/j.biopsych.2011.06.027
20 Higuera-Matas A, Ucha M, Ambrosio E. Long-term consequences of perinatal and adolescent cannabinoid exposure on neural and psychological processes. Neurosci Biobehav Rev 2015;55:119-46. doi: 10.1016/j.neubiorev.2015.04.020.
21 Jansson LM, Jordan CJ, Velez ML. Perinatal Marijuana Use and the Developing Child. JAMA. 2018;320(6):545-546. doi:10.1001/jama.2018.8401
22 Paul SE, Hatoum AS, Fine JD, et al. Associations Between Prenatal Cannabis Exposure and Childhood Outcomes: Results From the ABCD Study. JAMA Psychiatry. 2021;78(1):64-76. doi:10.1001/jamapsychiatry.2020.2902
23 Smith A, Kaufman F, Sandy MS, Cardenas A. Cannabis Exposure During Critical Windows of Development: Epigenetic and Molecular Pathways Implicated in Neuropsychiatric Disease. Curr Environ Health Rep 2020;7:325-342. doi:10.1007/s40572-020-00275-4
24 Reece AS, Hulse GK. Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. Mutat Res 2016;789:15-25. doi: 10.1016/j.mrfmmm.2016.05.002
25 Murphy SK, Itchon-Ramos N, Visco Z, Huang Z et coll. Cannabinoid exposure and altered DNA
methylation in rat and human sperm. Epigenetics 2018; 13:1208-21. doi:10.1080/15592294.2018.1554521
26 Young-Wolff KC, Ray GT, Alexeeff SE, et al. Rates of Prenatal Cannabis Use Among Pregnant Women Before and During the COVID-19 Pandemic. JAMA. 2021;326:1745-1747. doi:10.1001/jama.2021.16328
27 Jarlenski M, Tarr JA, Holland CL, Farrell D, Chang JC. Pregnant Women's Access to Information About Perinatal Marijuana Use: A Qualitative Study. Womens Health Issues. 2016;26(4):452-459. doi:10.1016/j.whi.2016.03.010
28 Dickson B, Mansfield C, Guiahi M, et al. Recommendations From Cannabis Dispensaries About First-Trimester Cannabis Use. Obstet Gynecol. 2018;131(6):1031-1038. doi:10.1097/AOG.0000000000002619
29
U.S. Food and Drug Administration.
What You Should Know About Using Cannabis, Including CBD, When Pregnant or Breastfeeding. Consumers updates
16 October 2019. Available at https://www.fda.gov/consumers/consumer-updates/what-you-should-know-abou... accessed 9 February 2022.
30 Committee on Obstetric Practice. Committee opinion no. 722: marijuana use during pregnancy and lactation. Obstet Gynecol 2017;130:e205-9. doi:10.1097/AOG.0000000000002354
31 Ryan SA, Ammerman SD, O’Connor ME; Committee on Substance Use and Prevention. Marijuana use during pregnancy and breastfeeding: implications for neonatal and childhood outcomes. Pediatrics 2018;e20181889A. doi:10.1542/peds.2018-1889A
Competing interests: No competing interests