Impact of cannabinoids on pregnancy, reproductive health, and offspring outcomes

      Cannabis is the most commonly used federally illegal drug in the United States and the world, especially among people of reproductive age. In addition, the potency of cannabis products has increased significantly in the past decade. This is concerning because the available evidence suggests an adverse effect of cannabis exposure on male and female reproductive health. Exposure to cannabinoids may have differential impacts on female reproductive health across a woman’s lifespan, from preconception to pregnancy, throughout lactation, and during menopause. Moreover, cannabis use has been associated with adverse effects on fetal outcomes and longer-term offspring health and developmental trajectories. Despite the prevalence of cannabis use, there is limited available evidence regarding its safety, especially in regard to reproductive health, pregnancy, and lactation. The biological effects of cannabis are mediated by the endocannabinoid system, and studies have reported the presence of cannabinoid receptors in the male and female reproductive tract, on sperm and the placenta, suggesting that the endocannabinoid system plays a role in regulating reproduction. Cannabis use can affect male and female fertility and has been associated with altered reproductive hormones, menstrual cyclicity, and semen parameters. Use of cannabis in male patients has also been associated with erectile dysfunction, abnormal spermatogenesis, and testicular atrophy. In female patients, cannabis use has been associated with infertility and abnormal embryo implantation and development. The main psychoactive component of cannabis, the delta-9-tetrahydrocannabinol, can also cross the placenta and has been detected in breast milk. Maternal cannabis use during pregnancy and lactation has been associated with adverse effects, including small-for-gestational-age infants, preterm birth, fetal neurodevelopmental consequences, and impaired offspring sociobehavioral and cognitive development. The prevalence of cannabis use for alleviating menopausal symptoms has also increased despite the limited information on its benefits and safety. Given that cannabis use is on the rise, it is critical to understand its impact on reproductive health and offspring developmental outcomes. This is an understudied but timely subject requiring much further information to guide healthcare providers and those interested in conceiving or who are pregnant and lactating, and those at the end of their reproductive time span.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • United Nations Office on Drugs and Crime
        World drug report 2021. 2021.
        (Available at:)
        • Center for Behavioral Health Statistics and Quality
        Key substance use and mental health indicators in the United States: results from the 2020 National Survey on Drug Use and Health.
        Substance Abuse and Mental Health Services Administration, Rockville, MD2021
      1. Substance Abuse and Mental Health Services Administration. (2021). Key substance use and mental health indicators in the United States: Results from the 2020 National Survey on Drug Use and Health (HHS Publication No. PEP21-07-01-003, NSDUH Series H-56). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Available at:

        • Young-Wolff K.C.
        • Ray G.T.
        • Alexeeff S.E.
        • et al.
        Rates of prenatal cannabis use among pregnant women before and during the COVID-19 pandemic.
        JAMA. 2021; 326: 1745-1747
        • Imtiaz S.
        • Wells S.
        • Rehm J.
        • et al.
        Cannabis use during the COVID-19 pandemic in Canada: a repeated cross-sectional study.
        J Addict Med. 2021; 15: 484-490
        • ElSohly M.A.
        • Chandra S.
        • Radwan M.
        • Gon C.
        • Church J.C.
        A comprehensive review of cannabis potency in the United States in the last decade.
        Biol Psychiatry Cogn Neurosci Neuroimaging. 2021; 6: 603-606
        • Wu C.S.
        • Jew C.P.
        • Lu H.C.
        Lasting impacts of prenatal cannabis exposure and the role of endogenous cannabinoids in the developing brain.
        Future Neurol. 2011; 6: 459-480
        • Martínez-Peña A.A.
        • Perono G.A.
        • Gritis S.A.
        • et al.
        The impact of early life exposure to cannabis: the role of the endocannabinoid system.
        Int J Mol Sci. 2021; 22: 8576
        • Dunne C.
        The effects of cannabis on female and male reproduction.
        BCMJ. 2019; 61: 282-285
        • Uhlén M.
        • Fagerberg L.
        • Hallström B.M.
        • et al.
        Proteomics. Tissue-based map of the human proteome.
        Science. 2015; 3471260419
        • Aquila S.
        • Guido C.
        • Santoro A.
        • et al.
        Human sperm anatomy: ultrastructural localization of the cannabinoid1 receptor and a potential role of anandamide in sperm survival and acrosome reaction.
        Anat Rec (Hoboken). 2010; 293: 298-309
        • Jensen B.
        • Chen J.
        • Furnish T.
        • Wallace M.
        Medical marijuana and chronic pain: a review of basic science and clinical evidence.
        Curr Pain Headache Rep. 2015; 19: 50
        • Gundersen T.D.
        • Jørgensen N.
        • Andersson A.M.
        • et al.
        Association between use of marijuana and male reproductive hormones and semen quality: a study among 1,215 healthy young men.
        Am J Epidemiol. 2015; 182: 473-481
        • Ryan K.S.
        • Mahalingaiah S.
        • Campbell L.R.
        • et al.
        The effects of delta-9-tetrahydrocannabinol exposure on female menstrual cyclicity and reproductive health in rhesus macaques.
        F S Sci. 2021; 2: 287-294
        • Ryan K.S.
        • Bash J.C.
        • Hanna C.B.
        • Hedges J.C.
        • Lo J.O.
        Effects of marijuana on reproductive health: preconception and gestational effects.
        Curr Opin Endocrinol Diabetes Obes. 2021; 28: 558-565
        • Alhusen J.L.
        • Lucea M.B.
        • Bullock L.
        • Sharps P.
        Intimate partner violence, substance use, and adverse neonatal outcomes among urban women.
        J Pediatr. 2013; 163: 471-476
        • Varner M.W.
        • Silver R.M.
        • Rowland Hogue C.J.R.
        • et al.
        Association between stillbirth and illicit drug use and smoking during pregnancy.
        Obstet Gynecol. 2014; 123: 113-125
        • Hayatbakhsh M.R.
        • Flenady V.J.
        • Gibbons K.S.
        • et al.
        Birth outcomes associated with cannabis use before and during pregnancy.
        Pediatr Res. 2012; 71: 215-219
        • El Marroun H.
        • Tiemeier H.
        • Steegers E.A.
        • et al.
        Intrauterine cannabis exposure affects fetal growth trajectories: the Generation R Study.
        J Am Acad Child Adolesc Psychiatry. 2009; 48: 1173-1181
        • Hurd Y.L.
        • Wang X.
        • Anderson V.
        • Beck O.
        • Minkoff H.
        • Dow-Edwards D.
        Marijuana impairs growth in mid-gestation fetuses.
        Neurotoxicol Teratol. 2005; 27: 221-229
        • Day N.L.
        • Goldschmidt L.
        • Thomas C.A.
        Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14.
        Addiction. 2006; 101: 1313-1322
        • Fernández-Ruiz J.J.
        • Berrendero F.
        • Hernández M.L.
        • Romero J.
        • Ramos J.A.
        Role of endocannabinoids in brain development.
        Life Sci. 1999; 65: 725-736
        • Goldschmidt L.
        • Richardson G.A.
        • Willford J.
        • Day N.L.
        Prenatal marijuana exposure and intelligence test performance at age 6.
        J Am Acad Child Adolesc Psychiatry. 2008; 47: 254-263
        • Gunn J.K.
        • Rosales C.B.
        • Center K.E.
        • et al.
        Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis.
        BMJ Open. 2016; 6e009986
        • Conner S.N.
        • Bedell V.
        • Lipsey K.
        • Macones G.A.
        • Cahill A.G.
        • Tuuli M.G.
        Maternal marijuana use and adverse neonatal outcomes: a systematic review and meta-analysis.
        Obstet Gynecol. 2016; 128: 713-723
        • Ko J.Y.
        • Farr S.L.
        • Tong V.T.
        • Creanga A.A.
        • Callaghan W.M.
        Prevalence and patterns of marijuana use among pregnant and nonpregnant women of reproductive age.
        Am J Obstet Gynecol. 2015; 213: 201.e1-201.e10
        • Dickson B.
        • Mansfield C.
        • Guiahi M.
        • et al.
        Recommendations from cannabis dispensaries about first-trimester cannabis use.
        Obstet Gynecol. 2018; 131: 1031-1038
        • ElSohly M.A.
        • Mehmedic Z.
        • Foster S.
        • Gon C.
        • Chandra S.
        • Church J.C.
        Changes in cannabis potency over the last 2 decades (1995-2014): analysis of current data in the United States.
        Biol Psychiatry. 2016; 79: 613-619
        • Grotenhermen F.
        Pharmacology of cannabinoids.
        Neuro Endocrinol Lett. 2004; 25: 14-23
        • National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice, Committee on the Health Effects of Marijuana
        An evidence review and research agenda. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. 2017.
        (Available at:)
        Date accessed: February 1, 2022
        • Subbaraman M.S.
        • Kerr W.C.
        Cannabis use frequency, route of administration, and co-use with alcohol among older adults in Washington state.
        J Cannabis Res. 2021; 3: 17
        • Young-Wolff K.C.
        • Adams S.R.
        • Wi S.
        • Weisner C.
        • Conway A.
        Routes of cannabis administration among females in the year before and during pregnancy: results from a pilot project.
        Addict Behav. 2020; 100106125
        • Huestis M.A.
        • Sampson A.H.
        • Holicky B.J.
        • Henningfield J.E.
        • Cone E.J.
        Characterization of the absorption phase of marijuana smoking.
        Clin Pharmacol Ther. 1992; 52: 31-41
        • Monte A.A.
        • Zane R.D.
        • Heard K.J.
        The implications of marijuana legalization in Colorado.
        JAMA. 2015; 313: 241-242
        • Goodwin R.S.
        • Gustafson R.A.
        • Barnes A.
        • Nebro W.
        • Moolchan E.T.
        • Huestis M.A.
        Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral administration of cannabinoids.
        Ther Drug Monit. 2006; 28: 545-551
        • Wall M.E.
        • Sadler B.M.
        • Brine D.
        • Taylor H.
        • Perez-Reyes M.
        Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women.
        Clin Pharmacol Ther. 1983; 34: 352-363
        • Gustafson R.A.
        • Moolchan E.T.
        • Barnes A.
        • Levine B.
        • Huestis M.A.
        Validated method for the simultaneous determination of delta 9-tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC in human plasma using solid phase extraction and gas chromatography-mass spectrometry with positive chemical ionization.
        J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 798: 145-154
        • Perez-Reyes M.P.
        • Lipton M.A.
        • Timmons M.C.
        • Wall M.E.
        • Brine D.R.
        • Davis K.H.
        Pharmacology of orally administered 9 -tetrahydrocannabinol.
        Clin Pharmacol Ther. 1973; 14: 48-55
        • Ohlsson A.
        • Lindgren J.E.
        • Wahlen A.
        • Agurell S.
        • Hollister L.E.
        • Gillespie H.K.
        Plasma delta-9-tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking.
        Clin Pharmacol Ther. 1980; 28: 409-416
        • Huestis M.A.
        Human cannabinoid pharmacokinetics.
        Chem Biodivers. 2007; 4: 1770-1804
        • Elsohly M.A.
        • Little Jr., T.L.
        • Hikal A.
        • Harland E.
        • Stanford D.F.
        • Walker L.
        Rectal bioavailability of delta-9-tetrahydrocannabinol from various esters.
        Pharmacol Biochem Behav. 1991; 40: 497-502
        • Chatterjee S.
        • Isaac M.K.
        American Psychiatric Association. Diagnostic and statistical manual of mental disorders (3rd edition, revised) (DSM-IIIR).
        1987: 971-979
        • Bahji A.
        • Stephenson C.
        • Tyo R.
        • Hawken E.R.
        • Seitz D.P.
        Prevalence of cannabis withdrawal symptoms among people with regular or dependent use of cannabinoids: a systematic review and meta-analysis.
        JAMA Network Open. 2020; 3e202370
        • Bahji A.
        • Meyyappan A.C.
        • Hawken E.R.
        • Tibbo P.G.
        Pharmacotherapies for cannabis use disorder: a systematic review and network meta-analysis.
        Int J Drug Policy. 2021; 97103295
        • Fergusson D.M.
        • Boden J.M.
        • Horwood L.J.
        Psychosocial sequelae of cannabis use and implications for policy: findings from the Christchurch Health and Development Study.
        Soc Psychiatry Psychiatr Epidemiol. 2015; 50: 1317-1326
      2. United Nations Office on Drugs and Crime. World Drug Report 2018. United Nations publication, Sales No. E. 18. XI. 9 2018. Accessed February 1, 2022.

        • Hasin D.S.
        • Kerridge B.T.
        • Saha T.D.
        • et al.
        Prevalence and correlates of DSM-5 cannabis use disorder, 2012-2013: findings from the National Epidemiologic Survey on Alcohol and Related Conditions–III.
        Am J Psychiatry. 2016; 173: 588-599
        • Gnofam M.
        • Allshouse A.A.
        • Stickrath E.H.
        • Metz T.D.
        Impact of marijuana legalization on prevalence of maternal marijuana use and perinatal outcomes.
        Am J Perinatol. 2020; 37: 59-65
        • Ammerman S.
        • Ryan S.
        • Adelman W.P.
        Committee on Substance Abuse, the Committee on Adolescence. The impact of marijuana policies on youth: clinical, research, and legal update.
        Pediatrics. 2015; 135: e769-e785
        • Kuhn C.
        • Ignar D.
        • Windh R.
        Endocrine function as a target of perinatal drug effects: methodologic issues.
        NIDA Res Monogr. 1991; 114: 206-232
        • Field E.
        • Tyrey L.
        Delayed sexual maturation in the female rat during chronic exposure to delta-9-tetrahydrocannabinol.
        Life Sci. 1984; 35: 1725-1730
        • Gupta D.
        • Elbracht C.
        Effect of tetrahydrocannabinols on pubertal body weight spurt and sex hormones in developing male rats.
        Res Exp Med (Berl). 1983; 182: 95-104
        • Jabeen S.
        • Raja G.K.
        • Akram M.
        • Ahmad A.
        • Qayyum M.
        • Rizvi S.R.
        Evidence of stimulation of pubertal development and suppression of growth rate in boys smoking marijuana in cigarettes.
        In Endocrine Abstracts. 2015; (May 1 (Vol. 37). Bioscientifica)
        • Smith A.M.
        • Ferris J.A.
        • Simpson J.M.
        • Shelley J.
        • Pitts M.K.
        • Richters J.
        Cannabis use and sexual health.
        J Sex Med. 2010; 7: 787-793
        • Pizzol D.
        • Demurtas J.
        • Stubbs B.
        • et al.
        Relationship between cannabis use and erectile dysfunction: a systematic review and meta-analysis.
        Am J Mens Health. 2019; 131557988319892464
        • Bhambhvani H.P.
        • Kasman A.M.
        • Wilson-King G.
        • Eisenberg M.L.
        A survey exploring the relationship between cannabis use characteristics and sexual function in men.
        Sex Med. 2020; 8: 436-445
        • Cone E.J.
        • Johnson R.E.
        • Moore J.D.
        • Roache J.D.
        Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects.
        Pharmacol Biochem Behav. 1986; 24: 1749-1754
        • Dalterio S.
        • Badr F.
        • Bartke A.
        • Mayfield D.
        Cannabinoids in male mice: effects on fertility and spermatogenesis.
        Science. 1982; 216: 315-316
        • Kolodny R.C.
        • Masters W.H.
        • Kolodner R.M.
        • Toro G.
        Depression of plasma testosterone levels after chronic intensive marihuana use.
        N Engl J Med. 1974; 290: 872-874
        • Hembree W.C.
        • Zeidenberg P.
        • Nahas G.G.
        Marihuana’s effects on human gonadal function.
        in: Marihuana. Springer, Berlin, Heidelberg1976: 521-532
        • HEMBREE III, W.C.
        • Nahas G.G.
        • Zeidenberg P.
        • Huang H.F.
        Changes in human spermatozoa associated with high dose marihuana smoking.
        Adv Biosci. 1978; 22–23: 429-439
        • Issidorides M.R.
        Observations in chronic hashish users: nuclear aberrations in blood and sperm and abnormal acrosomes in spermatozoa.
        Adv Biosci. 1978; 22–23: 377-388
        • Mendelson J.H.
        • Kuehnle J.
        • Ellingboe J.
        • Babor T.F.
        Plasma testosterone levels before, during and after chronic marihuana smoking.
        N Engl J Med. 1974; 291: 1051-1055
        • Mendelson J.H.
        • Ellingboe J.
        • Kuehnle J.C.
        • Mello N.K.
        Effects of chronic marihuana use on integrated plasma testosterone and luteinizing hormone levels.
        J Pharmacol Exp Ther. 1978; 207: 611-617
        • Schaefer C.F.
        • Gunn C.G.
        • Dubowski K.M.
        Letter: Normal plasma testosterone concentrations after marihuana smoking.
        N Engl J Med. 1975; 292: 867-868
        • Block R.I.
        • Farinpour R.
        • Schlechte J.A.
        Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women.
        Drug Alcohol Depend. 1991; 28: 121-128
        • Grimaldi P.
        • Orlando P.
        • Di Siena S.
        • et al.
        The endocannabinoid system and pivotal role of the CB2 receptor in mouse spermatogenesis.
        Proc Natl Acad Sci U S A. 2009; 106: 11131-11136
        • Dalterio S.
        • Bartke A.
        • Burstein S.
        Cannabinoids inhibit testosterone secretion by mouse testes in vitro.
        Science. 1977; 196: 1472-1473
        • Symons A.M.
        • Teale J.D.
        • Marks V.
        Proceedings: effect of delta9-tetrahydrocannabinol on the hypothalamic-pituitary-gonadal system in the maturing male rat. Proceedings of the effect of delta 9-tetrahydrocannabinol on the hypothalamic-pituitary-gonadal system in the maturing male rat.
        J Endocrinol. 1976; 68 (43P–4)
        • Smith C.G.
        • Moore C.E.
        • Besch N.F.
        • Besch P.
        Effect of delta-9 tetrahydrocannabinol (THC) on secretion of male sex-hormone in rhesus-monkey.
        In Pharmacologist. 1976; (Vol. 18, No. 2, pp. 248–248)
        • Murphy L.L.
        • Gher J.
        • Steger R.W.
        • Bartke A.
        Effects of delta 9-tetrahydrocannabinol on copulatory behavior and neuroendocrine responses of male rats to female conspecifics.
        Pharmacol Biochem Behav. 1994; 48: 1011-1017
        • Dixit V.P.
        • Gupta C.L.
        • Agrawal M.
        Testicular degeneration and necrosis induced by chronic administration of cannabis extract in dogs.
        Endokrinologie. 1977; 69: 299-305
        • Dixit V.P.
        • Sharma V.N.
        • Lohiya N.K.
        The effect of chronically administered cannabis extract on the testicular function of mice.
        Eur J Pharmacol. 1974; 26: 111-114
        • Thompson G.R.
        • Mason M.M.
        • Rosenkrantz H.
        • Braude M.C.
        Chronic oral toxicity of cannabinoids in rats.
        Toxicol Appl Pharmacol. 1973; 25: 373-390
        • Banerjee A.
        • Singh A.
        • Srivastava P.
        • Turner H.
        • Krishna A.
        Effects of chronic bhang (cannabis) administration on the reproductive system of male mice.
        Birth Defects Res B Dev Reprod Toxicol. 2011; 92: 195-205
        • Harclerode J.
        Endocrine effects of marijuana in the male: preclinical studies.
        NIDA Res Monogr. 1984; 44: 46-64
        • Hedges J.C.
        • Hanna C.B.
        • Bash J.C.
        • et al.
        Chronic exposure to delta-9-tetrahydrocannabinol impacts testicular volume and male reproductive health in rhesus macaques.
        Fertil Steril. 2022; 117: 698-707
        • Huang H.F.
        • Nahas G.G.
        • Hembree III, W.C.
        Effects of marihuana inhalation on spermatogenesis of the rat.
        Adv Biosci. 1978; 22–23: 419-427
        • Zimmerman A.M.
        • Zimmerman S.
        • Raj A.Y.
        Effects of cannabinoids on spermatogenesis in mice.
        Adv Biosci. 1978; 22–23: 407-418
        • Carroll K.
        • Pottinger A.M.
        • Wynter S.
        • DaCosta V.
        Marijuana use and its influence on sperm morphology and motility: identified risk for fertility among Jamaican men.
        Andrology. 2020; 8: 136-142
        • Pacey A.A.
        • Povey A.C.
        • Clyma J.A.
        • et al.
        Modifiable and non-modifiable risk factors for poor sperm morphology.
        Hum Reprod. 2014; 29: 1629-1636
        • Murphy S.K.
        • Itchon-Ramos N.
        • Visco Z.
        • et al.
        Cannabinoid exposure and altered DNA methylation in rat and human sperm.
        Epigenetics. 2018; 13: 1208-1221
        • Klonoff-Cohen H.S.
        • Natarajan L.
        • Chen R.V.
        A prospective study of the effects of female and male marijuana use on in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) outcomes.
        Am J Obstet Gynecol. 2006; 194: 369-376
        • Smith C.G.
        • Besch N.F.
        • Smith R.G.
        • Besch P.K.
        Effect of tetrahydrocannabinol on the hypothalamic-pituitary axis in the ovariectomized rhesus monkey.
        Fertil Steril. 1979; 31: 335-339
      3. Smith CG, Smith MT, Besch NF, Smith RG, Asch RH. Effect of delta-nine-tetrahydrocannabinol (THC) on female reproductive function. Marihuana: chemistry, biochemistry and cellular effects. 2nd ed. Pergamon Press: New York. 1 page

        • Asch R.H.
        • Fernandez E.O.
        • Smith C.G.
        • Pauerstein C.J.
        Precoital single doses of delta9-tetrahydrocannabinol block ovulation in the rabbit.
        Fertil Steril. 1979; 31: 331-334
        • Asch R.H.
        • Smith C.G.
        Effects of delta 9-THC, the principal psychoactive component of marijuana, during pregnancy in the rhesus monkey.
        J Reprod Med. 1986; 31: 1071-1081
        • Tyrey L.
        δ-9-tetrahydrocannabinol suppression of episodic luteinizing hormone secretion in the ovariectomized rat.
        Endocrinology. 1978; 102: 1808-1814
        • Dalterio S.
        • Bartke A.
        • Roberson C.
        • Watson D.
        • Burstein S.
        Direct and pituitary-mediated effects of delta9-THC and cannabinol on the testis.
        Pharmacol Biochem Behav. 1978; 8: 673-678
        • Chakravarty I.
        • Sheth A.R.
        • Ghosh J.J.
        Effect of acute delta9-tetrahydrocannabinol treatment on serum luteinizing hormone and prolactin levels in adult female rats.
        Fertil Steril. 1975; 26: 947-948
        • Ayalon D.
        • Nir I.
        • Cordova T.
        • et al.
        Acute effect of delta1-tetrahydrocannabinol on the hypothalamo-pituitary-ovarian axis in the rat.
        Neuroendocrinology. 1977; 23: 31-42
        • Dalterio S.L.
        • Mayfield D.L.
        • Bartke A.
        Effects of delta 9-THC on plasma hormone levels in female mice.
        Subst Alcohol Actions Misuse. 1983; 4: 339-345
        • Stouffer R.L.
        • Woodruff T.K.
        Nonhuman primates: a vital model for basic and applied research on female reproduction, prenatal development, and women’s health.
        ILAR J. 2017; 58: 281-294
        • Besch N.F.
        • Smith C.G.
        • Besch P.K.
        • Kaufman R.H.
        The effect of marihuana (delta-9-tetrahydrocannabinol) on the secretion of luteinizing hormone in the ovariectomized rhesus monkey.
        Am J Obstet Gynecol. 1977; 128: 635-642
        • Asch R.H.
        • Smith C.G.
        • Siler-Khodr T.M.
        • Pauerstein C.J.
        Effects of delta 9-tetrahydrocannabinol during the follicular phase of the rhesus monkey (Macaca mulatta).
        J Clin Endocrinol Metab. 1981; 52: 50-55
        • Jordan T.
        • Ngo B.
        • Jones C.A.
        The use of cannabis and perceptions of its effect on fertility among infertility patients.
        Hum Reprod Open. 2020; 2020: hoz041
        • White A.J.
        • Sandler D.P.
        • D’Aloisio A.A.
        • et al.
        AntiMüllerian hormone in relation to tobacco and marijuana use and sources of indoor heating/cooking.
        Fertil Steril. 2016; 106: 723-730
        • Jukic A.M.Z.
        • Weinberg C.R.
        • Baird D.D.
        • Wilcox A.J.
        Lifestyle and reproductive factors associated with follicular phase length.
        J Womens Health (Larchmt). 2007; 16: 1340-1347
        • Wise L.A.
        • Wesselink A.K.
        • Hatch E.E.
        • et al.
        Marijuana use and fecundability in a North American preconception cohort study.
        J Epidemiol Community Health. 2018; 72: 208-215
        • Kasman A.M.
        • Thoma M.E.
        • McLain A.C.
        • Eisenberg M.L.
        Association between use of marijuana and time to pregnancy in men and women: findings from the National Survey of Family Growth.
        Fertil Steril. 2018; 109: 866-871
        • Mueller B.A.
        • Daling J.R.
        • Weiss N.S.
        • Moore D.E.
        Recreational drug use and the risk of primary infertility.
        Epidemiology. 1990; 1: 195-200
        • Mumford S.L.
        • Flannagan K.S.
        • Radoc J.G.
        • et al.
        Cannabis use while trying to conceive: a prospective cohort study evaluating associations with fecundability, live birth and pregnancy loss.
        Hum Reprod. 2021; 36: 1405-1415
        • Nassan F.L.
        • Arvizu M.
        • Mínguez-Alarcón L.
        • et al.
        Marijuana smoking and markers of testicular function among men from a fertility centre.
        Hum Reprod. 2019; 34: 715-723
        • American College of Obstetricians and Gynecologists
        Marijuana use during pregnancy and lactation. 2017.
        (Available at:)
        • Martin C.E.
        • Longinaker N.
        • Mark K.
        • Chisolm M.S.
        • Terplan M.
        Recent trends in treatment admissions for marijuana use during pregnancy.
        J Addict Med. 2015; 9: 99-104
        • Volkow N.D.
        • Han B.
        • Compton W.M.
        • McCance-Katz E.F.
        Self-reported medical and nonmedical cannabis use among pregnant women in the United States.
        JAMA. 2019; 322: 167-169
        • Brown Q.L.
        • Sarvet A.L.
        • Shmulewitz D.
        • Martins S.S.
        • Wall M.M.
        • Hasin D.S.
        Trends in marijuana use among pregnant and nonpregnant reproductive-aged women, 2002-2014.
        JAMA. 2017; 317: 207-209
        • McCance-Katz E.F.
        The national survey on drug use and health: 2017. Substance Abuse and Mental Health Services Administration.
        • Fried P.A.
        • Watkinson B.
        • Grant A.
        • Knights R.M.
        Changing patterns of soft drug use prior to and during pregnancy: a prospective study.
        Drug Alcohol Depend. 1980; 6: 323-343
        • Chabarria K.C.
        • Racusin D.A.
        • Antony K.M.
        • et al.
        Marijuana use and its effects in pregnancy.
        Am J Obstet Gynecol. 2016; 215: 506.e1-506.e7
        • Beatty J.R.
        • Svikis D.S.
        • Ondersma S.J.
        Prevalence and perceived financial costs of marijuana versus tobacco use among urban low-income pregnant women.
        J Addict Res Ther. 2012; 31000135
        • Passey M.E.
        • Sanson-Fisher R.W.
        • D’Este C.A.
        • Stirling J.M.
        Tobacco, alcohol and cannabis use during pregnancy: clustering of risks.
        Drug Alcohol Depend. 2014; 134: 44-50
        • Ryan S.A.
        • Ammerman S.D.
        • O’Connor M.E.
        Marijuana use during pregnancy and breastfeeding: implications for neonatal and childhood outcomes.
        Pediatrics. 2018; 142e20181889
        • Office of the Surgeon General, US Department of Health and Human Services
        U.S. Surgeon General’s advisory: marijuana use and the developing brain.
        • Bayrampour H.
        • Zahradnik M.
        • Lisonkova S.
        • Janssen P.
        Women’s perspectives about cannabis use during pregnancy and the postpartum period: an integrative review.
        Prev Med. 2019; 119: 17-23
        • Woodruff K.
        • Scott K.A.
        • Roberts S.C.M.
        Pregnant people’s experiences discussing their cannabis use with prenatal care providers in a state with legalized cannabis.
        Drug Alcohol Depend. 2021; 227108998
        • Barbosa-Leiker C.
        • Brooks O.
        • Smith C.L.
        • Burduli E.
        • Gartstein M.A.
        Healthcare professionals’ and budtenders’ perceptions of perinatal cannabis use.
        Am J Drug Alcohol Abuse. 2022; 48: 186-194
        • Holland C.L.
        • Rubio D.
        • Rodriguez K.L.
        • et al.
        Obstetric health care providers’ counseling responses to pregnant patient disclosures of marijuana use.
        Obstet Gynecol. 2016; 127: 681-687
        • Chang J.C.
        • Tarr J.A.
        • Holland C.L.
        • et al.
        Beliefs and attitudes regarding prenatal marijuana use: perspectives of pregnant women who report use.
        Drug Alcohol Depend. 2019; 196: 14-20
        • Vanstone M.
        • Taneja S.
        • Popoola A.
        • et al.
        Reasons for cannabis use during pregnancy and lactation: a qualitative study.
        CMAJ. 2021; 193: E1906-E1914
        • Cristino L.
        • Di Marzo V.
        Fetal cannabinoid receptors and the “dis-joint-ed” brain.
        EMBO J. 2014; 33: 665-667
        • Kenney S.P.
        • Kekuda R.
        • Prasad P.D.
        • Leibach F.H.
        • Devoe L.D.
        • Ganapathy V.
        Cannabinoid receptors and their role in the regulation of the serotonin transporter in human placenta.
        Am J Obstet Gynecol. 1999; 181: 491-497
        • Lorenzetti V.
        • Solowij N.
        • Fornito A.
        • Lubman D.I.
        • Yucel M.
        The association between regular cannabis exposure and alterations of human brain morphology: an updated review of the literature.
        Curr Pharm Des. 2014; 20: 2138-2167
        • Marchand G.
        • Masoud A.T.
        • Govindan M.
        • et al.
        Birth outcomes of neonates exposed to marijuana in utero: a systematic review and meta-analysis.
        JAMA Network Open. 2022; 5e2145653
        • Fergusson D.M.
        • Horwood L.J.
        • Northstone K.
        • ALSPAC Study Team
        Avon Longitudinal Study of Pregnancy and Childhood. Maternal use of cannabis and pregnancy outcome.
        BJOG. 2002; 109: 21-27
        • National Academies of Sciences, Engineering, and Medicine
        The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research.
        The National Academies Press, Washington, DC2017
        • Shi Y.
        • Zhu B.
        • Liang D.
        The associations between prenatal cannabis use disorder and neonatal outcomes.
        Addiction. 2021; 116: 3069-3079
        • Corsi D.J.
        • Walsh L.
        • Weiss D.
        • et al.
        Association between self-reported prenatal cannabis use and maternal, perinatal, and neonatal outcomes.
        JAMA. 2019; 322: 145-152
        • Reece A.S.
        • Hulse G.K.
        Epidemiological overview of multidimensional chromosomal and genome toxicity of cannabis exposure in congenital anomalies and cancer development.
        Sci Rep. 2021; 1113892
        • van Gelder M.M.
        • Donders A.R.T.
        • 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
        • Shi Y.
        • Zhong S.
        Trends in cannabis use disorder among pregnant women in the U.S., 1993-2014.
        J Gen Intern Med. 2018; 33: 245-246
        • Gabrhelík R.
        • Mahic M.
        • Lund I.O.
        • et al.
        Cannabis use during pregnancy and risk of adverse birth outcomes: a longitudinal cohort study.
        Eur Addict Res. 2021; 27: 131-141
        • Sun X.
        • Dey S.K.
        Endocannabinoid signaling in female reproduction.
        ACS Chem Neurosci. 2012; 3: 349-355
        • Park B.
        • Gibbons H.M.
        • Mitchell M.D.
        • Glassa M.
        Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase (FAAH) in the human placenta.
        Placenta. 2003; 24: 473-478
        • Yao J.L.
        • He Q.Z.
        • Liu M.
        • et al.
        Effects of Δ(9)-tetrahydrocannabinol (THC) on human amniotic epithelial cell proliferation and migration.
        Toxicology. 2018; 394: 19-26
        • Costa M.A.
        • Fonseca B.M.
        • Marques F.
        • Teixeira N.A.
        • Correia-da-Silva G.
        The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.
        Toxicology. 2015; 334: 94-103
        • Chang X.
        • Bian Y.
        • He Q.
        • et al.
        Suppression of STAT3 signaling by Δ9-tetrahydrocannabinol (THC) induces trophoblast dysfunction.
        Cell Physiol Biochem. 2017; 42: 537-550
        • Benevenuto S.G.
        • Domenico M.D.
        • Martins M.A.G.
        • et al.
        Recreational use of marijuana during pregnancy and negative gestational and fetal outcomes: an experimental study in mice.
        Toxicology. 2017; 376: 94-101
        • Natale B.V.
        • Gustin K.N.
        • Lee K.
        • et al.
        Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta.
        Sci Rep. 2020; 10: 544
        • Maia J.
        • Almada M.
        • Midão L.
        • et al.
        The cannabinoid delta-9-tetrahydrocannabinol disrupts estrogen signaling in human placenta.
        Toxicol Sci. 2020; 177: 420-430
        • Lee C.C.
        • Chiang C.N.
        Maternal-fetal transfer of abused substances: pharmacokinetic and pharmacodynamic data.
        NIDA Res Monogr. 1985; 60: 110-147
        • Hutchings D.E.
        • Martin B.R.
        • Gamagaris Z.
        • Miller N.
        • Fico T.
        Plasma concentrations of delta-9-tetrahydrocannabinol in dams and fetuses following acute or multiple prenatal dosing in rats.
        Life Sci. 1989; 44: 697-701
        • Blackard C.
        • Tennes K.
        Human placental transfer of cannabinoids.
        N Engl J Med. 1984; 311: 797
        • Grzeskowiak L.E.
        • Grieger J.A.
        • Andraweera P.
        • et al.
        The deleterious effects of cannabis during pregnancy on neonatal outcomes.
        Med J Aust. 2020; 212: 519-524
        • Martínez-Peña A.A.
        • Lee K.
        • Petrik J.J.
        • Hardy D.B.
        • Holloway A.C.
        Gestational exposure to Δ9-THC impacts ovarian follicular dynamics and angiogenesis in adulthood in Wistar rats.
        J Dev Orig Health Dis. 2021; 12: 865-869
        • Nashed M.G.
        • Hardy D.B.
        • Laviolette S.R.
        Prenatal cannabinoid exposure: emerging evidence of physiological and neuropsychiatric abnormalities.
        Front Psychiatry. 2020; 11624275
        • Brummelte S.
        • Mc Glanaghy E.
        • Bonnin A.
        • Oberlander T.F.
        Developmental changes in serotonin signaling: implications for early brain function, behavior and adaptation.
        Neuroscience. 2017; 342: 212-231
        • Huizink A.C.
        Prenatal cannabis exposure and infant outcomes: overview of studies.
        Prog Neuropsychopharmacol Biol Psychiatry. 2014; 52: 45-52
        • El Marroun H.
        • Hudziak J.J.
        • Tiemeier H.
        • et al.
        Intrauterine cannabis exposure leads to more aggressive behavior and attention problems in 18-month-old girls.
        Drug Alcohol Depend. 2011; 118: 470-474
        • Day N.L.
        • Richardson G.A.
        • Goldschmidt L.
        • et al.
        Effect of prenatal marijuana exposure on the cognitive development of offspring at age three.
        Neurotoxicol Teratol. 1994; 16: 169-175
        • El Marroun H.
        • Bolhuis K.
        • Franken I.H.A.
        • et al.
        Preconception and prenatal cannabis use and the risk of behavioural and emotional problems in the offspring; a multi-informant prospective longitudinal study.
        Int J Epidemiol. 2019; 48: 287-296
        • Rompala G.
        • Nomura Y.
        • Hurd Y.L.
        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; 118e2016115118
        • Corsi D.J.
        • Donelle J.
        • Sucha E.
        • et al.
        Maternal cannabis use in pregnancy and child neurodevelopmental outcomes.
        Nat Med. 2020; 26: 1536-1540
        • Daha S.K.
        • Sharma P.
        • Sah P.K.
        • Karn A.
        • Poudel A.
        • Pokhrel B.
        Effects of prenatal cannabis use on fetal and neonatal development and its association with neuropsychiatric disorders: a systematic review.
        Neurol Psychiatry Brain Res. 2020; 38: 20-26
        • Paul S.E.
        • Hatoum A.S.
        • Fine J.D.
        • et al.
        Associations between prenatal cannabis exposure and childhood outcomes: results from the ABCD study.
        JAMA Psychiatry. 2021; 78: 64-76
        • Smid M.C.
        • Metz T.D.
        • McMillin G.A.
        • et al.
        Prenatal nicotine or cannabis exposure and offspring neurobehavioral outcomes.
        Obstet Gynecol. 2022; 139: 21-30
        • Torres C.A.
        • Medina-Kirchner C.
        • O’malley K.Y.
        • Hart C.L.
        Totality of the evidence suggests prenatal cannabis exposure does not lead to cognitive impairments: a systematic and critical review.
        Front Psychol. 2020; 11: 816
        • Bolhuis K.
        • Kushner S.A.
        • Yalniz S.
        • et al.
        Maternal and paternal cannabis use during pregnancy and the risk of psychotic-like experiences in the offspring.
        Schizophr Res. 2018; 202: 322-327
        • Lester B.M.
        • Conradt E.
        • Marsit C.J.
        Are epigenetic changes in the intrauterine environment related to newborn neurobehavior?.
        Epigenomics. 2014; 6: 175-178
        • Roth T.L.
        • Sweatt J.D.
        Annual Research Review: epigenetic mechanisms and environmental shaping of the brain during sensitive periods of development.
        J Child Psychol Psychiatry. 2011; 52: 398-408
        • Smith A.
        • Kaufman F.
        • Sandy M.S.
        • 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
        • DiNieri J.A.
        • 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
        • Zahm D.S.
        An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens.
        Neurosci Biobehav Rev. 2000; 24: 85-105
        • Zhu Z.
        • Wang G.
        • Ma K.
        • Cui S.
        • Wang J.H.
        GABAergic neurons in nucleus accumbens are correlated to resilience and vulnerability to chronic stress for major depression.
        Oncotarget. 2017; 8: 35933-35945
        • Bertrand K.A.
        • Hanan N.J.
        • Honerkamp-Smith G.
        • Best B.M.
        • Chambers C.D.
        Marijuana use by breastfeeding mothers and cannabinoid concentrations in breast milk.
        Pediatrics. 2018; 142e20181076
        • Wang G.S.
        Pediatric concerns due to expanded cannabis use: unintended consequences of legalization.
        J Med Toxicol. 2017; 13: 99-105
        • Moss M.J.
        • Bushlin I.
        • Kazmierczak S.
        • et al.
        Cannabis use and measurement of cannabinoids in plasma and breast milk of breastfeeding mothers.
        Pediatr Res. 2021; 90: 861-868
        • Perez-Reyes M.
        • Wall M.E.
        Presence of delta9-tetrahydrocannabinol in human milk.
        N Engl J Med. 1982; 307: 819-820
        • Baker T.
        • Datta P.
        • Rewers-Felkins K.
        • Thompson H.
        • Kallem R.R.
        • Hale T.W.
        Transfer of inhaled cannabis into human breast milk.
        Obstet Gynecol. 2018; 131: 783-788
        • Astley S.J.
        • Little R.E.
        Maternal marijuana use during lactation and infant development at one year.
        Neurotoxicol Teratol. 1990; 12: 161-168
        • Djulus J.
        • Moretti M.
        • Koren G.
        Marijuana use and breastfeeding.
        Can Fam Physician. 2005; 51: 349-350
        • National Library of Medicine
        Nutrition during lactation. 1991.
        (Available at:)
        • Tennes K.
        • Avitable N.
        • Blackard C.
        • et al.
        Marijuana: prenatal and postnatal exposure in the human.
        NIDA Res Monogr. 1985; 59: 48-60
        • Liston J.
        Breastfeeding and the use of recreational drugs-alcohol, caffeine, nicotine and marijuana.
        Breastfeed Rev. 1998; 6: 27-30
        • Lowry D.E.
        • Corsi D.J.
        Trends and correlates of cannabis use in Canada: a repeated cross-sectional analysis of national surveys from 2004 to 2017.
        CMAJ Open. 2020; 8: E487-E495
        • Slavin M.N.
        • Farmer S.
        • Earleywine M.
        Expectancy mediated effects of marijuana on menopause symptoms.
        Addict Res Theor. 2016; 24: 322-329
        • Bar-Lev Schleider L.
        • Abuhasira R.
        • Novack V.
        Medical cannabis: aligning use to evidence-based medicine approach.
        Br J Clin Pharmacol. 2018; 84: 2458-2462
        • Rawitch A.B.
        • Schultz G.S.
        • Ebner K.E.
        • Vardaris R.M.
        Competition of Δ9-tetrahydrocannabinol with estrogen in rat uterine estrogen receptor binding.
        Science. 1977; 197: 1189-1191
        • Chakrabarty I.
        • Sengupta D.
        • Bhattacharya P.
        • Ghosh J.J.
        Effect of cannabis extract on the uterine monoamine oxidase activity of normal and estradiol treated rats.
        Biochem Pharmacol. 1976; 25: 377-378
        • Mejia-Gomez J.
        • Phung N.
        • Philippopoulos E.
        • Murphy K.E.
        • Wolfman W.
        The impact of cannabis use on vasomotor symptoms, mood, insomnia and sexuality in perimenopausal and postmenopausal women: a systematic review.
        Climacteric. 2021; 24: 572-576
        • Young-Wolff K.C.
        • Gali K.
        • Sarovar V.
        • Rutledge G.W.
        • Prochaska J.J.
        Women’s questions about perinatal cannabis use and health care providers’ responses.
        J Womens Health (Larchmt). 2020; 29: 919-926