Prenatal tobacco and marijuana co-use: Sex-specific influences on infant cortisol stress response

Neurotoxicol Teratol. May-Jun 2020;79:106882. doi: 10.1016/ Epub 2020 Apr 11.


Although tobacco (TOB) and marijuana (MJ) are often co-used in pregnancy, little is known regarding the joint impact of MJ + TOB on offspring development, including the developing neuroendocrine stress system. Further, despite evidence for sex-specific impacts of prenatal exposures in preclinical models, the sex-specific impact of prenatal MJ + TOB exposure on offspring neuroendocrine regulation in humans is also unknown. In the current study, overall and sex-specific influences of MJ + TOB co-use on offspring cortisol regulation were investigated over the first postnatal month. 111 mother-infant pairs from a low-income, racially and ethnically diverse sample participated. Based on Timeline Followback data with biochemical verification, three groups were identified: (1) prenatal MJ + TOB, (2) TOB only, and (3) controls. Baseline cortisol and cortisol stress response were assessed at seven points over the first postnatal month using a handling paradigm in which saliva cortisol was assessed before, during, and following a standard neurobehavioral assessment (NICU Network Neurobehavioral Scale). A significant exposure group by offspring sex interaction emerged for baseline cortisol over the first postnatal month (p = .043); MJ + TOB-exposed males showed 35-36% attenuation of baseline cortisol levels vs. unexposed and TOB-exposed males (ps ≤ .003), while no effects of exposure emerged for females. Both MJ + TOB and TOB-exposed infants showed a 22% attenuation of cortisol stress response over the first postnatal month vs. unexposed infants (ps < .03), with evidence for sex-specific effects in exploratory analyses. Although results are preliminary, this is the first human study to investigate the impact of prenatal MJ exposure on infant cortisol and the first to reveal a sex-specific impact of prenatal MJ + TOB on cortisol regulation in humans. Future, larger-scale studies are needed to elucidate mechanisms and consequences of sex-specific effects of MJ and MJ + TOB on the developing neuroendocrine stress system.

Keywords: Cortisol; Infant; Marijuana; Pregnancy; Sex differences; Tobacco.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cannabis / adverse effects*
  • Cotinine / analysis
  • Female
  • Humans
  • Hydrocortisone / analysis*
  • Male
  • Marijuana Use / adverse effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / psychology*
  • Sex Factors
  • Stress, Psychological / chemically induced*
  • Tobacco / adverse effects*
  • Tobacco Use / adverse effects
  • Young Adult


  • Cotinine
  • Hydrocortisone