Determining the Link Between Prenatal Cannabis Use and Symptoms of Depression Using LC–MS/MS

To reassess the link between early pregnancy cannabis use and later depressive symptoms—and to explore how continued or heavy use compares with no use or use limited to the first trimester—researchers analyzed urine samples for 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) using liquid chromatography–tandem mass spectrometry (LC–MS/MS). A paper based on this research was published in Obstetrics & Gynecology (1).

Cannabis use during pregnancy has been on the rise, despite growing evidence linking it to adverse pregnancy outcomes, including impaired fetal growth (2). Pregnant individuals report that they use cannabis for reasons such as nausea and vomiting during pregnancy, anxiety, and depression (3–5). However, before the research highlighted in this article, the link between cannabis use during pregnancy and an increased risk of depressive symptoms remained unclear.Furthermore, previous studies that attempted to evaluate the association between perinatal depression and cannabis use were limited due to reliance on either self-reporting of cannabis use or clinical urine toxicology screenings rather than universal testing (4,5). These methods led to the misclassification of some cannabis users as unexposed, as reliance on self-reporting or selective testing often fails to detect all cases. Without comprehensive surveillance systems, this underreporting increases the likelihood of a negative ruling (1).

Clinical and demographic characteristics of the study’s participants were acquired through interviews, medical record reviews, and in-person clinical measurements as part of the parent study. From the enrollment visit during the first trimester, the following characteristics of each subject were collected: age, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), marital status, social support, insurance type, chronic conditions such as hypertension and preexisting diabetes, self-reported alcohol use in the previous month, mental health treatment, mean Edinburgh Postnatal Depression Scale (EPDS) score, and EPDS score higher than 10. Urine immunoassays of urine for THC-COOH, the most stable metabolite of cannabis, were performed on thawed specimens, with any positive results confirmed with LC–MS/MS (1).

While the authors report no connection between exposure to cannabis and later pregnancy increased depressive symptoms, a significant association between the ongoing use of cannabis use beyond the first trimester and higher odds of depressive symptoms in later pregnancy was detected. The odds were also increased with higher measured first-trimester and higher cumulative urine THC-COOH exposures, which the authors believe demonstrate a dose-dependent relationship (1).

The authors highlight several strengths of their study. It is a secondary analysis of a large, prospective cohort involving a diverse group of participants from across the country, which they believe results in more universal findings. Furthermore, maternal depressive symptoms across pregnancy were detailed using a standardized, validated instrument that is widely used in clinical practice. Cannabis use was assessed through the testing of urine at multiple time points and confirmed using MS. The use of cannabis was quantified at a time point in the first trimester and as a time-weighted cumulative average exposure during pregnancy. The authors believe that these measures allow for the assessment of a dose-dependent relationship (1).

However, the authors acknowledge certain limitations of their study. It was completed before the increasingly widespread use of cannabis and cannabinoid products and does not differentiate between recreational and medicinal use. In addition, while the pharmacologic treatment or psychotherapy for depression was adjusted, it did not differentiate between the two as covariates because this information was not obtained as part of the parent study. Finally, this study is limited by its observational nature. It is suggested by the research team that additional granular data on depressive symptoms, depressive diagnosis, and pharmacologic and nonpharmacologic treatment would be beneficial to achieve a greater understanding of the observed association (1).

Pregnant woman holding marijuana green cannabis leaf. © Elroi - stock.adobe.com

References

1. Pitt, T. L.; Allshouse, A. A.; Kim, P.; et al. Prenatal Cannabis Use and Depressive Symptoms. Obstet. Gynecol. 2025, 145 (4), 417–425. DOI: 10.1097/AOG.0000000000005860

2. Metz, T. D.; Allshouse, A. A.; McMillin, G. A.; et al. Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function. JAMA 2023, 330 (22), 2191–2199. DOI: 10.1001/jama.2023.21146

3. Gobbi, G.; Atkin, T.; Zytynski, T.; et al. Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood: A Systematic Review and Meta-Analysis. JAMA Psychiatry 2019, 76 (4), 426–434. DOI: 10.1001/jamapsychiatry.2018.4500

4. Goodwin, R. D.; Zhu, J.; Heisler, Z.; et al. Cannabis Use During Pregnancy in the United States: The Role of Depression. Drug Alcohol Depend. 2020, 210, 107881. DOI: 10.1016/j.drugalcdep.2020.107881

5. Mark, K.; Otieno, L.; Moore, E.; et al. Association Between Continued Cannabis Use During Pregnancy and Symptoms of Anxiety and Depression. Int. Rev. Psychiatry 2021, 33 (6), 528–533. DOI: 10.1080/09540261.2021.1898348