Endocannabinoid System: Cannabis, Pregnancy & Cytokines

Clinical Takeaway

Cannabis use during pregnancy is associated with measurable suppression of circulating maternal immune signaling proteins called cytokines, based on urine-verified exposure data. Because the immune system plays a critical role in supporting a healthy pregnancy, these findings raise important clinical concerns about cannabis use during gestation. Pregnant patients should be counseled that cannabis is not considered safe during pregnancy, and no trimester of use has been established as risk-free.

#25 Cannabis Use During Pregnancy Is Associated with the Suppression of Circulating Maternal Cytokines.

Citation: Alshaarawy Omayma et al.. Cannabis Use During Pregnancy Is Associated with the Suppression of Circulating Maternal Cytokines.. Cannabis and cannabinoid research. 2026. PMID: 41104491.

Study type: Journal Article  |  Topic area: Pediatrics  |  CED Score: 10

Design: 0 Journal: 1 N: 2 Recency: 3 Pop: 3 Human: 1 Risk: 0

Why This Matters
Prenatal cannabis use is increasingly common yet remains understudied regarding its immunological consequences, which this research addresses by demonstrating THC-associated suppression of circulating maternal cytokines, a finding with potential implications for maternal-fetal immune tolerance and infection susceptibility during pregnancy. Altered maternal immune cytokine profiles could affect placental function, fetal development, and postpartum infection risk, making this immunological mechanism clinically relevant for informed counseling and risk stratification of pregnant patients using cannabis. These findings establish a biological pathway through which prenatal cannabis exposure may influence pregnancy outcomes, warranting further investigation into dose-response relationships and long-term developmental consequences.

Abstract: INTRODUCTION: The prevalence of prenatal cannabis use has nearly doubled in the United States. Cannabinoid 2 receptors are predominately expressed in cells of the human immune system, and delta-9 tetrahydrocannabinol (THC), the primary active component of cannabis, has been shown to suppress immune responses. Despite these findings, there is very little evidence on the impact of cannabis use on maternal immune system. Here, we evaluate the association between urine-verified cannabis use and the levels of T helper cytokines in the maternal circulation. METHODS: This was an ancillary study of a prospective cohort of pregnant women who participated in the Michigan Archive for Research on Child Health study. Pregnant women (age ≥18 years) were recruited from 22 prenatal clinics in Michigan and matched on age, race, and tobacco smoking (n = 144). The urinary metabolite of delta-9 THC, 11-nor-9-carboxy-delta-9-THC (THC-COOH), was used to define cannabis use status. A bead-based assay was used for the simultaneous detection of maternal cytokines associated with cannabis use and pregnancy outcomes in previous studies. RESULTS: Repeated-measures linear mixed models indicated that urine-verified cannabis use was associated with the suppression of maternal pro-inflammatory cytokines including interferon gamma (β = -0.5; 95% confidence interval [CI] = -0.8, -0.1) and interleukin (IL)-12 (β = -0.3; 95% CI = -0.6, -0.05), as well as the anti-inflammatory IL-4 (β = -0.7; 95% CI = -1.3, -0.2) and IL-10 (β = -0.4; 95% CI = -0.7, -0.03). Similar results were observed when heavy cannabis use was defined using the top tertile of urinary THC-COOH at each trimester. CONCLUSIONS: Urine-verified cannabis use was associated with the suppression of pro- and anti-inflammatory T helper cytokines in a cohort of pregnant women, suggesting that cannabis use can lead to modest dysregulation of the maternal immune system. Additional studies are needed to investigate the role of maternal immune resp

Clinical Perspective

🤰 This study adds important mechanistic data suggesting that prenatal cannabis use may alter maternal immune function through suppression of circulating cytokines, a finding consistent with known cannabinoid receptor distribution in immune cells. However, several significant caveats warrant careful interpretation: the cross-sectional design prevents us from establishing causation or determining whether cytokine suppression is clinically harmful or beneficial in pregnancy, the study does not clarify whether observed immune changes translate to measurable adverse fetal or neonatal outcomes, and we lack data on cannabis potency, frequency, duration of use, or trimester-specific exposure, all of which could substantially affect immune response. Additionally, confounding variables such as maternal infection status, stress, nutrition, and concurrent substance use are potential alternate explanations for immune alterations. Pending prospective studies with clinical outcome measures, practitioners should continue counseling pregnant patients that cannabis use in pregnancy carries unknown risks to fetal development and that current evidence supports abstinence, while acknowledging that mechanistic studies like this one help us

Full Article  |  PubMed