THE AUTHORS of this neuroscience review synthesize human and animal data on prenatal cannabis exposure, with a particular focus on the developing immune system. Their synthesis foregrounds the interplay between mental health and immune functioning across central and peripheral pathways. They describe how cannabinoid receptor expression in immune cells, both centrally and peripherally, provides a biological route through which cannabis use during pregnancy might influence offspring mental health outcomes. The review emphasizes that current evidence is preliminary, yet it highlights converging signals that immune modulation may be an important intermediary.

Prenatal Cannabis Exposure and Immune System Pathways

Across studies that examine cannabis use during pregnancy, the placenta emerges as a key interface between maternal exposure and fetal development. In both human cohorts and rodent models that use vaporized exposure paradigms, prenatal cannabis exposure is associated with reduced levels of pro inflammatory cytokines in placental tissue. In humans these lower cytokine levels have been linked with greater anxiety, aggression, and hyperactivity behaviors in offspring, suggesting that altered immune signaling may track with later mental health risk. Data related to microglia remain limited, but the review notes that prenatal cannabis exposure appears to alter T cell dynamics in several organs, further supporting an immune focused mechanism.

Clinical Implications and Research Gaps

Despite decades of work on prenatal cannabis exposure, the authors conclude that the field remains too nascent for firm clinical recommendations based solely on immune findings. Crucially, direct causal links between immune cell changes and specific offspring mental health outcomes have not yet been established. For clinicians, the review reinforces the importance of careful counseling around cannabis use during pregnancy and supports a harm reduction approach that acknowledges uncertainty while highlighting potential neuroimmune vulnerability, psychological distress and the immune system, and the need for longitudinal data. Future research that integrates detailed immune profiling with long term mental health follow up will be essential to clarify risk and guide evidence-based guidance for pregnant patients.

Reference: Vecchiarelli HA et al. Effects of Prenatal Cannabis Exposure on Offspring Mental Health: A Focus on the Role of the Immune System. Neurosci Biobehav Rev. 2025;doi:10.1016/j.neubiorev.2025.106488.