Effects of prenatal cannabis exposure on offspring mental health: A focus on the role of the immune system

Globally, there is increasing legalization, permissiveness and acceptability of medical and recreational cannabis use-including among pregnant people. Yet, we lack a full understanding of cannabis' effects, including during pregnancy and in offspring who experienced prenatal cannabis exposure (PCE), despite decades of research. In particular, the ability of PCE to impact offspring mental health has been investigated in literature. Given the emerging link between mental health and immune system functioning (both centrally and peripherally) and that cannabinoid receptors are abundantly expressed in the immune system, it may be the case that PCE alters offspring mental health by impacting the immune system. In this review, we highlight current research on the effects of PCE and discuss differences among administration methods and across species, with a particular focus on changes in the immune system-focusing both on immune processes in the central nervous system and peripherally-relevant to altered offspring mental health. While the field is too nascent for robust conclusions, some interesting findings have been reported. Particularly in the placenta, in both humans and rodents (using vaporized exposure paradigms), cannabis use during pregnancy is associated with a reduction in pro-inflammatory cytokine levels, which is linked, in humans, to increased offspring anxiety, aggression and hyperactivity behaviors. Whereas data with regards to central nervous system immune cells, i.e., microglia, is limited, PCE seems to impact T cell dynamics in various organs. However, the link between offspring immune cell changes and offspring mental health requires further establishment. We conclude by discussing important future directions and a focus on harm reduction.