The First “Hit” to the Endocannabinoid System? Associations Between Prenatal Cannabis Exposure and Frontolimbic White Matter Pathways in Children

• Published in: Biological psychiatry global open science 2024-01, Vol.4 (1), p.11-18
• Main Authors: Evanski, Julia M., Zundel, Clara G., Baglot, Samantha L., Desai, Shreya, Gowatch, Leah C., Ely, Samantha L., Sadik, Nareen, Lundahl, Leslie H., Hill, Matthew N., Marusak, Hilary A.
• Format: Article
• Language: English
• Subjects: Development; Diffusion tensor imaging; Fractional anisotropy; Neuroimaging; Pregnancy; White matter
• ISSN: 2667-1743; 2667-1743
• DOI: 10.1016/j.bpsgos.2023.09.005

Cannabis is the most used federally illicit substance among pregnant people in the United States. However, emerging preclinical data show that a significant portion of cannabis constituents, such as Δ9-tetrahydrocannabinol and its bioactive metabolites, readily cross the placenta and accumulate in the fetal brain, disrupting neurodevelopment. Recent research using the Adolescent Brain Cognitive Development (ABCD) Study cohort has linked prenatal cannabis exposure (PCE) to greater neurobehavioral problems and lower total gray and white matter volume in children. Here, we examined the impact of PCE on frontolimbic white matter pathways that are critical for cognitive- and emotion-related functioning, show a high density of cannabinoid receptors, and are susceptible to cannabis exposure during other periods of rapid neurodevelopment (e.g., adolescence). This study included 11,530 children (mean ± SD age = 118.99 ± 7.49 months; 47% female) from the ABCD Study cohort. Linear mixed-effects models were used to examine the effects of caregiver-reported PCE on fractional anisotropy of 10 frontolimbic pathways (5 per hemisphere). PCE was associated with lower fractional anisotropy of the right (β = −0.005, p < .001) and left fornix (β = −0.003, p = .007), and these results remained significant after adjusting for a variety of covariates, multiple comparisons, fractional anisotropy of all fibers, and using a quality-control cohort only. In sum, we demonstrated small, yet reliable, effects of PCE on white matter integrity during childhood, particularly in the fornix, which plays a crucial role in emotion- and memory-related processes. Future studies are needed to understand the impacts of small changes in brain structure or function on neurodevelopment and risk of neurobehavioral problems.