# Poster Session II A328 INFLUENCE OF IN UTERO CANNABIS SMOKE EXPOSURE ON FETAL GUT-BRAIN AXIS DEVELOPMENT

## TL;DR

This study investigates how in utero exposure to high-THC cannabis smoke affects fetal gut-brain axis development in mice.

## Contribution

The study introduces a novel 'real-world' cannabis smoke inhalation model in mice to assess fetal gut-brain axis development.

## Key findings

- Cannabis-exposed dams had reduced weight gain and food intake during pregnancy.
- Fetal body weight was lower in cannabis-exposed groups, but brain weight was preserved.
- In utero cannabis exposure did not affect fetal meconium descent in the colon.

## Abstract

Cannabis legalization in Canada has highlighted the societal relevance of investigating the potential impacts of in utero cannabis exposure on fetal development. Recent Canadian market trends show a consistent rise in the concentration of delta-9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent, in recreationally available cannabis. The endocannabinoid system plays a key role in shaping the normal development of the gut-brain axis and could potentially be disrupted by in utero cannabis exposure. However, the impact of high-Δ9-THC cannabis smoke exposure on the developing gut-brain axis remains poorly understood.

We tested the hypothesis that in utero exposure to high-Δ9-THC cannabis smoke would influence fetal gut-brain axis development and initiate early meconium descent.

We developed a “real-world” cannabis smoke inhalation model where timed-pregnant CD-1 mice (n = 23) were exposed daily from embryonic day (E) 0.5 to E18.5 to the smoke from six high-Δ9-THC cannabis cigarettes (29.05% Δ9-THC) in a custom-built smoking chamber unit. Control dams (n = 14) were restrained and exposed to room air for an equivalent duration. Maternal weight and food intake were monitored during pregnancy (E0.5–E18.5). At E18.5, dams were sacrificed, and fetal biometrics were recorded. Fetal gastrointestinal tracts (stomach–distal colon) were dissected, and meconium descent was quantified in Fiji. Data were averaged per dam, analyzed using Welch’s t-test, and reported as mean ± SD.

Cannabis-exposed dams gained less weight (p < 0.0001) and consumed less food (p < 0.0001) during pregnancy than control dams. Interestingly, while fetal body weight was reduced (p = 0.0005), brain weight did not differ between groups (p = 0.0724), leading to a higher brain-to-body weight ratio in the cannabis-exposed fetuses (p = 0.0092). Lastly, in utero high-Δ9-THC cannabis exposure did not affect meconium descent, as measured by the furthest distance of migration [mm] from the cecum (Cannabis: 8.73±1.23; Control: 8.91±1.40; n.s.) and the total length of meconium [mm] in the colon (Cannabis: 3.99±1.23; Control: 4.77±1.58; n.s.).

We found that exposure to high-Δ9-THC cannabis smoke in utero reduced maternal food intake and weight gain. Fetuses from cannabis-exposed dams had lower body weight compared to controls, but brain weight was preserved. Lastly, high-Δ9-THC cannabis smoke exposure in utero did not affect the extent of meconium descent in the fetal colon. In the context of Canadian cannabis market trends, these findings underscore the need to further explore the influence of in utero exposure to high-Δ9-THC cannabis smoke on the developing gut-brain axis and subsequent offspring outcomes.

CIHRThe Azrieli Foundation