Developmental exposure to cannabidiol vapor has persistent impacts on adult exploratory behavior and learning

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid with purported benefits across a range of pediatric conditions. However, the relative nascency of its integration in human populations has precluded a longitudinal safety assessment when used during different developmental periods. We hypothesized that CBD’s pharmacodynamic actions underlying the purported therapeutic effects could impact brain development in a persistent manner that presents as behavioral alterations in adulthood. To test this hypothesis, we exposed cohorts of non-pathogenic male and female C57BL/6J mice to twice-daily 30-minute CBD (24.26 mg/ml) vapor sessions across 3 different two-week developmental windows (postnatal day 7-21, 14-28, 28-42) and measured its impacts on locomotor activity, anxiety-related exploratory behavior, and spatial learning and memory in adulthood. Although we did not observe any effects of CBD on gross locomotor activity in the open field, CBD-exposed groups performed worse during the acquisition phase of the Barnes Maze learning procedure and demonstrated impaired memory during the probe session. Additionally, mice exposed to CBD spent more time exploring the open arms of the elevated plus maze, consistent with lower anxiety in a novel environment. Together, our results suggest that daily CBD exposure during childhood impacts the developing brain in a manner that contributes to persistent changes in spatial learning, memory, and exploratory behaviors later in life. Nonetheless, the nature of these impacts needs to be considered in balance with the potential therapeutic benefits of CBD and further tested in disease-specific models.