Background and Purpose: Consumption of cannabis during pregnancy has increased, especially oral administration. Given that cannabis compounds readily cross the placenta, there could be unintended developmental consequences, especially when exposed to the modern obesogenic food environment. We explored the long-term effects of maternal voluntary cannabis consumption on adult offspring’s emotional behavioral and microbiota response to high fat diet (HFD) consumption. Experimental Approach: Pregnant mice voluntarily consumed cannabis extract equivalent to 5 mg/kg/day Δ9-tetrahydrocannabinol from gestational day 1.5 until postnatal day (PD) 10. Male and female offspring (PD49) consumed a HFD or low-fat control diet (LFD) for 12 weeks. We measured a battery of emotional behavioral tasks (elevated plus maze, light dark box, open field test, social interaction), changes in gut microbiota in dams and offspring, and inhibitory synaptic transmission in the lateral orbitofrontal cortex (lOFC). Key Results: Pre- and perinatal cannabis exposure (PPCE) did not influence weight gain of offspring on a HFD. Male offspring receiving HFD had decreased risk-taking behaviours that were exacerbated by PPCE. HFD exposure and PPCE had opposing effects on locomotor activity in male mice. Female mice were protected from PPCE influence on emotional behaviour as well as HFD-induced synaptic depression in the lOFC. Changes in offspring microbiota were associated with PPCE-altered maternal-offspring microbial transmission, particularly from maternal fecal microbiota during late gestation. Conclusion and Implications: PPCE sex-dependently influences HFD-induced anxiety and the gut microbiota of offspring. This raises concerns about differential effects of those exposed to gestational cannabis in the modern food environment.

Background and Purpose: Given the recent rise in cannabis legalization, accessibility and consumption by pregnant individuals, there are unintended developmental consequences considering the key role that the endocannabinoid system plays in fetal development and later-life energy homeostasis. Whether perinatal cannabis exposure (PCE) affects energy homeostasis positively or adversely in adulthood is unknown. We explored the long-term effects of maternal voluntary oral cannabis consumption on the metabolic outcomes of high fat diet (HFD) in adult offspring. Experimental Approach: Pregnant mice voluntarily consumed cannabis from gestational day 1.5 until postnatal day (PD) 10. Pregnancy and pup outcomes and active maternal behavior were recorded. Male and female offspring (PD49) were placed on a 12-week HFD or control diet; their weight gain, adiposity, glucose tolerance, insulin sensitivity, circulating hormones, and pancreas structure were measured. Key Results: PCE pup weight was reduced but was restored by PD16. PCE did not influence weight gain or metabolic characteristics of male mice on a HFD. However, PCE female offspring on a HFD had reduced accumulation of adipose tissue and lower insulin, leptin, and resistin independent of body weight and while PCE females on control diet showed altered basal insulin sensitivity likely due to increased glucagon levels in parallel with reduced islets of Langerhans size and enhanced gene expression of cannabinoid 2 receptors in white adipose tissue. Conclusion and Implications: PCE influences metabolic outcomes in female offspring; it adversely affected glycemic control in female offspring on control diet while it mitigated HFD-induced metabolic dysfunction. This raises concerns about the long-term effects of PCE on the metabolic health of offspring.