Prior nicotine exposure changed how THC affects the brain differently by age and sex

In 112 rats, chronic nicotine followed by a washout period altered responses to THC challenge. In adult males, nicotine pre-exposure reduced THC-induced locomotor suppression. In adolescent females, nicotine potentiated THC suppression. THC increased brain c-Fos in multiple regions, and nicotine pre-exposure further amplified this effect. Brain activation patterns differed by age (greater in adults) and sex (greater in females).

Animal study with 112 male and female adolescent and adult Sprague-Dawley rats receiving 14 days of nicotine (1 mg/kg/day) followed by 14-day washout, then acute THC challenge (5 mg/kg). Locomotor activity and c-Fos brain mapping assessed.

Cannabis and tobacco are frequently co-used, especially by adolescents. This study reveals that prior nicotine exposure creates lasting changes in how the brain responds to cannabis, and that the effects are dramatically different depending on age and sex.

The age and sex differences suggest that adolescents and females may be particularly sensitive to nicotine-cannabis interactions. This has implications for understanding why co-use patterns develop and why outcomes may differ across demographics.

Animal study with synthetic nicotine and THC; fixed dose protocol may not reflect human use patterns; 14-day washout is a specific timeframe; only one THC dose tested.