Long-term effects of adolescent THC exposure on anxiety-like behavior and cognitive function in male rats

As cannabis legalization and decriminalization have expanded, it is increasingly perceived as a low-risk substance. Concurrently, the potency of cannabis products and the number of young adults seeking treatment for cannabis use disorder have risen markedly. A growing body of research links early onset, frequent use, and high potency cannabis products to a range of adverse outcomes. This study aimed to examine whether frequent cannabis use during late adolescence affects cognitive functioning and increases the risk of developing anxiety in adulthood. Male Sprague-Dawley rats were administered tetrahydrocannabinol (THC; 5 mg/kg/day) or vehicle from postnatal day (PND) 42 to 62. After a drug-free period, anxiety-like behavior was assessed in the elevated plus maze (EPM) and Light-Dark transition tests, while cognitive function was evaluated in the novel object recognition and Morris water maze (MWM) tests. THC concentrations in blood and brain tissue were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The rats displayed blood THC concentrations comparable to human cannabis users and reduced body weight during the exposure period – an effect that persisted for over two months following the final injection. Adolescent THC exposure impaired novelty preference in young adult animals, whereas effects on spatial memory were less definitive. THC-exposed rats showed anxiety-like behavior in the EPM test, but not in the Light-Dark transition test. Our findings suggest that frequent cannabis exposure during adolescence may lead to long-term reductions in body weight, reduced novel object recognition, and increased vulnerability to certain aspects of anxiety-related behavior in adulthood.