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

RATIONALE: 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.

OBJECTIVE

This study aimed to examine whether frequent cannabis use during late adolescence affects cognitive functioning and increases the risk of developing anxiety in adulthood.

METHODS

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).

RESULTS

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.

CONCLUSION

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.