Long-term effects of adolescent THC exposure on anxiety-like behavior and cognitive function in male rats
Josephine Sena Lumor, Henriette Nyberg, Elisabeth Nerem, Jannike Mørch Andersen, Inger Lise Bogen
Psychopharmacology April 23, 2026 DOI: 10.1007/s00213-026-07067-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Dose | 5 mg/kg/day |
| Duration | Postnatal day 42 to 62 (20-day exposure), followed by a drug-free period and testing in young adulthood |
| Measures | Elevated plus maze (EPM), Light-Dark transition test, novel object recognition, Morris water maze (MWM), ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) |
| Topics | Anxiety Cannabis |
| Key findings | Adolescent THC exposure in rats produced blood levels comparable to human cannabis users, reduced body weight that persisted over two months after the final injection, impaired novelty preference in young adulthood, and anxiety-like behavior in the elevated plus maze but not the light-dark test; effects on spatial memory were less definitive. |
Abstract
Abstract 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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Adolescent THC exposure produced anxiety-like behavior in the elevated plus maze and impaired novelty preference in young adulthood.
Synthesized
Comparable studies
Other preclinical and animal studies on cannabis for anxiety, most cited first.