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Updated: Apr 26, 2026
Administration of Δ9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice
Published on: August 1, 2025
Permanent suppression of cortical oscillations in mice after adolescent exposure to cannabinoids: receptor mechanisms
Sylvina M Raver1, Asaf Keller1
1Program in Neuroscience and Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St. HSF II S241, Baltimore, MD 21201, USA.
Abstract:
Marijuana use in adolescence, but not adulthood, may permanently impair cognitive functioning and increase the risk of developing schizophrenia. Cortical oscillations are patterns of neural network activity implicated in cognitive processing, and are abnormal in patients with schizophrenia. We have recently reported that cortical oscillations are suppressed in adult mice that were treated with the cannabinoids WIN55,212-2 (WIN) or Δ(9)tetrahydrocannabinol (THC) in adolescence, but not adulthood. WIN and THC are cannabinoid-1 (CB1R) and CB2R agonists, and also have activity at non-cannabinoid receptor targets. However, as acute WIN and THC administration can suppress oscillations through CB1Rs, we hypothesize that a similar mechanism underlies the permanent suppression of oscillations by repeated cannabinoid exposure in adolescence. Here we test the prediction that cannabinoid exposure in adolescence permanently suppresses cortical oscillations by acting through CB1Rs, and that these suppressive effects can be antagonized by a CB1R antagonist. We treated adolescent mice with various cannabinoid compounds, and pharmacologically-evoked oscillations in local field potentials (LFPs) in vitro in adults. We find that WIN exposure for six days in early adolescence suppresses oscillations preferentially in adult medial prefrontal cortex (mPFC) via CB1Rs, and that a similar CB1R mechanism accounts for the suppressive effects of long-term (20 day) adolescent THC in adult somatosensory cortex (SCx). Unexpectedly, we also find that CB2Rs may be involved in the suppression of oscillations in both mPFC and SCx by long-term adolescent cannabinoid exposure, and that non-cannabinoid receptors may also contribute to oscillation suppression in adult mPFC. These findings represent a novel attempt to antagonize the effects of adolescent cannabinoid exposure on neural network activity, and reveal the contribution of non-CB1R targets to the suppression of cortical oscillations.
Insights
Adolescent cannabinoid exposure permanently suppresses brain oscillations via CB1Rs, potentially impacting cognitive function. These effects may be reversible with CB1R antagonists, suggesting therapeutic targets for mitigating marijuana's long-term neural consequences.
Area of Science:
- Neuroscience
- Pharmacology
- Adolescent development
Background:
- Adolescent marijuana use is linked to cognitive deficits and schizophrenia risk.
- Cannabinoids like THC and WIN55,212-2 affect neural network activity (cortical oscillations).
- Previous studies show adolescent cannabinoid exposure suppresses oscillations in adult mice.
Purpose of the Study:
- To investigate if adolescent cannabinoid exposure permanently suppresses cortical oscillations via CB1Rs.
- To determine if a CB1R antagonist can reverse these suppressive effects.
- To explore the roles of CB1R, CB2R, and non-cannabinoid receptors in these long-term effects.
Main Methods:
- Adolescent mice were treated with various cannabinoid compounds.
- Pharmacologically-evoked cortical oscillations in local field potentials (LFPs) were measured in adult mice.
- The effects of CB1R antagonists were assessed.
Main Results:
- WIN55,212-2 (WIN) exposure in adolescence suppressed adult medial prefrontal cortex (mPFC) oscillations via CB1Rs.
- Long-term THC exposure in adolescence suppressed adult somatosensory cortex (SCx) oscillations through a similar CB1R mechanism.
- CB2Rs and non-cannabinoid receptors were also implicated in oscillation suppression in both mPFC and SCx.
Conclusions:
- Adolescent cannabinoid exposure causes lasting suppression of cortical oscillations, primarily through CB1Rs.
- CB2Rs and other non-cannabinoid targets may also contribute to these long-term neural alterations.
- These findings offer novel insights into antagonizing the neural effects of adolescent cannabinoid exposure.
