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Study breakdown

Adolescent THC exposure caused lasting brain connectivity and social behavior changes in mice

Animal StudyModerate evidence
The takeaway

Mice exposed to THC during adolescence developed persistent social interaction deficits, sensorimotor gating problems, and long-lasting changes in cortico-striatal brain connectivity and dopamine receptor balance that persisted into adulthood.

Neuroscientists studying adolescent brain vulnerability, psychiatrists concerned about youth cannabis use, and policymakers evaluating age restrictions for cannabis.

What the researchers found

Adolescent THC exposure impaired social interaction and increased vulnerability to sensorimotor gating deficiencies (similar to those in heavy cannabis users). Long-term cortico-striatal dysconnectivity correlated with impaired social interactions in adulthood. Lasting molecular changes were found in the balance between dopamine D2, adenosine A2A, and cannabinoid CB1 receptors in the striatum.

Why it matters

This provides neurobiological evidence for why adolescent cannabis use is associated with increased psychosis risk. The combination of brain connectivity changes, receptor imbalances, and behavioral deficits creates a plausible mechanistic pathway from adolescent exposure to adult psychiatric vulnerability.

The numbers in context

Persistent effects found in: social interaction, sensorimotor gating, cortico-striatal connectivity, and D2/A2A/CB1 receptor balance in striatum. Social interaction deficits correlated with connectivity changes.

How the study worked

Mice treated with THC during adolescence were assessed for behavioral, connectivity, and molecular changes persisting into adulthood. Included social interaction testing, sensorimotor gating, brain connectivity imaging, and receptor expression analysis.

What this study cannot tell us

Mouse model may not fully translate to human adolescent brain development. THC dosing and exposure patterns may not match typical human use. Only assessed a limited set of behaviors and brain regions.

How to read the evidence

Multi-level evidence (behavioral, circuit, molecular) providing mechanistic insight, though limited to one animal model and dosing regimen.

When this study was published

2025 publication.

The bigger picture

Human epidemiological studies associate adolescent cannabis use with psychosis risk, but demonstrating mechanism requires animal models. This study provides three levels of evidence, behavioral, circuit, and molecular, all pointing to lasting mesolimbic dopamine system disruption.

Questions still open

  • Are the cortico-striatal connectivity changes reversible with extended abstinence?
  • Do specific genetic backgrounds make adolescent brains more vulnerable to these THC-induced changes?

Common questions

Why is the adolescent brain more vulnerable to THC?
The adolescent brain is still developing, particularly the prefrontal cortex and dopamine systems. THC exposure during this critical period can alter the trajectory of brain maturation, creating lasting changes that do not occur with equivalent adult exposure.
Do these findings apply to humans?
The behavioral effects (social withdrawal, sensorimotor gating deficits) mirror symptoms seen in heavy adolescent cannabis users and people with psychosis risk. The molecular findings align with theories about dopamine dysregulation in psychosis. However, direct translation from mice to humans requires caution.

Read the original research

Long-lasting behavioral, molecular and functional connectivity alterations after chronic THC exposure during adolescence in mice.

Progress in neuro-psychopharmacology & biological psychiatry, 140, 111422

Citation

Gómez-Acero, Laura; Varriano, Federico; Sánchez-Fernández, Nuria; Ciruela, Francisco; Soria, Guadalupe; Aso, Ester. (2025). Long-lasting behavioral, molecular and functional connectivity alterations after chronic THC exposure during adolescence in mice.. Progress in neuro-psychopharmacology & biological psychiatry, 140, 111422. https://doi.org/10.1016/j.pnpbp.2025.111422

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