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

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.

Gómez-Acero, Laura et al.·Progress in neuro-psychopharmacology & biological psychiatry·2025·Moderate EvidenceAnimal StudyAnimal Study
RTHC-06560Animal StudyModerate Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Animal Study
Evidence
Moderate Evidence
Sample
Not reported

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

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

Trust & Context

Key Stat:
lasting molecular changes in dopamine receptor balance in the striatum after adolescent THC exposure, correlated with behavioral deficits
Evidence Grade:
Multi-level evidence (behavioral, circuit, molecular) providing mechanistic insight, though limited to one animal model and dosing regimen.
Study Age:
2025 publication.
Original Title:
Long-lasting behavioral, molecular and functional connectivity alterations after chronic THC exposure during adolescence in mice.
Published In:
Progress in neuro-psychopharmacology & biological psychiatry, 140, 111422 (2025)
Database ID:
RTHC-06560

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal StudyOne case or non-human subjects
This study

Tests effects in animals (usually mice or rats), not humans.

What do these levels mean? →

Frequently Asked 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 More on RethinkTHC

Cite This Study

RTHC-06560·https://rethinkthc.com/research/RTHC-06560

APA

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

MLA

Gómez-Acero, Laura, et al. "Long-lasting behavioral, molecular and functional connectivity alterations after chronic THC exposure during adolescence in mice.." Progress in neuro-psychopharmacology & biological psychiatry, 2025. https://doi.org/10.1016/j.pnpbp.2025.111422

RethinkTHC

RethinkTHC Research Database. "Long-lasting behavioral, molecular and functional connectivi..." RTHC-06560. Retrieved from https://rethinkthc.com/research/gomez-acero-2025-longlasting-behavioral-molecular-and

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.