Adolescent THC Exposure Disrupts Brain Myelination in Female Rats
THC exposure during early-to-mid adolescence impaired myelination in the prefrontal cortex of female rats, with intensive exposure causing long-lasting effects into adulthood and increased risk-taking behavior.
Quick Facts
What This Study Found
Both CB1 receptor blockade and THC exposure during adolescence hindered prefrontal cortex myelination in female rats. THC effects were specific to early-to-mid adolescence and, with intensive exposure, persisted into adulthood. Disrupted myelination was associated with increased risk-taking and involved the AKT/Hippo/YAP signaling pathway.
Key Numbers
THC impaired myelin formation only during early-to-mid adolescence. Intensive exposure protocol produced long-lasting effects persisting into adulthood. Associated with increased risk-taking behavior.
How They Did This
Preclinical study examining CB1 receptor blockade and THC exposure during adolescence in female rats, measuring prefrontal cortex myelination, behavior (risk-taking), and AKT/Hippo/YAP signaling pathway changes.
Why This Research Matters
Adolescent brain development involves critical white matter formation. This study shows THC can disrupt this process in female rats during a specific developmental window, with potentially permanent consequences — directly relevant to rising teen cannabis use.
The Bigger Picture
White matter development continues through the mid-20s in humans. This animal evidence suggests a specific vulnerability window during early adolescence when THC exposure could permanently alter brain connectivity, with behavioral consequences like increased risk-taking.
What This Study Doesn't Tell Us
Female rats only — sex-specific findings may not apply to males. Rat adolescence timing differs from human. THC doses and routes may not reflect typical human use patterns.
Questions This Raises
- ?Do male rats show the same vulnerability?
- ?Does CBD co-administration protect against THC's myelination effects?
- ?What human adolescent behaviors might correspond to the rat risk-taking findings?
Trust & Context
- Key Stat:
- Evidence Grade:
- Well-designed preclinical study identifying specific developmental vulnerability, though sex-specific (female only) and animal-model limitations apply.
- Study Age:
- Recent study addressing the critical question of how adolescent cannabis exposure affects ongoing brain development.
- Original Title:
- Perturbations of CB1 receptor signalling during adolescence impair cortical myelination in female rats.
- Published In:
- Pharmacological research, 216, 107758 (2025)
- Authors:
- Zamberletti, Erica(6), Manenti, Cristina, Prini, Pamela(4), Gabaglio, Marina, Grimaldi, Annalisa, Pulze, Laura, Grassi, Riccardo, Rubino, Tiziana
- Database ID:
- RTHC-08020
Evidence Hierarchy
Frequently Asked Questions
Can cannabis permanently damage a teenager's brain?
This animal study suggests intensive THC exposure during early adolescence can cause lasting disruption to brain myelination (white matter development) in females, with behavioral consequences. Human studies are needed to confirm these findings.
Why only female rats?
The researchers focused on female rats, finding clear effects. Whether males show the same vulnerability is an important unanswered question, as sex differences in cannabinoid responses are increasingly recognized.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-08020APA
Zamberletti, Erica; Manenti, Cristina; Prini, Pamela; Gabaglio, Marina; Grimaldi, Annalisa; Pulze, Laura; Grassi, Riccardo; Rubino, Tiziana. (2025). Perturbations of CB1 receptor signalling during adolescence impair cortical myelination in female rats.. Pharmacological research, 216, 107758. https://doi.org/10.1016/j.phrs.2025.107758
MLA
Zamberletti, Erica, et al. "Perturbations of CB1 receptor signalling during adolescence impair cortical myelination in female rats.." Pharmacological research, 2025. https://doi.org/10.1016/j.phrs.2025.107758
RethinkTHC
RethinkTHC Research Database. "Perturbations of CB1 receptor signalling during adolescence ..." RTHC-08020. Retrieved from https://rethinkthc.com/research/zamberletti-2025-perturbations-of-cb1-receptor
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.