Adolescent cannabinoid exposure in mice caused lasting schizophrenia-like brain and behavior changes
Mice given a cannabinoid agonist during adolescence showed lasting deficits in sensorimotor gating and fear conditioning in adulthood, along with reduced hippocampal mGluR5 and altered endocannabinoid metabolism.
Quick Facts
What This Study Found
Mice received the CB1 agonist WIN55,212-2 during adolescence (postnatal days 30-35) or early adulthood (days 63-70) and were tested after postnatal day 120. Only adolescent exposure produced lasting behavioral changes.
Adolescent-treated mice showed deficits in prepulse inhibition (a measure of sensorimotor gating commonly disrupted in schizophrenia) and fear conditioning (hippocampal-dependent learning). The hippocampus of these mice showed significantly reduced mGluR5 (a receptor involved in fear conditioning and endocannabinoid signaling).
Endocannabinoid metabolism enzymes were also altered: increased MAGL and FAAH levels suggested faster endocannabinoid breakdown, meaning reduced endocannabinoid tone in the hippocampus. Adult-treated mice showed none of these lasting changes.
Key Numbers
Adolescent treatment: PND 30-35. Adult treatment: PND 63-70. Testing after PND 120. Adolescent treatment reduced mGluR5 and increased MGL and FAAH in hippocampus. Adult treatment produced no lasting changes.
How They Did This
Mice received WIN55,212-2 during adolescence (PND 30-35) or early adulthood (PND 63-70). Behavioral testing after PND 120 included prepulse inhibition and fear conditioning. Hippocampal molecular markers (mGluR5, DGL, MGL, FAAH) were quantified.
Why This Research Matters
This study provided a causal mechanism linking adolescent cannabis exposure to schizophrenia-relevant brain changes. The selectivity for adolescent but not adult exposure supported the epidemiological finding that earlier cannabis use carries higher psychosis risk.
The Bigger Picture
This study offered mGluR5 as a potential therapeutic target. If adolescent cannabinoid exposure reduces mGluR5 and this contributes to psychosis vulnerability, drugs targeting mGluR5 might help at-risk individuals.
What This Study Doesn't Tell Us
Mouse model using synthetic cannabinoid, not THC. Very brief exposure window (5 days). The schizophrenia-like phenotype was limited to two behavioral measures. Human adolescence is much longer and more complex than mouse adolescence.
Questions This Raises
- ?Would mGluR5 agonists reverse the deficits from adolescent cannabinoid exposure?
- ?Is there a critical window within adolescence when exposure is most harmful?
- ?Does CBD co-exposure prevent these lasting changes?
Trust & Context
- Key Stat:
- Adolescent exposure caused lasting changes; adult exposure did not
- Evidence Grade:
- Animal study with direct age-of-exposure comparison and molecular mechanism. Strong for causal inference within the mouse model but limited human translation.
- Study Age:
- Published in 2012. The mGluR5 connection to cannabis-psychosis vulnerability has been explored further in subsequent research.
- Original Title:
- Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia.
- Published In:
- Translational psychiatry, 2(11), e199 (2012)
- Authors:
- Gleason, K A, Birnbaum, S G, Shukla, A, Ghose, S
- Database ID:
- RTHC-00562
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Does this prove teen cannabis use causes schizophrenia?
This mouse study shows adolescent cannabinoid exposure can cause lasting brain changes relevant to schizophrenia. It strengthens the case for a causal link but mice are not humans, and schizophrenia involves many factors beyond cannabis exposure.
Why does age of exposure matter?
The same cannabinoid treatment during adolescence produced lasting brain and behavior changes, while identical treatment in adulthood did not. The adolescent brain is still developing, particularly the hippocampus, making it more vulnerable to lasting disruption.
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Cite This Study
https://rethinkthc.com/research/RTHC-00562APA
Gleason, K A; Birnbaum, S G; Shukla, A; Ghose, S. (2012). Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia.. Translational psychiatry, 2(11), e199. https://doi.org/10.1038/tp.2012.122
MLA
Gleason, K A, et al. "Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia.." Translational psychiatry, 2012. https://doi.org/10.1038/tp.2012.122
RethinkTHC
RethinkTHC Research Database. "Susceptibility of the adolescent brain to cannabinoids: long..." RTHC-00562. Retrieved from https://rethinkthc.com/research/gleason-2012-susceptibility-of-the-adolescent
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.