A cannabinoid receptor agonist that helped adult rats overcome learned fear had the opposite effect in adolescent rats, coinciding with lower CB1 receptor levels in younger brains.
Neuroscience researchers, people interested in adolescent brain development and cannabis
CB1 receptor protein decreased linearly from juvenile to adolescent to adult in prefrontal cortex and amygdala
What the researchers found
WIN55212-2, a CB1/CB2 receptor agonist, improved fear extinction in adult rats but impaired extinction acquisition in both adolescent and juvenile rats. CB1 receptor protein expression decreased linearly from juvenile to adolescent to adult stages in the prefrontal cortex and amygdala.
Why it matters
The developing brain may respond to cannabinoid receptor activation differently than the adult brain, particularly for processes tied to emotional regulation and fear learning.
The numbers in context
CB1 receptor protein showed a linear decrease across age in both medial prefrontal cortex and amygdala. Impaired extinction in adolescents was consistent across multiple drug doses.
How the study worked
Rats at juvenile, adolescent, and adult developmental stages received WIN55212-2 or vehicle before extinction training following fear conditioning. CB1 receptor protein was quantified via Western blot in the medial prefrontal cortex and amygdala.
What this study cannot tell us
Animal model; WIN55212-2 is a synthetic agonist that activates both CB1 and CB2 receptors, so effects may not directly translate to cannabis exposure in humans.
How to read the evidence
Single animal study using a synthetic agonist rather than plant-derived cannabinoids.
When this study was published
Published in 2020.
The bigger picture
These findings add to evidence that the endocannabinoid system undergoes significant maturation during adolescence, which could influence how cannabis exposure affects developing brains.
Questions still open
- Would similar age-dependent effects appear with THC or CBD rather than a synthetic agonist? Could these developmental differences explain varied therapeutic responses across age groups?
Common questions
Why did the same drug have opposite effects in young vs. adult rats?
Does this mean cannabis-based therapies for anxiety would not work in teenagers?
Read the original research
Developmental differences in the effects of CB1/2R agonist WIN55212-2 on extinction of learned fear.
Progress in neuro-psychopharmacology & biological psychiatry, 99, 109834
Citation
Bisby, Madelyne A; Richardson, Rick; Baker, Kathryn D. (2020). Developmental differences in the effects of CB1/2R agonist WIN55212-2 on extinction of learned fear.. Progress in neuro-psychopharmacology & biological psychiatry, 99, 109834. https://doi.org/10.1016/j.pnpbp.2019.109834
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