THC plus stress during adolescence impaired fear extinction in adult mice
Mice exposed to both THC and stress during adolescence showed impaired fear extinction in adulthood, along with reduced activity in the amygdala and prefrontal cortex, but neither factor alone produced this effect.
Quick Facts
What This Study Found
Adolescent mice given both THC and stress showed impaired cued fear extinction in adulthood, with decreased neuronal activity in the basolateral amygdala and infralimbic prefrontal cortex. These mice also had more immature dendritic spines in BLA pyramidal neurons and elevated corticosterone after fear conditioning. Crucially, neither THC nor stress alone produced these effects.
Key Numbers
THC + stress group showed impaired fear extinction. Decreased c-Fos in BLA and infralimbic cortex. Increased immature dendritic spines in BLA. Elevated corticosterone after fear conditioning. Neither THC nor stress alone produced these effects.
How They Did This
Adolescent mice received THC treatment and/or stress exposure. In adulthood, they underwent cued fear conditioning and extinction testing. Brain tissue was analyzed for neuronal activity (c-Fos), structural plasticity (dendritic spines), and corticosterone levels.
Why This Research Matters
Many adolescents who use cannabis are also experiencing significant stress. This study shows these two factors interact to produce long-lasting anxiety-related brain changes that neither factor would cause alone.
The Bigger Picture
This helps explain why some adolescent cannabis users develop anxiety disorders while others do not. The combination of cannabis and environmental stress may be the key risk factor, not cannabis exposure alone.
What This Study Doesn't Tell Us
Mouse model; human translation uncertain. Only one THC dose regimen and one type of stress were tested. Fear extinction is a model for anxiety but does not fully replicate human anxiety disorders.
Questions This Raises
- ?What types of real-world stressors interact most strongly with cannabis?
- ?Would CBD mitigate the combined THC + stress effects?
- ?Are there critical windows during adolescence when this interaction is most harmful?
Trust & Context
- Key Stat:
- Only THC + stress combined impaired adult fear extinction
- Evidence Grade:
- Preliminary: animal study with a specific interaction design, important but not directly translatable.
- Study Age:
- Published in 2019.
- Original Title:
- Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood.
- Published In:
- Neuropharmacology, 144, 345-357 (2019)
- Authors:
- Saravia, Rocio(2), Ten-Blanco, Marc, Julià-Hernández, Marina, Gagliano, Humberto, Andero, Raül, Armario, Antonio, Maldonado, Rafael, Berrendero, Fernando
- Database ID:
- RTHC-02277
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is fear extinction?
It is the process by which the brain learns that something previously associated with danger is no longer threatening. Impaired fear extinction is a hallmark of anxiety disorders like PTSD.
Why does the combination matter more than either alone?
Cannabis and stress may both alter the same brain circuits (amygdala and prefrontal cortex) during the critical developmental period of adolescence. Together, they push these circuits past a threshold that neither reaches alone.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-02277APA
Saravia, Rocio; Ten-Blanco, Marc; Julià-Hernández, Marina; Gagliano, Humberto; Andero, Raül; Armario, Antonio; Maldonado, Rafael; Berrendero, Fernando. (2019). Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood.. Neuropharmacology, 144, 345-357. https://doi.org/10.1016/j.neuropharm.2018.11.016
MLA
Saravia, Rocio, et al. "Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood.." Neuropharmacology, 2019. https://doi.org/10.1016/j.neuropharm.2018.11.016
RethinkTHC
RethinkTHC Research Database. "Concomitant THC and stress adolescent exposure induces impai..." RTHC-02277. Retrieved from https://rethinkthc.com/research/saravia-2019-concomitant-thc-and-stress
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.