Adolescent Mice That Self-Administered Synthetic Cannabinoid Developed Lasting Brain Changes
Adolescent mice voluntarily self-administered the synthetic cannabinoid JWH-018, and this exposure produced lasting compulsive-like behaviors and neuroinflammation in their adult brains.
Quick Facts
What This Study Found
Adolescent mice acquired JWH-018 self-administration behavior that was specifically reward-driven and blocked by a CB1 antagonist. As adults, exposed mice showed increased repetitive/compulsive behaviors (nestlet shredding, marble burying) and neuroinflammation: increased microglia in the caudate-putamen and nucleus accumbens, decreased astrocytes, and altered cytokines.
Key Numbers
JWH-018 dose: 7.5 ug/kg/infusion; CB1 antagonist AM251 blocked self-administration; increased IBA-1+ cells in caudate-putamen and NAc; decreased GFAP in caudate-putamen
How They Did This
Male CD1 adolescent mice self-administered JWH-018 intravenously (7.5 ug/kg/infusion) on fixed and progressive ratio schedules. Behavioral, neurochemical, and molecular evaluations were performed at adulthood.
Why This Research Matters
This is the first study showing voluntary self-administration of a synthetic cannabinoid during adolescence in mice, making the exposure model more relevant to human use than passive injection studies.
The Bigger Picture
Synthetic cannabinoid use is growing among adolescents. This study shows that even voluntary, self-dosed exposure during adolescence can cause lasting brain inflammation and behavioral abnormalities.
What This Study Doesn't Tell Us
Animal study in male mice only. Self-administration model may not perfectly mirror human use patterns. Neuroinflammatory changes measured at one timepoint in adulthood.
Questions This Raises
- ?Would female mice show similar or different effects?
- ?Do these compulsive behaviors parallel the psychiatric symptoms reported by human SCRA users?
- ?Are the neuroinflammatory changes reversible?
Trust & Context
- Key Stat:
- First study of voluntary synthetic cannabinoid self-administration in adolescent mice
- Evidence Grade:
- Novel animal study with self-administration paradigm and multiple verification methods, but limited to male mice.
- Study Age:
- Published in 2022
- Original Title:
- Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice.
- Published In:
- Psychopharmacology, 239(10), 3083-3102 (2022)
- Authors:
- Margiani, Giulia(2), Castelli, Maria Paola, Pintori, Nicholas(2), Frau, Roberto, Ennas, Maria Grazia, Pagano Zottola, Antonio C, Orrù, Valeria, Serra, Valentina, Fiorillo, Edoardo, Fadda, Paola, Marsicano, Giovanni, De Luca, Maria Antonietta
- Database ID:
- RTHC-04041
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What happened to mice that self-administered synthetic cannabinoids as adolescents?
As adults, they showed lasting compulsive-like behaviors and neuroinflammation in brain reward regions. The self-administration was specifically reward-driven and blocked by a CB1 receptor antagonist.
Why is self-administration important in this study?
Previous studies injected synthetic cannabinoids into animals. This study let mice choose to take JWH-018 themselves, making the exposure pattern more similar to how humans actually use these substances.
Read More on RethinkTHC
- THC-purity-potency-label-meaning
- dab-concentrate-addiction-withdrawal
- delta-8-addiction-withdrawal
- edible-addiction-withdrawal-different
- edibles-psychosis-emergency-room
- healthiest-way-to-consume-cannabis
- how-cannabis-products-made-concentrates-edibles
- laced-weed-fentanyl-contaminated-vape
- legal-weed-vs-street-weed-quality-safety
- quitting-dabs-withdrawal
- quitting-edibles-withdrawal
- sativa-vs-indica-difference-myth
- weed-potency-withdrawal
Cite This Study
https://rethinkthc.com/research/RTHC-04041APA
Margiani, Giulia; Castelli, Maria Paola; Pintori, Nicholas; Frau, Roberto; Ennas, Maria Grazia; Pagano Zottola, Antonio C; Orrù, Valeria; Serra, Valentina; Fiorillo, Edoardo; Fadda, Paola; Marsicano, Giovanni; De Luca, Maria Antonietta. (2022). Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice.. Psychopharmacology, 239(10), 3083-3102. https://doi.org/10.1007/s00213-022-06191-9
MLA
Margiani, Giulia, et al. "Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice.." Psychopharmacology, 2022. https://doi.org/10.1007/s00213-022-06191-9
RethinkTHC
RethinkTHC Research Database. "Adolescent self-administration of the synthetic cannabinoid ..." RTHC-04041. Retrieved from https://rethinkthc.com/research/margiani-2022-adolescent-selfadministration-of-the
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.