Adolescent mice voluntarily self-administered the synthetic cannabinoid JWH-018, and this exposure produced lasting compulsive-like behaviors and neuroinflammation in their adult brains.
Neuroscience researchers, parents, substance abuse prevention workers
First study of voluntary synthetic cannabinoid self-administration in adolescent mice
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Novel animal study with self-administration paradigm and multiple verification methods, but limited to male mice.
When this study was published
Published in 2022
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.
Questions still open
- 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?
Common questions
What happened to mice that self-administered synthetic cannabinoids as adolescents?
Why is self-administration important in this study?
Read the original research
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
Citation
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
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