Repeated exposure to a synthetic cannabinoid caused lasting cognitive and brain changes in mice
Seven days of JWH-018 exposure in mice produced psychotic-like symptoms and lasting impairments in memory, social behavior, and brain plasticity that persisted for at least 15 days after the drug was stopped.
Quick Facts
What This Study Found
Repeated JWH-018 treatment (6 mg/kg daily for 7 days) induced psychomotor agitation, reduced social dominance and recognition memory, impaired prepulse inhibition, disrupted hippocampal long-term potentiation, decreased BDNF expression, and altered endocannabinoid system components in the striatum and hippocampus, all persisting 15+ days after last exposure.
Key Numbers
6 mg/kg JWH-018 daily for 7 days; 15-16 day washout; reduced hippocampal CB1 receptor density; altered AEA and 2-AG levels; decreased BDNF, PSD95, and NMDA receptor subunit expression
How They Did This
Male CD-1 mice received daily injections of vehicle, JWH-018 (6 mg/kg), CB1 antagonist NESS-0327 (1 mg/kg), or co-administration for 7 days. After 15-16 days washout, behavioral, neurochemical, electrophysiological, and molecular assessments were performed.
Why This Research Matters
Synthetic cannabinoids are far more potent than plant cannabis and are associated with severe psychiatric outcomes in humans. This study provides mechanistic evidence for how repeated exposure produces lasting brain changes.
The Bigger Picture
The persistence of cognitive and neuroplasticity deficits well after drug cessation raises concerns about lasting brain damage from synthetic cannabinoid use, which is particularly relevant given the prevalence of these substances in unregulated markets.
What This Study Doesn't Tell Us
Used a single high dose in male mice only. JWH-018 is one of many synthetic cannabinoids with varying potency. Route of administration (injection) differs from typical human use (smoking). No female mice included.
Questions This Raises
- ?Are these neuroplasticity changes reversible with longer washout periods?
- ?Do lower doses or intermittent exposure produce similar lasting effects?
Trust & Context
- Key Stat:
- Cognitive and brain changes persisted 15+ days after stopping the drug
- Evidence Grade:
- Well-designed animal study with multiple outcome measures and CB1 antagonist control, but single dose level in male mice only limits generalizability.
- Study Age:
- Published 2023
- Original Title:
- Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice.
- Published In:
- British journal of pharmacology, 180(21), 2777-2801 (2023)
- Authors:
- Bilel, Sabrine(5), Zamberletti, Erica(6), Caffino, Lucia, Tirri, Micaela, Mottarlini, Francesca, Arfè, Raffaella, Barbieri, Mario, Beggiato, Sarah, Boccuto, Federica, Bernardi, Tatiana, Casati, Sara, Brini, Anna T, Parolaro, Daniela, Rubino, Tiziana, Ferraro, Luca, Fumagalli, Fabio, Marti, Matteo
- Database ID:
- RTHC-04417
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
How do synthetic cannabinoids affect the brain differently than plant cannabis?
This study found that repeated JWH-018 (a synthetic cannabinoid) exposure caused lasting changes to memory, social behavior, brain plasticity, and the endocannabinoid system itself. These effects persisted at least 15 days after the drug was stopped.
Were the cognitive effects reversible?
After 15-16 days without the drug, mice still showed impaired memory, reduced social dominance, disrupted brain plasticity, and altered endocannabinoid signaling. Whether longer recovery periods would allow reversal was not tested.
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Cite This Study
https://rethinkthc.com/research/RTHC-04417APA
Bilel, Sabrine; Zamberletti, Erica; Caffino, Lucia; Tirri, Micaela; Mottarlini, Francesca; Arfè, Raffaella; Barbieri, Mario; Beggiato, Sarah; Boccuto, Federica; Bernardi, Tatiana; Casati, Sara; Brini, Anna T; Parolaro, Daniela; Rubino, Tiziana; Ferraro, Luca; Fumagalli, Fabio; Marti, Matteo. (2023). Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice.. British journal of pharmacology, 180(21), 2777-2801. https://doi.org/10.1111/bph.16164
MLA
Bilel, Sabrine, et al. "Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice.." British journal of pharmacology, 2023. https://doi.org/10.1111/bph.16164
RethinkTHC
RethinkTHC Research Database. "Cognitive dysfunction and impaired neuroplasticity following..." RTHC-04417. Retrieved from https://rethinkthc.com/research/bilel-2023-cognitive-dysfunction-and-impaired
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.