Synthetic cannabinoid JWH-018 impairs memory by raising brain endocannabinoid levels and lowering BDNF
JWH-018 elevated brain endocannabinoid levels by suppressing their breakdown enzymes and reduced BDNF, a protein critical for learning and memory, with both effects reversible by a CB1 blocker.
Quick Facts
What This Study Found
JWH-018 elevated anandamide and 2-AG levels in the hippocampus by suppressing the enzymes that break them down (FAAH and MAGL). It simultaneously reduced BDNF, a key protein for synaptic plasticity. All effects were blocked by the CB1 antagonist AM251, confirming CB1-dependent mechanisms.
Key Numbers
JWH-018 significantly elevated both AEA and 2-AG levels. FAAH and MAGL activity were suppressed. BDNF levels decreased. All changes were reversed by CB1 antagonist AM251.
How They Did This
Acute JWH-018 administration in rats with hippocampal metabolomic profiling. Endocannabinoid levels, degradation enzyme activity, and BDNF levels measured with and without CB1 antagonist co-administration.
Why This Research Matters
Synthetic cannabinoids are often far more potent than natural cannabis. Understanding how they impair memory at the molecular level helps explain their cognitive dangers and may inform treatment strategies.
The Bigger Picture
This study reveals a cascade effect: a synthetic cannabinoid does not just activate CB1 directly but also raises the brain's own cannabinoid levels by blocking their degradation, creating a double hit on the endocannabinoid system that may explain the outsized cognitive impairment seen with synthetic cannabinoids.
What This Study Doesn't Tell Us
Acute single-dose study in rats. Chronic exposure effects not examined. Hippocampal metabolomics provides a snapshot, not a dynamic picture. JWH-018 is an older synthetic cannabinoid; newer variants may act differently.
Questions This Raises
- ?Do newer, more potent synthetic cannabinoids produce even greater endocannabinoid elevation?
- ?Could targeting the degradation enzyme pathway mitigate synthetic cannabinoid cognitive damage?
Trust & Context
- Key Stat:
- Double hit on endocannabinoid system
- Evidence Grade:
- Preliminary: single acute-dose rat study.
- Study Age:
- Published in 2019.
- Original Title:
- Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory.
- Published In:
- Scientific reports, 9(1), 9621 (2019)
- Authors:
- Li, Ren-Shi(2), Fukumori, Ryo, Takeda, Tomoki, Song, Yingxia, Morimoto, Satoshi, Kikura-Hanajiri, Ruri, Yamaguchi, Taku, Watanabe, Kazuhito, Aritake, Kousuke, Tanaka, Yoshitaka, Yamada, Hideyuki, Yamamoto, Tsuneyuki, Ishii, Yuji
- Database ID:
- RTHC-02138
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Why are synthetic cannabinoids worse for memory than natural cannabis?
This study suggests synthetics like JWH-018 not only directly activate CB1 receptors but also raise natural endocannabinoid levels by blocking their breakdown, creating a compounded effect on brain chemistry.
What is BDNF and why does it matter?
Brain-derived neurotrophic factor (BDNF) is a protein essential for synaptic plasticity, the process underlying learning and memory. JWH-018 reduced BDNF levels in the hippocampus.
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Cite This Study
https://rethinkthc.com/research/RTHC-02138APA
Li, Ren-Shi; Fukumori, Ryo; Takeda, Tomoki; Song, Yingxia; Morimoto, Satoshi; Kikura-Hanajiri, Ruri; Yamaguchi, Taku; Watanabe, Kazuhito; Aritake, Kousuke; Tanaka, Yoshitaka; Yamada, Hideyuki; Yamamoto, Tsuneyuki; Ishii, Yuji. (2019). Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory.. Scientific reports, 9(1), 9621. https://doi.org/10.1038/s41598-019-45969-4
MLA
Li, Ren-Shi, et al. "Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory.." Scientific reports, 2019. https://doi.org/10.1038/s41598-019-45969-4
RethinkTHC
RethinkTHC Research Database. "Elevation of endocannabinoids in the brain by synthetic cann..." RTHC-02138. Retrieved from https://rethinkthc.com/research/li-2019-elevation-of-endocannabinoids-in
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.