Synthetic cannabinoid JWH-018 and its halogenated derivatives JWH-018-Cl and JWH-018-Br impair Novel Object Recognition in mice: behavioral, electrophysiological and neurochemical evidence
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It is well known that an impairment of learning and memory function is one of the major physiological effects caused by natural or synthetic cannabinoid consumption in rodents, nonhuman primates and in humans. JWH-018 and its halogenated derivatives (JWH-018-Cl and JWH-018-Br) are synthetic CB1/CB2 cannabinoid agonists, illegally marketed as "Spice" and "herbal blend" for their Cannabis-like psychoactive effects. In the present study the effects of acute exposure to JWH-018, JWH-018-Cl, JWH-018-Br (JWH-018-R compounds) and Δ(9)-THC (for comparison) on Novel Object Recognition test (NOR) has been investigated in mice. Moreover, to better characterize the effects of JWH-018-R compounds on memory function, in vitro electrophysiological and neurochemical studies in hippocampal preparations have been performed. JWH-018, JWH-018-Cl and JWH-018-Br dose-dependently impaired both short- and long-memory retention in mice (respectively 2 and 24 h after training session). Their effects resulted more potent respect to that evoked by Δ(9)-THC. Moreover, in vitro studies showed as JWH-018-R compounds negatively affected electrically evoked synaptic transmission, LTP and aminoacid (glutamate and GABA) release in hippocampal slices. Behavioral, electrophysiological and neurochemical effects were fully prevented by CB1 receptor antagonist AM251 pretreatment, suggesting a CB1 receptor involvement. These data support the hypothesis that synthetic JWH-018-R compounds, as Δ(9)-THC, impair cognitive function in mice by interfering with hippocampal synaptic transmission and memory mechanisms. This data outline the danger that the use and/or abuse of these synthetic cannabinoids may represent for the cognitive process in human consumer.
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In the context of NPS, this is reminiscent of the identification of halogenated analogues of the synthetic cannabinoid receptor agonist JWH-018.
“In the context of NPS, this is reminiscent of the identification of halogenated analogues of the synthetic cannabinoid receptor agonist JWH-018 (Barbieri et al., 2016; Sabrine Bilel et al., 2020; Vigolo et al., 2015).”
From Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization (2024) · cites this paper as Barbieri et al., 2016
The supplied passages contain no match, and searches of our copy for JWH-018, its halogenated derivatives, and chlorine or bromine returned no passages. The paper’s title identifies those derivatives, but the required full-text evidence is unavailable to verify what the citing sentence attributes to it. (LLM, conf=0.65)
Experimental — accuracy not yet measuredApplication of JWH-018, a synthetic cannabinoid 1/2-R agonist, decreased potassium-evoked glutamate and GABA release and LTP in hippocampus slices.
“Application of JWH-018, a synthetic cannabinoid 1/2-R agonist, decreased potassium-evoked glutamate and GABA release and LTP in hippocampus slices”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Barbieri et al., 2016
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References 123 · Cited by 56
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- Authors
- Barbieri, M., Ossato, A., Canazza, I., Trapella, C., Borelli, A. C., Beggiato, S., Rimondo, C., Serpelloni, G., Ferraro, L., & Marti, M.
- Affiliations
- University of Ferrara (IT)
- University of Verona (IT)
- University of Florence (IT)
- Corresponding author
- Marti, M.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 109
- Pages
- 254-269
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2461974876
- Cited by
- 56
- References
- 123
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 1
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by-nc-nd)
- Funders
- Drug Policies Department, Presidency of the Council of Ministers, Italy (FAR 2013, FAR 2014, FAR 2015, NS-Drugs 2014)
- University of Ferrara
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- JWH-018, synthetic cannabinoids, novel object recognition, memory impairment, CB1 receptor, hippocampus, synaptic transmission, long-term potentiation, glutamate release, GABA release, Δ9-THC, cognitive function, AM251
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Hippocampus, Indoles, Male, Mice, Inbred ICR, Naphthalenes, Organ Culture Techniques, Recognition, Psychology, Receptor, Cannabinoid, CB1, Mice, Halogenation, Electrophysiological Phenomena
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