Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory

Ren Shi Li, Ryo Fukumori, Tomoki Takeda, Yingxia Song, Satoshi Morimoto, Ruri Kikura-Hanajiri, Taku Yamaguchi, Kazuhito Watanabe, Kousuke Aritake, Yoshitaka Tanaka, Hideyuki Yamada, Tsuneyuki Yamamoto, Yuji Ishii

Research output: Contribution to journalArticle

Abstract

The impairment of learning and memory is a well-documented effect of both natural and synthetic cannabinoids. In the present study, we aimed to investigate the effect of acute administration of JWH-018, a synthetic cannabinoid, on the hippocampal metabolome to assess biochemical changes in vivo. JWH-018 elevated levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The increase of endocannabinoid levels in response to JWH-018 could be inhibited by co-administration of AM251, a CB1 receptor antagonist. Biochemical analyses revealed that this was the result of suppression of two hydrolases involved in endocannabinoid degradation (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL]). Additionally, we showed that JWH-018 causes a reduction in the levels of brain-derived neurotrophic factor (BDNF), which is known to modulate synaptic plasticity and adaptive processes underlying learning and memory. The decrease of BDNF following JWH-018 treatment was also rescued by co-administration of AM251. As both endocannabinoids and BDNF have been shown to modulate learning and memory in the hippocampus, the alteration of their levels in response to JWH-018 may explain the contribution of synthetic cannabinoids to impairment of memory.

Original languageEnglish
Article number9621
Number of pages1
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Jul 3 2019

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory'. Together they form a unique fingerprint.

  • Cite this

    Li, R. S., Fukumori, R., Takeda, T., Song, Y., Morimoto, S., Kikura-Hanajiri, R., Yamaguchi, T., Watanabe, K., Aritake, K., Tanaka, Y., Yamada, H., Yamamoto, T., & Ishii, Y. (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