A CB2 receptor drug reduced cocaine-seeking behavior in rodents | Research

The takeaway

The CB2 inverse agonist Xie2-64 reduced cocaine self-administration and reinstatement in rats without affecting food-seeking behavior.

Addiction researchers, pharmacologists, and those interested in endocannabinoid system applications beyond cannabis.

Reduced cocaine self-administration without affecting food seeking

What the researchers found

Xie2-64, a CB2 receptor inverse agonist, dose-dependently reduced cocaine self-administration and blocked cocaine-primed reinstatement (relapse) in rats. Importantly, it did not reduce food-maintained responding, suggesting the effect was specific to drug reward rather than general motivation.

Why it matters

Current treatments for cocaine addiction are limited. This study suggests the CB2 receptor, part of the endocannabinoid system, could be a promising target for reducing cocaine abuse, opening a new therapeutic angle.

The numbers in context

Xie2-64 dose-dependently reduced cocaine self-administration; blocked cocaine-primed reinstatement at doses that did not affect food responding.

How the study worked

Animal study using rat models of cocaine self-administration, extinction, and reinstatement. Multiple dose levels of Xie2-64 were tested against vehicle controls.

What this study cannot tell us

Animal study; effects in rodents may not translate to humans. Only acute dosing was tested; long-term effects and safety are unknown. The specific compound (Xie2-64) has not been tested in humans.

How to read the evidence

Preliminary: animal study with a single compound; no human data available.

When this study was published

Published 2018.

The bigger picture

The endocannabinoid system keeps revealing unexpected connections to addiction beyond cannabis. CB2 receptors, once thought to exist mainly in immune cells, are now recognized in the brain and appear to modulate reward circuits involved in multiple substances.

Questions still open

Would CB2-targeting drugs work for other stimulant addictions? Could Xie2-64 or similar compounds eventually reach human clinical trials?

Common questions

What is a CB2 inverse agonist?

A drug that binds to CB2 cannabinoid receptors and produces the opposite effect of an agonist. Rather than activating the receptor, it reduces its baseline activity.

Could this lead to a cocaine addiction treatment?

Possibly. The results are promising but this is early-stage animal research. Human clinical trials would be needed to determine if CB2-targeting drugs are safe and effective for cocaine addiction.

Read the original research

Xie2-64, a novel CB2 receptor inverse agonist, reduces cocaine abuse-related behaviors in rodents.

Neuropharmacology, 176, 108241

View on PubMed ↗Publisher’s paper ↗

Citation

Jordan, Chloe J; Feng, Zhi-Wei; Galaj, Ewa; Bi, Guo-Hua; Xue, Ying; Liang, Ying; McGuire, Terence; Xie, Xiang-Qun; Xi, Zheng-Xiong. (2020). Xie2-64, a novel CB2 receptor inverse agonist, reduces cocaine abuse-related behaviors in rodents.. Neuropharmacology, 176, 108241. https://doi.org/10.1016/j.neuropharm.2020.108241