New CB1 Receptor Blocker Reduced Food Intake Without Rimonabant's Side Effects
A new compound called ENP11 reduced food intake and blocked anandamide-induced overeating in rats without affecting pain perception or motor control, potentially offering a safer alternative to rimonabant.
Quick Facts
What This Study Found
Researchers synthesized ENP11, a chemical analog of rimonabant (the CB1 receptor blocker that was withdrawn from the market due to psychiatric side effects), and tested it in rats at three doses.
ENP11 reduced food intake during the first hour after administration. At 1.0 mg/kg, it successfully blocked the overeating caused by anandamide (an endocannabinoid). It also blocked anandamide-induced hypothermia, confirming it acts at CB1 receptors.
Importantly, none of the tested doses affected pain perception or motor control, side effects that have been concerns with CB1-blocking compounds.
Key Numbers
Three doses tested: 0.5, 1.0, 3.0 mg/kg; 1.0 mg/kg blocked anandamide-induced overeating and hypothermia; no effects on pain or motor control at any dose
How They Did This
Rat study testing three doses of ENP11 (0.5, 1.0, 3.0 mg/kg) on food intake, pain perception, core temperature, and motor control. Also tested whether ENP11 could block anandamide-induced effects.
Why This Research Matters
Rimonabant showed that blocking CB1 receptors could powerfully reduce appetite, but psychiatric side effects led to its withdrawal. Finding compounds that retain the appetite-suppressing effects without the broader side effects is an active goal in obesity pharmacology.
The Bigger Picture
The endocannabinoid system remains a promising target for appetite regulation and obesity treatment. ENP11 represents an effort to develop safer CB1-modulating compounds, though the road from animal studies to approved medications is long.
What This Study Doesn't Tell Us
Early-stage animal study. Acute effects only (no chronic dosing). Psychiatric side effects (the main concern with rimonabant) cannot be assessed in rat behavioral tests. Human translation is uncertain.
Questions This Raises
- ?Does ENP11 avoid the psychiatric side effects that doomed rimonabant?
- ?Would chronic administration maintain the appetite-suppressing effect?
- ?Could ENP11 or similar compounds help with cannabis withdrawal?
Trust & Context
- Key Stat:
- Reduced food intake without affecting pain or motor control
- Evidence Grade:
- Early preclinical animal study. Demonstrates proof of concept but far from clinical application.
- Study Age:
- Published in 2015. The search for safe CB1-modulating drugs continues.
- Original Title:
- ENP11, a potential CB1R antagonist, induces anorexia in rats.
- Published In:
- Pharmacology, biochemistry, and behavior, 135, 177-81 (2015)
- Authors:
- Méndez-Díaz, Mónica(2), Amancio-Belmont, Octavio, Hernández-Vázquez, Eduardo, Ruiz-Contreras, Alejandra E, Hernández-Luis, Francisco, Prospéro-García, Oscar
- Database ID:
- RTHC-01016
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What happened to rimonabant?
Rimonabant was a CB1 receptor blocker approved in Europe for obesity treatment but was withdrawn in 2008 due to serious psychiatric side effects including depression and suicidal thoughts. It was never approved in the United States.
Could this drug help with weight loss?
ENP11 reduced food intake in rats, but this is a very early-stage finding. Human safety and efficacy testing would be required, and the key question is whether it avoids the psychiatric side effects that ended rimonabant.
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Cite This Study
https://rethinkthc.com/research/RTHC-01016APA
Méndez-Díaz, Mónica; Amancio-Belmont, Octavio; Hernández-Vázquez, Eduardo; Ruiz-Contreras, Alejandra E; Hernández-Luis, Francisco; Prospéro-García, Oscar. (2015). ENP11, a potential CB1R antagonist, induces anorexia in rats.. Pharmacology, biochemistry, and behavior, 135, 177-81. https://doi.org/10.1016/j.pbb.2015.06.007
MLA
Méndez-Díaz, Mónica, et al. "ENP11, a potential CB1R antagonist, induces anorexia in rats.." Pharmacology, 2015. https://doi.org/10.1016/j.pbb.2015.06.007
RethinkTHC
RethinkTHC Research Database. "ENP11, a potential CB1R antagonist, induces anorexia in rats..." RTHC-01016. Retrieved from https://rethinkthc.com/research/mendez-diaz-2015-enp11-a-potential-cb1r
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.