New CB1 Receptor Blocker Reduced Food Intake Without Rimonabant's Side Effects | Research

The takeaway

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.

Read this if you are interested in the endocannabinoid system's role in appetite and weight management.

Reduced food intake without affecting pain or motor control

What the researchers 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Researchers synthesized ENP11, a chemical analog of rimonabant (the CB1 receptor blocker that was withdrawn from the market due to psychiatric side effects), and tested it in rats at three doses.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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Early preclinical animal study. Demonstrates proof of concept but far from clinical application.

When this study was published

Published in 2015. The search for safe CB1-modulating drugs continues.

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.

Questions still open

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?

Common 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.

Read the original research

ENP11, a potential CB1R antagonist, induces anorexia in rats.

Pharmacology, biochemistry, and behavior, 135, 177-81

View on PubMed ↗Publisher’s paper ↗

Citation

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