The calorie-burning capacity of brown and beige fat has been extensively studied as research efforts focus on therapies targeted to treat obesity and diabetes. The drug 2,4-dinitrophenol , which also acts as a chemical uncoupler similarly to UCP1, was used for weight loss in the 1930s. However, it was quickly discontinued when excessive dosing led to adverse side effects including hyperthermia and death.  β3 agonists, like CL316,243, have also been developed and tested in humans. However, the use of such drugs has proven largely unsuccessful due to several challenges, including varying species receptor specificity and poor oral bioavailability. 
But Spain’s government is vehemently opposed to such a referendum even taking place. The country’s constitutional court has declared the referendum illegal, and the national police have arrested 14 senior Catalan officials and confiscated millions of ballot papers. Judges have ordered the police to seize any building or materials related to the referendum to ensure that a vote does not take place. These actions have prompted mass protests, and Spain’s Interior Ministry has deployed thousands of extra police to the region ahead of what it expects to turn into a violent day.