Joshua, 29, swapped Wembley Stadium for the Garden after promoter Hearn failed to secure an opponent, so is set to make his United States debut after almost six years as a professional to build a fanbase stateside.
Hearn tweeted: "We have been informed by Vada that there has been an adverse finding in Jarrell Miller's sample collected on March 20th, 2019".
The adverse finding is reported to be for GW1516, a metabolic modulator also known as cardarine and endurobol.
Miller was supposed to challenge Joshua for his heavyweight titles on June 1 at New York's Madison Square Garden.
Hearn, who promotes Joshua, said he had been informed of Miller's positive test by the Voluntary Anti-Doping Association (VADA), which works with athletes in boxing and mixed martial arts.
With Tyson Fury fighting on a rival broadcaster and Dillian Whyte declining earlier offers, Miller was his fourth choice for his United States debut.
Eddie Hearn, Joshua's promoter, told Telegraph Sport: "We'll wait to hear the news from Vada and the New York State Athletic Commission, but in the meantime we are talking to other potential opponents".
The situation is an enormous frustration for IBF, WBA and WBO champion Joshua, who had initially hoped to face Deontay Wilder in a unification, only for talks to fail. "AJ's preparation continues for June 1st".
The news takes on a heavy dose of irony considering that Miller himself accused Joshua of taking performance-enhancing drugs at their first press conference.
"We are in the process of obtaining further information about Vada's finding and will have more to say soon on this developing situation". The American was hit with a nine month ban when he tested positive during his kickboxing career.
The substance that he tested positive for this time, GW1516, is so risky that WADA in 2013 took the rare step of issuing an alert about the substance in order to try and protect athletes who may be using it.
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