Athletes who tested positive for meldonium before 1 March may have their bans overturned, after WADA said it was unable to establish how quickly the drug, outlawed since 1 January, cleared the human body.
The World Anti-Doping Agency's notice to national anti-doping bodies comes comes less than four months before the Rio de Janeiro Olympics, and is expected to have a major impact on many of the 172 athletes who have tested positive for the performance-boosting drug since January.
They include five-times Grand Slam tennis champion Maria Sharapova, who was among 40 Russian athletes who tested positive for the drug after it was added to WADA's list of banned substances.
Sharapova's lawyer, John Haggerty, said WADA handled the issue "poorly" and was now trying to make up for it.
WADA said there was a lack of clear scientific information on excretion times.
"As a result it is difficult to know whether an athlete may have taken the substance before or after January 1, when it became illegal," WADA said in a statement sent to anti-doping agencies and sports federations.
"In these circumstances, WADA considers that there may be grounds for no fault or negligence on the part of the athlete," it said, adding that the presence of less than one microgram of meldonium in the samples was acceptable.
The drug's Latvian manufacturer said traces could remain in the body for several months depending on doses, duration of treatment and sensitivity of testing methods, Reuters revealed last month.
The anti-doping body's notice could give hope to athletes who have tested positive for the drug since 1 March, depending on studies being carried out to determine how long it stays in the body.
"Since meldonium was prohibited on 1 January of this year, there have been 172 positive samples for the substance, for athletes across numerous countries and sports," WADA President Craig Reedie said.
"Concurrently there has been a call by stakeholders for further clarification and guidance," he said.
"WADA recognises this need -- that meldonium is a particular substance, which has created an unprecedented situation and therefore warranted additional guidance for the anti-doping community."
Sharapova, who said she had been taking meldonium for more than a decade because of health problems, was provisionally suspended by the International Tennis Federation (ITF) in March after announcing she had failed a test at the Australian Open. She said she had not used meldonium since 1 January.
Russian Sports Minister Vitaly Mutko welcomed WADA's decision.
"The Russian Sports Ministry supports and welcomes the decision made by WADA because it has shown a willingness to understand the situation, rather than stick to the rulebook," Mutko said in a statement.
Several Russian federations, including rugby, skating and cycling, are now confident their athletes who tested positive could be free to return to competition.
Meldonium, manufactured for people suffering from heart problems, can also increase blood flow and improve exercise capacity.