The US Drug Enforcement Administration has denied requests to stop classifying marijuana as a dangerous drug with no medical use, leaving users and businesses in limbo after many states have legalised it for medical or recreational purposes.
The DEA did relax certain restrictions on growing marijuana for research purposes.
For decades, cannabis has been listed as a 'Schedule I' drug, placing it on a par with heroin. The government has repeatedly rejected appeals for reclassification.
"Marijuana shouldn't be listed as Schedule I," US Representative Earl Blumenauer, a Democrat from Oregon, said in a statement. He said the decision left "patients and marijuana businesses trapped between state and federal laws."
Twenty-five states have sanctioned some forms of marijuana use for medical purposes. Alaska, Washington, Oregon, Colorado and the District of Columbia now allow recreational use for adults, while California and eight other states have recreational or medical marijuana proposals headed for their 2016 ballots.
The US government has maintained that legalisation of the drug violates federal law, creating difficulties for marijuana businesses with issues such as banking.
Thursday's DEA decision was a response to a 2011 petition by two former state governors who had urged federal agencies to re-classify marijuana as a drug with accepted medical uses.
In a letter to the petitioners, the DEA said it had asked the Department of Health and Human Services for a scientific and medical evaluation.
"HHS concluded that marijuana has a high potential for abuse, has no accepted medical use in the United States, and lacks an acceptable level of safety for use even under medical supervision," the letter said.
That assessment comes amid statistics showing zero overdose deaths due to marijuana each year at a time of an alarming rise of heroin-related deaths in the United States as politicians debate remedies for exploding opioid abuse.
Some experts have argued that medical marijuana could help cut opioid use.
Taylor West, deputy director of the National Cannabis Industry Association, said the DEA's decision would curtail research since marijuana would remain a criminal product.
"Research institutions are going to be somewhat hesitant if they think they will potentially jeopardise other research funding," she said. "This decision by the DEA really flies in the face of objective science."
Smart Approaches to Marijuana, an alliance of doctors, policy makers and treatment professionals who oppose legalisation, took a different view.
"I think it was a balanced decision and isn't surprising to the scientific community," said President Kevin Sabat.
The DEA will allow more growers to apply for certification by the agency to help supply researchers "with a more varied and robust supply of marijuana."