US President Donald Trump on Thursday signed an order directing the loosening of federal regulations on marijuana, a move that could further reverse decades of tough-on-weed policy.

Trump's order instructs the attorney general to quickly move ahead with reclassifying marijuana.

If that happens, the psychoactive plant would be listed alongside common painkillers, ketamine and testosterone as a less dangerous drug.

Such a decision would represent one of the most significant federal changes to marijuana policy in decades.

The Senate's Democratic leader, Chuck Schumer, welcomed the move, while dozens of lawmakers in Trump's own Republican Party blasted the decision.

Marijuana will still remain illegal federally and subject to a patchwork of local laws across the country, Trump said.

"We have people begging for me to do this, people that are in great pain for decades," Trump told reporters at the White House.

But the teetotaling president also said that controlled substances are risky and that experimentation was of no interest to ⁠him.

"I don't want it, okay," he said. "I'm not gonna be taking it. But a lot of people do want it. A lot of people need it."

Senior administration officials said the primary purpose of the order was to increase medical research of marijuana and related products to understand their risks and potential for treatment.

The Centres for Medicare and Medicaid Services plans to allow some beneficiaries to use hemp-derived CBD products as soon as April.

Dozens of Republicans in the US House of Representatives and Senate wrote to Trump on Thursday, pleading with him not to sign the order.

"Reclassifying marijuana as a Schedule III drug will send the wrong message to America's children, enable drug cartels, and make our roads more dangerous," they said.

Marijuana is the most widely used illicit drug in the world and the United States.

Nearly one in five US residents use it a year, according to the US Centres for Disease Control and Prevention.

Millions of Americans have been arrested for possession of the drug, even while growing businesses listed on stock exchanges sell cannabis-related products.

The Drug Enforcement Administration has to review the recommendation to list marijuana as a Schedule III drug under the US Controlled Substances Act and will decide on the reclassification.

The issue has been bogged down in bureaucratic process at the agency.

Under the act, marijuana is listed as a Schedule I substance like heroin, ecstasy and peyote.

That classification indicates it has a high potential for abuse and no currently accepted medical use.

Schedule III drugs are seen as less addictive and as carrying legitimate medical uses.

Even under a ⁠reclassification, marijuana would still be treated as a controlled substance on a federal level and its use subject to tight restrictions and criminal penalties. (Reuters)