Hundreds of Initiative 71 supporters celebrated Tuesday night as early returns showed the pro-pot law clearly on is way to victory. (Michael S. Williamson/The Washington Post)

Celebration quickly gave way to uncertainty on Wednesday for supporters of a voter-approved initiative to legalize marijuana in the District, with the reality sinking in that when the measure reaches Capitol Hill for review, the party least likely to support it will be in charge.

One conservative House Republican from neighboring Maryland immediately vowed to use all of his power to upend Initiative 71, which would allow D.C. residents and visitors to have up to 2 ounces of marijuana for personal use and would allow home cultivation of up to three plants.

But advocates for the initiative took refuge in the Election Day comments of Sen. Rand Paul (R), who suggested outside a Kentucky polling precinct that he considers the matter one for D.C. voters, who ended up backing it by an overwhelming margin of more than 2 to 1: “I haven’t really taken a stand on [Initiative 71], but I’m against the federal government telling them they can’t,” Paul told reporters.

And on Wednesday, another potential pitfall emerged when Muriel E. Bowser suggested in her first press conference as D.C. mayor-elect that she would not want Initiative 71 to proceed to congressional review without accompanying legislation to establish a system for selling and taxing the plant like in Colorado and Washington state.

The conflicting signs hinted at how uncertain implementation of the city’s marijuana initiative remains, given the District’s layer of federal oversight. The situation in the District stands in stark contrast to the two states where sales are now legal, and in Oregon and Alaska, where initiatives that passed Tuesday spell out how sales will begin, perhaps as soon as early 2016.

D.C. Police Chief Cathy L. Lanier said she respects “the clear intent of District voters” in their support of Initiative 71. “However, we need to recognize that the initiative cannot be immediately implemented,” she said in a prepared statement.

“I think everyone realizes that the Council will need to enact legislation to provide clarity to the public and law enforcement officers,” Lanier said. “If the initiative is held up in Congress, attorneys for the District will need to provide additional guidance.”

In a national teleconference with reporters on Wednesday, advocates for marijuana legalization sought to play down concerns that Congress would spend the energy to overturn the District’s measure, especially right after Republicans gain control of Congress.

In recent years, nearly 50 House Republicans also have sided with Democrats to give states more protections to carry on medical marijuana programs.

Advocates acknowledged that the D.C. measure could hasten the arrival of a national debate over marijuana legalization before a critical mass of states have tilted in favor. The drug has gained greater acceptance nationwide, and the country was closely divided at 49 percent in favor and 48 percent opposed earlier this year, according to a Washington Post-ABC News poll.

Ethan Nadelmann, executive director of the Drug Policy Alliance, said conservatives are the least likely to support marijuana legalization, but he said any debate would be a good thing for advocates’ ultimate goal of nationwide legalization.

To nullify the measure, Congress would have to take the extraordinary step of getting both chambers and the president to agree on a resolution of disapproval within 60 days.

That has happened only three times in 40 years. But there are far easier ways for one or more dedicated opponents to tie up a D.C. law in smaller, annual increments that can still add up to lengthy delays. Such was the case after D.C. voters approved sales of medical marijuana in 1998. Republican House members attached provisions to federal spending bills to keep it from taking effect for 11 years.

On Wednesday, Rep. Andy Harris , a Republican who represents Maryland’s Eastern Shore, said he would employ similar tactics to block the D.C. measure.

Harris said federal drug laws that still consider marijuana possession a crime punishable by up to a year in jail should be enforced in the federal district. A doctor by training, Harris blasted the vote as detrimental to adolescents.

“Actions by those in D.C. will result in higher drug use among teens,” Harris said in a written statement to The Washington Post. “I will consider using all resources available to a member of Congress to stop this action.”

This summer, Harris persuaded the House Appropriations Committee to back such a rider that would have upended the District’s decision to decriminalize marijuana. The D.C. Council voted in March to strip away criminal penalties and the threat of jail time for possession, citing studies that showed deep racial disparity in drug arrests for marijuana in the nation’s capital. The rider was backed by House Republicans but died in negotiations with Senate Democrats after President Obama threatened to veto the provision.

On the Senate side, where Republicans gained control, Paul is in line to chair a key committee with broad oversight power of the District. He has pushed for restructuring drug laws to make possession of marijuana and other substances a misdemeanor, not a felony.

He also has indicated he might be more interested in tinkering with other District affairs. Paul recently introduced a measure that would have made gun-control laws in the city among the most lenient in the country.

But Bowser’s comments indicating that she might seek a full regulatory framework for selling and taxing marijuana before the initiative is reviewed by Congress could change Paul’s thinking, his spokesman Brian Darling said.

Adam Eidinger, the head of the D.C. Cannabis Campaign, said he hopes Bowser will support the measure as voters approved it.

“She has said she would abide by the will of voters, and the will of voters is to make the initiative law,” Eidinger said. He added that in a conversation with Bowser, he told her it would be up to her as mayor to make the case with the council and public that D.C. was ready to take the next step and establish a system to sell and tax marijuana.

“What we should do immediately, under the initiative, is encourage home cultivation,” he said. “That is better than having it in stores, where you are selling and promoting it.”

Bowser said she is ready to expend political capital to press the issue with Congress if Republicans try to stand in the way of Initiative 71.

She plans to have a point person on her transition staff dedicated to marijuana to put “a system in place that will immediately make sense of the process,” Bowser said. “I see no reason we wouldn’t follow a regime similar to how we regulate and tax alcohol.”