Voters in Denver, a city at the forefront of the widening national debate over legalizing marijuana, have become the first in the nation to effectively decriminalize another recreational drug: hallucinogenic mushrooms.

The local ballot measure did not quite legalize the mushrooms that contain psilocybin, a naturally occurring psychedelic compound. State and federal regulations would have to change to accomplish that.

But the measure made the possession, use or cultivation of the mushrooms by people aged 21 or older the lowest-priority crime for law enforcement in the city of Denver and Denver County. Arrests and prosecutions, already fairly rare, would all but disappear.

Results posted by the city as a “final unofficial” tally late on Wednesday showed the “Yes” vote won by less than 2,000 ballots. The “No” vote had led throughout the day, until the last updated count by elections officials. Alton P. Dillard, the elections spokesman, said the passage appeared safe, but the final results would not be certified until May 16.

“We won!!!!” the group called Decriminalize Denver that had been pushing the measure, said in a jubilant post on Facebook.

Adoption of the measure, by a margin so close that the measure was initially thought to have been rejected, signaled fledgling public acceptance of a mind-altering drug, outlawed nationally for nearly 50 years, that recent research suggests could have beneficial medical uses. A similar effort failed to get on the ballot in California last year, but it could come up again in 2020; Oregon voters may also vote on a comparable measure next year.

“It’s surreal,” said Travis Tyler Fluck, a field organizer for the campaign to pass the measure, suggesting that Denver had a sizable population of “psychedelic constituents.”

“People just don’t see it as a threat,” he added. “Compared to the ‘sinister’ LSD, magic mushrooms are tame.”

Proponents of more lenient criminal enforcement of psilocybin cite studies indicating that the drug can be beneficial for treating depression and anxiety among cancer patients. Other studies have identified potential uses in therapy for alcoholics and people trying to quit smoking, and in treating depression in people who do not have cancer.

“Because psilocybin has such tremendous medical potential, there’s no reason individuals should be criminalized for using something that grows naturally,” said Kevin Matthews, the director of the pro-mushrooms campaign.

Mr. Matthews, 33, credits psilocybin mushrooms with helping pull him out of a major depression that forced him to withdraw from the United States Military Academy at West Point, where he was a cadet for three years in his 20s.

Dr. Matthew Johnson, an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, was one of the authors of a study last year recommending that the Food and Drug Administration reclassify the drug to acknowledge its potential medical uses and relatively low potential for abuse.

Psilocybin is not addictive, and “there’s no direct lethal overdose” of the drug on record, Dr. Johnson said.

Researchers who study psilocybin’s effects use a synthetic version of the drug in carefully controlled environments, he said, which is different from someone growing mushrooms and ingesting them at home.

The ballot measure, Initiated Ordinance 301, would also establish a panel to review the law’s impact on public health and safety.

In advance of the vote, Art Way, the Colorado state director for a pro-legalization advocacy group, the Drug Policy Alliance, praised the local effort in Denver to move psilocybin enforcement off the police’s radar. But he cautioned against tackling the issue piecemeal.

“Separating some drugs as good and some as bad will only stand to perpetuate the drug war,” he said.

Arrests in Denver for incidents involving psilocybin have not numbered more than 59 in any of the last three years, and only 11 cases were prosecuted in that time.

Beth McCann, the district attorney in Denver, opposed the ballot measure, according to a spokeswoman, Carolyn A. Tyler.

“We’re still in the very early stages of marijuana legalization, and we are still learning the impact of that substance on our city,” Ms. Tyler said. “And she is not in favor of Denver being the only city that doesn’t enforce the law.”

Mayor Michael Hancock was also against the proposal, his office said, without elaborating on his reasoning. The Denver Police Department declined to take a position.

Jack Healy contributed reporting.

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