The initiative, led by Decriminalize Denver, a movement focused on making the mushrooms legal, will appear on municipal election ballots on Tuesday.
The initiative does not legalize psilocybin or permit its sale by Denver's cannabis businesses.
The federal government argues that psilocybin - and all Schedule I classification drugs - have high abuse potential and no accepted medical value. Users describe seeing vivid colors and experiencing powerful emotions. "I don't think that people should be criminalized or looked upon differently because they are required to take something that can make them feel this much better", one 54-year-old patient now using psilocybin mushrooms told CBS Denver.
It took the pro-psilocybin organizers in Denver three tries to develop language approved by city officials for the ballot.
District Attorney Beth McCann, whose office handles all criminal charges in Denver, has said she appreciates the inclusion of a panel to study the effects of the change.
A California effort to decriminalize psilocybin failed to qualify for the statewide ballot in 2018.
Activists in California failed to get a similar initiative on the ballot a year ago, and supporters in OR are hoping to put the matter to a vote statewide in 2020. "Just being able to vote for this is a huge victory".
"Magic Mushrooms" have been used for recreation use for a long time. "We're still figuring out marijuana, and even though things are going well so far, we're still measuring the impacts on the people of Denver".
Mayor Michael Hancock, who is running for re-election, has told the Denver Post that he opposes the mushroom question.
Matthews says he's optimistic about his initiative's chances, telling Reason that the yes side's canvassing efforts have encountered few die-hard opponents.
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 previous year recommending that the Food and Drug Administration reclassify the drug to acknowledge its potential medical uses and relatively low potential for abuse.