Fourteen years after California decided marijuana could be used as a medicine and ignited a national movement, the state is likely to vote on whether to take another step into the vanguard of drug liberalization: legalizing the controversial weed for fun and profit.

On Wednesday, Los Angeles County elections officials must turn in their count of valid signatures collected in the county on a statewide legalization initiative. The number is virtually certain to be enough to qualify the initiative for the November ballot, according to a tally kept by state election officials.

That will once again make California the focal point of the long-stewing argument over marijuana legalization, a debate likely to be a high-dollar brawl between adversaries who believe it could launch or stifle another national trend.

The campaign will air issues that have changed little over the years. Proponents will cite the financial and social cost of enforcing pot prohibition and argue that marijuana is not as dangerous and addictive as tobacco or alcohol. Opponents will highlight marijuana-linked crimes, rising teenage use and the harm the weed causes some smokers.

But the debate also will play out against a cultural landscape that has changed substantially, with marijuana moving from dark street corners to neon-lit suburban boutiques. In the months since the Obama administration ordered drug agents to lay off dispensaries, hundreds have opened, putting pot within easy reach of most Californians. Whether voters view this de facto legalization with trepidation or equanimity could shape the outcome.

The measure’s supporters hope that this dynamic will shift the debate, allowing them to persuade voters to replace prohibition with controlled sales that could be taxed to help California’s cities and counties.

“They already accept that it’s out there. They want to see a smart strategy,” said Chris Lehane, a top strategist for the initiative.

But John Lovell, a Sacramento lobbyist for law enforcement groups, said he believes that voters will reject that argument.

“Why on Earth would you want to add yet another mind-altering substance to the legal array?” he asked.

California is not alone in weighing legalization. Several state legislatures have considered bills and two other Western states may vote on initiatives. In Nevada, a measure aimed for 2012 would allow state-licensed pot stores. And a campaign in Washington hopes to put a legalization measure on the fall ballot.

The 10-page California initiative would allow anyone 21 or older to possess, share and transport up to an ounce for personal use and to grow up to 25 square feet per residence or parcel. It would allow local governments, but not the state, to authorize the cultivation, transportation and sale of marijuana and to impose taxes to raise revenues.

To make the ballot, the measure needs 433,971 valid signatures. By Tuesday, it was just 15,000 short. Los Angeles County, where supporters collected 142,246 signatures, is expected to put it over the top.

The initiative’s main proponent, Richard Lee, has spent at least $1.3 million, mostly on a professional signature-gathering effort, and has assembled a team of experienced campaign consultants that includes Lehane, a veteran of the Clinton White House.

Lee, who owns half a dozen mostly pot-related businesses in Oakland, has said that he hopes to raise as much as $20 million. The last time pot was on the ballot, in 1996, proponents raised $2 million, with most of it from a few wealthy supporters.

Lehane said the campaign would have a major Internet component. Marijuana has a devoted following on the Web. When President Obama held an online town hall meeting after his inauguration, he was barraged with questions about legalization.

“There’s the potential to raise significant online resources,” he said.

Lovell has been assembling a coalition to defeat the measure. He thinks that he will be able to recruit business leaders because the initiative prohibits discrimination against anyone who uses marijuana, unless it affects job performance.

Lovell said he is not worried about “the deep pockets on that side.” He noted that opponents of Proposition 5, which would have let nonviolent drug offenders avoid prison, defeated it in 2008 despite being outspent.

“We don’t have to match the other side dollar for dollar,” he said.

In that case, Gov. Arnold Schwarzenegger and four former governors denounced the measure. All the major candidates for governor have shunned the pot initiative, including Democrat Jerry Brown, who as governor signed a law in 1975 that dramatically reduced marijuana penalties.

Lehane said the legalization campaign would soon roll out radio ads with former law enforcement officials.

Polls have shown that a slim majority of California voters want to legalize marijuana. Both sides will shape their arguments to take aim at the wavering voters in the middle.

The measure’s supporters say the undecided are primarily women in their 30s and 40s with children.

Proponents hope to persuade those voters that it is time for a fresh approach to a drug that is a fact of life in California, where it supports a multibillion-dollar economy. The wisest plan, they argue, is to allow cities and counties to regulate sales and impose taxes to help them escape their budget disasters.

Two independent pollsters, Mark Baldassare of the Public Policy Institute of California and Mark DiCamillo of the Field Poll, said the state’s grim financial situation may heighten the measure’s appeal.

“Whether voters are really there, whether they want to legalize marijuana, I would probably tend to say no, but given the drastic state of the budget, I don’t know,” said DiCamillo, calling the issue a wild card. “The climate may actually help it a bit.”

Opponents plan to remind voters of the chaos caused by cities and counties struggling with California’s medical marijuana law, noting that it had led to the explosive growth in dispensaries in Los Angeles County, where a quarter of the state’s voters live.

“It’s going to be a crazy quilt of 500 different marijuana nations,” Lovell said.

Lehane said the legalization campaign will unveil model ordinances to show voters how it could work and highlight separate state legislation to capture tax revenue from legal sales.

The adversaries will also debate the social costs, disputing the effect prohibition has on marijuana use, drug violence and the role of Mexican cartels.

Stephen Gutwillig, California director of the Drug Policy Alliance, said he hoped to highlight the increase in misdemeanor marijuana arrests, which tripled between 1990 and 2008.

“It really is on a scale that we have never seen,” he said.

Opponents will cite a national survey that found an increase in teenagers trying marijuana last year. And they are emphasizing the danger of drugged drivers. In a recent column, Ventura County Sheriff Bob Brooks cited a 2007 accident in which a driver high on marijuana crashed into a stopped vehicle, killing its driver and critically injuring a California Highway Patrol officer.

john.hoeffel@latimes.com