Otto Pérez Molina, the president of Guatemala, floated an audacious idea last December. His government was considering legalizing the production of opium poppy — the source of morphine, which is the principal ingredient of heroin — as an alternative to combating drug-fueled bloodshed in Central America, where the number of violent deaths today mirrors those of the 1980s, when the region was entangled in civil wars.

That seemingly fanciful proposal gained steam on Monday with the release of a pioneering report, “Take Control: Pathways to Drug Policies That Work.” In it a group of global luminaries calls for the decriminalization of all drug use and the legal regulation of psychoactive substances. The Global Commission on Drugs — headed by the likes of former U.N. Secretary General Kofi Annan, Reagan-era U.S. Secretary of State George Shultz and former presidents of Latin America — represents the most distinguished group of leaders to call for drastic drug policy alternatives.

Punitive drug laws, the commission says, must be replaced by public health principles and a focus on human rights. Treat drug users as patients, not criminals, its members say, and counter drug traffickers by regulating illegal drug markets and slicing into the money — and power — generated by drug syndicates, which the United Nations estimates rake in $330 billion a year.

“The call for experimentation with regulation is just common sense, given the failures of the current one-size-fits-all approach," said John Collins, coordinator of the London School of Economics’ IDEAS International Drug Policy Project. “It’s clear that the old approach is politically unsustainable as member states such as the U.S. and Uruguay move ahead with new models of regulation around cannabis.”

Latin America, which has suffered the greatest pains from the war on drugs, has already embraced one of the report’s central recommendations: Instead of punishing drug users, governments should target the most violent criminal groups. That was the inspiration behind Uruguayan President José Mujica’s drive to legalize recreational marijuana last year. And several other countries — Mexico, Argentina and Colombia — have decriminalized the possession of drugs for personal use. It represents a regional effort to direct scarce police resources away from low-level drug users and toward violent drug gangs.

“The report acknowledges that for the very first time, we’re not talking about drug policy reform in theoretical terms," said Lisa Sánchez, coordinator of drug policies at the Transform Drug Policy Foundation. “We have concrete experiences to show, and the commission does it. From the decriminalization models in Europe to the medical cannabis market in the U.S. ... reform has proven to be more effective than prohibition in terms of reducing the overall harms associated with the drug phenomena.”

Rethinking global drug policy will come with high costs. The United Nations, for example, estimates that $3.2 billion would be needed to fund drug-related public health initiatives. But the price tag, the commission says, is dwarfed by the expenditures on punitive laws that govern current drug politics. Over $100 billion is spent globally on enforcing the war on drugs each year. The United States, which steers global drug policy along with the U.N., spends about $15 billion annually on drug control. And Mexico spent $9 billion in 2010 fighting drug trafficking.

Faced with horrific drug violence, the presidents of Colombia, Mexico and Guatemala in 2012 called on the U.N. General Assembly to hold a special session on drugs — a plea that was granted after over 90 countries supported the initiative. Now members of the Global Commission hope that an international meeting, scheduled for 2016, will consider the report’s recommendations and revamp drug policy, guided by public health principles and scientific evidence.

“We need drug policies informed by evidence of what actually works rather than policies that criminalize drug use while failing to provide access to effective prevention or treatment,” Annan said in a statement. “The facts speak for themselves. It’s time to change course.”