In Fresno, California, last week three men bought and used what they believed to be cocaine. Within two minutes of snorting lines of the white powder, the men were unconscious, police said.

One of the three men, described as in their 20s and 30s, died at a hospital after the Jan. 7 overdose. The other two were treated and released. Five days later in Chico, California, about 275 miles to the north, 34-year-old Aris Turner died and 12 others were hospitalized with suspected overdoses. And on Monday in Oroville, California, a 30-minute drive from Chico, two men and a woman were treated for an overdose.

In the Fresno case, the drugs were determined to be "100 percent fentanyl," said Deputy Chief Pat Farmer of the city's police department. In Chico, fentanyl is suspected. And in Oroville, authorities are looking closely to determine whether fentanyl was involved, according to a statement from the Butte County Sheriff's Office.

As it mostly bypassed California — the state had one of the lowest per capita opioid overdose death rates in the nation — fentanyl wreaked deadly havoc mid-decade in the Midwest and on the East Coast, often as cheap filler or even as a replacement for the similar high of heroin or prescription painkillers like oxycodone. Now authorities fear the powerful synthetic opioid could be starting to lay siege to the nation's most populous state.

"We knew that there was a lot of cases on the East Coast and the mid-United States, and it was making its way to the West Coast," Farmer told reporters Monday. "Well, we can say with certainty that it’s here."

Overdoses by synthetic opioids were up 44 percent in California in 2017, the last year for which data was available, according to the Centers for Disease Control and Prevention. There were 536 synthetic opioid deaths reported in California that year, according to the CDC. The California Department of Public Health (CDPH) reports that 429 of those were blamed on fentanyl.

"We were lower than the national average on any metric, but fentanyl deaths are up steadily year over year," said Dr. Dan Ciccarone, a professor of family and community medicine at the University of California, San Francisco, who has been conducting research on heroin and fentanyl use. "There's something abuzz that has me worried."

Fentanyl is regulated by the Drug Enforcement Administration as a Schedule II narcotic, which means it has limited uses in hospital settings and can be used legally as an anesthetic.

"It will make people stop breathing or have very diminished breathing," said Dr. Patil Armenian, a UCSF-Fresno emergency physician and medical toxicologist who treated the Jan. 7 victims. "It is so potent, the concern is that even with one exposure it could be enough to make someone stop breathing and die."

Two police officers were treated at a hospital and released after the mass overdose in Chico. They felt ill after being near the drug, described as being 30 to 40 times more potent than heroin. The house where the people overdosed was declared a hazardous materials scene.

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In recent years, experts say, fentanyl has been produced in clandestine labs in China and either smuggled through Mexico or mailed directly to users and dealers in the United States who order it on the dark web.

It takes so little of it to get high that it's easily smuggled, experts say.

Last year, Ciccarone testified before a House subcommittee hearing on fentanyl's origins in China. He told representatives that in 2017 the volume of fentanyl smuggled into the U.S. was just 10 to 14 oil barrels worth — enough to kill tens of thousands.

Safe doses are hard to come by, said Bryce Pardo, a drug policy researcher with the RAND Corp. The fentanyl equivalent of "two grains of salt" could lead to death, he said. "The problem becomes dosing," Pardo said.

Sam Quinones, a Los Angeles journalist and author of 2015's "Dreamland: The True Tale of America's Opiate Epidemic," said a baggy of dark heroin mixed with fentanyl, which comes as a white powder, "would look like chocolate marble ice cream."

"You can get little bits of it or a huge amount," he said. "It all boils down to people not mixing well. And that's what’s going on."

It's been going on for 40 years.

Belgian pharmacologist Paul Janssen of Janssen Pharmaceutica is credited with the drug's invention in 1960, but it didn't have much of an impact on the black market until 1979, when two men in Orange County, California, died after overdosing on what they believed was heroin.

The deaths, determined to be a result of fentanyl analogs sold as "China white" heroin, were the start of a string of overdoses that reached San Diego, Los Angeles, Riverside and Santa Clara County counties in the early 1980s.

The CDC says fentanyl and its cousins were responsible for another wave of overdoses starting in 1999. The CDC calls the latest influx of street fentanyl its "third wave" of destruction, which started in 2013 and claimed the life of pop star Prince in 2016.

Experts believe that cheaper fentanyl invaded regions of the nation hard hit by addiction to other opioids, including heroin and prescription pills.

Ciccarone of UCSF said the wave has been supply driven, with fentanyl injected into the U.S. market by Mexican drug cartels.

In April the drug killed three victims in Los Angeles County: Gabriel Dirzo, 34; Gilbert Valenzuela Jr., 41, and Robert Ramirez, 36. Acute fentanyl intoxication was blamed, according to coroner's records.

Two men were charged by federal prosecutors in Southern California this week with suspicion of "Distribution of Fentanyl Resulting in Death," according to a statement from the U.S. Attorney in San Diego. The victim who overdosed Oct. 23 recovered at a hospital and, the following day, told her alleged dealer about it before asking for more drugs, which prosecutors say he supplied, according to the statement. That night, authorities said, the woman, who was not identified, died of a fatal overdose.

If fentanyl is working its way into California's black market, it could signal a shift in cartel strategy, namely that of the Sinaloa Cartel, which appears to have the most influence over the state's drug market, Ciccarone said.

In 2017 San Diego County, home to the state's second-largest city, saw a 155 percent increase in fentanyl-related overdose deaths, according to county data.

The city is part of the "Tijuana/San Diego smuggling corridor," largely controlled by the Sinaloa Cartel, according to the DEA. Tijuana is also the site of a bloody drug war, largely fought over sales of methamphetamine, which is also an increasingly cheap and common street drug in San Diego, authorities there said.

Fentanyl has appeared in drugs ranging from MDMA, better known as ecstasy, to fake prescription pills, from cocaine to methamphetamine. "We’re hearing more and more fentanyl showing up in a wide array of drugs, not just traditional heroin," said Tony Botti, spokesman for the Fresno County Sheriff’s Office.

Some experts believe that cartels and dealers might be including it in drugs as a way to expand and multiply sales by getting users hooked on a much more addictive substance.

"You can go days without cocaine," said Quinones, who's working on a new book about the fentanyl and meth explosion in America. "Your body cannot go without daily purchase consumption of this drug. One motivation might be that it would create a new, more dependent customer."

"Soon you will either get dead bodies or new addicts," Quinones said.