Hoffman, 46, who was found Feb. 2 with a needle in his arm on the floor of his Manhattan apartment, also had taken amphetamines and benzodiazepines, which are drugs such as Xanax and Valium that are widely prescribed for anxiety, trouble sleeping and other problems, said a spokeswoman for the medical examiner. The death was ruled accidental.
The medical examiner didn't provide the names of the drugs or the amounts found in the actor's system, making it impossible to determine which drug was the major factor, said Dr. Charles McKay, a medical toxicologist for Hartford Hospital in Connecticut and a spokesman for the American College of Medical Toxicology.
"There's a difference between a stimulant death, which would be cocaine and the amphetamines, and a narcotic death, like heroin," he said.
The first two can cause heart rhythm problems, a stroke or heart attack, whereas heroin, especially with sedatives such as benzodiazepines, can depress breathing.
In any case, McKay said, the combination of drugs "suggests someone who has been using drugs repetitively."
Police had been investigating Hoffman's death as a suspected drug overdose. Tests found heroin in samples from at least 50 packets in his Manhattan apartment. Authorities also found unused syringes, a charred spoon and various prescription medications, including a drug used to treat heroin addiction, a blood-pressure medication and a muscle relaxant.
More than half of overdose deaths in the U.S. involve a mix of drugs, said Dr. Len Paulozzi, a medical epidemiologist with the Centers for Disease Control and Prevention. At least a fifth also involve alcohol, he said. There were more than 38,000 drug overdose deaths nationwide in 2010, according to the most recent CDC figures.
If multiple drugs are listed on a death certificate, often "it means the coroner or medical examiner thought all of these contributed to the death," said Paulozzi, who researches overdose death trends.
"The drug of that combination that is most associated with overdose death is heroin," said Cindy Kuhn, a pharmacology professor at Duke University. "People just stop breathing. It's especially dangerous in combination with other sedatives like the benzodiazepines."
Hoffman, who won an Oscar for "Capote" and starred in numerous other movies as well as New York stage productions, had been frank about struggling with substance abuse. He told CBS' "60 Minutes" in 2006 that had he used "anything I could get my hands on" before getting clean at age 22. But in interviews last year, he said he'd relapsed, had developed a heroin problem and had gone to rehab for a time.
Heroin addicts often mix heroin with a stimulant like cocaine - a practice known as speedballing - to break the effect of the opiate, said addiction specialist Dr. Louis Baxter, a former president of the American Society of Addiction Medicine.
"They're doing self-medication or self-regulation," said Baxter. "It's just a part and parcel of what happens with long-term abuse of substances: People will go from just their drug of choice to experimentation and 'self-regulation' of other drugs."
A Hoffman family spokesperson didn't immediately return messages seeking comment. In his will, Hoffman bequeathed his estate to his longtime partner, Mimi O'Donnell, with a trust fund for their 11-year-old son. They also have two other children. Investigators have been probing how Hoffman may have obtained the heroin. Tests found it was not cut with a dangerous additive such as fentanyl, a synthetic form of morphine used to intensify the high that has been linked to deaths in other states.
A musician, veteran jazz player Robert Vineberg, was charged amid the investigation into Hoffman's death with keeping a heroin stash in a lower Manhattan apartment. Vineberg, who has said he was a friend of the Tony Award-nominated Hoffman, hasn't been charged in Hoffman's death and has said he didn't sell him the heroin found in his apartment.
AP Chief Medical Writer Marilynn Marchione in Milwaukee and Medical Writer Mike Stobbe in Atlanta contributed.