While the exact reasons surrounding the death of actor Heath Ledger, 28, will only be determined by further testing, police and forensic pathologists are already looking to drug interactions as a possible culprit.
And as the tales of celebrities who may have died from drug combinations accumulate, stories of people who appear to have indulged in chemical cocktails — and lived to tell about it — are also making the rounds on the entertainment news scene.
In one possible example of this behavior, a home video released this week by the British newspaper The Sun showed singer Amy Winehouse inhaling from a type of glass pipe commonly used to smoke crack cocaine — just a few minutes after she announced that she had taken six tablets of the anti-anxiety drug Valium.
New York-based forensic psychiatrist Michael Welner is chairman of the Forensic Panel, a national forensic science practice that consults on death investigations. He says that a number of factors could affect the likelihood of a given individual dying from a dangerous combination of prescription medicine.
And he notes that recklessness, like that apparently exhibited by Winehouse, is only part of the equation.
"What this says is that this is a person who has the experience of taking drug combinations and waking up the next day and being OK," Welner said. "When people have these types of experiences, they develop their own style of how they take and mix drugs."
With some medications, individuals will find that their tolerance of the drug grows the longer they have been taking it. With time, they may be able to safely take a dose of this drug that would pose a serious hazard for someone who has never taken it.
The specific combination of medications is another factor. Forensic specialists say that when taken together, drugs that have similar effects can conspire to create a more profound effect. A combination of two or three sedatives in their therapeutic doses, for instance, may pack a more dangerous punch than a moderate overdose of any one of the medications alone.
Taking all these factors into account, Welner says the victims of drug cocktails can be divided into one of three recurring types.
"You could have an indulgent person who takes pills in a reckless way, who just pops this pill and pops that pill without regard for the consequences," he says. "You could have an uneducated consumer, who has a certain lack of awareness of what they are doing and who may not be abusing drugs in the way that many people think of, but who takes sedatives and pills in a way that if they were an informed consumer they would not.
"And lastly, you could have a person who takes these medications, maybe even according to the proper doses, but just by the virtue of the unfortunate way in which his body reacts, dies suddenly."
Until the results of the pending toxicology report are released, Welner says, there is no way to tell which, if any, of these categories Ledger fits into.
"[A fatal drug overdose] can happen to someone who is very irresponsible, and it can also happen to someone who is tragically unlucky."
However, the evidence thus far does suggest that a drug cocktail could have been the cause behind Ledger's death.
According to police reports, Ledger was found on Tuesday afternoon, lying face down and naked on the floor of his rented SoHo loft. Police also note that bottles of various prescription medications, prescribed in Ledger's name, were found nearby.
Cyril Wecht, a forensic pathologist who has been involved with past celebrity drug overdose death investigations, says that the powerful medications, which reportedly included prescription sleeping pills and the anti-anxiety medications Diazepam and Alprazolam, could well have contributed to Ledger's death if taken in inappropriate amounts or in combination.
"You can assume that with a 28-year-old adult male in good health, it is not very likely that it was a natural death," he says. "Whether it proves to be suicide or accidental overdose is another matter."
Wecht says that while a very large quantity of a single medication is needed to bring about death, a combination of two or three prescription drugs could easily have profound combined effects -- especially if the pills are mixed with alcohol.
In these cases, Wecht says, "nine times out of 10, or even 10 times out of 10, it's an accidental death."
Such appears to be the case with at least two other celebrity drug overdose investigations Wecht has been involved with over the past two years. In the case of former Playboy playmate Anna Nicole Smith, an archaic sleeping medication known as chloral hydrate was part of a nine-drug cocktail that contributed to her demise, which was believed to be accidental.
The autopsy of Anna Nicole Smith's son, Daniel Smith, revealed a combination of methadone and the antidepressants Lexapro and Zoloft.
In each of these cases, Wecht says, death could result from the combined effects of small doses of these drugs. And he adds that in these past cases, the fatal overdoses did not appear to have been intentional.
"Most of these acute combined drug toxicity deaths are not suicide," Wecht says.
Headed for Disaster?
Still, to some, that all depends on how loosely you interpret the term "suicide."
Reports of Winehouse's behavior reveal a lifestyle that is, at the very least, risky. In December, a number of tabloids ran photographs of Winehouse that appeared to show her with a mysterious white powder in her nose. And some of her recent public appearances have shocked many of her fans, as she has occasionally appeared stumbling, slurring and otherwise disoriented.
But in Welner's view, past tragedies suggest that the threat of death by drug overdose hangs not only over the head of those young celebrities who indulge in prescription and illicit highs, but also those who do not pay adequate heed to the inherent dangers of certain medicines.
"Until we know what's in his system, it will be very hard to speculate," Welner says. "However, I think that if it's proven that he died of something he ingested, it forces us to look at the community of talented people who die of unexpected overdoses and ask to what degree they are influenced to self-treat by using medicines in as cavalier a way as a person might decide to take 500 or 1,000 milligrams of vitamin C.
"These are not citrus-flavored chewable vitamins. Yet there is something that they share that causes them to regard Xanax and Valium like they would Flintstones."
Radha Chitale and Lauren Cox contributed to this report.