The Other Opiate Problem

I used to love "60 Minutes." As a teenager, it was a favorite program in our house on Sunday evenings. The show featured all sorts of interesting people and places, with in-depth explorations that stimulated the imagination. Oh, how times have changed!

On February 24, 60 Minutes did a segment about a drug manufacturer who is calling out drug companies for "corrupt," "immoral," and "depraved" actions in marketing opioids.

Supposedly, the incentive for changing the labeling of opioids to allow for extended use is some sort of moral crime. David Kessler, former Commissioner of the FDA said, "There are no studies on the safety or efficacy of opioids for long-term use." (8:25 in the video)

Case closed! We need to restrict opioids to two or three days at most. Anything longer than that is bad medicine and gets people killed. But… There are no polite words for the perfidious implications of Kessler's comment. How do we know this? Let me count the ways.

First, opioids have been used for millennia. Chinese workers on the transcontinental railroad used opium on a weekly basis for years, without any notable adverse effects. American soldiers used them in Vietnam, and their performance in the field was not affected. Overdoses were unusual, since the usual heroin had well known potency. With 20% of the Army on drugs, you'd think that bad effects would be easy to find. Curiously, there was no evidence of mass addiction, either.

Why did they use drugs in their "off" time? They wanted to escape the war that none of them wanted to be part of. The Chinese laborers wanted a break from the brutal conditions on the railroad project. This is basically why urban professionals have beer at the end of a long hard week of work. Mild intoxication is therapeutic for them.

Second, while there may be no studies on extended use, those of us in medicine are painfully aware that while some patients do well without opioids, others require what Dr. Kessler would call "extended" use. This is a result of the Bell curve, or "normal distribution" of response to drugs.

The person whose knee replacement requires zero opioids is on the left side of this curve, while the one who needs them for two weeks is on the right. Most of us fall somewhere in the middle. Every surgeon and every anesthesiologist lives with this curve every day. Importantly, the difference between the left and right sides of the curve isn't two or three pain pills. The range is from zero to a hundred or more. And that leads to a key piece of information that 60 Minutes completely ignored.

Most physicians routinely use medications in "off-label" ways. To understand this, we have to point out one part of the Law of the Bureaucrat. Each FDA officer has been hired to "protect the public" from unsafe drugs. This means that people are too stupid to use drugs properly (Unfortunately, this is often all too true, even when explicit instructions are provided.) And it means that doctors are too stupid to prescribe them safely, leaving the bureaucrat charged with "protecting the public" as the smartest person in the room. That then means that the bureaucrat must create iron-clad instructions for how medical personnel with more training and experience than him or her should prescribe the drugs. These instructions become part of "the label."

Drug reps are only allowed to tell doctors exactly what the label says. They can't even provide reprints of newer studies with additional information. That would be "off-label marketing," and the FDA expressly prohibits that. Fortunately, doctors aren't prevented from reading those journal articles. Shortly, responsible doctors start prescribing in ways that are different from what the Feds said they should do. And millions of patients get new benefits that the Feds haven't approved.

With regard to opioids, the Feds never approved fentanyl or sufentanyl for the massive doses commonly used in heart surgery. But that never stopped me from administering literally gallons of both. The benefits were far too great to bother asking for permission I wasn't legally required to get. And with regard to longer term use, we've been helping patients with cancer pain and other chronic pain with opioids for decades. These people are physiologically dependent, but you wouldn't know it, because your co-worker with the bad back keeps coming to work. He's able to do that because his opioid prescription keeps getting refilled.

The long-term benefits of opioids have been well known for a very long time. The long-term side effects are equally well known. But the key side effect that is creating the panic does not come from long-term medical use. You heard me right. In spite of all the noise about "overprescribing," that simply is not a problem. Less than 1% of the addicts on the street got their start with prescription opioids. And chronic pain patients rarely die of overdoses.

When Ed Thompson of Pharmaceutical Manufacturing Research Services tells Bill Whitaker that "the root cause of this epidemic is the FDA's illegal approval of opioids for the treatment of chronic pain," he's simply wrong. This approval did create a marketing change, but for chronic pain patients, it didn't make a lot of difference. Most pain management specialists and oncologists were already prescribing the drugs when needed for long-term care. But this opened the door for unscrupulous doctors to ring the cash register in an already illegal market.

The problem in the US began in earnest when William Randolph Hearst capitalized on racist sentiments against Chinese workers in his newspaper campaign against the "coolee." He created the myth of the "opium fiend" who terrorized white women after smoking opium. It was a complete fabrication, but it sold the idea of opium restrictions to moralists and politicians. Who cares about facts when you can "Do something!"?

Next, when Andrew Kolodny says that "as the doses become higher [in response to drug tolerance] the drugs become more dangerous, and the risk of death goes up," he is not telling the truth as I see it. He is pandering to a political narrative. The basic fact is that when you give opioids for an extended period, the endorphin receptors become tolerant to their presence. You do need to give more drug to achieve the same effect. But that very tolerance is what makes the drugs safer in the tolerant patient. Allow me to translate from medical to English.

If I need 10 milligrams of morphine for pain relief after surgery, and I just keep on taking 10 mg, after a while, I won't get the relief. But my body will not need that degree of relief, so I will start spacing my doses out. This is something we saw in great detail when Patient Controlled Anesthesia (PCA) was introduced to pain management after surgery.

With the "morphine pump," a patient was able to give himself lots of little doses of an opioid to help with pain after surgery. The PCA was rigged to prevent a repeat dose until 6 minutes after the previous dose, giving it time to work. We never saw overdoses with PCA if the patient was the only person to push the button. Never. As in "not once." In fact, patients automatically weaned themselves off opioids. This was so safe that now the Acute Pain Service no longer exists in most hospitals. The surgeon signs a protocol sheet, and everything goes on autopilot.

The same thing happens when patients have pain pills at home after surgery. They taper off without thinking about it as the pain level subsides. But suppose they are in that 1% that stays on opioids. Their receptors get tolerant and need higher and higher doses to get the same response. This means it also takes higher and higher doses to stop the patient from breathing, which is how ODs kill. Kolodny has his facts wrong.

So, what kills addicts? Or, perhaps we should ask, why do addicts take overdoses? After all, overdoses given by someone else are rare. Even addicts don't often try to commit suicide. It's at this point that we have to step back from the final dose of a street drug, the proximate cause of the overdose, and look for the first step in a series of critical incidents. Like airplane crashes, it's never just one thing that causes ODs, even if politicians like to have one problem that they think only they can solve.

The first thing to note is that all opioids are, in a sense, the same drug. They all work at the same receptor, and they all have the same family of side effects. The primary differences revolve around how fast they start working (onset), how long they last (duration), and how much is required to reach a standard level of effect (potency). Of importance, the more potent a drug is, the more it binds only to the intended receptor, and the fewer side effects it will have (for example, nausea). That means that fentanyl is safer during surgery than morphine and explains why we rarely use morphine in surgery today.

The next factor is that all the opioids are dirt cheap to manufacture. Virtually all the cost is in distribution. But even including the cost of distribution, Portugal spends about $4 a day on maintaining addicts, Canada about $11, and we should expect similar economies here if implemented. So why is it that El Chapo was worth north of $14 billion from the drug trade? It wasn't the native cost of drugs. It came from distribution.

Why would anyone pay more than the price of aspirin for a drug that costs the same as aspirin? There's only one reason: Prohibition. Recall that the soldiers in Vietnam used heroin and the Chinese laborers used opium for stress relief during leave time. There is a relatively fixed portion of the population that wants such intoxicants. With the change in labeling, it became "legal" for unscrupulous doctors to supply those people. But if they can't get them "legally," they will find a way to get them illegally.

If there's a market for the illegal drugs, there will be a marketer. Enter El Chapo. He'll provide your drugs, but for a price. Since he's taking a legal risk, it will be high enough to compensate him for that risk. Economists call this a "risk premium." Next, since you are opening your wallet, you want the good stuff. You won't go back to the left street corner if you don't get quality. So the guy on the right street corner figures that out and adds fentanyl to your heroin. As the expression goes, "Aye, there's the rub."

We've described a vicious circle where higher price demands higher quality which again demands higher price. The higher price invites competition, but since the competition is in an illegal market, crime follows. And as users become addicted, they often find themselves committing crimes to pay for those high prices. Did I mention that Canada is able to maintain an addict legally for $11 per day?

Even the Drug Enforcement Agency has noted that prohibition creates massive profits for bad guys. That should raise alarms. If prohibition starts this vicious cycle, and a national experiment with decriminalization (Portugal) has basically eliminated ODs, shouldn't we start looking in that direction? Drug-related crime in the US was essentially nonexistent until Hearst's yellow journalism led to restrictions on heroin and other drugs. Crime accelerated as laws got stricter. In short, Congress created the drug cartels. Competition among drug cartels leads to adulteration of heroin with much more potent opioids, and this unknown potency leads people to take doses with unknown risks.

In maintenance programs, known-potency drugs are given to patients with extreme safety. And over time, Portugal has seen that about half of addicts will wean themselves off their drugs.

60 Minutes wasn't satisfied with its story until it slandered drug manufacturers and the FDA with this exchange: (13:40)

Whitaker: "(commentary)… also review new drugs, like Dsuvia, the most powerful opioid pill ever approved.  (to Kessler) Just a few weeks ago the FDA approved a new opioid that is a thousand times more powerful than morphine. And this is in the middle of this opioid epidemic. How is that possible?"

Kessler: "I don't get it. I get your question. I don't get the agency's action."

Whitaker: "Isn't the FDA supposed to be our watchdogs to protect us?"

Dsuvia is a tablet to be taken under the tongue when severe pain (chronic or cancer) "breaks through." It is faster in onset than morphine, with a shorter duration. The 30 micrograms in Dsuvia, is equal in effect to 30 milligrams of morphine, a common dose in that situation. Whitaker's phrasing was wrong. The FDA did not approve an opioid that was a thousand times more powerful than morphine. It was the same strength. It is a thousand times more potent, so AcelRx Pharmaceuticals created a pill carefully tailored to meet a specific need by only including a thousandth as much.

60 Minutes is complicit in the fear-mongering that is killing large numbers of Americans through poorly considered laws. The only way to eliminate the overdoses is to eliminate the laws. That will bankrupt the drug cartels. But the Overton Window for this sort of action has not yet opened. That means we will likely be seeing more and more examples of Einstein's Maxim.

"Insanity is when you do something a second time and expect a different answer."

Ted Noel, MD is a retired anesthesiologist. He comments on political issues in the Vidzette podcast at vidzette.libsyn.com.

I used to love "60 Minutes." As a teenager, it was a favorite program in our house on Sunday evenings. The show featured all sorts of interesting people and places, with in-depth explorations that stimulated the imagination. Oh, how times have changed!

On February 24, 60 Minutes did a segment about a drug manufacturer who is calling out drug companies for "corrupt," "immoral," and "depraved" actions in marketing opioids.

Supposedly, the incentive for changing the labeling of opioids to allow for extended use is some sort of moral crime. David Kessler, former Commissioner of the FDA said, "There are no studies on the safety or efficacy of opioids for long-term use." (8:25 in the video)

Case closed! We need to restrict opioids to two or three days at most. Anything longer than that is bad medicine and gets people killed. But… There are no polite words for the perfidious implications of Kessler's comment. How do we know this? Let me count the ways.

First, opioids have been used for millennia. Chinese workers on the transcontinental railroad used opium on a weekly basis for years, without any notable adverse effects. American soldiers used them in Vietnam, and their performance in the field was not affected. Overdoses were unusual, since the usual heroin had well known potency. With 20% of the Army on drugs, you'd think that bad effects would be easy to find. Curiously, there was no evidence of mass addiction, either.

Why did they use drugs in their "off" time? They wanted to escape the war that none of them wanted to be part of. The Chinese laborers wanted a break from the brutal conditions on the railroad project. This is basically why urban professionals have beer at the end of a long hard week of work. Mild intoxication is therapeutic for them.

Second, while there may be no studies on extended use, those of us in medicine are painfully aware that while some patients do well without opioids, others require what Dr. Kessler would call "extended" use. This is a result of the Bell curve, or "normal distribution" of response to drugs.

The person whose knee replacement requires zero opioids is on the left side of this curve, while the one who needs them for two weeks is on the right. Most of us fall somewhere in the middle. Every surgeon and every anesthesiologist lives with this curve every day. Importantly, the difference between the left and right sides of the curve isn't two or three pain pills. The range is from zero to a hundred or more. And that leads to a key piece of information that 60 Minutes completely ignored.

Most physicians routinely use medications in "off-label" ways. To understand this, we have to point out one part of the Law of the Bureaucrat. Each FDA officer has been hired to "protect the public" from unsafe drugs. This means that people are too stupid to use drugs properly (Unfortunately, this is often all too true, even when explicit instructions are provided.) And it means that doctors are too stupid to prescribe them safely, leaving the bureaucrat charged with "protecting the public" as the smartest person in the room. That then means that the bureaucrat must create iron-clad instructions for how medical personnel with more training and experience than him or her should prescribe the drugs. These instructions become part of "the label."

Drug reps are only allowed to tell doctors exactly what the label says. They can't even provide reprints of newer studies with additional information. That would be "off-label marketing," and the FDA expressly prohibits that. Fortunately, doctors aren't prevented from reading those journal articles. Shortly, responsible doctors start prescribing in ways that are different from what the Feds said they should do. And millions of patients get new benefits that the Feds haven't approved.

With regard to opioids, the Feds never approved fentanyl or sufentanyl for the massive doses commonly used in heart surgery. But that never stopped me from administering literally gallons of both. The benefits were far too great to bother asking for permission I wasn't legally required to get. And with regard to longer term use, we've been helping patients with cancer pain and other chronic pain with opioids for decades. These people are physiologically dependent, but you wouldn't know it, because your co-worker with the bad back keeps coming to work. He's able to do that because his opioid prescription keeps getting refilled.

The long-term benefits of opioids have been well known for a very long time. The long-term side effects are equally well known. But the key side effect that is creating the panic does not come from long-term medical use. You heard me right. In spite of all the noise about "overprescribing," that simply is not a problem. Less than 1% of the addicts on the street got their start with prescription opioids. And chronic pain patients rarely die of overdoses.

When Ed Thompson of Pharmaceutical Manufacturing Research Services tells Bill Whitaker that "the root cause of this epidemic is the FDA's illegal approval of opioids for the treatment of chronic pain," he's simply wrong. This approval did create a marketing change, but for chronic pain patients, it didn't make a lot of difference. Most pain management specialists and oncologists were already prescribing the drugs when needed for long-term care. But this opened the door for unscrupulous doctors to ring the cash register in an already illegal market.

The problem in the US began in earnest when William Randolph Hearst capitalized on racist sentiments against Chinese workers in his newspaper campaign against the "coolee." He created the myth of the "opium fiend" who terrorized white women after smoking opium. It was a complete fabrication, but it sold the idea of opium restrictions to moralists and politicians. Who cares about facts when you can "Do something!"?

Next, when Andrew Kolodny says that "as the doses become higher [in response to drug tolerance] the drugs become more dangerous, and the risk of death goes up," he is not telling the truth as I see it. He is pandering to a political narrative. The basic fact is that when you give opioids for an extended period, the endorphin receptors become tolerant to their presence. You do need to give more drug to achieve the same effect. But that very tolerance is what makes the drugs safer in the tolerant patient. Allow me to translate from medical to English.

If I need 10 milligrams of morphine for pain relief after surgery, and I just keep on taking 10 mg, after a while, I won't get the relief. But my body will not need that degree of relief, so I will start spacing my doses out. This is something we saw in great detail when Patient Controlled Anesthesia (PCA) was introduced to pain management after surgery.

With the "morphine pump," a patient was able to give himself lots of little doses of an opioid to help with pain after surgery. The PCA was rigged to prevent a repeat dose until 6 minutes after the previous dose, giving it time to work. We never saw overdoses with PCA if the patient was the only person to push the button. Never. As in "not once." In fact, patients automatically weaned themselves off opioids. This was so safe that now the Acute Pain Service no longer exists in most hospitals. The surgeon signs a protocol sheet, and everything goes on autopilot.

The same thing happens when patients have pain pills at home after surgery. They taper off without thinking about it as the pain level subsides. But suppose they are in that 1% that stays on opioids. Their receptors get tolerant and need higher and higher doses to get the same response. This means it also takes higher and higher doses to stop the patient from breathing, which is how ODs kill. Kolodny has his facts wrong.

So, what kills addicts? Or, perhaps we should ask, why do addicts take overdoses? After all, overdoses given by someone else are rare. Even addicts don't often try to commit suicide. It's at this point that we have to step back from the final dose of a street drug, the proximate cause of the overdose, and look for the first step in a series of critical incidents. Like airplane crashes, it's never just one thing that causes ODs, even if politicians like to have one problem that they think only they can solve.

The first thing to note is that all opioids are, in a sense, the same drug. They all work at the same receptor, and they all have the same family of side effects. The primary differences revolve around how fast they start working (onset), how long they last (duration), and how much is required to reach a standard level of effect (potency). Of importance, the more potent a drug is, the more it binds only to the intended receptor, and the fewer side effects it will have (for example, nausea). That means that fentanyl is safer during surgery than morphine and explains why we rarely use morphine in surgery today.

The next factor is that all the opioids are dirt cheap to manufacture. Virtually all the cost is in distribution. But even including the cost of distribution, Portugal spends about $4 a day on maintaining addicts, Canada about $11, and we should expect similar economies here if implemented. So why is it that El Chapo was worth north of $14 billion from the drug trade? It wasn't the native cost of drugs. It came from distribution.

Why would anyone pay more than the price of aspirin for a drug that costs the same as aspirin? There's only one reason: Prohibition. Recall that the soldiers in Vietnam used heroin and the Chinese laborers used opium for stress relief during leave time. There is a relatively fixed portion of the population that wants such intoxicants. With the change in labeling, it became "legal" for unscrupulous doctors to supply those people. But if they can't get them "legally," they will find a way to get them illegally.

If there's a market for the illegal drugs, there will be a marketer. Enter El Chapo. He'll provide your drugs, but for a price. Since he's taking a legal risk, it will be high enough to compensate him for that risk. Economists call this a "risk premium." Next, since you are opening your wallet, you want the good stuff. You won't go back to the left street corner if you don't get quality. So the guy on the right street corner figures that out and adds fentanyl to your heroin. As the expression goes, "Aye, there's the rub."

We've described a vicious circle where higher price demands higher quality which again demands higher price. The higher price invites competition, but since the competition is in an illegal market, crime follows. And as users become addicted, they often find themselves committing crimes to pay for those high prices. Did I mention that Canada is able to maintain an addict legally for $11 per day?

Even the Drug Enforcement Agency has noted that prohibition creates massive profits for bad guys. That should raise alarms. If prohibition starts this vicious cycle, and a national experiment with decriminalization (Portugal) has basically eliminated ODs, shouldn't we start looking in that direction? Drug-related crime in the US was essentially nonexistent until Hearst's yellow journalism led to restrictions on heroin and other drugs. Crime accelerated as laws got stricter. In short, Congress created the drug cartels. Competition among drug cartels leads to adulteration of heroin with much more potent opioids, and this unknown potency leads people to take doses with unknown risks.

In maintenance programs, known-potency drugs are given to patients with extreme safety. And over time, Portugal has seen that about half of addicts will wean themselves off their drugs.

60 Minutes wasn't satisfied with its story until it slandered drug manufacturers and the FDA with this exchange: (13:40)

Whitaker: "(commentary)… also review new drugs, like Dsuvia, the most powerful opioid pill ever approved.  (to Kessler) Just a few weeks ago the FDA approved a new opioid that is a thousand times more powerful than morphine. And this is in the middle of this opioid epidemic. How is that possible?"

Kessler: "I don't get it. I get your question. I don't get the agency's action."

Whitaker: "Isn't the FDA supposed to be our watchdogs to protect us?"

Dsuvia is a tablet to be taken under the tongue when severe pain (chronic or cancer) "breaks through." It is faster in onset than morphine, with a shorter duration. The 30 micrograms in Dsuvia, is equal in effect to 30 milligrams of morphine, a common dose in that situation. Whitaker's phrasing was wrong. The FDA did not approve an opioid that was a thousand times more powerful than morphine. It was the same strength. It is a thousand times more potent, so AcelRx Pharmaceuticals created a pill carefully tailored to meet a specific need by only including a thousandth as much.

60 Minutes is complicit in the fear-mongering that is killing large numbers of Americans through poorly considered laws. The only way to eliminate the overdoses is to eliminate the laws. That will bankrupt the drug cartels. But the Overton Window for this sort of action has not yet opened. That means we will likely be seeing more and more examples of Einstein's Maxim.

"Insanity is when you do something a second time and expect a different answer."

Ted Noel, MD is a retired anesthesiologist. He comments on political issues in the Vidzette podcast at vidzette.libsyn.com.