Month: September 2017

For all the ink American media outlets have spilled covering the increase in fentanyl-related overdose deaths, few of the stories I’ve read explain how fentanyl works or why it’s so deadly.

As a result, journalists have created the impression that fentanyl is a magically awful drug. In that sense, it has a lot in common with PCP, methamphetamine, and crack cocaine. “Using [crack] even once,” ABC’s Peter Jennings declared in a 1989 episode of World News Tonight, “can make a person crave cocaine for as long as they live.” If there’s an equally believable-but-untrue claim about fentanyl, it’s that simply touching the stuff can kill you.

I thought it might be useful for other reporters, and people who are simply concerned and/or curious about fentanyl, to figure out which oft-reported claims are true, partially true, or flat out wrong. So I got in touch with the Stanford anesthesiologist Steven Shafer, an expert in the pharmacology of pain medicine. I’ve edited our exchange for length and clarity.

Q: How do street-level doses of fentanyl—which seem to range from less than a milligram to a few milligrams—compare to surgical doses?

A: A milligram of fentanyl is a huge dose, one that would be fatal. For surgery we typically use doses of 0.1 milligram (100 micrograms). In terms of street drugs, the high potency has a very practical implication: The stuff is difficult to measure. There would be no obvious difference to a user given a packet of fentanyl-laced heroin if it had a very small amount of fentanyl, or a guaranteed fatal dose of fentanyl. The user would need to trust whomever weighed out the fentanyl used to lace the heroin.

Q: What makes illicitly used fentanyl deadlier than other opioids?

A: Fentanyl effect peaks at 5 minutes after an intravenous injection. The fast onset is more likely to be fatal than a slow onset, because the body doesn’t have time to build up carbon dioxide. With a slow onset opioid (e.g., morphine), breathing slows gradually as the drug starts to act, and carbon dioxide rises. As carbon dioxide rises, it drives ventilation, offsetting (somewhat) the effects of the morphine on breathing. With the rapid onset of fentanyl, there is little time for carbon dioxide to raise before there is full effect of the fentanyl on depressing breathing. That will result in more lethality for the same maximal opioid drug effect.

Q: What do we mean when we say fentanyl is “x times more potent” than other opioids?

A: Potency is usually given for opioids by the amount (by weight) of drug required to achieve a particular drug effect. For example, one could use the “Minimal Effective Analgesic Dose,” basically the lowest dose of a drug that produces some amount of pain relief. Potency can also be discussed in terms of tissue concentration, what is the plasma concentration of drug that produces a particular effect.

Because of differences in pharmacokinetics (drug uptake, distribution, and metabolism), differences in dose and differences in concentration may vary several-fold. The rate of blood brain equilibration also makes a difference. Fentanyl effect peaks at five minutes after an intravenous injection, and it’s washed out by 90 minutes. Because it has slow blood-brain equilibration, morphine effect is quite modest at five minutes, but peaks at 90 minutes. Thus, it’s tricky to talk about one drug being X-fold more potent than the next, because it depends on exactly when you measure drug effect. At five minutes? At 90 minutes? You will get very different answers for relative potency depending on exactly when you make your measurements.

If one says that fentanyl is 50 times stronger than drug X, you can’t tell from the statement if that means that it takes 1/50th of the dose, or if it requires 1/50th of the concentration. Thus, the key concept is that fentanyl is gobs more potent than drug X, so you need a very small fraction of fentanyl compared to the other drug to get a big effect. It’s not more scientific than that, because so many details affect how the potency is calculated and compared.

Q: Is it possible to develop a tolerance to fentanyl? Are users at higher risk of overdose due to lack of tolerance if they inadvertently take fentanyl mixed into a non-opioid formulation?

A: Tolerance develops to all opioids. Fentanyl is no better, or worse, than others. However, tolerance is shared: Tolerance to heroin will make the addict also tolerant to fentanyl. Tolerance also occurs with benzodiazepines. If an addict who is tolerant to valium mixes it with a “normal” amount of fentanyl, and then takes a whopping dose of valium, they may overdose from the fentanyl.

Q: EMTs have reported needing larger doses of naloxone to reverse fentanyl overdoses. Does that sound correct?

A: It depends on the dose. Fentanyl is displaced from the mu opioid receptor just like morphine, oxycodone, or any other opioid. Naloxone will work just fine. However, because fentanyl is so potent, the person mixing it into heroin might make a 10-fold dose error. In that case, it will take 10 times the amount of naloxone. So there’s nothing magic about fentanyl, other than that it is so potent that it’s hard to get the dose right when you are using crude scales to mix it together.

Q: Is fentanyl dangerous to touch, as several law enforcement agencies have reported?

A: No, fentanyl is not dangerous to touch. Transdermal fentanyl patches deliver fentanyl across the skin, but they require special absorption enhancers because the skin is an excellent barrier to fentanyl (and all other opioids). However, it is readily absorbed through mucus membranes, so snorted, rubbed in the mouth, or swallowed are all effective ways of administering fentanyl.

Q: Does fentanyl produce a better high than other opioids?

A: It isn’t fundamentally different from other opioids, like heroin, morphine, or oxycodone. In terms of drug effect, an opioid is an opioid is an opioid. They all bind at the mu opioid receptor, and they all have the same fundamental properties. So fentanyl isn’t going to give addicts a better high. Addicts like the “rush” of the fast onset, so they might prefer the fentanyl rush to the onset of a slower opioid like morphine. However, the net opioid effect will be the same.

Q: In terms of what various public health agencies are doing globally to reduce overdose rates, what kind of strategies do you think are worth trying in the U.S.?

A: This is a very complex question! There are several parts to the answer. First, we need to develop better strategies of managing pain. A lot of addiction starts with opioids given for pain management. This is because there is almost no pain that cannot be managed effectively for a short time by opioids. In other words, opioids are very effective short-term analgesics. There seems to be nothing else that can replace them. We need to find ways to limit opioid use for chronic pain, except at the end of life, because they cause addiction and lead to dependence. The other problem is that we need better ways to treat psychological pain. Psychological pain is handled by the same brain pathways that handle physical pain. That’s why we use the same word, “pain,” for both. Opioids are effective for psychological pain as well, but they are a terrible choice.

Q: Are there any harm reduction strategies that might reduce fentanyl overdose rates specifically? I know some facilities in Canada offer free reagent testing, but I’ve also seen it argued that reagent testing is not an effective way to identify fentanyl in a mixture.

A: That would work, as long as it is sufficiently sensitive. One could readily make over the counter fentanyl detection kits so that addicts could identify if their concoction has been laced with fentanyl. That would likely be a good idea.

Sens. Rand Paul, R-Ky., and John McCain, R-Ariz., will vote against the latest Republican-led effort to repeal parts of Obamacare, likely killing any slim chance that the proposal had of reaching the necessary 50 votes in the Senate.

Paul told the Associated Press he plans to vote against the Graham-Cassidy bill because it does not do enough to repeal Obamacare’s regulations and taxes.

McCain, in a statement issued later Friday, said he would not vote for the bill because he disagreed with the procedural shortcuts Republicans were taking to get the bill to the floor without committee hearings and the opportunity for amendments.

McCain, who cast the deciding vote against the Senate’s so-called “skinny repeal” bill in July over similar concerns about Senate GOP leaders abandoning “regular order,” said he would consider voting for the Graham-Cassidy bill “were it the product of extensive hearings, debate, and amendments” and only after getting a full CBO score of the bill, something that won’t be available before the end of the month.

“I cannot in good conscience vote for the Graham-Cassidy proposal,” McCain said Friday. “We should not be content to pass health care legislation on a party-line basis, as Democrats did when they rammed Obamacare through Congress in 2009. If we do so, our success could be as short-lived as theirs when the political winds shift, as they regularly do.”

I cannot in good conscience vote for Graham-Cassidy. A bill impacting so many lives deserves a bipartisan approach. https://t.co/2sDjhw6Era http://pic.twitter.com/30OWezQpLg

— John McCain (@SenJohnMcCain) September 22, 2017

By themselves, Paul and McCain would not be enough to sink the GOP health care bill. But at least two other Republican senators—Lisa Murkowski of Alaska and Susan Collins of Maine—are widely believed to be “no” votes on the bill. Collins confirmed Friday to the Associated Press that she’s leaning against the bill.

President Donald Trump on Friday threatened Republicans—and Paul in particular—who were considering voting against the bill. He said those who refused to support the Graham-Cassidy bill in the Senate “will forever…be known as ‘the Republican who saved Obamacare'”

In the tweet, Trump specifically identified Paul, who has so far been the only Republican to go on the record as opposing Graham-Cassidy, though at least two other Republican senators—Lisa Murkowski of Alaska and Susan Collins of Maine—are widely believed to be “no” votes on the bill. Murkowski and Collins, along with Sen. John McCain, R-Ariz., voted against the so-called “skinny repeal” bill in July.

Rand Paul, or whoever votes against Hcare Bill, will forever (future political campaigns) be known as “the Republican who saved ObamaCare.”

— Donald J. Trump (@realDonaldTrump) September 22, 2017

Trump’s threats have nothing to do with the policy of the bill, and the White House is only interested in a political win, Paul told the AP.

Paul’s assessment of the situation seems pretty accurate. Trump has never indicated much of an interest in the policy aspects of the health care debate that has raged on Capitol Hill since March, though he did quickly organize a Rose Garden press conference to celebrate the House’s passage of an earlier Obamacare repeal bill. A lack of White House engagement was widely noted in the wake of the “skinny repeal” bill’s embarrassing failure in July, but—aside from some bluster on Twitter—neither the president nor his top health officials have been particularly active in selling the Graham-Cassidy bill to potentially recalcitrant Republicans this week.

Indeed, even Republicans in the Senate who said they would vote for the Graham-Cassidy bill appeared this week to be having a difficult time explaining the merits of it. A vote on the bill is scheduled for next week, but that timeline is dictated more by the ticking clock than by any broad agreement that Graham-Cassidy is a good bill. Republicans only have until September 30 to pass a health care bill using the reconciliation process. After that a major rewrite of Obamacare will require 60 votes and therefore must have Democratic support.

Paul’s and McCain’s opposition creates some difficult math for GOP leaders. That’s why Republicans, as IJR‘s Haley Byrd reported yesterday, have dangled a carrot in front of Murkowski. In exchange for voting to scrap parts of Obamacare, her home state of Alaska will be allowed to keep Obamacare. It’s a blatantly political move to buy votes (the same kind of move that Republicans denounced when it was used to help pass Obamacare in the first place), and Paul is right to recognize it as such, which he did in his interview with the AP.

As for Trump’s promise to attack him in future political campaigns if he votes against the bill?

“I’m a big boy,” says Paul.

“In a first-in-the-nation lawsuit filed in federal court, the Colorado River is asking for judicial recognition of itself as a ‘person,’ with rights of its own to exist and flourish.” So declares a press release from the activist organization Deep Green Resistance. The lawsuit against Colorado’s governor is being filed in federal district court by the Community Environmental Legal Defense Fund (CELDF), which says it “seeks a ruling that the Colorado River, and its ecosystem, possess certain rights, including the right to exist, flourish, evolve, regenerate, and restoration.”

In support of the legal theory that rivers have rights, the suit cites Supreme Court Justice William Douglas’ famous dissent in Sierra Club v. Morton (1972). In that case, the Sierra Club sued to block the Disney company from building a ski resort at Mineral King in the Sequoia National Forest. The majority of the court ruled that the Sierra Club did not have legal standing—that is, that the group failed to demonstrate to the court sufficient connection to and harm from the law or action challenged to support that party’s participation in the case. (As it happens, the ski resort was never built anyway.)

In his dissent, Justice Douglas, with considerable legal poetry, argued:

Inanimate objects are sometimes parties in litigation. A ship has a legal personality, a fiction found useful for maritime purposes. The corporation sole—a creature of ecclesiastical law—is an acceptable adversary and large fortunes ride on its cases. The ordinary corporation is a “person” for purposes of the adjudicatory processes, whether it represents proprietary, spiritual, aesthetic, or charitable causes.

So it should be as respects valleys, alpine meadows, rivers, lakes, estuaries, beaches, ridges, groves of trees, swampland, or even air that feels the destructive pressures of modern technology and modern life. The river, for example, is the living symbol of all the life it sustains or nourishes—fish, aquatic insects, water ouzels, otter, fisher, deer, elk, bear, and all other animals, including man, who are dependent on it or who enjoy it for its sight, its sound, or its life. The river as plaintiff speaks for the ecological unit of life that is part of it. Those people who have a meaningful relation to that body of water—whether it be a fisherman, a canoeist, a zoologist, or a logger—must be able to speak for the values which the river represents and which are threatened with destruction.

The CELDF also cites a recently enacted provision in the constitution of Ecuador that confers rights on nature:

Nature, or Pachamama, where life is reproduced and occurs, has the right to integral respect for its existence and for the maintenance and regeneration of its life cycles, structure, functions and evolutionary processes. All persons, communities, peoples and nations can call upon public authorities to enforce the rights of nature.

Let’s just say that the law pertaining to the use of water is complex. I personally prefer common law riparian rights as a way to govern streams, rivers, and lakes. Riparian water rights give landowners along a stream rights to an undiminished quantity and quality of water. Consider the 1913 case Whalen v. Union Bag & Paper, in which a New York Court of Appeals ruled that a million-dollar paper mill employing 500 people did not have the right to pollute the water flowing past Robert Whalen’s 255-acre farm on Kayaderosseras Creek, near Albany, New York. The Court reasoned:

Although the damage to the [farmer] may be slight as compared with the [paper mill’s] expense of abating the condition, that is not a good reason for refusing an injunction. Neither courts of equity nor law can be guided by such a rule, for if followed to its logical conclusion it would deprive the poor litigant of his little property by giving it to those already rich.

It did not matter how much money had been invested or how many jobs were at stake; the paper company had violated Whalen’s right to an undiminished quantity and quality of water flowing past his farm.

In the western United States, the prior appropriation doctrine awarded water rights to individuals on a “first-in-time, first-in-right” basis. Those who first diverted water had first claim on water. State water laws also typically require that rightsholders divert water for use; otherwise, they forfeit it to other users. (In other words, use it or lose it.) Thus state intervention basically stymied the development of water markets that would enable farmers, cities, ranchers, fishers, canoeists, and environmentalists to bargain among themselves on the best ways to manage rivers and streams. The Property Environment Research Center* in Bozeman, Montana, describes how markets enable the nonprofit Scott River Trust in Siskiyou County, California, to lease water from rightsholders in order to maintain instream flows to support salmon runs. There is no need to confer rights on the Scott River when trading transferable rights to water make it possible to protect salmon.

Deep Green Resistance and CELDF have a point in that unowned natural goods are subject to a tragedy of the commons, in which users have an incentive to overexploit and ruin them. But instead of trying to confer rights on nature, the better course is to assign strong property rights to people, so that individual and common owners are empowered to protect resources and environmental amenities.

*Disclosure: I have been the happy beneficiary of grants, conferences, and intellectual enrichment from PERC for many years.

Hillary Clinton’s new book What Happened attempts to explain Trump’s upset victory in 2016 through a series of reasons which are not Hillary Clinton. The gambit runs from apathetic white lady voters to Russian meddling to the inscrutable popularity of Donald Trump. When Clinton’s focus turns to herself, however, she’s light on culpability. She admits she can be guarded, but that admission doesn’t encapsulate the relentless political ambition paired with shady financial dealings and a willingness to subvert national security that turned off much of the country.

In the end Clinton was also just a bad candidate.

In the latest Mostly Weekly Andrew Heaton explores Clinton’s new book, so you don’t have to.

View this article.