08/18/17

Public Health Time Bomb

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May came and went with the vast majority of people in the U.S.—including me—being totally unaware that it was Hepatitis Awareness month. May 19th was National Hepatitis Testing Day. Hepatitis-C (HCV) is the most common form of viral hepatitis in the U.S. The number of new HVC infections almost tripled between 2010 (850) and 2015 (2,436). We need to be more aware of this disease and its treatment because it kills more Americans than any other infectious disease, including HIV. Yes, more people than HIV. CDC data indicated nearly 20,000 Americans died from hepatitis-C-related causes in 2015; and the majority of those deaths were people 55 and older.

“Because hepatitis C has few symptoms, nearly half of people living with the virus don’t know they are infected and the vast majority of new infections go undiagnosed.” The highest rate of new infection occurs among 20- to 29-year-old injection drug users. But ¾ of the 3.5 million Americans living with hepatitis C are baby boomers born between 1945 and 1965. They are six times more likely to be infected with hepatitis C and are at much greater risk of dying from the virus. Around ½ of all the deaths from HCV in 2015 occurred within this age range. You can read the three CDC press releases this information was taken from here, here and here.

These press releases highlighted information in report, “A National Strategy for the Elimination of Hepatitis B and C” that suggested a strategy to eliminate both as public health problems by 2030. Immunization against hepatitis B (HBV) can prevent 95% of infections. There is no vaccine against HCV, but there are anti-viral drugs that can cure hepatitis C, but the costs are prohibitive. The introduction of the report said:

There is no longer any reason to disregard these diseases. There is an effective vaccine to prevent hepatitis B, advances in treatment can prevent most deaths in those chronically infected with HBV, and hepatitis C is now curable with a short course of easily tolerated treatment.

CDC data on HCV suggested that 75% to 85% of newly infected adults and adolescents develop chronic infections. From 2000 to 2002 incident rates for acute HCV decreased for all age groups except for persons aged 0-19. Then the rates remained fairly steady from 2002 through 2010. Between 2010 and 2015 rates increased for persons in all but the oldest (<60 years old) and youngest (0-19 years old) age categories. The largest increase was among persons between 20 and 29 years old. See the following graph of the reported CDC data.

The drug companies charge between $60,000 and $90,000 for a 12-week course of treatment. This is way out of proportion to the cost of treatment in third world countries. Eliminating HCV as a public health problem by 2030 would require mass treatment, but none of the direct-acting agents come off patent before 2029. In the long run, HCV treatment is cost-effective, but that doesn’t address the upfront costs charged by pharmaceutical companies for their drugs. So the cost of antivirals that cure HCV is a major obstacle. 

These drugs have strained the budgets of public and private payers alike. Faced with the unenviable task of allocating scarce treatment, payers gave first priority to the sickest patients, those at most immediate risk of death. Many also imposed sobriety restrictions, fearing the risk of re-infection in active drug users too great to justify the expense of treatment. Such restrictions have met with criticism. Overt drug rationing offends the American public, but it is difficult to know how else to act in the face of such high prices.

One of the recommendations of the report is for the federal government to purchase the rights to one of the direct-acting antiviral treatments for use with neglected populations such as individuals on Medicaid, in prisons and those treated through the Indian Health Services. This would be a voluntary transaction between the government and the pharmaceutical companies providing the antivirals. The company would be guaranteed reasonable compensation and the licensed drug would only be used in the limited markets (noted above) the companies aren’t now reaching.

Calculations show that the licensing rights should cost about $2 billion, after which states would pay about $140 million to treat 700,000 Medicaid beneficiaries and prisoners. By comparison, the status quo would cost about $10 billion over the next 12 years to treat only 240,000 similar patients.

Critics of the strategy suggest it sets a dangerous precedent by having the government negotiating a license for a costly medicine. Actually, it seems that the federal government’s reluctance to interfere with the pharmaceutical industry may have emboldened it to initially set the extremely high prices foe HCV drugs.

The Senate Finance Committee’s 2014 investigation into the pricing of sofosbuvir [Solvadi] concluded that Gilead had deliberately elevated the price in an effort to raise the market floor, ensuring continued high prices for all future hepatitis C treatments. Action now might discourage other companies from pursuing this strategy in the future.

A CNN article on the report by Susan Scutti noted the hardest hit areas of the U.S. in terms of new HCV infections are parts of Appalachia and rural areas of the Midwest and New England. Seven states, Indiana, Kentucky, Maine, Massachusetts, New Mexico, Tennessee and West Virginia, have infection rates that are two times or more than the national average. Ten other states have rates above the national average: Alabama, Montana, New Jersey, North Carolina, Ohio, Oklahoma, Pennsylvania, Utah, Washington and Wisconsin.

There is a website, HepVu, presented by the Rollins School of Public Health at Emory University, which partnered with Gilead Sciences, the original price gauging pharmaceutical company with its antivirals, Solvadi and Harvoni. The original drug development research into Solvadi was done at Emory. Despite the Gilead partnership, HepVu has some helpful information, including an interactive map by state in the U.S. The home page stated there are an estimated 3.9 million people in the U.S. living with past or current hepatitis C infection. You can look up each state’s individual profile.

For example, within my home state of Pennsylvania, there are an estimated 142,100 people living with Hepatitis C. The HCV mortality rate is 4.952 per 100,000 persons, with 629 hepatitis C deaths in 2014. In West Virginia, there are an estimated 24,400 people living with Hepatitis C. The HCV mortality rate is 5.9 per 100,000 persons, with 110 hepatitis C deaths in 2014. In Ohio, there are an estimated 119,100 people living with Hepatitis C. The HCV mortality rate is 4.9 per 100,000 persons, with 567 hepatitis C deaths in 2014. Go to the site and check out your own state’s data.

The outrageous price of medications to treat hepatitis C illustrates how pharmaceutical companies are feeding off of the problems they had a hand in creating. The rise in hepatitis C infections comes as a result of increased IV drug use, which resulted from the prescription opioid epidemic leading individuals to switch from prescription opioids to heroin. And the public health problems with hepatitis C will only get worse since it often goes undiagnosed for years. It’s a public health time bomb.

The above recommendation to have the federal government negotiate a license for one of the existing Hepatitis C treatments is a good one. It just might deter other companies from trying the same pricing trick in the future with other medications. But the cozy lobbying relationship between Pharma and Congress could prevent it.

For more on this issue, see: “Is There No Balm in Gilead?,” “I Guess I’m a Little Bit Socialist,” “Riding the Hep C Gray Train,” “Impeccable Timing” and “Hepatitis Hostages.” Also see “Pharma Companies Hunt in Packs” for more information on the issues of the high cost of prescription drugs.

08/15/17

Erasing the Providence of God

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“One cannot give thought to the Church’s confession of faith in Providence without very soon being impressed by the distance between this confession and modern thought.” With these words, the theologian G. C. Berkouwer opened his classic work, Studies in Dogmatics: The Providence of God. He went on to note how modern scientific and philosophical thought—as well as that of the ordinary person—is engrossed in the question of the meaning of the world and its history and the purpose of human life. A series of revolutionary, catastrophic events have led many moderns to ask: Can life still be said to make sense or be meaningful? “This is now a pre-eminently existential question whose persistence we cannot avoid.”

One of the most eloquent expressions of human insignificance was expressed by the astronomer Carl Sagan in his book, A Pale Blue Dot. At Sagan’s suggestion to NASA, Voyager 1— at a distance of 3.7 billion miles from earth—turned and took one last photographic look at earth before it continued on its journey out of the solar system. Reflecting on the resulting photo, he said:

Our posturings, our imagined self-importance, the delusion that we have some privileged position in the universe, are challenged by this point of pale light. Our planet is a lonely speck in the great enveloping cosmic dark. In our obscurity, in all this vastness, there is no hint that help will come from elsewhere to save us from ourselves.

You can watch and listen to a YouTube video with a section from the audio book containing the quote above from A Pale Blue Dot here.

Berkouwer said that when God’s hand presses hard upon life, the question becomes: WHY? Where is God? That question underlies everything happening in our time. It reverberates through the estrangement of humanity from the rest of creation; through our secularization and alienation from God. “God is estranged from man; and man becomes a stranger in His world.” He said the following three motifs play an important role in modern secularization.

The first is the influence of modern science on faith in God. When nature is repeatedly explained through natural causes, the premise of God’s preservation and rule is set aside. For the scientifically-minded person, the doctrine of Providence was “convenient for pre-scientific naivete.” But it is rendered irrelevant by the insights of the scientific method. The reality of God is a relic of the pre-scientific age.

Though many are beginning to talk again about the limitations of the scientific method and though one hears occasional murmurs against its imperialism, the inevitable conclusion of modern science is that it has no room left for God.

The second motif is seeing religion as nothing more than a projection or reflection of human thought. It appears in the writings of several influential thinkers of the nineteenth and twentieth centuries: Karl Marx, Ludwig Feuerbach, Friedrich Nietzsche, Sigmund Freud, and others. Religion is an opiate of the people (Marx); man’s god is man (Feuerbach); religion as a “universal obsessional neurosis” (Freud); Christianity is “Platonism for the people” (Nietzsche). When religion is a projection or reflection of human thought, it becomes expendable. Here, belief in Providence is dangerous, as it is only “a lust for safety and protection against the threats to our existence.”

The third motif is refuting God’s Providence through catastrophe: “How could an all-loving, all-powerful God allow …” The meaninglessness of a crisis seems to cut off any perspective that reveals purpose. “The Providence doctrine fails to give an explanation of the gruesome reality that holds life in its grip.” Faith affirms meaning and purpose in life. “But where can one point to purpose or reality in the radically ungarnished life of our times?”

Does not honesty tell us to limit ourselves realistically to what lies before our eyes, and without illusions face the order of the day? How can we overcome the catastrophic by a return to a confidence in the meaning of life, when the possibility of meaning itself is in question? Realism and a facing of facts have come to fetter the human heart. The beautiful story of Providence and the Hand of God, it is said, is a religious fancy, and belief in it an illusionary escape from reality.

There is a fundamental flaw embedded in each of these motifs, namely that understanding the world around us—including the meaning of our lives within it—must have a human starting point. This seems to be what Berkouwer meant by secularization; what we see is what we get. Science explains, or will explain, what was previously unexplainable. As the French mathematician Pierre-Simon Laplace said when Napoleon asked him where God fit into his mathematical work, “Sir, I have no need of that hypothesis.” Belief in God then becomes a projection of human thought. Christian faith is mistakenly interpreted as a Christian version of fate or determinism.

When this happens, it means that an abstract concept of sovereignty has replaced the God of revelation. God is construed as a “super power,” a potentia absoluta, which is another God than He of Scripture. Sovereignty “in itself” is a compassionateless concept quite as inspiring of dread as is blind fate. Biblical thinking is always directed to the sovereignty of God, that is, to the real, the true, and living God, the God of revelation.

Berkouwer encouraged his readers to turn to the Scriptures to overcome the modern crisis with the doctrine of Providence. He said as the Scriptures rule our thinking and speaking, as they fill the preaching of the Church, “so the Word of God will speak to the distressed and disordered life of our times.”

J. I. Packer said in the New Bible Dictionary that providence is normally seen in Christian theology as the unceasing activity of the Creator God. In Scripture, it is presented as a function of the sovereignty of God. “God is king over all, doing just what he wills (Psalms 103:19; 135:6; Daniel 4:35; Ephesians 1:11).” Packer said this conviction is throughout the Bible and must be distinguished from the following: pantheism, deism, dualism, indeterminism, determinism, chance, and fate.

Pantheism absorbs the world into God, while deism cuts creation off from him. Dualism divides control of creation between God and another power, where indeterminism denies there is any control at all. On the other hand, determinism imagines a control that obliterates human moral responsibility. Chance denies that the controlling power is rational, while fate denies that it is benevolent. Whenever these views creep into our understanding of God and his interaction with creation, they dilute a biblical sense of God’s providence. Packer said by God’s providence:

He upholds his creatures in ordered existence (Acts 17:28; Colossians 1:17; Hebrews 1:3), guides and governs all events, circumstances and free acts of angels and men (cf. Psalm 107; Job 1:12; 2:6; Genesis 45:5–8), and directs everything to its appointed goal, for his own glory (cf. Ephesians 1:9–12).

When humans deny the continued work of God in his creation through secular views of science and philosophy, they are trying to erase what God has written across creation with indelible ink. As the apostle Paul said in Acts 17: 28: “In him we live and move and haves our being.” What can be known about God is plainly revealed in the creation. Since the creation of the world his eternal power and divine nature have been clearly perceived in the things that were made. “So they are without excuse. For although they knew God, they did not honor him as God or give thanks to him, but they became futile in their thinking, and their foolish hearts were darkened” (Romans 1:19-21).

08/11/17

Drug Bust

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The FDA approval of Addyi (flibanserin) to treat hypoactive sexual desire disorder (HSDD) in premenopausal women on August 18, 2015, to a large extent, was due to the efforts of the marketing campaign of an organization called Even the Score.  A press release applauding the approval of Addyi listed 26 organizations, including the National Organization for Women, who were supporters of Even the Score. “Even the Score was established to serve as a voice for American women who believe that it’s time for the FDA to level the playing field when it comes to the treatment of hypoactive sexual desire disorder (HSDD).” But less than two years since its assistance in bringing about “a breakthrough moment for women’s health,” the organization is gone; vanished.

The Even the Score press release that celebrated the approval of Addyi noted there had been a steady drumbeat of support for women’s sexual dysfunction treatment from lawmakers, women’s rights groups, medical experts and consumer organizations. See the press release for a listing of these organizations. The Chair of the Even the Score campaign, Susan Scanlan, said: “Women deserve the safety and peace of mind that comes with access to FDA-approved medical treatments for HSDD.” Dr. Lisa Larkin, the Scientific Co-Chair of Even the Score said:

We applaud the FDA for acknowledging the clear science that supported approval of flibanserin, for starting a conversation that will define the next generation of progress in sexual rights and sexual health, and for empowering women to take control of their health in ways they never thought possible.”

But according to Alycia Hogenmiller, Alessandra Hirsch and Adriane Fugh-Berman, Even the Score was a fake feminist group created by Sprout Pharmaceuticals “so that they could get a bad drug approved by the Food and Drug Administration.” Writing for The Hastings Center in “The Score is Even,” the co-authors described how Sprout Pharmaceuticals hired Blue Engine Media, a PR firm, to create Even the Score. The Hastings Center is a nonpartisan bioethics research institute. And the coauthors of “The Score is Even” are affiliated with PharmedOut, a research and education project of the Georgetown University Medical Center that “promotes rational prescribing and exposes the effect of pharmaceutical marketing on prescribing practices.”

The Even the Score ad campaign hired two women who were both well-known to women’s groups. “Even the Score recruited and paid consumer advocacy groups to pressure the FDA into approving flibanserin for Hypoactive Sexual Desire Disorder—a condition previously created by industry to sell another drug.” The coalition did a Viagra commercial parody in 2014, which it said was “created to highlight the absurdity of the continued gender disparity in sexual health.” There is a link to the video in the press release. Members of Even the Score called Addyi: “the biggest breakthrough for women’s sexual health since the pill.” It was suggested there was possible “unconscious gender bias at the FDA.”

Two days after the approval of Addyi, Sprout sold the drug to Valeant Pharmaceutical for one billion dollars. Although Even the Score promised “to be there every step of the way” in the fight for true gender equality in sexual health, the victory video posted the day after Addyi was approved was the last posting on the Even the Score site. Completely dormant for many months, it disappeared entirely several months ago ( I couldn’t find it either). The last tweet from @eventhescore was from January 29, 2016 (I looked). The last post to the Even the Score Facebook page was January 28, 2016 (I looked there too).

In an earlier article for The Hastings Center on flibanserin, “The Drug that Cried ‘Feminism’”, Hirsch, Fugh-Berman and Rebecca Holliman described the drug as “Spanish fly, or horny goat weed, or one of the other aphrodisiacs that have been disappointing humans for millennia.” They noted how Sprout managed to convince the public and some women’s groups that flibanserin was a feminist cause. First, they created a narrative that branded anyone opposed to flibanserin as anti-woman. Then they hired two feminists to lobby women’s groups. They convinced NOW to join the cause. When there was some opposition from feminist groups about their feminist rhetoric, Even the Score and Sprout focused on the “scientific” evidence for flibanserin.

The point at which Sprout Pharmaceuticals’ innovative marketing bends sinister is in its misappropriation of feminist concepts. An oft-heard argument for approving flibanserin is “choice,” with the unstated subtext that women should decide about the risks and benefits of a drug on their own, sans pesky government interference. This implies that the FDA, the government agency charged with protecting the public from unsafe and ineffective drugs, is superfluous. That’s the way it was in the 19thcentury, pre-FDA, when we were giving children cocaine toothache drops.

A similar critique of Addyi (flibanserin) can be found in “Flibanserin: The Female Viagra is a Failed Me-Too Antidepressant.” The article was co-authored by Emily Wheeler, Madeline Brodt, Shannon Peters, and Lisa Cosgrove. The authors noted that HSDD (Female Sexual Interest/Arousal Disorder or FSI/AD in the DSM-5) is a classic example of disease mongering—creating a disease to promote a drug to treat it. A former president of the American Psychiatric Association admitted the possibility of such action in an article he wrote for the Harvard Review of Psychiatry:

The flexible boundaries of many psychiatric diagnostic categories, in the absence of definitive diagnostic tests, may encourage expansive definitions of affected populations and create opportunities for industry to promote treatments for people who would not previously been seen as having a disorder.

The empirical data supporting the diagnosis is weak, as is the clinical trial data used to approve Addyi (flibanserin). “Numerous researchers, clinicians, and policy experts, have questioned the validity of FFD and HSDD.” A systematic review and meta-analysis by Jaspers et al. in JAMA Internal Medicine, concluded that the benefits of flibanserin were marginal, particularly when the concurrent adverse effects are considered. “Treatment with flibanserin, on average, resulted in one-half additional SSE per month while statistically and clinically significantly increasing the risk of dizziness, somnolence, nausea, and fatigue. Overall, the quality of the evidence was graded as very low.”

Sprout admitted the effect is mild, only increasing the number of “satisfying sexual events” by less than one event per month. These events could include masturbation, but not necessarily orgasm. One of the statistics used in the Even the Score ad campaign, stating that 43% of women experience sexual dysfunction was from an older, highly criticized study. The often-repeated statistic of 1 in 10 women having HSDD was from a study funded by the pharmaceutical company that developed flibanserin, Boehringer Ingelheim. They sold the rights of the drug to Sprout Pharmaceuticals. The researchers conducting the study were either employees of Boehringer Ingelheim or paid consultants for the company.

The clinical effectiveness of Addyi (flibanserin) is questionable. The marketing campaign by Even the Score had significant influence on its approval process with the FDA. The so-called disorder it treats is mythical. But the numerous side effects from the drug are real. These potential side effects are so serious, that the FDA required special training and certification before providers could prescribe it. When flibanserin was approved, Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research (CDER), said:

Because of a potentially serious interaction with alcohol, treatment with Addyi will only be available through certified health care professionals and certified pharmacies . . . Patients and prescribers should fully understand the risks associated with the use of Addyi before considering treatment.

Addyi can cause hypotension (severely low blood pressure) and loss of consciousness. These risks are increased and become more severe when used with alcohol, or when Addyi is taken along with CYP3A4 inhibitors such as: Prozac (fluoxetine), Luvox (fluvoxamine), and grapefruit juice. Here is a list of CYP3A4 inhibitors. Common side effects include dizziness, sleepiness, nausea, fatigue insomnia and dry mouth. Because of the sedation effects, it is recommended to take flibanserin at bedtime. Stop and think a minute. Addyi is a drug to treat sexual desire disorder that you take before going to bed … BECAUSE IT MAKES YOU SLEEPY!

The head of the National Women’s Health Network, Cindy Person, said: “This is a risky drug about which women and their doctors don’t get enough information.” Her organization produced an abysmal “report card” for Addyi. Among the listed concerns were that Addyi shouldn’t be taken with common medicines used to treat yeast infections, Chlamydia, syphilis, HIV and Hepatitis C. And taking hormonal birth control increased the risk of serious complications with Addyi. Writing for STAT News, Ed Silverman said: “Although some had great expectations for the drug, Addyi has, so far, been a bust.”  For more on Addyi, see “A Pill for a Mythical Ill.”

08/8/17

Kratom: Part of the Problem or a Solution?

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In August of 2016 the DEA announced that it would temporarily classify kratom as a Schedule I substance. The public outcry against this plan influenced the DEA to reverse itself and delay scheduling kratom in October of 2016. The DEA announcement said before taking further action, it would solicit public comments and review the FDA’s “scientific and medical evaluation” of the proposed scheduling of kratom. Once the DEA has received and considered the information, it would decide how to proceed. But while we await the DEA’s decision, kratom is being sold in vending machines.

Advocates for kratom were overjoyed with the DEA’s decision. Chris Ingraham reported for The Washington Post that researchers welcomed the decision to delay scheduling kratom, but were concerned that the future of their research was still up in the air. After its October 2016 announcement, the DEA set a period for public comments on the potential scheduling of kratom until December 1st of 2016. As of August 6th, 2017, there has not been a public announcement about its decision or its review of the FDA report on kratom.

Since the DEA delayed a decision on kratom, it is still unregulated and will remain available for anyone to use without a prescription. And research into the risks and benefits of kratom can continue unhindered by a temporary Schedule I classification.

Andrew Kruegel of Columbia University is working to develop new painkillers from compounds contained in kratom. He commented: “I am encouraged that they will now be having more serious input on this important policy decision.” While the DEA announcement might be good news for now, studies with the methodology of rigorous, controlled trials typical of FDA evaluations don’t exist for kratom. So will the DEA wait for the months or years it could take to complete rigorous kratom studies before deciding whether or not to schedule it?

According to the American Kratom Association (here) and PinneyAssociates (here), Jack Henningfield did an “8-factor analysis” with kratom, which is the legal framework used by the FDA to assess the abuse potential of substances. Henningfield concluded that kratom had a low toxicity level; and that scheduling it as a controlled substance was not warranted.

It’s important to understand that although kratom has some mild effects similar to opioids, its chemical make-up is different, and it appears overall much safer, with apparently relatively small effects on respiration. In fact, kratom’s analgesic effects and impact on energy, combined with its favorable safety profile supports continued access by consumers to appropriately regulated kratom products while research on its uses continues.

STAT News identified another person doing research with kratom, Edward Boyer, who is currently at UMass Memorial Medical Center and Boston Children’s Hospital. Boyer has been interested in kratom since 2006. Even then there was a Catch-22 of sorts when trying to get government funding for kratom. “The National Institute on Drug Abuse didn’t want to fund kratom projects, saying it was a complementary and alternative medicine, while the National Center for Complementary and Integrative Medicine didn’t want to fund them because it was a drug of abuse.”

In 2008, Boyer and two colleagues filed a patent to use kratom or its chemical compounds as a new treatment method for opioid withdrawal, one of the ways it is currently used informally and non-medically. Two large freezer bags of kratom he obtained still sit in a cabinet of the UMass Memorial Medical Center’s toxicology office. Boyer said the bureaucratic nightmare of running the FDA gauntlet to do a clinical trial stopped them cold.

Andrew Kruegel’s research has had some promising initial results. His team was able to demonstrate that the main components of kratom primarily stimulated the painkilling response, while having minimal effects on the proteins that caused other side effects. But these findings need to be repeated in mice and then humans, “before they could claim that they have used kratom to create an opioid-like painkiller without as many risky side effects.” But there is a problem obtaining kratom of the quality needed for his research and the red tape involved in the process of obtaining it. “There is nowhere to buy the plant unless I am going to go to Indonesia and contact plantation owners.”

In the mean time, you can order kratom on the Internet from several vendors. And if you live near the East Coast Super Subs shop in Tucson Arizona, you can buy it out of a vending machine. Eric Boodman reported for STAT News that the vending machine there attracted five customers in an hour. The servers at the sub shop said it gets even busier around opening and closing time. Using cash or a credit card, a customer can buy as little as 10 grams for $5, or up to 120 grams for $50.

The almost-scheduling of kratom seems to have been good advertising for the herbal product. Drew Pickett, the owner of a second kratom vending machine company, Arizona Kratom, said many people discovered kratom because of the bad publicity. “People were like, ‘Wow, if the government doesn’t want me to have it, I want to try it.’” He estimated the aborted ban triggered a 400% boost in his sales.

One person said kratom helped him stop using heroin six years ago. Last year he relapsed, and was back using heroin for several months before he used kratom to wean himself off heroin for the second time. He found the Tucson Kratom vending machine when the kratom he used to get from head shops became too pricey. Now he wants to wean off of kratom as well. “I start with a lot of it initially … and then I taper down. I’ve been doing it very gradually and probably in the next two or three months, I’ll be done with it.”

But things aren’t all sunshine and happiness with the kratom vending machine. Dr. Mazda Shirazi, the medical director of the Arizona Poison and Drug information Center first heard about the machine when a patient of his began to show signs of liver toxicity from using kratom from the machine on a daily basis. He’s worried about the lack of regulation with kratom, meaning you can’t be sure of the purity of what you are buying.  He’s also concerned that using kratom to wean off of opioids will give some addicts false hope. “I think it actually prolongs the addiction cycle and puts the patient in a dangerous situation, whereas by getting help they might be better off.”

Susan Ash, the founder of the American Kratom Association, saw the vending machine as a sign of how pervasive the opioid epidemic has become. “Maybe a person who is going to walk into that sandwich store and has never heard of kratom — maybe that will be their first day off of opiates.” She liked the idea of people not having to wait a day or longer for their kratom to arrive in the mail. But she worried the vending machine made kratom available to children under 18. “There’s not enough research to know how the substance affects developing brains.”

And there’s the rub: there simply isn’t enough reliable, replicated research with kratom to make an informed decision on how to use it or whether to schedule kratom. Henningfield’s study is suggestive of a good safety profile for kratom, but can’t be regarded as conclusive since it was funded by the American Kratom Association. In contrast to Henningfield’s safety assessment of kratom, others have said there is a real probability of becoming addicted with kratom.

The National Institute on Drug Abuse (NIDA) noted how two compounds in kratom, mitragynine and 7-hydroxymitragynine, interact with opioid receptors in the brain, and produce the same effects of sedation, pleasure and decreased pain as opioids. There are symptoms of withdrawal when an individual stops using kratom and some users have reported becoming addicted to kratom. Adverse health effects from kratom use include: sensitivity to sunburn, nausea, sweating, loss of appetite, and sometimes psychotic symptoms. Chronic use of kratom has been linked with liver problems, as noted above. Kratom by itself hasn’t been linked with deaths, but if mixed with other substances, it has been part of a fatal drug cocktail. See “Krypton Can Kill You” and  “The Secret of Kratom” for more on this.

While it isn’t a federally controlled substance at this time, six U.S. states and three cities have listed kratom as a Schedule I substance. Globally, several countries have either regulated or banned kratom. In Europe, kratom is a controlled substance in Denmark, Latvia, Lithuania, Poland, Romania, Sweden and the UK. It is a controlled narcotic in Australia and New Zealand. Possession of kratom is illegal in Thailand and its use is prohibited in Malaysia. Canada has made it illegal to market it for human consumption.

What is clear is the need for reliable, replicated research with kratom. Edward Boyer said: “Is it an effective treatment for opioid withdrawal, or is it another pathway to addiction? I don’t think anybody has a defined concept of where it actually lies on that continuum.” Nevertheless, it seems there is growing anecdotal evidence of some level of dependence or addiction with kratom. If the DEA delays its decision to regulate kratom much longer, it might become part of the problem instead of a solution to the opioid epidemic.

08/4/17

Not a Ghost in the Machine

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There is a story told about René Descartes, that he traveled with a life-sized mechanical doll he named Francine, after his illegitimate daughter. Francine died tragically when she was five. The doll was supposed to be so lifelike, that it was virtually indistinguishable from a real person. One source said he constructed it “to show that animals are only machines and have no souls.” His biographer, Stephen Gaukroger, said Descartes kept the doll in trunk beside him while he slept. Supposedly, on a voyage over the Holland Sea, the captain of the ship quietly stole into Descartes’ cabin one night and opened the trunk. Horrified to see the mechanical monstrosity, he dragged the doll from the trunk and threw her overboard.

In Descartes: An Intellectual Biography, Gaukroger said there is no truth to the tale; that it was likely a piece of propaganda in the eighteenth-century struggle against the materialism that grew out of Descartes’ philosophy. In his essay on Descartes for Galileo Goes to Jail, Peter Harrison said Descartes could be the most maligned and misunderstood philosopher who ever lived. “Indeed, there seems to be something about Descartes’ person and his philosophy that invites slander and simplistic mischaracterization.” Both Gaukroger and Harrison pointed to another misconception, that Descartes initiated the radical separation of mind and body, which then had disastrous consequences on Western philosophy.

Descartes did make a mind-body distinction. The Internet Encyclopedia of Philosophy said one of the most lasting legacies of his philosophy is what is now called mind-body dualism.  He argued that the nature or substance of the mind (a thinking non-extended thing) was completely different from that of the body (an extended, non-thinking thing). Harrison noted where the Oxford philosopher Gilbert Ryle derisively referred to this Cartesian doctrine of mind and body as “the myth of the ghost in the machine.” Such dualism, according to Ryle, was “fundamentally antiscientific.”

But there is a technical point missing in this portrayal of Descartes’ thinking. He considered the body and mind to be distinct substances. “A substance is something that does not require any other creature to exist—it can exist with only the help of God’s concurrence.” As a consequence, each could exist without the other. “However, this does not mean that these substances do exist separately.” Harrison said Descartes carefully rejected the kind of separation implied by Ryle and others.

In fact, Descartes took pains to deny such a separation, asserting that mind and body are “intermingled” so as to form a “unitary whole.” Mind and body, he insists, form a “substantial union.” He also unambiguously states (pace Dennett) that the mind is not in the body “as a pilot in his ship.” . . . In fact, the doctrine of a radical separation of mind and body is one that should more properly be laid at the feet of Aristotle or Plotonius, rather than Descartes.

Some commentators have suggested the interaction of mind and body was so central a concern for Descartes that it is misleading, to a certain extent, to refer to him as a dualist. He sought to understand the world in terms of three basic kinds of entity—matter (extended material things), minds (thinking things) and persons (mind-body composites). Correlations between mental events and bodily movements are merely natural properties of this body-mind complex. “The relations of mind and body, on this account, are explained in terms of psychophysical laws that constitute our very nature as embodied beings.” Harrison then gave this summation.

In sum, Descartes’ views about mind, body, and their relation are subtle, sophisticated, and complex. They bear little resemblance to the simplistic caricatures that often pose as authoritative accounts of his work. Descartes gave a central place to the emotions in his psychology, and he took very seriously the embodied nature of human beings. Because of Descartes’ insistence that the mind-body amalgam was a real entity, some commentators have gone as far as to suggest that he no longer be numbered in the ranks of the dualists.

Writing for BioLogos, philosophy professor Edward Fesler said to the extent that this separation and conception is seen as “an abstraction from concrete material reality, and not the whole of material reality,” there is nothing wrong with it. However, there must be a clear acknowledgement of its limitations. “It captures only those aspects [of reality] that are susceptible both of mathematical modeling and of detection vie experimental techniques by which the models may be tested. But anything else falls short.” Unlike Harrison, Fesler does see Descartes as responsible for many of the philosophical problems that came after his conception of mind and matter.

This bizarre re-conception of human nature—man as a “ghost in a machine,” as Gilbert Ryle famously parodied it—opened up a host of philosophical problems which persist to this day. The materialist “solution” to the problems has been to reject one of Descartes’ reified abstractions (the res cogitans) while keeping the other, the material world conceived as if the equations of physics exhausted its nature. Unsurprisingly, this has led to theories of the relationship of mind to body which seem implicitly to deny, rather than to explain, the existence of mind, consciousness, meaning, and free choice.

The materialist resolution of the mind-body problem raised by Cartesian philosophy, subsuming the mind as an extension of bodily neurological functions, raises a problem for a biblical understanding of human nature. While there is a clear sense of a kind of dualism in Scripture, Christians cannot assume such a materialist position. Biblically speaking, humans are material and immaterial, body and soul. Fesler’s suggestion is to reject Descartes’s abstractions and rediscover the human being “as an irreducible psychophysical whole,” with our mental and physical as two aspects of one thing. There is both unity and distinction—what theologian Anthony Hoekema referred to as a psychosomatic unity of body (soma) and soul (psyche). See “We Are But Thinking Reeds” for a more in depth discussion of this idea.

But there is a third kind of Cartesian entity to consider—the mind-body composite of personhood. It is an essential aspect of human existence as it makes possible the relationship between individual humans, between embodied thinking things. An it makes possible a relationship with God. So it cannot be easily dismissed as merely a ghost in the machine.

Abeba Birhane offered a revision of Descartes for Aeon that adds a community aspect to Carteasian thought. Drawing upon Ubuntu philosophy, she said selfhood is acquired over time. She illustrated this concept by quoting the Kenyan-born philosopher John Mbiti: “I am because we are, and since we are, therefore I am.” Note the rephrasing of Descartes’ famous quote: “I think, therefore I am.” Birhane said we know from everyday experience that personhood is partly formed in community. Who we are depends upon many others—family, friends, culture, etc. She quoted a Zulu phrase, saying it was a better and richer account of personhood than Descartes cogito argument: “A person is a person through other persons.”

Biblically speaking, human personhood is also the result of being created in the image of God. Humanity, “being made in the image of God, was made to have a personal relationship with him.” In Escape from Reason, Francis Schaeffer said that when speaking of God to modern humans, it is important to emphasize that the Bible speaks of God as both a personal God and an infinite God. This is the kind of God who is there; who actually exists. And He is no ghost in the machine.

08/1/17

Repeating Past Mistakes

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At 4:45 a.m. on September 1, 1939, 1.5 million German troops invaded Poland. Two days later Britain and France declared war on Germany and World War II had begun. This “blitzkrieg” strategy became a blueprint of how Hitler intended to wage war. Generally unknown, one of the key tools in the success of the German Wehrmacht was their use of a methamphetamine called Pervitin. The troops were literally on cloud nine about Pervitin, as were their commanders.

Reports from the front lines on the drug included the following glowing testimonies:

Everyone fresh and cheerful, excellent discipline. Slight euphoria and increased thirst for action. Mental encouragement, very stimulated. No accidents. Long-lasting effect.The feeling of hunger subsides. One particularly beneficial aspect is the appearance of a vigorous urge to work. The effect is so clear that it cannot be based on imagination.

Not surprisingly, addiction became a problem. In April and May of 1940 alone, the Nazis shipped 35 million units of Pervitin and similar medications to its troops. Troops at the front sent letters home begging for more Pervitin. “Everybody, from generals and their staffs to infantry captains and their troops, became dependent on methamphetamine.” A lieutenant colonel leading a Panzer division wrote the following in a report:

Pervitin was delivered officially before the start of the operation and distributed to the officers all the way down to the company commander for their own use and to be passed on to the troops below them with the clear instruction that it was to be used to keep them awake in the imminent operation. There was a clear order that the Panzer troop had to use Pervitin.

“Speed” or amphetamine is in ADHD medications like Adderall (amphetamine/dextroamphetamine), Vyvanse (lisdexamfetamine). Methylphenidate (Concerta, Ritalin, Daytrana) is their close chemical relative. By the way, don’t be fooled by the creative spelling done by Shire for Vyvanse: “lisdexamfetamine” instead of “lisdexamphetamine.” Writing for The Guardian, Alexander Zaitchik noted  how the phonetic sleight-of-hand of Shire with Vyvanse and its aggressive marketing contributed to its success in getting the FDA to approve Vyvanse to treat “Binge Eating disorder.”

The company’s neo-phoneticism is intended to put more distance between its new golden goose and the deep clinical literature on speed addiction, not to mention last century’s disastrous social experiment with widespread daily speed use, encouraged by doctors, to temper appetites and control anxiety.

What follows is a history of amphetamines gleaned primarily from two sources: a paper on Amphetamines from the Center for Substance Abuse Research (CESAR) of the University of Maryland and a 2008 article by Nicolas Rasmussen for the American Journal of Public Health, “America’s First Amphetamine Epidemic 1929-1971.”

Amphetamine was first synthesized by a German chemist in 1887, but its stimulant effects weren’t noticed until the early 1930s, when it was rediscovered by accident. The chemist was trying to make ephedrine, a decongestant and appetite suppressant. Branded as Benzedrine, amphetamine was marketed as an inhaler for nasal congestion by the pharmaceutical company, Smith, Kline & French starting in 1933. It didn’t take some people long to figure out how to use Benzedrine for its euphoric effect. They cracked the container open and swallowed the Benzedrine-coated paper strip or steeped it in coffee.

Its use grew rapidly as medical professionals recommended amphetamine for alcohol hangover, depression, narcolepsy, weight-loss, hyperactivity in children and morning sickness in pregnant women. “The use of amphetamine grew rapidly because it was inexpensive, readily available, had long lasting effects, and because medical professionals purported that amphetamine did not pose an addiction risk.” During World War II, amphetamines or methamphetamine (a derivative of amphetamine) were used by both Allied and Axis troops to increase their alertness and endurance, as well as to improve their mood.

By 1945, over 500,000 civilians were using amphetamine psychiatrically or for weight loss. Between 1945 and 1960 commercial competition drove amphetamine use higher. After a patent expired in 1949, the FDA estimated the production of amphetamine and methamphetamine rose almost 400% by 1952. By 1962, production of amphetamines was approaching 43 standard 10-mg doses per person. This compares to concerns with the 65 doses per year in the present decade that social critics of our cultures point to as evidence of the overuse of psychotropic medications.

The adverse effects of amphetamine were becoming more evident by 1960. Amphetamine psychosis had been known since the 1930s, but was initially attributed to the drug unmasking latent schizophrenia. This claim is eerily similar to current interpretations of antidepressant activation unmasking latent bipolar disorder, rather than being seen as an adverse side effect of antidepressant medication. There were also concerns that amphetamines were addictive. But this didn’t stop individuals like President John F. Kennedy from using regular injections of vitamins, hormones and 15 mg of methamphetamine to help maintain his image of youthful vigor.

Large quantities of amphetamines were dispensed in the 1960s directly by diet doctors and weight loss clinics. Calculations of amphetamine use and misuse in 1970 estimated that at least 9.7 million Americans had used the drugs in the past year. And of those 9.7 million users, 3.8 million do so for nonmedical reasons and 2.1 million of those abused the drugs. Rasmussen said this first amphetamine epidemic was iatrogenic, “created by the pharmaceutical industry and (mostly) well-meaning prescribers.”  The current problem with the misuse of amphetamines has reached the peak of the original epidemic, namely about 3.8 million past-year nonmedical amphetamine users, with an estimated 320,000 of whom are addicted.

Parallel to this trend has been the surge in the legal supply of amphetamine-type ADHD medications such as Ritalin, Adderall and Vyvanse. American doctors, unlike those in other countries, have found it hard to resist prescribing these drugs. According to DEA production data, since 1995 medical consumption of these drugs has quintupled. In 2005, it exceeded the amphetamine consumption of 2.5 billion 10-mg amphetamine base units for medical use in 1969—compared to 2.6 billion base units in 2005. The following graph, taken from Rasmussen’s article, illustrates this increase. The data is based upon DEA production quotas and expressed as common dosage units of 10-mg amphetamine and 30-mg methylphenidate.

Rasmussen downplayed a causal connection between childhood stimulant treatment for ADHD and later nonmedical amphetamine consumption, but others don’t (See more on this below). However, he did think the wide distribution of ADHD stimulants, noted in the above graph, created a hazard. He cited data from a study that indicated 600,000 reported using stimulants other than methamphetamine nonmedically in the past month. So, “legally manufactured attention deficit medications like Adderall and Ritalin appear to be supplying frequent, and not just casual, misusers.”

An analysis of stimulant abuse in recent national household drug surveys found that half of the 3.2 million reporting past-year nonmedical use of stimulants in the U.S. only used psychiatric stimulants. And 750,000 of those reported they had never used anything but attention deficit pharmaceuticals in their entire lives. “On this evidence alone, one can fairly describe the high production and prescription rates of these medications as a public health menace of great significance.”

Another problem is the widespread acceptance of prescription amphetamines as a legal and relatively harmless drug that can be given to small children. Rasmussen said it is difficult to make a convincing case that the same drug is harmful if used nonmedically. Therefore he concluded any attempt to deal harshly with methamphetamine users today in the name epidemic control, without touching medical stimulant production and prescription was practically impossible and hypocritical.

There is some evidence of a connection between childhood stimulant treatment and later abuse or use of stimulants. See “ADHD: An Imbalance of Fire Over Water or a Case of the Fidgets?” on this website for a discussion of the association of addiction and ADHD medications as well as other adverse effects.

Nadine Lambert did a longitudinal study of ADHD children and normal controls. Her participants were followed through their childhood and adolescence and then evaluated three times as young adults. “ADHD was also significantly associated with amphetamine dependence.” However, being diagnosed with ADHD did not increase the odds of lifetime use of stimulants. She found that treatment with stimulants increased the odds of lifetime use of amphetamine and cocaine/amphetamines.

Commenting on Lambert’s findings in Brain Disabling Treatments in Psychiatry, Peter Breggin said:

It is not ADHD but the treatment for ADHD that puts children at risk for future drug abuse. This conclusion is entirely consistent with the fact that animals and humans cross addict to Ritalin, amphetamine and cocaine and that exposure to Ritalin in young animals causes permanent changes in the brain.

Hitler and his generals wanted victory at any cost and Pervitin (methamaphetamine), was part of that solution. German pilots called it “pilot’s chocolate”; soldiers on the front called it “Panzerschokolade” or “tank chocolate.” But towards the end of WW II, Vice Admiral Hellmuth asked German pharmacologists to develop a miracle drug. They had a wonder drug with Pervitin, but now they needed a miracle drug. So Gehard Orxzechowski synthesized D-IX. It was supposed to keep soldiers ready for battle even when they were asked, “to continue beyond what was considered normal.” It contained 5 mm of cocaine, 3mm of Pervintin and 5mm of morphine. It seems it was a good thing the war ended before they could distribute it widely to their troops.

We have a lesson to learn from the German Wehrmacht’s failure to make a better, smarter, stronger soldier through chemicals. The American war on drugs needs to recognize its greatest casualties are now coming from within—as with ADHD medications. And I think we need to reflect on the words of George Santayana in The Life of Reason: “Those who cannot remember the past are condemned to repeat it.”