Cocaine and Addiction

May 31, 2009

I chanced upon this article. Its subject is the advisability of legalizing marijuana. It’s at the usual level of coherence that typifies public discussion of the subject. It sees no conflict between an individual’s right to engage in behavior that harms only himself and society’s right to stop him, indeed to lock him up for a very long time. We have managed to fill our prisons to beyond surfeit by making mere possession of forbidden substances a felony. We’ve even managed to destroy at least one other country as a consequence of our drug laws.

The article cited above says,”While marijuana is not addictive in the way that a drug like crack-cocaine is…” One of the characteristics of popular journalism is that it can pontificate at length without a lot of knowledge of a subject beyond the superficial. Let’s stick to cocaine and addiction rather than confronting the whole subject of addiction much less discussing whether marijuana should be legal or not. I may return to this issue in a later post.

The lay press and the myriad of “professionals” who earn their living from having as many drugs and behaviors as possible accepted as addiction or even as disease, and who get paid for their services as would an internist for treating diabetes, rarely use the medical definition of drug addiction. They typically confuse habituation with addiction. A drug is addictive when it cause habituation, dependence, tolerance and withdrawal. Cocaine produces no gross physiological withdrawal symptoms (Gawin, Science, 251:1580, 1991; DSM IV [psychiatry’s diagnostic handbook], 1994 p 225). In 1990 the NIDA found that 11.5% of Americans had used cocaine, but only 0.9% in the last month; only 0.09% used it weekly (DHHS Publication # ADM 91-1732). The vast majority of cocaine users do not become chronic users.

Why does the popular press and the public think that cocaine is even more addictive than opium? It’s because of statements such as this: “Cocaine-driven humans will relegate all other drives and pleasures to a minor role in their lives…. If we were to design deliberately a chemical that would lock people into perpetual usage it would (be) cocaine (Cohen, US Govt Printing Off, 1984).” Or this:”Repeated doses of addictive drugs – opiates, cocaine, and amphetamine – cause drug dependence and afterward, withdrawal (Hyman, Science 273:611, 1996).” The latter makes no distinction between cocaine and opium even though opium meets all the criteria for an addictive drug while cocaine does not. Both statements are hysterically wrong.

“After 10 years, 60% (of cocaine users) had become completely abstinent, and 40% remained occasional users. Most drug users ultimately stop. Drugs no longer fit their lifestyle. They get jobs, they have to get up early, they stop going to the disco, they have kids. (Peter Cohen, Centre for Drug Research, University of Amsterdam).”

Let’s get a few thing clear. Cocaine is a dangerous drug which occasionally is associated with dependence and habituation, but it is not addictive; most users spontaneously stop using it. Filling our prisons with people who have harmed no one but themselves is cruel and unusual punishment.

“The only purpose for which power can be rightfully exercised over any member of a civilised community, against his will, is to prevent harm to others. His own good, either physical or moral, is not a sufficient warrant. He cannot rightfully be compelled to do or forbear because it will be better for him to do so, because it will make him happier, because, in the opinion of others, to do so would be wise, or even right. These are good reasons for remonstrating with him, but not for compelling him, or visiting him with any evil in case he do otherwise. Over himself, over his own body and mind, the individual is sovereign.” JS Mill, On Liberty, 1859. Mill’s vision of liberty still remains an unrealized ideal.

“Many [drug users] receive mandatory sentences of 5-10 years for possession of a few grams of drugs. Congress set small quantities for no better reason than ignorance, politicking, and a lack of fluency in the metric system.” Eric Sterling, Criminal Justice Foundation. The press and the public seem unable to distinguish drug abuse from drug addiction. It hard to justify life in prison for either. Illicit drugs can remain illegal without sending people to the penitentiary solely for possession.

The Editorial Board of The Christian Science Monitor is entitled to express any opinion it wishes. This opinion, however, may not have any standing as an expert or even informed opinion. It just offers the usual journalistic “omniscience” on anything that’s in the public’s consciousness. Deep knowledge or even familiarity with the subject is incidental.

Caveat lector.

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Drowning in a Sea of Similes

May 29, 2009

Before turning the last page, I’ve been trying to reread some of the masterpieces of literature that I was force fed as a youth when ill equipped to digest them. The past few months I’ve been chewing on French literature. I started small (in length not quality) with Stendhal and Flaubert. The Rossini crazed Stendhal was an appropriate beginning. Julian Sorel’s misadventures in The Red and the Black were dazzlingly depicted and I was swept away. The understated eroticism was palpable. How could I have missed all this as a student?

Madame Bovary had bored a tattoo on my brain as a high school student which still pulsates. Yet when, with much trepidation, I took it up again I couldn’t put it down. Unlike almost everybody else I found Emma Bovary a sympathetic character. She’s trying to make something of her life; no matter that she does it badly. She’s not the maddeningly masochistic and solipsistic woman that is Anna Karenina whom everyone seems to find sympathetic. I snuck the Tolstoy in between Flaubert and Proust. I couldn’t wait for the fatal train to arrive. Again unlike many critics I didn’t think Anna Karenina anywhere near War and Peace. The former a good novel by a great author, the latter the greatest of novels.

Back to Flaubert’s whose dazzling style and uncanny humor make the novel (Madame Bovary) as good as any before or since. The scene in the coach is a tour de force. In keeping with this site’s connection to opera the novel contains a scene at a performance of Lucie Di Lammermoor.

Thus warmed up I approached the biggest elephant in the canon. Proust’s monument to the prolix had defeated me on many previous excursions into Remembrance of Things Past (or In Search of Lost Time if you prefer). I had never before gotten more than 300 pages into it. But this time I made it all the way through.

I have a friend whose intelligence and discernment I greatly admire even if he is a devout Wagnerian. He has constantly urged me to attempt Proust one more time as he thinks the dinotherian novel one of the great masterpieces of art. I did and I did – get through it. I think my first reflection after this feat was stupefaction. It was much the same as my reaction to Gray’s Anatomy which long as it is is only half the size of Proust’s novel. As I was making my way to the end (of the novel, I never did get through Gray’s Anatomy) I was swept away by the seemingly infinite procession of similes. They’re as numerous as the suns in the Milky Way and almost as luminous.

My interest in the book never flagged though it was the same as I get from solving an interesting problem of pathophysiology. I love the problem, but only for its solution. With Proust there is no solution. Nevertheless, I can see why so many are so taken with him. The atomization of the mundane can be fascinating. I can also understand why just as many are bored or put off by the semi-antisemitic supercilious snobbish narrator. Proust, who is the narrator no matter how he tries to disguise it, thought he was not Jewish even though his mother was. Had he lived another 20 years he would have discovered that a malign authority thought him such.

He feelings towards homosexuality seems as conflicted as that to his Jewishness. His use of “invert” to depict a homosexual and his fear of Albertine’s homosexuality seem at odds with his own position as an “invert”. So what to make of this strange and unique novel? I suppose that one should react to it the same as if one discovered that the Great Pyramid of Cheops were made of spider webs.

Next I turned to another pachyderm of French literature – Hugo’s Les Miserables. A smaller great beast, to be sure, but still a monster. In Hugo you have humanity writ large. His great digressions which always have a reason – eventually. [Hugo’s digressions are much more pertinent than Tolstoy’s reflection on inexorable history. The Russian learned a lot from Les Miserables when he wrote War and Peace.]  His great language. His great characters. His vitality. All put him at the highest level of art. His magnificent ability to craft a scintillating plot without descending to the artifice of Scribe or Sardou.

Plays (which are remembered mostly for the operas they spawned especially Ernani and Rigoletto), poetry which I lack the ability to read, and the great novels which allow translation make him a prodigy of energy and revelation. He is the equal of Tolstoy and Dickens. Proust is to Hugo as Massenet is to Verdi. Hugo had the vulgarity that only the greatest geniuses achieve. It’s hard to believe that Hugo and Berlioz on the one hand and Flaubert and Proust on the other were all French. The 2 million Frenchmen who turned out for his funeral show how he touched the heart. He still does, but only if the particular heart is not cold. And he could also draw and paint. See the art of Victor Hugo.

Hugo - Town with tumbledown bridge, 1847

Hugo - Town with tumbledown bridge, 1847

Balzac and Zola are next. Then I may recross the channel.

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Recording of the Week: Roberto Sierra “Fandangos”

May 24, 2009

Sierra

Born in Puerto Rico in 1953, Roberto Sierra studied with György Ligeti in Germany. He currently is professor of composition at Cornell University. His music has been played by many of the world’s leading symphony orchestras.

Recorded in 2008 by Albany Records the disc begins with Sierra’s 2002 composition Fandangos. Mainly based on a fandango by Antonio Soler the 11 minute piece is an orchestral tour de force. Written in variation form the piece is reminiscent of Ravel’s Bolero. Not that it sounds like it, but in its duration, brilliant orchestration, and economy of material. Though one can hear suggestions of Ligeti at about the five and a half mark, it’s written in an accessible idiom.

Here are the last couple of minutes of Fandangos. Turn the volume up if you have good speaker attached to your computer. The Sinfonia Da Camera is conducted by Ian Hobson.

The remainder of the disc includes Louis Moreau Gottschalk’s Souvenir de Porto Rico played by Hobson. This is followed Sierra’s Reflections on a Souvenir also played by Hobson. Sierra’s Variations on a Souvenir is played by Hobson with the orchestra conducted with vigor and sharpness  by Eduardo Diazmuñoz. The Variations is a 30 minute work that explores Gottschalk’s music at greater length than the solo piano piece.  Hobson’s playing is brilliant throughout. The original Gottschalk piano solo is interesting and worth several listens.

The recording concludes with Sierra’s Toccata for piano played again by Hobson. Sierra clearly deserves the attention he has garnered in recent years.

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Licorice and Hypokalemia

May 23, 2009

I’ve been asked about licorice and hypokalemia. So here’s the short answer. The adrenal cortex make two classes of steroids – glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Steroid hormones initiate their effect by activating an intracellular receptor. I’ll limit my discussion to the effect of aldosterone on the principal cell of the cortical collecting tubule. There aldosterone stimulates the Na-K-ATPase (directly or indirectly). This results in sodium reabsorption and potassium secretion. Excess of aldosterone leads to hypertension (because of the sodium retention) and hypokalemia because of excess potassium secretion and consequent urinary loss. It also causes increased acid excretion and thus metabolic alkalosis via a mechanism I have omitted.

The kidney could distinguish cortisol from aldosterone by having mineralocorticoid specific receptors which it has; but most of the steroid receptors are nonspecific responding to either cortisol or aldosterone. In a failure of Occam’s razor God decided to deal with this problem using a more complicated scheme. This is not the only time God forsook Occam when designing the kidney – bicarbonate reabsorption is another example.

To ensure that every time you get a surge of cortisol you don’t get a mineralocorticoid response God (you can substitute evolution if it makes you happier) created 11-beta-hydroxysteroid dehydrogenase. This enzyme metabolizes cortisol to cortisone which does not activate the renal steroid receptors preventing an inappropriate mineralocorticoid response.

Licorice contains glycyrrhizic acid which inhibits 11-beta-hydroxysteroid dehydrogenase thus allowing cortisol to exert an aldosterone like effect; ie cortisol is not metabolized to cortisone and thus stimulates sodium retention, potassium wastage, and acid excretion. A licorice glutton presents with high blood pressure and hypokalemic metabolic alkalosis. He looks just like a patient with primary hyperaldosteronism, but when aldosterone levels in the blood are measured they are zero. A history of large consumption of licorice makes the diagnosis.

Only natural licorice has this effect because only it contains glycyrrhizic acid. Most of the licorice sold has artificial flavoring and thus does not convey risk. An interesting example of organic being worse than artificial. How much natural licorice consumption will cause this syndrome is not known, but it’s a lot. So if you like natural licorice and you take it in moderate amounts there’s nothing to worry about.

Since biology operates under the rule that anything that can go wrong will go wrong, patients have been described with a genetic defect in 11-beta-hydroxysteroid dehydrogenase. Thus they present with a syndrome identical to that caused by licorice gluttony only they haven’t taken licorice. With all the perils nature hurls at us it’s remarkable that life exists on Earth.

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Cola and Hypokalemia

May 20, 2009

Belonging in the same category as “Repeatedly Banging Your Head against a Brick Wall Can Cause Headaches” is the report “Excess cola can cause super-sized muscle trouble“. Briefly, the article describes a paper soon to be published from Greece which reports two patients who developed hypokalemia associated with drinking huge amounts of cola soft drinks. Forsaking false modesty, let me start by stating that I know as much about hypokalemia as anybody in the world.

One of the effects of hypokalemia (the word just means low blood potassium) is muscle weakness or muscle injury. Both the patients described by the Greek doctors  imbibed prodigious amounts of cola – three to nine liters a day. Nine liters is about 2 gallons. They apparently did this for long periods.

Cola contains, among other things, sugar and caffeine. Sugar (glucose and fructose) stimulates insulin release which drives potassium into cells. Caffeine is a weak beta agonist which also drives potassium into cells. Colas are mainly water which is excreted by the kidney. High rates of flow of tubular urine along the distal nephron will increase urinary potassium excretion. And if you’re drinking so much cola you’re likely on a diet low in potassium. Combine all these effects for a long time and hypokalemia severe enough to be symptomatic may result. But you’d have to drink a lot more cola than most sane people would do for a very long time to be at risk for hypokalemia.

The potential difference across a muscle cell is a function of the ratio of extracellular to intracellular potassium. As most of the potassium in the body is inside the cell small changes in extracellular potassium can have a marked effect on this ratio and hence on muscle PD. This is why a sudden shift of potassium into the cell can cause weakness or even paralysis. Hypokalemic periodic paralysis is classic example of this phenomenon. Hyperthyroidism is the commonest cause of this uncommon syndrome.

Cola consumption is almost certain to be a less common cause of hypokalemia than licorice ingestion which in turn is less common than hypokalemic periodic paralysis. You probably didn’t know about licorice. You’re on you own with this one. If you just can’t contain your curiosity ask me and I’ll tell you about licorice and hypokalemia.

One of the two patients was said to be vomiting. Vomiting itself is a well known cause of hypokalemia. So I can’t be sure that this patient’s hypokalemia was related alone or in part to the consumption of cola.

If you do anything to excess, bad things often happen. Drinking too much water may cause hyponatremia (low blood sodium) also known as water intoxication. I’d worry more about the calories from soda than I would about the remote chance of hypokalemia. There are about 3600 calories in nine liters of cola. Drink diet cola if you like the taste. Excess of diet cola would likely cause water intoxication before hypokalemia.

Don’t worry your self breathless about rare manifestations of bizarre behavior, there’s enough common stuff that’s sufficiently scary without focusing on the semi-imaginary.

There’s a good review on hypokalemia in the 5 May 2009 issue of the Annals of Internal Medicine: Narrative Review: Evolving Concepts in Potassium Homeostasis and Hypokalemia.

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Reality Strikes

May 19, 2009

The May 14 issue of the New England Journal of Medicine contains an article, Picking the Right Poison — Options for Funding Health Care Reform, that sets a new tone for the journal. It looks at health care reform through a clear lens. Funding universal health care is going to cost a lot of money. Be assured that whatever the estimate of its cost now is, its true cost will be many multiples of whatever number is currently presented.

Jonathan Oberlander the author of the perspective piece rightly concludes that health care reform cannot pay for itself by making the system more efficient. Rather expansion of coverage will generate additional costs. Raising taxes seems inevitable, hence picking the right poison. This choice usually means taxing someone else.

Reducing benefits is another option. This, of course, will be presented as getting rid of fat. One man’s meat is another man’s fat. Oberlander’s statement, “There is, then, no easy way to pay for comprehensive health care reform,” may get him thrown out of the club of right thinking analysts for whom nothing good is hard.

He compounds his truth telling by adding that “reformers may have to retreat from the goal of providing all Americans with comprehensive insurance.” That such a radical approach to healthcare reform made it into the NEJM suggests that hard reality may be intruding on good intention, that intent and outcome are not the same.

Remember the immortal words of Russell Long, Huey’s boy, “Don’t tax you, don’t tax me, tax that guy behind the tree.”

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Recording of the Week: Gubaidulina Offertorium

May 14, 2009

gubaidulina - offertorium

Born in Chistopol in the Tartar Republic of the Soviet Union in 1931 Sofia Gubaidulina is a composer now living in Germany. She has a large reputation among a relatively small number of lovers of contemporary music. Her music has been championed by Gidon Kremer who is the soloist on this recording of her violin concerto Offertorium.  Originally released in 1989 it was reissued in 2002 as part of DG’s Echo 20/21 series of contemporary music. The Boston Symphony Orchestra is conducted by Charles Dutoit.

The remainder of the disc contains the composer’s Hommage à T.S. Eliot, a seven part piece for soprano (Christine Whittlesey) and octet. The Hommage contains a few lines from three of Eliot’s Four Quartets. It’s connection to Eliot’s long poems is slender.

The concerto is a deconstruction of the royal theme from JS Bach’s A Musical Offering. The technique is that of Webern. If you like the 2nd Viennese School you’ll love the Offertorium. My younger musician friends are great admirers of Gubaidulina. Here’s the first three minutes of the piece (Offertorium ) with the Bach theme and the start of its dissection. If your tastes are less adventuresome I’ll put up a newer composition next week that is a little easier for tired ears.

There’s little melody and very little rhythmic drive in the concerto. There’s a lot of brilliant orchestration, complicated harmonies, and unusual timbres to the composition. It’s obviously going to attract a specialized audience.

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