Wednesday, December 14, 2022

It Is Time to Legalize Cocaine

 The US is gradually moving towards legalizing recreational use of marijuana.  It has taken a long time and there is still a long way to go, but it seems it is going to happen.  And the nation moves on with no dire consequences.  Nevertheless, it was still a bit startling for the relatively conservative magazine, The Economist, to declare the time has come to legalize Cocaine.  A compelling argument is made that the efforts to wipe out the cocaine economy are only making matters worse.  Before considering that perspective, a brief diversion into the history of recreational drugs and the motivations behind their illegalization is useful. 

David F. Musto has written the definitive history of anti-drug legislation in the United States: The American Disease: Origins of Narcotic Control.  Drugs such as opium, morphine, and cocaine were freely available throughout the nineteenth century.  The drugs were regularly used by physicians as medications and were widely available in commercial formulations generically referred to as “patent medicines.”  Cocaine could even be purchased in a syringe for self-injection.  Until 1903, Coca Cola contained cocaine.  Afterward, the cocaine was replaced with a new stimulant: caffeine.  Children were subjected to narcotics as a remedy for crankiness and sleeping difficulties.

“In the United States the exhilarating properties of cocaine made it a favorite ingredient of medicine, soda pop, wines and so on.  The Parke Davis Company, an exceptionally enthusiastic producer of cocaine, even sold coca-leaf cigarettes and coca cheroots to accompany their other products, which provided cocaine in a variety of media and routes such as a liquor-like alcohol mixture called Coca Cordial, tablets, hypodermic injections, ointments, and sprays.”

The addictive properties of these drugs were known and the personal and societal disruption they could cause were recognized.  There were movements to restrict or eliminate their use.   These actions were always countered by those who made money from the drug usage.  All legislative attempts at drug restrictions were ultimately driven by politics rather than science.  Legislation restricting cocaine provided the prime example.

This use of a targeted minority to focus popular disgust in order to obtain desired legislation was effective and became the normal approach with respect to criminalizing drug usage.

“The most passionate support for legal prohibition of narcotics has been associated with fear of a given drug’s effect on a specific minority.  Certain drugs were dreaded because they seemed to undermine essential social restrictions which kept these groups under control: cocaine was supposed to enable blacks to withstand bullets which would kill normal persons and to stimulate sexual assault.  Fear that smoking opium facilitated sexual contact between Chinese and white Americans was also a factor in its total prohibition.  Chicanos in the Southwest were believed to be incited to violence by smoking marijuana.  Heroin was linked in the 1920s with a turbulent age group: adolescents in reckless and promiscuous urban gangs.  Alcohol was associated with immigrants crowding into large and corrupt cities.”

The association of cocaine with blacks was intimately tied to the repressive conditions that the South believed were necessary to keep blacks in their “place.”  First their guns were taken away, then their civil rights, followed by prohibition of alcohol and a call to stop the selling of something called “Coca Cola.”  As usual, the Southern bloc of legislators was needed to get laws passed. To obtain their votes, the fear mongering they engaged in by relating blacks to cocaine became an important part of the political dialogue.

“The fear of the cocainized black coincided with the peak of lynchings, legal segregation, and voting laws all designed to remove political and social power from him.  Fear of cocaine might have contributed to the dread that the black would rise above ‘his place,’ as well as reflecting the extent to which cocaine may have released defiance and retribution.  So far, evidence does not suggest that cocaine caused a crime wave but rather that anticipation of black rebellion inspired white alarm.  Anecdotes often told of superhuman strength, cunning, and efficiency resulting from cocaine.  One of the most terrifying beliefs about cocaine was that it actually improved pistol marksmanship.  Another myth, that cocaine made blacks almost unaffected by mere .32 caliber bullets, is said to have caused southern police departments to switch to .38 caliber revolvers.  These fantasies characterized white fear, not the reality of cocaine’s effects, and gave one more reason for the repression of blacks.”

Cocaine and opiate products would become illegal in 1914, but racial politics did not go dormant.  Fears of black usage of the drug would arise anew during the 1970s and 1980s.  Extremely severe sentences for drug possession or sale came after a period of high crime rate and urban rioting.  In circumstances eerily reminiscent of the post-Reconstruction-era South, whites feared that the blacks, in their segregated urban sectors, might be getting out of control.  Drugs were already prohibited but, nevertheless, were widely available.  The goal of legislation then turned to pouring more resources into crime/drug control.  Can it possibly surprise anyone that the tried-and-true tactic of scaring people with suggestions of cocaine-crazed blacks on a crime spree was resurrected?

Carl Hart has also written a book for a general readership: High Price: A Neuroscientist’s Journey of Self-Discovery That Challenges Everything You Know About Drugs and Society.  In it he provides a perspective on addiction that is counter to conventional wisdom.  He suggests all our favorite addictive drugs, including alcohol and nicotine, can be categorized similarly. 

“…more than 75 percent of drug users—whether they use alcohol, prescription medications, or illegal drugs—do not have this problem [harmful addiction].  Indeed, research shows repeatedly that such issues affect only 10-25 percent of those who try even the most stigmatized drugs, like heroin and crack.”

Even the person who becomes a regular user of the drug continues to maintain the ability to choose to take the drug or not depending on the given circumstances.  The image of the addict being driven mad with desire for his drug just doesn’t happen.  Hart suggests that the desire for the drug is more closely analogous to the desire humans feel for sex and food—both being cravings difficult but possible to control. 

If the more prevalent and more damage-producing drugs such as alcohol, nicotine, and legal psychotropic drugs are not destroying societies, why are we so concerned with cocaine?

In The Economist, the political realities of the failure of “wars on drugs” are detailed to make a case for legalization.  The relevant article is Booming cocaine production suggests the war on drugs has failed. 

“When Richard Nixon, then America’s president, launched his “war on drugs” in 1971, the flow of cocaine into America was a trickle. Despite billions of dollars spent every year on arrests, asset seizures and destroying coca bushes, it has become a flood. About 2% of North Americans—roughly 6m people—are thought to use the stuff. New shipping routes are bringing the drug to consumers in Africa, Asia and Europe…”

The number of people using cocaine thought to have a serious addiction is about 20% or about 0.4% of the population.

The issue is supply and demand.  The supply is in relatively poor South American countries, the demand is in the relatively wealthy countries of the world. 

“According to Jeremy McDermott of InSight Crime, a website that analyses organised crime, Mexican gangs can buy a kilo of cocaine for $3,000 in Colombia. He estimates that a kilo is worth between $8,000 and $12,000 in Central America, $20,000 in the United States, $35,000 in Europe, $50,000 in China and $100,000 in Australia.”

Much of the “warfare” has taken place in the producing countries.  They are beginning to be more aggressive in propagating the notion that the effort has failed and something new must be done.

“Plenty of Latin American presidents have said the war is not working—though as Jonathan Caulkins, a drug expert at Carnegie Mellon University, points out, they tend to do so only once they have safely left office. Now some of those in power are beginning to speak up, too. In an interview with The Economist, Gustavo Petro, Colombia’s new president, talked of leniency for repentant gang members, decriminalising coca-leaf production and creating places where Colombians could consume cocaine in a supervised environment. Felipe Tascón, a member of Mr Petro’s campaign team who had been tipped for a role as his drug ‘tsar’, has flirted with the possibility of outright legalisation, and has talked of collaborating with other Andean countries which produce the drug.”

Even if producing countries legalized production successfully, that would have little impact on demand.  As Carl Hart points out in his book, drug use and addiction are only partly explained by the nature of the drug, they also depend on the needs of the members of the society.  Animals, including humans, are less likely to need to seek satisfaction from drugs if they have stable social and economic standing in their community.

“’The problem is in consumption, not production,’ says Mr Petro. His view is that ‘the competitive society…the ideology of the last few decades…is the one that generates addiction. And it is what generates widespread drug use.’ Mr Petro’s explanation is dubious. But his diagnosis is surely correct. So long as cocaine remains illegal in the rich countries that consume it, then legalising it in the poorer places that produce it will have only a small effect.” 

Is there any hope that legalization could come to a country like the US? 

“Full-on decriminalisation, let alone legalisation, is not about to happen in the West. But attitudes have shifted notably in the past few years. In 2020 the state of Oregon decriminalised the possession of all drugs, cocaine included. Portugal has had a similar policy since 2001. On October 7th Femke Halsema, Amsterdam’s mayor, told a meeting of European justice ministers that she thought that the war on drugs had failed, and that cocaine should be decriminalised. If decriminalisation happens in Latin America, it could put more momentum behind such ideas.”

There is another factor to consider.  It has become common for drug gangs to improve their profit margins by diluting their product with cheaper drugs.

“These days much of the cocaine that is shipped north to the United States comes mixed with fentanyl, a powerful and addictive opioid painkiller. The UNODC reckons that toxic combination is the main reason why cocaine-related deaths in America have risen fivefold since 2010…” 

Many lives could be saved with a regulated and safe source of cocaine.

 

Thursday, December 8, 2022

Psychopharmacology and Depression

Twelve years ago, I came across an article that changed my view of the pharmaceutical industry forever.  It appeared in the London Review of Books: Which came first, the condition or the drug?.  In it, Mikkel Borch-Jacobsen wrote a review of a book authored by David Healy titled “Mania: a Short History of Bipolar Disorder”.  The case was made that what was known as bipolar disorder seemed not to exist until a marketing campaign by the pharmaceutical industry produced a high level of diagnoses.  This condition was said to involve individuals who would switch between depressive states and manic states.  The work of Healy in inspecting the history of patient diagnoses over several decades, found that such a finding was extremely rare, but for some reason the diagnosis was now quite common.   Borch-Jacobsen provides this background information.

“…Healy arrives at a figure of ten cases per million each year, that is 0.001 per cent of the general population. This figure is striking, as today the incidence of bipolar disorder is supposed to be much higher. In 1994, for example, the US National Comorbidity Survey estimated that 1.3 per cent of the American population suffered from bipolar disorder. Four years later, the psychiatrist Jules Angst upped the figure to 5 per cent: 5000 times higher than the figure suggested by Healy.”

The implication was that the drug companies had created a new category of illness and proceeded to make it a popular medical diagnosis. 

“Healy tells the story of the launch of bipolar disorder at the end of the 1990s. A specialised journal, Bipolar Disorder, was established, along with the International Society for Bipolar Disorders and the European Bipolar Forum; conferences were inundated with papers commissioned by the industry; a swarm of publications appeared, many of them signed by important names in the psychiatric field but actually ghost-written by PR agencies. Once the medical elites were bought and sold on the new disease, armies of industry representatives descended on clinicians, to ‘educate’ them and teach them how to recognise the symptoms of bipolar disorder. Bipolar patient advocacy groups sprang up, generously supported by pharmaceutical companies; freelance journalists were hired to write magazine articles on the latest advances in psychiatric science; websites were created, such as IsItReallyDepression.com (sponsored by AstraZeneca), where you can fill out a ‘mood assessment questionnaire’ at the end of which you’ll inevitably be dispatched to the nearest doctor. As a British blogger noticed recently, the Wikipedia entries ‘Bipolar Disorder’ and ‘Bipolar Spectrum’ were edited from a computer belonging to AstraZeneca, ensuring that everyone is on the same diagnostic page as the industry.”

Depression is one of the most common features of life, easily recognized and apparently easily treated by medications—more on that later.  That market for antidepressant drugs was large and growing.  Apparently, the goal of establishing bipolar disorder as a common illness was to expand the depression market to allow the sale of stronger and more dangerous antipsychotic drugs—with the collaboration of the psychiatric community.  If one reads the list of symptoms in the psychiatrist created DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition) one finds almost exactly the same set of symptoms as normal depression, a set so broad that every human on Earth could be diagnosed with the condition.

“A series of prominent lawsuits has been brought over the past few years in the United States against the manufacturers of anticonvulsants and atypical antipsychotics for having hidden their side effects and for having marketed them ‘off label’ towards patient populations not approved by the FDA. The sums paid out in fines or settlements by the pharmaceutical companies involved are staggering, and they give an idea of how disastrous the effects of their medications have been: Warner-Lambert/Parke-Davis (now Pfizer) has paid more than $430 million for marketing Neurontin for bipolar disorder; Lilly had to pay a total of $2.6 billion for the illegal marketing of Zyprexa; Pfizer was forced to pay $301 million for the illegal marketing of the atypical antipsychotic Geodon. AstraZeneca has agreed to pay $520 million to settle federal investigations into its marketing of Seroquel and has already spent $593 million in legal fees defending itself against the 10,381 individual lawsuits brought by patients for the side effects caused by the drug. Johnson & Johnson and its subsidiary Janssen have been sued by nine American states for the off-label marketing of Risperdal.”

Recall that the article discussed was published twelve years ago.  Time has not stood still.  The industry now refers to bipolar disorder as bipolar depression.  Perhaps the mania aspect was so rare that they had to change the strategy and focus on bipolar depression being a more serious form of depression requiring more serious medications.  And the drugs continued to fly off the shelves.

If one accumulates evidence that supports the notion that the pharmaceutical industry behaves in the manner described above when mental illness is involved, one is met with incredulous stares.  No one believes that such things can happen in our country.  One is viewed as some weird kind of conspiracy theorist. 

Two of the firmest tenets of psychopharmacology are that depression, and other mental illnesses, are caused by a chemical imbalance in our brains, and that medications act to control that chemical imbalance.  The chemical imbalance assumption began as an hypothesis.  It has never been proved, yet it has become dogma because both psychiatrists and the pharmaceutical companies found it profitable to assume it was true.  Evidence from depression drug trials indicate that almost as many participants who receive a placebo, perhaps a sugar pill, claim improved symptoms as do those who received the actual medication.  This demonstrates that a placebo effect is the dominant cause of most responses.  This fact has been known by both psychiatrists and drug companies for several decades.  Both can claim that the pills they give patients are often helpful at improving their symptoms, so what is the problem?  The problem is that the drugs alter brain function and often produce unpleasant side-effects and addiction. This source provides some perspective.

“The problem is that lots of people who do not need antidepressants are already on them, refilling prescriptions written years or even decades ago. They should be helped to get off the drugs. The side-effects are often life-limiting and, as people age, become life-threatening. They include sexual dysfunction (which sufferers describe as “genital anaesthesia”), lethargy, emotional numbness, increased risk of birth defects when taken during pregnancy, and, in older people, strokes, falls, seizures, heart problems and bleeding after surgery. This is a threat to health-care systems as long-term users age.”

In addition, patients who choose to stop their medications often face severe withdrawal symptoms.  This is yet another of the bizarre realities of the psychopharmacological industry that people find incredible.

A recent article in The Economist finally noticed data that had been around for over a decade and concluded that something should be done about it: How to make better use of antidepressants.  It details what is known about the most common antidepressant drugs: selective serotonin reuptake inhibitors (SSRIs).

“…new drugs called selective serotonin reuptake inhibitors (SSRI), which appeared in the 1980s, specifically block the serotonin transporters, so are much safer—so much so that by the 1990s they had become a lifestyle drug, prescribed widely for normal emotional reactions to events such as bereavement or work burnout.”

“For many years drug companies, the main source of research on SSRIs, tended not to publish in scientific journals the results of clinical trials that cast doubt on their products’ utility. That practice biased scientific reviews of the field in the drugs’ favour. But companies are nevertheless required by America’s medicines regulator, the Food and Drug Administration (FDA), to submit to that agency all the data collected during their trials, making them available for others to examine.”

“The most recent such analysis, published in the BMJ in June, combined the results of all trials of antidepressants filed to the FDA between 1979 and 2016. It found that the drugs had a substantial effect on depression beyond that of a placebo for only 15% of patients.”

“A study published in 2010, which examined research on two common SSRIs, estimated that for people with less severe depression the odds of improving by taking the drugs were just 6% higher than they were for taking a placebo. For those with more severe depression they were 25% higher.”

These studies confirm the claim that the majority of those benefiting from antidepressants are merely benefitting from a placebo effect.  More on this placebo effect can be found in Antidepressant Drugs versus PlacebosThe Economist also agrees there has not been any evidence to confirm a relationship between serotonin and depression. 

“Moreover, while all this has been going on the serotonin hypothesis has come crashing down. Researchers have looked from many directions for a relationship between serotonin and depression. They have found little or no evidence to link the two.”

So, if antidepressants provide no benefit other than as a placebo for most users, are the dangers of taking unnecessary brain-altering drugs sufficient to convince users that they are not worth the risk.  The potential side-effects have already been mentioned.  An equally important concern involves the difficulties associated with withdrawal symptoms experienced when quitting the drugs.

“A review of the research published on that topic, carried out in 2019, found that between 27% and 86% of people attempting to come off antidepressants experienced withdrawal symptoms, and that nearly half of them described those symptoms as severe. The variation in these results may have several causes. How long people took the drugs for, and the dose they took, are two.”

Little attention has been paid to the issue of antidepressant drug withdrawal.  Drug companies have no interest in it, and psychiatrists mostly assumed quitting drugs was easy.  It was also convenient to confuse withdrawal symptoms with relapse of the original problem.  This situation seems to be changing, in the UK at least, as healthcare systems ponder the cost effects of aging antidepressant users. 

“Dr Taylor and Mark Horowitz, of University College, London, began the research that led to what has become known as the Horowitz-Taylor method. Drawing on brain images of serotonin-transporter blockage by SSRIs, they proposed a biological explanation for this difference in withdrawal symptoms. Their study found that the effect of the drug on the brain increases steeply at small doses but levels off at higher ones…In other words, reducing SSRIs more slowly at lower doses is needed to produce a gradual decline in their effect—and thus minimise withdrawal symptoms.”

If the requirement is that over time small decreases in the drug level, how does the patient accomplish that?  Pills only come in a few discrete dosage levels.  Liquid drugs could fill the need if they were available.  Some external assistance is needed by most sufferers to ease the transition.

“As things stand, doctors rarely suggest to patients that they should stop taking the drugs. ‘It’s a systems issue. We just don’t have systems to start de-prescribing,’ says Dee Mangin of McMaster University, in Canada. Such cessation is usually initiated by patients who…decide that the side-effects are no longer worth it. The sexual-dysfunction problem is one of the reasons most commonly cited, particularly when people meet a new partner. ‘There is really no way of combating the sexual side-effects other than stopping the drug,’ says Dr Turner. Another is people realising, because of the scary effects on their brain after they have accidentally missed a dose (by forgetting to order a refill, for example), that they have developed a strong physical dependency on them.”

“…the liquid formulations of antidepressants needed for the preparation of small doses are expensive—a month’s worth may cost as much as an annual supply of the pills. And not all antidepressants are available in liquid form, because there are no incentives for drug companies to produce something that will help people stop taking their drugs.”

“’Tapering strips’—prescriptions of pills that contain smaller and smaller amounts of a drug—are available in the Netherlands and have been shown to result in a 70% quit rate. But the Netherlands is an exception, and the strips are too expensive for a lot of those in other countries who try to import the Dutch versions. An alternative is to obtain tapering doses from a compounding pharmacy (a business which can measure out minuscule amounts of the pills). But that, too, is expensive—and not usually covered by health insurance. So patients are stuck.”

Too much short-term thinking has hindered a concerted effort to address antidepressant drug addiction and withdrawal effects.

“Nor do the economic incentives stack in favour of cessation. Most SSRIs are off-patent and therefore cheap. In Britain, a year’s supply of the pills may cost around £40-50 ($35-44). ‘Getting people off them doesn’t save the NHS much in terms of the cost of the drugs,’ says Dr Kendrick. ‘The problem is that when people try to come off if you get only one or two people to have a severe relapse and end up in hospital, that would cost an awful lot,’ he says. This leads to a reluctance to promote quitting.”

“This unwillingness to ante-up is, though, short-sighted. Health-care systems face a risk of there being growing numbers of ageing patients who start to experience the worst side-effects of the long-term use of antidepressants. There will be extra falls, strokes, seizures, heart problems, surgery complications and more. Pay now. Or pay double later.” 

What is startling about depression is the strength of the placebo effect, which is essentially just the power of suggestion.  This suggests that there should be other, less dangerous methods for changing peoples’ view of their lives.  In Treating Depression: It’s Free, It’s Healthy, and It Works, it was pointed out that exercise seems to work better at combating depression than at least one popular antidepressant.  Perhaps therein lies a clue.

 

  

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