U.N. Drug Chief predicts 3rd World “Health Disaster.”

The neo-colonialism of drug dependence.

For the developed world, drug abuse is a plague, a law enforcement problem, a budget line item, a therapeutical industry.  But in the developing world, rampant drug use can be a health disaster of immense proportions. Heroin use is skyrocketing in East Africa, while cocaine abuse is increasing in West Africa. The underground synthetic drug market is booming in the Middle East and parts of Southeast Asia.

“The developing world lacks the treatment facilities and law enforcement to control drugs,” according to a recent address to the Commission on Narcotic Drugs by Antonio Maria Costa, the executive director of the United Nations Office on Drugs and Crime (UNODC). “Why condemn the Third World, already ravaged by so many tragedies, to the neo-colonialism of drug dependence?”

The Commission on Narcotic Drugs (CND) is the UN’s primary policymaking body for drug-related issues. Costa told the commission, which is meeting in Vienna this week, that inequality within and between states marginalizes poor people who lack access to treatment. Reminding the commission that “the medical use of narcotic drugs continues to be indispensible for the relief of pain and suffering,” the UNODC director said: “We must not only stop the harm caused by drugs: let’s unleash the capacity of drugs to do good.” He called on member nations to overcome the socioeconomic factors “that deny a Nigerian suffering from AIDS or a Mexican cancer patient the morphine offered to Italian or American counterparts.”

Costa’s UNODC also works with the World Health Organization (WHO) and the Joint UN Programme on HIV/AIDS (UNAIDS) to pursue universal access to drug treatment and the reduction of disease transmission due to injectable drugs.

Costa said that drug penalties and addiction treatment in some countries amount to little more than cruel and unusual punishment. Noting the millions of people, including children, who are sent to jail for drug use, Costa said: “People who use drugs, or are behind bars, have not lost their humanity or their human rights.” The director cited the Balkans, Central and West Asia, and East and West Africa as regions requiring increased assistance in matters of security and justice related to drug use.

Costa said that the UN sees drug trafficking as a growing security threat, and noted that “few issues have received as much attention as drug trafficking in the Security Council over the past few months.”

Photo Credit: http://www.unodc.org/

The Perils of Fair-Weather Cocaine

The higher the temp, the higher the death rate.

As spring approaches, cocaine users might take note of further evidence of a connection between high ambient air temperatures and accidental overdoses.

A study published recently in the journal Addiction used mortality data from the Office of the Chief Medical Examiner in New York City from 1990 to 2006 to determine the frequency of cocaine-related overdoses (itself an enterprise fraught with uncertainty and argument over listed causes of death).  The researchers cross-referenced the mortality data with temperature records from the National Oceanic and Atmospheric Association (NOAA).  

As reported in Addiction Journal, “accidental overdose deaths that were wholly or partly attributable to cocaine use rose significantly as the weekly ambient temperature passed 24 degrees Celsius [75 degrees F].”

Previous research, the authors write, had indicated that significantly higher temperatures—in the high 80s F--were required before cocaine mortality rates showed an increase. The researchers said they did not detect a corresponding rise in other types of drug overdoses during days over 75 degrees.

What is the mechanism connecting temperature to cocaine overdose? Cocaine intoxication raises core body temperature. Overheated cocaine users risk overdosing on smaller doses of the drug because their bodies are already under the strain of mild hyperthermia, or increased body temperature.

Specifically, the researchers from the University of Michigan and elsewhere found that above 75 degrees, there were 0.25 more drug overdoses per 1,000,000 residents per week for every two-degree rise in temperature, according to Addiction Journal. Applied to New York City, these numbers suggest and additional two cocaine deaths per week for every two degrees increase in average temperature over 75.

Lead author Dr. Amy Bohnert of the University of Michigan Medical School said in a press release that cocaine users are already “at a high risk of negative health outcomes and need public health attention, particularly when the weather is warm.”  During the study period, New York City had average weekly temperatures in the >24 C range roughly seven weeks per year.

The idea is quite plausible, given that ambient air temperature can affect many other metabolic processes.  Earlier investigations led to the discovery of a fairly well established diurnal AND seasonal variation for measurements of blood pressure. Researchers at Emory University data-mined 2 million  electronic records of participating patients and discovered that the odds of having high blood pressure were lowest during the morning, and generally increased throughout the day. Seasonally, high blood pressure occurred more often in winter, and was at its lowest in the summer. 

Graphics Credit: http://flatbushgardener.blogspot.com/

Bohnert, A., Prescott, M., Vlahov, D., Tardiff, K., & Galea, S. (2010). Ambient temperature and risk of death from accidental drug overdose in New York City, 1990-2006 Addiction DOI: 10.1111/j.1360-0443.2009.02887.x

Drug Abuse Coverage Leaves Out the Science

How the media covers harm reduction.

Lewis Mehl-Madrona, a graduate of the Stanford University School of Medicine, recently wrote a piece for Futurehealth.org that zeroes in on a series of highly pertinent questions about the manner is which the America media tends to cover drug policy stories. Questions like: Why is the existence of credible scientific research rarely mentioned when drug controversies are in the headlines? Why does science not matter when it comes to the coverage of drug policy issues?

Mehl-Madrona cites the example of U.S. television coverage of Vancouver’s Insite project in Canada, which provides addicts with clean needles and a supervised injection room. Such “consumption rooms” are also available in Europe, and are being tried sporadically in the U.S. (See my earlier post on drug injection sites) Here is his reaction:

“The American TV was awash with criticisms of this policy, the primary one being that it promoted drug abuse and caused people to abuse drugs even more than they otherwise would. What amazed me was the complete lack of attention to data in the American media. Substantial research has been conducted on Insite and on harm reduction models. It is known that programs like Insite reduce the spread of HIV/AIDS and of hepatitis C and reduce drug overdose. No evidence exists to support its spreading drug abuse.”

One of the primary concerns raised by the media was whether the Insite facility would encourage addiction by making injections safer and easier. Yet a reliable study in the British Medical Journal showed no substantial increase in relapse or decrease in quit rates among a group of Insite users.

Another concern was that the Insite facility would discourage drug addicts from seeking treatment. However, a study published in the New England Journal of Medicine in 2006, involving more than 1,000 users of the facility, found that “individuals who used Insite at least weekly were 1.7 times more likely to enroll in a detox program than those who visited the centre less frequently,” according to Mehl-Madrona.

Moreover, the study confirmed that onsite addiction counselors were successfully increasing the number of addicts who signed up for detox. Rather than discouraging addicts from seeking treatment, the study confirmed that Insite was “facilitating entry into detoxification services among its clients.”

“I don't have an answer for why ideology trumps scientific evidence in the United States and its media” Mehl-Madrona writes. “Why are the opinions of ordinary people in cities across the United States considered more valid than three dozen rigorous scientific studies? Is this just the American way?”

Graphics Credit: http://abortmag.com

Book Review: Thinking Simply About Addiction

Of bicycles, swimming, and drugs.

Back when I first became interested in the science of addiction, I was fascinated by an article in Parabola magazine by Dr. Richard Sandor, a Los Angeles psychiatrist with many years of experience treating alcoholics and other drug addicts. In the article, Sandor suggested that a good deal of addictive behavior could profitably be viewed as a form of dissociation. I quoted from that article in my book about addiction, and now he has published a book of his own.

Thinking Simply About Addiction: A Handbook for Recovery, focuses on the current controversy over Alcoholics Anonymous and its 12-Step variants, and takes a reasoned, thoughtful approach to the so-called spiritual aspects of recovery.

Happily, this is not another southern California feel-good self-help tome, though the author does not shy away from tweaking the neuroscience establishment for “delving deeper and deeper into the biochemistry of the alcoholic and drug-addicted brain, endless promising a ‘cure’ and yet never quite delivering the goods.”

While acknowledging that addiction is “correctly understood as a disease,” Sandor diverges a bit from the mainstream disease theory of addiction, believing that addictions are “diseases of automaticity—automatisms—developments in the central nervous system that cannot be eliminated but can be rendered dormant.”

As examples of simple automatisms, Sandor cites bicycle riding and swimming, two behaviors it is impossible to “unlearn.” Consider swimming: If, for some reason, it became extremely dangerous for you to swim (pollution, a heart condition, sharks), the problem is that “you literally cannot choose not to swim. Your only reliable choice is to stay out of the water, to become abstinent.”

Much of the confusion over addiction, the author maintains, is that “we miss the essential quality that defines addiction as a disease: Something someone has rather than something they’re doing.”

What his addicted patients frequently tell him, Sandor writes, is that “the core experience of being addicted is powerlessness, the experience of having lost control over the use of alcohol or a drug.” As one addiction expert put it, addicts “have lost the freedom to abstain.” Like other forms of rehabilitation, says Sandor, “treatment doesn’t work or not work. The patient works. It seems obvious. If the very nature of addiction is automaticity—the loss of control—then recovery is the restoration of choice, not handing choices over to someone else.”

On controlled drinking, or a return to social drinking, Sandor writes that “studies that have followed reliably diagnosed alcoholics for long enough periods of time reveal what clinicians and AAs have known for a long time: Abstinence is necessary for recovery…. If you follow true alcoholics for years, you discover that those who continue to drink get worse and those who remain abstinent don’t. Presumably, the same is true for all other addictions.”

Problem drinkers who do return to moderate drinking “were people who had had enough problems with drinking to land in treatment but who were never physically addicted and therefore didn’t have to become abstinent in order to stop the progression of the disease.”

Where does the “Higher Power” concept fit into all this? Sandor endorses the wider view taken by many psychologists and thinkers, from Gregory Bateson to C.G. Jung. In line with his theme of keeping it simple, Sandor suggests that thinking about a Higher Power may mean coming to realize that “the body’s capacity to restore itself is part of something much larger than our operations and medications… If you like, it comes from God. If you don’t like, it comes from a Higher Power, from Nature, from five billion years of the evolution of life on Earth, from the created universe, from whatever you want to call it.”

It is the simplest of simple ideas: “We all belong to something beyond ourselves.”

Graphics Credit: www.thesecondroad.org

Of Mice and Methamphetamine

Diabetes drug being tested for addiction.

It’s a mouthful: peroxisome proliferator activated receptor gamma (PPAR-gamma). 

Peroxisomes are specialized subunits inside cells that help metabolize various substances, including fatty acids and certain toxins. A blockbuster member of this drug family—Avandia—is a much disputed but immensely lucrative diabetes medicine that may cause heart failure.

(Partial Agonist Ppar Gamma Cocrystal)--------->

PPAR gamma agonists belong to a class of drugs known as thiazolidinediones. Clinical research has pointed toward additional therapeutic applications for thiazolidinediones in the areas of inflammation and cancer. The only approved use for thiazolidinediones is in the treatment of diabetes, but the drug class has also been studied for treatment of polycystic ovary syndrome, psoriasis, autism—and now drug addictions. A PPAR compound will soon undergo testing under the auspices of the Omeros Corporation, with funding from the National Institute on Drug Abuse (NIDA).

Omeros says it has developed a novel drug “for the prevention and treatment of addiction to substances of abuse, such as opioids nicotine and alcohol, as well as other compulsive behaviors, including eating disorders.” Phase 2 clinical studies on opiate addiction by Dr. Sandra D. Comer and associates at the New York State Psychiatric Institute will begin soon, according to an Omeros press release.

Such claims add up to a tall order for any anti-craving drug. In fact, no drug currently exists for the treatment of so wide a spectrum of addictive disorders. Nonetheless, Omeros claims to have demonstrated a previously unknown link between a variant of this family of diabetes medications and addiction.

The heart problems linked to the PPAR marketed as Avandia may be a special case. According to an article by Gardiner Harris in the New York Times, based on government reports obtained by the newspaper: “If every diabetic now taking Avandia were instead given a similar pill named Actos, about 500 heart attacks and 300 cases of heart failure would be averted every month because Avandia can hurt the heart. Avandia, intended to treat Type 2 diabetes, is known as rosiglitazone and was linked to 304 deaths during the third quarter of 2009.” Actos, another thiazolidinedione, has not been linked to any heart trouble.

 GlaxoSmithKline is disputing the findings. A number of other pharmaceutical houses—AstraZeneca, and Eli Lilly among them—discontinued their first generation PPAR drugs. The derivative marketed as Avandia is not the compound under study by Omeros.

There is little clinical evidence to bolster the PPAR theory. A recent Spanish study suggested the possibility that PPAR gene variants may be associated with higher alcohol consumption in a small sampling of Mediterranean drinkers.

The most comprehensive study may be a 2007 paper in Neuropsychopharmacology by Takehiko and coworkers, demonstrating that PPARs can have an effect on behavioral sensitization to methamphetamine in mice.

Behavioral sensitization is the name for the progressive increase in meth-driven locomotor activity over time. The researchers found that a PPAR variant “plays an inhibitory role in the expression” of sensitization to methamphetamine. The action takes place in the brain’s nucleus accumbens, where repeated hits of meth cause an increase in PPAR expression, according to the researchers: “These results indicate that [an isotope of PPAR] in the reward system is involved in behavioral sensitization to METH.”

What is the mechanism of action? The researchers speculate that upregulation and activation of PPAR in the meth-crazy mice may be due in part to an inflammatory response. PPAR, in theory, exerts anti-inflammatory activity in brain cells.  And psychostimulants, according to the researchers, “upregulate the expression of target genes via activation of inflammatory-responsive transcriptional factors.”

Maeda, T., Kiguchi, N., Fukazawa, Y., Yamamoto, A., Ozaki, M., & Kishioka, S. (2006). Peroxisome Proliferator-Activated Receptor Gamma Activation Relieves Expression of Behavioral Sensitization to Methamphetamine in Mice Neuropsychopharmacology, 32 (5), 1133-1140 DOI: 10.1038/sj.npp.1301213

Graphics Credit: http://www.prostaglandinresearch.com

Alcohol: The Genetic Puzzle (3 of 3)

What about other drugs?

Do the same genetic relationships demonstrated in the alcohol adoption studies prove true for other drugs? Was it conceivable that heroin addiction or cigarette smoking could be traits (disorders, really) that men and women inherited?

“There have been a number of animal studies showing genetic differences in sensitivity to nicotine,” said Dr. Neal Benowitz of the Clinical Pharmacology Unit at San Francisco General Hospital, one of the nation’s premier nicotine research centers. And Professor Ovide Pomerleau, the Director of Behavioral Medicine at the University of Michigan Medical School, who collaborated with Cloninger’s group on genetic studies of nicotine and alcohol, told me: “Some people are drawn to smoking, and some people are not. Everybody pretty much goes through the same kind of peer pressures, the same kind of socialization pressures, and then you have some people who emerge as smokers, and some people who don’t. Some people who start smoking give it up easily, and there are others who can’t. Well, why? My answer is that I think there are innate differences in susceptibility.” 

The Cadoret group looked into the question and reported in the Archives of General Psychiatry that alcohol problems in biological relatives appeared to correlate highly with drug abuse in siblings. “Some theorists have suggested that multiple addictions to a wide variety of substances constitute evidence against a genetic interpretation of addiction,” wrote Cadoret. “The present data appear to refute that position, suggesting instead some underlying biochemical foundation involved in all of the substances abused….” 

Dr. Janice Keller Phelps, the drug treatment specialist from Seattle, maintained that “a large number of addicted people I have treated over the years had strong family histories of addiction. Time and again I encountered heroin addicts, cocaine addicts, or speed addicts with one or both parents addicted to alcohol, for example, or with one or more brothers or sisters also addicted—though not necessarily to the same drug. It is known and acknowledged that many alcoholics have one or more alcoholic parents; the large number of children of alcoholics who are not alcoholic but instead are addicted to other substances, however, is not so well recognized.”

In many ways, the genetic findings by Goodwin, Cloninger, and others were as far from the old problems-in-living approach, the Freudian approach, as it was possible to get. As Dr. Edward Sellers, who directed the psychopharmacological research program at the University of Toronto’s Addiction Research Foundation during the 1990s, explained to me: “One simplified way of looking at it is that every cell, every hormone, every membrane in the body has got genetic underpinnings, and while many of the genetic underpinnings are similar in people, in fact there are also huge differences. So on one level, the fact that there is a genetic component to addiction is not very surprising. What is surprising is that you could ever have it show up in a dominant enough way to be something that might be useful in anticipating risk.”

If there existed a set of genes that predisposed people to alcoholism, and possibly other addictions, then these genes had to control the expression of something specific. That’s what genes did. 

However, addiction researchers could not even agree on the matter of where they should be looking for such physical evidence of genetic difference. In the brain? Among the digestive enzymes? Blood platelets? A gene, or a set of genes, coding for…what? Substance H? Production of certain neurotransmitters? What was it they were supposed to be looking for?

What set of genes coded for happiness?

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008.

Graphics Credit: http://www.drugabuse.gov

Alcoholism: The Genetic Puzzle (Cont.)

Type 1s and Type 2s

The alcoholics in the Cloninger-Bohman studies fell into two distinct categories. Type 1, the more common form, developed gradually, later in life, and did not necessarily require structured intervention. Type 1 alcoholic men did not always experience the dramatic declines in health and personal circumstances so characteristic of acute alcoholism. These people sometimes straddled the line between alcoholism and “problem drinking.” For Type 1 alcoholics, the genetic inheritance was more like a latent tendency; a propensity that did not automatically show up in every case. It was as if some environmental triggering mechanism, some outside set of circumstances, was required for the inheritance to express itself.

Type 2 alcoholism was a different story altogether. It was bad business from the start; a very unlucky roll of the dice indeed. Type 2 alcoholics were in serious trouble starting with their first taste of liquor during adolescence. Their condition worsened with horrifying speed. They frequently had a history of violent and antisocial behavior, and they often ended up in prison. They were rarely able to hold down normal jobs or sustain workable marriages for long. Type 2s, also known as “familial” or “violent” alcoholics, were even more likely to have had an alcoholic parent. They were, in short, severely addicted to alcohol.

Almost 20 per cent of children born to Type 2 alcoholics became alcoholics themselves. At first glance, this rate does not seem particularly high. The numbers are not as neat and clean as classic Mendelian genetics would have it. But recessive traits are like that. In the case of a recessive gene, inheritance rates are much lower. “Most behaviors,” writes Tabitha Powledge in Bioscience, “do not wend their way through generations in the manner of Mendel’s smooth and wrinkled peas.”  Viewed in that light, 20 per cent is a very high number, and the Stockholm Adoption Study constituted strong evidence for the inheritability of the condition known as alcoholism.

Goodwin’s Danish studies and the Cloninger-Bohman studies were not the only evidence for a genetic connection in at least some cases of alcoholism. In the United States, Remi Cadoret and a team at the University of Iowa studied Iowa adoptees, and came up with similar results. In fact, more than a dozen major studies of twins pointed to the same conclusion:  In alcoholic families, there is a marked difference in alcoholism rates when identical twins (who share the same genes) are compared with fraternal twins (whose genetic makeup differs). If one identical twin is alcoholic, the likelihood that the other identical twin is also alcoholic turns out to be nearly twice as high as it is with fraternal twins. Alcoholism begets alcoholism, even when the alcoholic parent is nowhere on the scene.

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008.

Graphics Credit: http://brainlink.org/