A View From the Other Side: What Disease?

A psychiatrist takes issue with the semantics of addictive disease in SLATE.

See "Medical Misnomer: Addiction isn't a brain disease, Congress."
By Sally Satel and Scott Lilienfeld

Food Addiction

Carbohydrates on the Brain, Food Rehab in the Future

Earlier this month, Yale University hosted the first-ever conference on Food and Addiction. Dr. Nora Volkow of the National Institute on Drug Abuse told the collection of experts on nutrition, obesity and drug addiction that “commonalities in the brain’s reward mechanisms” linked compulsive eating with addictive drug use. “Impaired function of the brain dopamine system could make some people more vulnerable to compulsive eating,” Volkow said.

Moreover, animal studies and brain imaging research in humans strongly support the notion of food addiction. In particular, research has pointed toward a form of food addiction known as “carbohydrate-craving obesity.” Dr. Mark Gold, chief of addiction studies at the McKnight Institute at the University of Florida, and a well-known authority on cocaine abuse, argued that “failed diets and attempts to control overeating, preoccupation with food and eating, shame, anger, and guilt look like traditional addictions.”

Conference organizer Kelly Brownell, director of the Rudd Center for Food Policy and Obesity at Yale, conceded that “it wasn’t obesity experts who got interested in addiction, it was the addiction scientists who got interested in food.” Brownell suggested that psychologists have been slower to grasp the import of food addiction “in part because of a bias that obesity is all about failure and personal responsibility, so why look at biology?”

As Dr. Gold summed it up, “It turns out that food and drugs compete for the same reward system in the brain.”

SOURCES:

--“Yale Hosts Historic Conference on Food and Addiction.” Yale University Office of Public Affairs. July 9, 2007. http://www.yale.edu/opa/newsr/07-07-09-01.all.html

--Hellmich, Nancy. “Does food ‘addiction’ explain explosion of obesity?” USA Today, July 9, 2007.

--“Yale Hosts Historic Conference on Food Addiction.” Medical News Today. 11 July 2007. www.medicalnewstoday.com

--Hathaway, William. “Experts Chew Over Eating as Addiction.” The Hartford Courant. July 11, 2007. http://www.courant.com/news/health

European Tree Yields New Alcoholism Treatment in Early Tests

Anti-Smoking Drug Also Curbs Alcohol Craving

A drug approved last year for smoking cessation has also shown promise for use against alcoholism, researchers at the University of California, San Francisco (UCSF), announced yesterday.

Varenicline, currently marketed by Pfizer for smoking cessation under the trade name Chantix, dramatically curbed drinking in alcohol-preferring rats, according to the study, which will be published online this week by “The Proceedings of the National Academy of Sciences.”

The synthetic drug was modeled after a cytosine compound from the European Labumum tree, combined with an alkaloid from the poppy plant.

Since an estimated 85 per cent of alcoholics are also cigarette smokers, varenicline could have an immediate effect on this common dual addiction. The drug has already been approved by the Food and Drug Administration (FDA) for human use, so Pfizer is likely to be granted a speedy approval for the new indication, sources say. The drug is likely to join Antabuse (disulfiram), Revia (naltrexone), and Campral (acamprosate) as FDA-approved treatments for alcoholism.

Selena Bartlett of the UCSF-affiliated Gallo Clinic and Research Center, a co-author of the study, said that the drug works by disrupting the neuronal “reward pathway” of the brain. Specifically, the drug binds to acetylcholine receptors, a neurotransmitter involved in arousal and attention. Through a cascade effect, stimulating these receptors causes a release of dopamine, one of the primary pleasure chemicals in the brain. Varenicline prevents alcohol and nicotine from causing a release of dopamine at those sites.

“Treatments for alcoholism today are like those for schizophrenia in the ‘60s,” Bartlett said. “People don’t talk about it. There are very few treatments, and most drug companies are not interested in it.”

Bartlett said she hoped the research would spur additional studies of drugs for alcoholism. “It’s a disease. If you’ve inherited a gene variant, of if some other cause leads you to alcohol dependence, it should be treated--like any disease.”

Sources:

“Drug to curb smoking also cuts alcohol dependence.” University of California, San Francisco, News Office. 09 July 2007. http://pub.ucsf.edu/newsservices/releases/200707063/

“Need a Cigarette and a Cocktail? Just Pop a Pill Instead.” ScientificAmerican.com July 09, 2007

Fearing Medicine

By Dirk Hanson

Have Americans become afraid of their doctors?

Once upon a time, Americans went to their doctors to get pills. Doctors complained that patients believed competent medical care consisted of being handed a prescription. In the absence of that piece of paper with the unintelligible signature, a patient was apt to claim that the doctor’s visit had been a waste of time. What was the point of seeing a doctor if the doctor didn’t give you anything that would cure what ailed you?

That was then. Patients now demand that doctors and pill makers come clean about the safety of the products they offer (long overdue), and that the pills themselves be absolutely benign in their effects (utterly impossible). In ever-greater numbers, Americans are coming to fear prescription drugs. This condition, in extremis, is a phobia with a recognized set of diagnostic criteria: pharmacophobia—an abnormal fear of medicine.

Today, Americans go to their doctors to be healthy and “drug-free.” If they are taking prescription medications, their goal is to get off them. Yesterday, patients demanded pills for conditions they didn’t have, or for which pills were ineffective. Today, patients are routinely filing lawsuits, demanding to know why their doctor gave them pills. Ironically, one of the major hindrances to health care, from a doctor’s point of view, is “patient non-compliance”—sick people often don’t take their pills properly. (This may be a good place to note that I do not work for, or with, or against Big Pharma, as the drug companies are now called. I don’t work for anybody.)

The drug industry, one of the most tightly regulated industries in America, is the kind of corporate villain Americans understand. What particularly rankles many critics is that the drug companies advertise.

“Presumably,” Joseph Davis concedes in his jeremiad against drug advertising in the journal Hedgehog Review, “some percentage of those who identify their face and their feelings with those signified in the ads actually suffer from a debilitating condition. So much to the good.”

But of little significance, it seems. The central issue for Davis is: What if people who don’t need those pills are exposed to those ads? Normal people might think they need those pills—and they don’t! And very soon, as you can easily see, you’ve got trouble in River City. In the same issue of Hedgehog Review, biomedical ethics professor Leigh Turner professes similar shock, recounting with indignation “a world where a host of marketing strategies are used to package tidy, authoritative, and often profoundly misleading claims” about the safety and effectiveness of products. You can imagine how I felt when I learned that commercial advertisers were capable of doing that.

For lack of a better term, we will have to settle for calling it the real world, where soap, life insurance, housing, cars, psychiatric care, and legal advice are all marketed in misleading ways, to people who don’t always need them. And so it is with pills. However, where once patients desired this, they now resent the offer. Writing in the May 2007 issue of Harper’s, Gary Greenberg declares that “Under the agreement we’ve made—that they are doctors, that I am sick, that I must turn myself over to them so they can cure me—the medicine must be treated with the reverence due a communion wafer.”

Previously, patients wanted their communion wafers, and doctors were often accused of withholding them. Now, as Greenberg makes clear, patients fear doctors will drag them to the altar and force the holy wafers down their throats. One cannot help wondering what manner of pact Greenberg would like to arrive at with his treating physicians. His approach does not seem like a particularly promising step forward in doctor-patient relations.

Interestingly, Americans have shown little interest in a thorough examination of the adverse side effects of non-pharmaceutical approaches to health. Talk therapists and holistic practitioners of every stripe operate in a virtually regulation-free environment. Where, for example, can one find a list of common side effects associated with the practice of various forms of psychotherapy, from post-Freudian talk therapy to, say, the increasingly popular varieties of cognitive therapy? Where, I would like to know, is the list of unwanted side effects that can occur as the result of an on-air encounter with that manipulative bruiser, Dr. Phil?

Science writer Sharon Begley, in a June 18 Time column entitled “Get Shrunk at Your Own Risk,” declares: “What few patients seeking psychotherapy know is that talking can be dangerous, too—and therapists have not exactly rushed to tell them so.”

Among many other examples, Begley reminds us of the “recovered memory” therapies that tore families apart and sent innocent people to prison for the alleged sexual abuse of children. And “stress debriefing,” a method of re-experiencing traumatic events in an effort to eliminate Post Traumatic Stress Disorder, sometimes leads to increased stress and higher levels of anxiety, compared to PTSD victims who do not undergo such therapy. I’ll privilege an upset stomach and occasional loose stools from pills over that kind of deep-seated trauma any day.

Begley also cites a 2000 study of professional grief counseling which concluded that four out of ten people grieving for the death of a loved one through formal therapy would have been better off with no therapy at all. Compared to a control group, 40 per cent of mourners in professional therapy experienced increased depression and grief. (In some cases, the most benign contraindication is when the treatment doesn’t do anything at all.)

The side effects associated with talk therapies remain shrouded in mystery. “The number of people undergoing potentially risky therapies reaches into the tens of thousands,” Begley concludes. “Vioxx was yanked from the market for less.”

New World Nicotine: A Brief History

“Drinking the Smoke”

The prototypically North American contribution to the world drug trade has always been tobacco. Tobacco pipes have been found among the earliest known Aztec and Mayan ruins. Early North Americans apparently picked up the habit from their South American counterparts. Native American pipes subjected to gas chromatography show nicotine residue going back as far as 1715 B.C. “Drinking” the smoke of tobacco leaves was an established New World practice long before European contact. An early technique was to place tobacco on hot coals and inhale the smoke with a hollow bone inserted in the nose.

The addicting nature of tobacco alarmed the early missionary priests from Europe, who quickly became addicted themselves. Indeed, so enslaved to tobacco were the early priests that laws were passed to prevent smoking and the taking of snuff during Mass.

New World tobacco quickly came to the attention of Dutch and Spanish merchants, who passed the drug along to European royalty in the 17th Century. In England, American tobacco was worth its weight in silver, and American colonists fiercely resisted British efforts to interfere with its cultivation and use. Sir Francis Bacon noted that “The use of tobacco is growing greatly and conquers men with a certain secret pleasure, so that those who have once become accustomed thereto can later hardly be restrained therefrom.” (As a former smoker, I am hard pressed to imagine a better way of putting it.)

Early sea routes and trading posts were determined in part by a desired proximity to overseas tobacco plantations. The expedition routes of the great 17th and 18th Century European explorers were marked by the strewing of tobacco seeds along the way. Historians estimate that the Dutch port of Amsterdam had processed more than 12 million pounds of tobacco by the end of the 17th Century, with brisk exports to Scandinavia, Russia, Prussia, and Turkey. (Historian Simon Schama has speculated that a few enterprising merchants in the Dutch tobacco industry might have “sauced” their product with cannabis sativa from India and the Orient.)

Troubled by the rising tide of nicotine dependence among the common folk, Bavaria, Saxony, Zurich, and other European states outlawed tobacco at various times during the 17th Century. The Sultan Murad IV decreed the death penalty for smoking tobacco in Constantinople, and the first of the Romanoff czars decreed that the punishment for smoking was the slitting of the offender’s nostrils. Still, there is no evidence to suggest that any culture that has ever taken up the smoking of tobacco has ever wholly relinquished the practice voluntarily.

A century later, the demand for American tobacco was growing steadily, and the market was worldwide. Prices soared, with no discernible effect on demand. “This demand for tobacco formed the economic basis for the establishment of the first colonies in Virginia and Maryland,” according to drug researcher Ronald Siegel. Furthermore, writes Siegel, in his book “Intoxication”:

"The colonists continued to resist controls on tobacco. The tobacco industry became as American as Yankee Doodle and the Spirit of Independence…. British armies, trampling across the South, went out of their way to destroy large inventories of cured tobacco leaf, including those stored on Thomas Jefferson’s plantation. But tobacco survived to pay for the war and sustain morale."

In many ways, tobacco was the perfect American drug, distinctly suited to the robust American lifestyle of the 18th and 19th Centuries. Tobacco did not lead to debilitating visions or rapturous hallucinations—no nodding out, no sitting around wrestling with the angels. Unlike alcohol, it did not render them stuporous or generally unfit for labor. Tobacco acted, most of the time, as a mild stimulant. People could work and smoke at the same time. It picked people up; it lent itself well to the hard work of the day and the relaxation of the evening. It did not act like a psychoactive drug at all.

As with plant drugs in other times and cultures, women generally weren’t allowed to use it. Smoking tobacco was a man’s habit, a robust form of relaxation deemed inappropriate for the weaker sex. (Women in history did take snuff, and cocaine, and laudanum, and alcohol, but mostly they learned to be discreet about it, or to pass it off as doctor-prescribed medication for a host of vague ailments, which, in most cases, it was.)

Excerpted from The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009.
By Dirk Hanson

Drug Rehab in China

After two years of a nationwide “people’s war” against drug addiction in China, government authorities are claiming major accomplishments—but treatment, which is mostly compulsory, remains limited and largely ineffective, Chinese doctors say.

The Chinese surge against drugs was credited with numerous successes almost before it had begun. Zhou Yongkang, Minister of Public Security, told the official news agency Xinhua that officials had seized more than two tons of methamphetamine, and three million “head-shaking pills”--otherwise known as Ecstasy tablets.

Two years later, in June of 2007, Minister Yongang, claimed that the number of drug abusers in China had been cut from 1.16 million to 720,400 due to compulsory rehabilitation measures. “The effort has yielded remarkable results,” Yongang told the China Daily. (Other drug experts estimate the number of Chinese drug addicts to be 3 million or more.)

However, a recent paper co-authored by several Chinese physicians, published in the Journal of Substance Abuse Treatment, suggests that things are not so rosy. The report, titled, “Attitudes, Knowledge, and Perceptions of Chinese Doctors Towards Drug Abuse,” paints a dismal picture: Less than half the Chinese doctors working in drug abuse had any formal training in the treatment of drug addicts, the report found. Moreover, less than half of the treatment physicians believed that addiction was a disorder of the brain. (One cannot help wondering whether the percentage for American doctors would be any higher.)

The study could find no coherent doctrine or set of principles for drug rehabilitation being employed in China, beyond mandatory detox facilities. In the Chinese government’s White Paper on “Narcotics Control in China,” the practice of “reeducation-through-labor” is considered to be the most effective form of treatment. Another name for this form of treatment would be: prison.

There are perhaps as many as 200 voluntary drug treatment centers as well. These centers emphasize treating withdrawal symptoms, and feature more American-style group interaction and education, but observers say such centers are often used by people evading police or running from their parents.

In addition, the lack of formal support from the Chinese government has led to the closing of several such facilities after only a few months. The American origins of such treatment modalities have not helped sell such programs to government officials. Pharmaceutical treatments for craving remain unavailable in China.

SOURCES:

--Fan, Maureen. “U.S.-Style Rehabs Take Root in China as Addiction Grows.” Washington Post Foreign Service, A14, January 19, 2007.

--Yi-Lang Tang, et. al. “Attitudes, Knowledge, and Perceptions of Chinese Doctors Towards Drug Abuse.” Journal of Substance Abuse Treatment. vol. 29 no. 3. 215-220.

--“Anti-Drug Campaign Yields Result.” China Daily. June 16, 2007. http://www.china.org.cn.

--“With Prohibition Failing, China Calls for ‘People’s War’ on Drugs.” Drug War Chronicle. vol. 381. 4/8/05 http://stopthedrugwar.org

Is Marijuana Addictive?

The argument continues.

For more, see Marijuana Withdrawal.
See also Marijuana Withdrawal Revisited

Marijuana may not be a life-threatening drug, but is it an addictive one?

There is little evidence in animal models for tolerance and withdrawal, the classic determinants of addiction. For at least four decades, million of Americans have used marijuana without clear evidence of a withdrawal syndrome. Most recreational marijuana users find that too much pot in one day makes them lethargic and uncomfortable. Self-proclaimed marijuana addicts, on the other hand, report that pot energizes them, calms them down when they are nervous, or otherwise allows them to function normally. They feel lethargic and uncomfortable without it. Heavy marijuana users claim that tolerance does build. And when they withdraw from use, they report strong cravings.

Marijuana is the odd drug out. To the early researchers, it did not look like it should be addictive. Nevertheless, for some people, it is. Recently, a group of Italian researchers succeeded in demonstrating that THC releases dopamine along the reward pathway, like all other drugs of abuse. Some of the mystery of cannabis had been resolved by the end of the 1990s, after researchers had demonstrated that marijuana definitely increased dopamine activity in the ventral tegmental area. Some of the effects of pot are produced the old-fashioned way after all--through alterations along the limbic reward pathway.

By the year 2000, more than 100,000 Americans a year were seeking treatment for marijuana dependency, by some estimates.

A report prepared for Australia’s National Task Force on Cannabis put the matter straightforwardly:

There is good experimental evidence that chronic heavy cannabis users can develop tolerance to its subjective and cardiovascular effects, and there is suggestive evidence that some users may experience a withdrawal syndrome on the abrupt cessation of cannabis use. There is clinical and epidemiological evidence that some heavy cannabis users experience problems in controlling their cannabis use, and continue to use the drug despite experiencing adverse personal consequences of use. There is limited evidence in favour of a cannabis dependence syndrome analogous to the alcohol dependence syndrome. If the estimates of the community prevalence of drug dependence provided by the Epidemiologic Catchment Area Study are correct, then cannabis dependence is the most common form of dependence on illicit drugs.

While everyone was busy arguing over whether marijuana produced a classic withdrawal profile, a minority of users, commonly estimated at 10 per cent, found themselves unable to control their use of pot. Addiction to marijuana had been submerged in the welter of polyaddictions common to active addicts. The withdrawal rigors of, say, alcohol or heroin would drown out the subtler, more psychological manifestations of marijuana withdrawal.

What has emerged is a profile of marijuana withdrawal, where none existed before. The syndrome is marked by irritability, restlessness, generalized anxiety, hostility, depression, difficulty sleeping, excessive sweating, loose stools, loss of appetite, and a general “blah” feeling. Many patients complain of feeling like they have a low-grade flu, and they describe a psychological state of existential uncertainty—“inner unrest,” as one researcher calls it.

The most common marijuana withdrawal symptom is low-grade anxiety. Anxiety of this sort has a firm biochemical substrate, produced by withdrawal, craving, and detoxification from almost all drugs of abuse. It is not the kind of anxiety that can be deflected by forcibly thinking “happy thoughts,” or staying busy all the time. A peptide known as corticotrophin-releasing factor (CRF) is linked to this kind of anxiety.

Neurologists at the Scripps Research Institute in La Jolla, California, noting that anxiety is the universal keynote symptom of drug and alcohol withdrawal, started looking at the release of CRF in the amygdala. After documenting elevated CRF levels in rat brains during alcohol, heroin, and cocaine withdrawal, the researchers injected synthetic THC into 50 rats once a day for two weeks. (For better or worse, this is how many of the animal models simulate heavy, long-term pot use in humans). Then they gave the rats a THC agonist that bound to the THC receptors without activating them. The result: The rats exhibited withdrawal symptoms such as compulsive grooming and teeth chattering—the kinds of stress behaviors rats engage in when they are kicking the habit. In the end, when the scientists measured CRF levels in the amygdalas of the animals, they found three times as much CRF, compared to animal control groups.

While subtler and more drawn out, the process of kicking marijuana can now be demonstrated as a neurochemical fact. It appears that marijuana increases dopamine and serotonin levels through the intermediary activation of opiate and GABA receptors. Drugs like naloxone, which block heroin, might have a role to play in marijuana detoxification.

In the end, what surprised many observers was simply that the idea of treatment for marijuana dependence seemed to appeal to such a large number of people. The Addiction Research Foundation in Toronto has reported that even brief interventions, in the form of support group sessions, can be useful for addicted pot smokers.

--Excerpted from The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009.

addiction drugsmedical marijuana

Vaccinating Against Vices

Developing a pill or a vaccine for a specific drug addiction has long been one of the tantalizing potential rewards of addiction research. Now a company in Florida has garnered national attention, a spate of clinical trails, and a positive response from the National Institute on Drug Abuse (NIDA) with a compound called NicVAX, aimed at nicotine addiction. In addition, Celtic Pharma in Bermuda is working on a similar product for cocaine addiction.

The idea of vaccinating for addictions is not new. If you want the body to recognize a heroin molecule as a foe rather than a friend, one strategy is to attach heroin molecules to a foreign body--commonly a protein which the body ordinarily rejects--in order to switch on the body’s immune responses against the invader. The idea of a vaccine for cocaine, for example, is that the body’s immune system will crank out antibodies to the cocaine vaccination, preventing the user from getting high. A strong advantage to this approach, say NIDA researchers, is that the vaccinated compound does not enter the brain and therefore is free of neurological side effects.

Preliminary research at the University of Minnesota showed that a dose of vaccine plus booster shots markedly reduce the amount of nicotine that reaches the brain. Animal studies have shown the same effect. NicVAX, from Nabi Biopharmaceuticals, consists of nicotine molecules attached to a protein found in a species of infectious bacteria. When smokers light up, antibodies attack the protein-laden nicotine molecules, which, further encumbered by these antibodies, can no longer fit through the blood-brain barrier and allow the user to enjoy his smoke.

That, at least, is the idea. It is a difficult and expensive proposition, the closest thing to a miracle drug for addiction, but it does not specifically attack drug craving in addicted users. The idea of vaccination is that, once a drug user cannot get high on his or her drug of choice, the user will lose interest in the drug.

This assertion is somewhat speculative, in that users of the classic negative reinforcer, Antabuse, have found ways to circumvent its effects--primarily by not taking it. There remain a wealth of questions related to the effects of long-lasting antibodies. And it is sometimes possible to “swamp” the vaccine by ingesting four or five times as much cocaine or nicotine as usual.

Drugs that substantially reduce the addict’s craving may yet prove to be a more fruitful avenue of investigation. While several anti-craving medications have been approved for use by the Food and Drug Administraton (FDA), no vaccines have made it onto the approved least yet.

For more on pharmaceutical approaches to fighting drug addiction, see my website at http://www.dirkhanson.org

New Drug For Smokers

First there was Wellbutrin, an antidepressant which helped cut down on the cravings and nicotine withdrawal symptoms for many addicted smokers when it was marketed as the smoking cessation aid Zyban. In May, the Food and Drug Administration (FDA) okayed a second medication for the treatment of nicotine addiction. Chantix, the trade name for varenicline tartrate, works on the dopamine system to reduce withdrawal and craving symptoms, like Zyban. In randomized, placebo-controlled clinical studies involving more than 3,500 smokers, Chantix outperformed both placebos and Zyban. Common side effects included nausea, headache and vomiting. Two studies published in the Journal of the American Medical Association (JAMA) showed that about 22 per cent of smokers on Chantix were abstinent at the one-year mark, compared to 15 per cent for Zyban, and 9 per cent for placebos.

Zyban and Chantix are frequently used by doctors in combination with nicotine replacement therapy, such as gum or patches. Zyban was the first major success story in the burgeoning field of pharmacological treatments for addiction--fighting fire with fire.

According to the Centers of Disease Control and Prevention (CDC), more than 44 million American adults continue to smoke cigarettes, a fifth of whom suffer from smoking-related illnesses.

See more on anti-craving drugs at http://dirkhanson.org

Sources:

--”FDA Approves Novel Medication for Smoking Cessation.” U.S. Food and Drug Administration. www.fda.gov/bbs/topics/NEWS/2006/NEW1370.html. May 11, 2006.

Kotulak, Ronald. “New Drug Shows Promise in Helping Smokers Quit.” Chicago Tribune July 5 2006.