Gambling and Parkinson’s Disease

An addendum to the previous post.

Today, a group of Australians taking medications for Parkinson's Disease have filed a class action suit against makers of the drugs, according to a report in the Sydney Morning Herald.

 The Australian newspaper said that "The group includes people who sustained losses of hundreds of thousands of dollars and were involved in family breakdowns as a result of compulsive gambling allegedly linked to drugs they took between 1997 and last year. Most of the claimants developed gambling addictions but a few exhibited compulsive sexual behavior such as looking at pornography on the Internet.”

The drugs involved are dopamine agonists Cabaser and Permax. An agonist binds to particular receptor sites and mimics the action of the substance that normally occupies the site.

A study published in the May issue of Archives of Neurology concluded that, “Dopamine agonist treatment in PD (Parkinson's Disease) is associated with 2- to 3.5-fold increased odds of having an ICD (impulse control disorder)."

According to the study, 13% of the patients were adversely affected by the drugs, exhibiting impulse control problems with gambling (5 percent), sexual behavior (3.5 percent), shopping (5.7 percent) and binge eating (4.3 percent).

The case is not without precedent, according to the Herald. In 2008, “a jury in Minnesota awarded $8.2 million to a man who became a compulsive gambler after using Mirapex (made by Boehringer Ingelheim) to treat his Parkinson's disease. Other lawsuits are being considered in Canada, Britain and France.”


Photo Credit: http://gamingzion.com/

Triple Play for Addicts

Why cigarettes, alcohol and gambling are such a perfect fit.

The newer views of addiction as an organic brain disorder cast strong doubt on the longstanding assumption that different kinds of people become addicted to different kinds of drugs. By 1998, the Archives of General Psychiatry had already flatly stated the reverse: “There is no definitive evidence indicating that individuals who habitually and preferentially use one substance are fundamentally different from those who use another.” This quiet but highly influential breakthrough in the addiction paradigm has paid enormous dividends ever since.

From a genetic standpoint, the implication was that an addiction to alcohol, heroin, or speed did not necessarily “breed true.” The sons and daughters of alcoholics could just as easily grow up to be heroin addicts, and vice versa, due to the same brain anomalies.

There are numerous examples at hand. Recovering alcoholics and heroin addicts tend to be notorious chain-smokers, for one. Many prominent nicotine researchers lean toward the theory that those Americans who continue to be hard-core smokers, unwilling or unable to stop, may represent a biological pool of people who are genetically prone to addiction. Alcohol researcher George Vaillant,  who directed the seminal Harvard Medical School longitudinal studies, sees it the same way: “Alcoholism is a major reason that people don’t stop smoking. Those who keep on smoking after age 50 tend to be alcoholics.” 

There you have it. Throw a lasso around America’s cigarette smokers, and you are likely to snare the lion’s share of “drug abusers” and “problem drinkers” as well. This may also explain why there is such a huge overlap between gamblers and alcoholics, and between gambling and cigarette addiction. It is no secret to anyone who has been inside a casino that a striking percentage of the patrons are also smokers and drinkers. If gambling were truly capable of producing the hallmark symptoms of addiction, we would also expect to see such manifestations as continued use despite adverse circumstances, escalating use, and various forms of self-destructive behavior. It depends on whether the dopamine/serotonin patterns produced by addiction, involving midbrain dopamine neurons with divergent connections to the frontal cortex and other forebrain regions, are the same in compulsive gamblers as in alcoholics and other addicts. Many researchers simply do not believe that the alterations in neurotransmission brought about by behaviors are as powerful as the chemical surges produced by drugs, and therefore cannot result in a state technically called addiction. Others disagree.

Nonetheless, human neurostudies continue to show intriguing dopamine patterns during gambling and certain other forms of game playing. Part of what drives the destructive gambling cycle appears to be the intense, dopamine-driven arousal produced by the anticipation of reward—the jackpot.  Recent research has focused on the part played by midbrain dopamine in the anticipation of reward, otherwise known by addicts as “waiting for the man.” In the world of gaming, it is known as the classic “gambler’s fallacy—the expectation that after a series of losses, a win is “due.” Statistics say otherwise, and gamblers certainly know all about house percentages. Yet, the expectation effects of beating those odds may produce the same anticipatory effect on a disordered metabolism as drug-related activities. A very small, speculative, and intriguing study at Duke University suggested that dopamine agonists given for Parkinson’s disease might sometimes be a catalyst for excessive gambling behaviors in elderly patients, even those who had never shown an interest in gambling before.

As for shopping and sex, even an informed guess seems premature at this point.

Photo Credit: http://www.health.com/

Life After Cigarettes: Book Review

Why Women Smoke.

Women are different from men. Well, maybe you already knew that.  But did you know that women smoke differently than men, and quit smoking differently than men?

Dr. Joseph Califano, the U.S. Secretary of Health, Education, and Welfare under President Jimmy Carter, once said that even though he gained thirty pounds when he quit cigarettes, he did not then appreciate the importance to women of the link between smoking cessation and weight gain. As Dr. Cynthia Pomerleau, formerly the director of the Nicotine Research Laboratory at the University of Michigan and now Research Professor Emerita in the Department of Psychiatry, remarks in her new book, Life After Cigarettes: “If we’d had a woman HEW Secretary at that time, and she had stopped smoking, I’m sure a thirty-pound weight gain would have grabbed her attention!”

In her book, Dr. Pomerleau makes clear that the challenges of quitting smoking are even greater for women than they are for men. She is refreshingly frank: “Face it; There are definitely some plusses to smoking. If there weren’t, you wouldn’t have done it, and neither would anyone else.”

For women, one of the primary pluses is, and has always been, weight control.  Pomerleau offers up the image of smoking ballerinas, women performing in a business where gaining two pounds can mean the loss of a job. Models, gymnasts, and ice skaters have also looked to cigarettes for help with weight control.

When women quit smoking, here are the facts of the matter: They will begin gaining weight almost the minute they quit—as much as three pounds in the first week—and will stabilize within three to six months. The average weight gain for women, writes Pomerleau, is ten pounds, with a quarter of female quitters gaining five pounds or less, and about a quarter gaining more than 15 pounds.  And the longer women smoke, the harder it is to battle the weight gain when they eventually quit.

The problem, Pomerleau discovered when screening patients for her Nicotine Research Lab, was that 75 per cent of the women who wanted to quit smoking said that they were unwilling to gain more than five pounds while doing so. 40 per cent of the women responded that they were unwilling to gain ANY pounds in pursuit of tobacco abstinence.

In an email exchange with Addiction Inbox, Professor Pomerleau was kind enough to expand on her message.  

When I asked her about reports that the dopamine D2 receptor gene has been implicated in both weight gain and smoking, she responded:

“In a laboratory study of food reward in smokers attempting to quit, Caryn Lerman and colleagues found that carriers of the DRD2 A1 minor allele exhibited significant increases in the rewarding value of food following abstinence from smoking, and that higher levels of food reward after quitting predicted a significant increase in weight by 6-month follow-up in participants receiving placebo.  Both effects were attenuated in participants receiving bupropion, leading them to conclude that bupropion’s efficacy in attenuating abstinence-induced weight gain may be attributable, in part, to decreasing food reward.  How well these findings will hold up to further scrutiny in larger samples remains to be seen.”

On smoking and bulimia: “As I’m sure you’re aware, the question of ‘self-medication’ is a complicated one, but it seems likely that some women ‘use’ nicotine to hold the symptoms of bulimia in check; when they quit, the underlying predisposition reemerges – which helps to explain why these women may be more prone to larger weight gain than other quitting smokers.” 

On smoking as a weight management tool: “Using a variety of different measures, it’s probably safe to say that around 40% of women qualify as serious weight-control smokers.  (The proportion is much lower in men.)  By the way, though findings are mixed, these women don’t necessarily fare worse than other women when they quit, even if they do gain weight; the real challenge is bringing them to the point of even considering quitting.”

And finally, when I asked Professor Pomerleau about the role of primary care physicians in promoting smoking cessation, she noted that she was “concerned about possible attempts to downplay the amount of weight quitters can expect to gain or to overstate the ease with which it can be avoided – which can backfire and lead to relapse when the needle on the scale begins to creep up.  I personally think it’s better to be realistic about the likelihood of weight gain after quitting and to concentrate on keeping it in the 5-10 pound range (approximately one unit of BMI and less than a dress size) – something that is in fact an achievable goal for most women.”

Photo Credit: http://www.mapleplaceventures.com/

X-ed Out.

Another look at MDMA and serotonin.

A study by Canada’s Centre for Addiction and Mental Health (CAMH) has confirmed earlier findings that chronic users of ecstasy (MDMA) have abnormally low levels of serotonin transporter molecules in the cerebral cortex.

While a decade of research on the effects of ecstasy on brain serotonin has been controversial and largely inconclusive, the latest study used drug hair analysis to confirm levels of MDMA in 49 users and 50 controls. An additional division was made between chronic X users who also tested positive for methamphetamine, and those who did not. Regular usage of MDMA was defined as two tablets twice a month.

The Canadian study, funded by the U.S. National Institute on Drug Abuse (NIDA) and published in the journal Brain, suggests that the serotonin surge responsible for ecstasy’s effects results in a net depletion in regular X users. That is not a new finding--but the Canadian study goes further, suggesting that the serotonin depletion is localized in one area of the brain.

“We were surprised to discover that SERT was decreased only in the cerebral cortex and not throughout the brain,” said study leader Stephen Kish in a press release, “perhaps because serotonin nerves to the cortex are longer and more susceptible to changes.”

Low serotonin transporter (SERT) levels in the cerebral cortex were found in all X users, with or without amphetamine. Dr. Kish noted that the CAMH findings replicate what Kish referred to as “newer data” from Johns Hopkins University. In 1999, a controversial serotonin study of ecstasy users at Johns Hopkins laboratory was criticized for overestimating the level of danger posed by ecstasy-induced serotonin impairments.

Okay, the finding is becoming more robust. But what does it mean? According to co-author Isabelle Boileau, a low SERT level does “not necessarily” indicate structural brain damage. “There is no way to prove whether low SERT is explained by physical loss of the entire serotonin nerve cell, or by a loss of SERT protein within an intact nerve cell.”

For his part, Dr. Kish indicated that his concerns centered on the connection between lower serotonin measurements and MDMA tolerance levels. “Most of the ecstasy users of our study complained that the first dose is always the best, but then the effects begin to decline and higher doses are needed,” he said. “The need for higher doses, possibly caused by low SERT, could well increase the risk of harm caused by this stimulant drug.” The published study concluded that “behavioural problems in some ecstasy users during abstinence might be related to serotonin transporter changes limited to cortical regions.”

However, in addition to the confounding variable of methamphetamine (see my post, “How Pure is Ecstasy?”), it remains unclear whether the SERT alterations detected in the study are transient or permanent. Moreover, the nature of the link that “might” exist between lower SERT levels and cognitive impairment in the brains of regular ecstasy users remains a subject of dispute in the drug research community, as in this earlier post.  (And just to emphasize that drugs are complicated things, a spate of promising recent research has suggested that ecstasy might be an effective option for treating people with post-traumatic stress disorder).

The CAMH, affiliated with the University of Toronto, is Canada’s largest mental health and addiction teaching hospital.

Kish, S., Lerch, J., Furukawa, Y., Tong, J., McCluskey, T., Wilkins, D., Houle, S., Meyer, J., Mundo, E., Wilson, A., Rusjan, P., Saint-Cyr, J., Guttman, M., Collins, D., Shapiro, C., Warsh, J., & Boileau, I. (2010). Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[11C]DASB and structural brain imaging study Brain DOI: 10.1093/brain/awq103

Graphics Credit: pubs/teaching/teaching4/Teaching3.html

Cannabis for Multiple Sclerosis

Nasal spray to be approved in Europe.

A cannabis-based nasal spray will receive approval later this month for marketing in the United Kingdom and Spain as a medicine for multiple sclerosis, makers of the compound announced this week.

GW Pharmaceuticals, makers of Sativex, won earlier regulatory approval for the use of Sativex in Canada in 2005. Users spray the cannabis mist under their tongues for the relief of spasticity due to M.S. It is intended primarily as an “add-on treatment for symptom improvement,” according to The Pharma Letter, in patients “who have not responded adequately to other anti-spasticity medication.”

The London Evening Standard reported that the company, which grows its marijuana in undisclosed locations in England, expects the treatment to be offered as early as June under marketing agreements with Bayer of Germany and Almirall of Spain. A Japanese pharmaceutical firm has marketing rights to Sativex in the U.S., but the drug has not garnered any significant attention or approval here.  The Evening Standard reported that marketing rights from Bayer and Almirall could add up to more than $20 million when the medicine is formally approved.

European regulatory officials stress that they still have to finalize local wording on product packaging and associated documents before final marketing approval can be granted.

GW Pharmaceuticals has been working on Sativex for more than a decade now, as a medication for  multiple sclerosis patients, as well as patients suffering from advanced cancers. Chairman Geoffrey Guy said that the company was “transitioning from a late-stage development company to a commercial pharmaceutical business with excellent growth prospects.”

Photo Credit:  http://www.medicinskmarijuana.com

Al Hubbard, the Johnny Appleseed of LSD

“The Original Capt. Trips.”

The scientists, therapists, and artists who experimented with LSD therapy in the late 1950s were not prepared for the likes of Timothy Leary, novelist Ken Kesey, poet Allen Ginsberg, and the assorted freaks, pranksters, con artists and runaways of the Woodstock Generation. Ken Kesey, in particular, delighted in stinging the Feds by insisting that it was Uncle Sam who first got him high, paying Kesey and others to take LSD, guinea pig-style, in certain government-funded research programs in Palo Alto and at Stanford University in the early 1960s.

It made a great story, and it happened to be true. However, the original chapter of the acid story began ten years earlier, when a former intelligence agent, rogue businessman, and general intellectual gadfly named Al Hubbard took his first LSD trip. Captain Alfred M. Hubbard, who has been dubbed the “Original Capt. Trips,” was part of a select cadre of World War II veterans who had been involved in creating intelligence institutions like the Office of Strategic Services and the CIA, and who had immersed themselves in cryptology and truth serums and interrogation drugs in the service of the war effort. (Thomas Pynchon caricatured some of this work in his novel, Gravity’s Rainbow.) Hubbard broke ranks with the intelligence community early on, but continued to share his clandestine stash of LSD with certain friends and acquaintances. This odd and extraordinary businessman is said to have arranged private LSD sessions in the late 1950s for scientists, captains of industry, members of the British parliament, UN representatives, prime ministers, and various artists. For a time, Al Hubbard settled in Vancouver, where he became Canada’s only legally licensed, FDA-approved importer of Sandoz LSD. In certain North American research circles, Al became a very popular man.

Hubbard is credited by various parties with being the man who put together the basics of the North American psychedelic therapy sessions and hippie acid tests to come—high doses of LSD, amplified music, strobe lights, and experiments with ESP. Along with Huxley, Hubbard came to believe that the more mystical or “transpersonal” experiences LSD sometimes afforded might hold considerable psychotherapeutic potential. With LSD provided by Hubbard, Canadians Abram Hoffer, Ross Mclean, and Humphrey Osmond pursued the idea of LSD as a treatment for alcoholism. In the U.S, research on LSD and alcoholism was undertaken by Oscar Janiger, Sanford Unger, and others on the West Coast.

Throughout this period, there were LSD clinics operating in England and Europe. European LSD therapists tended to use very low doses as an adjunct to traditional psychoanalytic techniques. But North American researchers took a different, bolder approach. When “psychedelic” therapy began to catch on in Canada and the United States, therapists typically gave patients only one or two sessions at very high doses. These early efforts were aimed at producing spontaneous breakthroughs or recoveries in alcoholics through some manner of religious epiphany or inner conversion experience. The only other quasi-medical approach of the day, the Schick Treatment Center’s brand of “aversion therapy,” was not seen to produce very compelling long-term recovery rates, and subsequently fell out of favor.

In this light, the early successes with LSD therapy, sometimes claimed to be in the 50-75 per cent range, looked noteworthy indeed. However, the design and criteria of the LSD/alcoholism studies varied so widely that it has never been possible to draw definitive conclusions about the work that was done, except to say that LSD therapy seemed to be strikingly effective for certain alcoholics. Some patients were claiming that two or three trips on LSD were worth years of conventional psychotherapy—a claim not heard again until the advent of Prozac thirty years later.

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

Photo Credit: http://www.declarepeace.org.uk/

Feel Lucky, Drunk?

Sobering stats on alcohol-impaired driving.

Somewhere just before the stages veteran drinkers sometimes refer to as “bulletproof” and “invisible” comes a stage known as, “Can I drive home drunk, and avoid arrest?”

In the small town where I live, the college kids have it lucky: They can park their cars at the afterparty, and walk, or rather weave, to their respective domiciles, leaving a trail of frustrated cops parked in squad cars, waiting for fresh meat to slide drunkenly behind the wheel.  Not much point in breathalyzing pedestrians. 

Summer is approaching, and with it, new opportunities for drunk driving. Your chances of safely driving home drunk, without arrest, are 49 out of 50, according to figures from the AAA Foundation for Public Safety. Roughly 1 in 50 drunk drivers gets arrested while driving. However, considering the stiff penalties associated with DUI and DWI-type offenses, are those odds really good enough to take the risk?

Consider a few additional numbers from the Centers for Disease Control and Prevention (CDC): The annual cost of drunk-driving crashes is somewhere in the neighborhood of $51 billion. Every day, 32 people in the United States die in crashes that involve an alcohol-impaired driver.  This results in a truly appalling number: 1 in 45, or 1 death due to drunk driving every 45 minutes--all day, every day.  Almost one-third of all traffic-related deaths in the U.S. each year. That is the true cost, the daily dice throws, caused by being drunk behind the wheel.

But there is another set of equally appalling numbers, relating to that 1 in 50 figure we started with. In 2008, over 1.4 million drivers were arrested for driving under the influence of alcohol or narcotics--less than one percent of the 159 million self-reported episodes of alcohol-impaired driving among U.S. adults each year. The CDC estimates that 2.5 million parents drive under the influence of alcohol each year. Drunk drivers involved in fatal crashes were eight times more likely to have a prior conviction for DWI than were drivers with no alcohol.

Oh yes, and here is another number you should remember: 0.08 per cent.  That is the blood-alcohol content limit in all 50 states, at this writing.  According to the CDC, fatal alcohol-related crashes have dropped by 7 per cent since the adoption of the 0.08 standard.

Photo Credit: http://letsfightalcoholism.wordpress.com/