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Articles and health studies about addiction and alcoholism, including the most recent scientific and medical findings.
Prohibition and the “tobacco control endgame.”
Despite all our efforts in recent years to reduce the percentage of Americans who smoke cigarettes—currently about one in five—the idea of full-blown cigarette prohibition has not gained much traction. That may be changing, as prominent nicotine researchers and public police officials start thinking about what is widely referred to as the “tobacco control endgame.”
Considering the new regulatory powers given the FDA under the terms of the Tobacco Control Act of 2009, as a commentary in Tobacco Control framed it, “will the government be a facilitator or barrier to the effective implementation of strategies designed to achieve this public health goal?”
Two newer approaches have gained some traction in the research community: Reduce the level of nicotine in cigarette products (the FDA is prohibited by law from reducing nicotine content to zero), and continuing to emphasize the non-combustible forms. Plus, everybody pretty much agrees on higher prices.
Here are the six arguments for going all the way:
1) Death. Six million of them a year, worldwide, a number that will grow before it starts shrinking. A billion deaths this century, compared to 100 million in the 20th Century. Robert Proctor, author of The Golden Holocaust and a professor of history at Stanford, whose six arguments these are, calls the cigarette “the deadliest object in the history of human civilization.” So there’s that.
2) Other product defects. The cigarette is defective, Proctor writes in defense of his six arguments in Tobacco Control, because it is “not just dangerous but unreasonably dangerous, killing half its long-term users.” Indeed, it is hard to imagine the FDA green-lighting a drug product like that today. In addition, Proctor claims cigarettes are defective because the tobacco has been altered by flue curing to make it far more inhalable than would otherwise be the case. “The world’s present epidemic of lung cancer is almost entirely due to the use of low pH flue-cured tobacco in cigarettes, an industry-wide practice that could be reversed at any time.”
3) Financial burdens. These can be reckoned principally in terms of the costs of treating smoking-related illnesses. This, in turn, leads to diminished labor productivity, especially in the developing world, a process that “in many parts of the world makes the poor even poorer,” Proctor observes.
4) Big Tobacco’s impact on science. By sponsoring shoddy and distracting research, by publishing “decoy” findings and by otherwise confusing and corrupting scientific discourse on the cigarette question in the advertising-dependent popular media. The tobacco industry has proved to everyone’s satisfaction that it can put politicians and regulators under intense pressure to see things its way. Not to mention other institutions that have been “bullied, corrupted or exploited,” according to Proctor: The AMA, The American Law Institute, sports organizations, Hollywood, the military, and the U.S. Congress, for starters. (Until 2011, American submarines were not smoke-free.)
5) Environmental harms. More than you might think falls into this category: Deforestation, pesticide use, loss of savannah woodlands for charcoal used in flue curing, fossil fuels for curing and transport, fires caused by burning cigarettes, etc.
6) Smokers want to quit. Smoking is not a recreational drug, as Proctor takes pains to point out. Most smokers hate it and wish they could quit. This makes cigarettes different from alcohol or marijuana, Proctor insists. He quotes a Canadian tobacco executive, who said that smoking isn’t like drinking; it’s more like being an alcoholic. This rings true to for the majority of addicted smokers I know, and was certainly true of me when I was a smoker.
So there it is, the case for tobacco prohibition. But hasn’t all this prohibition business been tried and found wanting? We know the results of drug and alcohol prohibition, whatever their rationales: Smuggling, organized crime, increased law enforcement, more money. This argument, says Proctor, has been central to the cigarette industry since forever: “Bans are ridiculed as impractical or tyrannical. (First they come for your cigarettes…)”
Proctor’s response is that smuggling is already common, and people should be free to grow tobacco for their personal use. He advocates a ban on sales, not possession.
There are at least two major obstacles to cigarette prohibition. First, an enormous amount of tax revenue is generated by the production and sale of cigarettes. And the troubling question of a steep rise in black marketeering goes largely ignored or unaddressed. In the same special issue of Tobacco Control, Peter Reuter has sobering thoughts on that front: “Cigarette black markets are commonplace in high tax jurisdictions. For example, estimates are that contraband cigarettes now account for 20-30% of the Canadian market, which has restrained government enthusiasm for raising taxes further. All the proposed ‘endgame’ proposals for shrinking cigarette prevalence toward zero run the risk of creating black markets.”
In the end, Proctor argues that the cigarette industry itself has repeatedly promised to quit the business if its products where ever found to be profoundly harmful to consumers. As recently as 1997, Philip Morris CEO Geoffrey Bible swore under oath that if cigarettes were found to cause cancer “I’d probably… shut it down instantly to get a better hold on things.” Incredible statements like this by company executives go back to the 1950s. Perhaps it’s time to let them stop lying. “The cigarette, as presently constituted,” writes Proctor, “is simply too dangerous—and destructive and unloved—to be sold.”
Proctor R.N. (2013). Why ban the sale of cigarettes? The case for abolition, Tobacco Control, 22 (Supplement 1) i27-i30. DOI: 10.1136/tobaccocontrol-2012-050811
Photo: AAP/April Fonti
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Proctor R. N. (2013) Why ban the sale of cigarettes? The case for abolition. Tobacco Control, 22(Supplement 1). DOI: 10.1136/tobaccocontrol-2012-050811
If Valium makes you groggy, and Ambien makes you sleepwalk…
A compound that blocks a brain receptor you probably have never heard of may hold the key to the next generation of sleeping pills—and there is always a next generation of sleeping pills.
A new class of hypnotic compounds that serve as antagonists for the neurotransmitter orexin may combat insomnia without the “confusional arousals” that have come to plague some users of zolpidem, otherwise known as Ambien. Sleepwalking, sleep driving, and sleep sex are common among the reports. Orexin is involved in central nervous system arousal. So-called DORAs, or dual orexin receptor antagonists, discovered in 1998, are being seen as potential therapies for insomnia, without the daytime drowsiness and rebound insomnia typical of existing treatments. The sleep disorder narcolepsy, which is in many ways the exact opposite of insomnia, is caused by “an autoimmune attack against neurons that express orexin,” according to Emmanuel Mignot of Stanford’s Center for Sleep Sciences, in an article for Science magazine.
If these drugs are already being thought of as potential insomnia therapies, their addiction potential will have to be much lower than that of earlier generations of sleep medications. But that just might be the case, since DORA-style drugs don’t appear to promote sleep by inhibiting brain activity through neurotransmitter systems for GABA, as most existing treatments do. A study last month in Science Translational Medicine by J.M. Uslaner and coworkers asserted that DORA-type drugs caused less cognition and memory impairment in rats than Valium or Ambien, and are effective at lower doses. With drugs that modulate the orexin system, the hope is that there would be less rebound insomnia, less memory loss, less addiction, and less weird wandering around like a zombie in the middle of the night.
The search for safer sleep drugs was recently given a shot in the arm by a disturbing report from the U.S. Substance Abuse & Mental Health Services Administration (SAMHSA). Emergency room visits caused by Ambien more than doubled from 2005 to 2010, and patients 45 years and up accounted for 74% of adverse zolpidem reactions. Overall, male ER visits went up by 144%, whereas female ER visits went up almost twice as much. Overall, women made up two-thirds of all Ambien-related emergency visits—a bald fact that led the Food & Drug Administration (FDA) in January 2013 to cut the recommended dose for females in half. Lower doses were also recommended for men as well.
But a closer look at the report shows the typical confusion of polydrug use: 50% of emergency department visits for Ambien involved its use in combination with other drugs. And in 37% of cases, Ambien was used specifically in combination with other central nervous system depressants. “Although short-term medications can help patients,” SAMSHA Administrator Pamela Hyde said in a prepared statement, “it is exceedingly important that they be carefully used and monitored.”
A new class of medications based on orexin-active drugs would follow three earlier generations of sleeping pills. And each new generation of sleeping pills seems to bring its own history of unintended consequences.
In the beginning, there was meprobamate, the postwar tranquilizer known as Miltown. In additional, powerful barbiturates like phenobarbital were marketed as miracle drugs for the anxious insomniac. By the 1950s, it had become clear that these drugs were seriously addictive, and dangerous in overdose. Emmanuel Mignot noted that in high doses, barbiturates “lead to pulmonary arrest and death, outcomes that gained further notoriety with the deaths of celebrities Marilyn Monroe and Jimi Hendrix.” Barbiturates do their work by activating chloride channel receptors for the inhibitory neurotransmitter GABA. In addition, strong sedatives were increasingly being used on psychotic patients in the 1950s, and found their way into the treatment of insomnia.
The continued promise of a safe and effective hypnotic for insomnia drove research that led to the development of the first benzodiazepines, and eventually to Valium. The benzodiazepines like Valium were safer in overdose, came in a bewildering variety of flavors, and found widespread use for sleep induction—but also as anticonvulsants, anti-anxiety agents, and muscle relaxers. The benzos bound to GABA receptor sites just like the barbiturates, but the effects were less extensive. Still, it was not long before Valium, another “perfect” drug, showed it’s adverse side, in the form of sedation, memory problems, and addiction.
Then, in 2007 came the 3rd generation, in the form of the now wildly popular “Z-drugs”—zolpidem, (Ambien) zopiclone (used overseas), and zaleplon (Sonata). And again, the side effect profiles looked better in testing, the effective dose was lower, and the binding site—GABA again—looked like the right place to bring on slower brain activity and more inclination toward sleep without the “knockout effect” of earlier barbiturates and benzos. These drugs are now the default treatment for insomnia. But over time, predictably, problems revealed themselves: “Occasional problems with dependence, tolerance, and ‘confusional arousals’ are still reported with Z-drugs…. And viewed with some suspicion by doctors and patients,” writes Mignot.
Put simply, any sleep treatment that relies on the broad-brush inhibition of GABA will likely produce a range of unwelcome side effects. There are only about 70,000 orexin-producing neurons in the hypothalamus, researchers have found. But this small band of neurons has projections to histamine systems, as well as “the adrenergic locus coeruleus, and various cholinergic and aminergic cell groups,” as Mignot sums up the research. “Blocking orexin may thus be closer to treating the underlying issue of excess alertness in insomnia compared to promoting sleep by inhibiting brain activity.”
That’s the idea, at least. And it may represent a change in thinking. Researchers are no longer looking for a better knockout drug by bludgeoning the brain into inactivity. Instead, they are looking for ways to combat hyper-alertness as a key component of insomnia.
Uslaner J.M., Tye S.J., Eddins D.M., Wang X., Fox S.V., Savitz A.T., Binns J., Cannon C.E., Garson S.L. & Yao L. & (2013). Orexin Receptor Antagonists Differ from Standard Sleep Drugs by Promoting Sleep at Doses That Do Not Disrupt Cognition, Science Translational Medicine, 5 (179) 179ra44-179ra44. DOI: 10.1126/scitranslmed.3005213
Photo Credit: F Delventhal under license from Creative Commons.
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Uslaner J. M., Tye S. J., Eddins D. M., Wang X., Fox S. V., Savitz A. T., Binns J., Cannon C. E., Garson S. L., & Yao L. (2013) Orexin Receptor Antagonists Differ from Standard Sleep Drugs by Promoting Sleep at Doses That Do Not Disrupt Cognition. Science Translational Medicine, 5(179), 179-179. DOI: 10.1126/scitranslmed.3005213
Study says laser light can turn cocaine addiction on and off in rats.
Francis Collins, the director of the National Institutes of Health (NIH), had one word for it: “Wow.”
Writing in the director’s blog at the online NIH site, Collins said that a team of researchers from NIH and UC San Francisco had succeeded in delivering “harmless pulses of laser light to the brains of cocaine-addicted rats, blocking their desire for the narcotic.”
Wow, indeed. It didn’t take long for the science fiction technology of optogenetics to make itself felt in addiction studies. The idea of using targeted laser light to strengthen or weaken signals along neural pathways has proven surprisingly robust. The study by the NIH and the University of California at San Francisco, published in Nature, showed that lab rats engineered to carry light-activated neurons in the prefrontal cortex could be deterred from seeking cocaine. Conversely, laser light used in a way that reduced signaling in this part of the brain led previously sober rats to develop a taste for the drug. As Collins described the work:
The researchers studied rats that were chronically addicted to cocaine. Their need for the drug was so strong that they would ignore electric shocks in order to get a hit. But when those same rats received the laser light pulses, the light activated the prelimbic cortex, causing electrical activity in that brain region to surge. Remarkably, the rat’s fear of the foot shock reappeared, and assisted in deterring cocaine seeking.
All this light zapping took place in a brain region known as the prelimbic cortex. In their paper, Billy T. Chen and coworkers said that they “targeted deep-layer pyramidal prelimbic cortex neurons because they project to brain structures implicated in drug-seeking behavior, including the nucleus accumbens, dorsal striatum and amygdala.” These three subcortical regions are rich in dopamine receptors. In rats that had been challenged with foot shocks before being offered cocaine, “optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition significantly increased compulsive cocaine seeking.”
What this demonstrates is that similar regions in the human prefrontal cortex, known to regulate such actions as decision-making and inhibitory response control, may be “compromised” in addicted people. This abnormally diminished excitability in turn “impairs inhibitory control over compulsive drug seeking…. We speculate that crossing a critical threshold of prelimbic cortex hypoactivity promotes compulsive behaviors”
This all sounds vaguely unsettling; sort of a cross between phrenology and lobotomy. But it is no such thing, and the study authors believe that stimulation of the prelimbic cortex “might be clinically efficacious against compulsive seeking, with few side effects on non-compulsive reward-related behaviors in addicts.” For now, the researchers confess that they don’t know whether the reduction in cocaine seeking is caused by altered emotional conditioning, or pure cognitive processing.
Actually, nobody expects optogenetics to be used in this way with humans. The thinking is that transcranial magnetic stimulation, the controversial technique that employs noninvasive electromagnetic stimulation at various points on the scalp to alter brain behavior, would be used in place of invasive zaps with lasers. Expect to hear about clinical trials to test this theory in the near future. David Shurtleff, acting deputy director at the National Institute on Drug Abuse (NIDA), said in a prepared statement that the research “advances our understanding of how the recruitment, activation and the interaction among brain circuits can either restrain or increase motivation to take drugs.”
Chen B.T., Yau H.J., Hatch C., Kusumoto-Yoshida I., Cho S.L., Hopf F.W. & Bonci A. (2013). Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking, Nature, 496 (7445) 359-362. DOI: 10.1038/nature12024
Photo credit: Billy Chen and Antonello Bonci
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Chen Billy T., Yau Hau-Jie, Hatch Christina, Kusumoto-Yoshida Ikue, Cho Saemi L., Hopf F. Woodward, & Bonci Antonello. (2013) Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature, 496(7445), 359-362. DOI: 10.1038/nature12024
Heavy tokers may be at higher risk, but alcohol is the hidden confounder.
Young people don’t suffer from strokes, as a rule. And when they do, at least half the time there is no obvious cardiovascular explanation. So it’s not surprising that drugs are often invoked as the culprit.
A New Zealand study earlier this year once again raised the specter of a possible link between stroke and marijuana smoking. As reported by Maia Szalavitz at Time Healthland, the confounding issue, as is typical of such studies, is the coexisting use of other drugs, like alcohol and cigarettes. As Szalavitz writes:
The stroke study, which incorporated preliminary data, is the first trial of its kind to study a possible connection between marijuana use and stroke. It included 160 patients aged 18 to 55 who had suffered a stroke connected to a blood clot in the brain, and who agreed to have their urine tested for marijuana within 72 hours of the stroke. These results were compared to those from 160 controls who had not had a stroke but came to the hospital for other reasons. They were matched on age, gender and ethnic background, all of which can also affect the risk for this type of stroke. About 16% of the stroke patients showed traces of marijuana in their urine, compared to 8% of those in the control group, suggesting a doubling of the risk of stroke.
However, because of nicotine and other confounding variables, that study was considered inconclusive. In an earlier study published in Stroke, the journal of the American Heart Association, Valerie Wolff and colleagues from the University of Strasbourg in France searched the medical literature and found 59 cases of stroke in which cannabis could be considered a cardiovascular risk factor. The investigators used only cases that had been confirmed by neuroimaging. The researchers focused on cases where a stroke had occurred while smoking marijuana, or within a half hour after the last joint or bong hit.
But proving a cause and effect relationship is tricky. Assuming, for now, that all of the strokes in question were not caused or compounded by alcohol or drugs other than marijuana, the French scientists postulated several mechanisms that could conceivably account for a cannabis-related ischemic stroke (a stroke caused by obstruction of a blood vessel). These include orthostatic hypotension, altered cerebral vasomotor function, major swings in blood pressure, and cardiac arrhythmias. However, the only solid commonality in cannabis-related strokes was that the users were more likely to be heavy smokers.
In the 50 strokes the researchers were able to confirm by cerebral imaging, the patterns in some patients were similar to those observed in a syndrome called reversible cerebral vasoconstriction syndrome (RCVS). RCVS is marked by severe headaches, strokes, and brain edema, but symptoms typically resolve in a few months. “Reversibility of the vasoconstriction within 12 weeks is a key point of this syndrome,” the authors write. “The long duration of stenosis [blockage] argues in favor of a drug-induced immunoallergic vasculitis rather than vasospasm. Our point of view is that this disorder may be considered as a variant of RCVS,” rather than as a garden-variety ischemic stroke triggered by excessive use of cannabis.
According to the French study, “The most frequently presented characteristics of cannabis users who experienced a stroke are young male chronic tobacco and cannabis abusers who have had an unusual high consumption of cannabis and alcohol before stroke.” The most convincing mechanism to explain ischemic strokes in young people, the researchers say, is “reversible cerebral angiopathy involving several arteries, associated with cannabis consumption in association with tobacco and alcohol use.”
And there you have it. Smoke weed, and you appear to have a slight risk of suffering stroke, which, under age 50, is an extremely uncommon medical event. Add tobacco, and the stroke risk goes up. Add alcohol, and the stroke risk ratchets even higher. By itself, marijuana appears to be a minor factor in strokes—but it appears likely that pot is indeed the culprit at least some of the time.
“Cannabis-related stroke is not a myth,” the scientists conclude, “and a likely mechanism of stroke in most cannabis users is the presence of reversible multifocal intracranial stenosis (MIS) induced by this drug. The reality of the relationship between cannabis and stroke is, however, complex, because other confounding factors have to be considered (ie, lifestyle and genetic factors).”
Wolff V., Armspach J.P., Lauer V., Rouyer O., Bataillard M., Marescaux C. & Geny B. (2013). Cannabis-related Stroke: Myth or Reality?, Stroke, 44 (2) 558-563. DOI: 10.1161/STROKEAHA.112.671347
Graphics Credit: http://www.strokegenomics.org/
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Color coding allows smokers to easily identify their former brands.
The tobacco industry has once again made a mockery of the Food and Drug Administration’s attempts to ban ‘light” cigarettes from the marketplace, by simply eliminated the objectionable wording and substituting an easily-decoded color scheme. In a brochure prepared for cigarette retailers marked “For trade use only: not to be shown or distributed to customers,” tobacco giant Philip Morris wrote that “some cigarettes and smokeless packaging is changing, but the product remains the same.”
Research done at Harvard demonstrates "the continued attempts of the industry to avoid reasonable regulation of tobacco products,” said Hillel Alpert, co-author of a new study on light cigarettes, in a prepared statement. The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 highlights the banning of light cigarettes as a critical mission, since cigarettes marketed in this way are in fact no safer than regular cigarettes. What makes a cigarette Light or Ultra-light is a series of tiny holes drilled through the filter (See earlier post). This “filter ventilation” was calibrated to the descriptors: Ultra-lights had more holes drilled in the filter than Lights. Studies have demonstrated conclusively that such filter schemes do not make smoking safer or cut down on related diseases. A 2001 report from the National Cancer Institute documented how smokers were compensating for the ventilation holes by smoking more cigarettes, smoking them more intensely, or by blocking the filter holes with fingers or lips.
In a study for Tobacco Control, Gregory Connolly and Hillel Alpert of the Harvard School of Public Health documented the process. In 2010, Philip Morris sent manuals to retailers detailing how they were to deal with the new sales situation. Philip Morris made clear that “current pack descriptors such as light, ultra-light and mild will be removed from all packages.” All well and good. However, the Philip Morris material also specified how a series of new package names were to be doled out. Marlboro Light became Marlboro Gold. Marlboro Mild morphed into Marlboro Blue. And Marlboro Ultra-light reemerged as Marlboro Silver.
When the researchers commissioned a large public survey to document the state of affairs one year after the official “light” ban, they found that “88%-91% of smokers found it either ‘somewhat easy’ or ‘very easy’ to identify their usual brand of cigarettes by the banned descriptor names, Lights, Mediums or Ultra-Lights.” Sales figures for these brands in the first two quarters of 2010 were essentially unchanged, the authors report. They conclude that “the majority of smokers of brands in all categories correctly identified their brands’ pack color.”
The lesson here may well be that countries like Australia and the UK are on the right track: Plain packaging may be best. If lawmakers allow “misleading numbers, the use of colors, imagery, brand extensions, and other devices that contribute to deception” in place of words, nothing has really changed. “The findings of the present research strongly suggest that tobacco manufacturers have evaded one of the most important provisions of the FSPTCA for protecting the public health from the leading cause of preventable death and disease,” the authors conclude.
In a press release, co-author Gregory Connolly, director of the Center for Global Tobacco Control at Harvard, explained that the industry “was found guilty by a federal court in 2006 for deceptively promoting ‘light’ cigarettes as safer after countless smokers who switched to lights died prematurely, thinking they had reduced their health risks.”
Connolly G.N. & Alpert H.R. (2013). Has the tobacco industry evaded the FDA's ban on 'Light' cigarette descriptors?, Tobacco Control, PMID: 23485704
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Connolly Gregory N, & Alpert Hillel R. (2013) Has the tobacco industry evaded the FDA's ban on 'Light' cigarette descriptors?. Tobacco control. PMID: 23485704
Caffeinated plants provide an unforgettable experience.
Honeybees rewarded with caffeine remember the smell of specific flowers longer than bees given only sucrose, according to a study published in Science. “By using a drug to enhance memories of reward,” the study says, “plants secure pollinator fidelity and improve reproductive success.”
Many drugs used by humans come from plants. But what role do the drugs play for the plants themselves? Frequently, they play the role of toxic avenger, providing a chemical defense against attacks by herbivores. But in smaller doses, they often have pharmacological effects on mammals. The researchers looked at two genera of caffeine-producing plants—Coffea and Citrus. “If caffeine confers a selective advantage when these pants interact with pollinators,” the investigators reasoned, “we might expect it to be commonly encountered in nectar.” And it was. Caffeine at very low doses was measured in the nectar of several of the caffeine-producing plant species, including several Coffea species, as well as some citrus nectars—grapefruit, lemons, and oranges among them.
Next, the researchers wanted to find out if the caffeine-laced nectar could affect learning and memory in pollinating bees. They trained individual honeybees to associate various floral scents with sucrose containing various concentrations of caffeine. This pairing of odor and reward, with high-concentration sucrose as the control, demonstrated that low doses of caffeine had almost no effect on the rate of honeybee learning—but a profound effect on long-term memory. Three times as many caffeinated bees remembered the conditioned floral scent 24 hours later, “and responded as if it predicted reward.” Twice as many bees remembered the scent at the 72-hour mark.
What’s the trick? Caffeine’s ability to influence mammalian behavior is due to its action as an adenosine receptor antagonist. “In the hippocampal region,” the authors write, “inhibition of adenosine receptors by caffeine induces long-term potentiation, a key mechanism of memory formation." The Kenyon cells in mushroom bodies of the insect brain, which showed “increased excitability” under the influence of caffeine, are similar in function to hippocampal neurons, they write. “Remembering floral traits is difficult for bees to perform at a fast pace as they fly from flower to flower and we have found that caffeine helps the bee remember where the flowers are,” said Geraldine Wright of the UK’s Newcastle University, who was lead author on the study. “So, caffeine in nectar is likely to improve the bee’s foraging prowess while providing the plant with a more faithful pollinator.”
It is an interesting balancing act by nature: Too much caffeine makes the nectar toxic and repellent to honeybees. Too little, and there is no behavioral effect on bee memory. “This implies that pollinators drive selection toward concentrations of caffeine that are not repellent but still pharmacologically active,” says the report. Humans have selected for a not-too-much, not-too-little dose of caffeine in the form of soda drinks and coffee. Is it possible that the humble coffee bean is pharmacologically manipulating us into taking good care of it? And do we drink it when we read or study because, for one thing, it enhances long-term memory? And speaking of memory, people often forget where they tucked the oregano, but they usually have little difficulty remembering where they stashed the coffee.
More pragmatically, honeybees on caffeine may lead researchers toward a better understanding of the foraging strategies of pollinator insects, and allow for improved management of crops and landscapes.
Wright G.A., Baker D.D., Palmer M.J., Stabler D., Mustard J.A., Power E.F., Borland A.M. & Stevenson P.C. (2013). Caffeine in Floral Nectar Enhances a Pollinator's Memory of Reward, Science, 339 (6124) 1202-1204. DOI: 10.1126/science.1228806
Photo credit: http://www.coorgblog.orangecounty.in
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Wright G. A., Baker D. D., Palmer M. J., Stabler D., Mustard J. A., Power E. F., Borland A. M., & Stevenson P. C. (2013) Caffeine in Floral Nectar Enhances a Pollinator's Memory of Reward. Science, 339(6124), 1202-1204. DOI: 10.1126/science.1228806
Two long-term studies yield grim stats, and women are no exception.
We know that smoking kills. But until the results of 50 years’ worth of observations on British male smokers was published by Richard Doll and coworkers in the British Journal of Medicine in 2004, we didn’t know how many. Cigarettes will kill at least half of those who smoke them past the age of 30—possibly more. In older, specific populations, possibly as many as 2/3.
It took a prospective study of more than 34,000 British doctors, starting in 1951 and ending in 2001, to establish the grim parameters with some degree of precision. As the study authors of the 2004 summary paper put it: “A substantial progressive decrease in the mortality rates among non-smokers over the past half century… has been wholly outweighed, among cigarette smokers, by a progressive increase in the smoker v non-smoker death rate ratio due to earlier and more intensive use of cigarettes.” In other words, the great reduction in disease mortality rates achieved in the 20th Century, courtesy of better prevention and treatment, effectively never happened for long-term male smokers. Smoking in Britain and America took off in a major way between the two world wars, and sufficient time has now passed to conclude that “men born in 1900-1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers.”
As for women, it took a few decades longer to nail down the truth, because women did not begin smoking in peak numbers until the 1960s. While men born between 1900 and 1930 took to cigarettes in a big way, women born around 1940 were the first cohort of female smokers to consume a substantial number of cigarettes throughout their adult lives. This 20-year lag is crucial, because it means that solid numbers for female mortality rates require solid figures on mortality rates in the 21st Century. And now we have them, courtesy of the Million Women Study in the UK. The results were recently published in The Lancet by Kirstin Pirie and others. They are just as bad as you might have guessed, putting women on a firm equal footing with their male counterparts when it comes to smoking deaths.
The Million Women Study, a database originally used for the UK’s National Health Service Breast Screening Program, recruited female volunteers between the ages of 50 and 69. The figures were eerily similar to those from the earlier study of male British doctors: “If combined with 2010 UK national death rates, tripled mortality rates among [female] smokers indicate 53% of smokers and 22% of never-smokers dying before age 80 years, and an 11-year lifespan difference…. Although the hazards of smoking until age 40 years and then stopping are substantial, the hazards of continuing are ten times greater.” In this study, the researchers found little difference between female smokers and nonsmokers when it came to confounding variables like weight, blood pressure, or lipid profile. A four-year head start—beginning to smoke at the age of 15 rather than 19, say—can put women at a measurably greater risk for lung cancer deaths. And a little goes a long way: “Even those smoking fewer than ten cigarettes per day at baseline had double the overall mortality rate of never-smokers.” Low-tar won’t save them, either. “Low-tar cigarettes are not low-risk cigarettes,” the investigators write, “and the Million Women Study shows that more than half of those who smoke them will eventually be killed by them, unless they stop smoking in time to avoid this.”
There it is again: Half of all smokers are going to die from smoking. As the authors of the Lancet study wrote: “If women smoke like men, they die like men.”
In summary, those who stop smoking at age 50 gain about six years of life expectancy. Quit at 40, and you get an extra nine years. A non-smoker’s chances of living from 70 to 90 are three times higher than a smoker’s. The researchers found that the doctors who stopped smoking by age 30 managed to avoid almost all of the lifespan penalties associated with smoking—primarily lung cancer, COPD, and heart disease. (Only about 3% of smoking deaths are due to fires, accidents, poisonings, etc.). And even lifelong smokers who do not quit until the age of 60 are still rewarded with an extra three years of life span, on average.
Perhaps the saddest thing about the findings is the ways in which they suggest that British and American military commanders may have been sentencing countless numbers of soldiers to death for decades, through the simple act of giving away cigarettes in K-rations, and selling them cheaply in other circumstances. As the report in the British Medical Journal states, “widespread military conscription of 18 year old men, which began again in 1939 and continued for decades, routinely involved provision of low cost cigarettes to the conscripts. This established in many 18 year olds a persistent habit of smoking substantial numbers of manufactured cigarettes, which could well cause the death of more than half of those who continued.” In a perverse reminder of the Agent Orange scandal in Vietnam, American and British military command may have exposed their soldiers to a much greater threat, for a much longer period, with worse odds for survival.
One obvious confounding variable in such studies is alcohol. It requires a sensitive statistical analysis to work through correlations between drinking, smoking, and, say, liver disease. But “the large majority of the excess overall mortality among smokers is actually caused by smoking,” the Lancet researchers maintain with confidence. The overall point seems clear: These long-term results show that the risks from continual cigarette smoking are even greater than we thought.
The dismal bottom line of the two smoking studies is that we appear to be right for meeting the UN’s prediction of one billion tobacco deaths in this brave new century.
Pirie, K., Peto, R., Reeves, G., Green, J., & Beral, V. (2012). The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK The Lancet DOI: 10.1016/S0140-6736(12)61720-6
Photo Credit: Ianier67 via Creative Commons.
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Pirie, K., Peto, R., Reeves, G., Green, J., & Beral, V. (2012) The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. The Lancet. DOI: 10.1016/S0140-6736(12)61720-6
Meth is a risk factor for hemorrhagic stroke.
When a stroke happens to anyone under the age of 55, a major suspect is drugs, specifically the stimulants—methamphetamine and cocaine. In a recent issue of the journal Stroke, researcher Brett Kissela and his associates provided additional evidence to support that unpleasant truth.
(Stroke death rates by state)------>
“We know that even with vascular risk factors that are prevalent—smoking, high blood pressure—most people still don’t have a stroke until they’re older,” Kissela said in a Reuters article. “When a young person has a stroke, it is probably much more likely that the cause of their stroke is something other than traditional risk factors.”
The modest study involved residents of Cincinnati and Northern Kentucky who had suffered a stroke before turning 55. The researchers found that the rate of substance abuse among the stroke group was higher than in control populations. This doesn’t prove that drug or alcohol addiction lead directly to strokes, since drug users often have additional risk factors for stroke and heart disease, particularly if they are also cigarette smokers.
(Meth use by state)-------->
But the suspected link between strokes and young drug abusers is by no means a new one. In 2007, scientists at the University of Texas Southwestern Medical Center in Dallas published a massive survey of more than 3 million records of Texas hospital patients from 2000 through 2003 in the Archives of General Psychiatry. This gigantic database gave the researchers access to the records of virtually every stroke patient in the state of Texas. The researchers found that strokes associated with amphetamine use among young people 18 to 44 years of age represented a rapidly growing category. In fact, the Texas group found that “the rate of strokes among amphetamine abusers was increasing faster than the rate of strokes among abusers of any other drug.”
Curiously, amphetamine and cocaine are responsible for different kinds of strokes. An ischemic stroke, the classic blood clot, is caused by a blockage of blood vessels to the brain. Hemorrhagic strokes result from bleeding caused by the rupture of a weakened blood vessel. In general, hemorrhagic strokes are more severe and more likely to cause death. And what the researchers found was more bad news for speed freaks: “Amphetamine abuse was strongly associated with hemorrhagic stroke, but not with ischemic stroke.” Cocaine abuse was more robustly linked to ischemic strokes. So, it’s not surprising that when it comes to drug and fatal strokes, the clear winner was amphetamine. It’s not entirely clear what causes the difference, but the investigators pointed out that meth injections in lab animals can cause microhemorrhaging, heart attacks, fragmentation of capillary beds, and something called “poor vascular filling.” For cocaine, the culprits are vasoconstriction and disrupted regulation of blood pressure.
More than 14 percent of strokes in hospitals “were accounted for by abuse of drugs,” the researchers wrote. The data showed that for patients with hemorrhagic strokes, “only amphetamine abuse, coagulation defects, and hypertension were strong independent predictors of in-hospital death.”
So what can we conclude? Either the number of speed users in these communities is increasing, or the existing speed communities are using the drug more intensely. Since the rate of increase of speed use was relatively modest during the study years, the researchers concluded that “increased rate in our hospital population is because of the increased intensity of methamphetamine use.” Meaning higher dosages, stronger meth, and more needles.
Sadly, much of this has been known since it least 1990. In that year, research published in the Annals of Internal Medicine, based on a study of stroke victims at San Francisco General Hospital, concluded that “the possibility of serious and sometimes fatal cerebrovascular accidents in people taking potent stimulants and using the intravenous route of administration is not as widely known as it needs to be.”
About 800,000 people in the U.S. suffer a stroke each year, according to figures from the U.S. Centers for Disease Control and Prevention. Strokes are considered America’s leading cause of serious long-term disability.
de los Rios F., Kleindorfer D.O., Khoury J., Broderick J.P., Moomaw C.J., Adeoye O., Flaherty M.L., Khatri P., Woo D. & Alwell K. & (2012). Trends in Substance Abuse Preceding Stroke Among Young Adults: A Population-Based Study, Stroke, 43 (12) 3179-3183. DOI: 10.1161/STROKEAHA.112.667808
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de los Rios F., Kleindorfer D. O., Khoury J., Broderick J. P., Moomaw C. J., Adeoye O., Flaherty M. L., Khatri P., Woo D., & Alwell K. (2012) Trends in Substance Abuse Preceding Stroke Among Young Adults: A Population-Based Study. Stroke, 43(12), 3179-3183. DOI: 10.1161/STROKEAHA.112.667808
What happens to some smokers when they cut out the cannabis.
People who say they are addicted to marijuana tend to exhibit a characteristic withdrawal profile. But is cannabis withdrawal, if it actually exists, significant enough to merit clinical attention? Does it lead to relapse, or continued use despite adverse circumstances? Should it be added to the list of addictive disorders in the rewrite of the Diagnostic and Statistical Manual of Mental Disorders (DSM) currently in progress?
Marijuana fits in fairly well with the existing criteria for clinical addiction—except for one common diagnostic marker. Among the identifying criteria currently used in the DSM, we find: “The presence of characteristic withdrawal symptoms or use of substance to alleviate withdrawal.” Opponents of marijuana’s inclusion as an addictive drug have long insisted that cannabis has no characteristic withdrawal symptoms, but this position has been severely eroded of late, as new research has consistently identified a withdrawal syndrome for marijuana, which includes drug cravings, despite decades of controversy over this basic medical question.
A group of researchers at the University of New South Wales, Australia, along with Dr. Alan J. Budney of the Geisel School of Medicine at Dartmouth, New Hampshire, writing in PLOS ONE, presented evidence that the characteristic withdrawal symptoms displayed by addiction pot smokers are in fact strong enough to be considered clinically significant.
(For more on the marijuana withdrawal profile, see HERE, and HERE. For a bibliography of relevant journal articles, go HERE).
But how does one go about determining if withdrawal reactions rise to the level of clinical significance? The researchers wanted to know whether functional impairment reported during abstinence was clinically significant, whether it correlated with severity of addiction, and whether it was predictive of relapse. 46 survey volunteers who were not seeking any formal treatment for marijuana addiction were recruited in Sydney, Australia. Users ranged in age from 18 to 57, with an average age of 30. After a one-week baseline phase, the participants underwent two weeks of monitored abstinence. Using a “Severity of Dependence Scale” (SDS) to measure variability in functional impairment, the researchers compared a high SDS subgroup to a low SDS subgroup in an effort to tease out whether functional impairments in high SDS participants were predictive of relapse. The researchers noted that earlier work had established that the symptoms most likely to cause impairment to normal daily functioning were: Trouble getting to sleep, angry outbursts, cravings, loss of appetite, feeling easily irritated, and nightmares or strange dreams.” The investigators broke these symptoms into two groups: “somatic” and “negative affect” variables.
The researchers then examined self-reports about the impact of cannabis withdrawal on normal daily activities. While the common yardstick for withdrawal is typically taken to be intensity of cravings, the authors argue that this reliance on craving “may mask the extent to which symptoms led to functional impairment, as those who maintained abstinence may still have experienced clinically significant negative consequences from cannabis withdrawal (e.g. relationship or work problems resulting from the withdrawal syndrome.”)
As might have been expected, higher levels of cannabis dependence were associated with greater functional impairment. And while the average level of functional impairment caused by cannabis is “mild for most users, it appears comparable with tobacco withdrawal which is of well established clinical significance.”
And certain symptoms were, in fact, correlative: “Increased somatic withdrawal symptoms are predictive of relapse, and…. increased physical tension is a significant predictor of relapse.”
Physical distress, a “somatic” variable, mattered more, in terms of relapse, than the amount of marijuana smoked, or any other symptom on the roster of functional impairments—including mood and other negative affect variables.
“In conclusion,” the investigators write, “cannabis withdrawal is clinically significant because it is associated with elevated functional impairment to normal daily activities, and the more severe the withdrawal is, the more severe the functional impairment is. Elevated functional impairment from a cluster of cannabis withdrawal symptoms is associated with relapse in more severely dependent users.”
Furthermore: “Targeting the withdrawal symptoms that contribute most to functional impairment during a quit attempt might be a useful treatment approach (e.g. stress management techniques to relieve physical tension and possible pharmacological interventions for alleviating the physical aspects of withdrawal such as loss of appetite and sleep dysregulation.)”
As with most studies, there are limitations. As noted, the participants were not in a formal cessation program. And while urine tests were used, there was no external corroboration of the self reports.
Allsop, D., Copeland, J., Norberg, M., Fu, S., Molnar, A., Lewis, J., & Budney, A. (2012). Quantifying the Clinical Significance of Cannabis Withdrawal PLoS ONE, 7 (9) DOI: 10.1371/journal.pone.0044864
Graphics Credit: http://www.addictionsearch.com/
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Allsop, D., Copeland, J., Norberg, M., Fu, S., Molnar, A., Lewis, J., & Budney, A. (2012) Quantifying the Clinical Significance of Cannabis Withdrawal. PLoS ONE, 7(9). DOI: 10.1371/journal.pone.0044864
Time for a change in strategy?
The Summer Olympics are fast approaching, and that can only mean one thing: drugs. After more than a decade, you might wonder, how goes the so-called “War on Doping?”
Not so good, but thanks for asking. The World Anti-Doping Agency, established in 1999 and backed by the UNESCO anti-doping convention, will be operating 24/7 during the games, protecting the “purity” of Sport, trying to ferret out everything from cannabis and cocaine to steroids and arcane metabolites unfamiliar to the world at large. Marijuana as a “performance enhancing” drug? Doesn’t sound likely, but cannabis derivatives are on the banned list anyway. As Bengt Kayser and Barbara Broers of the Institute of Movement Sciences and Sports Medicine at the University of Geneva write in the Harm Reduction Journal, marijuana seems to have been included “largely because of pressure from the ‘war on drugs’ movement, even though there are no known proven performance enhancing effects but rather evidence for the contrary.”
No matter. That’s just for starters. As in life, an athlete can be busted for a banned substance taken days earlier, in some other recreational context, and not intended as a sports enhancer, if the metabolites linger too long in the body. The current policy, Kayser and Broers write, “is still essentially based on repression and surveillance from a zero-tolerance viewpoint.”
Did they say “surveillance?” Top athletes are not like you and me. Jocks operate under a “strict liability” rule: It doesn’t matter how it got in your body, or why. If they find proscribed metabolites, you’re busted. It’s entirely possible to get banned from your sport for life. In 2003, British sprinter Dwain Chambers tested positive for a proscribed substance and was subsequently banned from competition for life by the British Olympic Association. (Chambers recently won an appeal, and continues to compete.)
And to make sure that the Olympic Committee can be diligent about the ever-growing list of banned substances, Olympic-level athletes are subject to something called the “whereabouts” rule, say the authors. Elite athletes must “inform the anti-doping authorities where they will be each day of the year, to allow unannounced out-of (and in)-competition testing…” This requirement is clearly impossible for almost anyone to honor, certainly including globetrotting athletes. But Sebastian Coe, chairman of the London Organizing Committee for the Olympic Games, didn’t let even a ray of ambiguity enter the picture, stating: “I don’t think there is room for drugs cheats in sport.”
However inartfully phrased, this sentiment reflects the Olympic Committee’s desire to increase testing, even though the Geneva sports scientists believe that the “probability for false positives rises with the number of tests performed, as well as with a drop in prevalence of actual doping. Furthermore, for some forms of doping practices, there exist no laboratory tests.” The result? “A greater number of tests would lead to a greater number of false positives, wrongly accusing innocent citizens.”
In fact, you can now be busted even though no trace of a banned drug was found in your blood or urine. Here’s how it works:
Longitudinal testing, looking for fluctuations in certain blood parameters compatible with doping, is now also being introduced. This practice, known as the "athlete biological passport" (ABP), has recently led to the first indictments of athletes, based on indirect indices of presumed doping rather than laboratory tests directly showing the presence of the forbidden substance or their metabolites.
This practice is even shakier, write Kayser and Broers, producing even more false positives “due to analytical variability and outlying individual patterns resulting from the effects of behavior (training, altitude exposure) and genetics.
But the purpose of anti-doping—to celebrate the “clean” and upright athlete as exemplar of everything good and fair—is unrealistic, say the authors. “Doping has always been a part of sports…. Performance enhancement is a logical and essential ingredient of competitive sport. Athletes look for ways to get better, by changing their training paradigm, by eating differently, by taking vitamins, by taking licit medication, by taking supplements.” In short: “The line between licit and illicit fluctuates and has dimensions that can be perceived as arbitrary.”
The essay asks us to consider whether anti-doping tests might one day be logically applied to coaches, trainers, and referees as well—not to mention students studying for a final exam.
So what do we do? Just throw the doors open to any and all drug taking at the Olympics? Since the paper was published in the Harm Reduction Journal, the authors have some thoughts on that. “The argument that it would change sports into an arena akin to Formula 1 where the best engineering team wins is only partly correct,” they write. Which is only partly reassuring. But the authors hasten to argue that “such a scenario is already in place anyway; today well-assisted athletes may engage in complex training regimes and strategic doping while remaining undetected.” They advocate shortening the list of forbidden substances, banning only those with “actually proven performance enhancing effects and major health hazards.” In amateur sports, the authors urge the establishment of so-called steroid clinics, where jocks could get syringes, anonymous service, and professional advice from medical staff.
It would require a major change of heart, and a whole different way of viewing competitive sports. Throttling back the anti-doping program would not sit well with many sports parents of young athletes. The authors are aware of this need, and note that “since athletic careers often start very early, the protection of young talents would be mandatory.”
As a former collegiate athlete, I don’t have an answer to this dilemma. Not even a clue, really. Testing is cumbersome and intrusive and puts the innocent under suspicion. On the other hand, performance-enhancing drugs are unfair and unevenly applied—but so are things like good coaching and state-of-the-art equipment. The answer, perhaps, is to begin viewing anti-doping efforts as wholly distinct from drug war efforts—different rationale, logistics, and deployment.
Kayser B, and Broers B (2012). The Olympics and harm reduction? Harm reduction journal, 9 (1) PMID: 22788912
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Addiction expert calls for reduced-nicotine tobacco.
For years now, nicotine researcher Neal Benowitz has been a man on a mission. Dr. Benowitz, a professor of medicine at the University of California in San Francisco, has been pushing a Big Idea about how to eliminate cigarette smoking in America: Reduce the amount of nicotine in cigarettes.
In essence, Benowitz is calling for a national nicotine taper. Whether the FDA is interested remains an open question. But the result, several years down the road, would be a nation of teenagers confronted with only weakly addictive tobacco products.
It is an old idea, often viewed with great suspicion because of the failure of “light” and “low-tar” cigarettes to reduce nicotine intake, and in fact causing smokers to smoke harder. But Benowitz, one of the nation’s premier tobacco scientists, believes that when it comes to the roughly one out of five Americans who still smoke, a new generation of so-called “low-nicotine delivery” cigarettes is the answer.
In a controlled study of 135 smokers of various ages, participants smoked cigarettes with progressively lower nicotine over a two-year period, and did so “without evidence of compensation”—meaning that they did not smoke more cigarettes or smoke differently when using the low-nicotine offerings. This varies dramatically from the behavior associated with light cigarettes and special filters—innovations that were marketed as “safer” cigarettes—that simply increase ventilation. The light cigarettes themselves contain the same amount of nicotine as a “regular” cigarette. And smokers quickly learn to puff harder, or cover small holes in the filter paper with their fingers, in order to extract more nicotine from each cigarette.
But with low-nicotine delivery cigarettes, you can’t get more nicotine, no matter what kind of smoker’s gyrations you perform. And the result, according to a paper by Benowitz and coworkers in Cancer, Epidemiology, Biomarkers and Prevention, is that “when the nicotine content of cigarettes is progressively decreased at monthly intervals over 6 months there is a progressive decline in nicotine intake by smokers, with only a small degree of compensation at the lowest nicotine content levels.”
The two-year study was randomized but unblinded, in order to simulate situations in which smokers are fully aware of using cigarettes with progressively less nicotine. A control group smoked their usual brands of cigarettes throughout the study. Benowitz, who led the studied, said in prepared remarks that the U.S. Food and Drug Administration (FDA) now has the authority to regulate the nicotine content of cigarettes sold in the U.S. (Benowitz is a member of the FDA’s Tobacco Products Scientific Advisory Committee.) “The idea is to reduce people’s nicotine intake, so that they get used to the lower levels, and eventually get to the point where smoking is no longer satisfying.”
The study was small, and there were dropouts. As always, further long-term study will be needed to track smokers during this kind of long-term nicotine taper. Traditionally, tapering has not been an effective method of breaking a nicotine addiction. But the reason for that may have to do with the easy availability of full-strength cigarettes in every store and gas station. The obvious goal for Benowitz is the reduction of nicotine in cigarettes to the point where they are no longer addictive. But would a robust black market in strong cigarettes leap up if nicotine reduction were a federally mandated program?
“Progressive reduction of the nicotine content of cigarettes as a national regulatory policy might have important potential benefits for the population,” the authors write, adding that “some people who had no intention of quitting upon entry into the study had… either quit spontaneously or were thinking about quitting in the near future after smoking reduced-nicotine content cigarettes.” Low-nicotine cigarettes could be produced by extracting nicotine from existing tobacco, or by genetically engineering tobacco with a lower nicotine content.
“Adolescents initiate smoking for social reasons, with friends, and later begin to smoke for pharmacologic reasons related to dependence,” the authors conclude. “Presumably a cigarette with very low nicotine content would be less likely to support the transition from social to dependent smoking, although the threshold level of nicotine to prevent this transition is not yet known.”
Benowitz NL, Dains KM, Hall SM, Stewart S, Wilson M, Dempsey D, & Jacob P 3rd (2012). Smoking behavior and exposure to tobacco toxicants during 6 months of smoking progressively reduced nicotine content cigarettes. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 21 (5), 761-9 PMID: 22354905
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Benowitz NL, Dains KM, Hall SM, Stewart S, Wilson M, Dempsey D, & Jacob P 3rd. (2012) Smoking behavior and exposure to tobacco toxicants during 6 months of smoking progressively reduced nicotine content cigarettes. Cancer epidemiology, biomarkers , 21(5), 761-9. PMID: 22354905
Bariatrics and booze don’t always mix.
For many people with obesity, bariatric surgery has proven to be a lifesaver. But for a subset of post-operative patients, the price for losing five pounds every time you step on the scale turns out to be an increased appetite for alcohol.
In a study of almost 2,000 patients who underwent surgery for severe obesity, the patients had either gastric bypass surgery (RYGB) in which a portion of the stomach and small intestine are removed, or gastric banding, a process by which an adjustable “lap band” is tightened around the entrance to the stomach. Those who opted for gastric bypass showed an increase in alcohol consumption two years after surgery, according to a recent study by Wendy C. King and coworkers in the Journal of the American Medical Association.
The notion that weight loss surgery, known as bariatric surgery, was related to increased use of alcohol had been an anecdotal staple among obese patients for years. Oprah Winfrey based one of her daytime television shows on the rumor back in 2006. Dr. King and a diverse group of associates concluded last month at the American Society for Metabolic and Bariatric Surgery annual meeting that “a significantly higher prevalence of alcohol use disorder” was associated with the second year following gastric bypass surgery. (During the first postoperative year, patients are strongly advised not to drink at all.)
Moreover, some of the patients who showed high-risk alcohol intake had not been problem drinkers before surgery. Some had not been drinkers at all. But the effects of gastric bypass, coupled with permission to drink a year after surgery, lead to an increase in alcohol abuse and alcoholism. While the overall increase was relatively modest, patients who had gastric bypass surgery were twice as likely to drink heavily than patients who underwent the lap band procedure.
“It’s a great study,” says Dr. Stephanie Sogg, staff psychologist at the Massachusetts General Hospital Weight Center and assistant professor in the Department of Psychiatry at Harvard Medical School, who was not associated with the study group. In an interview for this article, Sogg called the distinction between surgeries “an extremely important finding. They saw changes in alcohol use patterns with gastric bypass, but not with gastric banding. That’s exactly what we would expect.”
The findings make biochemical sense: “Gastric bypass surgery bypasses a part of the stomach that secretes alcohol dehydrogenase,”—a primary enzyme of alcohol metabolization, says Sogg. “And in gastric bypass, the alcohol is not coming into contact with the first part of the intestine, the duodenum. “That’s going to cause some changes in the way the body processes alcohol that aren’t true of gastric banding. If this were a case of people who are addicted to food having to change their eating and thus becoming addicted to alcohol, we would expect to see the same changes whether the person had gastric bypass or gastric banding.”
It would be natural to assume that people with prior drinking problems would have the most trouble with alcohol control postoperatively. But things are rarely that simple in medicine. “Previous alcohol history sets up people for risk of relapse, but there’s a significant subset of people having trouble with alcohol who never drank at all,” says Dr. Sogg. “That’s where the real story is.”
Dr. David B. Sarwer, associate professor of psychology and director of clinical services for the Center for Weight and Eating Disorders at the University of Pennsylvania, called the King study “the most definitive evidence to date on the prevalence of alcohol use disorders in persons who undergo bariatric surgery.” In an email exchange, Sarwer said: “Individuals with a history of alcohol or substance abuse are informed that the stress of the dietary and behavioral requirements of bariatric surgery, like all major life stressors, could threaten their sobriety or abstinence. However, we simply do not know enough about the use of alcohol and other substances after surgery to predict this with a great degree of certainty.”
Dr. Sogg agrees. For the bariatric surgery population, the pharmacokinetics of alcohol changes. They become more sensitized to its effects—a little now goes a long way. The main problem, she says, is that “we’re not good yet at predicting exactly whom it’s going to happen to.”
But she has some thoughts about vulnerable subsets. “Some people with obesity have poor coping skills,” she says. “And now alcohol is so much more potent and reinforcing for them that alcohol becomes the coping strategy. When this biological change with alcohol happens, they may be the ones who are at higher risk of responding to that change by developing problems with alcohol.”
Warning patients about alcohol risks of weigh-loss surgery is becoming more common, says Dr. Sogg. “It doesn't change my decision-making about whether somebody should or shouldn't have surgery. But we can evaluate people's coping skills before surgery and point out to them that it is important for them to develop other ways of dealing with negative emotions besides eating."
She also thinks that “people who have a history of actually becoming abstinent after drug or alcohol dependence may be better equipped for surgery. They will be less likely to put themselves in the path of alcohol use, and they have experience at making major successful long-term behavior changes. Basically, we should not consider past encounters with substance abuse as contraindications for surgery. But we should be carefully evaluating whether people are currently using substances at the time of surgery.”
In the end, she said, “I tell every one of my patients before surgery that they need to be aware of the risks of problem drinking after surgery, monitor their alcohol intake, and come back to us immediately at the first sign of any concerns about their drinking.”
King WC, Chen JY, Mitchell JE, Kalarchian MA, Steffen KJ, Engel SG, Courcoulas AP, Pories WJ, & Yanovski SZ (2012). Prevalence of Alcohol Use Disorders Before and After Bariatric SurgeryAlcohol Use Disorders and Bariatric Surgery. JAMA : the journal of the American Medical Association, 1-10 PMID: 22710289
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King WC, Chen JY, Mitchell JE, Kalarchian MA, Steffen KJ, Engel SG, Courcoulas AP, Pories WJ, & Yanovski SZ. (2012) Prevalence of Alcohol Use Disorders Before and After Bariatric SurgeryAlcohol Use Disorders and Bariatric Surgery. JAMA : the journal of the American Medical Association, 1-10. PMID: 22710289
What we know and don’t know about synthetic speed.
Call bath salts a new trend, if you insist. Do they cause psychosis? Are they “super-LSD?” The truth is, they are a continuation of a 70-year old trend: speed. Lately, we’ve been fretting about the Adderall Generation, but every population cohort has had its own confrontation with the pleasures and perils of speed: Ritalin, ice, Methedrine, crystal meth, IV meth, amphetamine, Dexedrine, Benzedrine… and so it goes. For addicts: Speed kills. Those two words were found all over posters in the Haight Ashbury district of San Francisco, a few years too late to do the residents much good.
While the matter of the addictiveness of Spice and other synthetic cannabis products remains open to question, there no longer seems to be much doubt about the stimulant drugs known collectively as bath salts. To a greater or lesser degree, these off-the-shelf synthetic stimulants appear to be potentially addictive. And that’s not good news for anyone.
Last week, the U.S. Congress added 26 additional synthetic chemicals to the Controlled Substances Act, including the designer stimulants mephedrone and MDPV, at the behest of the Drug Enforcement Administration. Mephedrone and MDPV are cathinones, sold as bath salts or plant food, and chemically similar to amphetamine and ephedrine. (Methcathinone, often called MCAT, is to cathinone as methamphetamine is to amphetamine)
The research news on bath salts at the annual meeting of the College on Problems of Drug Dependence (CPDD) in Palm Springs recently was complex and confusing. For example, the phemonenon of overheating, or hyperthermia, that plagues ravers on MDMA and sends some of them to the hospital is a function of certain temperature-sensitive effects of Ecstasy. But it is not as much of a problem with MDPV and mephedrone. The bath salts, like meth, don’t seem to cause overheating as readily.
On another front, William Fantegrossi, assistant professor in the Department of Pharmacology and Toxicology at the University of Arkansas for Medical Sciences, told the panel audience that at very high doses and very high temperatures, stimulants like Ecstasy and MDPV “can cause self-mutilation in animals.” Fantegrossi’s statement was the closest anybody has come to providing a possible scientific basis for popular press accounts linking bath salts to flesh-eating frenzies by psychotic users. But this remains speculative, as there are still no reliable toxicological findings available in such cases.
The symposium on bath salts at the CPDD played to a packed conference hall, a sure sign that professional scientists who study addiction for a living were interested in the subject. The panel was titled “A Stimulating Soak in ‘Bath Salts’: Investigating Cathinone Derivative Drugs,” and was co-chaired by Dr. Michael Taffe of the Scripps Research Institute in La Jolla, CA, and pharmacology professor Dr. Annette Fleckenstein of the University of Utah.
Fantegrossi characterized the overall problem of designer stimulants as “dirty pharmacology” on both sides, pointing to the desperate efforts underway by government-funded scientists to “throw antagonists [blocking drugs] at these things.”
The late Alexander Shulgin, the grandfather of the modern psychedelic movement, invented MDMA and hundreds of variants in his backyard laboratory in the Bay Area over the years. Shulgin, better than anyone, knew that legitimate research and dirty recreational chemistry are only a molecule away. In their book Pihkal: A Chemical Love Story, Alexander Shulgin and his wife Ana recall that cartoonist Gary Trudeau captured the truth of the situation as far back as 1985, when the MDMA story became front-page news:
Way back in mid-1985, the cartoonist-author of Doonesbury, Gary Trudeau, did a two-week feature on it, playing it humorous, and almost (but not quite) straight, in a hilarious sequence of twelve strips. On August 19, 1985 he had Duke, president of Baby Doc College, introduce the drug design team from USC in the form of two brilliant twins, Drs. Albie and Bunny Gorp. They vividly demonstrated to the enthusiastic conference that their new drug "Intensity" was simply MDMA with one of the two oxygens removed. "Voila," said one of them, with a molecular model in his hands, "Legal as sea salt."
Jeffrey Moran of the Arkansas Department of Health noted that despite the cat-and-mouse game continuously played between illegal drug designers and the law, government bans on mephedrone and MDPV, the two most common forms of designer stimulant, cause only temporary downturns in supply. They are no longer as legal as sea salt, but it doesn’t seem to matter. There are always new ones in the pipeline. Moran told the audience that at least 48 different compounds had been identified in more than 200 distinct bath salt-style products in his state alone. Sorting out the specific chemistry involves specialized assays designed to detect a bewildering array of molecules: methylone, mephedrone, paphyrone, butylone, 4-MEC, alpha-PVP, and a host of others, some old, some new, some reimagined by underground chemists.
Terry Boos of the U.S. Drug Enforcement Agency explained that most designer stimulants currently in play are not manufactured stateside. Most originate in Asia and arrive through various ports of call, where they are repackaged for sale in the U.S. Purity of the cathinone ranges from 30 to 95 per cent, Boos said.
Annette Fleckenstein of the University of Utah emphasized that scientists shouldn’t be fooled by overall structural similarities among such drugs as meth, mephedrone, MDMA, and MDPV. In a 2011 study published with her colleagues at the University of Utah, Fleckenstein lamented that mephedrone’s recent emergence on the drug scene had exposed the fact that “there are no formal pharmacodynamic or pharmacokinetic studies of mephedrone.”
But she has managed to show that methamphetamine causes lasting decreases in serotonin functions, as well as the better-known dopamine alterations, and that MDMA and mephedrone are intimately involved in the accumulation of serotonin in the brain’s nucleus accumbens, where addictive drugs produce many of their rewarding effects. “Rats will self-administer mephedrone,” said Fleckenstein—always a troubling clue that the drug in question may have addictive properties. Since the high in humans only last for three to six hours, there is a tendency to reinforce the behavior through repeated dosings.
Other behavioral clues have been teased out of rat studies. The Taffe Laboratory at Scripps Research Institute has focused on the cognitive, thermoregulatory, and potentially addictive effects of the cathinones. Rats will self-administer mephedrone, MDPV, and of course methamphetamine. However, Dr. Taffe told the audience that MDMA does not produce these classic locomotor stimulant effects at low doses and that it is “more difficult to get them to self-administer” Ecstasy. Nonetheless, Taffe told me he believes that MDMA is, in fact, potentially addictive. “Our data suggest that MDPV is highly reinforcing,” Taffe said in an email exchange after the conference, “and at least as readily self-administered as methamphetamine, at approximately the same per-infusion doses. But it is a very complicated story.”
Scripps researchers have carried the investigation forward with a new study, currently in press at the journal Drug and Alcohol Dependence. Pai-Kai Huang and coworkers studied the differing effects of designer stimulants on voluntary wheel-running activity in rats, adding additional evidence to the basic behavioral split among club drugs of the moment. Taffe, one of the study’s co-authors, said the researchers had predicted that the two drugs with the strongest serotonin activity—MDMA and the mephedrone variants—would decrease wheel running activity in the rats. Methedrine and MDPV, they predicted, would increase activity.
And that’s how it turned out. What that means for human users is still not entirely clear. But MDPV in particular, it now seems evident, has some rather direct and disturbing affinities with crystal meth and cocaine. And the vagaries of the market have led to sharp increases in the percentage of MDPV found in bath salt products in the last two years. Are we seeing the wholesale replacement of MDMA by a more dire... Read more »
Huang PK, Aarde SM, Angrish D, Houseknecht KL, Dickerson TJ, & Taffe MA. (2012) Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. Drug and alcohol dependence. PMID: 22664136
Hadlock GC, Webb KM, McFadden LM, Chu PW, Ellis JD, Allen SC, Andrenyak DM, Vieira-Brock PL, German CL, Conrad KM.... (2011) 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse. The Journal of pharmacology and experimental therapeutics, 339(2), 530-6. PMID: 21810934
It’s getting harder to interpret genetics studies, and that’s a good thing.
Reporting the results of published studies concerned with genetic risk factors has always been a tricky proposition. Beyond the inevitable, and too often ideological nature/nurture split, there has been an unfortunate history of false positives in the rush to make news with a “gene for” alcoholism or schizophrenia or belief in God.
But single gene theories are mostly a thing of the past, and results tend to be broader and more tentative, as befits the state of our knowledge about genes and risk in a post-epigenetic landscape. Nonetheless, there’s no denying that genes play a strong role in all kinds of behaviors and processes. A large group of U.S. tobacco researchers went looking for associations between genetic risk factors and the ability to stop smoking successfully, and published their results in the American Journal of Psychiatry. The group came down strongly in favor of the proposition that genetic variations in the chromosome 15q25 region help dictate who manages to quit smoking and who does not.
The genetic variants in question are for nicotine receptors, and are called CHRNA5-CHRNA3-CHRNB4. They compose a “high-risk haplotype” that Li-Shiun Chen and coworkers believe to be involved in the ability to quit. (A haplotype is a combination of DNA sequences on a chromosome that are transmitted as a unit). People with these genetic variants “quit later than those at low genetic risk; this difference was manifested as a 2-year delay in median quit age.” However, this association tended to wash out at very high levels of smoking. Nonetheless, “pharmacological cessation treatment significantly increased the likelihood of abstinence in individuals with the high-risk haplotype,” compared to the low-risk group.
The suspicious haplotypes did not reliably predict tobacco abstinence across all groups that were studied. And any pharmacological treatment at all vastly increases abstinence rates, compared to placebo, while those who smoke the fewest cigarettes per day have the best shot at abstinence no matter what. In one sense, all the study is saying is that anti-craving drugs are more likely to be effective in smokers “who are biologically predisposed to have difficulty quitting.” Other smokers may not need them at all as a quitting aid—which is very much as common sense would have it. But further research in this area may allow medical workers to genetically identify smokers who will definitely require a pharmacological booster shot to overcome their crippling addiction.
In brief, the study says that success in quitting may be directly modulated by certain types of genetic variation among smokers. And genetic variations influencing quitting success may be different from gene variants controlling for “severity of nicotine dependence” (how many cigarettes you smoke), and whether you get addicted in the first place. It is all very complicated. But it’s the sort of thing that gives researchers hope when they contemplate deploying forms of personalized medicine in addiction treatment.
Study limitations abound. The work looked at only one genetic locus, while the success of smoking cessation might depend on multiple gene sites. The placebo arm was relatively small, and the smoking reports were obtained through a combination of biochemical confirmation and self-reporting.
Baker, T. (2012). Interplay of Genetic Risk Factors (CHRNA5-CHRNA3-CHRNB4) and Cessation Treatments in Smoking Cessation Success American Journal of Psychiatry DOI: 10.1176/appi.ajp.2012.11101545
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Baker, T. (2012) Interplay of Genetic Risk Factors (CHRNA5-CHRNA3-CHRNB4) and Cessation Treatments in Smoking Cessation Success. American Journal of Psychiatry. DOI: 10.1176/appi.ajp.2012.11101545
The sons of Red Bull are sporting record concentrations of caffeine.
Are energy drinks capable of pushing some people into caffeine-induced psychotic states? Some medical researchers think so, under the right set of conditions.
Red Bull, for all its iconic ferocity, is pretty tame, weighing in at approximately half a cup of coffee. Drinks like Monster Energy and Full Throttle push it up to 100-150, or the equivalent of a full cuppa joe, according to USDA figures at Talk About Coffee. That doesn’t sound so bad—unless you’re ten years old. A little caffeine might put you on task, but an overdose can leave you scattered and anxious—or worse. If you cut your teeth on Coke and Pepsi, then two or three energy drinks can delivery an order-of-magnitude overdose by comparison.
Readers are entitled to ask: Are you serious? Can’t we just ignore the inevitable view-this-with-alarm development in normal kid culture, and move on?
My interest began when I ran across a 2009 case report in CNS Spectrums, describing an apparent example of “caffeine-induced delusions and paranoia” in a very heavy coffee drinking farmer. “Convinced of a plot against him,” the psychologists write, “he installed surveillance cameras in his house and on his farm…. He became so preoccupied with the alleged plot that he neglected the business of the farm…. and he had his children taken from him because of unsanitary living conditions.”
The patient was not known to be a drinker, reporting less than a case of beer annually. He had shown no prior history of psychotic behaviors. But for the past seven years, he had been consuming about 36 cups of coffee per day, according to his account. Take that number of cups times 125 milligrams, let’s say, for a daily total of 4500 milligrams. At that level, he should be suffering from panic and anxiety disorders, according to caffeine toxicity reports, and he would be advised to call the Poison Control Center. And that certainly seems to have been the case. “At presentation,” the authors write, “the patient reporting drinking 1 gallon of coffee/day.”
On the one hand, the idea of caffeine causing a state resembling chronic psychosis is the stuff of sitcoms. On the other hand, metabolisms do vary, and the precise manner in which coffee stimulates adenosine receptors can lead to anxiety, aggression, agitation, and other conditions. Could caffeine, in an aberrant metabolism, break over into full-blown psychosis? At the Caffeine Web, where psychiatrists and toxicologists duke it out over all things caffeinated, Sidney Kay of the Institute of Legal Medicine writes: “Coffee overindulgence is overlooked many times because the bizarre symptoms may resemble and masquerade as an organic or mental disease.” Symptoms, he explains, can include "restlessness, silliness, elation, euphoria, confusion, disorientation, excitation, and even violent behavior with wild, manic screaming, kicking and biting, progressing to semi-stupor.”
That doesn’t sound so good. In “Energy drinks: What is all the hype?” Mandy Rath examines the question in a recent issue of the Journal of the American Academy of Health Practitioners.
Selling energy drinks to kids from 6 to 19 years old is a $3.5 billion annual industry, Rath asserts. And while “most energy drinks consumed in moderation do not pose a huge health risk,” more and more youngsters are putting away higher and higher doses of caffeine. At the level of several cans of Coke, or a few cups of strong coffee or, an energy drink or three, students can expect to experience improved reaction times, increased aerobic endurance, and less sleepiness behind the wheel. Most people can handle up to 300 mg of caffeine in a concentrated blast. Certainly a better bargain, overall, than three or four beers.
But first of all, you don’t need high-priced, caffeine-packed superdrinks to achieve that effect. A milligram of caffeine is a milligram of caffeine. But wait, what about the nifty additives in Full Throttle and Monster and Rockstar? The taurine and… stuff. Taurine is an amino acid found in lots of foods. Good for you in the abstract. Manufacturers also commonly add sugar (excess calories), ginseng (at very low levels), and bitter orange (structurally similar to norepinephrine). However, the truly interesting addition is guarana, a botanical product from South America. When guarana breaks down, it’s principal byproduct is, yes, caffeine. Guarana seeds contain twice the caffeine found in coffee beans. Three to five grams of guarana provide 250 mg of caffeine. Energy drink manufacturers don’t add that caffeine to the total on the label because—oh wait, that’s right, because makers of energy drinks, unlike makers of soft drinks, don’t have to print the amount of caffeine as dietary information. And on an ounce-for-pound basis, kids are getting a lot more caffeine with the new drinks than the older, labeled ones.
All of this increases the chances of caffeine intoxication. Rath writes that researchers have identified caffeine-related increases among children in hypertension, insomnia, motor tics, irritability, and headaches. Chronic caffeine intoxication results in “anxiety, emotional disturbances, and chronic abdominal pain.” Not to mention cardiac arrhythmia, seizures, and mania.
So what have we learned, kids? Energy drinks are safe—if you don’t guzzle several of them in a row, or substitute them for dinner, or have diabetes, or an ulcer, or happen to be pregnant, or are suffering from heart disease or hypertension. And if you do OD on high-caffeine drinks, it will not be pleasant: Severe palpitations, panic, mania, muscle spasms, etc. Somebody might even want to take you to the emergency room. Coaches and teachers need to keep a better eye out for caffeine intoxication.
Note: There is a “caffeine calculator” available at the Caffeine Awareness website, designed to determined whether you are a coffee addict. I can by no means swear to its scientific accuracy, but, based on my own, distinctly non-young person daily intake, the test told me that my consumption was likely to manifest itself as “high irritability, moodiness & personality disorders.” Can I blame it all on those endless cokes we had as kids? Growing up in the Baby Boom suburbs, we all drank carbonated caffeine beverages instead of water. Nothing much has changed except the caffeine levels.
Rath, M. (2012). Energy drinks: What is all the hype? The dangers of energy drink consumption Journal of the American Academy of Nurse Practitioners, 24 (2), 70-76 DOI: 10.1111/j.1745-7599.2011.00689.x
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Rath, M. (2012) Energy drinks: What is all the hype? The dangers of energy drink consumption. Journal of the American Academy of Nurse Practitioners, 24(2), 70-76. DOI: 10.1111/j.1745-7599.2011.00689.x
Smoked marijuana reduced spasticity in a small trial of MS patients.
The leading wedge of the medical marijuana movement has traditionally been centered on pot as medicine for the effects of chemotherapy, for the treatment of glaucoma, and for certain kinds of neuropathic pain. From there, the evidence for conditions treatable with marijuana quickly becomes either anecdotal or based on limited studies. But pharmacologists have always been intrigued by the notion of treating certain neurologic conditions with cannabis. Sativex, which is sprayed under the under-the-tongue as a cannabis mist, has been approved for use against multiple sclerosis, or MS, in Canada, the UK, and some European countries. (In the U.S., parent company GW Pharma is seeking FDA approval for the use of Sativex to treat cancer pain).
There is accumulating evidence that cannabinoid receptors may be involved in controlling spasticity, and that anandamide, the brain’s endogenous form of cannabis, is a specific antispasticity agent.
Additional evidence that researchers may be on to something appeared recently in the Canadian Medical Association Journal. Dr. Jody Corey-Bloom and coworkers at the University of California in San Diego conducted a small, placebo-controlled trial with adult patients suffering from poorly controlled spasticity. Thirty participants were randomly divided into two groups. Those in the first group were given a daily joint, and those in the second group received “identical placebo cigarettes.” After three days, the investigators found that smoked marijuana resulted in a reduction in treatment-resistant spasticity, compared to placebo.
Clearly, it’s hard for a study of this sort to be truly blind: Participants, one presumes, had little trouble distinguishing the medicine from the placebo. And in fact, an appendix to the study shows this to be true: “Seventeen participants correctly guessed their treatment phase for all six visits… For the remaining participants, cannabis was correctly guessed on 33/35 visits.” This raises the question of various kinds of self-selection bias and expectancy effects, and the study authors themselves write that the results “might not be generalizable to patients who are cannabis-naïve.” On the other hand, cannabis-naïve patients were in the minority. The average age of the participants was 50, and fully 80% of them admitted to previous “recreational experience” with cannabis. (I don’t have a good Baby Boomer joke for the occasion, but if I did, this is where it would go).
I asked Dr. Corey-Bloom about this potential problem in an email exchange: “The primary outcome measure was the Ashworth Spasticity Scale, which is an objective measure, carried out by an independent rater,” she wrote. “Their job was just to come in and feel the tone around each joint (elbow, hip, knee), rate it, and leave. That's why we think it was so important to have an objective measure, rather than just self-report.”
With all this in mind, the study found that “smoking cannabis reduced patient scores on the modified Ashworth scale by an average of 2.74 points.” The authors conclude: “We saw a beneficial effect of smoked cannabis on treatment-resistant spasticity and pain associated with multiple sclerosis among our participants.”
Other studies have found similar declines in spasticity from cannabinoids, but have tended not to use marijuana in smokable form.
Corey-Bloom, J., Wolfson, T., Gamst, A., Jin, S., Marcotte, T., Bentley, H., & Gouaux, B. (2012). Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial Canadian Medical Association Journal DOI: 10.1503/cmaj.110837
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Corey-Bloom, J., Wolfson, T., Gamst, A., Jin, S., Marcotte, T., Bentley, H., & Gouaux, B. (2012) Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. Canadian Medical Association Journal. DOI: 10.1503/cmaj.110837
Researchers get good results with gabapentin.
Marijuana, as researchers and pundits never tire of pointing out, is the most widely used illegal drug in the world, by a serious margin. And while the argument still rages, for some years now drug researchers have been migrating to the camp that sees marijuana as an addictive drug for a minority of people who exhibit a propensity for addiction. The scientific literature supporting the contention of marijuana as addictive for some users is robust and growing, as is the body of anecdotal evidence. It’s also clear that in many countries, cultures, and subcultures, combining cannabis with tobacco is a common practice that increases health risks all around.
Ongoing works at the Scripps Research Institute’s Pearson Center for Alcoholism and Addiction Research in La Jolla, California, has focused in part on the lack of FDA-approved medical therapies for treating marijuana addiction. Barbara J. Mason and coworkers at Scripps have reported preliminary success in a 12-week, double-blind, placebo-controlled pilot study with 50 treatment-seeking volunteers, using the anti-seizure drug gabapentin. Gabapentin, sold as Neurontin, pops up as a possible treatment for various forms of pain and anxiety, and sharp-eyed readers will recall that gabapentin was one of the ingredients in the now-defunct addiction drug Prometa.
Marijuana addiction numbers are hard to come by, and often inflated, since many small-time pot offenders end up in mandatory treatment programs, where they tend to be classified as marijuana addicts, whether or not that is objectively the case. Nonetheless, there are plenty of people seeking treatment on their own for cannabis dependence. For people strongly addicted to pot, the problems are very real, and withdrawal and abstinence pose serious challenges. People for whom marijuana poses no addictive threat should bear this in mind, the way casual drinkers bear in mind the existence of alcoholism in others.
The study, published recently in Neuropsychopharmacology, says that “activation of brain stress circuitry caused by chronic heavy marijuana use” can lead to withdrawal symptoms that persist “for weeks or even months, as in the case of marijuana craving and sleep disturbances.” A variety of existing medications have been tested in recent years, including buspirone, an anti-anxiety medication; Serzone, an antidepressant; and Wellbutrin, an antidepressant commonly used for smoking cessation. None of these treatments have shown any effect on cannabis use or withdrawal, according to Mason.
Gabapentin, as the name suggests, was modeled after the neurotransmitter GABA, and works via a transporter protein to raise GABA levels. Effective only for partial-onset seizures, common side effects include drowsiness, dizziness, and possible weight gain. It is a popular anti-epileptic drug, because it is relatively safe, with a low side-effect profile, compared to many of the medications in its class. For the same reasons, it is a common treatment for neuropathic pain. In addition to neuralgia, it has found some use as a migraine preventative.
Gabapentin normalizes GABA activation caused by corticotrophin-releasing factor, or CRF. CRF is a major player in the brain’s stress responses. As it turns out, withdrawal from both cannabis and alcohol ramp up anxiety levels by increasing CRF release in the amygdala, animal studies have shown. “Gabapentin had a significant effect in decreasing marijuana use over the course of treatment, relative to placebo,” the authors report. In addition, gabapentin produced “significant reductions in both the acute symptoms of withdrawal as well as in the more commonly persistent symptoms involving mood, craving, and sleep.”
As a bonus, the researchers discovered that “overall improvement in performance across cognitive measures was significantly greater for gabapentin-treated subjects compared with those receiving placebo.” Gabapentin was associated with improvement in “tasks related to neurocognitive executive functioning”—things like attention, concentration, visual-motor functioning, and inhibition. Counseling alone, represented by the placebo group, “resulted in less effective treatment of cannabis use and withdrawal, and no improvement in executive function.”
As in the case of Chantix for cigarette cessation, a treatment, which now requires additional caveats about possible suicidal ideation, researchers looking for a treatment for drug withdrawal, must weigh the benefits of pharmacological treatment against the possible side effects of the treatment itself. Does gabapentin for marijuana withdrawal pass the “Do No Harm” test? According to Mason, it does. “Gabapentin was well tolerated and without significant side effects” in the admittedly small trial study. The two groups did not differ in the number of adverse medical events reported in the first two weeks, when dropout rates due to side effects are highest in these kinds of studies. The investigators were not relying solely on self-reporting, either. They used urine drug screens, and verified that only 3% of the study sample tested positive for other drugs.
In short, the authors report that gabapentin reduced cannabis use and eased withdrawal with an acceptable safety profile and no signs of dependence. Gabapentin, the authors conclude, “may offer the most promising treatment for cannabis withdrawal and dependence studied to date.” Further clinical research is needed, of course, but the positive results of this proof-of-concept study should make funding those a bit easier.
Mason, B., Crean, R., Goodell, V., Light, J., Quello, S., Shadan, F., Buffkins, K., Kyle, M., Adusumalli, M., Begovic, A., & Rao, S. (2012). A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults Neuropsychopharmacology DOI: 10.1038/npp.2012.14
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Mason, B., Crean, R., Goodell, V., Light, J., Quello, S., Shadan, F., Buffkins, K., Kyle, M., Adusumalli, M., Begovic, A.... (2012) A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults. Neuropsychopharmacology. DOI: 10.1038/npp.2012.14
Why do so many smokers combine tobacco with marijuana?
People who smoke a combination of tobacco and marijuana, a common practice overseas for years, and increasingly popular here in the form of “blunts,” may be reacting to some unidentified mechanism that links the two drugs. Researchers believe such smokers would be well advised to consider giving up both drugs at once, rather than one at a time, according to an upcoming study in the journal Addiction.
Clinical trials of adults with cannabis use disorders suggest that “approximately 50% are current tobacco smokers,” according to the report, which was authored by Arpana Agrawal and Michael T. Lynskey of Washington University School of Medicine, and Alan J. Budney of the University of Arkansas for Medical Sciences. “As many cannabis users smoke a mixture of cannabis and tobacco or chase cannabis use with tobacco, and as conditioned cues associated with smoking both substances may trigger use of either substance,” the researchers conclude, “a simultaneous cessation approach with cannabis and tobacco may be most beneficial.”
A blunt is simply a marijuana cigar, with the wrapping paper made of tobacco and the majority of loose tobacco removed and replaced with marijuana. In Europe, smokers commonly mix the two substances together and roll the combination into a single joint, the precise ratio of cannabis and nicotine varying with the desires of the user. “There is accumulating evidence that some mechanisms linking cannabis and tobacco use are distinct from those contributing to co-occurring use of drugs in general,” the investigators say. Or, as psychiatry postdoc Erica Peters of Yale put it in a press release, “There’s something about tobacco use that seems to worsen marijuana use in some way.” The researchers believe that this “something” involved may be a genetic predisposition. In addition to an overall genetic proclivity for addiction, do dual smokers inherit a specific propensity for smoked substances? We don’t know—but evidence is weak and contradictory so far.
Wouldn’t it be easier to quit just one drug, using the other as a crutch? The researchers don’t think so, and here’s why: In the few studies available, for every dually addicted participant who reported greater aggression, anger, and irritability with simultaneous cessation, “comparable numbers of participants rated withdrawal associated with dual abstinence as less severe than withdrawal from either drug alone.” So, for dual abusers, some of them may have better luck if they quit marijuana and cigarettes at the same time. Why? The authors suggest that “absence of smoking cues when abstaining from both substances may reduce withdrawal severity in some individuals.” In other words, revisiting the route of administration, a.k.a. smoking, may trigger cravings for the drug you’re trying to quit. This form of “respiratory adaption” may work in others ways. For instance, the authors note that, “in addition to flavorants, cigarettes typically contain compounds (e.g. salicylates) that have anti-inflammatory and anesthetic effects which may facilitate cannabis inhalation.”
Studies of teens diagnosed with cannabis use disorder have shown that continued tobacco used is associated with a poor cannabis abstention rate. But there are fewer studies suggesting the reverse—that cigarette smokers fair poorly in quitting if they persist in cannabis use. No one really knows, and dual users will have to find out for themselves which categories seems to best suit them when it comes time to deal with quitting.
We will pass up the opportunity to examine the genetic research in detail. Suffice to say that while marijuana addiction probably has a genetic component like other addictions, genetic studies have not identified any gene variants as strong candidates thus far. The case is stronger for cigarettes, but to date no genetic mechanisms have been uncovered that definitively show a neurobiological pathway that directly connects the two addictions.
There are all sorts of environmental factors too, of course. Peer influences are often cited, but those influences often seem tautological: Drug-using teens are members of the drug-using teens group. Tobacco users report earlier opportunities to use cannabis, which might have an effect, if anybody knew how and why it happens.
Further complicating matters is the fact that withdrawal from nicotine and withdrawal from marijuana share a number of similarities. The researchers state that “similar withdrawal syndromes, with many symptoms in common, may have important treatment implications.” As the authors sum it up, cannabis withdrawal consists of “anger, aggression or irritability, nervousness or anxiety, sleep difficulties, decreased appetite or weight loss, psychomotor agitation or restlessness, depressed mood, and less commonly, physical symptoms such as stomach pain and shakes/tremors.” Others complain of night sweats and temperature sensitivity.
And the symptoms of nicotine withdrawal? In essence, the same. The difference, say the authors, is that cannabis withdrawal tends to produce more irritability and decreased appetite, while tobacco withdrawal brings on an appetite increase and more immediate, sustained craving. Otherwise, the similarities far outnumber the differences.
None of this, however, has been reflected in the structure of treatment programs: “Emerging evidence suggests that dual abstinence may predict better cessation outcomes, yet empirically researched treatments tailored for co-occurring use are lacking.”
The truth is, we don’t really know for certain why many smokers prefer to consume tobacco and marijuana in combination. But we do know several reasons why it’s not a good idea. Many of the health-related harms are similar, and presumably cumulative: chronic bronchitis, wheezing, morning sputum, coughing—smokers know the drill. Another study cited by the authors found that dual smokers reported smoking as many cigarettes as those who only smoked tobacco. All of this can lead to “considerable elevation in odds of respiratory distress indicators and reduced lung functioning in those who used both.” However, there is no strong link at present between marijuana smoking and lung cancer.
Some researchers believe that receptor cross-talk allows cannabis to modify receptors for nicotine, or vice versa. Genes involved in drug metabolism might somehow predispose a subset of addicts to prefer smoking. But at present, there are no solid genetic or environmental influences consistent enough to account for a specific linkage between marijuana addiction and nicotine addiction, or a specific genetic proclivity for smoking as a means of drug administration.
Agrawal, A., Budney, A., & Lynskey, M. (2012). The Co-occurring Use and Misuse of Cannabis and Tobacco: A Review Addiction DOI: 10.1111/j.1360-0443.2012.03837.x
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Agrawal, A., Budney, A., & Lynskey, M. (2012) The Co-occurring Use and Misuse of Cannabis and Tobacco: A Review. Addiction. DOI: 10.1111/j.1360-0443.2012.03837.x
“A potentially life-threatening situation.”
Earlier this month, state officials became alarmed by a cluster of puzzling health problems that had suddenly popped up in Casper, Wyoming, population 55,000. Three young people had been hospitalized with kidney injuries, and dozens of others were allegedly suffering from vomiting and back pain after smoking or snorting an herbal product sold as “blueberry spice.” The Poison Review reported that the outbreak was presently under investigation by state medical officials. “At this point we are viewing use of this drug as a potentially life-threatening situation,” said Tracy Murphy, Wyoming state epidemiologist.
It is beginning to look like acute kidney injury from the newer synthetic stimulants may be a genuine threat. And if that wasn’t bad enough, continuing research has implicated MDMA, better known as Ecstasy, as another potential source of kidney damage. Recreational druggies, forewarned is forearmed.
Bath salts first. In the Wyoming case, while the drug in question may have been one of the synthetic marijuana products marketed as Spice, it’s entirely possible that the drug in question was actually one or more of the new synthetic stimulants called bath salts. (Quality control and truth in packaging are not part of this industry). The American Journal of Kidney Diseases recently published a report titled “Recurrent Acute Kidney Injury Following Bath Salts Intoxication.” It features a case history that Yale researchers believe to be “the first report of recurrent acute kidney injury associated with repeated bath salts intoxication.” The most common causes for emergency room admissions due to bath salts—primarily the drugs MDPV and mephedrone—are agitation, hallucinations, and tachycardia, the authors report. But the case report of a 26-year old man showed recurrent kidney injury after using bath salts. The authors speculate that the damage resulted from “severe renal vasospasm induced by these vasoactive substances.” (A vasoactive substance can constrict or dilate blood vessels.)
A possible secondary mechanism of action for kidney damage among bath salt users is rhabdomyolysis—a breakdown of muscle fibers that releases muscle fiber contents into the bloodstream, causing severe kidney damage. Heavy alcohol and drug use, especially cocaine, are also known risk factors for this condition. The complicating factor here is that rhabdomyolysis has also been described in cases of MDMA intoxication, and here we arrived at the second part of the story.
In 2008, the Clinical Journal of the American Society of Nephrology published “The Agony of Ecstasy: MDMA and the Kidney.” In this study, Garland A. Campbell and Mitchell H. Rosner of the University of Virginia Department of Medicine found that “Ecstasy has been associated with acute kidney injury that is most commonly secondary to nontraumatic rhabdomyolysis but also has been reported in the setting of drug-induced liver failure and drug-induced vasculitis.”
Chemically, MDMA is another amphetamine spinoff, like mephedrone and other bath salts. Many people take this club drug regularly without apparent harm, whereas others seem to be acutely sensitive and can experience serious toxicity, possibly due to genetic variance in the breakdown enzyme CYP2D6. The authors trace the first case report of acute kidney injury due to Ecstasy back to 1992, but “because most of these data are accrued from case reports, the absolute incidence of this complication cannot be determined.”
Campbell and Rosner believe that nontraumatic rhabdomyolysis is a likely culprit in many cases, and speculate that the condition is “greatly compounded by the ambient temperature, which in crowded rave parties is usually elevated.” If a physician suspects rhabdomyolysis in an Ecstasy user, “aggressive cooling measures should be undertaken to lower the patient’s core temperature to levels that will lessen further muscle and end-organ injury.” This complication can have far-reaching effects: The authors note the case history of “transplant graft loss of both kidneys obtained from a donor with a history of recent Ecstasy use.”
In addition, there may be undocumented risks to the liver as well. An earlier study by Andreu et. al. claims that “up to 31% of all drug toxicity-related acute hepatic failure is due to MDMA… Patients with severe acute hepatic failure secondary to ecstasy use often survive with supportive care and have successfully undergone liver transplantation.”
But the picture is far from clear: “Unfortunately, no case reports of acute kidney injury secondary to ecstasy have had renal biopsies performed to allow for further elucidation…” And attributing firm causation is difficult, due to the fact that MDMA users often use other drugs in combination, some of which, like cocaine, can cause kidney problem all by themselves.
A study by Harold Kalant of the University of Toronto’s Addiction Research Foundation, published in the Canadian Medical Association Journal, proposed that “dantrolene, which is a drug used to stop the intense muscle contractures in malignant hyperthermia, should also be useful in the hyperthermic type of MDMA toxicity. Numerous cases have now been treated in this way, some with rapid and dramatic results even when the clinical picture suggested the likelihood of a fatal outcome.”
Adebamiro, A., and Perazella, M. (2012). Recurrent Acute Kidney Injury Following Bath Salts Intoxication American Journal of Kidney Diseases, 59 (2), 273-275 DOI: 10.1053/j.ajkd.2011.10.012
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Adebamiro, A., & Perazella, M. (2012) Recurrent Acute Kidney Injury Following Bath Salts Intoxication. American Journal of Kidney Diseases, 59(2), 273-275. DOI: 10.1053/j.ajkd.2011.10.012
“Morning people” have more caffeine-related sleep problems.
Let me start by saying that I love this caffeine study for personal reasons. As a lifelong night owl, I have been chastised by wife, family, and friends over the years for my regular habit of drinking coffee after 10 pm. (And falling easily asleep two or three hours later, if I choose to.) Other coffee drinkers have told me how rare and weird this is. If we have a cup, they tell me, or even an afternoon sip, we toss and turn all night.
As it turns out, I was talking to the wrong kind of coffee drinkers. I needed to consult my crowd, and that’s what I did. I checked in with a few confirmed fellow night owls, and yes, a few of them reported that they had no problems going to sleep after a late night cup or two.
Anecdotal, of course—but a recent clinical study published in Sleep Medicine backs me up. The study, “Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: Preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep,” sets out to examine the effects of caffeine on the sleep patterns of college students. Researchers at Stanford told the students to keep sleep logs and to wear an actigraphy wristband to record rest/activity cycles. The students filled out daily questionnaires about their caffeine intake at different times of the day, and gave saliva samples for caffeine assessments.
The scientists were able to accurately predict salivary caffeine concentrations based on the questionnaires, which was the primary intent of the study. But in the process, they discovered what they believe to be “a novel relationship between the effects of caffeine on sleep and genotype and chronotype.” What the researchers ended up with was some seriously suggestive evidence about the relationship of caffeine and natural sleep rhythms. (Here’s a nifty little test to determine whether you are a lark or an owl, i.e., your chronotype.)
Typically, clinical trials with caffeine are limited to the basic question: How much coffee did you drink today? But the Stanford researchers wanted to include the many variables that modulate caffeine intake—things like the timing of ingestion, the variations in the amount of caffeine among beverages, individual variations in caffeine metabolism, and the wide differences in half-life that caffeine can exhibit under various circumstances. They attempted to establish the students’ genotypes for adenosine receptors, where caffeine does most of its work, and to select volunteers who had “statistically indistinguishable” differences in adenosine receptor gene frequencies.
As you might expect, even among students, caffeine intake progressively decreased throughout the day in the study group. However, a small number of participants continued their intake of caffeine well into the night. The metric known as “wake after sleep onset,” or WASO, was used as the primary measurement of sleep disruption. “Our data indicate caffeine strongly influences WASO in those who self-identify as morning-type,” the researchers found. “It affects WASO less so in those who are neither type, and does not appear to affect WASO in those who are evening-type. To our knowledge, there have been no previous reports linking the effects of caffeine and chronotype.”
Some warnings on the study: It involved only 50 college students. And they were students, meaning their schedules were highly erratic by definition, and they were chronically sleep-deprived by habit. The study authors attempted to turn this defect into a virtue, noting that “the students were under such homeostatic pressure that their mood had little effect on their sleep.” Nonetheless, we will need to see if the findings hold up using less, er, unpredictable subjects.
If they do hold up, it will make it easier for people to understand the homily delivered by the coffee-drinking grandmother of a friend of mine: “The only time coffee ever kept me awake was when I knew there was another cup in the pot.”
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Nova, P., Hernandez, B., Ptolemy, A., & Zeitzer, J. (2012). Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: Preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep Sleep Medicine DOI: 10.1016/j.sleep.2011.11.011... Read more »
Nova, P., Hernandez, B., Ptolemy, A., & Zeitzer, J. (2012) Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: Preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep. Sleep Medicine. DOI: 10.1016/j.sleep.2011.11.011
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