Wednesday, December 16, 2015

Annual NIDA Survey Shows Declines in Teen Drug Use


The kids are all right.

Every year, the National Institute of Drug Abuse (NIDA), under the auspices of the National Institutes of Health, conducts its Monitoring the Future survey of drug use among American young people in the 8th, 10th, and 12th grades.

This year, students got very good marks. “We are heartened to see that most illicit drug use is not increasing, non-medical use of prescription opioids is decreasing, and there is improvement in alcohol and cigarette use rates,” said Dr. Nora Volkow, Director of NIDA.

Here are some highlights from this year’s study:

— Despite nationwide concerns over prescription opioid and heroin abuse, heroin use among students has hit historic lows, while “narcotics other than heroin” continue to decline as well. Only 4.4% of high school seniors reported Vicodin use in the past year, compared to more than 10% in 2003.

—The downward trend in teen cigarette smoking continues, and is presently at the lowest rate in the study’s history. 5.5% of high school seniors had smoked, compared to 10.7% in 2010. The highest rate of smoking recorded among seniors was 25% in 1997. Among 10th graders, daily smoking has been cut in half in the past five years, down to 3%.

—For the first time since the annual study began, marijuana use exceeds cigarette use among 12th graders. 35% of high school seniors reported past-year cannabis use, and 6% reported daily use. (Daily use of cigarettes was 5.5%). Disapproval rates concerning regular smoking have continued to rise, even as the disapproval rates concerning marijuana risk continue to fall among teens.

—Alcohol use continues its slow but steady downward trend among teens, “with significant reductions seen in the past five years in nearly all measures.” However, it remains the most commonly used drug, 58% of seniors having used it in the past year.

—Synthetic marijuana, the class of Spice/K2/herbal incense drugs, continues to decline in popularity, presumably due to fears about adverse side effects.

—16% of 12th graders reported using e-cigarettes in the past month, although only one out of five student users said they were vaping nicotine. 13% of 8th graders said they had no idea what was in the e-cigarette device they were using. Other answers ranged from flavorings to marijuana.

Sunday, November 22, 2015

The Great Gateway Theory

Smoke pot, shoot smack?

The Great Gateway Hypothesis has had a long, controversial run as a central tenet of American anti-drug campaigns. As put forth by Denise B. Kandell of Columbia University and others in 1975, and refined and redefined ever since, the gateway theory essentially posits that soft drugs like alcohol, cigarettes, and marijuana—particularly marijuana—make users more likely to graduate to hard drugs like cocaine and heroin. What is implied is that gateway drugs cause users to move to harder drugs, by some unknown mechanism. The gateway theory forms part of the backbone of the War on Drugs. By staying tough on marijuana use, policy makers believe they will have much broader impacts on hard drug use down the road.

This notion is virtually an article of faith in the drug prevention community. It just feels intuitively right: Scratch a junkie, and you’ll find a younger, embryonic pot smoker or furtive teenage drinker. Ergo, prevent teen pot smoking, and you will block the blossoming of a multitude of future hard drug addicts.

For years, the gateway hypothesis has had its share of contentious opponents. The countervailing theory is known primarily as CLA, for Common Liability to Addiction, the genetically based approach that lines up with the notion of addiction as a chronic disease entity. Most genetic association studies have failed to record risk variations for addiction that are specific to one addictive drug. Writing in 2012 in Drug and Alcohol Dependence, Michael M. Vanyukov of the University of Pittsburgh, along with a large group of prominent addiction researchers, argued that the gateway hypothesis is essentially a form of circular reasoning. “It is drug use itself that is viewed as the cause of drug use development,” they write. The staged progression from one drug to another “is defined in a circular manner: a stage is said to be reached when a certain drug is used, but this drug is supposed to be used only upon reaching this stage. In other words, the stage both is identified by the drug and identifies the drug. In effect, the drug is identical to the stage.”

The researchers reject any causal claims on behalf of the gateway hypothesis and insist there is no necessary usage of soft drugs at an earlier stage to pave the way for hardcore addiction, however watertight the idea might sound. The high correlations are “artifactual,” they argue, “because they are estimated among hard drug users, without taking into account the large population of those who try or even habitually use marijuana but never transition to harder drugs.” A common cause, such as an underlying vulnerability to all drugs of abuse, seems more to the point, they insist. There is nothing out there to suggest that “these stages are either obligatory or universal, nor that all persons must progress through each in turn… the initiation order is frequently reversed even for the licit-to-illicit sequence.” There is only one stage that universally precedes hard drug use, they argue. And that is non-use. “It is the non-use then, which should be the actual gateway condition.”

The leading theory supporting the gateway hypothesis is that some as yet undetermined mechanism of “sensitization” occurs after using a gateway drug. But there is no science supporting this notion. “If sensitization does occur,” the researchers say, “it is equivalent to an increase in individual liability at the level of neurochemical mechanisms of addiction.”

The paper in Drug and Alcohol Dependence notes that in Japan, where marijuana is used by less than 5 percent of young people, “cannabis is not used first by a staggering 83.2% of the users of other illicit drugs, thus violating the gateway sequence.” Japan also handily knocks down the idea of alcohol as a gateway drug: Whereas the prevalence of aldehyde dehydrogenase deficiency—the so-called alcohol flush reaction—keeps many Asians from drinking alcohol regularly, this does not correlate with lower rates of non-alcohol substance use in that population.

All of this would seem to put the last nail in the notion that “involvement in various classes of drugs is not opportunistic but follows definite pathways,” as Vanyukov et. al. put it. Common sense seems to be ahead of official drug policy in this regard.

For proponents of common liability to addiction models, any staged sequencing of drug use is considered opportunistic and trivial. Which, interestingly, is how many addicts tend to view the gateway theory. But the idea of marijuana or alcohol as a gateway drug just feels intuitively correct to many people. Part of the problem is chronological. “At the relatively distal time when genetic relationships are usually evaluated,” the authors maintain, “the role of this early-acting factor may be as difficult to detect as it is to find a match that started a forest fire.” Your genetic endowment is with you from birth, while your first drink or toke of marijuana does not happen for a decade or two. Individual environmental conditions, from epigenetic changes to a move to a different neighborhood, determine how it will play out down the road, but these factors are mostly invisible at the time of addiction.

All of this matters from a policy point of view, because research “may be hindered or misdirected if a concept lacking substance, validity and utility is accorded prominence.” However, even when the gateway hypothesis is taken as a given, different legal and social outcomes are still possible. The best example is found in The Netherlands. The prevailing belief there is that “the pharmacological effects of cannabis increase adolescents’ likelihood of using other drugs,” as stated  by Wayne Hall, a professor of public health policy at the University of Queensland, Australia. Writing in Addiction, Hall says that drug policy analysts in The Netherlands have argued that the fabled gateway “is a consequence of the fact that cannabis and other illicit drugs are sold in the same black market; they have advocated for the decriminalization of cannabis use and small retail sales in order to break the nexus between cannabis use and the use of other illicit drugs.”

This “Marijuana Shop” approach may have direct relevance in the U.S., in the wake of cannabis legalization in Washington and Colorado. James Anthony, a professor of epidemiology at the Bloomberg School of Public Health at Johns Hopkins, writes about the real-world ramifications of the cannabis shop in Addiction: “Do we actually achieve a near-term delay in the time to a young person’s first chance to try cocaine or heroin... [or] do we run the risk of accumulating more cases of dependence on marijuana, or other hazards attributable to non-essential marijuana use?

The true gateways to addiction appear to be behavioral. As part of their genetic endowment, budding addicts are far more likely than other people to exhibit behavioral “dysregulation” when young, in the form of disinhibition, impulsivity, and antisocial behaviors. More than half of all addicts are co-morbid, meaning they also have a psychological or behavioral disorder in addition to addiction. Further analysis of this fact would seem to be a more fruitful research avenue than simply prodding at alcohol or marijuana in an effort to uncover their chemical “secrets” for compelling future drug use.

First published April 14, 2013.

Saturday, October 31, 2015

Freud and his Drug Demons


Cocaine addiction and psychoanalysis.

That Sigmund Freud was a cocaine abuser for some portion of his professional life is by now well known. Reading An Anatomy of Addiction by Howard Markel, M.D., which chronicles the careers of Freud and another famed cocaine abuser, Johns Hopkins surgeon William Halsted, I was struck by the many ways in which even the father of modern psychotherapy could not see the delusions, evasions and outright lies that were the byproducts of his very own disease of the body and mind: drug addiction. Markel makes the case that in several important ways Freud’s cocaine addiction was hopelessly entangled with, and partially responsible for, his theorizing about the workings of the mind.

In 1884, Freud published his book, On Coca, a treatise on the wonders of cocaine. To his fiance, he wrote: “I have other hopes and intentions about [cocaine]. I take very small doses of it regularly against depression and against indigestion and with the most brilliant of success.” The book, a comprehensive review of cocaine’s effects, had an “n of 1”: “I have carried out experiments and studied, in myself and others, the effect of coca on the healthy human body.”

One of the defects of On Coca was its assertion that the drug was an effective antidote to serious morphine and alcohol abuse. Most astonishingly, however, Freud “skimmed over cocaine’s most important clinical use as a local anesthetic.” That discovery was later championed by ophthalmologist Carl Koller, whom Freud never forgave, even though the mistake was Freud’s alone. It seems reasonable to suggest that a moody doctor, who happened to be treating a close friend for morphine addiction at the time, might tend to focus on cocaine’s use against depression and drug abuse. And two years later, Freud vigorously fought back against an influential American doctor’s unambiguous assertion that cocaine was addictive. The U.S. physician had written that a “doctor self-prescribing cocaine was the equivalent of the lawyer representing himself in court: each had a fool for a patient or client.”

Markel notes that it is “also telling that he does not reveal to [his fiancé] the precise amount of cocaine he was ingesting. In fact, throughout his notes during this period, Freud minimizes the amount and frequency of his cocaine dosage, using such terms as ‘a little cocaine’ or a ‘bit of cocaine,’ a tactic many substance abusers employ to avoid the disapproval or intervention of others.”

Writing in his capacity as a physician, Markel states:

In light of the physical symptoms Freud suffered during this period, in my medical opinion, there is ample evidence that he was abusing significant amounts of cocaine during the early 1890s and that he was using it in a dependent, if not outright addictive fashion. In fact, cocaine likely had a negative effect on virtually every aspect of Sigmund’s personal relationships, behavior, and health. We can make such a declarative statement because his letters to Wilhelm Fleiss tells us precisely so…. Sigmund explained that he was suffering from a Fliessian syndrome of ‘crossed reflexes’ of the nose, brain, and genitals that had led to severe migraine headaches. The excruciating pain, not surprisingly, could only be interrupted by the multiple doses of cocaine prescribed by Dr. Fliess.

It was not pretty: “From a diagnostic standpoint, Sigmund’s nasal stuffiness is intriguing… Sigmund’s need for cauterization—the placement of a hot knife against swollen, blocked nasal tissue to, literally, burn open a passage for air—in concert with his disinclination to write suggests serious cocaine abuse.” And also telling is Freud’s habit of smoking 20 or more cigars each day.

By 1894, Markel writes, “the cardiac symptoms associated with cocaine use and the severe depression and headaches after its use—similar to what Sigmund was experiencing—were finally being reported in the medical journals of the day.” And, much like an alcoholic explaining away his chronic stomach troubles, “Freud continued to search for alternative explanations for his chest pain rather than seriously contemplate cocaine’s potential role in the matter.”

For readers in need of socioenvironmental triggers for addiction, Freud had a ready supply: “risk taking, resentments, loneliness, alienation, emotional pain, traumatic family experiences, phobias, neuroses, depression, denials and secretiveness about his sexuality, a possible sexual relationship with his sister-in-law, a brief flirtation with excessive drinking, and his self-documented cocaine abuse, to name some of his demons.”

About 1896, Freud stopped discussing his use of cocaine, and more or less dropped the subject altogether. Later in life, he speculated on whether his love of cigars (which eventually killed him) had helped keep him away from the task of working out his own psychological problems. “One wonders,” writes Markel, “whether his compulsive cocaine abuse from 1884 to 1896 was one of those unexplored problems.”

From 1896 to 1900, presumably cocaine-free years, Freud suffered from “depression, cocaine urges, occasional binge drinking, sexual affairs, caustic behaviors, and emotional absence.” To Markel, this adds up to the classic portrait of a “dry drunk,” AA’s description of someone who has given up drinking and drugs, and is miserable about it, and is making everyone around them miserable as well.

Markel points to the theory promulgated by historian Peter Swales to the effect that Freud’s entire concept of the libido “is merely a mask and a symbol for cocaine; the drug, or rather its invisible ghost, haunts the whole of Freud’s writing to the very end.”

Monday, October 12, 2015

Cannabis Receptors and the Runner’s High

[First published August 4 2010]

Maybe it isn't endorphins after all.

What do long-distance running and marijuana smoking have in common? Quite possibly, more than you’d think. A growing body of research suggests that the runner’s high and the cannabis high are more similar than previously imagined.

The nature of the runner’s high is inconsistent and ephemeral, involving several key neurotransmitters and hormones, and therefore difficult to measure. Much of the evidence comes in the form of animal models. Endocannabinoids—the body’s internal cannabis—“seem to contribute to the motivational aspects of voluntary running in rodents.” Knockout mice lacking the cannabinioid CB1 receptor, it turns out, spend less time wheel running than normal mice. 

A Canadian neuroscientist who blogs as NeuroKuz suggests that “a reduction in CB1 levels could lead to less binding of endocannabinoids to receptors in brain circuits that drive motivation to exercise.” NeuroKuz speculates on why this might be the case. Physical activity and obtaining rewards are clearly linked. The fittest and fleetest obtain the most food. “A possible explanation for the runner’s high, or ‘second wind,’ a feeling of intense euphoria associated with going on a long run, is that our brains are stuck thinking that lots of exercise should be accompanied by a reward.”

In 2004, the British Journal of Sports Medicine ran a research review, “Endocannabinoids and exercise,” which seriously disputed the “endorphin hypothesis” assumed to be behind the runner’s high. To begin with, other studies have shown that exercise activates the endocannabinoid system.

“In recent years,” according to the authors, “several prominent endorphin researchers—for example, Dr Huda Akil and Dr. Solomon Snyder—have publicly criticised the hypothesis as being ‘overly simplistic,’ being ‘poorly supported by scientific evidence’, and a ‘myth perpetrated by pop culture.’” The primary problem is that the opioid system is responsible for respiratory depression, pinpoint pupils, and other effects distinctly unhelpful to runners.

The investigators wired up college students and put them to work in the gym, and found that “exercise of moderate intensity dramatically increased concentrations of anandamide in blood plasma.” The researchers break the runner’s high into four major components. Exercise, they say, “suppresses pain, induces sedation, reduces stress, and elevates mood.” Some of the parallels with the cannabis high are not hard to tease out: “Analgesia, sedation (post-exercise calm or glow), a reduction in anxiety, euphoria, and difficulties in estimating the passage of time.”

There are cannabinoid receptors in muscles, skin and the lungs. Intriguingly, the authors suggest that unlike “other rhythmic endurance activities such as swimming, running is a weight bearing sport in which the feet must absorb the ‘pounding of the pavement.’” Swimming, the authors speculate, “may not stimulate endocannabinoid release to as great an extent as running.” Moreover, “cannabinoids produce neither the respiratory depression, meiosis, or strong inhibition of gastrointestinal motility associated with opiates and opioids. This is because there are few CB1 receptors in the brainstem and, apparently, the large intestine.”

A big question remains: What about running and the “motor inhibition” characteristic of high-dose cannabis? (An inhibition that may make cannabis useful in the treatment of movement disorders like tremors or tics.) Running a marathon is not the first thing on the minds of most people after getting high on marijuana.  The paper maintains, however, that at low doses, “cannabinoids tend to produce hyperactivity,” at least in animal models. The CB1 knockout mice were abnormally inactive, due to the effect of cannabinoids on the basal ganglia. Practiced, automatic motor skills like running are controlled in part by the basal ganglia. The authors predict that “low level skills such as running, which are controlled to a higher degree by the basal ganglia than high level skills, such as basketball, hockey, or tennis, may more readily activate the endocannabinoid system.

The authors offer other intriguing bits of evidence. Anandamide, one of the brain’s own cannabinoids, “acts as a vasodilator and products hypotension, and may thus facilitate blood flow during exercise.” In addition, “endocannabinoids and exogenous cannabinoids act as bronchodilators” and could conceivably facilitate breathing during steady exercise. The authors conclude: “Compared with the opioid analgesics, the analgesia produced by the endocannabinoid system is more consistent with exercise induced analgesia.”

Thursday, September 17, 2015

Caffeine, Energy Drinks, and Everything Else


It's the everything else that adds up.

A couple of years ago, coffee drinkers were buoyed by the release of a massive study in the New England Journal of Medicine that “did not support a positive association between coffee drinking and mortality.” In fact, the analysis by Neal D. Freedman and associates showed that even at the level of 6 or more cups per day, coffee consumption appeared to be mildly protective against diabetes, stroke, and death due to inflammatory diseases. Men who drank that much coffee had a 10% lower risk of death, and women in this category show a 15% lower death risk. Coffee, it seemed, was good for you.

Hooray for coffee—but lost in the general joy over the findings was the constant association of coffee with unhealthy behaviors like smoking, heavy alcohol, use, and consumption of red meat. And the happy coffee findings did not consider the consumption of caffeine in other forms, such as energy drinks, stay-awake pills, various foodstuffs, and even shampoos.

One of the earliest battles over “energy drinks” was an action taken in 1911 under the new Pure Food and Drug Act—the seizure by government agents of 40 kegs and 20 barrels of Coca-Cola syrup in Chattanooga. Led by chemist Harvey Wiley, the first administrator of the Food and Drug Administration (FDA), agents of the fledgling organization acted on the belief that the soft drink contained enough caffeine to pose a significant public health hazard. The court case went on forever. Eventually Coca-Cola cut back on caffeine content, and the charges were dropped.

Jump cut to 2012, and watch the FDA grapple with the same question a hundred years later, citing concerns about undocumented caffeine levels in so-called energy drinks in the wake of an alleged link between the caffeinated soft drinks and the death of several young people. According to Dr. Kent Sepkowitz, writing in the Journal of the American Medical Association, while only 6% of young American men consume the drinks, “in a recent survey of U.S. overseas troops, 45% reported daily use.” In 2006, more than 500 new energy drinks hit the market. By 2011, sales of energy drinks in the U.S. climbed by more than 15% to almost $9 billion.

Death by caffeine has long been a subject of morbid interest, and an article in the Journal of Caffeine Research  by Jack E. James of Iceland’s Reykjavik University questions these prevailing assumptions, and brings together the latest research on this perennial question, including, yes, a consideration of whether the time has come to regulate caffeine as some sort of controlled substance.

In 2013, the FDA released reports that attributed a total of 18 deaths to energy drinks. Somewhere between 3 and 10 grams of caffeine will kill you, especially if you are young, old, or suffer from various health problems. The generally accepted lethal dose is 10 g. The wide gap in estimates and mortality reports reflects the wide variation in caffeine’s effects.  Half the lethal dose can kill a child, and some adults have survived 10 times that amount. As I wrote in an earlier post (“Energy Drinks: What’s the Big Deal?”): “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 hearth disease or hypertension. And if you do OD on high caffeine intake, it will not be pleasant: Severe cardiac arrhythmias, palpitations, panic, mania, muscle spasms, and seizures.”

Warning signs include racing heart, abdominal pain, vomiting, and agitation. Since the average cup of coffee weighs in at about 100 milligrams, there doesn’t seem to be much to worry about in that regard. Nonetheless, the American National Poison Data System (NPDS) has more than 6,000 “case mentions” related to caffeine. One of these cases generated considerable press coverage: the death of a 14 year-old girl with an inherited connective tissue disorder.

In his article for the Journal of Caffeine Research, James starts by noting other fatalities, including two confirmed caffeine-related deaths in New Mexico, and four in Sweden, among other long-standing historical reports. Still, not much there to wring your hands over—but James insists that data on poisonings “do not show what contributory role caffeine may have had in cases where fatal and near-fatal outcomes were deemed to have been due to other compounds also present.”

Fair enough. But here is where the argument gets interesting. “Considerably smaller amounts of caffeine,” writes James, "may be fatal under a variety of atypical though not necessarily rare circumstances.” Among these, he singles out: 1) Prior medical conditions predisposing patients toward unusual caffeine metabolism. 2) Unknown interactions and synergies with prescription, over-the-counter, and illegal drugs. 3) Physical stress and high-intensity sports. 4) Children, for whom caffeine is easily available.

James claims we don’t know enough to insist caffeine is essentially harmless, let along good for us in large doses. He compiled this eye-opening list of foods and other products that sometimes contain caffeine: ice cream, chewing gum, yogurt, breakfast cereal, cookies, flavored milk, beef jerky, cold and flu medications, weight-loss compounds, breath-freshener sprays and mints, skin lotion, lip balm, soap, shampoo, and, most notably, as a contaminant in illegal drugs. James says that the largest category of incidents with over-caffeinated young people involve “miscellaneous stimulants and street drugs…”

As for energy drinks themselves: “As a nonselective adenosine receptor antagonist, caffeine counteracts the somnogenic effects of acute alcohol intoxication, and alcohol may in turn ameliorate the anxiogenic effects of caffeine.” It’s an age-old practice: caffeine doesn’t sober up drunks, but it does keep them awake. James believes the evidence shows that the combination of caffeine and alcohol increases the risks of unprotected sex, sexual assault, drunk driving, violence, and emergency room visits.

Furthermore, “the ubiquity of caffeine is such that it has become a biologically significant contaminant of freshwater and marine systems….”

Finally, James offers a vision of a caffeine-regulated future, noting that Denmark, France, and Norway have already introduced sales restrictions on energy drinks. Restrictions on the sale of powdered caffeine may follow, as a valid public health measure. “Canada requires labeling in relation to the same product, advising that it should not be mixed with alcohol.” Other countries have labeled energy drinks as “high caffeine content” beverages. And Sweden regulates the number of caffeine tablets that can be purchased at one time from a drugstore.  Meanwhile, in the U.S., makers of energy drinks, unlike makers of soft drinks, do not even have to print the amount of caffeine on the label as dietary information, although this is in the process of changing. Major energy drink makers are moving to put caffeine content labels on their products, in part to shift their relationship with the FDA. Last year, The Food and Drug Administration advised consumers to avoid powdered caffeine due to health risks.

Originally published March 13, 2013


Tuesday, July 21, 2015

Marijuana Deconstructed


What's In Your Weed?

Australia has one of the highest rates of marijuana use in the world, but until recently, nobody could say for certain what, exactly, Australians were smoking. Researchers at the University of Sydney and the University of New South Wales recently analyzed hundreds of cannabis samples seized by Australian police, and put together comprehensive data on street-level marijuana potency across the country. They sampled police seizures and plants from crop eradication operations. The mean THC content of the samples was 14.88%, while absolute levels varied from less than 1% THC to almost 40%.  Writing in PLoS one, Wendy Swift and colleagues found that roughly ¾ of the samples contained at least 10% total THC. Half the samples contained levels of 15% or higher—“the level recommended by the Garretsen Commission as warranting classification of cannabis as a ‘hard’ drug in the Netherlands.”

In the U.S., recent studies have shown that THC levels in cannabis from 1993 averaged 3.4%, and then climbed to THC levels in 2008 of almost 9%. By 2015, marijuana with THC levels of 20% were for sale in Colorado and Washington.

CBD, or cannabidiol, another constituent of cannabis, has garnered considerable attention in the research community as well as the medical marijuana constituency due to its anti-emetic properties. Like many other cannabinoids, CBD is non-psychoactive, and acts as a muscle relaxant as well. CBD levels in the U.S. have remained consistently low over the past 20 years, at 0.3-0.4%. In the Australian study, about 90% of cannabis samples contained less than 0.1% total CBD, based on chromatographic analysis, although some of the samples had levels as high as 6%.

The Australian samples also showed relatively high amounts of CBG, another common cannabinoid. CBG, known as cannabigerol, has been investigated for its pharmacological properties by biotech labs. It is non-psychoactive but useful for inducing sleep and lowering intra-ocular pressure in cases of glaucoma.

CBC, yet another cannabinoid, also acts as a sedative, and is reported to relieve pain, while also moderating the effects of THC. The Australian investigators believe that, as with CBD, “the trend for maximizing THC production may have led to marginalization of CBC as historically, CBC has sometimes been reported to be the second or third most abundant cannabinoid.”

Is today’s potent, very high-THC marijuana a different drug entirely, compared to the marijuana consumed up until the 21st Century? And does super-grass have an adverse effect on the mental health of users? The most obvious answer is, probably not. Recent attempts to link strong pot to the emergence of psychosis have not been definitive, or even terribly convincing. (However, the evidence for adverse cognitive effects in smokers who start young is more convincing).

It’s not terribly difficult to track how ditch weed evolved into sinsemilla. It is the historical result of several trends: 1) Selective breeding of cannabis strains with high THC/low CBD profiles, 2) near-universal preference for female plants (sinsemilla), 3) the rise of controlled-environment indoor cultivation, and 4) global availability of high-end hybrid seeds for commercial growing operations. And in the Australian sample, much of the marijuana came from areas like Byron Bay, Lismore, and Tweed Heads, where the concentration of specialist cultivators is similar to that of Humboldt County, California.

The investigators admit that “there is little research systematically addressing the public health impacts of use of different strengths and types of cannabis,” such as increases in cannabis addiction and mental health problems. The strongest evidence consistent with lab research is that “CBD may prevent or inhibit the psychotogenic and memory-impairing effects of THC. While the evidence for the ameliorating effects of CBD is not universal, it is thought that consumption of high THC/low CBD cannabis may predispose users towards adverse psychiatric effects….”

The THC rates in Australia are in line with or slightly higher than average values in several other countries. Can an increase in THC potency and corresponding reduction in other key cannabinoids be the reason for a concomitant increase in users seeking treatment for marijuana dependency? Not necessarily, say the investigators. Drug courts, coupled with greater treatment opportunities, might account for the rise. And schizophrenia? “Modelling research does not indicate increases in levels of schizophrenia commensurate with increases in cannabis use.”

One significant problem with surveys of this nature is the matter of determining marijuana’s effective potency—the amount of THC actually ingested by smokers. This may vary considerably, depending upon such factors as “natural variations in the cannabinoid content of plants, the part of the plant consumed, route of administration, and user titration of dose to compensate for differing levels of THC in different smoked material.”

Wendy Swift and her coworkers call for more research on cannabis users’ preferences, “which might shed light on whether cannabis containing a more balanced mix of THC and CBD would have value in the market, as well as potentially conferring reduced risks to mental wellbeing.”


Swift W., Wong A., Li K.M., Arnold J.C. & McGregor I.S. (2013). Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile., PloS one, PMID: 23894589

(First published at Addiction Inbox Sept. 3 2013)

Graphics Credit: https://budgenius.com/marijuana-testing.html

Monday, July 13, 2015

Such Stuff As Dreams Are Made On: Marijuana and Sleeping


Study sheds potential light on indica vs. sativa debate.

[Thanks to Ivan Oransky (@ivanoransky) for alerting me to this study.]

Anyone who has smoked marijuana more than a couple of times knows that cannabis can alter how you sleep. The effect of cannabis on sleep is even part of the never-ending debate over Cannabis indica vs. Cannabis sativa, the two major species of the marijuana plant. Indica smokers typically report a marijuana high that is body-intensive and often soporific, sometimes leading to the condition aptly known as “couch lock.” Whereas sativa smokers, according to marijuana lore, experience a more cerebral, energetic “head high,” with fewer somatic effects. Not surprisingly, hybrid strains incorporating the alleged characteristics of both indica and sativa strains are popular in the medical marijuana community.

Although there is no official sanction for it in the medical community, marijuana is often dispensed medically for sleep problems. One piece of common wisdom holds that the higher the THC content of marijuana, the more helpful it will be in promoting sleep and improving poor sleep. The stronger the better, in other words. Similarly, indica strains are assumed to promote sleep more than sativa strains.

In an effort to clear the air, so to speak, a group of researchers, writing in Addictive Behaviors, sought to “document naturalistic choice of particular medical cannabis types among individuals who self-report using cannabis for the treatment of sleep problems…. Little research has documented species or cannabinoid concentration preferences among individuals who use medical cannabis for particular conditions…. We also evaluated the interaction between the type of cannabis used and diagnosis of cannabis use disorder among study participants.”

The researchers recruited participants from a medical cannabis dispensary in California under procedures approved by the VA and Stanford University review boards. 163 people with a mean age of 40, who used cannabis twice a day on average, provided self-reported information on their cannabis use for the study. 81 participants reported using cannabis for the management of insomnia, and another 14 reported using cannabis to reduce nightmares. (Frequent smokers insist they dream less. THC does appear to decrease the density of REM cycles, leading to more restful, dream-free sleep, according to some studies. )

So what did they find?

—“Individuals who reported using cannabis for nightmares, compared to those who did not, preferred sativa to indica.” (Small effect.)

Indica, considered the “heavier” high, might have seemed the likely choice here.

—"Individuals who self-report using cannabis to treat symptoms of insomnia and those with greater self-reported sleep latency reported using cannabis with significantly higher concentrations of CBD.” (Large effect.)

Again, a somewhat counterintuitive finding, since it is widely believed that CBD conduces toward a more wakeful state than THC alone.

—“Individuals who used sleep medication less than once/week used cannabis with higher THC concentrations than those who used sleep medication at least once a week.” (Large effect.) “There were no differences in THC concentration as a function of self-reported sleep quality, or use for insomnia or nightmares.”

Pretty straightforward finding: THC makes you sleepy. It is not clear, however, that above a certain threshold, more THC makes you even sleepier. In fact, some researchers would consider this finding unexpected, given that high THC concentrations have been shown to have a stimulating effect.

“Older individuals were less likely to have cannabis use disorder compared to those younger….

No surprise about the older folks, since prior studies show a decrease in the prevalence of cannabis use disorders with age.

“Individuals who preferred sativa or primary sativa hybrid strains were less likely to have cannabis use disorder compared to those who preferred indica or primary indica hybrid strains.” (Small effect.)

If replicated, this finding could have significant implications; both in strengthening programs to reduce marijuana smoking among the very young, and it warning consumers that some evidence suggests indica strains may be more addictive than sativa strains in plants with similar THC/CBD levels and ratios.

—“Neither concentration of THC nor CBD were associated with cannabis use disorder.”

Common sense, but useful to remember. In other addictive behaviors, such as heroin and alcohol abuse, the relative strength of the drug is not the primary determinant of its addictive potential.

Caveats and design limitations: The survey relied on retrospective reports of sleep quality and pot preferences. Also lacking is an examination of additional variables such as PTSD and co-occurring substance abuse.



Tuesday, May 12, 2015

Jack London and his Alcoholic Memoirs


Meet John Barleycorn.

In the early years of the 20th Century, writer Jack London was the equivalent of a rock star. A ruggedly good-looking sportswriter, globetrotting war correspondent, successful novelist and short story writer, London came up the hard way on the Oakland docks in California. He had his first drink at the age of 5, ran an oyster smuggling operation as a teenager, and allegedly brought the sport of surfing from Waikiki to the West Coast. At least one critic has referred to him as the Norman Mailer of the early 1900s.

In 1913, the author of the Call of the Wild published what was arguably his least successful book, John Barleycorn, a non-fiction account carrying the subtitle Alcoholic Memoirs. John Sutherland, professor of English Literature at University College in the UK, wrote in his introduction to the Oxford edition of Jack London’s book that London had pitched the book as “the bare, bald, absolute fact… of my own personal experiences in the realm of alcohol.” As Sutherland notes, “The drunk’s stigma was, however, indelible in 1913. No one of London’s public standing had ever come clean on the question of problem drinking before—at least not while at the zenith of their power and fame.”

Yet what are we to make, Sutherland asks, of London’s assertions, “three times in the first five pages, that drinker he may be, but ‘I was no hereditary alcoholic… I have no constitutional predisposition for alcohol.’”? Is this, the critic asks, “self-delusion or self-knowledge?”

After reading the book, I would have to say a little bit of both, given the limitations of medical knowledge at the time.  In London’s view, common back then, “dipsomania” was a chemical, congenital defect, much maligned and considered to be as rare as one in every several thousand drinkers. Nonetheless, several prominent London biographers have asserted that Jack London was chronically drunk-sick in his later years, ultimately dying of uremia and other complications brought on by years of excessive drinking. Writer Upton Sinclair claimed in 1915 that he had seen London wandering Oakland “dazed and disagreeably drunk.” Still others claim London’s bar bills were always modest and much of John Barleycorn is fiction. Yet London writes frankly of his morning shakes and hair-of-the-dog drinking and suicidal impulses. Describing his life in 1910, London writes: “I achieved a condition in which my body was never free from alcohol. Nor did I permit myself to be away from alcohol…. There was no time in all my waking time, that I didn’t want a drink.”

Was Jack London a Hemingway-style brawler or a hopeless alcoholic? As we have come to understand, it is sometimes possible to be both, for a while. Jack London was not writing for a medical journal, he was relating the experiences of his own life. And when the battle for universal suffrage began in earnest, London was an early an enthusiastic backer, on the grounds that if women got the vote, alcohol prohibition would surely follow, and the children of American would be saved from the wiles of John Barleycorn.

The lack of enthusiasm for the book when it was published stemmed, in part, from these built-in ambiguities. In addition, writes Sutherland, “John Barleycorn is an extended meditation on pessimism, or alcohol induced melancholy.” These days, we are more likely to refer to this condition as depression. This was not the Jack London his fans had come to know and love, even though London insisted in the book that he was “writing of the effects of alcohol on the normal, average man. I have no word to say for or about the microscopically unimportant excessivist, the dipsomaniac.”

For all the hedging, there is plenty of recognizable plain talk about the devotees of Mr. Barleycorn: “When good fortune comes, they drink. When they have no fortune, they drink to the hope of good fortune. If fortune be ill, they drink to forget it. If they meet a friend, they drink. If they quarrel with a friend and lose him, they drink…. He coarsens and grossens them, twists and malforms them out of the original goodness and fineness of their natures.”

In another passage describing the tavern life of tradesmen and laborers, he “saw men doing, drunk, what the would never dream of doing sober…. Time and again I heard the one explanation: If I hadn’t been drunk I wouldn’t a-done it.”

And as time passes, Jack London, the resolutely non-alcoholic, highly-regarded novelist, finds the terrain underneath his own feet is changing: “And the thing began so imperceptibly, that I, old intimate of John Barleycorn, never dreamed whither it was leading me…. It was at this time I became aware of waiting with expectancy for the pre-dinner cocktail. I wanted it, and I was conscious that I wanted it…. And right there John Barleycorn had me. I was beginning to drink regularly, I was beginning to drink alone.”

These developments shook up London sufficiently for him to ask himself: “Had I, a non-alcoholic, by long practice, become an alcoholic?” He has no trouble marshaling evidence for the argument: “The more I drank the more I was required to drink to get an equivalent effect…. Whenever I was in a hurry, I ordered double cocktails. It saved time.”

There were other warnings: “Where was this steady drinking leading? But trust John Barleycorn to silence such questions. ‘Come on and have a drink and I’ll tell you all about it,’ is his way.”

London concludes, before taking most of it back in later pages: “There are hundreds of thousands of men of this sort in the United States to-day, in clubs, hotels, and in their own homes—men who are never drunk, and who, though most of them will indignantly deny it, are rarely sober. And all of them fondly believe, as I fondly believed, that they are beating the game.”

And finally, this: “But a new and most diabolical complication arose: The work refused to be done without drinking. It just couldn’t be done. I had to drink in order to do it.”

In the end, let us hear from his last wife, Charmian, who made the following entry in her diary on July 1, 1912: “I know now that Jack, facing the writing of John Barleycorn, intends to drink moderately in the future, just to prove to an unbelieving public that he is the opposite of an ‘alcoholic’, that he is not afraid of being an alcoholic, and never was an alcoholic. Perhaps he is right, but I feel a trifle dashed.”





Monday, May 4, 2015

Alcohol Industry Turns Moderation Into a Sales Message


A warning or an advertisement?

You almost have to admire the tenacity shown by the liquor industry in its passive aggressive method of turning a warning label into additional advertising.

Perhaps it was foolish to suppose that forcing the liquor industry to brand all bottles and advertisements with the catch-phrase, “Drink Responsibly,” or “Drink Moderately,” or some responsible variation on that theme, would do any good—or would be observed in good faith by alcohol companies.

To begin with, a majority of heavy or at-risk drinkers consider their intake to be moderate already, says Alcohol Concern, a national charity in the UK. According to a survey of drinkers in Wales, respondents thought they’d had enough to drink when they lost control or felt unwell: ‘when the rooms starts to spin’ or ‘when I have to be put in a taxi.’”

Secondly, the alcohol industry won’t play fair when it comes to displaying these modest messages. Alcohol Concern conducted a small study of alcohol advertising in a selection of consumer lifestyle magazines commonly available in supermarkets. Specifically, the study looked at the presence and placement of “drink responsibly” or “enjoy responsibly” messages in the advertising—a message alcohol companies have pledged to place voluntarily on labels.

The group sampled 18 issues, primarily food and diet magazines, sold at low cost, or sometimes given away in-store. Alcohol advertising represented as high as 40% of total advertising in some of the issues. The web address of Drinkaware, another public education charity, funded by the alcohol industry, was found in 94% of the alcohol advertisements. But as the study points out, “referencing an educational website hardly constitutes pulling out all the stops to make, as one leading drinks company ABInBev puts it, responsible drinking ‘a fundamental part of our dream to be the Best Beer Company bringing people together for a Better World.”

In total, “36% of alcohol adverts and advertorials included a specific drink responsibly message…. only in a minority of cases were the drink responsibly messages kept simple….” The Better World, it seems, will include a whole lot of branding.

Examples of industry embellishment are everywhere: Bacardi Rum ads asked you to “Live Passionately, Drink Responsibly,” while Martini cuts right to the point with its version, “Enjoy Martini Responsibly.” Grey Goose’s creative alternative is “Sip Passionately, Drink Responsibly,” while Diageo wants you to “Celebrate Life Responsibly.”

My personal UK favorites come from Jack Daniels: “Play with your Heart. Drink with Care. Live Freely. Drink Responsibly.”. Another example from Jack Daniels also illustrates the dichotomy: “Makes This Season a Winter to Remember. Drink Responsibly.” They read almost like a set of opposing commands: Play recklessly while you drink carefully. Live wild and free, except for your responsible drinking.

In sum, the UK alcohol industry just can’t play it straight. And while the U.S. record is better—Alcohol Concern cites American studies showing some sort of responsibility message in 9 out of 10 U.S. advertisements—U.S. distributors are not above a little brand promotion in the message, either. A random search for American alcohol ads quickly yielded Miller High Life’s “Great Beer. Great Responsibility. #IamRich.” Bud Light recently found itself in the gaffe business, forced to pull the cute little tagline on its cans: “Perfect Beer For Removing ‘No’ From Your Vocabulary For the Night. #UpForWhatever.” As Mashable covered the controversy on Twitter, “Bud Light campaign tells drunk people to remove ‘No” from their vocab.”

Perhaps the richest example unearthed by Alcohol Concern in UK supermarket magazines was the drink responsibly message found on one ad, where “the magazine pages had to be physically pulled back in order to read the message, in tiny type (known as ‘mouseprint’), along the left margin of the advert.”

To return to the first question: What, exactly, does responsible drinking mean? “If it’s sticking to current government-endorsed recommended limits,” the study asks, “then why does this advice not appear in a single alcohol advert or advertorial captured in this study?

Monday, April 20, 2015

Moderate Drinking Doesn’t Help Your Heart


Mendelian meta-analysis and the alcohol “flush” allele.

Less than a year after the massive Mendelian randomization meta-analysis published in the British Medical Journal, a group of researchers recently wrote an editorial in the journal Addiction, which would seem to put a lid on the matter:

The foundations of the hypothesis for protective effects of low-dose alcohol have now been so undermined that in our opinion the field is due for a major repositioning of the status of moderate alcohol consumption as protective…. Health professionals should not recommend moderate alcohol consumption as a means of reducing         cardiovascular risk for patients. At the policy level, the hypothesis of health benefits from moderate drinking should no longer play a role in decision making.

To recap: In the Mendelian meta-analysis, drinkers with a genetic variant linked to the so-called alcohol flush reaction, which leads to lower consumption among those who drink, also correlated with a decreased risk of cardiovascular disease. “Carriers of the rs1229984 A-allele had lower levels of alcohol consumption and exhibited lower levels of blood pressure, inflammatory biomarkers, adiposity measures, and non-HDL cholesterol, and reduced odds of developing coronary heart disease, compared with non-carriers of this allele.”

But as it turned out, this relationship only held for drinkers, not for abstainers.

Why, then, have so many epidemiologists agreed for several decades now that “moderate” alcohol intake has a protective effect against heart diseases? According to the editorial authors—drug researchers from Australia, Canada, the U.S., and Sweden—earlier research tended to use “abstainers” as the key reference group to which drinkers were compared. Studies that separated former drinkers and occasional drinkers from abstainers got different results—they didn’t show significant protection correlating with moderate alcohol consumption. The theory, say the researchers, is that non-addicted drinkers spontaneously reduce their alcohol intake with age and medical concerns. Some of these people with a declining health profile are counted as “abstainers.” But when former and current drinkers are combined, then compared with life-long abstainers to address selection bias, “the observed disparity in health status between abstainers and low-dose drinkers was eliminated.”

But it’s not quite over. Michael Rioerecke and Jurgen Rehm at the Center for Addiction and Mental Health in Toronto, argue in another Addiction editorial that there are still a few things unaccounted for: The allele in question is assumed to be randomly spread throughout the population, which may or may not be true, especially since allele carriers are relatively rare in several European countries. The allele is also assumed to be mediated by average alcohol intake. Binge drinking, which allele carriers presuming engage in less, is not assessed in the study.  In short, they write, “we do not know if the average level of alcohol intake of the allele carriers within the strata of average consumption was indeed lower than that of the non-carriers.” Nonetheless, even Rioerecke and Rehm concede that the evidence continues to look promising for this revision of conventional drinking wisdom. More than 100 studies have shown relatively stable associations between alcohol and heart disease, and absent a new breakthrough method of epidemiological study, this one stands a good chance of holding firm.


Thursday, April 2, 2015

Alcohol and Refugee Populations


How displaced peoples are harmed and helped by alcohol.

Although it is impossible to know with certainty, 50 million is the current U.N. estimate of the number of human beings around the world categorized as refugees or displaced persons due to war and other violence. These "conflict-affected populations" suffer in a thousand different ways, but widely overlooked is the frightening prevalence of alcohol and other drug use disorders in these groups. The humanitarian health sector’s understandable focus on “immediate life-saving activities” means that longer-term chronic and behavioral issues remain unexamined.

What are the risks of ignoring alcohol use disorders in these populations? Bayard Roberts and Nadine Ezard, in an editorial for the journal Addiction, suggest that they are formidable. For conflict-affected groups, the “risk environment” includes loss of home and livelihood, exposure to war trauma, PTSD, anxiety, violence, and depression. In such environments, alcohol and other drugs are capable of producing a familiar and depressing litany of results are enumerated in setting after setting: Disruptions to household economies, alcohol-related suicides, violence against women, increased HIV and other blood-born viruses, unsafe sex practices, and increased mental health problems.


Nadine Ezard, co-author of the editorial in Addiction, was also lead author of a 2011 paper, “Six rapid assessments of alcohol and other substance use in populations displaced by conflict,” published in the journal Conflict and Health. Ezard and colleagues conducted extensive interviews on substance use and abuse in a range of populations displaced by conflict in Kenya, Liberia, Uganda, Iran, Pakistan, and Thailand. The work resulted in the development of a field guide for rapid assessment of alcohol and other substance use used by the United Nations High Commissioner for Refugees and the World Health Organization (WHO).

The aim of the study was to describe current substance use patterns in the study populations, and to identify possible interventions. As Ezard et al. write, “A number of effective interventions exist for problem substance use, but little attempt has been made to adapt these interventions to populations displaced by conflict.”

The six assessments took place between 2006 and 2008. Populations included refugees both in and out of camps, residents of nearby communities, returning populations, in both urban and rural settings.

Kenya

The main study group was located in Kakuma Refugee Camp and nearby Kakuma town, each with about 100,000 people. The camp was established in 1992 to house Sudanese refugees, but at the time of assessment there were refugees in the camp from nine countries. Alcohol production and use was common, while cocaine and heroin were relatively rare. Food rations provided a workable source for fermentation products. Local women produced a cereal-based brew, busaa, and a stronger distilled version, changa’a. These were important sources of income in the area. The distilled product was illegal and associated with family disruption, violence, and gender abuse. One woman told researchers: “I brew because I want my children to survive. When my customers buy my brew and buy my body, even if I die, my children will inherit my brewing business.”

Liberia

In 2003, a 14-year civil war ended after 250,000 casualties and near-total destruction of infrastructure. Nearly a million refugees and displaced persons, supported largely by non-government organization, have been there ever since. Alcohol and marijuana were cheap, easily available, and widely consumed. Distilled cane juice liquor and palm wine were popular. “Beer is drunk like water,” said one respondent, “assuming that people can afford it.” Cannabis is popular with young people, who use it, according to one youthful observer, “to stop the bad dreams.” Benzodiazepines were also in play, with sex workers reporting that diazepam was frequently used in the bars as a date rape drug.  Cocaine was also available, particularly when smoked with marijuana in a mix called a “dugee.” No respondents indicated any drug injection. There were no specific alcohol or drug treatment services available in the region.

Uganda

At the time of the assessment, more than 2 million people, displaced due to protracted civil conflicts, were scattered across an archipelago of more than 100 displaced persons camps. Alcohol was readily available, acknowledged to be a serious problem, and health care was limited. The usual results of alcohol abuse were in evidence in the disruption of community cohesion that “left families short of food and children hungry.” Both male and female respondents “drew causal links between dispossession and alcohol use. Dispossession promoted alienation, idleness and loss of traditional gender roles among men…. As a result, cultural norms were changing, as one woman explained: ‘now there are no rules for drinking alcohol.’” As one youth said, “how can I respect these older men when I see them becoming drunk and falling down in the dirt.” Yet once again, alcohol brewing was a crucial source of income for many women in poverty.

Iran

For the past 20 years, Iran has been host to Afghan refuges, an undocumented million of which live outside the camps. The prevailing drug problem in this population is widespread opiate use, rather than alcohol. According to the study, “Refugees are permitted access to basic education and health care on the same basis as Iranian citizens. Service utilization by Afghans is thought to be low due to a combination of barriers such as poverty, lack of awareness, and perceived discrimination,” as well as fear of the authorities. “Newer opiates were becoming more popular, such as heroin, Iranian ‘crack’ and crystal (highly concentrated forms of heroin), and there was some transition to injection. Nevertheless, respondents perceived opiate as less prevalent among the Afghan refugee population than the host population.” Respondents also reported a number of benefits to opiate use: “pain relief, pleasure and socialization.”

Pakistan

In 2007, Pakistan contained an estimated 3 million Afghans, half of them living in so-called “refugee villages” along the border. In this region, the main substance use classes included opium, plus hashish for men, and benzodiazepines, commonly, for women.  There were not specialist drug abuse services available in the villages. “Although each refugee village context was distinct, substance use patterns were characterized as a continuation or exaggeration of pre-displacement use modified under the influence of patterns of availability and village livelihood options…. For example, in urban, but not rural areas substances were sometimes injected, reflecting the substance use patterns of the host population.” Alcohol use was uncommon and confined to home-brew made from sugarcane or grapes and predominantly used by young people. In fact, “one third of the women interviewed said that they knew someone who had a serious problem with hashish and gave accounts of domestic violence associated with its use. Respondents believed that limited skills, education and employment opportunities promoted substance use.”

Thailand

Refugees from civil war in Myanmar have been in Thailand now for decades. Out of the millions of undocumented migrants, the study group concentrated on 150,000 refugees living in nine camps along the border.  Access to health care was considered good, and in this case there were residential substance abuse treatment programs available in the camps. Alcohol was the primary public health concern. Home-brewed distilled rice liquor was the primary source. Less prominent drugs included meth and caffeine were available, as were diazepam, cough syrup, opiates, and marijuana.  The results were predictable: “dependence, high risk sexual behavior, family disruption, and gender-based violence.” Young people had three choices, according to one young man: “They can leave the camp and look for work, they can lead a traditional life which means they will have lots of babies, or they can drink alcohol.”


Despite all this, the authors sensibly urge that public health workers should not ignore “the perception in some communities that substance use may have important social functions…. The combined effect of substance use problems may inhibit community capacity to recover from conflict, yet some types of substance use may be important for social cohesion in some settings.”

The authors believe that conflict-affect populations require, as a minimum, “screening and brief intervention for high risk alcohol use” as well as “identification and treatment of severe mental illness (as both a cause and consequence of substance use).” In addition, “primary health services should be capable of managing withdrawal and other acute problems.”

What else needs to be done?

—Brief community-based interventions, which have proven cost-effective in higher income settings.

—Gender-sensitive interventions.

—More epidemiological research on alcohol risks and comorbidity with mental health disorders including depression and anxiety.

—Evaluation of feasibility and cost-effectiveness of interventions, including the use of experimental designs.

“This requires a public health approach,” Ezard and Roberts write, “for example, ensuring that work on non-communicable diseases addresses underlying risk factors as well as treatment; exploring community-based responses; supporting better coordination between different sectors such as health and protection or mental health and psychosocial support with communicable disease control activities…. And ensuring that the needs of conflict-affected civilians are recognized in global alcohol control activities.”

There is, however, one clear-cut approach to drug abuse problems in such communities that the authors most definitely do not recommend, and it is the most time-honored modality of all: “Despite their popularity among many service providers and community groups, general public information campaigns and school-based education for primary prevention programs have been shown to be ineffective to reduce alcohol-related harm.”

What would be the benefits of tackling alcohol disorders in these beleaguered, violence-prone communities? Roberts and Ezard argue for several:

—Improved mental and physical health.

—Reduced risk of disease, injuries, and accidents.

—Reduced harm and violence to others.

—Improved family relations and social networks.

—Improved economic productivity.

—Reduced health care costs.

The editorial concludes that “without greater engagement, alcohol use disorder and its consequences among conflict-affected civilians will remain neglected and the multiple benefits of tackling it will continue to be ignored.”




Friday, February 27, 2015

The Blunt Facts About Blunts


Mixing 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 published in the journal Addiction, and authored by Arpana Agrawal and Michael T. Lynskey of Washington University School of Medicine, with 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. 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 other 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

Photo credit: http://www.hightimes.com/

(First published at Addiction Inbox on March 22, 2012).

Monday, February 16, 2015

Troubling Link Between Shoplifting and Suicide


Compulsive theft can lead to tragic results.

In the fall of 2011, 71-year old Julia Grodinsky of London was convicted of shoplifting ornamental crystals and sentenced to 18 months of probation. What made the case unusual was that Grodinsky had been convicted of shoplifting 63 times over the past 60 years. It seems likely that the elderly thief will continue to steal, given her history of poor decision-making.

In The Republic, Plato asked whether thieves are made or born. It’s an excellent question. Kleptomania, as it is traditionally called, is a special class of theft behavior: a chronic condition marked by compulsive stealing, often committed by people who could easily afford to buy what they steal. Brian L. Odlaug, a visiting researcher with the faculty of health and medical sciences at the University of Copenhagen, believes that kleptomania’s primary feature is that it strikes "people who had a good marriage, nice home, great job—and yet could not stop from stealing inconsequential items." It is a rare disorder, he notes, “while sociopathy and theft for gain are quite common.”

Curiously, the stealing never seems to be about money: The most recent study measuring income and shoplifting shows that people in the United States with incomes over $70,000 shoplift 30 percent more than those earning less than $20,000 a year. Today, compulsive shoplifting is labeled in the DSM-IV as an impulse control disorder. But historically this controversial diagnosis was variously seen as a biological disorder brought on by female agitation in department stores, an expression of repressed Freudian sexual desire, or a socially constructed disease that blossomed as a reaction to modernity. (A modest majority of shoplifters are women). Some observers in the early 20th Century even described kleptomania as a clever trick by psychiatrists to worm their way into law courts as purveyors of expert testimony.

Researchers today are more likely to be interested in what researcher Jon E. Grant, professor of psychiatry and behavioral neuroscience at the University of Chicago’s Pritzker School of Medicine, calls the “neurocognitive sequelae of shoplifting.” Grant and Orlaug are part of a group of psychiatric researchers who have been studying compulsive shoplifting for more than a decade. In the Archives of Suicide Research, lead author Odlaug documented abnormally high suicide rates among a group of 107 participants with kleptomania, 24.3 percent of whom had reported at least one suicide attempt. That figure is “6 to 24 times higher than in the United States general population,” according to the report—roughly similar to the rate of suicide attempts among patients with schizophrenic disorders. It is higher than the rate of suicide attempts reported in cases of major depressive disorder (16.5 percent).

93 percent of the participants reported that their suicide attempt “was directly or indirectly due to their kleptomania symptoms (e.g., shame over the behavior; legal or personal problems resulting from shoplifting).” Believed to be the first attempt to survey the association between suicide and shoplifting, the study also teased out a strong association between bipolar spectrum disorder and kleptomania symptoms. The odds of a past suicide attempt were five times greater for kleptomania subjects who had also been diagnosed with bipolar disorder.

“The suicide data are very troubling,” says Grant. “No one screens for this behavior, or when they are told about, most clinicians are very dismissive of it. There is definitely an attitude about kleptomania that it is more of a criminal problem.”

Dr. Howard Shaffer, an associate professor at Harvard Medical School and director of the division on addiction at The Cambridge Health Alliance, who was not involved in the research, says that the work “seems a reasonable heads-up for clinicians to consider the role of impulsivity and its impact on suicidal ideation and behavior; kleptomania is one kind of proxy for impulsivity.”

Compulsive shoplifting is commonly associated with substance abuse, pathological gambling, personality disorders, and bipolar syndrome, while sometimes overlapping with other impulse control disorders. Does it share common neurobiological deficits with these conditions? In a report published in Comprehensive Psychiatry, Grant and co-workers recruited young adults with no history of substance abuse or recognized mental health disorders, and ran them through a barrage of psychological testing. For the investigators, the important question was whether compulsive stealing is associated with certain neuropsychological dysfunctions that make kleptomaniacs different from other people. As it turned out, people with kleptomania risked more points in a test called the Cambridge Gambling Task, with results “similar to previous reports in people with damage to the ventromedial prefrontal cortices.” It was an admittedly small study, but the researchers think the results show that shoplifting is not just a rash act, but one associated with “specific decision-making and working memory deficits.”

A small neuromaging study published by Grant in 2006 showed evidence of “compromised white matter microstructure in inferior frontal areas,” suggesting to Grant that the frontal parts of the brain involved in decision making “may not be as healthy.” For his part, Odlaug thinks this finding may help explain “why so many patients report an 'irresistible' impulse to steal and a failure to inhibit that impulse.” Odlaug cautions that while deficits of executive functioning appear to be involved, “I think it is far too early to suggest cognitive predictors of kleptomania or other disorders characterized by impulse control deficits.”

Neuroscientist Marc Lewis, professor of human development and applied psychology at Radboud University in Nijmegen, The Netherlands, and author of Memoirs of an Addicted Brain, also questions whether sufficient data existed for asserting a link between impulsive behavior and working memory deficits. However, Lewis agrees that kleptomania “is seemingly its own disorder,” and “overlaps only partially with other psychiatric categories.”

Can kleptomania be cured, or treated successfully? In 2009, in an article for Biological Psychiatry, Grant and colleagues recorded the results of their work with 25 patients with kleptomania who were given high doses of naltrexone, a drug that blocks opioid receptors and is used to treat alcoholism and heroin addiction. All of the participants had been arrested, and had spent at least one hour per week stealing. The 8-week study, believed to be the first placebo-controlled trial of a drug for the treatment of shoplifting, resulted in a remission of symptoms in two-thirds of those on naltrexone. Says Odlaug: “With such a dearth of treatment data available, naltrexone appears to be the first-line treatment at this time. We have found that naltrexone at slightly higher doses is beneficial for a number of folks with kleptomania.” Some researchers are also investigating use of cognitive behavioral therapies.

“Kleptomania is thought of as a behavioral addiction within addiction circles,” Odlaug adds, while conceding that not everyone agrees with the concept of addiction to behaviors rather than substances. The neuropsychological approach to uncontrollable shoplifting as by no means unanimous. Writing in Global Society, Thomas Lenz and Rachel MagShamhrain argue that kleptomania is an “invented disease,” coinciding with the rise of the department store and strong beliefs in feminine “hysteria.”

“I think the general view,” says Grant, “is that criminal issues, or potential criminal issues, are not as biological as, say, depression. It then becomes a vicious cycle, as lack of research then continues to justify why people say it is not really biological or psychological.”

Lamentably, the connection between bipolar syndrome and shoplifting did not become apparent until recently, because people with bipolar symptoms are routinely ruled out of clinical studies of impulse control disorders. “Screening for people with co-occurring bipolar affective disorder and kleptomania is extremely important,” Odlaug stresses. “Especially in psychiatric settings where kleptomania and other impulse control disorders often go unrecognized by clinicians.”

(By Dirk Hanson. Originally published February 11, 2013, by the Dana Foundation.)


Thursday, February 5, 2015

Update on Synthetic Drug Surprises


Spicier than ever.


Four drug deaths last month in Britain have been blamed on so-called “Superman” pills being sold as Ecstasy, but actually containing PMMA, a synthetic stimulant drug with some MDMA-like effects that has been implicated in a number of deaths and hospitalizations in Europe and the U.S. The “fake Ecstasy” was also under suspicion in the September deaths of six people in Florida and another three in Chicago. An additional six deaths in Ireland have also been linked to the drug. (See Drugs.ie for more details.)

PMMA, or paramethoxymethamphetamine, causes dangerous increases in body temperature and blood pressure, is toxic at lower doses than Ecstasy, and requires up to two hours in order to take effect.

In other words, very nearly the perfect overdose drug.

Whether you call them “emerging drugs of misuse,” or “new psychoactive substances,” these synthetic highs have not gone away, and aren’t likely to. As Italian researchers have noted, “The web plays a major role in shaping this unregulated market, with users being attracted by these substances due to both their intense psychoactive effects and likely lack of detection in routine drug screenings.” Even more troubling is the fact that many of the novel compounds turning up as recreational drugs have been abandoned by legitimate chemists because of toxicity or addiction issues.

The Spice products—synthetic cannabinoids—are still the most common of the novel synthetic drugs. Hundreds of variants are now on the market. Science magazine recently reported on a UK study in which researchers discovered more than a dozen previously unknown psychoactive substances by conducting urine samples on portable toilets in Greater London. Call the mixture Spice, K2, Incense, Yucatan Fire, Black Mamba, or any other catchy, edgy name, and chances are, some kids will take it, both for the reported kick, and for the undetectability. According to NIDA, one out of nine U.S. 12th graders had used a synthetic cannabinoid product during the prior year.

“Laws just push forward the list of compounds,” Dr. Duccio Papanti, a psychiatrist at the University of Trieste who studies the new drugs, said in an interview for this article. “The market is very chaotic, bulk purchasing of pure compounds are cheaply available from China, India, Hong-Kong, but small labs are rising in Western Countries, too. Some authors point out that newer compounds are more related to harms (intoxications and deaths) than the older ones. You can clearly see from formulas that newer compounds are different from the first ones: new constituents are added, and there are structural changes, so although we have some clues about the metabolism of older, better studied compounds, we don't know anything about the newer (and currently used) ones."

The problems with synthetic cannabinoids often begin with headaches, vomiting, and hallucinations. At the Department of Medical, Surgical, and Health Sciences at the University of Trieste, researchers Samuele Naviglio, Duccio Papanti, Valentina Moressa, and Alessandro Ventura characterized the typical ER patient on synthetic cannabinoids, in a BMJ article: “On arrival at the emergency department he was conscious but drowsy and slow in answering simple questions. He reported frontal headache (8/10 on a visual analogue scale) and photophobia, and he was unable to stand unassisted. He was afebrile, his heart rate was 170 beats/min, and his blood pressure was 132/80 mm Hg.”

According to the BMJ paper, the most commonly reported adverse symptoms include: "Confusion, agitation, irritability, drowsiness, tachycardia, hypertension, diaphoresis [sweating], mydriasis [excessive pupil dilation], and hallucinations. Other neurological and psychiatric effects include seizures, suicidal ideation, aggressive behavior, and psychosis. Ischemic stroke has also been reported. Gastrointestinal toxicity may cause xerostomia [dry mouth], nausea, and vomiting. Severe cardiotoxic effects have been described, including myocardial infarction…”

In a recent article (PDF) for World Psychiatry, Papanti and a group of other associates revealed additional features of synthetic cannabimemetics (SC), as they are officially known: “For example, inhibition of γ-aminobutyric acid receptors may cause anxiety, agitation, and seizures, whereas the activation of serotonin receptors and the inhibition of monoamine oxidases may be responsible for hallucinations and the occurrence of serotonin syndrome-like signs and symptoms.”

Papanti says researchers are also seeing more fluorinated drugs. “Fluorination is the incorporation of fluorine into a drug,” he says, one effect of which is “modulating the metabolism and increasing the lipophilicity, and enhancing absorption into biological membranes, including the blood-brain barrier, so that a drug is available at higher concentrations. An increasing number of fluorinated synthetic cannabinoids are available, and fluorinated cathinones are available, too.”

A primary problem is that physicians are still largely unacquainted with these chemicals, several years after their current popularity began. This is entirely understandable. In addition to the synthetic cathinones, several new mind-altering substances based on compounds discovered decades ago have also surfaced lately. Papanti provided a partial list of additional compounds that have led to official concern in the EU:

—Synthetic opioids (the best known are AH-7921, MT-45)
—Synthetic stimulants (the best known are MDPV, 4,4'-DMAR)
—New synthetic psychedelics (the NBOMe series)
—New dissociatives (Methoxetamine, Methoxphenidine, Diphenidine)
—New performance enhancing drugs (Melanotan, DNP)
—Gaba agonists (Phenibut, new benzodiazepines)

Most of the new and next-generation synthetics are not readily detected by standard drug screen processes. Spice drugs will not usually show up on anything but the most advanced test screening, using gas chromatography or liquid chromatography-tandem mass spectrometry—high tech tools which are rarely available for anything but serious (and costly) forensic investigations.

“Testing is a big problem,” Papanti declares. “From a clinical point of view, do you need the test to make a diagnosis of intoxication, for following up an addiction treatment, or for forensic purposes? With the new drugs, maybe taken together, with different pharmacology, we are not very sure about this yet. If I want to have confirmation of a diagnosis of SC intoxication, I need two weeks as an average, in order to obtain the result. Your patient has been discharged by that time, or in the worse case, he is dead.”

 Another major problem, according to Papanti, “is that the machines need sample libraries in order to recognize the compound, and samples mean money. Plus, they need to be continuously updated.”

In summary, there is no antidote to these drugs, but intoxication is general less than 24 hours, and the indicated medical management is primarily supportive. If you plan to take a drug marketed as Ecstasy, or indeed any of the spice or bath salt compounds, Drugs.ie notes that there are some basic rules of conduct that will help maximize the odds of a safe trip:

—If you don’t “come up” as quickly as anticipated, don’t assume you need another pill. PMMA can take two hours or more to take effect. Do not “double drop.”

—If you don’t feel like you expected to feel, and are noticing a “pins-and-needles” feeling or numbness in the limbs, consider the possibility that another drug is involved.

—Don’t mix reputed Ecstasy with other drugs, especially alcohol, as PMMA reacts very dangerously with excessive alcohol.

—Remember to hydrate, but don’t overhydrate. If you go dancing, figure on about a pint per hour.