A Roundtable Discussion on Cannabis Use Disorder

Addressing the habit-forming aspects of marijuana.

A trio of leading marijuana scientists participated in a panel discussion moderated by Dr. Daniele Piomelli from the School of Medicine at the University of California-Irvine, and published in a recent issue of the journal Cannabis and Cannabinoid Research.

Dr. Margaret Haney is with the New York State Psychiatric Institute at Columbia University Medical Center; Dr. Alan J. Budney is affiliated with the Geisel School of Medicine at Dartmouth College; and Dr. Pier Vincenzo Piazza works at the Magendie Neurocenter in Bordeaux, France.

Excerpts from the long discussion appear below:

It seems that most specialists in the field agree that Cannabis is addictive. If you had to choose one piece of evidence, either clinical evidence or animal experiment evidence, in support of this conclusion, which one would you pick?

Dr. Margaret Haney: “One of the key features for me is demonstrating that there is a pharmacologically specific withdrawal from Cannabis use…. We can demonstrate that daily smokers go through a time-dependent and pharmacologically specific withdrawal when they abstain from Cannabis…. I think another really important feature is the clinical data showing how high relapse rates are with Cannabis. Although Cannabis may have a lower abuse liability than other drugs like cocaine or nicotine, once somebody has developed a dependence on the drug, then quitting becomes extremely difficult.

Dr. Alan J. Budney: “If I had to pick out the ‘smoking gun’ to convince the public and the scientific world that Cannabis Use Disorder (CUD) is real, then it would be the data from clinical epidemiological research…. the data on CUDs are remarkably similar to the other substance use disorders…. for a substantial number of people, Cannabis use causes similar and substantial problems that are comparable to other types of drugs that we all agree have addictive potential.”

Dr. Pier Vincenzo Piazza: “[In] Australia, Canada, the United States, and the European Union, over the last two years Cannabis represents the highest new entries for treatment in specialized centers…. Since these four countries have very different rates of referral of patients by the judicial system, these figures really mean that patients experience a discomfort high enough to spontaneously seek treatment…. In France, for example, as well as in many other European countries, referral from the judicial system is very low. Nevertheless, the demand for treatment for CUD is now the highest of all drugs, legal and illegal.”

What is curious is that we now accept the concept that Cannabis is addictive, but for many years we have been told that it was not. Why is it that, for so long, the scientific community failed to recognize the addictive properties of Cannabis?

Dr. Margaret Haney: “I have been speaking about Cannabis addiction for 20 years and was met by full-on boredom for the first 15 years because I felt that scientists, like the public at large, just viewed Cannabis as a benign compound not too different from caffeine in a way…. THC is lipophilic, and so long-lasting, withdrawal takes quite a while to manifest…. if an individual is dependent on nicotine, he or she cannot go a couple of hours without experiencing withdrawal. A heavy Cannabis user, by contrast, has to go quite a while before experiencing withdrawal, and so it was not quite as obvious to people that withdrawal existed.”

Dr. Alan J. Budney: “Moreover, many of those that have experience with using Cannabis, do not get addicted, develop problems, or experience withdrawal. Although the same is true for those who have used alcohol or even opiates, for reasons that are not completely clear, the personal experience of those who used Cannabis and did not develop problems or experience withdrawal, seems to lead to the perception that Cannabis is not a substance that others can become addicted to.”

Dr. Pier Vincenzo Piazza: “What we know now is that, since cannabidiol is an antagonist of THC, the greater the ratio between THC and cannabidiol the greater the risk for Cannabis to be addictive…. Now, we are up to a 5- to 10-fold difference in favor of THC, making Cannabis more addictive.”

How addictive is Cannabis? Is it more addictive than, say, tobacco or alcohol? Is it less addictive? Is this question even correctly asked? Is there a better way to ask it?

Dr. Alan J. Budney: [I] would like to emphasize a point so that our audience does not think we are going way overboard and engaging in reefer madness related to the severity of Cannabis addiction. All factors held constant, the pharmacology of opiates would probably produce a more severe addiction…. Access, dose, route of administration, societal acceptance, perceived risk, cost, societal consequences for use or intoxication, and multiple other factors contribute to the real-world question of how addictive a drug is compared to another.”

Dr. Margaret Haney: “My opinion is that Cannabis has a lower abuse liability than something like cocaine [but] even if Cannabis has a lower abuse liability, the sheer number of people using it will result in a large number of people with a use disorder….”

Dr. Pier Vincenzo Piazza: “If we try to express abuse liability in numbers, the abuse liability for Cannabis… is between 10% and 15%, depending on the survey you look at. However, I believe that abuse liability should also be measured by a second factor; that is, how easy it is to quit if you have developed a substance use disorder. My understanding… is that stopping Cannabis use, if you have developed CUD, is not easier than other drugs.”

The major point, all three experts agree, is that marijuana cannot be considered a completely benign drug. “Cannabis is not the worst drug,” says Dr. Haney, “but it is not a drug without consequences. Again, societal attitudes often seem to skew one way or the other; it is all good or it is all bad, when it is clearly both.”

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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.

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.

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.”

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.”

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The Zendo Project

The Zendo Project

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

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