In Praise of Neurogenesis

A little sweat pays big dividends in recovery.

Scientists have long known that activities like learning, socialization and physical activity—key components of “environmental enrichment”—lead to the growth and development of nerve tissue that will become new brain cells, a process called neurogenesis. Such enrichment can include all manner of stimuli, but a group of researchers at the National Institute on Aging and the National Institute on Drug Abuse (NIDA) wanted to find out exactly how much of that neurogenic stimulus is due solely to exercise. Writing in the journal Learning and Memory, Tali Kobilo and coworkers went back to that most basic of lab experiments, mice running on an exercise wheel. Using a variety of conditions to permutate the mix of enrichment, running, running with other enrichment, and controls, the investigators concluded: “Here we show that running is the critical factor in stimulating adult hippocampal neurogenesis and enhancing mature BDNF [brain-derived neurotrophic factor] peptide levels. Moreover, enrichment in the absence of running does not increase adult hippocampal neurogenesis or BDNF levels in the hippocampus.” In addition: “New cell proliferation, survival, neuron number, and neurotrophin levels were enhanced only when running was accessible” to the test animals. “We conclude that exercise is the critical factor mediating increased BDNF levels and adult hippocampal neurogenesis.”

As a treatment modality for drug and alcohol addiction, physical exercise is often effective, quite well studied—and free. It is the most boring, the most mundane, the most predictable exhortation of them all—or perhaps the second most predictable, after the admonition to Eat Less.

Perhaps, suggests Jennifer Matesa in her book, The Recovering Body , it would be well to remember that doctors are not “paid to prescribe exercise.” She quotes Harvard’s biology professor Daniel E. Lieberman: “It is often said that exercise is medicine, but a more correct statement is that insufficient regular exercise is abnormal and pathological.” Matesa musters a chorus of trainers and exercise-oriented recovery experts to bolster her argument that simple exercise remains the single most overlooked element in most people’s recovery programs.

Matesa, whom I first encountered as the author of the excellent blog Guinevere Gets Sober, and later worked with at the online addiction and recovery magazine, The Fix, offers advice to “clean up the wreckage and recover the body’s health” during sobriety, and divides her book into five practices: exercise, nutrition, sleep, sexuality, and mindfulness meditation.

Body recovery is complex, Matesa writes. “You’re raising the levels of endorphins and dopamine in the body. You’re reregulating the body’s metabolism—its capacity to burn energy efficiently. You’re not just exercising biceps and triceps and deltoids or even chest, back, legs, and core. You’re also exercising the internal organs: heart, lungs, circulatory system, central nervous system (including the brain), and digestive system. You’re even exercising the skin by making it sweat.”

While one of the best things about exercise is that you can start at any point, with or without prior experience, there is a sense in which former jocks may have an edge here. Matesa interviews a former sports freak and recovering heroin addict who found her way back to the “cognitive- and muscle-memory” that gave her a head start in understanding what a fitness program is composed of. One thing that prevents people from working out, the former jock says, “is that they don’t know what to do and they feel overwhelmed. And we addicts get overwhelmed easily.”

A medical director of a Palm Beach detox center suggested that “twelve minutes of exercise per day with a heart rate of greater than one hundred twenty beats per minute” is enough to restore healthy sleeping patterns, for example. “The people who do that, their sleep architecture returns to normal in half the time that it takes people who don’t exercise. Twelve minutes.”

Matesa’s credentials as a recovering addict are impressive: alcohol abuse and opiate addiction, compulsive overeating, and shoplifting. As with many addictive shoplifters, she didn’t even need the things she stole. “The security woman pulled me into a messy, windowless back room, shut the door, looked me up and down, noted my Coach bag and middle-class clothing, regarded the stolen property in her hand [cheap earbuds], and said slowly, ‘you need to seek help.’” The book is published by Hazelden, and Matesa hews to the basic structure of 12 Step recovery programs. She also backs the controversial thinking of Dr. Gabor Mate, who believes that all addictions are the result of adverse childhood experiences, not genetics or any other physiological predilection.

Despite the years she logged with opiates, “my first chemical of abuse was sugar, my first addictive behavior was eating…. I eat sugar because it does all kinds of things drugs do…. when I was a kid, my diet was at least 80 percent refined and processed food, and almost all of that, essentially, was sugar. At age ten, I looked forward to my after-school snack the way my Dad looked forward to his first beer when he got home.”

She notes that a number of published studies have shown that “addicts in the first six months of recovery use sweet foods and refined, processed foods—junk food—to satisfy cravings for drugs and alcohol.” In addition, “sensible eating habits are seldom part of recovery strategies in detox and rehab facilities—this was a concern echoed by a number of treatment experts I talked with.”

“Recovery does not promise beauty or riches, everlasting affection and security or even sustained peace of mind,” Matesa concludes. “It promises that we’ll be able to negotiate one day—this one—in our right minds, awake. We get good at what we practice.”

Graphics Credit: http://www.thesportinmind.com/articles/exercise-addiction/

Alcohol and Your Heart

Health benefits of moderate drinking come under fire.

One of those things that “everybody knows” about alcohol is that a drink or two per day is good for your heart. But maybe not as good for your heart as no drinks at all.

Joint first authors Michael V. Holmes of the Department of Epidemiology and Public Health at University College in London, and Caroline E. Dale at the London School of Hygiene & Tropical Medicine in London, recently published a multi-site meta-analysis of epidemiological studies centering on a common gene for alcohol metabolization. The report, published in the UK journal BMJ, brings “the hypothesized cardioprotective effect of alcohol into question,” according to the authors.

People who are born with a particular variant in the gene controlling for the expression of alcohol dehydrogenase, the major enzyme involved in converting alcohol into waste products, will show the familiar flush reaction when they drink. Alcohol, literally, can make many of them sick. This genetic variant, in combination with other enzymes, can be strongly protective against alcohol, and is much more commonly found among Asian populations. Roughly 40% of Japanese, Korean, and Northeastern Chinese populations show the characteristic “Asian glow” to one degree or another if they choose to drink.  (One reason why this effect isn't better known is that the condition is close to nonexistent in Westerners).

 People with this alcohol dehydrogenase deficiency, the researchers found, not only consume less alcohol, for obvious reasons, but “had lower, not higher, odds of developing coronary heart disease regardless of whether they were light, moderate, or heavy drinkers.”  Here are the conclusions in detail: “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.”

The authors conclude that "reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.”

How does this work? The researchers aren’t completely sure, but note that the “most widely proposed mechanism” is an increase in high-density lipoprotein (HDL) cholesterol. “Although an HDL cholesterol raising effect of alcohol has been reported in experimental studies, the small sample size and short follow-up means existing studies may be prone to bias,” thereby limiting their usefulness. Moreover, the BMJ study itself found “no overall difference between allele carriers and non-carriers in HDL concentration.”

Like most meta-studies, this one has its strengths and weaknesses. The study used a large sample size, used detailed alcohol phenotypic data, and didn't have to deal with the inherent biases of observational-type studies. On the minus side, the lack of a connection between the allele in question and HDL levels is troubling, and stroke data was lacking.

But overall, the authors believe that "social pressure in heavier drinking cultures is unlikely to override the effect of the genetic variant on alcohol consumption."

In retrospect, there have been some trouble spots along the way: A 2008 study in Current Atherosclerosis Reports concluded:

In the absence of large randomized trials of moderate alcohol consumption and heart failure, we cannot exclude residual confounding or unmeasured confounding as possible explanations for the observed relationships. Thus, for patients who do not consume any alcohol, it would be premature to recommend light-to-moderate drinking as a means to lower the risk of heart failure, given the possible risk of abuse and resulting consequences.

At present, the American Heart Association does not recommend drinking any amount of wine or other alcoholic beverages in order to gain potential health benefits.


Holmes M.V.,  L. Zuccolo,  R. J. Silverwood,  Y. Guo,  Z. Ye,  D. Prieto-Merino,  A. Dehghan,  S. Trompet,  A. Wong &  A. Cavadino &  (2014). Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data, BMJ, 349 (jul10 6) g4164-g4164. DOI: http://dx.doi.org/10.1136/bmj.g4164

Photo credit: http://qsystem.gblifesciences.com/

The Chemistry of Modern Marijuana

Is low-grade pot better for you than sinsemilla?

First published September 3, 2013.

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  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 soared to THC levels in 2008 of almost 9%. THC loads more than doubled in 15 years, but that is still a far cry from news reports erroneously referring to organic THC increases of 10 times or more.

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 ordinary marijuana evolved into sinsemilla. Think Luther Burbank and global chemistry geeks. 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.”

Graphics Credit: http://www.ironlabsllc.co/view/learn.php

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

Synthetic Cannabis Can Cause Cyclic Vomiting

Another reason to skip "Spice."

Cannabinoid hyperemesis,  as it is known, was not documented in the medical literature until 2004. Case studies of more than 100 patients have been reported since then. The biomedical researcher who blogs as Drugmonkey has documented cases of hyperemesis that had been reported in Australia and New Zealand, as well as Omaha and Boston in the U.S.

As Drugmonkey reported, patients who are heavy marijuana smokers, and who experience cyclic nausea and vomiting, “discovered on their own that taking a hot bath or shower alleviated their symptoms. So afflicted individuals were taking multiple hot showers or baths per day to obtain symptom relief.”

A recent report in Mayo Clinic Proceedings by Dr. Benjamin L. Bick and colleagues documents the 3rd reported case of the syndrome in a regular user of synthetic Spice-style products, rather than marijuana. It’s now clear that THC isn’t necessary for triggering the rare but highly unpleasant vomiting cycle in a small fraction of users.

“A 29-year-old man presented with a 2-year history of recurrent episodes of severe nausea and vomiting with epigastric pain,” according to the authors. Drug tests were negative, including tests for THC. “For his more recent symptoms, he was evaluated multiple times in the primary care setting and emergency department. At each visit he denied use of any ‘illicit substances or drugs’ since he quit using marijuana.”

“Hot showers for up to an hour provided relief. He reported experiencing similar symptoms more than 5 years previously when he was regularly smoking marijuana, and these symptoms resolved with the cessation of cannabis.”

The patient eventually admitted to regularly smoking products sold as K2 and Kryptonite, containing “unidentified and uncertain synthetic cannabinoid agonists marketed as ‘legal’ herbal incense.”

The Mayo clinicians offer diagnostic criteria for cannabis hyperemesis, which include “long-term cannabis use, cyclic nausea and vomiting, resolution with cessation of cannabis, relief of symptoms with hot showers, abdominal pain, and weekly use of marijuana.” And theirs is the third published report of cannabis hyperemesis in a male patient after synthetic cannabinoid use. “After 6 months abstinence,” they report, “he noted complete resolution of symptoms.”

The researchers conclude that “synthetic cannabinoids can be potent agonists of the cannabinoid CB1 receptors, which are the same receptors by which THC produces its effects.” While only three Spice-related incidents of hyperemesis syndrome have thus far been identified, it may go unrecognized in patients using synthetic cannabinoids:

 A urine drug screen negative for THC may point physicians away from this syndrome, and patients may not report use if they believe they are using herbal products rather than illicit drugs. Therefore, regardless of negative urine drug screen results and patient denial of cannabis use, physicians should have a high index of suspicion for synthetic CH syndrome in patients who present with classic symptoms of cyclic emesis.

Sarah A. Buckley and Nicholas M. Mark at the NYU School of Medicine, after reviewing 16 published papers on the syndrome,  asked the obvious question: "How can marijuana, which is used in cancer clinics as an anti-emetic, cause intractable vomiting? And why would symptoms abate in response to high temperature?"

We don't know the answer, but Buckley and Mark note that "cannabis disrupts autonomic and thermoregulatory functions of the hippocampal-hypothalamic-pituitary system," which is loaded with CB-1 receptors. The researchers conclude, however, that the link between marijuana and thermoregulation "does not provide a causal relationship" for what they refer to as "this bizarre learned behavior.”

Bick B.L. &  Thomas F. Mangan (2014). Synthetic Cannabinoid Leading to Cannabinoid Hyperemesis Syndrome, Mayo Clinic Proceedings, 89 (8) 1168-1169. DOI: http://dx.doi.org/10.1016/j.mayocp.2014.06.013

Photo credit: http://www.aquaticcreationsnc.com/custom.htm

Avoid the ‘Noid: Synthetic Cannabinoids and “Spiceophrenia”

Like PCP all over again.

Synthetic cannabis-like “Spice” drugs were first introduced in early 2004, and quickly created a global marketplace. But the drugs responsible for the psychoactive effects of Spice products weren’t widely characterized until late 2008. And only recently have researchers made significant progress toward understanding why these drugs cause so many problems, compared to organic marijuana.

Synthetic cannabinoids (SC), as a class of drugs, are generally more potent at cannabinoid receptors than marijuana itself.  As full agonists, synthetic cannabinoids show binding affinities between 5 and 10,000 times higher than THC at these receptors.

A recent literature study by Duccio Papanti at the University of Trieste and coworkers sheds additional light on the problematic nature of these drugs. In an article for Advances in Dual Diagnosis titled “’Noids in a nutshell: everything you (don’t) want to know about synthetic cannabimimetics,” the researchers note that “Spice products’ effects have been anecdotally described by users as intense and ‘trippy’ marijuana-like, with hallucinatory experiences being associated with higher levels of intake. In comparison with cannabis, SC compounds may be associated with quicker ‘kick off’ effects; significantly shorter duration of action; larger levels of hangover effects; and more frequent paranoid feelings.”

The study also points out a trouble spot: “Super-concentrations of synthetic cannabinoids (e.g. ‘hot-spots’) in herbal blends, originating from a non-optimal homogenization between synthetic cannabinoids and the vegetal substrate, can result in overdoses/intoxications and ‘bad trips’ in users.” In other words, the chemical powder is often so poorly mixed with the vegetable matter that potencies in the batch can be way too high, depending upon the luck of the draw, and are bound to vary from batch to batch in any event.

Nonetheless, there is a cluster of specific health effects that brings users to the emergency room. The typical set of symptoms—bearing in mind that polydrug use always complicates the picture—include elevated heart rate, elevated blood pressure, visual and auditory hallucinations, agitation, anxiety, nausea, vomiting, and seizures.

The authors note that “nausea and seizures are very uncommon in marijuana use, due to the suggested anticonvulsant/antiemetic properties of cannabis.” In fact, misusers who present doctors with vomiting as a symptom are often assumed to be free of cannabis-type drugs. Not so with synthetic cannabinoids. In an email interview, lead author Duccio Papanti told me that “many users describe the occurrence of vomiting, even with a non-recurrent and low use of these compounds. My idea is that this may be due to the smoking of hot-spotted blends, and that at high concentrations these compounds can work more on 5-HT receptors (in fact, vomit and seizures are signs of a serotonin syndrome).”

Less common, luckily, are other medical issues like heart attack, kidney injuries, and stroke. Of primary concern, the authors warn, are the reported incidents of “transient psychotic episodes,” “relapse of a primary psychosis,” and “‘ex novo’ psychosis in previous psychosis-free subjects.”

As for the mechanism behind the reported hallucinogenic effects: “A number of synthetic cannabinoids contain an indole moiety, either in their basic structure or in their substituents.” Indoles are molecular groups structurally similar to serotonin, and are active in drugs like LSD and DMT.

“According to this finding,” Papanti says, “their use could interfere with serotonin 5-HT neurotransmission more than THC. It is possible that the indole moieties incorporated in the molecules of synthetic cannabinoids can bind 5-HT2 receptors, acting as an hallucinogenic drug (in fact visual hallucinations are not uncommon in SC use).”

 One of the main problems, of course, is that physicians know almost nothing about detecting and treating acute overdoses of synthetic cannabinoid products. And even if an OD victim was lucky enough to wash up at a health facility that had access to instant chromatography detection testing, “[due to] the lack of appropriate reference samples, SC compounds are difficult to identify.”

The risk here is not evenly distributed, obviously. Young people, and anybody subject to marijuana urine testing, are the clear market for these products. This includes students, athletes, members of the Armed Forces, transportation workers, mining workers, and many others. Spice users are overwhelmingly male.

How many people are taking the risk? An estimate of student use comes from the U.S. 2013 “Monitoring the Future” survey, which shows that about 8% of 17-18 year-olds have tried Spice products. For 12th graders, Spice products are second only to marijuana itself in many districts. And yet there is a dearth of longitudinal studies in humans to evaluate the long-term impact of using synthetic cannabinoids.

Papanti and colleagues call for the creation of an international agency dedicated to “toxicovigilance” based on a “non-biased ‘real-time’ database,” including adverse drug effects, as a way of clarifying and promoting appropriate clinical guidelines for Spice drugs. “These substances are dangerous, and they have been associated with a number of deaths,” Papanti says. He would like to see a “network in which users report their adverse effects. Such an online system already exists in the Pharmacovigilance program at the Lareb Centre in the Netherlands. They collect reports of medications’ adverse effects from both patients and doctors and it works very well.”

Tolerance, dependence, and withdrawal have all been documented in several categories of Spice products. Spice withdrawal effects can be severe, the authors say, and may include craving, tremor, profuse sweating, insomnia, anxiety, irritability and depression.

Graphics Credit:  http://www.caregroupnz.org.nz/drug-prevention-education-campaign/

Getting Spiced

Synthetic cannabis is stronger than it used to be.

First published 10/07/2013

I wish I could stop writing blog posts about Spice, as the family of synthetic cannabinoids has become known. I wish young people would stop taking these drugs, and stick to genuine marijuana, which is far safer. I wish that politicians and proponents of the Drug War would lean in a bit and help, by knocking off the testing for marijuana in most circumstances, so the difficulty of detecting Spice products isn’t a significant factor in their favor. I wish synthetic cannabinoids weren’t research chemicals, untested for safety in humans, so that I could avoid having to sound like an alarmist geek on the topic.  I wish I didn’t have to discuss the clinical toxicity of more powerful synthetic cannabinoids like JWH-122 and JWH-210. I wish talented chemists didn’t have to spend precious time and lab resources laboriously characterizing the various metabolic pathways of these drugs, in an effort to understand their clinical consequences. I wish Spice drugs didn’t make regular cannabis look so good by comparison, and serve as an argument in favor of more widespread legalization of organic marijuana.

A German study, published in Addiction, seems to demonstrate that “from 2008 to 2011 a shift to the extremely potent synthetic cannabinoids JWH-122 and JWH-210 occurred…. Symptoms were mostly similar to adverse effects after high-dose cannabis. However, agitation, seizures, hypertension, emesis, and hypokalemia  [low blood potassium] also occurred—symptoms which are usually not seen even after high doses of cannabis.”

The German patients in the study were located through the Poison Information Center, and toxicological analysis was performed in the Institute of Forensic Medicine at the University Medical Center Freiburg. Only two study subjects had appreciable levels of actual THC in their blood. Alcohol and other confounders were factored out. First-time consumers were at elevated risk for unintended overdose consequences, since tolerance to Spice drug side effects does develop, as it does with marijuana.

Clinically, the common symptom was tachycardia, with hearts rates as high as 170 beats per minute. Blurred vision, hallucinations and agitation were also reported, but this cluster of symptoms is also seen in high-dose THC cases that turn up in emergency rooms. The same with nausea, the most common gastrointestinal complaint logged by the researchers.

But in 29 patients in whom the presence of synthetic cannabinoids was verified, some of the symptoms seem unique to the Spice drugs. The synthetic cannabinoids caused, in at least one case, an epileptic seizure. Hypertension and low potassium were also seen more often with the synthetics. After the introduction of the more potent forms, JWH-122 and JWH-210, the symptom set expanded to include “generalized seizures, myocloni [muscle spasms] and muscle pain, elevation of creatine kinase and hypokalemia.” The researchers note that seizures induced by marijuana are almost unheard of. In fact, studies have shown that marijuana has anticonvulsive properties, one of the reason it is popular with cancer patients being treated with radiation therapy.

And there are literally hundreds of other synthetic cannabinoid chemicals waiting in the wings. What is going on? Two things. First, synthetic cannabinoids, unlike THC itself, are full agonists at CB1 receptors. THC is only a partial agonist. What this means is that, because of the greater affinity for cannabinoid receptors, synthetic cannabinoids are, in general, stronger than marijuana—strong enough, in fact, to be toxic, possibly even lethal. Secondly, CB1 receptors are everywhere in the brain and body. The human cannabinoid type-1 receptor is one of the most abundant receptors in the central nervous system and is found in particularly high density in brain areas involving cognition and memory.

The Addiction paper by Maren Hermanns-Clausen and colleagues at the Freiburg University Medical Center in Germany is titled “Acute toxicity due to the confirmed consumption of synthetic cannabinoids,” and is worth quoting at some length:

The central nervous excitation with the symptoms agitation, panic attack, aggressiveness and seizure in our case series is remarkable, and may be typical for these novel synthetic cannabinoids. It is somewhat unlikely that co-consumption of amphetamine-like drugs was responsible for the excitation, because such co-consumption occurred in only two of our cases. The appearance of myocloni and generalized tonic-clonic seizures is worrying. These effects are also unexpected because phytocannabinoids [marijuana] show anticonvulsive actions in humans and in animal models of epilepsy.

The reason for all this may be related to the fact that low potassium was observed “in about one-third of the patients of our case series.” Low potassium levels in the blood can cause muscle spasms, abnormal heart rhythms, and other unpleasant side effects.

One happier possibility that arises from the research is that the fierce affinity of synthetic cannabinoids for CB1 receptors could be used against them. “A selective CB1 receptor antagonist,” Hermanns-Clausen and colleagues write, “for example rimonabant, would immediately reverse the acute toxic effects of the synthetic cannabinoids.”

The total number of cases in the study was low, and we can’t assume that everyone who smokes a Spice joint will suffer from epileptic seizures. But we can say that synthetic cannabinoids in the recreational drug market are becoming stronger, are appearing in ever more baffling combinations, and have made the matter of not taking too much a central issue, unlike marijuana, where taking too much leads to nausea, overeating, and sleep.

(See my post “Spiceophrenia” for a discussion of the less-compelling evidence for synthetic cannabinoids and psychosis).

Hermanns-Clausen M., Kneisel S., Hutter M., Szabo B. & Auwärter V. (2013). Acute intoxication by synthetic cannabinoids - Four case reports, Drug Testing and Analysis,   n/a-n/a. DOI: 10.1002/dta.1483

Graphics Credit: http://www.aacc.org/

Hunting For the Marijuana-Dopamine Connection

Why do heavy pot smokers show a blunted reaction to stimulants?

Most drugs of abuse increase dopamine transmission in the brain, and indeed, this is thought to be the basic neural mechanism underlying the rewarding effects of addictive drugs. But in the case of marijuana, the dopamine connection is not so clear-cut. Evidence has been found both for and against the notion of increases in dopamine signaling during marijuana intoxication.

Marijuana has always been the odd duck in the pond, research-wise. Partly this is due to longstanding federal intransigence toward cannabis research, and partly it is because cannabis, chemically speaking, is damnably complicated. The question of marijuana’s effect on dopamine transmission came under strong scrutiny a few years ago, when UK researchers began beating the drums for a theory that chronic consumption of strong cannabis can not only trigger episodes of psychosis, but can be viewed as the actual cause of schizophrenia in some cases.

It sounded like a new version of the old reefer madness, but this time around, the researchers raising their eyebrows had a new fact at hand: Modern marijuana is several times stronger than marijuana in use decades ago. Selective breeding for high THC content has produced some truly formidable strains of pot, even if cooler heads have slowly prevailed on the schizophrenia issue.

One of the reports helping to bank the fires on this notion appeared recently in the Proceedings of the National Academy of Sciences (PNAS). Joanna S. Fowler of the Biosciences Department at Brookhaven National Laboratory, Director Nora Volkow of the National Institute on Drug Abuse (NIDA), and other researchers compared brain dopamine reactivity in healthy controls and heavy marijuana users, using PET scans. For measuring dopamine reactivity, the researchers chose methylphenidate, better known as Ritalin, the psychostimulant frequently prescribed for attention-deficit hyperactivity disorder (ADHD). Ritalin basically functions as a dopamine reuptake inhibitor, meaning that the use of Ritalin leads to increased concentrations of synaptic dopamine.

In the study, heavy marijuana users showed a blunted reaction to the stimulant Ritalin due to reductions in brain dopamine release, according to the research. “The potency of methylphenidate (MP) was also reported to be stronger by the controls than by the marijuana abusers." And in marijuana abusers, Ritalin caused an increase in craving for marijuana and cigarettes.

 “We found that marijuana abusers display attenuated dopamine responses to MP including reduced decreases in striatal distribution volumes,” according to the study’s conclusion. “The significantly attenuated behavioral and striatal distribution volumes response to MP in marijuana abusers compared to controls, indicates reduced brain reactivity to dopamine stimulation that in the ventral striatum might contribute to negative emotionality and drug craving.”

Down-regulation from extended abuse is another complicated aspect of this: “Although, to our knowledge, this is the first clinical report of an attenuation of the effects of MP in marijuana abusers, a preclinical study had reported that rats treated chronically with THC exhibited attenuated locomotor responses to amphetamine. Such blunted responses to MP could reflect neuroadaptations from repeated marijuana abuse, such as downregulation of DA transporters.”

 Animal studies have suggested that these dopamine alterations are reversible over time.

Another recent study came to essentially the same conclusions. Writing in Biological Psychiatry, a group of British researchers led by Michael A.P. Bloomfield and Oliver D. Howes analyzed dope smokers who experienced psychotic symptoms when they were intoxicated. They looked for evidence of a link between cannabis use and psychosis and concluded: “These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.” And again, the higher the level of current cannabis use, the lower the level of striatal dopamine synthesis capacity.  As for mechanisms, the investigators ran up against similar causation problems: “One explanation for our findings is that chronic cannabis use is associated with dopaminergic down-regulation. This might underlie amotivation and reduced reward sensitivity in chronic cannabis users. Alternatively, preclinical evidence suggests that low dopamine neurotransmission may predispose an individual to substance use.”

The findings of diminished responses to Ritalin in heavy marijuana users may have clinical implications, suggesting that marijuana abusers with ADHD may experience reduced benefits from stimulant medications.

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

Drugs and Disease: A Look Forward

First published 2/18/2014.

Former National Institute on Drug Abuse (NIDA) director Alan Leshner has been vilified by many for referring to addiction as a chronic, relapsing “brain disease.” What often goes unmentioned is Leshner’s far more interesting characterization of addiction as the “quintessential biobehavioral disorder.”

Multifactorial illnesses present special challenges to our way of thinking about disease. Addiction and other biopsychosocial disorders often show symptoms at odds with disease, as people generally understand it. For patients and medical professionals alike, questions about the disease aspect of addiction tie into larger fears about the medicalization of human behavior.

These confusions are mostly understandable. Everybody knows what cancer is—a disease of the cells. Schizophrenia? Some kind of brain illness. But addiction? Addiction strikes many people as too much a part of the world, impacted too strongly by environment, culture, behavior, psychology, to qualify. But many diseases have these additional components. In the end, the meaning of addiction matters less than the physiological facts of addiction.

One of the attractions of medical models of addiction is that there is such an extensive set of data supporting that alignment. Specifically, as set down in a famous paper by National Institute of Drug Abuse director Nora Volkow and co-author Joanna Fowler: “Understanding the changes in the brain which occur in the transition from normal to addictive behavior has major implications in public health…. We postulate that intermittent dopaminergic activation of reward circuits secondary to drug self-administration leads to dysfunction of the orbitofrontal cortex via the striato-thalamo-orbitofrontal circuit.” This cascade of events is often referred to as the “hijacking” of the brain by addictive drugs, but nothing is really being hijacked. Rather, the abusive use of drugs changes the brain, and that should come as no surprise, since almost everything we do in the world has the potential of changing the brain in some way. “Why are we so surprised that when you take a poison a thousand times, it makes some changes in your head?” said the former director of a chemical dependency treatment program at the University of Minnesota. “It makes sense that [addictive drugs] change things.”

Critics like Fernando Vidal object to a perceived shift from “having a brain” to “being a brain.” He is saying that he cannot see the point of “privileging” the brain as a locus for the study of human behavior. In “Addiction and the Brain-Disease Fallacy,” which appeared in Frontiers in Psychiatry, Sally Satel and Scott Lillienfeld write that “the brain disease model obscures the dimension of choice in addiction, the capacity to respond to incentives, and also the essential fact people use drugs for reasons (as consistent with a self-medication hypothesis).”

An excellent example of the excesses of the anti-brain discussions is an article by Rachel Hammer of Mayo Clinic and colleagues, in the American Journal of Bioethics-Neuroscience. “Many believed that a disease diagnosis diminishes moral judgment while reinforcing the imperative that the sick persons take responsibility for their condition and seek treatment.” But only a few paragraphs later, the authors admit: “Scholars have theorized that addiction-as-disease finds favor among recovering addicts because it provides a narrative that allows the person simultaneously to own and yet disown deviant acts while addicted.” Furthermore: “Addiction reframed as a pathology of the weak-brained (or weak-gened) bears just as must potential for wielding stigma and creating marginalized populations." But again, the risk of this potentially damaging new form of stigma “was not a view held by the majority of our addicted participants…”

And so on. The anti-disease model authors seem not to care that addicted individuals are often immensely helped by, and hugely grateful for, disease conceptions of their disorder, even though Hammer is willing to admit that the disease conception has “benefits for addicts’ internal climates.” In fact, it often helps addicts establish a healthier internal mental climate, in which they can more reasonably contemplate treatment. Historian David Courtwright, writing in BioSocieties, says that the most obvious reason for this conundrum is that “the brain disease model has so far failed to yield much practical therapeutic value.” The disease paradigm has not greatly increased the amount of “actionable etiology” available to medical and public health practitioners. “Clinicians have acquired some drugs, such as Wellbutrin and Chantix for smokers, Campral for alcoholics or buprenorphine for heroin addicts, but no magic bullets.” Physicians and health workers are “stuck in therapeutic limbo,” Courtwright believes.

“If the brain disease model ever yields a pharmacotherapy that curbs craving, or a vaccine that blocks drug euphoria, as some researchers hope,” Courtwright says, “we should expect the rapid medicalization of the field. Under those dramatically cost-effective circumstances, politicians and police would be more willing to surrender authority to physicians.” The drug-abuse field is characterized by, “at best, incomplete and contested medicalization.” That certainly seems to be true. If we are still contesting whether the brain has anything essential to do with addiction, then yes, almost everything about the field remains “incomplete and contested.”

Sociologists Nikolas Rose and Joelle M. Abi-Rached, in their book Neuro, take the field of sociology to task for its “often unarticulated conception of human beings as sense making creatures, shaped by webs of signification that are culturally and historically variable and embedded in social institutions that owe nothing substantial to biology.”

And for those worried about problems with addicts in the legal system, specifically, over issues of free will, genetic determinism, criminal culpability, and the “diseasing” of everything, Rose and Abi-Rached bring good news: “Probabilistic arguments, to the effect that persons of type A, or with condition B, are in general more likely to commit act X, or fail to commit act Y, hold little or no sway in the process of determining guilt.” And this seems unlikely to change in the likely future, despite the growing numbers of books and magazine articles saying that it will.

Opponents of the disease model of addiction and other mental disorders are shocked, absolutely shocked, at the proliferation of “neuro” this and “neuro” that, particularly in the fields of advertising and self-improvement, where neurotrainers and neuroenhancing potions are the talk of the moment. Sociologists claim to see some new and sinister configuration of personhood, where a journalist might just see a pile of cheesy advertising and a bunch of fast-talking science hucksters maneuvering for another shot at the main chance. When has selling snake oil ever been out of fashion?

For harm reductionists, addiction is sometimes viewed as a learning disorder. This semantic construction seems to hold out the possibility of learning to drink or use drugs moderately after using them addictively. The fact that some non-alcoholics drink too much and ought to cut back, just as some recreational drug users need to ease up, is certainly a public health issue—but one that is distinct in almost every way from the issue of biochemical addiction. By concentrating on the fuzziest part of the spectrum, where problem drinking merges into alcoholism, we’ve introduced fuzzy thinking with regard to at least some of the existing addiction research base. And that doesn’t help anybody find common ground.

Graphics Credit: http://www.docslide.com/disease-model/

Vitamin C and Pregnant Women Who Smoke

Improving pulmonary function in newborns.

500 mg of daily vitamin C given to pregnant smoking women “decreased the effects of in-utero nicotine” and “improved measures of pulmonary function” in their newborns, according to a study  by Cindy T. McEvoy and others at the Oregon Health and Science University in Portland, published in a recent issue of the Journal of the American Medical Association (JAMA).

Researchers have long known that smoking during pregnancy can harm the respiratory health of newborns. Maternal smoking during pregnancy can interfere with normal lung development, resulting in lifelong increases in asthma risk and other pulmonary complications. The researchers note that “more than 50% of smokers who become pregnant continue to smoke, corresponding to 12% of all pregnancies.” That adds up to a lot of newborns each year who will start off with more wheezing, respiratory infections, and childhood asthma than their counterparts born to non-smoking mothers.

McEvoy and her colleagues wanted to find out whether a daily dose of vitamin C would improve the results of pulmonary function tests in newborns exposed to tobacco in utero.

It did. In an accompanying editorial, Graham L. Hall calls the randomized, double-blind, placebo-controlled clinical trial “well-conceived and executed…. Lung function during the first week of life was statistically significantly better (by approximately 10%) among infants born to mothers randomized to receive Vitamin C compared with infants born to mothers randomized to received placebo.” Moreover, the prevalence of wheezing in the first year was reduced from 40% in the placebo group to 21% in the Vitamin C group.

The decreases in asthma and wheezing in the Vitamin C newborns were documented through the first year of life. 

A 10% reduction does not sound like a lot, but, as Hall writes, “small population-level changes in lung function may lead to significant public health benefits, and the improvements in lung function reported here could be associated with future benefit.”

In their paper, the researchers conclude: “Vitamin C supplementation in pregnant smokers may be an inexpensive and simple approach (with continued smoking cessation counseling) to decrease some of the effects of smoking in pregnancy on newborn pulmonary function and ultimately infant respiratory morbidities, but further study is required.”

Pregnant women should not smoke, and quitting is by far the healthiest option.  As Hall writes: “By preventing her developing fetus and newborn infant from becoming exposed to tobacco smoke, a pregnant woman can do more for the respiratory health and overall health of her child than any amount of vitamin C may be able to accomplish.”

McEvoy C.T.,  Nakia Clay,  Keith Jackson,  Mitzi D. Go,  Patricia Spitale,  Carol Bunten,  Maria Leiva,  David Gonzales,  Julie Hollister-Smith &  Manuel Durand &  (2014). Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants, JAMA, 311 (20) 2074. DOI: http://dx.doi.org/10.1001/jama.2014.5217

Graphics Credit: http://www.quitguide.com/

Gone in June

Alcohol takes a friend.

What good does it do: You write about addiction, research it, think about it, formulate new ideas about it. You try to be of service.

What good does it do: One of your best friends ever, a talented writer you have talked to and argued with and smoked with and paddled with for more than two decades, lies dead this morning of alcohol-related liver failure at 62.

What good does it do: I couldn’t save him, couldn’t turn the head of that runaway horse, not through encouragement, shame, praise, incentive, disgust, indifference, furious anger. Not through any of that.

What good does it do: His doctor, with my help, presented a program of 30-day detox and Ativan for the rough parts. He ordered the pills, never picked them up at the pharmacy. He never went back to the doctor, claiming a lack of health insurance. He never quit. He tried, like so many deluded alcoholics, to cut back on his drinking. He kept the phone number for the local AA group in a desk drawer, but never called. When his girlfriend told him it was either her or the bottle, he picked the bottle.

What good does it do: We cajoled, we watched him, we tripped over bags of empties in the basement and he didn’t care. We couldn’t save him. I couldn’t save him. I know more about alcoholism than most addiction therapists, and I couldn’t save him. I saved myself, 25 years ago, but could not save him.

What good does it do: I don’t know how to treat alcoholism, and save alcoholics, and neither do you. And if anybody tells me today, the day of my friend’s death, that alcoholism is a lifestyle choice, I promise to throw a swift right cross and knock them out on the spot.

The only possible light on the horizon is continued scientific research aimed at better elucidating the mechanisms behind addiction. Without that, one idea is about as good as another.

NIDA’s Dark View of Teen Marijuana Use

Federal study also discusses medical marijuana.

Considering the impasse on marijuana policy between state and federal governments in the U.S., the primary government agency in charge of drug research—NIDA, the National Institute on Drug Abuse—would seem to be caught between a rock and a hard place. Neuroscientists and other marijuana investigators who do research under NIDA grants have a fine line to walk in their efforts to disseminate research findings on cannabis.

From a public health point of view, NIDA is expected to keep up the pressure against drug legalization, or at least keep out of the fight, while also researching the medical pros and cons of cannabis. So it was with some interest that drug policy officials took in a recent article in the New England Journal of Medicine by NIDA director Nora Volkow titled “Adverse Health Effects of Marijuana Use.”

While the press has understandably centered on the risk of marijuana use among teens, which is the focus of the study, the report also contains some surprising admissions about marijuana’s health benefits as well as its addictive potential.

The teen risk emphasis comes from recent studies on two fronts—impaired driving and impaired brain function. The first is seriously confounded by dual use with alcohol, and the second is based, at least in part, on a controversial long-term study showing that marijuana use in the early years demonstrably lowers adult IQs.

No one would suggest that heavy marijuana smoking is good for developing teen brains, and there is sufficient evidence to worry about impairment to memory and to certain so-called “executive” cognitive functions. It is not clear how lasting these effects can be, but lead author Volkow is confident enough to say in a prepared statement that “Physicians in particular can play a role in conveying to families that early marijuana use can interfere with crucial social and developmental milestones and can impair cognitive development.” 

That these negative effects can be the outcome of heavy pot smoking in the teen years seems established beyond reasonable doubt. The extent and duration of these negative outcomes remain the topic of vociferous debate—although it is increasingly clear that the body’s endogenous cannabinoid system plays a key role in synapse formation during early brain development.

Meanwhile, the report re-emphasized the fact that marijuana is an addictive drug for some users—a fact that should not need re-emphasizing, but, lamentably, does. As Volkow and her co-authors write: “The evidence clearly indicates that long-term marijuana use can lead to addiction. Indeed, approximately 9% of those who experiment with marijuana will become addicted.”

Moreover, as regular readers of Addiction Inbox already know, “there is also recognition of a bona fide cannabis withdrawal syndrome (with symptoms that include irritability, sleeping difficulties, dysphoria, craving, and anxiety), which makes cessation difficult and contributes to relapse.” And, in line with the report’s overall theme, “those who begin in adolescence are approximately 2 to 4 times as likely to have symptoms of cannabis dependence within 2 years after first use.”

To their credit, the investigators decline to endorse the claim that marijuana use exacerbates or initiates episodes of illness in patients with schizophrenia and other psychoses, noting that “it is inherently difficult to establish causality in these types of studies because factors other than marijuana use may be directly associated with the risk of mental illness.” Furthermore, while early marijuana use is associated with an increased risk of dropping out of school, “reports of shared environmental factors that influence the risks of using cannabis at a young age and dropping out of school suggest that the relationship may be more complex…. The relationship between cannabis use by young people and psychosocial harm is likely to be multifaceted, which may explain the inconsistencies among studies.”

Indeed. The report also declares that the effects of long-term pot smoking on the risk of lung cancer are “unclear,” and that “the smoking of cigarettes containing both marijuana and tobacco products is a potential confounding factor with a prevalence that varies dramatically among countries.”

In conclusion, the strict demands of causality mean that the long-term effect of chronic marijuana exposure is not known with any certainty. It is possible, even likely, that these effects can vary dramatically from one smoker to another. But the equally persuasive demands of common sense dictate that inhaling dried, super-heated vegetable matter on a regular basis is likely to degrade your health, the more so if you are young and healthy to begin with.

As for other health issues: “The authoritative report by the Institute of Medicine, Marijuana and Medicine, acknowledges the potential benefits of smoking marijuana in stimulating appetite, particularly in patients with the acquired immunodeficiency syndrome (AIDS) and the related wasting syndrome, and in combating chemotherapy-induced nausea and vomiting, severe pain, and some forms of spasticity. The report also indicates that there is some evidence for the benefit of using marijuana to decrease intraocular pressure in the treatment of glaucoma.”

A detailed section titled “Clinical Conditions with Symptoms That May Be Relieved by Treatment with Marijuana or other Cannabinoids” brought additional research to light:

—Glaucoma: “More research is needed to establish whether molecules that modulate the endocannabinoid system may not only reduce intraocular pressure but also provide a neuroprotective benefit in patients with glaucoma.”

—Nausea: “THC is an effective antiemetic agent in patients undergoing chemotherapy, but patients often state that marijuana is more effective in suppressing nausea…. Paradoxically, increased vomiting (hyperemesis) has been reported with repeated marijuana use. [See various blog posts by Drugmonkey and me, starting with this and this.]

—AIDS-associated conditions: “Smoked or ingested cannabis improves appetite and leads to weight gain and improved mood and quality of life among patients with AIDS.”

—Chronic pain: “Studies have shown that cannabinoids acting through central CB1 receptors, and possibly peripheral CB1 and CB2 receptors, play important roles in… various models of pain. These findings are consistent with reports that marijuana may be effective in ameliorating neuropathic pain, even at very low levels of THC.”

—Inflammation: “Cannabinoids (e.g., THC and cannabidiol) have substantial anti-inflammatory effects…. Animal models have shown that cannabidiol is a promising candidate for the treatment of rheumatoid arthritis and for inflammatory diseases of the gastrointestinal tract (e.g., ulcerative colitis and Crohn’s disease).”

—Multiple sclerosis: “Nabiximols (Sativex, GW Pharmaceuticals), an oromucosal spray that delivers a mix of THC and cannabidiol, appears to be an effective treatment for neuropathic pain, disturbed sleep, and spasticity in patients with multiple sclerosis. Sativex… is currently being reviewed in phase 3 trials in the United States in order to gain approval from the Food and Drug Administration.”

—Epilepsy: In a recent small survey of parents who use marijuana with a high cannabidiol content to treat epileptic seizures in their children, 11% reported completed freedom from seizures…. Although such reports are promising, insufficient safety and efficacy data are available on the use of cannabis botanical for the treatment of epilepsy. However, there is increasing evidence of the role of cannabidiol as an antiepileptic agent in animal models.”

Volkow N.D., Baler R.D., Compton W.M. & Weiss S.R.B.  Adverse health effects of marijuana use., The New England journal of medicine,    PMID: 24897085

Tripling the Tax on Alcohol

Would it do any good?

A recent article in Slate by Reihan Salam, a sort of modest proposal on behalf of a big boost in alcohol excise taxes, caught considerable flack from free market advocates and conservative bloggers last week.

Salam says Americans agree on the fact that marijuana is not as dangerous a drug as alcohol, and that this agreement offers us an opportunity to “regulate alcohol more stringently than we regulate marijuana.” In fact, Salam argues, why not push the envelope: “Raise the alcohol tax to a point just shy of where large numbers of people will start making moonshine in their bathtubs.”

Salam tries to head off some of the usual criticisms by noting that Prohibition was an unmitigated disaster, but that “what most of us forget is that the movement for Prohibition arose because alcohol abuse actually was destroying American society in the first decades of the 20th Century," and that companies like Anheuser Busch and MillerCoors are plotting with national retail chains as you read this, scheming to make alcohol as cheap and easy to buy as humanly possible.

Salam further justifies a tripling of alcohol taxes by viewing it as a tactical offset to the efforts of liquor companies to focus on their best customers: “the small minority of people who drink the most.” Salam says that right now, it costs about two bucks per inebriated hour to get your drink on. Can we really argue that this price level is just too unsustainably high? Drug expert Mark Kleiman, Professor of Public Policy at UCLA, agrees.  In his book Marijuana Legalization: What Everyone Needs to Know, Kleiman and co-authors argue that “tripling the tax would raise the price of a drink by 20 percent and reduce the volume of drinking in about the same proportion. Most of the reduced drinking would come from heavy drinkers, both because they dominate the market in volume terms and because their consumption is more price-sensitive…."

Minnesota legislators recently passed a bill that opponents say would increase state excise taxes on alcoholic beverages to six times the current levels. Supporters of the alcohol tax say it means an extra $200 million per year to the state, at a cost to drinkers of about seven cents per drink. Or, in Salam's example: “Charging two-drink-per-day drinkers an extra $12 per month seems like a laughably small price to pay to deter binge drinking…. If you’re going to tax tanning beds and sugary soft drinks, why on earth wouldn’t you raise alcohol taxes too?”

Why wouldn’t you? Because it doesn’t accomplish what you want to accomplish, writes Michelle Minton at openmarket.org, the blog of the Competitive Enterprise Institute.  After a bit of throat clearing about the Nanny State, Minton writes that “fortunately, a society’s relationship with alcohol isn’t based solely on the price of alcohol…. Research shows that alcohol price is not an effective means of achieving lower total consumption or reducing binge drinking.” As evidence, Minton points to studies showing that Luxembourg and the Czech Republic “have both the highest priced alcohol and the highest rates of consumption in Europe.”

As for a comparison favored by Salam—New York’s anti-smoking campaign—Minton admits that the new higher cost of cigarettes cut the adult smoking rate dramatically, but points out that “New York is now the number-one market for smuggled cigarettes—which account for more than half of all cigarettes smoked in the state.” This is a powerful argument. If we triple the taxes on alcohol, do we risk a black market of dangerous home-brew bootlegger booze?

In my view, such threats are real, but they are theoretical. The current costs of alcohol in socioeconomic terms are enormous and undeniable. Tripling the alcohol tax might be asking for trouble, but we could get there in stages if Americans saw it as a desirable goal. Arguments against tax increases tend to ignore the fact that alcohol is a different kind of product, capable of addicting a significant minority of users, in addition to killing a certain percentage of drinkers outright through alcohol poisoning and traffic accidents. If we ignore the issue of drug dependence, and the health and legal costs of assorted alcohol-related mayhem, and simply lean on the fact that most people who drink use alcohol responsibly, then it gets easier to argue against increases in alcohol and cigarette taxes. Alcohol is not like other household products, and needn't be regulated like them.

Smoking Is Over If You Want It

Happy World No Tobacco Day

It’s one of the annual days of note concocted by the World Health Organization (WHO). The motive is undeniably noble, and the goofy negative title makes it a favorite of mine: Saturday, May 31, is the annual World No Tobacco Day.

This year, WHO and its partner organizations around the world are focusing on the economics of the global tobacco trade by urging nations to raise taxes on tobacco products. Raising taxes has two potential effects: It drives down consumption and it provides revenue for government health spending on tobacco-related illness and prevention. This latter concern will only grow in the U.S., as the aging boomer cohort reaches the decade of maximum ravagement from smoking-related diseases.

A tax increase that boosts the price of tobacco by 10% “decreases tobacco consumption by about 4% in high-income countries and by up to 8% in most low- and middle-income countries,” according to the organization. And this sweetener: “The World Health Report 2010 indicated that a 50% increase in tobacco excise taxes would generate a little more than US$ 1.4 billion in additional funds in 22 low-income countries. If allocated to health, government health spending in these countries could increase by up to 50%.”

What is the alternative? A bleak epidemic that will be killing more than 8 million people every year by 2030. “More than 80% of these preventable deaths will be among people living in low-and middle-income countries,” says WHO. The tax hammer is not as widely used for tobacco control as common sense might suggest. WHO says that “only 32 countries, less than 8% of the world's population, have tobacco tax rates greater than 75% of the retail price.” Even so, tobacco tax revenues are on average 175 times higher than spending on tobacco control, WHO data shows.

WHO also urges continued ad bans as a means of lowering consumption. “Only 24 countries, representing 10% of the world’s population, have completely banned all forms of tobacco advertising, promotion and sponsorship. Around one country in three has minimal or no restrictions at all on tobacco advertising, promotion and sponsorship.”

For more info, write the WHO Media Centre at mediainquiries@who.int.

Single Bout of Binge Drinking Linked to Immune System Effects

The hazards of a leaky gut.

Biology for $1000, Alex: An integral part of the cell walls of Gram-negative bacteria, these toxic compounds can trigger inflammation and other immunological responses after a single episode of heavy drinking.

Answer: What are endotoxins?

The outer membranes of gram-negative bacteria contain toxic elements known as endotoxins, or lipopolysaccharides. An endotoxin is released when a bacterial cell wall is breached, allowing virulent proteins to enter the bloodstream. When endotoxins engage with the immune system, the result is inflammation—a necessary part of healing, yet potentially damaging to surrounding cells and tissue. When you come down with a cold, those aches and pains come are caused by your immune system inducing inflammation to fight the virus. Chronic inflammation is not a good thing. Higher levels of circulating endotoxins have been linked to numerous health issues.

Binge drinking: Almost everybody does it now and then, and some drinkers do it every day. So what is binge drinking, anyway? The NIAAA defines it as a drinking pattern that results in a blood alcohol level of 0.08 or above. This means about four drinks for women and five for men over a period of about two hours. “In chronic alcohol use activation of the inflammatory cascade is a major component of organ damage in the brain and liver,” according to researchers at the University of Massachusetts Medical School.  “Alcohol binge can cause altered immune functions that can also contribute to immunosuppression and reduced immune-mediated host defense to pathogens.”

Nobody ever claimed binge drinking was good for you. But the work done by researchers at the University of Massachusetts Medical School on a small group of drinkers shows that a single episode of five drinks or more “can cause damaging effects such as bacterial leakage from the gut into the blood stream,” said Dr. George Koob, director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The work was funded by the National Institutes of Health (NIH). The study “tested the effects of acute binge drinking on serum endotoxin and bacterial 16S rDNA in normal human adults.” Led by Gyongyi Szabo, a professor at the University of Massachusetts Medical School, the study in PLOS ONE  documented increases in endotoxin levels in the blood and evidence of bacterial DNA from the gut.

The investigators found that the concentration of endotoxin observed in the serum after an acute binge had significant biological activity, in particular a “significant induction of inflammatory cytokines.” In a prepared statement, Szabo said: “We found that a single alcohol binge can elicit an immune response, potentially impacting the health of an otherwise health individual. Our observations suggest than an alcohol binge is more dangerous than previously thought.” Fever, hypotension, and septic shock may develop due to endotoxins.

Compounding the harm to internal organs caused by alcohol is “gut permeability,” meaning that toxins have a better chance of escaping through the intestinal wall, wandering to other parts of the body, where they do harm. When you combine greater gut permeability with increased levels of circulating endotoxins, you get alcohol-related liver damage and other problems. Binge drinking, the researchers believe they have shown, is a good way to speed up that process.

In short, binge drinking helps gram-negative bacteria break the gastric barrier, escape the stomach, and colonize the small intestine, which puts them into systemic circulation. Bad news. The only bacteria that should be colonizing the small intestine is your neighborhood-friendly graham-positive Lactobaccilus, which aids digestion.

Unfortunately, the study also added to the growing mountain of evidence showing the ways in which alcohol affects women differently than men (See my report on gender-specific alcohol treatment in Scientific American.) Binge drinking showed a greater effect on women with respect to both endotoxemia and bacterial DNA levels.

According to the report: “Compared to men, women showed a slower decreased in blood alcohol levels (BAL), and even 24 hours after the alcohol binge BALs were higher in women than that in men…. Serum endotoxin levels were also higher in women after alcohol intake and a significant difference in endotoxin level was observed at 4 hours between men and women.”

Bala S., Marcos M., Gattu A., Catalano D. & Szabo G. (2014). Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals., PloS one,  PMID: 24828436

Why the CDC Director Hates E-Cigarettes

The pros and cons of getting your vape on.

Last month, the Food and Drug Administration (FDA) began a new era—regulating e-cigarettes. With a non-controversial first step, the FDA banned the sale of e-cigarettes to minors, required health warnings, prohibited health claims, and outlined a plan to register and license all electronic nicotine products at some future date. The FDA’s proposed rules would also give the agency the power to regulate the currently unregulated mixture of chemicals and flavorings that are heated during e-cigarette use.  Whatever regulations the FDA promulgates for electronic cigarettes will also apply to nicotine gels, water pipe tobacco, and hookahs.

Perhaps what rankles e-cigarette activists the most is the FDA’s insistence that companies will have to provide scientific evidence before making any implied claims about risk reduction for their product, compared with cigarettes. The FDA did not restrict advertising or prohibit flavorings (bubble gum, apple-blueberry, gummi bear, and cappuccino are popular).

Within a few days after the FDA’s announcement, Chicago, New York City, and other major cities placed e-cigarettes under the same municipal smoking bans as cigarettes. 

The battle over e-cigarettes is both a public health issue and a private enterprise war for market share. Corporate giants Altria and Lorillard, which dominate the corporate tobacco landscape in the U.S., are fighting for a piece of what has become nearly a $2 billion market in a few short years. (Altria recently boosted  its growth forecast to 6-9% growth for 2014). Lorillard has been making heavy acquisitions of its own, and commands more than half the present market with its Blu brand. Altria has made its own vapor acquisitions, and is launching its own brand, MarkTen.

So far, the moves being contemplated by the FDA do not have these companies shaking in their boots. They anticipated the ban on sales to minors, a system of formal FDA approval, a disclosure of ingredients, and health warnings about the addictive nature of nicotine. And Congress gave the FDA legal authority to draft a set of rules for e-cigarettes five years ago, so the FDA’s reluctance to step in on liquid nicotine delivery systems has been evident.

In an interview with the Los Angeles Times, Tom Frieden, director of the Center for Disease Control and Prevention (CDC), listed the reasons for his opposition to electronic cigarettes:

—E-cigarettes are an additional means of hooking another generation of kids on nicotine, making them more likely to become adult smokers.

—Smokers who might have quit smoking will maintain their nicotine addiction, remaining highly vulnerable to tobacco craving.

—Ex-smokers might make themselves more vulnerable to relapse if they take up vaping.

—Smokers might forego medications that could help them quit, in favor of the unproven promise of tobacco abstention via e-cigarette.

—E-cigarettes might have the cultural effect of “re-glamorizing” smoking.

—E-cigarette users might be exposing children and pregnant women to nicotine via secondhand smoke mechanisms.

—E-cigarette users can refill cartridges with liquid cannabis products and other drugs.

Dr. Michael Siegel, a tobacco expert at the Boston University School of Public Health, worries that smaller players will be squeezed out due to costs associated with the FDA approval process, driving sales toward the traditional cigarette industry leaders. Go-go analysts have predicted market penetration of as much as 50% for e-cigarettes, but Siegel is more pessimistic, and believes the e-cigarette share could top out at 10% if FDA regulations set back efforts by vaping proponents to position their product as a safer and healthier alternative to tobacco cigarettes. And that, says Siegel, would be a shame. He told the Boston Globe: “There simply is no product on the market that’s more dangerous than tobacco cigarettes, and nobody in their right mind would argue that cigarette smoking is less hazardous or even equally hazardous to vaping.”

Frieden at the CDC is sympathetic to the fact that many smokers have indeed quit smoking tobacco with the aid of e-cigarettes. “Stick to stick, they’re almost certainly less toxic than cigarettes.” But like many tobacco experts, he sees the possibility of a new generation of nicotine addicts. Almost two million high school kids have tried e-cigarettes, Frieden told the LA Times, “and a lot of them are using them regularly…. That’s like watching someone harm hundreds of thousands of children.”  The CDC reported that the percentage of high school students who have used an e-cigarette jumped from 4.7% in 2011 to 10% in 2012. Calls to poison control centers involving children and e-cigarettes have increased sharply as well.

Frieden views the Food and Drug Administration as David under siege by Goliath. The FDA, he said, “tried to regulate e-cigarettes earlier, and they lost to the tobacco industry…. So the FDA has to balance moving quickly with moving in a way that’s going to be able to survive the tobacco industry’s highly paid legal challenge.” If E-cigarette makers really want to market to people trying to quit smoking, Frieden told the LA Times, “then do the clinical trials and apply to the FDA. But they don’t want to do that.” (See my post on Big Tobacco’s move into the e-cigarette market).

“It’s really the wild, wild West out there,” a beleaguered FDA commissioner Margaret Hamburg told the press.   “They’re coming in different sizes, shapes and flavors in terms of the nicotine in them.”

On May 4, the New York Times published a report by Matt Richtel, based on an upcoming paper in the journal Nicotine and Tobacco Research. Nicotine researchers discovered that high-end electronic cigarette systems with refillable tanks produce formaldehyde, a known carcinogen, as a component of the exhaled nicotine vapor. Moreover, unlike disposable e-cigarettes, tank systems require users to refill them with liquid nicotine, itself a potent toxin. “Nicotine is a pesticide, fundamentally,” Michael Eriksen, dean of the School of Public Health at Georgia Statue University, told CNN. “We take so many precautions about pesticides for our lawns and how to wear gloves. But what precautions do consumers take when they put the nicotine vials in?”

This was not good news for harm reductionists, who view the advantages of e-cigarettes as self-evident. The New York Times report says that the toxin is formed “when liquid nicotine and other e-cigarette ingredients are subjected to high temperatures,” according to the research. “A second study that is being prepared for submission to the same journal points to similar findings.” In addition, a new study by researchers RTI International documents the release of tiny metal particles, including tin, chromium and nickel, which may worsen asthma and bronchitis.

Eric Moskowitz at the Boston Globe  reported that “thousands of gas stations and convenience stores statewide carry e-cigarettes, usually stocking disposable or cartridge-based versions that resemble traditional cigarettes.”

In U.S. News, Gregory Conley, president of the trade group American Vaping Association, predicted “a huge influx of anti-e-cigarette legislation in the last half of 2014 and especially in 2015 when the legislative sessions get going again.” 

According to Carl Tobias, a law professor at the University of Richmond, “it may be years before  regulations are imposed. The lobbying at FDA and Congress will be intense.”

Effectively regulated, e-cigarettes have the potential to drastically reduce deaths from tobacco-related diseases among cigarette smokers. In an editorial for the journal Addiction, Sara Hitchman, Ann McNeill, and Leonie Brose of King’s College, London, wrote: “E-cigarettes may offer a way out of the smoking epidemic or a way of perpetuating it; robustly designed, implemented and accurately reported scientific evidence will be the best tool we have to help us predict and shape which of these realities transpires.”

Photo credit: http://ecigarettereviewed.com