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The Mysteries of the Blunt

Why do so many smokers combine tobacco with marijuana?

People who smoke a combination of tobacco and marijuana, a common practice overseas for years, and increasingly popular here in the form of “blunts,” may be reacting to some unidentified mechanism that links the two drugs. Researchers believe such smokers would be well advised to consider giving up both drugs at once, rather than one at a time, according to an upcoming study in the journal Addiction.

Clinical trials of adults with cannabis use disorders suggest that “approximately 50% are current tobacco smokers,” according to the report, which was authored by Arpana Agrawal and Michael T. Lynskey of Washington University School of Medicine, and Alan J. Budney of the University of Arkansas for Medical Sciences.  “As many cannabis users smoke a mixture of cannabis and tobacco or chase cannabis use with tobacco, and as conditioned cues associated with smoking both substances may trigger use of either substance,” the researchers conclude, “a simultaneous cessation approach with cannabis and tobacco may be most beneficial.”

A blunt is simply a marijuana cigar, with the wrapping paper made of tobacco and the majority of loose tobacco removed and replaced with marijuana. In Europe, smokers commonly mix the two substances together and roll the combination into a single joint, the precise ratio of cannabis and nicotine varying with the desires of the user. “There is accumulating evidence that some mechanisms linking cannabis and tobacco use are distinct from those contributing to co-occurring use of drugs in general,” the investigators say. Or, as psychiatry postdoc Erica Peters of Yale put it in a press release, “There’s something about tobacco use that seems to worsen marijuana use in some way.” The researchers believe that this “something” involved may be a genetic predisposition. In addition to an overall genetic proclivity for addiction, do dual smokers inherit a specific propensity for smoked substances? We don’t know—but evidence is weak and contradictory so far.

Wouldn’t it be easier to quit just one drug, using the other as a crutch? The researchers don’t think so, and here’s why: In the few studies available, for every dually addicted participant who reported greater aggression, anger, and irritability with simultaneous cessation, “comparable numbers of participants rated withdrawal associated with dual abstinence as less severe than withdrawal from either drug alone.” So, for dual abusers, some of them may have better luck if they quit marijuana and cigarettes at the same time. The authors suggest that “absence of smoking cues when abstaining from both substances may reduce withdrawal severity in some individuals.” In other words, revisiting the route of administration, a.k.a. smoking, may trigger cravings for the drug you’re trying to quit. This form of “respiratory adaption” may work in other ways. For instance, the authors note that, “in addition to flavorants, cigarettes typically contain compounds (e.g. salicylates) that have anti-inflammatory and anesthetic effects which may facilitate cannabis inhalation.”

Studies of teens diagnosed with cannabis use disorder have shown that continued tobacco used is associated with a poor cannabis abstention rate. But there are fewer studies suggesting the reverse—that cigarette smokers fair poorly in quitting if they persist in cannabis use. No one really knows, and dual users will have to find out for themselves which categories seems to best suit them when it comes time to deal with quitting.

We will pass up the opportunity to examine the genetic research in detail. Suffice to say that while marijuana addiction probably has a genetic component like other addictions, genetic studies have not identified any gene variants as strong candidates thus far. The case is stronger for cigarettes, but to date no genetic mechanisms have been uncovered that definitively show a neurobiological pathway that directly connects the two addictions.

There are all sorts of environmental factors too, of course. Peer influences are often cited, but those influences often seem tautological: Drug-using teens are members of the drug-using teens group. Tobacco users report earlier opportunities to use cannabis, which might have an effect, if anybody knew how and why it happens.

Further complicating matters is the fact that withdrawal from nicotine and withdrawal from marijuana share a number of similarities.  The researchers state that “similar withdrawal syndromes, with many symptoms in common, may have important treatment implications.” As the authors sum it up, cannabis withdrawal consists of “anger, aggression or irritability, nervousness or anxiety, sleep difficulties, decreased appetite or weight loss, psychomotor agitation or restlessness, depressed mood, and less commonly, physical symptoms such as stomach pain and shakes/tremors.” Others complain of night sweats and temperature sensitivity.

And the symptoms of nicotine withdrawal? In essence, the same. The difference, say the authors, is that cannabis withdrawal tends to produce more irritability and decreased appetite, while tobacco withdrawal brings on an appetite increase and more immediate, sustained craving. Otherwise, the similarities far outnumber the differences.

None of this, however, has been reflected in the structure of treatment programs: “Emerging evidence suggests that dual abstinence may predict better cessation outcomes, yet empirically researched treatments tailored for co-occurring use are lacking.”

The truth is, we don’t really know for certain why many smokers prefer to consume tobacco and marijuana in combination. But we do know several reasons why it’s not a good idea. Many of the health-related harms are similar, and presumably cumulative: chronic bronchitis, wheezing, morning sputum, coughing—smokers know the drill. Another study cited by the authors found that dual smokers reported smoking as many cigarettes as those who only smoked tobacco. All of this can lead to “considerable elevation in odds of respiratory distress indicators and reduced lung functioning in those who used both.” However, there is no strong link at present between marijuana smoking and lung cancer.

Some researchers believe that receptor cross-talk allows cannabis to modify receptors for nicotine, or vice versa. Genes involved in drug metabolism might somehow predispose a subset of addicts to prefer smoking. But at present, there are no solid genetic or environmental influences consistent enough to account for a specific linkage between marijuana addiction and nicotine addiction, or a specific genetic proclivity for smoking as a means of drug administration.

Agrawal, A., Budney, A., & Lynskey, M. (2012). The Co-occurring Use and Misuse of Cannabis and Tobacco: A Review Addiction DOI: 10.1111/j.1360-0443.2012.03837.x

Photo credit:  http://stuffstonerslike.com

Nicotine and the Humphrey Bogart Gene

You can lead a fish to water, but can you make it smoke?

Zebrafish embryo showing axon tracts in green, viewed from lateral (top) and dorsal (bottom) orientations------>

Common denizens of home aquariums, the humble zebrafish may dart about the tank like any other small tropical specimen, but zebrafish have become one of the hot genetic research tools of the moment. The lab rat may have met its match in the lab zebrafish, a popular non-mammalian organism that is currently playing a leading role in government-sponsored research on the genetic aspects of nicotine addiction.

Scientists are fond of these new fishy animal models because zebrafish are cheap, develop rapidly, and are more biologically similar to humans than anyone might naively assume. Their transparent embryos allow researchers to inject flourescent proteins into living animals, and in some cases to track the regulation of gene expression as it is happening.

Research funded by the National Institute on Drug Abuse (NIDA) and  published in the Proceedings of the National Academy of Sciences used zebrafish in a hunt for genes

affecting nicotine exposure. Like rats, the fish show characteristic behaviorial responses to low doses, high doses, and the nicotine sensitization process. According to NIDA, the scientists “induced mutations in particular DNA segments of the zebrafish and looked at changes in the nicotine response profile of mutant carriers compared to their siblings.” The changes in nicotine response observed between the groups were mediated by two genes, which the scientists dubbed bdav/cct8 (bette davis) and hbog/gabbr1.2 (humphrey bogart), named after “celebrities that suffered from tobacco-related cancers.” These two genes, when expressed, caused zebrafish to respond more positively to nicotine.

“We all know how hard it is to quit smoking,” Dr. Ekker told Mayo’s online research magazine, Discovery’s Edge. “What most people don’t know is that genetic differences significantly contribute to the degree of nicotine dependence. We want to understand the genetics behind different responses to nicotine and come up with more effective and individualized treatments for people addicted to nicotine.”

The Mayo Clinic in Minnesota has taken a leading role in developing the fish for research, having established the Zebrafish Core Facility in 2007 under the direction of Dr. Stephen Ekker. Mayo’s zebrafish are now being used in various research laboratories for research in the fields of developmental biology and functional genomics. The fish are now a crucial part of biological research on cancer and heart disease, as well as addiction.

Graphics Credit: http://www.ucl.ac.uk/

Petzold AM, Balciunas D, Sivasubbu S, Clark KJ, Bedell VM, Westcot SE, Myers SR, Moulder GL, Thomas MJ, & Ekker SC (2009). Nicotine response genetics in the zebrafish. Proceedings of the National Academy of Sciences of the United States of America, 106 (44), 18662-7 PMID: 19858493

Life After Cigarettes: Book Review

Why Women Smoke.

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

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

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

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

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

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

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

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

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

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

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

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

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

Rethinking the Patch

Quitters do better on 6-month regimen.

It may sound like dream propaganda for the makers of nicotine patches. And it is. Moreover, at least one of the study authors has worked in the past as a consultant for GlaxoSmithKline, maker of Nicoderm CQ, one of the best-selling brands of transdermal nicotine patches.

So there is every reason to dismiss a recent study by researchers at the University of Pennsylvania School of Medicine, published in the Annals of Internal Medicine, which strongly suggests that the currently recommended regimen of two months isn’t long enough. It should be tripled. Which also triples sales.

There’s only one catch: There is reason to believe that the results are legitimate, and that smokers who are trying to quit would be more successful if they stuck with the patch for longer periods than currently recommended on the manufacturer’s box.  For some time now, tobacco addiction researchers, and centers such as Mayo Clinic’s Stop Smoking facilities, have recognized the need for extending the manufacturer’s suggested period of use.

Referring to the patch on its Stop Smoking web site, Mayo Clinic says: “You typically use the nicotine patch for eight to 12 weeks. You may need to use it longer if cravings or withdrawal symptoms continue.”

And from the field come reports of abstaining smokers independently choosing to use the patch longer, often by cutting the patches into eighths or sixteenths in order to accomplish a long, slow taper at the end of the process. By following this route, a nicotine addict need not be aware of the precise day or moment when his nicotine fix from the patch has dropped to placebo levels—further evidence that nicotine addiction is a chronic condition that may not respond to treatments of only two to three months in duration. 

One early development during the marketing of the patch that helped set the short-term use pattern were reports in the 1990s of heart attacks by patch users. Subsequent research showed that rare cardiac problems had arisen in patients who had continued heavy smoking while on the patch, and that there was little evidence of a direct link between nicotine patches and heart attacks. (Recent heart attack victims are advised to wait six weeks and use patches with caution.)

The study concludes: “Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy.”

One limitation of this particular study, acknowledged as such by the authors, is that “participants were smokers without medical comorbid conditions who were seeking treatment.” In other words, the study cohort consisted of highly motivated smokers.

And another problem is cost: Few health insurance companies cover the full cost of patches, including Medicaid. The additional cost per quitter, the study found, was about $2,400 for the extended regimen.

Nonetheless, any uptick in success rates for smoking cessation programs should be noted and taken under consideration.

Photo Credit: www.drugabuse.gov