Cigarettes: Should the FDA Mandate a National Taper?

Addiction expert calls for reduced-nicotine tobacco.

For years now, nicotine researcher Neal Benowitz has been a man on a mission. Dr. Benowitz, a professor of medicine at the University of California in San Francisco, has been pushing a Big Idea about how to eliminate cigarette smoking in America: Reduce the amount of nicotine in cigarettes.

In essence, Benowitz is calling for a national nicotine taper. Whether the FDA is interested remains an open question. But the result, several years down the road, would be a nation of teenagers confronted with only weakly addictive tobacco products.

It is an old idea, often viewed with great suspicion because of the failure of “light” and “low-tar” cigarettes to reduce nicotine intake, and in fact causing smokers to smoke harder. But Benowitz, one of the nation’s premier tobacco scientists, believes that when it comes to the roughly one out of five Americans who still smoke, a new generation of so-called “low-nicotine delivery” cigarettes is the answer. 

In a controlled study of 135 smokers of various ages, participants smoked cigarettes with progressively lower nicotine over a two-year period, and did so “without evidence of compensation”—meaning that they did not smoke more cigarettes or smoke differently when using the low-nicotine offerings. This varies dramatically from the behavior associated with light cigarettes and special filters—innovations that were marketed as “safer” cigarettes—that simply increase ventilation. The light cigarettes themselves contain the same amount of nicotine as a “regular” cigarette. And smokers quickly learn to puff harder, or cover small holes in the filter paper with their fingers, in order to extract more nicotine from each cigarette.

But with low-nicotine delivery cigarettes, you can’t get more nicotine, no matter what kind of smoker’s gyrations you perform. And the result, according to a paper by Benowitz and coworkers in Cancer, Epidemiology, Biomarkers and Prevention, is that “when the nicotine content of cigarettes is progressively decreased at monthly intervals over 6 months there is a progressive decline in nicotine intake by smokers, with only a small degree of compensation at the lowest nicotine content levels.”

The two-year study was randomized but unblinded, in order to simulate situations in which smokers are fully aware of using cigarettes with progressively less nicotine. A control group smoked their usual brands of cigarettes throughout the study. Benowitz, who led the studied, said in prepared remarks that the U.S. Food and Drug Administration (FDA) now has the authority to regulate the nicotine content of cigarettes sold in the U.S. (Benowitz is a member of the FDA’s Tobacco Products Scientific Advisory Committee.) “The idea is to reduce people’s nicotine intake, so that they get used to the lower levels, and eventually get to the point where smoking is no longer satisfying.”

The study was small, and there were dropouts. As always, further long-term study will be needed to track smokers during this kind of long-term nicotine taper. Traditionally, tapering has not been an effective method of breaking a nicotine addiction. But the reason for that may have to do with the easy availability of full-strength cigarettes in every store and gas station. The obvious goal for Benowitz is the reduction of nicotine in cigarettes to the point where they are no longer addictive. But would a robust black market in strong cigarettes leap up if nicotine reduction were a federally mandated program?

“Progressive reduction of the nicotine content of cigarettes as a national regulatory policy might have important potential benefits for the population,” the authors write, adding that “some people who had no intention of quitting upon entry into the study had… either quit spontaneously or were thinking about quitting in the near future after smoking reduced-nicotine content cigarettes.” Low-nicotine cigarettes could be produced by extracting nicotine from existing tobacco, or by genetically engineering tobacco with a lower nicotine content.

“Adolescents initiate smoking for social reasons, with friends, and later begin to smoke for pharmacologic reasons related to dependence,” the authors conclude. “Presumably a cigarette with very low nicotine content would be less likely to support the transition from social to dependent smoking, although the threshold level of nicotine to prevent this transition is not yet known.”

Benowitz NL, Dains KM, Hall SM, Stewart S, Wilson M, Dempsey D, & Jacob P 3rd (2012). Smoking behavior and exposure to tobacco toxicants during 6 months of smoking progressively reduced nicotine content cigarettes. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 21 (5), 761-9 PMID: 22354905

Photo Credit: http://chronicle.uchicago.edu

Does Menthol Really Matter?

Nicotine experts say menthol makes addiction more likely--but differ over what to do about it.

Back in the 1920s, Lloyd “Spud” Hughes of Mingo Junction, Ohio, was working as a restaurant cashier when, legend has it, he smoked some cigarettes that had been casually stored in a tin that contained menthol crystals. Menthol, a compound found in mint plants and also manufactured synthetically, is used medicinally, and as a food flavoring. Back in Spud’s day, menthol was mostly derived by extracting crystals from the Japanese Mint plant. What we know for certain is that the mentholated cigarettes tasted so good to Spud that he patented the mixture. In 1925, the Spud Cigarette Corporation of Wheeling, West Virginia, was born, and Spud Cigarettes quickly became the 5th best selling cigarette brand in America. 

Dr. Neal L. Benowitz, Professor of Medicine and Bioengineering & Therapeutic Sciences, and Chief of the Division of Clinical Pharmacology at the University of California in San Francisco, says that Spud Hughes had “accidentally identified an additive whose pharmacologic actions reduce the irritating properties of smoke generally and nicotine specifically.” Menthol accomplishes this because it acts on receptors involved in the detection of physical stimuli like temperature and chemical irritation. “Menthol contributes to perceptions of cigarettes’ strength, harshness, or mildness, smoothness, coolness, taste, and aftertaste.” That would seem to just about cover it. But no: In their article for the New England Journal Of Medicine—“The Threat of Menthol Cigarettes to U.S. Public Health"—Benowitz and Jonathan M. Samet also claim that “menthol has druglike characteristics that interact at the receptor level with the actions of nicotine.”

And nicotine hardly needs much help establishing its grip over addiction-prone individuals. “It’s not that it’s so intensive,” Dr. Benowitz told me some years ago, when I was researching my book, The Chemical Carousel, “it’s just that it’s so reliable. Nicotine arouses you in the morning; it relaxes you in the afternoon. It’s a drug that you can dose many times per day for the purpose of modulating your mood, and it becomes highly conditioned, more than any other drug, because it’s used every single day, multiple times per day.” Benowitz, along with Dr. Michael Siegel of the Boston University School of Public Health, recently sparked intense debate when they both championed electronic cigarettes as a safe alternative to smoking tobacco cigarettes, despite the FDA’s earlier wish to keep e-cigarettes out of the country. And last month, an advisory report for the FDA by a group that included Benowitz and Samet concluded that mentholated cigarettes were no more harmful, and no more likely to cause disease, than regular cigarettes. A study in the Journal of the National Cancer Institute of 440 lung cancer patients and more than 2,000 matched patients without lung cancer showed no correlation at all between menthol and cancer. In fact, the researchers were surprised to discover that menthol smokers appear to have a lower risk of lung cancer than other smokers. Asked whether menthol cigarettes are more toxic than non-menthol cigarettes, the study's author William Blot of Vanderbilt University definitively responded: “The answer is, no, they are not.”

However, the advisory report suggested that, while menthol cigarettes may not be more dangerous, they might be more addictive than regular cigarettes.  In the May 4 New England Journal of Medicine article, Benowitz and Samet argue that because menthol cigarettes attract younger smokers by making tobacco easier to smoke, and because more of these smokers go on to become lifelong nicotine addicts due to this same cooling effect, "menthol cigarettes increase the likelihood of addiction and the degree of addiction in new smokers." Further adding to menthol’s tendency to create lifelong smokers is the fact that “some consumers, particularly blacks, hold beliefs about implicit health benefits of menthol cigarettes that may interfere with their quitting."

This is a substantial indictment of menthol as a component of cigarettes, despite the belief among some experts that it is much ado about nothing. But if that’s the case, Benowitz and Samet suggest, why has the tobacco industry fought so ferociously to exempt menthol from the list of banned flavorings over the years? And why has the industry so consistently linked its marketing of menthol cigarettes to images of “freshness” and health? The authors estimated that “by 2020 about 17,000 more premature deaths will have occurred and two million more people will have started smoking than would have been the case if menthol cigarettes were not available.” Two million additional cigarette smokers by the end of the decade does not sound especially trivial. Nonetheless, the FDA advisory report that Benowitz helped to shape stopped short of recommending an outright ban on nicotine, saying only that removal of menthol would “benefit public health.”

While not disputing the findings of the FDA Advisory Committee, Dr. Michael Siegel of Boston University expressed dismay that “despite these conclusions, the [committee] did not recommend a ban on menthol cigarettes.” There are almost 20 million menthol smokers in the U.S., Siegel argues. If even a fraction of them quite smoking due to a ban on menthol in cigarettes, “it would have a profound effect on public health.” This is, Siegel insists, precisely why politicians managed to exempt menthol from bans on various flavor additives in the first place. The Black Congressional Caucus had “vigorously denounced the exclusion of menthol” at the time, while Lorillard, maker of Newports--the leading brand of menthol cigarettes--argued that banning menthol would result in the creation of a huge black market.  Because of all this, Seigel charges, Benowitz and the committee simply “punted the issue back to the FDA.” And if anyone harbored doubts about who benefited from this non-action, in Siegel’s view, one need only look at the fact that Lorillard’s stock enjoyed a nice run-up of about 8% after the public announcement of the FDA panel’s recommendations.

Because of all this, Siegel does not believe the FDA will ever ban menthol cigarettes. In his view, the Obama administration doesn’t need the grief of added health care complexities just now, and there is no movement in Congress to make additives an issue. And since the FDA has chosen not to demand the banning of menthol, Siegel thinks the committee’s findings will serve as a convenient smokescreen for Congress. And for the makers of menthol cigarettes, it will be business as usual. A window of opportunity on the menthol issue is now closing, says Siegel, who confesses to difficulty understanding a policy that bans “every other type of cigarette flavoring—including chocolate, strawberry, banana, pineapple, cherry, and kiwi—yet exempts the one flavoring that is actually used extensively by tobacco companies to recruit and maintain smokers… Menthol is a major contributor to smoking initiation and continued addiction, and for this reason, it will continue to enjoy the protection of a federal government that seems afraid to alienate any corporation, whether it’s part of Big Pharma, Big Insurance, or Big Tobacco.”

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

Bio Firm Working on New Technology for E-Cigarettes

Key tobacco scientist endorses “going vape.”

Cypress Bioscience of San Diego hopes to enter the controversial and potentially lucrative market for so-called e-cigarettes, which deliver nicotine by heating it to produce an inhalable, smoke-free vapor. The company announced last week that it had acquired a $5 million license for Staccato nicotine technology—“A novel electronic multidose delivery technology designed to help people stop smoking.”

The company claims that the “the electronics embedded within the Staccato delivery system could allow for the programmed, over-time reduction in the overall daily dose of nicotine, and ultimately may lead to the better management of nicotine cravings and eventual sustained smoking cessation”

Critics of e-cigarettes have maintained that the devices were not meant to curb smoking but to enable it, by allowing smokers to circumvent no-smoking regulations. Fears have also been voiced that children might be tempted to make use of them. Makers of electronic cigarettes, primarily in Asia, have maintained that the devices are perfect for the management of nicotine cravings when smokers quit, and may have significant advantages over nicotine gums and patches.

The press release from Cypress Bioscience makes the claim explicitly: “The Staccato technology may be capable of mimicking the pharmacokinetics of smoking cigarettes through the delivery of optimally-sized nicotine particles to the deep lung. Staccato nicotine may also provide some of the psychological aspects of smoking (e.g., hand-to-mouth movement, oral inhalation) and could allow smokers to self-administer and possibly titrate to the dose to treat cravings.”

Up until now, electronic cigarettes have been opposed by the Food and Drug Administration (FDA) on the grounds that e-cigarettes were novel and untested drug delivery systems. Signaling a possible change in official attitudes, Dr. Neal Benowitz, professor of Medicine at the University of California, San Francisco--and a prominent nicotine researcher for many years--said in the Cypress Bioscience press release that a delivery device like Staccato nicotine “may be useful in addressing a pressing pharmacological problem in overcoming nicotine addiction; namely, that acute cravings during quit attempts are inadequately treated by current nicotine replacement therapies.” Dr. Benowitz called the nicotine delivery device “an advancement that the field has been waiting for.”

Cypress Bioscience said it plans to take the technology into Phase 1 clinical trials next year. The company reported a net loss of 5 cents per share in the second quarter, compared to a loss of 23 cents per share during the same period a year ago.

The Centers of Disease Control and Prevention (CDC) estimate that almost 450,000 people die annually in the U.S. from smoking. One in five deaths in the U.S. are due to smoking-related illness, according to the CDC.

Earlier posts:

Leave Cigarettes Along, Judge Tells FDA

E-Cigarettes: Another Look

Graphics Credit: http://www.ecigarettebuyer.co.uk/

Marijuana Withdrawal: A Survey of Symptoms (Part 1)

By Dirk Hanson

[Originally published in The Praeger International Collection on Addictions. Ed. by Angela Browne-Miller. Westport, Connecticut: Praeger, 2009. Vol. 2 Ch. 7 pp.111-124.]

(See also Marijuana Withdrawal Post)

More than 14 million Americans smoke marijuana regularly, making it the most commonly used illicit drug in America. In 2006, marijuana was the only drug used by 52.8 percent of illegal drug users (U.S. Department of Health and Human Services, 2006).

Over the past 15 years, as addiction researchers have been busily mapping out the chemical alterations in the human nervous system caused by alcohol, cocaine, nicotine, heroin, and tranquilizers, America’s most popular illegal drug has remained largely a scientific mystery. Marijuana, the drug millions of Americans have been using regularly for years, is the least studied drug of all.

Why has cannabis research lagged behind that of other drugs of abuse? For decades, the prevailing belief among users and clinical researchers alike was that marijuana did not produce dependency and therefore could not be responsible for major withdrawal symptoms. This thinking is based, quite understandably, on the widespread observation that most marijuana users do not have difficulty going without marijuana, either by choice or by necessity. However, marijuana withdrawal effects are frequently submerged in the welter of polyaddictions common to active addicts. The withdrawal rigors of, say, alcohol or heroin tend to drown out the subtler manifestations of cannabis withdrawal. As Barbara Mason, director of the Laboratory of Clinical Psychopharmacology at Scripps Research Institute, has explained: “People are deciding every day whether to use or not to use marijuana, for medical purposes or otherwise, and there is little scientific information to advise this decision” (2008).

Marijuana withdrawal, which typically affects only heavy smokers, has not been well characterized by the research community. Until recently, there was scant evidence in animal models for marijuana tolerance and withdrawal, the classic determinants of addiction. Now, however, several researchers have identified the existence of symptoms brought on by the abrupt discontinuation of regular marijuana use in both animal and human studies (de Fonseca et al., 1997, p. 2050). A growing body of evidence supports the existence of a clinically significant marijuana withdrawal syndrome in a subset of marijuana smokers. The syndrome is marked by irritability, restlessness, generalized anxiety, hostility, depression, difficulty sleeping, excessive sweating, loose stools, loss of appetite, a general “blah” feeling, and a mental state that has been described as “inner unrest.”

Recent clinical research, combined with anecdotal field reports collected by the author, demonstrate the existence of marijuana withdrawal and the consistency of the most common symptoms of withdrawal and detoxification.

Background

In 1992, molecular biologists identified the elusive brain receptor where THC, the primary active ingredient in marijuana, did its work. Shortly after that discovery, researchers at Hebrew University in Jerusalem identified the body’s own form of THC, which uses the same CB1 receptors as THC. They christened the internally manufactured substance anandamide, after the Sanskrit ananda, or “bliss” (Fackelmann, 1993).

Anandamide has a streamlined three-dimensional structure that THC mimics. Both molecules slip easily through the blood brain barrier. Some of the mystery of marijuana’s effects was resolved after researchers demonstrated that marijuana definitely increased dopamine activity in the limbic area of the brain. Tanda, Pontieri, and Di Chiara demonstrated that dopamine levels in the nucleus accumbens doubled when rats received an infusion of THC (1997, p. 2048). It appears that marijuana raises dopamine and serotonin levels through the intermediary activation of opiate and GABA receptors (Wilson & Nicoll, 2001, p. 588). THC may perform a signaling function in neurons containing GABA and glutamate.

THC and its organic cousin, anandamide, make an impressive triple play in the brain: They effect movement through receptors in the basal ganglia, they alter sensory perception through receptors in the cerebral cortex, and they impact memory by means of receptors in the hippocampus. It is clear that some of the effects of cannabis are produced in much the same way as the effects of other addictive drugs—by means of neurotransmitter alterations along the limbic system’s reward pathway.

A great deal of the early research was marred by inconsistent findings and differing definitions of addiction and withdrawal. Most recreational marijuana users find that too much pot in one day makes them lethargic and uncomfortable. Self-proclaimed marijuana addicts, on the other hand, report that pot energizes them, calms them down when they are nervous, or otherwise allows them to function normally. Heavy marijuana users claim that tolerance does build. And when they withdraw from use, many report strong cravings.

Work by Jones, Benowitz, and Herning had helped establish certain baseline symptoms—irritability, insomnia, and lack of appetite—as early as 1981 (p. 143). Studies by Budney, Novy, and Hughes in 1999 further outlined the syndrome in heavy daily marijuana smokers (p. 1311). But the abstinence effects were often inconsistent, and frequently hard to measure. Moreover, their clinical relevance was not always evident.

For marijuana withdrawal to be considered a clinical fact, several criteria had to be met. First, the typically transient pattern of withdrawal effects must be distinguishable from rebound effects. (A rebound effect is defined as the reappearance of a preexisting symptom, and is thus not considered a true withdrawal effect.) In addition, the symptoms must occur reliably, as demonstrated by comprehensive prospective studies (Budney, Hughes, Moore, & Vandrey, 2004, p. 1970). The symptoms under consideration must also be considered clinically significant. Finally, there needs to be a clear and repeatable timeline in evidence for the withdrawal effects.

It has been suggested that the reported symptoms of abrupt marijuana cessation do not rise to the level of withdrawal typically associated with drug detox. It is now possible to lay out the neurochemical basis of marijuana withdrawal, and to demonstrate that marijuana acts on the brain in a fashion similar to other addictive drugs.

There is solid experimental evidence that chronic, heavy cannabis users develop tolerance to its subjective and cardiovascular effects. “In summary,” Budney et al. write, “cannabis withdrawal effects clearly occur in the majority of heavy, daily users” (2004, p. 1974). As a rough estimate, approximately 10 percent of marijuana users are at risk for dependence and withdrawal, the classic determinants of drug addiction (Joy, Watson, & Benson, 1999, p. 92). There is clinical and epidemiological evidence that some heavy cannabis users experience problems in controlling their cannabis use, and continue to use the drug despite experiencing adverse personal consequences of use (Hall, Solowij, & Lemon, 1999). Moreover, there is strong clinical evidence that some users experience a withdrawal syndrome upon the abrupt cessation of cannabis use. The timeline is similar to withdrawal from other addictive drugs.

In 2004, a group at the University of Vermont, funded by the National Institute of Drug Abuse (NIDA), undertook a critical review of all major relevant studies of the validity and clinical significance of marijuana withdrawal (Budney et al., p. 1967). The review of studies demonstrated with certainty that there are people with a propensity for heavy marijuana use who suffer a clearly delineated, verifiable, and frequently vivid set of withdrawal symptoms when they try to quit. One of the most striking pieces of evidence for this is the similarity of symptom sets emerging from the clinical studies to date. The most common “reliable and clinically significant” effects of abrupt withdrawal in heavy pot smokers, according to the University of Vermont research group, included “severity of craving and sleep difficulty, decreased appetite, and increased aggression, anger and irritability” (Budney, Hughes, Moore, & Novy, 2001, p. 917; Kouri, 2002, p. 30).

As another study author concluded: “Marijuana withdrawal doesn’t include dramatic physical symptoms such as the pain, nausea, heavy sweating, and cramps associated with opiate withdrawal. Nevertheless, the symptoms of marijuana withdrawal appear clinically significant” (Zickler, 2002).

A recent comprehensive outpatient study (Kouri & Pope, 2000, p. 483) with prewithdrawal baselines showed greater levels of anxiety, negative mood, physical discomfort, and decreased appetite during abstinence but not at baseline, compared with two control groups. Moreover, in a “home environment” study, researchers worked with marijuana users who provided self-ratings during marijuana withdrawal; these users smoked an average of 3.6 times daily, did not use other drugs or abuse alcohol, and were free of major psychiatric disorders. The same symptoms predominated, and onset of symptoms occurred reliably within 48 hours of cessation. Moreover, “telephone interviews with collateral observers living with the participants confirmed participants’ reports of increased irritability, aggression, and restlessness during abstinence. . . . [T]he validation of symptoms by home-based observers suggested that the effects were of a clinically significant magnitude” (Budney et al., 2004, p. 1971).

Other studies by Budney and colleagues expanded on the list of symptoms that changed significantly from baseline during withdrawal: “anger and aggression, decreased appetite, irritability, nervousness, restlessness, shakiness, sleep difficulty, stomach pain, strange dreams, sweating, and weight loss” (2003, p. 393; 2004, p. 1972). Although most effects were transient, generally lasting no more than two weeks, “strange dreams and sleep difficulties showed significant elevations throughout the study” (2003). Budney et al. conclude that, since most symptoms returned to baseline levels in the former users, “these findings were not rebound effects indicative of symptoms that existed before the use of cannabis” (2004, p. 1972).

More recent studies by Haney and others “controlled for potential confounders by using placebo conditions and excluding persons who abused other substances, had an active psychiatric disorder, or were taking psychoactive medication” ().

Overall, the research cited above confirms that the most common marijuana withdrawal symptom is low-grade anxiety and dysphoria. Anxiety of this sort has a firm biochemical substrate. A peptide known as corticotrophin-releasing factor (CRF) is primarily responsible. Neurologists at the Scripps Research Institute in La Jolla, California, found that CRF levels in the amygdalas of animals in marijuana withdrawal were as much as three times higher than the levels found in animal control groups (Wickelgren, 1997, p. 1967). Long-term marijuana use alters the function of CRF in the limbic system in a manner similar to other addictive drugs (de Fonseca et al., 1997, p. 2051). (CRF receptors in the amygdala also play a direct role in alcohol withdrawal.)

Method

Personal observations and selected case histories of frequent marijuana users were gathered from anonymous, unedited comments posted on a blog site maintained by the author. Punctuation, capitalization, and spelling have been normalized in the excerpts included here. Most of the people who have posted comments thus far (more than 100) arrived at the site by means of the search term marijuana withdrawal. This may indicate that a large number of posters are heavy smokers seeking information about abstinence symptoms. The popularity of this search phrase on the Google search engine seems to suggest an interest in, and a need for, scientific information about marijuana withdrawal.

What has surprised many observers is that the idea of treatment for marijuana dependence seems to appeal to such a large and diverse group of people. NIDA has been able to find a cohort of withdrawal-prone smokers with relative ease. According to the principal investigator of one NIDA marijuana study, “We had no difficulty recruiting dozens of people between the ages of 30 and 55 who have smoked marijuana at least 5,000 times. A simple ad in the paper generated hundreds of phone calls from such people” (NIDA, 1999). This would be roughly equivalent to 14 years of daily pot smoking.

Comments gathered from anonymous users at an open Web forum created for the discussion of marijuana withdrawal symptoms cannot be controlled for confounding variables such as other addictions or psychological disorders. The comment section of the Web site is open to anyone. What such surveys can accomplish, however, is the demonstration of parallels, or lack of them, between findings in an experimental setting and anecdotal reports from the field. Survey studies cannot offer indisputable proof. Nonetheless, when combined with the results of formal clinical studies, such surveys offer a window into real-world experience, thus complementing the growing scientific data concerning marijuana withdrawal syndrome.

The comments were generated in large part by heavy, regular smokers who either recognized or have begun to recognize in themselves an addictive propensity toward marijuana. As a group, they have great difficulty—and suffer similar symptoms—whenever, and for whatever reason, they choose to abstain.

Perhaps, most important, the present survey adds to the growing documentation of the contention that withdrawal symptoms are a frequent cause of relapse in marijuana smokers attempting to achieve abstinence.

Cont. in Part 2.

References

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Budney, A. J., Hughes, J. R., Moore, B. A., & Novy, P. L. (2001). Marijuana abstinence effects in marijuana smokers maintained in their home environment. Archives of General Psychiatry, 58(10), 917–924. Retrieved February 27, 2008, from http://archpsyc.ama assn.org/cgi/content/full/58/10/917?cknck

Budney, A. J., Hughes, J. R., Moore, B. A., & Vandrey, R. (2004, November). Review of the validity and significance of cannabis withdrawal syndrome. American Journal of Psychiatry, 161, 1967–1977. Retrieved April 21, 2008, from http://ajp.psychiatryonline.org/cgi/content/full/161/11/1967

Budney, A. J., Moore, B. A., Vandrey, R., & Hughes, J. R. (2003). The time course and significance of cannabis withdrawal. Journal of Abnormal Psychology, 112, 393–402.

Budney, A. J., Novy, P. L., & Hughes, J. R. (1999, September 1). Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction, 94, 1311–1322.

Copeland, J., Swift, W., & Rees, V. (2001, January). Clinical profile of participants in a brief intervention program for cannabis use disorder. Journal of Substance Abuse Treatment, 20(1), 45–52. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11239727

Cui, S. S., Gu, G. B., Hannesson, D. K., Yu, P. H., & Zhang, X. (2001, December 15). Prevention of cannabinoid withdrawal syndrome by lithium: Involvement of oxytocinergic neuronal activation. Journal of Neuroscience, 21(24), 9867–9876. Retrieved April 27, 2008, from http://www.jneurosci.org/cgi/content/abstract/21/24/9867

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Haney, M., Hart, C. L., Vosburg, S. K., Nasser, J., Bennetti, A., Zubaran, C., et. al. (2004). Marijuana withdrawal in humans: Effects of oral THC or divalproex. Neuropsychopharmacology, 29, 158–170.

Haney, M., Hart, C. L., Ward, A. S., & Foltin, R. W. (2003, January). Nefazodone decreases anxiety during marijuana withdrawal in humans. Psychopharmacology, 165(2), 157–165.

Haney, M., Ward, A. S., Comer, S. D., Foltin, R. W., & Fischman, M. W. (1999, February). Abstinence symptoms following smoked marijuana in humans. Psychopharmacology, 141(4), 395–404.

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Lichtman, A. H., & Martin, B. R. (2002). Marijuana withdrawal syndrome in the animal model. Journal of Clinical Pharmacology, 42, 20s–27s.

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Vandrey, R. G., Budney, A. J., Hughes, J. R., & Liguori, A. (2008, January 1). A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug and Alcohol Dependence, 92, 48–54.

Wickelgren, I. (1997, June 27). Marijuana: Harder than thought? Science, 76, 1967–1968.

Photo Credit: http://hubpages.com/

Marijuana Withdrawal Syndrome: A Bibliography

Selected science references.

The idea of marijuana addiction and withdrawal remains controversial in both private and scientific circles. For an unlucky few, a well-identified set of symptoms characterizes abstinence from heavy, daily use of pot. In this respect, marijuana addiction and withdrawal does not differ greatly from alcoholism--the vast majority of recreational users and drinkers will never experience it.

For those that do, however, the withdrawal symptoms of marijuana abstinence can severely impact their quality of life. Since discussions of this topic frequently veer off into sociopolitical arguments, leaving the science behind, I offer below a sampling of the growing medical and psychiatric literature on this aspect of drug use and abuse.

For additional comments and discussions about symptoms, see Marijuana Withdrawal.

References

Aharonovich, E., Liu, X., Samet, S., Nunes, E., Waxman, R., & Hasin, D. (2005). Postdischarge Cannabis Use and Its Relationship to Cocaine, Alcohol, and Heroin Use: A Prospective Study. American Journal of Psychiatry, 162(8), 1507-1514.

Budney, Alan J., Hughes, J.R., Moore, B.A., & Vandrey, R. (2004, November). Review of the Validity and Significance of Cannabis Withdrawal Syndrome. American Journal of Psychiatry, 161, 1967-1977.

Budney, A.J., Moore, B.A., Vandrey, R., Hughes, J.R. (2003). The time course and significance of cannabis withdrawal. Journal of Abnormal Psychology, 112, 393-402.

Budney, A.J., Hughes, J.R., Moore, B.A., & Novy, P.L. (2001). Marijuana Abstinence Effects in Marijuana Smokers Maintained in Their Home Environment. Archives of General Psychiatry, 58(10), 917-924.

Budney A. J., Novy P. L., & Hughes, J. R. (1999, September 1). Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction, 94, 1311-1322.

Copeland, J., Swift, W., & Rees, V. (2001 January). Clinical profile of participants in a brief intervention program for cannabis use disorder. Journal of Substance Abuse Treatment, 20(1), 45-52.

Cui, S.S., Gu, G.B., Hannesson, D.K., Yu, P.H., & Zhang, X. (2001, December 15). Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. Journal of Neuroscience, 21(24), 9867-9876.

de Fonseca, F.R., Rocío, M., Carrera, A., Navarro, M., Koob, G.F., & Weiss, F. (1997, June 27). Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal. Science, 276, 2050 - 2054.

Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. (2006). Results from the 2006 National Survey on Drug Use and Health: National Findings. Rockville, MD: Office of Applied Studies. Retrieved March 12, 2008, from http://www.oas.samhsa.gov/NSDUH/2k6NSDUH/2k6results.cfm#Ch2

Fackelmann, K.A. (1993, February 6). Marijuana and the brain: scientists discover the brain's own THC-delta-9-tetrahydrocannabinol. Science News.

Hall, W., Solowij, N., & Lemon, J. (1999). The health and psychological consequences of cannabis use. (National Task Force on Cannabis Australia, Monograph Series No. 25). Sydney, NSW: University of New South Wales, National Drug and Alcohol Research Centre.
Haney, M., Hart, C.L., Vosburg, S.K., Nasser, J., Bennetti, A., Zubaran, C., et. al. (2004). Marijuana Withdrawal in Humans: Effects of Oral THC or Divalproex. Neuropsychopharmacology, 29, 158–170.

Haney, M., Hart, Carl L., Ward, Amie S., & Foltin, R. W. (2003, January). Nefazodone decreases anxiety during marijuana withdrawal in humans. Psychopharmacology, 165(2), 157-165.

Haney, M., Ward, A.S., Comer, S.D., Foltin, R.W., & Fischman, M.W. (1999, February). Abstinence symptoms following smoked marijuana in humans. Psychopharmacology, 141(4), 395-404.

Jones, R.T., Benowitz, N.L., & Herning, R.I. (1981, August-September). Clinical relevance of cannabis tolerance and dependence. Journal of Clinical Pharmacology, 8-9 Suppl., 143-152.

Joy, J.E., Watson, S.J.,Benson, J.A. (1999). Marijuana and Medicine: Assessing the Science Base. p.92. Institute of Medicine, Division of Neuroscience and Behavioral Health. Washington. D.C.: National Academy Press. Retrieved March 5, 2008, from

Kouri, E.M., & Pope, H.G., Jr. (2000, November). Abstinence symptoms during withdrawal from chronic marijuana use. Experimental and Clinical Psychopharmacology, 8(4), 483-492.

Kouri, E.M. (2002, February 1). Does Marijuana Withdrawal Syndrome Exist? Psychiatric Times, 19(2).

Lichtman, A.H., and Martin, B.R. (2002). Marijuana Withdrawal Syndrome in the Animal Model. Journal of Clinical Pharmacology, 42, 20s-27s.

National Institute on Drug Abuse. (1999, April 20). Chronic Marijuana Users Become Aggressive During Withdrawal. NIDA News Release. Rockville, MD: National Institutes of Health, National Institute on Drug Abuse.

Schuckit, M.A., Daeppen, J-B., Danko, G.P., Tripp, M.L., Li, T-K., Hesselbrock, V.M., et. al. (1999). Clinical implications for four drugs of the DSM-IV distinction between substance dependence with and without a physiological component. American Journal of Psychiatry, 156, 41-49.

Scripps given $4M grant to study effects of marijuana. (2008, March 15). North County Times.

Somers, T. (2008, March 14). Study aims to clear haze surrounding pot addiction. San Diego Union-Tribune.

Tanda, G., Pontieri, F.E., & Di Chiara, G. (1997, June 27). Cannabinoid and Heroin Activation of Mesolimbic Dopamine Transmission by a Common µ1 Opioid Receptor Mechanism. Science, 276, 2048 - 2050.

Vandrey, R.G., Budney, A.J., Hughes, J.R., & A. Liguori. (2008, January 1). A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug and Alcohol Dependence, 92, 48-54.

Wickelgren, I. (1997, June 27). Marijuana: Harder Than Thought? Science, 76, 1967-1968.

Wilson, R.I. & Nicoll, R.A. (2001, March 29). Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature, 410, 588-592.

Zickler, P. (2002, October 17). Study Demonstrates That Marijuana Smokers Experience Significant Withdrawal. NIDA Notes, 17(3). Bethesda, MD: National Institutes of Health, National Institute on Drug Abuse.

The Tobacco Industry as Disease Vector

A review of The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition

Part II

The famous Surgeon General’s Report of 1964, officially warning Americans about the dangers of smoking, and publicizing the cancer connection, is typically seen as a triumphal moment in American medical history. But according to Stanford history professor Robert Proctor in his book, The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition, the report was “flawed in a number of interesting respects.” [The author, above, with paraphernalia] For one thing, members of the advisory committee consulting on the report, many of them congressman friendly to the tobacco cause, succeeded in their attempts to have smoking referred to as a “habit” rather than as addiction—a shameful Orwellian turn that went uncorrected for 25 years.

Meanwhile, the industry continued to fund new institutes, and continued to give out research grants for “red herring” research. As an example, the highest-ranking officer of the American Heart Association received money from one of the industry’s fraudulent research arms.

As late as the early 80s, most smokers believed they suffered from a bad habit, rather than an addiction—even though a majority of them wished they didn’t smoke. That is an odd kind of consumer “choice.” Cigarette makers have spent millions to perpetuate this myth. Proctor views tobacco industry executives and lawyers as a unique form of disease vector, spreading the pernicious health consequences of smoking across the globe.

The 2008 World Health Organization (WHO) Report on the Global Tobacco Epidemic fleshes out this metaphor, suggesting that all epidemics have a means of contagion, “a vector that spreads disease and death. For the tobacco epidemic, the vector is not a virus, bacterium or other microorganisms—it is an industry and its business strategy.”

In an email exchange, I asked Professor Proctor to expand on this notion of a disease vector:

“We tend to divide "communicable" from "non-communicable" diseases,” Proctor told me, “when the reality is that many "non-communicable" diseases are in fact spread by communications.”

Examples? “Through ignorance and propaganda, for example, which can spread like a virus,” Proctor wrote. “We don't count the anthropogenic communications, oddly enough, even though these can be just as dangerous, and just as deadly. And just as preventable--by changing our exposure environments.”

In a recent article for Tobacco Control, Proctor laid out how the calculus of the disease vector plays out. We know, for example, that smoking will cause roughly 6 million deaths in 2015. And about a third of those will be from lung cancer. We know that 25 acres of tobacco plants will result in about 10 lung cancer deaths per year, starting 20 or 30 years down the road. Here’s a sick equivalence: “A 40 ft container of the sort shipped overseas or trucked by highway houses 10 million cigarettes, which means that each container will cause about 10 deaths.” Proctor works out the numbers for the value of a human life:

“Cigarette companies make about a penny in profit for every cigarette sold, or about $10,000 for every million cigarettes purchased. Since there is one death for every million cigarettes sold (or smoked), a tobacco manufacturer will make about $10,000 for every death caused by their products…. The value of a human life to a cigarette manufacturer is therefore about $10,000.” 

Proctor has even produced a “factories of death” chart, illustrating that arguably the world’s most lethal production plant is Philip Morris’s Richmond cigarette facility, which churned out 146 billion cigarettes in 2010, which adds up to about 146,000 deaths per year.

By 1964, researchers at Harvard had already identified the presence of radioactivity in the form of polonium 210 in cigarette smoke, and the cry went up for safety. As for the notion of safer cigarettes, Proctor says all cigarette filters function the same way—“basically like drinking through a somewhat thinner straw.” He goes even further, arguing that “filters have reduced smoke particle size, producing cancers deeper in the lungs, making them harder to identify and harder to treat.” (Scientists determined that the radiation source was the newer “superphosphate” fertilizers being used heavily on tobacco plants.)

 Next came mandated “tar and nicotine numbers,” which turned out to be misleading measures obtained from smoking robots. Then, “an opportunity presented itself to game the system, as we find in the brilliant trick of ventilation.” Manufacturers pricked tiny holes in the paper near the mouthpiece of cigarettes brands like Carlton and True, which consumers got around by covering the holes with fingers or with “lipping” behavior. “Low tars were a fraud, just as “lights” would be,” Proctor writes. Smokers just smoked harder, or differently, or more frequently. In 1983, pharmacologist Neal Benowitz at UCSF broke the official news in the New England Journal of Medicine: Smokers got just as much nicotine, whether they smoked high-, low-, filtered, unfiltered, regular, light, or ultra-light.  The industry itself had known this for more than 20 years. “Nicotine in the actual rod was rarely allowed to drop below about 10 milligrams per cigarette,” Proctor asserts, “and no cigarette was ever commercially successful with much less than this amount.” (A Philip Morris psychologist compared nicotine-free cigarettes to “sex without orgasm.”)

Indeed, almost every design modification put in place by tobacco companies over the past century, from flue-curing to filters, has served to make cigarettes deadlier than before. “Talk of ‘safer cigarettes’ is rather like talking about safer terrorism, or safer smallpox, or safer forms of drowning,” Proctor concludes.

And the industry testing continues. The point of tobacco-sponsored research is not simply to discredit an individual researcher’s work, but to create an aggregate bias in the pattern of research—a lot of “noise” in the signal. In other words, “you basically fund lots of research to dispute a hazard, then cite this same research to say that lots of scholars dispute it.” We are told about “mucociliary escalators,” which dredge the tar up and out of smokers’ lungs. We learn that “a rabbit will scream if nicotine is introduced into the eye.” We read excerpts from anguished letters to tobacco companies: “Do you suppose if I continue to smoke Camel Ultra Light Cigarettes and I should develop cancer it will be ‘Ultra Light Cancer?’”

Proctor brings us up to date: Harm reduction, he writes, has become the industry’s new mantra. “The companies now want us to believe that less hazardous products can be and are being made and marketed.” Proctor thinks harm reduction “may end up causing even greater harm” if products touted as “safer” make smokers less likely to quit. As for public health campaigns, “consumers are encouraged to stop consuming,” Proctor writes, “but producers are never discouraged from producing.” Or, as Louis Pasteur once wrote: “When meditating over a disease, I never think of finding a remedy for it, but, instead, a means of preventing it.”

So, what comes next? A glimpse of the future may already be here, in the form of cinnamon- and mint-flavored Camel Orbs, “which look like Tic Tac candy and contain about a milligram of nicotine in a highly freebased form.”

As for the industry’s success in corrupting scientists and academics through various means, the story is just as bad as you think it is: “It would take many thousands of pages to chronicle the full extent of Big Tobacco’s penetration of academia; the scale of such collaborations is simply too vast. From 1995 to 2007 alone, University of California researchers received at least 108 awards totaling $37 million from tobacco manufacturers….”

Part II of III.

Photo Credit: http://theloungeisback.wordpress.com/

Are E-Cigarettes a Good Idea or a Bad Idea?

A group of nicotine researchers argue for an alternative.

Electronic cigarettes are here to stay. If you're not familiar with them, e-cigarettes are designed to look exactly like conventional cigarettes, but they use batteries to convert liquid nicotine into a fine, heated mist that is absorbed by the lungs. Last summer, even though the FDA insisted on referring to e-cigarettes as “untested drug delivery systems,” Dr. Neal Benowitz of the University of California in San Francisco--a prominent nicotine researcher for many years--called e-cigarettes “an advancement that the field has been waiting for.” And recently, Dr. Michael Siegel of the Boston University School of Public Health wrote: “Few, if any, chemicals at levels detected in electronic cigarettes raise serious health concerns.” Furthermore, Dr. Siegel took a swipe at the opposition: “The FDA and major anti-smoking groups keep saying that we don’t know anything about what is in electronic cigarettes. The truth is, we know a lot more about what is in electronic cigarettes than regular cigarettes.”

Harm reduction advocates are ecstatic. But do e-cigarettes simply reduce harm by eliminating combustion by-products--or do they perpetuate nicotine addiction, frustrate the efforts of smoking cessation experts, and give false hope to smokers that they can have their cake and eat it, too?

Dr. Siegel conducted a survey of e-cigarette users and found that 66% reported a reduction in the number of cigarettes smoked at the six-month point. “Of respondents who were not smoking at 6 months, 34.3% were not using e-cigarettes or any nicotine-containing products at the time.” Pretty impressive--although Siegel himself refers to the findings as “suggestive, not definitive”--and seemingly a giant leap forward for harm reduction.

However, even though they have dramatically altered the harm reduction landscape, e-cigarettes will not change anything for smokers who are attempting to completely quit using nicotine. When they inhale their last e-cigarette mist, several hours later they will begin to suffer the same withdrawal pains as regular cigarette smokers: “Irritability, craving, depression, anxiety, cognitive and attention deficits, sleep disturbances, and increased appetite,” as NIDA summarizes it. Current smokers are keenly interested in the new products, partly because of health concerns, and partly, it seems safe to venture, because a new generation of nicotine-based products like e-cigarettes “will enable them to put off the need to quit smoking,” as Dr. Dorothy Hatsukami, director of the Tobacco Use Research Center at the University of Minnesota, has asserted.

Harm reduction advocates for the electronic cigarette often make it sound like once the smoker is only inhaling nicotine, his or her problems are solved. But nicotine, of course, is the addictive part. Nicotinic receptors are present in moderate to high density in the brain areas containing dopamine cell bodies--the ventral tegmental area and the nucleus accumbens—the same pattern as almost every other addictive drug.

Even that part wouldn’t be a problem if addiction to nicotine were utterly benign. But it isn’t--although you wouldn’t know it from the pro-electronic cigarette propaganda. Nicotine in the blood is correlated with increases in arterial vasoconstriction, and is strongly suspected of playing a role in arteriosclerosis and other cardiovascular diseases. Nicotine increases LDL cholesterol, causes brochoconstriction, and has been implicated in the origin of lung tumors. There are also strong suggestions of links between nicotine and low birth weights in newborns.

So, it’s important not to kid ourselves about the hazards of nicotine, even though it may also be a medicine under certain conditions, like many other addictive drugs. Nicotine, you may recall, found industrial use as a farm crop insecticide. A poison, in other words. Nonetheless, what nicotine is NOT linked to certainly matters as well. Nicotine does not cause chronic obstructive pulmonary diseases, like emphysema—a huge plus. Nicotine won’t worsen asthma, as cigarettes do. And in the form of the electronic cigarette, it won’t cause secondhand smoke—another major plus for the e-cig.

There is another approach to regulating the harm caused by cigarettes. A group of scientists has been calling for a major effort at reducing the amount of nicotine in cigarettes so that, over time, a non-addictive level of nicotine would be reached--and cigarettes would no longer be addictive. Study after study has shown that if such were the case, about 80 to 90% of smokers would quit. And teens who experimented with truly low-nicotine cigarettes wouldn’t get hooked—unlike the “light” cigarette scandal, where the supposedly safer cigarettes may actually have turned out to be more dangerous because they forced smokers to smoke more in order to get the desired effect. Dr. Hatsukami and five other prominent nicotine experts contend that extremely low-nicotine cigarettes do not cause smokers to smoke more, “because it is harder to compensate for very low nicotine intake,” according to Hatsukami. Especially if there are no high-nicotine alternatives for sale—legally, at least. Mitch Zeller, who along with Hatsukami, co-chairs the National Cancer Institute’s Tobacco Harm Reduction Network, painted this picture: “Imagine a world where the only cigarettes that kids could experiment with would neither create nor sustain addiction."

Nonsense, counters Dr. Gilbert Ross of the American Council on Science and Health. “Asserting that smokers won’t smoke more cigarettes to get the nicotine they crave is a fairy tale,” he said. “The likely result is a major increase in cigarette-related diseases.”

These are the competing visions of our nicotine-addicted future. In one scenario, smokers stay addicted to nicotine, with its accompanying heath risks and all the other negative aspects of being addicted. But the immediate harm to their health is lessened due to fewer inhaled carcinogens, and they don’t create secondhand smoke. In the opposing scenario, smokers continue to smoke, and society continues to deal with secondhand smoke through no-smoking policies, while medical research agencies, under government mandate, oversee the gradual reduction of nicotine in cigarettes to a level below what is needed for addiction.

The optimistic thought here is that either of these approaches would bring much-needed improvement to the semi-controlled anarchy and hypocrisy of the current situation.

Photo Credit: http://whyquit.com 

The Year in Drugs

Top Posts at Addiction Inbox.

By the look of it, readers had marijuana on their minds in 2012. Of the posts at Addiction Inbox with the highest number of page views, an overwhelming majority are concerned with marijuana, and specifically, with marijuana addiction, withdrawal, and brain chemistry. Of the 9 most heavily trafficked posts of the year, only one involved alcohol. Readers were also interested in the safety of e-cigarettes, and the mysteries of neurotransmitters like serotonin and dopamine. Happily, all the top posts were patently science-oriented articles.

See you in the New Year.

•  Marijuana Withdrawal

For Some Users, Cannabis Can Be Fiercely Addictive.

For a minority of marijuana users, commonly estimated at 10 per cent, the use of pot can become uncontrollable, as with any other addictive drug. Addiction to marijuana is frequently submerged in the welter of polyaddictions common to active addicts. The withdrawal rigors of, say, alcohol or heroin tend to drown out the subtler, more psychological manifestations of cannabis withdrawal.

•  Serotonin and Dopamine: A Primer

The Molecules of Reward

Serotonin and dopamine are part of a group of compounds called biogenic amines. In addition to serotonin and dopamine, the amines include noradrenaline, acetylcholine, and histamine. This class of chemical messengers is produced, in turn, from basic amino acids like tyrosine, tryptophan, and choline.

•  Marijuana Fact and Fiction

Why cannabis research is a good idea.

There is little doubt among responsible researchers that marijuana--although it is addictive for some people--is sometimes a clinically useful drug. However, there is little incentive for commercial pharmaceutical houses to pursue research on the cannabis plant itself, since they cannot patent it.

• Anandamide: The Brain’s Own Marijuana

Anxiety and the THC receptor.

Several years ago, molecular biologists identified the elusive brain receptor where THC, the active ingredient in marijuana, did its work. Shortly after that discovery, researchers at Hebrew University in Jerusalem identified the body’s own form of THC, which sticks to the same receptors, in pulverized pig brains.

•  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 ResearchBlogging.orgsome 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.

•  Are E-Cigarettes a Good Idea or a Bad Idea?

A group of nicotine researchers argue for an alternative.

Electronic cigarettes are here to stay. If you're not familiar with them, e-cigarettes are designed to look exactly like conventional cigarettes, but they use batteries to convert liquid nicotine into a fine, heated mist that is absorbed by the lungs. Last summer, even though the FDA insisted on referring to e-cigarettes as “untested drug delivery systems,” Dr. Neal Benowitz of the University of California in San Francisco--a prominent nicotine researcher for many years--called e-cigarettes “an advancement that the field has been waiting for.”

•  Cannabis Receptors and the “Runner’s High”

Maybe it isn't endorphins after all.

A perennial favorite, the runner’s high post shows what long-distance running and marijuana smoking have in common. Quite possibly, more than you’d think. A growing body of research suggests that the runner’s high and the cannabis high are more similar than previously imagined….Endocannabinoids—the body’s internal cannabis—“seem to contribute to the motivational aspects of voluntary running in rodents.” Knockout mice lacking the cannabinioid CB1 receptor, it turns out, spend less time wheel running than normal mice. 

• Topamax for Alcoholism: A Closer Look

Epilepsy drug gains ground, draws fire as newest anti-craving pill.

A drug for seizure disorders and migraines continues to show promise as an anti-craving drug for alcoholism, the third leading cause of death in America, the Journal of the American Medical Association (JAMA) reported in its current issue.

•  Is Marijuana Addictive?

The argument continues.

Marijuana may not be a life-threatening drug, but is it an addictive one?
There is little evidence in animal models for tolerance and withdrawal, the classic determinants of addiction. For at least four decades, million of Americans have used marijuana without clear evidence of a withdrawal syndrome. Most recreational marijuana users find that too much pot in one day makes them lethargic and uncomfortable. Self-proclaimed marijuana addicts, on the other hand, report that pot energizes them, calms them down when they are nervous, or otherwise allows them to function normally.


Graphics Credit:  http://1.bp.blogspot.com (Creative Commons)

Low-Nicotine Cigarettes: Deadlier Than Regular Brands?

More tars, more cancer.

Now that the U.S. Congress has passed legislation enabling the Food and Drug Administration (FDA) to monitor the tobacco industry for the first time in history (see my earlier post), one of the primary issues the agency must deal with are health claims on behalf of allegedly less-toxic brands of “low-nicotine” cigarettes.

It has long been understood, and demonstrated clinically, that people addicted to nicotine will smoke “light” cigarettes harder, and in greater numbers, in order to compensate and obtain the same amount of nicotine they are used to--thereby staving off withdrawal. [See graphic at right for the secret of why light cigarette smokers must puff harder.]

As prominent tobacco researcher N.L. Benowitz wrote in a National Cancer Institute (NCI) monograph:

“In brief review—when faced with lower yield cigarettes, smokers can smoke more cigarettes per day, can take more and deeper puffs, can puff with a faster draw rate, and/or can block ventilation holes. Using these last four techniques, a smoker can increase his or her smoke intake from a particular cigarette several fold above the machine-predicted yields.”

In the description of a patent for a low-tar and low-nicotine technique in 1995, Duke University Researchers wrote:

“Unfortunately, it has been discovered that only a small proportion of the total smoking population (e.g., less than 25%) has substituted low tar cigarettes (e.g., cigarettes that deliver less than 10 milligrams of tar) for conventional and more hazardous cigarettes. Also of note, only about 2.0-3.0% of total cigarette sales are accounted for by very low tar cigarettes (e.g., cigarettes that deliver less than 3 milligrams of tar). Moreover, even among the cigarette smokers who have substituted low tar cigarettes for conventional cigarettes, it has been discovered that these individuals will tend to smoke low tar cigarettes more intensively in order to extract more tar and nicotine than the nominal values listed on the pack. This, of course, defeats part of the objective of the low tar cigarettes.”|

Moreover, there has never been any significant body of evidence to suggest that switching to lights or ultra-lights in a way actually contributes to the success of smoking cessation efforts. According to the National Cancer Institute, there are no health benefits for smokers of light cigarettes, period.

In a letter published in the August 21 issue of Science, Marshall E. Deutsch argues that cigarettes with reduced nicotine may in fact “increase tobacco related death and disease” and are therefore potentially more dangerous than regular smokes.

Deutsch’s argument is that by smoking more cigarettes with lower concentration of nicotine, smokers “will be subjected to more of the ‘tars’ (the cancer-causing ingredients of the smoke) in their attempts to get their usual dosage of nicotine, (the ingredient responsible for heart disease and stroke). In the end, smokers of low-nicotine cigarettes will remain at the same risk for heart disease and stroke but increase their chances of developing cancer.”

It’s never too late to quit, and the earlier the better: The National Cancer Institute tells us that smokers who quite before age 50 cut their risk of dying by 50 % over the next 15 years, compared to those who keep smoking.

Graphics Credit: www.tobaccoinaustralia.org.au

addiction drugs smoking nicotine

Alcohol: The Genetic Puzzle (3 of 3)

What about other drugs?

Do the same genetic relationships demonstrated in the alcohol adoption studies prove true for other drugs? Was it conceivable that heroin addiction or cigarette smoking could be traits (disorders, really) that men and women inherited?

“There have been a number of animal studies showing genetic differences in sensitivity to nicotine,” said Dr. Neal Benowitz of the Clinical Pharmacology Unit at San Francisco General Hospital, one of the nation’s premier nicotine research centers. And Professor Ovide Pomerleau, the Director of Behavioral Medicine at the University of Michigan Medical School, who collaborated with Cloninger’s group on genetic studies of nicotine and alcohol, told me: “Some people are drawn to smoking, and some people are not. Everybody pretty much goes through the same kind of peer pressures, the same kind of socialization pressures, and then you have some people who emerge as smokers, and some people who don’t. Some people who start smoking give it up easily, and there are others who can’t. Well, why? My answer is that I think there are innate differences in susceptibility.” 

The Cadoret group looked into the question and reported in the Archives of General Psychiatry that alcohol problems in biological relatives appeared to correlate highly with drug abuse in siblings. “Some theorists have suggested that multiple addictions to a wide variety of substances constitute evidence against a genetic interpretation of addiction,” wrote Cadoret. “The present data appear to refute that position, suggesting instead some underlying biochemical foundation involved in all of the substances abused….” 

Dr. Janice Keller Phelps, the drug treatment specialist from Seattle, maintained that “a large number of addicted people I have treated over the years had strong family histories of addiction. Time and again I encountered heroin addicts, cocaine addicts, or speed addicts with one or both parents addicted to alcohol, for example, or with one or more brothers or sisters also addicted—though not necessarily to the same drug. It is known and acknowledged that many alcoholics have one or more alcoholic parents; the large number of children of alcoholics who are not alcoholic but instead are addicted to other substances, however, is not so well recognized.”

In many ways, the genetic findings by Goodwin, Cloninger, and others were as far from the old problems-in-living approach, the Freudian approach, as it was possible to get. As Dr. Edward Sellers, who directed the psychopharmacological research program at the University of Toronto’s Addiction Research Foundation during the 1990s, explained to me: “One simplified way of looking at it is that every cell, every hormone, every membrane in the body has got genetic underpinnings, and while many of the genetic underpinnings are similar in people, in fact there are also huge differences. So on one level, the fact that there is a genetic component to addiction is not very surprising. What is surprising is that you could ever have it show up in a dominant enough way to be something that might be useful in anticipating risk.”

If there existed a set of genes that predisposed people to alcoholism, and possibly other addictions, then these genes had to control the expression of something specific. That’s what genes did. 

However, addiction researchers could not even agree on the matter of where they should be looking for such physical evidence of genetic difference. In the brain? Among the digestive enzymes? Blood platelets? A gene, or a set of genes, coding for…what? Substance H? Production of certain neurotransmitters? What was it they were supposed to be looking for?

What set of genes coded for happiness?

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008.

Graphics Credit: http://www.drugabuse.gov