Tag: Monitoring the Future

04/30/19

Not the End of Smoking

© Tatiana Chekryzhova | 1234rf.com

America’s teens reported a striking increase in their vaping in the previous 12 months, from 27.8 % in 2017 to 37.3% in 2018. Reported vaping in the 30 days prior to the survey almost doubled among high school seniors, going from 11% in 2017 to 20.9% in 2018. Nora Volkow, the director of the National Institute on Drug Abuse (NIDA), said: “Teens are clearly attracted to the marketable technology and flavorings seen in vaping devices; however, it is urgent that teens understand the possible effects of vaping on overall health; the development of the teen brain; and the potential for addiction.” She went on to say research shows that teens who vape may be at risk of transitioning to smoking cigarettes.

The increase in vaping rates for 2017-2018 was consistent with the findings of the National Youth Tobacco Survey, which said e-cigarettes were the most commonly used tobacco product among U.S. middle school and high school students. The most selected reason for e-cigarette use was they were available in flavors like mint, candy, fruit or chocolate. The lead author for the Monitoring the Future study, which annually surveys 12th, 10th and 8th grade students, said in a letter to The New England Medical Journal the increases in the prevalence of vaping nicotine translated into roughly 1.3 million additional adolescents vaping.

Put in historical context, the absolute increases in the prevalence of nicotine vaping among 12th-graders and 10th-graders are the largest ever recorded by Monitoring the Future in the 44 years that it has continuously tracked dozens of substances. These results indicate that the policies in place as of the 2017–2018 school year were not sufficient to stop the spread of nicotine vaping among adolescents. The rapid entry of new vaping devices on the market, the latest example of which is the Juul, will require continual updates and modification of strategies to keep adolescents from vaping and its associated negative health effects.

Scott Gottlieb, the former commissioner of the FDA, who had been active in efforts to thwart this trend, sent 1,300 warning letters over the summer of 2018 to online and brick-and-mortar stores for selling e-cigarette products to underage consumers. He also sent out warning letters to five manufacturers, asking them to address the popularity of their products with underage consumers or risk the removal of “some or all of their flavored products.”  In the letter sent to Juul Labs, the FDA requested that within 60 days, “you provide a written response to this letter that includes a detailed plan, including specific timeframes, to address and mitigate widespread use by minors.” Giving suggestions for that plan, the letter said Juul Labs could:

  • Discontinue sales to retail establishments that have been subject to an FDA civil monetary penalty for sale of tobacco products to minors within the prior 12 months;
  • Develop or strengthen any internal program you have to check on retailers, and report to FDA the name and address of retailers that have sold products to minors;
  • Eliminate online sales, whether through Internet storefronts controlled by your company or other retailers, or provide evidence to demonstrate that your company’s online sales practices do not contribute to youth use of JUUL products;
  • Revise your current marketing practices to help prevent use by minors;
  • Remove flavored products from the market until those products can be reviewed by FDA.

Then unexpectedly, in the middle of his crusade against teen vaping, Scott Gottlieb resigned as the commissioner of the FDA, effective April of 2019. His stated intention was to spend more time with his wife and three daughters. He said: “There’s perhaps nothing that could pull me away from this role other than the challenge of being apart from my family for these past two years and missing my wife and three young children.” Gottlieb said the policies he initiated will move forward as planned, including the proposed restrictions recently announced on the sale of flavored e-cigarette products. The New York Times said retailers were on Capitol Hill lobbying against the FDA proposals. “Conservative groups and vaping trade associations also have come out in opposition, saying that the agency’s efforts to regulate the e-cigarette industry amount to government overreach.” Yet some public health advocates think the action steps were too late.

A December 2018 investigation reported in JAMA Network Open sought to estimate the concentration of tobacco-related toxins among e-cigarette users. Findings suggested that exclusive e-cigarette use resulted in measurable exposure to tobacco-related toxicants, generally at lower levels than with cigarette smoking. Dual users had higher concentrations of exposure to nearly all biomarkers when compared with cigarette-only smokers. “Several biomarkers measured in this study are metabolites of known carcinogens as well as respiratory, cardiovascular and/or reproductive/developmental toxicants.” The data clearly showed e-cigarette users were exposed to known tobacco-related toxicants.

Another study presented at the American College of Cardiology’s 68ith Annual Scientific Session shoed that adults using e-cigarettes are significantly more likely to have a heart attack, coronary disease and depression when compared to nonusers. The study’s lead author said: “Until now, little has been known about cardiovascular events relative to e-cigarette use. These data are a real wake-up call and should prompt more action and awareness about the dangers of e-cigarettes.”

This study found that compared with nonusers, e-cigarette users were 56 percent more likely to have a heart attack and 30 percent more likely to suffer a stroke. Coronary artery disease and circulatory problems, including blood clots, were also much higher among those who vape — 10 percent and 44 percent higher, respectively. This group was also twice as likely to suffer from depression, anxiety and other emotional problems.

Scott Gottlieb said that if the 2019 National Youth Tobacco Survey shows another spike in teen use of e-cigarettes, “We’re going to be back making new policy in the fall.” One of those possible changes could be taking all pod-based e-cigarettes off the market. “At some point, the youth use of those products becomes so intolerable that they have no redeeming public health value, and we’ll just have to sweep the market of those products. And that includes Juul. Those are the products being abused by the children.”

In a statement released on Wednesday, March 13, 2019, Juul Labs said they are committed to reducing youth usage of their products, while preserving their opportunity to “eliminate combustible cigarettes.” They noted how in November of 2018 they stopped the sale of flavored Juul pods to retail stores, strengthened their retail compliance and secret shopper program, enhanced their online age-verification and exited their Facebook and Instagram accounts.

We support category-wide action including the responsible, restricted sale of flavored products and will review today’s draft guidance as we continue to work with FDA, state Attorneys General, local municipalities, and community organizations as a transparent and responsible partner in combating underage use.

So, what is the bottom line on the risks of e-cigarettes for teens? The CDC has a page of “Quick Facts on the Risks of E-Cigarettes.” It said the use of e-cigarettes in not safe for teens and young adults. They contain nicotine, which is highly addictive “and can harm the adolescent brain development.” Young people who use e-cigarettes may also be more likely to smoke cigarettes in the future, which points to the motive underlying Gottlieb’s crusade.

Finally, what about Juul Labs desire to use its e-cigarette to eliminate combustible cigarettes? One of the strongest arguments for vaping is that it can help people taper off from their addiction to tobacco smoking. A group of researchers sought to generate evidence on the ‘real world’ use of e-cigarettes on the quit rates of adult smokers. They recruited 1284 current, established smokers and then re-contacted them after a year. Although 16% had stopped smoking, they found no evidence that electronic nicotine delivery systems (or ENDS) were helping adults quit “at a higher rate than smokers who did not use these products, despite ENDS users being more likely to make a quit attempt.” In other words, they did not put an END to smoking.

Our study suggests that use of current ENDS products in real world conditions do not seem to improve the chances of quitting for smokers, and, under the current landscape, may not be the disruptive technology that increases the population quit rate and reduces the harm of combustibles. Additional steps may be needed to spur innovation to create low-harm and low-risk products that adequately deliver nicotine, address the misperceptions of relative harm of ENDS compared to cigarettes, and encourage cessation and complete switching from combustibles to low-harm and low-risk products among smokers who do not want to quit smoking.

Changes to their design, to how e-cigarettes are marketed and regulated may be too slow and ineffectual to lead to the above changes on their own, according to the lead author of the ‘real world’ study published in PLoS One. But for now, it seems e-cigarettes are more likely to become an add-on to smokers than an effective tool to stop smoking. “People who use both tobacco and e-cigarettes are actually less likely to quit smoking than people who only stick to tobacco.”

02/23/18

Priming Young Adults with Vaping

© Oleg Gavrilov | 123rf.com

The National Institute of Health announced that recent national survey research discovered that almost 1 in 3 (27.8%) 12th graders reported some kind of use of a vaping device in the past year, while the use of hookahs and regular cigarettes is declining. When asked what they thought was in the mist they inhaled, 51.8% said it was just flavoring, 32.8% said the mist contained nicotine, and 11.1% said they were smoking marijuana or hash oil. Nora Volkow, the director of NIDA, said: “We are especially concerned because the survey shows that some of the teens using these devices are first-time nicotine users.” Recent research suggests some of them could move on to regular cigarette smoking … or other drugs. And some additional research suggests many teens don’t actually know what is in the device they are using.

Monitoring the Future (MTF) is a yearly survey of 8th, 10th and 12th graders in school nationwide. The MTF survey is done by the Institute for Social Research at the University of Michigan for NIDA, the National Institute on Drug Abuse. When the survey asked about vaping over the past month, 11% of 12th graders reported vaping nicotine and 4.9% reported vaping marijuana. See the following chart from the NIH news release.

According to the CDC, e-cigarettes are now the most commonly used form of tobacco by youth in the U.S. Dual use, using both regular cigarettes and e-cigarettes, is also common among young adults 18-25. The reasons reported by young people for trying e-cigarettes include curiosity, taste and the belief they are less harmful than other tobacco products. Over 80% of teens and young adults who use e-cigarettes said they use flavored e-cigarettes.

Back in June of 2016 the FDA finalized a rule that extended its regulatory authority to all tobacco products, including e-cigarettes, cigars, hookahs and pipe tobacco. The rule requires health warnings and bans free samples. It also restricts youth access to newly regulated tobacco products by not allowing their sale to those younger than 18 and requiring a photo ID. Manufacturers will have up to two years to continue selling their products while they submit a new tobacco product application (and an additional year while the FDA reviews the application).

The rule will help prevent young people from starting to use these products, help consumers better understand the risks of using these products, prohibit false and misleading product claims, and prevent new tobacco products from being marketed unless a manufacturer demonstrates that the products meet the relevant public health standard.

If the new technology in e-cigarettes helps reduce toxicity compared to conventional cigarettes, encourages current smokers to switch completely and/or are not widely used by youth, they potentially could reduce disease and death. “But if any product prompts young people to become addicted to nicotine, reduces a person’s interest in quitting cigarettes, and/or leads to long-term usage with other tobacco products, the public health impact could be negative.” The FDA encouraged manufacturers to explore product innovations that would maximize potential benefits and minimize risks. The revised rule allows the FDA to further evaluate the impact of these products on the health of both users and non-users.

Psychiatric Times reported e-cigarettes were first developed and commercialized in China in 2003. They entered the US market in 2006. During their first ten years on the market, before the FDA ruling discussed above, advertising and sales of e-cigarettes increased exponentially every year. “While tobacco advertising has been banned from television and radio since 1970, e-cigarettes are promoted widely on these media channels, on the web, and in social media, with many ads reaching youth.” Mislabeling has been a problem with some products labeled as nicotine-free containing nicotine and others having higher concentrations of nicotine than labeled.

The evidence for e-cigarettes as a cessation aid to quit regular cigarette smoking is limited. Dual use of regular cigarettes and e-cigarettes is common. One study reported half of current smokers report regular use of e-cigarettes. A meta-analysis of twenty controlled studies found the odds of quitting cigarettes was 28% lower in individuals who used e-cigarettes. However only 2 randomized controlled trials have been done, and: “The quality of evidence was judged to be low grade, and in both trials, e-cigarettes with nicotine were no different in efficacy for quitting smoking than placebo (nicotine-free) e-cigarettes.”

So at this point in time, the evidence does not support the use of e-cigarettes as an aid to stop smoking regular cigarettes. It should be noted that the American Heart Association’s policy statement of e-cigarettes does not recommend their use. However, if a patient has tried and failed other cessation methods or is unwilling to try them, the AHA does recommend trying e-cigarettes for smoking cessation.

There is evidence that smoking e-cigarettes increases the risk of cardio vascular problems. Swedish researchers, in Antoniewicz et al., demonstrated that in healthy volunteers, ten puffs from an e-cigarette caused an increase in endotheial progenitor cells (EPSs) of the same magnitude as smoking one traditional cigarette. The average e-cigarette user takes 230 puffs per day, raising the prospect that prolonged use could result in serious health consequences. “These findings suggest that a very short exposure to ECV [e-cigarette vapor] caused a rapid EPC mobilization in blood, which may indicate an impact on vascular integrity leading to future atherosclerosis [hardening of the arteries].” A heart specialist for the European Society of Cardiology was quoted in the Daily Mail as saying: “It really surprises me that so little vapour from an e-cigarette is needed to start the heart disease ball rolling. It’s worrying that one e-cigarette can trigger such a response.”

Researchers at the University of Connecticut found evidence that e-cigarettes containing a nicotine-based liquid are potentially as harmful as unfiltered cigarettes in causing DNA damage. The study’s lead author said the results surprised him. “I never expected the DNA damage from e-cigarettes to be equal to tobacco cigarettes.” He was shocked the first time he saw the result, so he diluted the samples and ran the controls again. “But the trend was still there – something in the e-cigarettes was definitely causing damage to the DNA.”

Researchers at the University of North Carolina found that not only do e-cigarettes trigger the same immune responses as regular cigarettes, they also trigger some unique reactions. E-cigarette users uniquely showed significant increases with neutrophil-extracellular-trap (NET)-related proteins in their airways. “Left unchecked neutrophils can contribute to inflammatory lung diseases, such as COPD and cystic fibrosis.” The study also found that e-cigarettes produced negative consequences known to occur in regular cigarettes such as an increase of biomarkers of oxidative stress and activation of defense mechanisms associated with lung disease. They also found an over secretion of mucus secretions that have been associated with diseases like chronic bronchitis, bronchiectasis and asthma.

Another study by Eric and Denise Kandel, “A Molecular Basis for Nicotine as a Gateway Drug” has raised concerns with e-cigarettes as “pure nicotine-delivery devices.” Their study demonstrated that nicotine acted like a gateway drug for cocaine on the brain of mice, “and this effect is likely to occur whether the exposure is from smoking tobacco, passive tobacco smoke, or e-cigarettes.”

These results provide a biologic basis and a molecular mechanism for the sequence of drug use observed in people. One drug affects the circuitry of the brain in a manner that potentiates the effects of a subsequent drug.Although the typical e-cigarette user has been described as a long-term smoker who is unable to stop smoking, the use of e-cigarettes is increasing exponentially among adolescents and young adults. Our society needs to be concerned about the effect of e-cigarettes on the brain, especially in young people, and the potential for creating a new generation of persons addicted to nicotine. The effects we found in adult mice are likely to be even stronger in adolescent animals. Priming with nicotine has been shown to lead to enhanced cocaine-induced locomotor activity and increased initial self-administration of cocaine among adolescent, but not adult, rats. Whether e-cigarettes will prove to be a gateway to the use of combustible cigarettes and illicit drugs is uncertain, but it is clearly a possibility.

Don’t be too quick to dismiss the Kandels’ nicotine-gateway theory. They were doing basic research on the effects of nicotine on specific areas of the brain. Priming with nicotine enhanced the effects of cocaine in the nucleus accumbens. “Priming with nicotine appeared to increase the rewarding properties of cocaine by further disinhibiting dopaminergic neurons in the ventral tegmental area.” They only observed the priming effect of nicotine when mice were given cocaine at the same time as nicotine. For more on Denise Kandel’s gateway hypothesis see: “Rebirth of the Gateway Hypothesis.”

03/25/16

A “God Moment” with DXM

© iofoto | 123rf.com
© iofoto | 123rf.com

One of the most coincidental encounters I’ve ever had in my experiences working with addicts and alcoholics involved someone intending to get high on DXM. One day when I was on my lunch break, I went to a local supermarket to get some hot food from their deli counter. When I was about fifty feet from the automatic doors, one of the individuals I knew from the treatment program exited the store and immediately made a left when he saw me. I called out a hello, which he answered as he just kept walking, saying he had just bought something to eat. Normally a friendly person, his behavior was unusual.

I wondered what could be going on as I went into the store. Then for some reason, I had the thought to go check the isle with the over-the-counter cold medications. The section was completely empty of cough suppressant capsules containing DXM, dextromethorphan. After I bought my lunch, I walked in the direction I has seen him hotfoot it away from me earlier and now saw him coming out of a sandwich shop. Hmm, I thought, he must be really hungry today.

I told him what I had found in the grocery store and then reminded him he had told me he bought something to eat there. Now he had some thing else from the sandwich shop. I also showed him a plastic bag with the grocery store’s logo that contained empty boxes of DXM cough suppressant. I told him that it had been on the top of a garbage can just outside the sandwich shop. He said he bought a drink in the grocery store before buying his sandwich and denied any knowledge of the empty DXM shelves in the grocery store. Of course he didn’t know how the empty DXM packets got there either. Then he left to meet the person giving him a ride home.

Back at the outpatient office, as I was telling the other staff members the above story, he walked in admitted that he had bought the DXM capsules. He said he hadn’t taken any and after I confronted him, he threw his baggy of capsules away. We talked of how close he had come to a lapse into active drug use and I encouraged him to not waste this pretty amazing intervention. We both agreed it seemed to be a “God moment” that put me in front of the store just as he was coming out. The last I heard, he was abstinent; but it took a few more tries at treatment before he got it.

Dextromethorphan (DXM) is a synthetic substance found in about 70 over-the-counter products mainly as a cough suppressant and expectorant. Other medical uses include the other symptoms from hayfever, colds, allergies and the flu: the temporary relief of sinus congestion, runny nose, cough, sneezing, itching of the nose and throat, and watery eyes. DXM was approved by the FDA in 1958 as a cough suppressant. As early as 1962, it was being used recreationally. Ironically it had been substituted for codeine in cough suppressant medications to cut down on abuse. When it became a popular recreational drug with “young heads,” DXM was temporarily removed from the OTC market in 1973.

By 1977 pharmaceutical companies reintroduced DXM cough syrup with an unpleasant taste when used in the large quantities necessary for a high. Within a short time those same manufacturers began to produce forms of DXM syrup with an “appealing flavoring.” Used as prescribed, DXM products do not lead to the altered states sought after by those who abuse it. Doses approximate 30 mg of DXM every four to six hours. A single recreational dose can range from 240 to 1500 mg. “Heavier users have been known to ingest up to 3 or 4 bottles a day.”

In high doses, DXM is a dissociative anesthetic with powerful psychedelic effects. Sometimes it is compared to PCP and ketamine, two other dissociative anesthetics. High dose DXM can lead to toxic psychosis and a host of other physiological and behavioral problems. See the link above and Medline Plus for further information and treatment for DXM overdose.

Dose dependent effects can vary from a mild stimulant effect with distorted visual perceptions to a sense of complete dissociation from your body. A bad DXM experience described on the pro-drug website Erowid said: “My DXM experience was even scarier than my shrooming experience when I thought that I’d lost my face and that I would never return from being completely and utterly confused.”

DXM abuse is largely done by teens looking for a cheap, accessible high. The guy I described above was in his early 20s. Katie McBride, writing for The Fix, described how one teenage boy named Nic had two nearly fatal DXM overdoses in “The Dangers of DXM.” She related information on the SAMHSA website from 2006 that reported an estimated 1 million people between the ages of 12 and 25 had abused OTC cough and cold medication in the previous year. I was not able to find more recent data on DXM or abuse of OTC cough and cold medication. Although there has been data gathered on nonprescription cold and cough medications, since 2006 it was not included in the annual National Surveys on Drug Use and Health (NSDUH).

Beginning in 2006 Monitoring the Future, an ongoing study of the behaviors, attitudes and values of American high school students, began tracking the use of DXM among 8th, 10th, and 12th grade students. Respondents were asked how often they used cough or cold medications to get high in the past year. All the surveyed grade levels reported decreased use from 2006 to 2014. The percentages in 2006 who had used DXM were as follows: 8th graders: 4.2%; 10th graders: 5.3%; 12th graders: 6.9%. By 2014, the percentages were: 8th graders: 2.0%; 10th graders: 3.7%; 12th graders: 4.1%.

The DXM Abuse Prevention Act of 2015 (H.R. 3250) has been introduced to amend the Federal Food, Drug and Cosmetic Act. H.R. 3250 would restrict the sale of DXM products to individuals under the age of 18, except with a valid prescription. Retailers would have to verify that they are not selling DXM to individuals under 18. It would also create a series of penalties for retailers violating the sales restrictions to under aged individuals. The FDA Law Blog reported:

In determining civil penalty amounts for violations, the bill would require consideration of whether the retailer “has taken appropriate steps to prevent subsequent violations,” including establishing a documented training program for all employees who sell dextromethorphan. The bill has received strong support by a number of anti-drug abuse, healthcare and industry organizations including the Consumer Healthcare Products Association, Drug Abuse Resistance Education (“D.A.R.E.”) and Partnership for Drug-Free Kids.”

According to the Monitoring the Future data, DXM use among teenagers has been decreasing. But we should keep in mind that 2% to 4.1% of high school students using DXM in the past year to get high is still a significant number. I’m not sure that H.R. 3250 will ever get out of committee and become law, but it has some good ideas, like restricting the sale of DXM products to individuals over 18, unless they have a prescription. The restrictions on pseudophedrine seem to work in keeping it out of the hands of wanna-be Walter Whites. Something similar should work with DXM products as well.