Update from CDC on vape-related lung injury: No single cause yet

The CDC has posted a MMWR report on the 2019 spate of serious lung injuries reported as a consequence of vaping. The first culprit to hit the news was vitamin E, it turns out this is not a unique factor after all.

Schier and colleagues report: No consistent e-cigarette product, substance, or additive has been identified in all cases, nor has any one product or substance been conclusively linked to pulmonary disease in patients. … authors identified lipids within alveolar macrophages from the three bronchoalveolar lavage (BAL) specimens stained with oil red O. All five patients reported using marijuana oils or concentrates in e-cigarettes, and three also reported using nicotine (3). In a report describing the clinical course and outcomes of six patients from Utah, health care providers described the potential diagnostic utility of identification of lipid-laden macrophages from BAL specimens (4). Among the 53 cases from Illinois and Wisconsin, however, the pathologic findings were heterogeneous. Whereas almost half (24/53) of these patients underwent BAL, seven reports described the use of oil red O stain that identified lipid-laden macrophages

Perrine and colleagues report: Among 514 patients with information on substances used in e-cigarettes, or vaping products, in the 3 months* preceding symptom onset, 76.9% reported using THC-containing products, and 56.8% reported using nicotine-containing products; 36.0% reported exclusive use of THC-containing products, and 16.0% reported exclusive use of nicotine-containing products. *erratum for the original which says “30 days”.

It’s frustrating that the takeaway message so far is that nobody knows if there even is a unique cause or set of causes for the recent spate of lung injuries. We certainly don’t know the cause. We probably don’t even know if the injuries *are* recently occurring or have always been a consequence of vape device use that simply wasn’t connected to the e-cigarette device use. We know how long it took to recognize that cannabis was causing a hyperemesis syndrome, after all.

My suspicion at the start was that it wasn’t anything to do with cannabinoids, specifically. This reported diversity would appear to confirm that. It always seemed more likely to me that if there was a unique cause that appeared to be associated with cannabis vape cartridges that this is a classic case of a third variable. Perhaps a new vehicle constituent or an extraction method that was being used only, or primarily, with cannabis vape preparation. Well, clearly even that is not the case since there seem to be some nicotine-only users who have experienced lung injury.

Keep your eye on PubMed for updates on this health crisis.

Schier JG, Meiman JG, Layden J, et al. Severe Pulmonary Disease Associated with Electronic-Cigarette–Product Use — Interim Guidance. MMWR Morb Mortal Wkly Rep 2019;68:787–790. DOI: http://dx.doi.org/10.15585/mmwr.mm6836e2external icon

Perrine CG, Pickens CM, Boehmer TK, et al. Characteristics of a Multistate Outbreak of Lung Injury Associated with E-cigarette Use, or Vaping — United States, 2019. MMWR Morb Mortal Wkly Rep 2019;68:860–864. DOI: http://dx.doi.org/10.15585/mmwr.mm6839e1

Erratum: Vol. 68, No. 39. MMWR Morb Mortal Wkly Rep 2019;68:900. DOI: http://dx.doi.org/10.15585/mmwr.mm6840a5

Vaping: Known Unknowns

Unless you have been hiding under a rock, you know about e-cigarettes. These are devices which deliver a nicotine dose using a battery-heated element which vaporizes propylene glycol, polyethylene glycol, vegetable glycerin (mostly) and/or some other vehicles in which the nicotine has been dissolved.

These devices appeal to users as cessation aids to help quit smoking tobacco and as a safer alternative to cigarettes.

They also appeal to adolescents, apparently.

You will hear the occasional grand pronouncement hit the media circusit with more assertions than questions leaving people wondering.

Here is my general take on just about anything having to do with e-cigarettes: We don’t really know and we need to do some more science to figure it out.

So here are the key questions all amenable to research, some of which is no doubt ongoing.

Do e-cigs help people quit smoking? The question is, in my view, do they do any better than cold turkey (accounting for subpopulations) and are they as effective or better than any other replacement therapy like the gum or patch.

Do e-cigs prolong nicotine use in individuals who would otherwise have quit smoking cigarettes? Very tricky question, this one. But if you have an individual who would have quit smoking but keeps using nicotine via e-cig, you’ve increased harm.

Do e-cigs cause novel harms? In other words, presumably the nicotine harm is the same (once individuals learn how to get their desired nicotine dose from these). But are there constituents of the vehicles, the flavorants or products created by the vaporization process that cause health risks? And no, just showing an ingredient is present is not evidence of harm. We need careful toxicology studies with relevant exposure doses and regimens.

Do e-cigs prevent well-established harms? The chronic smoking of tobacco, typically via the modern cigarette products, has very well established and very bad health consequences. Nicotine exposure is the cause of only a subset of the harms, even if it is the thing responsible for continued use. So getting combusted tobacco smoke exposure out of the situation cannot help but be a huge win. Huge. I don’t see how this can really be argued until and unless we find some whopping big harms of the vapor exposure.

Do e-cigs addict new individuals to nicotine? One of the big fears of those concerned with e-cigs is that early data show that adolescents are more likely to try e-cigs than to try smoking cigarettes. There will be some work showing that daily nicotine users started off with e-cigs rather than tobacco cigarettes but as you know, it is impossible to establish causality with real human populations. The best we have, overwhelmingly likely causal relationships, has to wait on a whole lot of data. Which we won’t have for many years.

Bonus Round:
Are e-cigs used without nicotine or other psychoactive? One parent I know has asserted that perhaps some adolescents are using e-cig devices with just the flavored vehicles and not to ingest nicotine or any other drug. Obviously this goes back to the above question about harms from the vehicle. But it also links to another concern…

Are e-cigs used to deliver other psychoactive drugs? The devices are very readily and broadly available. They are being used with crude marijuana extracts for certain sure. There have been media allegations that they are being used to ingest “flakka” (here, here, here). For a time, one assumes that by pretending to be smoking nicotine or the flavorant (see above) peope will be able to stroll about ingesting illegal substances in public view. Including adolescents, my friends. Yes, kids.

ASPET 2014: Vaccinating against the effects of nicotine

This platform presentation was in symposium 166. New Preclinical and Clinical Perspectives for Smoking Cessation on Sun, Apr 27, 3:00 – 5:30 PM at the 2014 Experimental Biology meeting.

R. I. Desai (University website, PubMed) presented new results from a study of a vaccine designed to attenuate the effects of nicotine.

I previously discussed the principles involved in anti-cocaine vaccination, and NIDA has generated this handy video explainer on the basic principle of vaccination against drugs of abuse

Desai noted at the outset that there have been four anti-nicotine vaccines developed by drug companies with some of them advancing to Phase II or even Phase III trials. As he remarked, they have all been viewed as failures. Nevertheless it is the case that some of the failures have been due to insufficient antibody titer having been produced in a relatively large proportion of the subjects. Thus, it may be that the principle is still sound but that the vaccines need to be improved in terms of generating more consistent, high antibody titers.

This study used the SEL-068 nano particle vaccine described here in abstract form. Although Desai did not hammer home the point in his presentation, one presumes that this new nanoparticle vaccine is hypothesized to generate higher antibody levels in animals.

This particular study used the drug discrimination procedure (see here for description) to evaluate the interoceptive stimulus or subjective properties of nicotine in squirrel monkeys. The animals were trained to discriminate nicotine from saline pretreatment with a stimulus-termination procedure; one lever was correct when nicotine had been administered and the other lever was correct when saline had been administered. Control animals learned the discrimination well within 30 sessions and some evidence of learning could be observed as early as 3-4 sessions of training.

The control animals received vaccination only after the nicotine/saline discrimination had been learned. The training drug was changed to epibatidine ( a nicotine acetylcholine receptor agonist, i.e., similar to nicotine in pharmacological action) during the vaccination to avoid complicating interpretation of the discrimination behavior. After a few weeks of the vaccination treatment, discrimination for epibatidine was high, however the animals were now unable to discriminate the original training dose of nicotine. A follow-up nicotine dose-substitution challenge showed that only a minor rightward shift of the dose-response function had been produced. A slightly higher dose of nicotine engendered over 80% responding on the lever associated with epibatidine (and previously nicotine).

The effect of vaccination could be overcome by slight increases in the dose, at least in animals previously experienced with nicotine.

Interestingly, the animals that were vaccinated prior to the start of any discrimination training did not learn the nicotine discrimination. Over about 30 training sessions, there was no selective responding on the nicotine paired lever when nicotine had been administered. This indicates that the subjective feeling of the training dose of nicotine had been attenuated to the point where it wasn’t reliably different from vehicle exposure.

The research team then went on to train the vaccinated group to discriminate epibatidine from saline. In this case, the discrimination was established with about the same time course as was seen for nicotine in the non-vaccinated group. It is structurally different, thus antibodies specific to nicotine that were generated by the vaccine would not be expected to recognize epibatidine. This part of the study shows that the vaccinated animals would still be able to form a discriminative set based on the activity of receptors through which a major part of nicotine’s action is conferred.

One of the most interesting outcomes of this study was that the learning of a discrimination based on nicotine could be blocked by vaccination. This tends to suggest that the most effective clinical target will be to vaccinate children before they have any experience with nicotine.

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also see Would you vaccinate against drug abuse?

Regulatory Science at NIH

One of the more fascinating things I attended at the recent meeting of the College on Problems of Drug Dependence was a Workshop on “Novel Tobacco and Nicotine Products and Regulatory Science”, chaired by Dorothy Hatsukami and Stacey Sigmon. The focus on tobacco is of interest, of course, but what was really fascinating for my audience was the “Regulatory Science” part.

As background the Family Smoking Prevention and Tobacco Control Act became law on June 22, 2009 (sidebar, um…four years later and..ahhh. sigh.) This Act gave “the Food and Drug Administration (FDA) the authority to regulate the manufacture, distribution, and marketing of tobacco products to protect public health.”

As the Discussant, David Shurtleff (up until recently Acting Deputy Director at NIDA and now Deputy Director at NCCAM), noted this is the first foray for the NIH into “Regulatory Science”. I.e., the usual suspect ICs of the NIH will be overseeing conduct of scientific projects designed directly to inform regulation. I repeat, SCIENCE conducted EXPLICITLY to inform regulation! This is great. [R01 RFA; R21 RFA]

Don’t get me wrong, regulatory science has existed in the past. The FDA has whole research installments of its very own to do toxicity testing of various kinds. And we on the investigator-initiated side of the world interact with such folks. I certainly do. But this brings all of us together, brings all of the diverse expert laboratory talents together on a common problem. Getting the best people involved doing the most specific study has to be for the better.

In terms of specifics of tobacco control, there were many on this topic that you would find interesting. The Act doesn’t permit the actual banning of all tobacco products and it doesn’t permit reducing the nicotine in cigarettes to zero. However, it can address questions of nicotine content, the inclusion of adulterants (say menthol flavor) to tobacco and what comes out of a cigarette (Monoamine Oxidase Inhibiting compounds that increase the nicotine effect, minor constituents, etc). It can do something about a proliferation of nicotine-containing consumer products which range from explicit smoking replacements to alleged dietary supplements.

Replacing cigarette smoking with some sort of nicotine inhaler would be a net plus, right? Well…..unless it lured in more consumers or maintained dependence in those who might otherwise have quit. Nicotine “dietary supplements” that function as agonist therapy are coolio….again, unless they perpetuate and expand cigarette use. Or nicotine exposure…while the drug itself is a boatload less harmful than is the smoking of cigarettes it is not benign.

There are already some grants funded for this purpose.

NIH administers several and there was a suggestion that this is new money coming into the NIH from the FDA. Also a comment that this was non-appropriated money, it was being taken from some tobacco-tax fund. So don’t think of this as competing with the rest of us for funding.

I was enthused. One of the younger guns of my fields of interest has received a LARGE mechanism to captain. The rest of the people who seem to be involved are excellent. The science is going to be very solid.

I really, really (REALLY) like this expansion of the notion that we need to back regulatory policy with good data. And that we are willing as a society to pay to get it. Sure, in this case we all know that it is because the forces *opposing* regulation are very powerful and well funded. And so it will take a LOT of data to overcome their objections. Nevertheless, it sets a good tone. We should have good reason for every regulatory act even if the opposition is nonexistent or powerless.

That brings me to cannabis.

I’m really hoping to see some efforts along these lines [hint, hmmmm] to address both the medical marijuana and the recreational marijuana policy moves that are under experimentation by the States. In the past some US States have used state cigarette tax money (or settlement money) to fund research, so this doesn’t have to be at the Federal level. Looking at you, Colorado and Washington.

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As always, see Disclaimer. I’m an interested party in this stuff as I could very easily see myself competing for “regulation science” money on certain relevant topics.

The NIDA/NIAAA merger, NCI, smoking and extramural PIs who are losing their natural minds

It is officially time to get a grip.
Over at writedit’s voluminous comment thread discussing NIH scores and paylines I ran across this gem:

rumor has it that NCI is limiting funding of new projects there, to prevent losing Institute dollars when that part of the portfolio moves to the new addiction institute

So if you’ve been following along, the NIH is planning to disband NIDA and NIAAA and launch a new Institute on Substance Abuse / Substance Use Disorders. Name is yet to be determined.
Also yet to be determined is the portfolio of such a new institute. It did not escape the attention of the sharp-eyed that there are substantial amounts of addictive-disorders related funding being handled by the NCI, a comparatively much larger Institute. So the present state of affairs appears to be an effort to take an accounting of various existing grant portfolios that are related to substance use and therefore might be best placed in the new Institute for all addiction-related science. This taskforce/working group accounting and proposing effort appears to be the latest kicking-the-ball-down-the-road strategy* for Francis Collins, Director of the NIH.

DrugFacts 2010 Repost: Comparing Cannabis and Nicotine Withdrawal

This is Drug Facts Week, an effort of NIDA to promote understanding of the effects of recreational drugs. I have a little bit of interest in such things. Unfortunately, I’ve been a bit busy and will continue to be so this week. So I thought I would get at least partially in the game with a series of re-posts. This post originally went up at Scienceblogs.com on April 29, 2008.

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For some reason many people are in denial about cannabis dependence and wish to assert that there is no such thing, or if there is, it is somehow of lesser importance than is dependence on other substances of abuse. There are many ways to assess importance of course. What gets me going, however, are the assertions about cannabis abuse and dependence that are informed by anecdote and personal experience with a handful of users instead of an understanding of the available evidence.
To provide a little context for todays’ post, I took MarkH of denialism blog to task for his expression of what I viewed as standard cannabis science denialism a fair while ago. In a comment following his post, MarkH specifically identified nicotine withdrawal as being worse than cannabis withdrawal. This is the perfect setup since there are two recent papers which set out explicitly to test this hypothesis. Let us see what they found, shall we?

Who smokes?

A bit of a followup to a recent post on smoking bans-my route to the infographic was a tip from DirkH of Addiction Inbox blog.

Source MyHealthNewsDaily.com, your online source for news and information about the latest medical research, health news and trends.

Tobacco smoke is bad for you…but there’s another story here

…and this is a story about political attitudes and behavior.
First, the bottom line from PalMD:

While many may cringe at the paternalistic nature of public health laws, few complain about the availability of clean water and the notable absence of open sewers.

I lived through the smoking ban enacted in bars and restaurants and I couldn’t be more delighted. Although I was never particularly bothered by the smoke, no more than most that is, I certainly noticed the lack after the bans went through. No more smelly hair and clothes. No more changing the pillowcases after a night out because the smoke smell went from hair to the pillow like clockwork.
Since I’m not a smoker there was no problem.
But oh, you should have heard the caterwauling. Personal liberty was being infringed! (Never mind the liberty of others to be free from annoyance of smoke, eh? Why do the libertarians always forget that?) Business will be AffEcTed! Bars will close. Nobody will buy alcohol anymore! Nobody will go out to dine.
Naturally this never came to pass in my region of the world. Nor did it in a myriad of other jurisdictions that passed smoking bans.
Including NYC.
And here is a tale from a bartender who was practically on the ramparts to oppose the smoking ban. Changing. His. Mind. Based on the results of the policy as he personally experienced it.

And it was at that moment, silently of course, that I grudgingly had to thank old Mayor Bloomberg. For regardless of what his motivation was and regardless of the fact that he did it with an iron fist, the son-of-a-gun when it’s all said and done was right. The good, as it all turns out, outweighs the bad. And not just because of the major things, of which we are all aware, but the minor things of which you’re about to read…

Test out a policy change, evaluate the outcome. If you are originally opposed to the policy….what do you do? Do you leave your ego at the door and really look at the data? Or do you stick to your guns no matter what the evidence?
Scribbler is a standup guy for admitting he was wrong. May we all be able to do the same when public policies have results that are demonstrably better than our initial preferences.

Does one drug cause the user to be more annoying?

As a bit of a followup to the poll we ran on whether or not cigarettes make you high, I offer context and my thoughts. As of this writing, btw, the votes are running 44% “Yes”, 47% “No”, the balance “other” with a fair bit of commentary to the effect that “high” is not exactly the right description for nicotine.
For the background, we might as well start with the comment from SurgPA:

This started with an email from PalMD asking why doctors react much more negatively to narcotics abusers than alcohol or nicotine abusers. I hypothesized that most people view acute use of the various drugs differently. Specifically I suspected that most doctors’ gut reactions when seeing someone light a cigarette are qualitatively (and vastly) different from seeing someone shoot heroin (or snort crushed oxycontin). In short that we don’t see the act of smoking as an acute intoxication by a neuroactive substance, even if we understand it intellectually.

A simple poll on the smoking experience

Today’s question comes from a reader and occasional commenter.

Does smoking a cigarette get you high?Market Research

I have the sneaking suspicion there will be a lot of people wanting to add caveats and modifications to these simple choices….have at it in the comments here because for some reason the polldaddy doesn’t seem to make the ‘other’ comments easily viewable.

Faces of Drug Abuse Research: Laura E. O'Dell, Ph.D.

Laura E. O’Dell, Ph.D. is Assistant Professor in the Psychology Department at the University of Texas at El Paso (CV, PubMed, O’Dell Lab, Department Profile, Research Crossroads) where she investigates the rewarding and dependence-inducing properties of nicotine using rodent models.
I chose Professor O’Dell to overview in part because she is about 4 years into her Asst Prof appointment and therefore represents the recently-transitioned scientists that are a good part of our audience and blog-focus here. I think many in the drug abuse fields would view her career at present as reflecting one of our up-and-coming and highly promising young scientists who will shape our field significantly over the next few decades of her career.

Hi-larious ciggie ads

Click on over to retrocomedy.com for this collection of cigarette ads.

Quitter!!

Are you a smoker? Thinking about quitting? Well, friend of the blog, consistent commenter and blogger DuWayne Brayton has launched a new group blog to discuss smoking cessation from the viewpoint of those trying to quit.

This is a blog for folks who have quit smoking to share their experience. It is also a blog for folks who are trying to quit or want to quit, to share their experiences. And it is a blog for folks who work in healthcare, addiction, research or other areas that deal with tobacco addiction or addictions in general, to share their knowledge and experience.