Yale Psychiatry Grand Rounds: May 14, 2021

May 14, 2021

Information

"Contemporary Issues in the Regulation of Tobacco Products"

Suchitra Krishnan-Sarin, PhD, Professor of Psychiatry, Yale School of Medicine

ID6592

To CiteDCA Citation Guide

00:00As well as those of you who
00:03were listening on just heard,
00:06we have three incredible presentations
00:08coming up in the next three weeks.
00:13Next week is the inaugural.
00:17The first of two inaugural lectures
00:20that have been endowed by an alumnus
00:24of our Department named Byram.
00:26Karasu, Doctor Karasu was a
00:29longtime chair of psychiatry
00:32at Einstein School of Medicine.
00:35And very active in in the in the American
00:40Psychiatric Association and other places an.
00:44That has endowed one lecture,
00:46the first of which will be next
00:48week in the second lecture,
00:50which we hope to hold over this summer.
00:52The first lecture is related to.
00:57Psychotherapy the humanities.
01:02And and sort of a more humanistic
01:05aspects of psychiatry and to kick
01:08off that lecture we have urban
01:10yellow who as you know is both a
01:14leading psychotherapy researcher
01:15from Stanford and also a novelist.
01:18In case any of you have read any of his
01:22novels, including when I read about it,
01:26a murder set around a psychoanalytic
01:28Institute. Fun, fun, read.
01:32Anyway, so so we will watch and
01:35edited interview conducted by David
01:37Ross of Irving Yellow next week.
01:39Then you have the opportunity to discuss
01:42it and that should be a lot of fun.
01:46Yellow is obviously one of the
01:49great leaders in psychotherapy.
01:51Of his generation in our time.
01:55The following week is the last minute
01:57word lecture and the Lustman awardee's,
01:59literally in the 10 minutes
02:01before this lecture,
02:02just received their notifications
02:03of words so they will have as much
02:06time to prepare their lecture
02:07as I will have to prepare the
02:10state of Department lecture,
02:11which is going to be the
02:13following week on June 4th and
02:15which I'm looking forward to.
02:19But today's lecture is a special a
02:23special lecture for us, and our lecture
02:28is Professor Suchitra Krishnan Sarin.
02:31She's obviously a professor in
02:34our Department and chair of one
02:37of the IRB committees at Yale.
02:39She got her bachelor's degree in India,
02:42then PhD in pharmacology at Purdue,
02:45and then she came to Yale 1994
02:48to pursue addiction research,
02:50training, and the rest.
02:52As they say, is history.
02:56You know she's really been
02:58a pioneer in so many areas.
03:01One of the most important areas
03:04where she's really had an enormous
03:06impact has been in trying to
03:09understand and develop treatments
03:11for addictions in adolescence,
03:14particularly adolescent smoking and
03:16and her development of research in that
03:19area coincided with the emergence of vaping,
03:22the so-called safe alternative to smoking,
03:25which turns out not to be.
03:29So safe and so in two large major
03:35national initiatives that that Doctor
03:40Krishnan Sarin is led with with.
03:45Stephanie O'Malley and other
03:46faculty in the Department, the.
03:51The teacher can now the transdisciplinary
03:53regulation Smoking Regulation
03:54Center for regulatory science.
03:55I knew it.
03:56It's going to need to look
03:58at it to get the name right.
04:04Sojitra has really led an important
04:07initiative to both understanding intervene
04:10in adolescent smoking and vaping,
04:12but also to understand and better inform
04:16the regulatory process and the payoff
04:20of their work and that of others has
04:23had enormous impact on public health.
04:26It's no accident, for example,
04:29that the FDA banned.
04:33Inclusion of menthol in cigarettes,
04:36which is a remarkable remarkable
04:40statement about the FDA's awareness about
04:44how various aspects besides nicotine,
04:48can drive addiction,
04:50and particularly in in
04:54vulnerable populations. Anne.
04:57Although her lecture today is
05:00not going to focus on this,
05:02she's contributed to many other areas,
05:05and in particular for me have been
05:07a really important valued can key
05:10investigator in our in IEEE supported
05:12Center for the translational
05:14neuroscience of alcoholism,
05:16where she's LED projects in the in the
05:19laboratory studying the pharmacology
05:21of Alcohol Self Administration,
05:23which is really been been
05:25fascinating and informative.
05:27So she should also leads an American
05:31Heart Association funded center in
05:33addition to as if that wasn't enough,
05:36the American Heart Association funded Center,
05:39which is developing youth focus prevention
05:42and cessation interventions for E
05:44cigarettes and tobacco use behavior,
05:46and she's really been an extremely
05:50productive investigator with
05:51over 217 research publications.
05:54As I alluded to in talking
05:57about the impact of her work,
05:59Suchitra is really been an important
06:01national leader in the area of smoking.
06:04She's been involved in several
06:06Surgeon General's reports,
06:07an adult and youth tobacco use behaviors.
06:10She served as a member of the FDA's
06:12Tobacco Product Scientific Advisory
06:14Committee on the CDC's Interagency
06:16Committee on Smoking and Health,
06:18led by the Surgeon General,
06:20and she's been involved
06:22in other organizations.
06:23A consultant to the Tobacco Free Initiative
06:25of the World Health Organization.
06:28She for 20 to 21 has been president of the
06:32Society for Research on Nicotine and Tobacco.
06:37She plays editorial roles in three journals,
06:41including including being a senior
06:44editor of Tobacco Regulatory Science,
06:46and she's also been incredibly
06:49public spirited,
06:50involved in educational initiatives,
06:53community initiatives doing
06:55doing a Ted Med Talk.
06:58A really somebody who is not just
07:01generating the research but but paying
07:04it back to in ways that that have
07:07an important effect on our community
07:09on our educational environment.
07:11In our research community.
07:13Through her role in the hics so so teacher,
07:17I want to acknowledge your very special
07:20contributions not only as an investigator,
07:22but also as a leader and and
07:25how much we appreciate that.
07:27So without further ado.
07:29Please take it away and tell us about
07:32the advances in regulatory regulation.
07:35You thank you.
07:36Thank you,
07:36John.
07:37Thank you
07:38for that very very kind and
07:40very nice invitation unblushing.
07:41In case you can see it on screen.
07:44But that was that was really very nice I've.
07:47I think one of the things I always
07:50tell people is that I enjoy every
07:53little bit of what I do and I enjoy
07:56the signs that comes with it so it
07:59makes life interesting and exciting.
08:01So let me share my screen here.
08:04And well, I'm already at the bottom sorry,
08:07I just did a run through my slides.
08:17OK can you see my slides now?
08:20Trisha yes yes alright so.
08:23So like John said,
08:24I do a lot of work in the tobacco
08:27area as well as in the alcohol area.
08:30I'm not going to talk about the
08:32alcohol area today and I really
08:34thought I would give you a flavor
08:36for what we're doing and some very
08:39contemporary issues in tobacco
08:40regulation which are coming up.
08:44You know today and over the next few
08:47months in state legislatures as well as
08:52federale legislatures for consideration.
08:55Just start out just to let you all
08:57know that I and this is always a
09:00very important issue for anybody
09:01working in the field of tobacco.
09:03To acknowledge that I do not have
09:05any tobacco industry funding and
09:07all everything I'll be talking
09:09about is funded through NIH or FDA.
09:15Scoop up, take a so the basics basic
09:18problem are why this issue of tobacco
09:21regulation become became very important,
09:24as probably many of you know is
09:27because of the cigarette epidemic.
09:29You know cigarette consumption went
09:32up significantly after the World Wars
09:35in in the US and all over the world.
09:38A commercial cigarette consumption.
09:40And as this graph clearly shows,
09:42there were a lot of regulatory.
09:46Not a lot of laws and other kinds
09:48of mechanisms that were put into
09:49place in the US to try and stem this
09:52increase in cigarette consumption.
09:53And you see,
09:54some of those listed on this slide.
09:57Now, despite all this,
09:58there are still people who smoke
10:00cigarettes and smoke quite a lot,
10:02and therefore one of the things the
10:04FDA had been trying to do for a very
10:07long time was to get the authority
10:09to actually regulate the components
10:11of the constituents of cigarettes so
10:13that they could make it safe for use.
10:16Because the tobacco industry has been
10:18known over the years to manipulate
10:20the content contents of these products
10:22to make them more addictive and get
10:24more people using these products
10:26and addicted to these products.
10:28And as you know,
10:29as we all know,
10:31cigarette consumption are cigarette.
10:32Smoking is still one of the biggest public
10:35health problems in the US and worldwide.
10:38So in 2009,
10:39President Obama signed what's
10:40called the Family Smoking
10:42Prevention and Tobacco Control Act,
10:44and this act gave the FDA the authority for
10:47the first time to regulate the manufacture,
10:50distribution and marketing
10:51of tobacco products.
10:52Now I have underlying manufacturer
10:54here because that is what was
10:57really a key feature of this act.
10:59The distribution and marketing
11:01was something that was already
11:02being controlled by various laws,
11:04but the FDA never had any control over
11:07what actually went into a cigarette,
11:09and this is since 2009 they
11:11have had that authority.
11:12That's when they got this authority.
11:14They realized that they had very little
11:16signs to support how to do this work.
11:19Like how do we regulate it?
11:21What level of nicotine is safe?
11:23What level of what pH is safe?
11:25What?
11:25How can we make the product less addictive?
11:28So on and so forth?
11:30So many questions that they had.
11:32They did not know how to do it,
11:35so they decided to come up with a
11:37comprehensive plan for how they would
11:39approach tobacco and nicotine regulation.
11:41And some of these are listed on the slide.
11:44They really wanted to have
11:46regulatory policies on addiction,
11:47appeal and sensation and assigned
11:49space review of all tobacco products
11:51and a youth tobacco prevention plan.
11:53These are the three key features
11:55of this comprehensive plan that the
11:58FDA has and from investigators.
11:59What they really want.
12:01You know, was how do we implement this?
12:04How do we go about doing this so
12:06they look for and occasionally
12:08they will come out and tell us we
12:11are looking for evidence on this
12:13or this particular
12:14issue and we as a tobacco center are
12:16will will put our efforts into creating
12:19that scientific evidence to support
12:21whatever legal course they're taking.
12:23And some of the things that they highlighted
12:25in what they were interested in,
12:28was it dramatical product,
12:29standard for nicotine levels
12:31in combustible cigarettes so?
12:32The question they had is it can be lower
12:35the levels of nicotine in cigarettes,
12:37straight minimal or non addictive
12:39level and created a product nicotine
12:41standard which would decrease the
12:43addictive potential of these products.
12:45Another issue that they were very
12:47interested in was the regulation of
12:49flavors in tobacco products and they
12:52continue to this day try to figure
12:54out how to regulate these product.
12:56So what I'm going to go through
12:58over the next few slides is tell
13:01you a little bit about.
13:03What's going on in each of these areas?
13:06And then also tell you as about E
13:09cigarettes and what the public health
13:11debate around this is and what scientific
13:14evidence we have for this product.
13:16So anyway,
13:17in order to do this,
13:19generate all the scientific
13:21evidence the FT established tobacco
13:23Center of regulatory science,
13:24and that's what you see on this slide here.
13:28These are. There are nine centers.
13:30This is actually the second iteration.
13:33In the first situation,
13:34there were 14 centers,
13:35and then nine were renewed for
13:38another five years and we were
13:40fortunate to be one of the ones
13:42that was ripped that were renewed.
13:44And this is this shows you where the
13:46nine centers are in the US as far as the
13:49year Tobacco Center of Regulatory Science,
13:52our goal is to really examine how
13:54the constituents and characteristics
13:55of tobacco products alter appeal.
13:57Addictive potential use behaviors
13:58and toxicity of these products.
14:00So really generate the science to support.
14:03If you're religious.
14:05This is a very busy slide,
14:07but this is Anna probably
14:08missing a few people here,
14:10but there are.
14:10This is everyone who's involved
14:12in our tobacco center so far,
14:14and they have all made amazing
14:16contributions to the field so far
14:18and I will be showing you some data
14:20from any of these individuals.
14:22Throughout my talk.
14:25So the first issue is that of flavors.
14:31For those of you who have
14:32smoked or use any black product,
14:35you know that flavors exist in almost
14:37every tobacco product on the market.
14:39You see here, Flavors in their
14:41flavors and in cigarettes.
14:43There are flavors in smokeless tobacco
14:45in cigars cigarillos which you see
14:48on the left hand side here and then
14:50also of course now in E cigarettes
14:52which have over 15,000 flavors.
14:54So flavors are an important
14:56component of most tobacco products,
14:58and the thought is that.
14:59Flavors in some way make the product
15:02more palatable and more easy to use,
15:05so the inclusion of flavors is
15:07not by accident or something which
15:09Michael industry purposefully
15:11introduced into products.
15:12Now flavored tobacco products
15:14are also very important,
15:16as you can see here on this is the
15:19proportion of current tobacco product
15:21users who report using flavored products,
15:24and they seem to be very important
15:26from an initiation perspective.
15:28There people were starting use of these.
15:31Products really need the flavors to help
15:34them get through the initial irritant.
15:36Effects of tobacco are that tobacco
15:39nicotine produces in your throat.
15:41They also seem to be important
15:44for continuing the diction and
15:47preventing people from quitting.
15:50Nine,
15:502009 there was a statutory ban on all
15:53flavors and cigarettes other than mental.
15:56So cigarettes only combustible cigarettes
15:58have not had flavors since 2009,
16:00but menthol is still existed
16:03in these products.
16:05There has been a lot of moves
16:07along with reports created by the
16:09safety community asking the FDA
16:10to remove mental from cigarettes.
16:13For example,
16:13the FDS tobacco product
16:15Scientific advisory committee.
16:16This was before I served on the committee.
16:18They wrote a report and recommended
16:20that removal of mental from the
16:23marketplace would benefit public health
16:25in the United States and they said
16:27this based on a lot of evidence which
16:29essentially I have tried to summarize here,
16:31which showed that the presence of menthol
16:34cigarettes and associated marketing.
16:35Increased experimentation,
16:36regular smoking,
16:37especially among youth and African Americans,
16:39that it increased addiction among
16:41young people who smoke and the to
16:44decrease the chances of smoking
16:45cessation among African Americans who smoke.
16:48Now,
16:48why am I specifically talking about
16:51African Americans?
16:51It is pretty well known that the
16:54tobacco industry has targeted different
16:56populations for a very long time and in
16:59the US there there have been very slow.
17:02It's been very specific targeting
17:04of specific populations and.
17:06Two populations that stand out
17:07our youth because they knew that
17:09they could get them hooked young.
17:11Then they would stay using their
17:12products for a much longer period of
17:15time and after the African American
17:17population there have been very
17:18specific ads like what you see here.
17:20That have been used to target
17:23this population,
17:24and if you look at the left hand side
17:26figure it shows you if you consider
17:29just menthol cigarette use it shows
17:31you menthol cigarette use among
17:33different subgroups and you can see
17:35that really the rates of use amongst
17:38Blacks is the highest in the US.
17:40This is evidence of very nice drive
17:42put together by the truth initiative,
17:44so this is a very important issue
17:46because you have the industry
17:48targeting a particular subgroup.
17:50How do we counteract this?
17:52Issue and how do we get rid of these mental
17:55cigarettes so we don't get continue to
17:58get people addicted to these products?
18:01Now our center here retail has
18:03done a lot of work to support,
18:06provide more supports the
18:08support of scientific evidence.
18:10We have really focused on trying to
18:12understand how does mentored really change
18:15or make these products easier to use.
18:18There wasn't so much evidence
18:20earlier on this.
18:21This is.
18:22Animal work generated by Spaniard
18:23and his group where they
18:25looked at tobacco cigarettes.
18:27Actually in animal models.
18:29Looking at use of tobacco cigarettes
18:31and then also use of E cigarette vapors.
18:34You're welcome to that a little bit later,
18:37but just focus on the left hand side
18:40graph what you can see here is Ben.
18:43Animals are given cigarettes that
18:45contain just regular cigarettes
18:46without menthol versus when they
18:48contain in their given cigarettes.
18:50With menthol there is a definite.
18:53Change in the amount of time that
18:55they hold their breath or breath.
18:57Holding is basically called breaking
18:59or how long the animal is the animal.
19:02Find something irritating.
19:03They hold their breath so when you when
19:06you give them just regular smoke they
19:08they hold their breath a lot longer.
19:10But then when you give them
19:12smoke that also contains mental.
19:13So this basically tells you that
19:15menthol is definitely altering
19:17the irritating properties of
19:18cigarette smoke in in animals.
19:20And then there was this very
19:22elegant study done by Christian.
19:23Old in our center where she used
19:26human experimental model to examine.
19:29If you gave people who were mental
19:31smokers and told them they could
19:34only use non ventilated cigarettes.
19:36I'm not presenting the entire
19:38design to you here,
19:40but essentially she recruited menthol
19:42smokers and gave them only non menthol.
19:45Same brand non menthol cigarettes to use.
19:48And then she examined what happened
19:51to their use behaviors and what
19:53this clearly shows is when.
19:55They are given the non menthol
19:58cigarettes their cigarette smoking
19:59actually goes down and so did
20:01their dependence scores and they
20:03also expressed interest in study
20:05more interest in quitting smoking.
20:07So this data tells you that removing
20:09mental is definitely going to have
20:11an impact on menthol smokers,
20:13in that they're probably going
20:15to decrease their smoking.
20:16They they may also have decreased
20:18independence and may want to have
20:21increased interest in quitting smoking.
20:23So this again just drives home the point,
20:25how important the inclusion of menthol is.
20:28Instagram's in fact there have
20:30been some modeling studies that
20:32have actually been done.
20:33This is not work done in RT cores but
20:36by other T course that show that the
20:39prevalence of mental cigarettes may
20:41actually have reduced the decline in
20:44cigarette problems over the years.
20:46And you see some numbers that they're
20:49citing here on the right hand side,
20:51they predict that that from 1980 to 2018,
20:54menthol cigarettes were responsible
20:56for reducing the decline in
20:58cigarette prevalence by 2.6%.
20:59And these are the number of extra smokers and
21:03lives years lost because of the continued
21:07presence of these products in the market.
21:10So based on all this evidence,
21:13a lot of countries have
21:15banned menthol already,
21:16and The Who has made a specific.
21:20Put out a statement stating that
21:23menthols should be banned by Paul.
21:25Cigarettes should be banned and
21:27the EU just banned the menthol
21:30cigarettes in just in May 2022.
21:32Now in the US the response
21:36has been much lower the.
21:39The in in in April 12,
21:412013 because there was no
21:44action in this on this issue,
21:46there was a citizen's petition that
21:49was filed asking the US FDA to stop
21:53and remove mental from cigarettes.
21:55This was put together by a lot of very
21:59prominent health organizations in the US,
22:02including the American Medical Association,
22:04American Cancer Society, and the
22:07Variety of American Heart Association.
22:09But there was no movement and
22:11based on that and June 17th,
22:132020,
22:13the FDA was sued over menthol cigarettes.
22:16This was a suit put forward by the I'm sorry.
22:19I don't mean glasses here because
22:21I have a very small screen by the
22:24American Tobacco Control Leadership
22:25Council and the action on Smoking and
22:28Health and they were joined in this
22:30by a variety of other organizations
22:32and they sued the FDA over their
22:34lack of action on menthol cigarettes.
22:36And the FDA actually had to provide
22:39a comment.
22:40Response to the suit by April 30th or
22:42April 29th, I believe of this year,
22:45which is what they did so the
22:47Biden administration as you saw,
22:49put out a statement stating that
22:51they actually plan to remove
22:52mental from cigarettes.
22:54But I'll tell you this,
22:55it's not that the story is not done here.
22:58There's more to come because they're
23:00still open to the issue of legal
23:03action by the tobacco industry.
23:04The tobacco industry can still
23:06Sue them for this action,
23:08and there's a lot of concern about.
23:10A loss of revenue at the at the local level.
23:14Mental cigarettes account for a huge
23:16amount of sales in many communities.
23:18And there's also concern about black market.
23:21And while a scientist Sweet thinks
23:23mentor should be removed from cigarettes,
23:25one example of how this is these kind
23:27of concerns are coming into place is
23:30showing up in Connecticut itself.
23:32Connecticut actually had a law they
23:34were considering that they were
23:36proposing to ban menthol cigarettes and
23:38and a lot of flavors in E cigarettes.
23:41And we just saw a different version
23:43of the law there.
23:45The menthol cigarette language
23:46is actually been put aside and I
23:49think this is based on the fact
23:51that when this was presented to
23:53the Connecticut legislature,
23:54the issue of loss of revenue was
23:57front and center and was proposed
23:59to be pretty high and that may
24:02have raised a lot of concerns,
24:04but I would still say that removing
24:06mentor from cigarettes is probably,
24:08in my view a social justice
24:10issue and it should happen.
24:12And it should happen quickly.
24:13But you know there is more
24:15to come on this issue.
24:20So I've talked a lot about
24:21many flavors and cigarettes,
24:22but what about other tobacco products, right?
24:24So the cigarettes are not the only
24:26tobacco product in the market.
24:27There are a variety of others
24:29now as far as the others,
24:30the evidence is not so clear.
24:32And why is that?
24:34There is reason to be concerned
24:36about use of other about flavors and
24:38tobacco products because this is data
24:41from a study called the Path study,
24:43which the FDA and NIH grant,
24:45which is a large student study looking at
24:48tobacco use behaviors that started in 2013,
24:50and this paper shows you that one of
24:53the meeting reasons for non cigarette
24:55trabocco product to use amongst past
24:5830 day tobacco users in youth who
25:00were 12 to 17 year olds was I used
25:02the product because they come in.
25:05Flavors and this applies across the board
25:07for all different kinds of products,
25:09ranging from E cigarettes,
25:10cigars, hookahs,
25:11so these flavors are obviously a
25:13very important issue in attracting
25:14people to to use these products.
25:16Just giving an example of E cigarettes and
25:19I'm taking a little bit of a diversion here,
25:22but just focusing on that 'cause we've
25:24done a lot of work in this area.
25:26This is the flavors in E cigarettes count.
25:29There are over 15,000 flavors and
25:31they have all these very unusual
25:33names that you see here,
25:34like.
25:35Cupcake man an appletini and if
25:37they get even worse than that,
25:39Dragon's blood and so on and so
25:41forth that really bring you to using
25:43and wanting to use these products.
25:45This is data from Bonnie how
25:46confession and her group in Stamford,
25:48who showed that you truly believe that
25:50they are being targeted using these flavors,
25:52and these flavored products.
25:54They do not believe that older adults
25:56have any use for these products
25:57and you can see that very clearly
25:59in something like the cupcake man.
26:01They really believe that flavor
26:03which is called a cupcake man,
26:05is really targeted at younger age.
26:06Populations are perhaps even their age,
26:08but definitely not older populations.
26:10So you truly believe these flavors
26:13and these products are for them.
26:15This is some of our data collected
26:19in Connecticut which shows you
26:21the different flavors.
26:23And again here, this represents.
26:25As I said this over 15,000 flavors,
26:27maybe even more if you mix
26:29and match the flavors.
26:30And there are youth really love
26:32fruit flavors and candy flavors.
26:34Very few like the tobacco flavors.
26:36They actually become even smaller
26:38over the years,
26:39and they also like mint flavors and
26:42some of the other flavors listed here.
26:45Now,
26:45the experimental work that we have
26:47done in our center with Eliquis
26:49going back to the mental issues
26:51I was saying telling you earlier,
26:53has also shown that mental and
26:55illiquid significantly improves
26:56the taste of eliquids,
26:58so if you see the left hand side
27:00figure here even very low levels
27:02of menthol significantly improve
27:03the taste of eliquids and how much
27:06people like eliquids that they're
27:08vaping. And if you look at the right
27:10hand side panel here it shows you that
27:13there is actually an interaction between.
27:15The Mental Joes and nicotine dose.
27:17So if there's a high mental concentration
27:20which is very similar to what you see in
27:23commercial mental mental atede products,
27:25people are more likely to like the
27:27taste of high nicotine concentration.
27:29So essentially this is telling us
27:31that this meant or maybe interacting
27:33with nicotine to actually increase the
27:35appeal of the palatability of eliquids.
27:38And we're showing we're actually
27:40conducting similar tests like this
27:42in with other flavors as well.
27:44In the same study also showed that
27:48mental increased some of what we
27:51would consider in our field as.
27:53Issues being more important for addiction,
27:56so it increases you know liking
27:58wanting the cigarette and it also
28:01improves craving for the cigarettes.
28:03So again,
28:04say telling us that meant only be important,
28:08not just for the initial appetitive
28:10affects but also for how much
28:13people continue to like an crave.
28:15These cigarettes and how much is
28:18related to it may have an influence
28:22on predicted potential.
28:24However,
28:24this story is not so simple because again,
28:28work from RT course has shown that
28:30flavors may also be important
28:32for small for those who smoke who
28:35are trying to quit smoking,
28:37and this is data that was examined
28:40using the path launch general data
28:43that I mentioned earlier by Doctor
28:45Friedman an she shows here that
28:48wild flavors are important for,
28:50you know,
28:51used by youth and also used by
28:53emerging adults from an initiation.
28:56Respective flavors are also important
28:58from a cessation perspective.
28:59For adults who smoke,
29:00and so the question really is the
29:03question that the public health
29:05debate that's going on now is.
29:07How do you regulate use of flavors
29:09in this product where they can
29:12still be beneficial?
29:13Potentially,
29:13if they are beneficial for people
29:15who smoke who are trying to quit
29:18smoking versus how do you regulate
29:20the flavors so you keep keep it,
29:22make it less attractive,
29:24and keep it away from.
29:26So this is these are ongoing experiments
29:28that we are conducting in our centers
29:30and many centers on the FDA is very
29:33interested in the answer to this question,
29:35which we don't have yet, by the way.
29:38So the other issue,
29:40the FDA, as I said,
29:41is interested in his nicotine.
29:43Now most of you know you've
29:45probably heard from other people
29:46in the Department about nicotine
29:48and its importance in the body.
29:50It targets a nicotinic acetylcholine
29:52system and it is the primary addictive
29:54ingredient in tobacco products.
29:55And as I like to tell people when
29:58I'm talking about nicotine and I'm
30:00sure I'm preaching to the choir,
30:02here is nicotine has a lot of
30:04effects and it affects almost
30:06every organ of the human body.
30:08Now,
30:09in an early paper by Benowitz Neal
30:11Benowitz and Jack Henningfield,
30:13they had positive that there might be
30:15a threshold for nicotine addiction,
30:17which is that they might be
30:19a low level of
30:20nicotine, which could be
30:22allowed in cigarettes,
30:23which would make the product addictive.
30:25But if you went below that threshold,
30:27product might not be so addictive,
30:29so there is a lot of
30:31ongoing work in this area.
30:33Loading In at Yale here,
30:35and this is work done by
30:37men and see for glue.
30:39There he is actually using his Ivy
30:42nicotine paradigm and has a very
30:45interesting paradigm where people
30:47administer different nicotine doses
30:50and he uses that information to
30:52determine the threshold that produces
30:55consistent nicotine reinforcement.
30:56And this recent paper from his group shows
31:00that the threshold for producing continuous,
31:03consistent nicotine reinforcement,
31:05as determined by whether
31:07people favor and nicotine.
31:09However,
31:09they favor sailing was about .2
31:11milligrams for 70 kilograms,
31:13so there is evidence emerging that there
31:15might be a threshold that could be
31:18established in some of these products,
31:21and in fact work done by others in the field.
31:24Eric, Tony,
31:25and Dorothy had to call me have
31:27done clinical trials that cigarettes
31:30that have reduced nicotine content.
31:33Let's have reduced the dose to you.
31:35See some of the different doses.
31:37I'm not showing you the different
31:39doses they tried.
31:40Sorry,
31:41they tried a whole bunch of different
31:43doses and they try to see how reducing
31:46the dose of nicotine in a cigarette all turn.
31:49Use behaviors,
31:50quit attempts,
31:51whether it changed.
31:53And other people there was any
31:55compens atory smoking and they found
31:57overall that reducing the dose.
31:592.4 milligrams per gram of tobacco
32:01actually reduced the number of
32:03cigarettes smoked by people,
32:05reduce dependence and resulted
32:06in no compens atory smoking.
32:08In fact,
32:09other groups have shown similar outcomes.
32:11With these reduced nicotine cigarettes
32:13in many vulnerable populations,
32:14including people with psychiatric
32:16conditions as well as youth
32:18and non daily smokers.
32:19So the FDA is very interested in this idea.
32:22The earlier FDA commissioner was
32:24very interested in the idea.
32:26Of moving forward with this idea of
32:29reducing nicotine concentration in
32:30tobacco and in cigarettes rather sorry.
32:32I mean be clear in cigarettes
32:34and Dorothy and Eric have also
32:37shown that the best approach,
32:38the best way to do this might be
32:41by having an immediate reduction
32:43in the level of nicotine.
32:45Instead of having one one of the
32:47things the FDA was considering,
32:49whether they should have a tapered or
32:52a gradual reduction in nicotine levels
32:54in commercially available nicotine.
32:56Levels in commercial cigarettes,
32:58but they've shown that an
33:00immediate approach might be the
33:01best way to achieve this goal,
33:03so this is something that is being
33:06considered by the FDA and they
33:08have not taken action on it yet.
33:10But it seems that they might be starting
33:12to get interested in this issue again,
33:15and so you may see more news articles or more
33:18actions being discussed about this issue.
33:21No, that does nicotine in cigarettes.
33:23Again, what about nicotine
33:24and other tobacco products?
33:26Again,
33:26here we don't have a clear.
33:28We don't have clear direction
33:30because all the work is
33:31only been done with cigarettes
33:33and cigarette as a delivery device
33:35is very different than cigar or E
33:37cigarettes as a delivery device for
33:39nicotine and this is particularly
33:41concerning because E cigarettes like
33:43the secrets that you heard about like
33:45Jewel which are on the market which
33:47are very very popular with the youth
33:49contain what is code word containing
33:51katien solves now nicotine sauce.
33:53Normally, nicotine in most cigarettes
33:55is freebase nicotine which is
33:57irritating to the throat and you
33:59know that's if any of you have smoke.
34:01That's the reason you kind of cough.
34:03Then you take your first love,
34:05but the nicotine salts,
34:06which are in many liquids like
34:08jewel and many of the newer obvious
34:10products contain assault like
34:11nicotine benzoate weight,
34:13which is what you're so shown here.
34:15Now these soles are proposed to be
34:17less harsh and they say that it makes
34:20the product a lot more palatable
34:22and a lot more easier to use.
34:24As a result, some of these products,
34:27like June,
34:28contain very high levels of nicotine.
34:30Juul goes as far as 60 milligrams
34:33of nicotine in the product itself,
34:36which is compares to almost 2
34:39packs of cigarettes,
34:40and this this shows these products are
34:43really marketed very widely and there is,
34:46as I said, you truly love them.
34:49So there is a lot of concern
34:52about what to do about.
34:54These kinds of products and there
34:56is no clear guidance and nuclear
34:58science to support this as yet,
35:00and this is a lot of the work that
35:03we're focusing on in our center.
35:05And not to confuse the issue anymore,
35:07but I just have to tell you that
35:09there is another player in the
35:11market which is synthetic nicotine.
35:13This was just introduced in
35:14the market recently and.
35:16Overall, the FDA,
35:17the family smoking tobacco prevention and
35:19Control Act that I mentioned earlier,
35:22is really directed at nicotine
35:23that comes from tobacco products,
35:25so their authority does not
35:27extend to synthetic nicotine.
35:29So it seems like some people have found
35:31out a way of creating synthetic nicotine,
35:34and now many of these products,
35:36like E cigarettes and the
35:38oral tobacco products,
35:39are using synthetic nicotine in them,
35:42and one of the questions that
35:44we have as a community.
35:46Of researchers and advocates in
35:48this area is are these even can't
35:50even be regulated by the FDA.
35:52So what I'm trying to tell you is
35:54that the industry changes and it
35:56changes depending on what laws are
35:58coming into the market and this is
36:01a battle of heavy fight on a daily
36:03basis and somebody really needs
36:05to address this issue of nicotine
36:07and other products.
36:09So that was so essentially
36:10exactly what I just said.
36:11We need a lot more scientific evidence
36:13to support both flavor and nicotine
36:15regulation issues in tobacco products.
36:17Now I'm going to move on to telling
36:20you a little bit about E cigarettes.
36:23Most of you have seen these products,
36:24I'm sure on the market,
36:25but I'm not sure if you know
36:27the history behind these.
36:28So I thought I would just tell you a
36:30little bit about why we are where we are.
36:33These products were created
36:34with a very good intention.
36:36They were created by Chinese Spanish.
36:38This pharmacist in 2003.
36:39He wanted to be able to provide those
36:42who smoke with a cleaner form of
36:44nicotine to help them quit smoking,
36:47which is a very Noble intention.
36:49The device purses are very
36:50simple devices shown here.
36:52It has a power source.
36:53It has a control button.
36:55There is a there is an illiquid
36:57or a juice which is in a container
37:00and you ignite or heat up the
37:03juice using the power source.
37:05And then it creates a vapor and you,
37:07the individual,
37:08can inhale the vapor through
37:10the mouthpiece that you see on
37:12the extreme right here today.
37:14There are over 400 E cigarette
37:16brands and many,
37:17many different kinds of devices
37:19on the market.
37:20This market has basically developed
37:22unregulated and that is the
37:24unfortunate part of the story when
37:26they first came on into the US,
37:28the US,
37:28the FTA,
37:29wanted to reject the entry of
37:31these devices and classify them
37:33as a drug delivery device because.
37:35That's essentially what they are.
37:37They deliver a drug that can
37:39be used to deliver anything.
37:41But this company called Smoking Everywhere
37:43or later changed their name to enjoy,
37:45had a lawsuit against the FDA,
37:47and they said that these
37:49electronic cigarettes are not
37:51drugs or drug delivery systems.
37:52They're tobacco products.
37:53According to the Family Smoking
37:55Tobacco Prevention and Control Act,
37:57and in December 2010,
37:58the US Court of Appeals ruled
38:00that the FDA can only regulate E
38:02cigarettes as a tobacco product
38:04unless therapeutic claims are made.
38:06This is very important,
38:08so if you look at an E cigarette.
38:11Now that you'll see they never
38:13make any therapeutic claims is
38:14they make a therapeutic claim.
38:16They have to go down the pathway in FDA
38:19that many of us are very familiar with,
38:21but they cannot do that and
38:23therefore they can only be
38:25regulated as a tobacco product.
38:27And yet they are being used by millions
38:29of people who smoke to quit smoking.
38:31So it's it's it's.
38:33It's really an interesting situation.
38:34So what this means is that E
38:36cigarettes were not covered.
38:38I said this for our tobacco product
38:40because there not a drug delivery.
38:42Got it but the family smoking provide
38:45prevent tobacco prevention and Control Act.
38:47Did not cover E cigarettes to 2016.
38:49Therefore,
38:49from 2010 to 2016 they were basically
38:52unregulated and they continue to
38:54stay unregulated because the FDA
38:55is now what the FDA did is they
38:58asked all these companies to submit
39:00applications to them called PMT?
39:01Is that they could review to see what
39:04the constituents of the products were,
39:06what they contained and they had.
39:08They wanted all these applications
39:10submitted to them by September 9th,
39:112020 which was just last year and.
39:14What I understand they have millions
39:16of applications, so I think they will
39:18probably remain unregulated through 2022.
39:19Now this does not mean that there aren't
39:22rules about marketing and sales to you.
39:24Then all those all those law still continue,
39:26but the actual regulation of the product
39:28informing people about what's in them
39:30and whether they are safe or not.
39:32That's something that is not going to happen.
39:34May not happen for a while.
39:36In the meantime,
39:37this is a great market is just exploded.
39:39These are some of the kinds of E
39:42cigarettes you find on the market.
39:44They started out with these
39:45very cigarette like products.
39:46Moved on to things called vape pens,
39:49which basically had the E liquid in
39:51a tank like I showed you earlier.
39:53You have these box mods which are
39:56very very used a lot by people who
39:58use it in for recreational purposes
40:00like producing vape clouds,
40:02and you know participating in
40:03competitions and things like that.
40:05You can really do a good job
40:07adjusting the voltage and the device.
40:09The temperature of the device,
40:11what you put in the device so you
40:14know there are a lot of things
40:16that you can change.
40:18And then there are these newer
40:19devices called Pod devices,
40:21and these are the ones like the
40:23jewel that you see here and then on
40:25the right hand side at the bottom.
40:27Here you see these newest newest
40:29products called Puff Bars which
40:31are very similar to the jewel,
40:32but they are disposable devices that
40:34again contain the nicotine salts.
40:36Like I told you earlier and coming
40:38up variety of flavors which are
40:40very very attractive to you.
40:42This shows you sales of these
40:44products and how it has dramatically
40:46increased over the years.
40:48These are considered to be a very
40:50good product to invest in and
40:52many investors unfortunately and
40:54there is an ongoing debate in the
40:57Community about what are the benefits
40:59versus harms of these products.
41:01Now I'm just trying to present
41:03both sides of it here for you.
41:05The benefits is that if these products
41:08help smokers to quit smoking,
41:10then it would definitely be
41:12reduced disease risk.
41:13For these current smokers,
41:14if they switch to E cigarettes or
41:17reduce or quit test cigarettes,
41:19there would be reduced disease
41:21morbidity for those with heart and lung
41:23disease who switched to E cigarettes.
41:25And we can also think about it from a
41:28psychiatric population condition issue.
41:30You know there there may be changes
41:32even in their disease morbidity
41:34and risks for other diseases.
41:36But there are also harms that
41:38need to be considered,
41:40particularly with relationship to youth,
41:42because these products being.
41:43Expose them to increase concentrations
41:45of nicotine and leave to lead to
41:47nicotine addiction and greater
41:48initiation of conventional tobacco
41:50products and kind of a renormalization
41:52of tobacco use behaviors.
41:53All these years we've been telling you,
41:55cigarettes are bad.
41:56Don't use them and now you have these
41:59products out on the market which are really,
42:02you know, re normalizing this
42:03tobacco use behaviors amongst you.
42:05So this is a big concern.
42:07There's also concern among adults
42:09because many adults unfortunately
42:10are not switching completely over
42:12to E cigarettes but are using them.
42:14For what I call Julie's behavior,
42:16so they smoke when they can,
42:18and if it then they can.
42:20So the concern is is this slowing
42:22sensation by smokers or complete quitting
42:24by smokers and the other concern is
42:26is also leading to a reinitiation of
42:29nicotine addiction and former smokers.
42:30There are many people who have
42:32quit smoking who are now coming
42:34back to using these products.
42:36So you know these are a
42:38lot of concerns that exist.
42:40So let me just walk you through some
42:42of these issues until end something.
42:45Even some things to consider.
42:46So let's consider hormone toxicity now.
42:48This when you compare cigarettes
42:50to E cigarettes.
42:51If you were looking to if you wanted
42:53to do an apples to apples comparison,
42:55which it really isn't.
42:57But if you wanted to look specifically
43:00at select a massive natural.
43:02The Big the bad boys in cigarette
43:05products that cause a lot of cancers.
43:07So if you look at nitrosamine's and
43:09other toxins and you compare cigarettes
43:11to E cigarettes and absolutely without
43:13a doubt the levels of nitrosamine's
43:16is less than cigarette in E cigarettes
43:18when you compare it to cigarettes
43:20suggesting that they probably may have
43:22reduced cancer risk then E cigarettes too.
43:25Although we don't have,
43:26you know the long term studies to show that,
43:29but definitely this data
43:30suggests that they may.
43:32However there are a lot of other
43:34components introduced in a liquid.
43:36That we know very little about and
43:38this list some of those components.
43:41There are some vehicles that are used like
43:43propylene glycol and vegetable cursory.
43:45There are a number of flavors that
43:47constitute all the flavor components.
43:49There are sweeteners and there's nicotine.
43:51And then there's also metals
43:53that come from the coil heating
43:55of the coil in the E cigarette.
43:57So there are other concerns that we have.
44:01I'm going to specifically focus on
44:03flavors for a little bit because this
44:05is a great interest in our center.
44:07It was an ad.
44:10Many people may not know are
44:12not just benign chemicals,
44:13they're actually the.
44:14Each flavor is made up of a number of
44:17different chemicals and this just gives
44:19you a little bit of a flavor of some
44:22of the aldehydes that are contained
44:24in some of these flavored E liquids.
44:26And there is a lot of concern about
44:29exposure to high levels of some of
44:31these aldehydes and what they might do.
44:33Many of these inhaled flavors are
44:35known to have health effects now.
44:37These flavors are commonly used for
44:39a lot of terrible products and.
44:41So in your Cheerios or your flavored
44:43cereals and other flavored products
44:45where they are considered to be grass,
44:47which is generally recognized as
44:49safe but they are not classified
44:50as grass for inhalation.
44:52And that is how they are
44:54being used in this product.
44:55So there's a lot of inhaled health
44:57effects that we still don't understand,
44:59but there is emerging evidence
45:01that flavors can be toxic to
45:03cells as you see in this slide.
45:05These are some of the flavors
45:07listed on the bottom of the slide,
45:09and many of these flavors are comma.
45:11Are aldehydes as can be listed
45:14here and aldehydes are known to be
45:16carcinogenic and it will all depend
45:18on what the level of the flavor is,
45:21how it is being used to.
45:23People heat the product excessively so that
45:26do they inhale more of these aldehydes?
45:28All these concerns that we have
45:30and there are some examples in
45:32the literature of flavors like
45:34diacetyl that increase the risk of
45:36things like popcorn lung disease.
45:38Interestingly,
45:38this was something that was found in
45:41people who were working in buttered.
45:43In popcorn factories where they were
45:45adding butter into the popcorn and
45:47they found that many of these workers
45:49actually had popcorn lung disease,
45:51hence the name.
45:52Now this flavor diacetyl is
45:53included in many flavorings to
45:55produce that buttery flavor.
45:57Again,
45:57this is not.
45:58I'm not saying that all these
46:00things have been shown to happen,
46:02but these are the concerns which are
46:04coming up and it's going to be very
46:06concentration dependent in terms
46:08of what these effects are and these
46:10are things we need to determine.
46:12Our center is also shown that Wendy's.
46:14Unicorns are sitting on a
46:17shelf they actually produce.
46:18They actually result in some common
46:21some chemical transformations I should
46:24say and produce these acetals acetals
46:27are basically aldehydes combined
46:28with some of the the dialogues
46:31that I was talking about earlier,
46:33like propylene glycol and vegetable glycerin,
46:36and these acetals are produced
46:38in the standing illiquid even
46:40before somebody inhales.
46:41These eliquids and data from
46:44our sector also shows that.
46:47At these acetals are actually more
46:49irritating than the parent aldehydes,
46:51and therefore there is concern about
46:53what the presence of these acetals
46:55might do when humans are exposed to it.
46:58So this is again evidence that
47:01needs to be collected.
47:02So obviously we have concerns about toxicity,
47:05and there's a lot of other evidence
47:07coming out about cardiovascular risks
47:09and pulmonary risks related to eliquids
47:12that I'm not going to be talking about,
47:15but there is.
47:16Emerging evidence on this issue.
47:18So based on that,
47:19the National Academy of Science
47:21report in 2019 put out the
47:23statement which basically said that
47:25E cigarettes are not risk free.
47:27They suggest if the current evidence
47:29suggests that it's far less harmful
47:31than combustible tobacco cigarettes,
47:33but we still need a lot more data
47:35to assess risk of these products
47:38from morbidity perspective.
47:40Now coming back to this slide
47:42that I showed you earlier,
47:43as I told you,
47:44one of the biggest discussions in
47:46the field is the balance of benefits
47:48versus cons for smokers versus youth.
47:51And let me show you some of
47:53the evidence on
47:54that. Now in as the rates of these use
47:56of these products have been growing used
47:58by you testing growing dramatically,
48:00national data collected about use
48:02of E cigarettes amongst youth in
48:04the United States and this red line
48:06shows you how the rates that the
48:08cigarette use has gone up dramatically.
48:10And how they continue to rise?
48:12They experienced a little bit
48:14of a dip last year,
48:15but still they're not back down to,
48:18you know, very low levels.
48:19They're still at what was seen in 2018.
48:22There's a similar data and
48:24middle school students,
48:25and we actually get calls from even
48:27students who are younger than that
48:29from schools telling us that they have
48:31caught students with these products in
48:33their backpack or using these products.
48:36E Cigarettes are the first product
48:38tobacco product used by most youth today.
48:40This is data we collected in Connecticut.
48:42Really asked the youth what is
48:44the first tobacco product you used
48:46and you can see that almost 70%
48:48of them said the first tobacco
48:50product they used was E cigarettes.
48:52So this is very concerning.
48:53You also use multiple devices.
48:55I showed all the devices earlier that
48:57there are many different types of devices.
48:59We have found that you'd use
49:01whatever devices available to them.
49:02They may use a friends device,
49:04they use their own device but they use.
49:07Of all the devices that are available
49:09and their use behavior changes as
49:11new devices come into the market and
49:13that is something that we have really
49:15struggled to keep up with because we
49:18have to constantly keep introducing
49:20new terms and assessing the use
49:22of new devices in the surveys that
49:24we do with youth in high schools.
49:27You don't sound really like and this
49:29speaks to the addiction issue or the
49:32electric potential of these products.
49:34In a survey that we did when in
49:36Connecticut high schools students,
49:38we found that they most people among the
49:41youth who used E cigarettes or juuls.
49:43In this case they said that they
49:45really like the buzz or the kind of
49:48stimulating effect they were getting
49:50from these products and this is
49:52concerning because if you look at
49:54these two groups, the Blue Group.
49:56Are non current jewel users which
49:58means people who kids who use Juul
50:00in the past but had not currently
50:03using and these are current Julie
50:05users and there is a significant
50:07difference between the two groups
50:09and that the noncurrent Juul users
50:10say they did not like the they did
50:13not like the buzz in jewels as much
50:15as the current Juul users too.
50:17So the question really is are these
50:19this continuation of behavior that
50:21you see in the current users?
50:23Is it related to the fact that they
50:25like this plus or the stimulating
50:27effects from nicotine?
50:29And again some other things to
50:31point out on these slides.
50:32Also,
50:33is that your thoughts are really
50:35like these Juul products for flavors,
50:37and because their friends use it,
50:39these are in fact some of the top
50:42three issues that came out as why
50:45you'd like these products now.
50:47Further evidence from that same paper
50:49showed that the these pharmacological
50:50effects that I showed you earlier.
50:53Like you know, these ability
50:55changing ability to concentrate,
50:56feeling more energetic.
50:57All these effects and the product
51:00characteristics like liking the size.
51:01Making the shape these were
51:03related to frequency of Julius,
51:06so the the more they like the.
51:10Logical effects of product characteristics.
51:12The more likely they were too.
51:16Interesting Lee pure influences
51:17was negatively related,
51:18so our thinking on this is that perhaps
51:20peer influences are more important
51:22for initiation of use of this product.
51:24But once they have developed
51:26a regular use behavior,
51:27it's more the pharmacological
51:28effects and other effects which
51:30really maintain these behaviors.
51:31So again, you can see this is moving
51:33along the addiction area here,
51:35and we worry a lot about
51:38nicotine use and you because.
51:40Indian Ocean brain it's times
51:42of rain for addiction it onto a
51:44settlement of insuring it changes,
51:46learning memory and attention.
51:47In fact,
51:48the earlier surgeon General had
51:50actually labeled one of our earlier.
51:52Sorry if the Commissioners
51:53and actually labeled nicotine
51:55addiction as a pediatric disease
51:57because he said that if you get
51:59addicted prior to the age of 18,
52:01you have worse health outcomes,
52:02more dependence and a harder time quitting.
52:05So we have a lot of concerns about you.
52:08Queues of such high levels of nicotine's.
52:10What you see in jewel on these
52:12other products you are also using
52:14these products for other behaviors.
52:16They use them for vape tricks,
52:18they can easily adapt these products
52:20to do produce different vape clouds
52:22like you see here and they they
52:24participate in weight competitions.
52:26They use it for behaviors like dripping,
52:28which basically means opening up
52:30the device and dropping the liquid
52:32directly on the heated coil in
52:34inhaling it and they are now starting
52:37to use it for vaping cannabis
52:38to the cannabis story is very
52:40interesting because they use cannabis.
52:42Devices and then they also hack
52:44E cigarette devices to introduce
52:46cannabis into it.
52:47So these presence of these devices
52:49is introducing you to a variety
52:51of these other behaviors that we
52:54know very little about the risk of.
52:56And our daughter centers also
52:58shown that E cigarette use also
53:00leads to cigarette use.
53:01This is using longitudinal data
53:03that we collected in Connecticut.
53:05We showed that youth who started with
53:08the cigarettes were more likely to
53:10move onto cigarettes in the future.
53:13So we have a lot of concerns
53:15that I highlighted very quickly
53:16for you amongst youth.
53:18What about smoking cessation?
53:19You know the other aspect of it is,
53:21is there evidence on whether these
53:24products or smoking cessation?
53:25So 2016 contribution.
53:29By that time,
53:30a very small sentence with limited samples.
53:33And you basically said that they
53:34probably help people smoking stop
53:36smoking and they probably work
53:38better than nicotine replacement
53:39therapy and nicotine free cigarettes.
53:41But you see that use the word probably
53:44in May a lot in this in this review,
53:47essentially suggesting that more
53:48reliable evidence was needed.
53:49But if you talk to smokers,
53:51there are multiple observation.
53:53ULL studies in which people will tell
53:56you that I quit using 60 cigarettes
53:58and I have no doubt that they did.
54:00But the clinical trial evidence
54:02is still emerging on this issue.
54:04In fact,
54:05they were trying to bring some
54:07clinical trials that came out,
54:09one by teacher hike which looked
54:11at which look very
54:12promising. This one compared E
54:15cigarettes to nicotine replacement
54:17therapy and found that people who
54:19use E cigarettes actually did
54:21better than those who got in RT at.
54:23Interestingly, he also found
54:24that the respiratory symptoms,
54:26relative risk of respiratory symptoms
54:28like shortness of breath, wheezing,
54:30caused all that was reduced in people who
54:33use E cigarettes versus those who use NRT.
54:36And this is a movie flyer by Natalie
54:39Walker from New Zealand that again
54:41compared combining nicotine Patch
54:43with E cigarettes that either contain
54:46nicotine or did not contain nicotine.
54:49And she found that combining these
54:51nicotine Patch with the cigarettes
54:53that contain nicotine actually
54:55had greater benefits and repent.
54:58Increased produced better quit rates
55:00during follow up then having the
55:03circus that did not contain nicotine.
55:05So just to summarize very briefly.
55:08There is a concern about impact on you.
55:11That huge concern because youth
55:13and young adults and this is a
55:15summary from the National Academy of
55:17Science report that youth and young
55:19adults may be more likely to use
55:21these products and try cigarettes.
55:23And there is a big concern
55:25about nicotine exposure.
55:26There is emerging limited evidence that E
55:28cigarettes may help people stop smoking,
55:30but and you know really the goal
55:32should be for complete switching from
55:35cigarettes to E cigarettes and that goal
55:38is if you can achieve that goal then.
55:40You can definitely reduce exposure
55:42to a number of toxic toxin toxicants
55:45and carcinogens found in cigarettes.
55:47There are some moves considering
55:50which are considering how to regulate
55:52E cigarettes so they can remain
55:55beneficial for smokers,
55:56smokers and yet reduce attractiveness
55:59for you.
56:00Then some of these being considered
56:02things like regulating nicotine levels.
56:04The EU for example only allows 20
56:08milligrams of nicotine in there.
56:11Products as I told you,
56:13Juul contains up to 60 but the concern
56:15is that maybe smokers may need higher
56:17levels of nicotine to quit smoking.
56:20There is some consideration of removing
56:22all flavors in eliquids like Canada has,
56:24but then there is a concern.
56:26Like I told you that smokers may
56:28need flavors to quit smoking.
56:30And there is some move towards regulating
56:32the kinds of devices available.
56:34So these are all things that we're
56:37generating scientific evidence for in
56:39our center and in the other centers.
56:41Well,
56:41there are a lot of ongoing regulations
56:43and these are my last few slides.
56:45I promise there are a lot of regulations
56:48that have been applied to these
56:50products to potentially reduce their
56:52use by youth and we are doing a lot of
56:55education of students, parents and teachers.
56:57I think we have.
56:58My group has gone to over
56:59100 schools in Connecticut,
57:01educating students,
57:02parents and teachers and Trisha
57:04Doll whom many of you know very
57:06well is very closely involved in
57:07these efforts to make sure that they
57:10understand the risks of these products.
57:12And we're also through this American
57:14Heart Association funded center,
57:15developing both prevention and
57:16individual cessation programs,
57:17which I don't have time to tell
57:19you about right
57:20now, but hopefully at some point in the
57:23future, once we have more evidence,
57:25I'll be telling you more able to tell
57:28you more about how these efforts pan out.
57:31Now my very last slide is.
57:33What can you do?
57:34You heard me talk a lot about all
57:36these products and present some of
57:38the nuances and conflicts to you.
57:41I would say as clinicians you should continue
57:43to encourage your patients to quit smoking.
57:46Quitting combustible cigarettes use is
57:48probably the best thing anybody can do.
57:51Or to improve their help,
57:53encourage them to use treatments
57:54that have been shown to work that
57:56that is good scientific evidence
57:58for like behavioral interventions,
58:00like pharmacological interventions
58:01that are available,
58:02like NRT and appropriate on an Chantix.
58:04But if nothing else works on your
58:06patient wants to use these cigarettes,
58:09then I would support them.
58:10But you know,
58:11warn them not to over use the E cigarettes,
58:14use it as they would their cigarettes.
58:17Encourage them to put cigarettes completely,
58:19none.
58:19None of this dual use behavior
58:21because that's going to be.
58:23You know,
58:23even could get them exposed to
58:25even more nicotine than they.
58:27Then they are normally used to being
58:30exposed to and encourage them to come
58:32up with a plan to quit cigarettes as well.
58:35I would also encourage you
58:37to educate your patients,
58:38educate communities and local schools,
58:40other community organizations,
58:41and Lastly help us collect
58:43scientific evidence on E cigarettes.
58:45The we needed.
58:46The FDA needs it to really regulate
58:48these products well.
58:50And I will stop there and I have.
58:52I know I presented a lot of
58:54information to you,
58:55but I'm happy to answer any
58:56questions that you might have.
59:11So people can either put their questions
59:13in chat or you can just ask her out loud.
59:19Do you want me to just look at the chat?
59:21Trisha? No question there yet but
59:25chat yet, but but certainly I'm happy
59:27to help moderate as well.
59:29If you need an eye on the chat while
59:31you're asking while you're answering
59:33questions, thank you, Marina.
59:36I did have a quick question Suchitra
59:39and that was around tobacco flavor and
59:42I know that early on you did a study
59:46where you showed that youth with Berry
59:49that you showed that you really don't
59:51like tobacco flavored E cigarettes.
59:54And if I remember from that study,
59:57independent smokers didn't mind it.
60:00And I wondered if you could comment on
01:00:03whether tobacco flavored E cigarettes
01:00:05might be a good compromise between
01:00:08the smoking cessation advantages
01:00:09and the likelihood of youth uptake.
01:00:12So the
01:00:14thing I would say about that is
01:00:16honestly the the in the in some of
01:00:19the studies initial studies we did.
01:00:21We did nobody like tobacco flavored
01:00:23E cigarettes and the reason being
01:00:25that they all said that the tobacco
01:00:28flavors was nothing like the
01:00:29flavor they get in cigarettes.
01:00:31But this this is become quite
01:00:33sophisticated overtime and we haven't
01:00:35looked at some of the newer flavors,
01:00:38but there are now flavors which say they
01:00:40match exactly with Marlboro cigarettes.
01:00:42So they match exactly with certain.
01:00:45Flavors that you get because as you know,
01:00:47most of these tobacco products vary a lot
01:00:49in flavor of the tobacco because of how
01:00:51they're processed and where they come from.
01:00:54I got, I talked to a tobacco farmer once,
01:00:56who gave me a whole history of Burling,
01:00:59tobacco, and how it's processed
01:01:00and where it comes from,
01:01:01which was fascinating.
01:01:02So I think they're doing a better
01:01:04effort of matching these flavors,
01:01:06and I can't answer that question today
01:01:08like I don't know how it would be
01:01:10approached today or how they would like it,
01:01:13but you definitely don't like them.
01:01:15That's for sure.
01:01:15I don't know about the adult smokers.
01:01:19There is a question in the chat from
01:01:22Schuber Rodriguez who says is anyone
01:01:24studying evidence for decreased lung
01:01:26disease morbidity with E cigarettes?
01:01:29Yes, there are many many center
01:01:31studying is that in fact we're doing
01:01:34some studies along those lines.
01:01:36Also to try to look at some
01:01:39biomarkers which might potentially
01:01:40be reflective of lung health.
01:01:43There are other centers
01:01:45doing studies of biomarkers,
01:01:46reflective of of cardiovascular health also.
01:01:49That I'm trying to understand
01:01:51both in people in smokers.
01:01:53What happens when they explain their they
01:01:55completely change over to E cigarettes
01:01:57and then also what happens to some
01:02:00of these biomarkers when you finish,
01:02:02she ate so there's both kinds of
01:02:04studies ongoing and there is.
01:02:06There are some studies which suggest
01:02:08there is there are long changes both
01:02:11in terms of pathology as well as
01:02:13some of the inflammatory pathways
01:02:15which are activated in the line.
01:02:17And there are other studies
01:02:19which suggest that.
01:02:20That is not the case,
01:02:22so again,
01:02:23emerging story.
01:02:25Lots of questions in the chat now.
01:02:28I'll keep going for for our chatters.
01:02:31Zach Carbonek asks what are your thoughts
01:02:33on the potential cardiorespiratory
01:02:34downsides of higher dose nicotine via
01:02:37eproducts compared to the carcinogens?
01:02:39Plus nicotine with traditional cigarettes?
01:02:41So there's a lot of concern about
01:02:44that. One of the T cores that is,
01:02:47that is our sister T course is
01:02:49the Americas that equals from
01:02:51the American Heart Association.
01:02:53And they're actually looking at.
01:02:56Markers like endothelial dysfunction,
01:02:57which is, you know,
01:02:59something that is can be changed
01:03:01with immediate exposure as well
01:03:03as changes in blood pressure.
01:03:05And they showed you that figure that
01:03:07nicotine alters a variety of organ
01:03:09systems and there is evidence emerging
01:03:11that things like endothelial function is
01:03:13altered by exposure to high nicotine levels.
01:03:16Again, as I said,
01:03:18it all depends on how much
01:03:20nicotine you're exposed to.
01:03:21That is why they are considering reducing the
01:03:24nicotine levels in products like Juul, which.
01:03:27In my mind contain an unbelievable
01:03:29amount of nicotine to lower levels,
01:03:32so maybe that effect might also be less.
01:03:43I think Marina
01:03:44froze. I think social Doctor Tech wants
01:03:47some more information about nicotine salts.
01:03:52Nicotine salts check.
01:03:53I'm happy to talk to you about this,
01:03:56but nicotine salts are very
01:03:58interesting and there are probably
01:04:00other people in our center were better
01:04:03at this who can give you better
01:04:06information like I know and sairam,
01:04:08but the nicotine salts toxicity is
01:04:11something that is still emerging
01:04:13and we know that Nick people who
01:04:16use nicotine salts say it's a lot
01:04:19less irritating to the throat.
01:04:21And therefore it makes use of
01:04:23these high levels of nicotine
01:04:25products like Juul much easier.
01:04:28That's really all the information
01:04:29I have right now,
01:04:31but I can connect with you later
01:04:33and maybe give you direct you to
01:04:35some more papers on this issue.
01:04:39Doctor Berger wants to know with low
01:04:41smoking rates, any comments on effects
01:04:44of taxation and the politics of this.
01:04:48Specifically related related to
01:04:50smoking or related to vaping.
01:04:55If you could clarify
01:04:57Doctor Berger, you can
01:04:58unmute yeah on either one
01:05:00so taxation has been used a lot in in
01:05:03smoking as you know to really and in
01:05:06fact that was one of the issues that
01:05:09came up in the menthol cigarette issue
01:05:11I was explaining to you earlier that
01:05:13Connecticut was considering potentially
01:05:15regulating menthol cigarettes and removing
01:05:17menthol cigarettes from the market.
01:05:18I understand one of the big issues that
01:05:21came up in the debate at that point was
01:05:24that the state gets an amazing amount of
01:05:27income from taxation of these products.
01:05:29Millions of dollars and
01:05:31the question really was,
01:05:32can we do this at this point or not?
01:05:35Can we afford to take the financial
01:05:37burden of removing these products on
01:05:39the market so it's a conversation
01:05:41that continues and taxation has a
01:05:43huge influence on that conversation?
01:05:45Taxation also has had has been
01:05:47shown to have a huge influence on
01:05:49youth use of cigarettes,
01:05:51so you the very sensitive
01:05:53very price sensitive.
01:05:54So if the prices of cigarettes
01:05:56go up you QS goes down.
01:05:58Now that model could be applied
01:06:00to E cigarettes also but that.
01:06:02That move has not happened because
01:06:04the concern is again of being
01:06:06able to provide these products for
01:06:08smokers who want to quit smoking,
01:06:10but so the concern is if you start
01:06:12taxing those products too much
01:06:14then smokers will not use them.
01:06:16So you know this debate is ongoing there.
01:06:18I hope that answered your question.
01:06:22It helps, thank you.
01:06:29Anything else, sorry I can
01:06:30see. I'm going West into Trisha
01:06:32'cause all my my chats disappeared.
01:06:34OK, it's all good.
01:06:37Prior to Covid, there were a
01:06:38number of young adults suffering
01:06:40respiratory failure and lung damage,
01:06:43which appeared to be caused from an
01:06:45ingredient in the vape capsules.
01:06:47Has there been any follow up
01:06:49studies on this?
01:06:50Yes, you're referring to a Valley
01:06:53which was can never remember
01:06:55the full what it they give you.
01:06:57These acronyms for everything?
01:06:59If Allie was was seen in the US
01:07:02population primarily at I mean at least
01:07:04wasn't reported from anywhere else.
01:07:06Besides primarily in youth
01:07:08and young adults in the US,
01:07:10and it was the CDC's last word.
01:07:13On this has been that it is
01:07:15potentially related to the use of
01:07:18a product called vitamin E acetate,
01:07:20which is a solvent that is used in in,
01:07:23not commercial supposedly,
01:07:24but black market cannabis products.
01:07:26So the so, as I told you,
01:07:29there is a lot of intersection between
01:07:31cannabis vaping and nicotine vaping,
01:07:33and supposedly there was a
01:07:35solvent called vitamin E acetate.
01:07:37In black market cannabis products,
01:07:39which has been identified as being
01:07:41responsible for the value that said,
01:07:44I don't think the book is closed
01:07:46on that issue yet.
01:07:48Covid just has changed the
01:07:50attention from the Valley to Covid.
01:07:52I understand from a lot of investigators.
01:07:54In fact there is in our group,
01:07:57Steve Baldassarre is doing this work,
01:07:59continuing to examine cases of
01:08:02Valley and how it relates to E
01:08:05cigarette use in the ER at Yale so.
01:08:07There is concern about this and it
01:08:10just has dropped off the CDC's radar
01:08:13because coding became the and rightfully so.
01:08:16An important issue.
01:08:19Alright, Kristen would like to know
01:08:21what would you say in response to the
01:08:23concerns about loss of revenue that
01:08:25might be causing hesitation or pushback
01:08:27on the menthol cigarette ban issue,
01:08:30and what can we do as scientists
01:08:32to advance and support this. So
01:08:35these are all hypothetical situations, right?
01:08:37So there is mental was banned in Canada.
01:08:40I think we need to look at the
01:08:43science and see what happened.
01:08:45There are instances where
01:08:46mental has been banned.
01:08:48We can learn from those what happened there.
01:08:51I think there is no just showing
01:08:53that the impact of a mental balance
01:08:55cigarettes is not as enormous as
01:08:58most people are contemplating.
01:09:00That is going to be there is a
01:09:02recent paper that just came out
01:09:05in 2021 where they model this.
01:09:07Issue and I forget what data they used,
01:09:10but it was based on data that
01:09:12was collected in Minnesota.
01:09:14I think in one County and there's
01:09:16also data from the Canada ban showing
01:09:19that this is not really an issue.
01:09:21I really feel as a scientist that banning
01:09:24menthol in cigarettes as I said earlier,
01:09:27is a social justice issue
01:09:28and it should happen because
01:09:30particular communities like Youth,
01:09:32an African Americans were targeted
01:09:34with these products and there was
01:09:36increasing use of these products.
01:09:38Among those communities and we need
01:09:40to remove mental from cigarettes
01:09:42so we can help these communities.
01:09:47We have great cover on an he says the
01:09:50purchase age was recently increased 21
01:09:53years old in Connecticut and nationally.
01:09:55What effect is this having on initiation?
01:09:59Good question. Unfortunately I
01:10:01can't answer that right now.
01:10:03The reason being that all our our
01:10:05abilities to do surveys and collect
01:10:07all this data over the past year
01:10:09after the Tobacco 21 law passed was
01:10:12significantly affected by covid.
01:10:14So both national surveys and local
01:10:16surveys have been, you know,
01:10:18have had really have been stopped because
01:10:20we haven't been able to collect the
01:10:23data because schools were not in session.
01:10:25You know, how do you collect the data?
01:10:28I'm sure there's somebody
01:10:30collecting data on this.
01:10:31And we will see that pretty soon,
01:10:33but I don't have an answer for you right now.
01:10:35But you know,
01:10:36keep your eyes on the literature.
01:10:37I'm sure there will be
01:10:38something that come out.
01:10:42That is all in chat and less
01:10:44somebody else has a question that
01:10:46they'd like to ask out loud.
01:10:53Hi, can I ask a question course?
01:10:55I think so. Hey, this is Andrew Weinstein.
01:10:58I'm I'm calling via phone as I walk
01:11:01an amazing presentation. Thank you.
01:11:03I was wondering and I joined a
01:11:05little bit early so you might have a
01:11:08justice are is there any increase in
01:11:10gastrointestinal problems as related
01:11:12to E cigarettes and then also are we
01:11:15seeing or is it too early yet to see?
01:11:18Are there other sorts of cancers that are?
01:11:21Typically associated with smoking tobacco
01:11:24that we're seeing with E cigarette.
01:11:28So
01:11:28gastrointestinal issues I
01:11:29cannot answer that, Andrew.
01:11:31I'm sure there's data on this,
01:11:33but I'm not familiar with it.
01:11:35My apologies.
01:11:36I know nicotine has GI effects,
01:11:38so I don't know if there is anything
01:11:40that has been shown directly
01:11:42about that as far as cancers.
01:11:44I think it's going to take a little
01:11:47while longer because you know,
01:11:49I'll remind you that there is an actual
01:11:51graph that shows that lung cancer
01:11:53rates in the US followed the cigarette
01:11:56epidemic or the rise and cigarettes.
01:11:58Used by about 10 years.
01:12:00I'm hoping we you know that
01:12:02we don't get to that point,
01:12:04but you know it takes awhile for cancer
01:12:06change effects to actually show up with it.
01:12:09So it will take awhile with E cigarettes.
01:12:11That said,
01:12:12at my Marina can correct me on this.
01:12:15I don't think there is so I don't know
01:12:17if how much evidence there is on direct
01:12:20effects of nicotine on cancer processes.
01:12:22I think that is literature that
01:12:24is still very small and still
01:12:26emerging and I'm not sure there's
01:12:28any good direction there so.
01:12:30Nicotine person causing cancer
01:12:31is something that I don't know
01:12:33that we know enough about yet.
01:12:34So sorry,
01:12:35that's I think we'll have to
01:12:37wait a couple of years to see
01:12:39what the evidence shows on that.
01:12:41Thank you Ann. Actually,
01:12:43in terms of the gastrointestinal piece,
01:12:45I was wondering if there's a
01:12:46difference for disposable devices
01:12:48versus devices that are reused.
01:12:49Because I'm thinking if they're reused
01:12:51and they're not cleaned up, what?
01:12:53What sort of bacteria is going on?
01:12:55You may not have the answer,
01:12:57but I was curious about
01:12:59that. Yeah, I don't have the
01:13:01answer for that. I'm sorry.
01:13:02I do know that devices that are shared
01:13:05like devices like hookers that are
01:13:07shared are associated with greater rates
01:13:09of infections and I would assume if
01:13:11these devices are shared across people.
01:13:13That same issue would apply,
01:13:14but I don't have direct evidence of that.
01:13:23Can I think we are?
01:13:25I don't see any other questions.
01:13:29Good.
01:13:31Wonderful presentation and discussion. Toxic
01:13:33chitrik. Thank you so much. Thank
01:13:35you, thank you for inviting me
01:13:37and for the great questions.