What led you to the field of smoking cessation?

I am a pulmonologist with an avid interest in interventional bronchoscopy.  In other words, I like to spend my time zapping cancers and opening airways.  I started looking to early lung cancer detection with autoflorescent bronchoscopy, spiral CT scanning and sputum cytology around 1998.  I kept on trying to find cancers earlier. This naturally lead to trying to prevent cancer altogether.  The best way to do this is smoking cessation.  Unfortunately, utilizing our standard methods of lecturing patients, writing a script and wishing good luck, my patient’s quit rates were around 15%.  It was discouraging. I hated wasting my time because it seemed that they never listened.  I only did it because I knew the importance of smoking cessation and the impact of smoking cessation advice from a physician.

One day a patient of mine, a 35 year-old woman with lymphangiolyomyomatosis (LAM) asked me about a “shot to quit smoking”.  I told her that I knew about the Nicovax that was several years from reaching the market and anything else was probably “snake oil”.  I advised her not to waste her money.  She did not listen to me and had the shot.  She quit smoking.  This was a lady that I had tried many times to help quit, without success.  This piqued my curiosity, so I did my due diligence reviewing medical databases and could only find the original Bachynsky article published in The International Journal of Addiction in 1986.  Beyond this, there was no information.  So I started a trial clinic after office hours, keeping track of my success.

 

What sort of success did you find in that trial clinic?

Initially I was naive. I thought that I could see a patient and give them a shot in the hip and send them on their way, sort of the same way I did with writing scripts for smoking cessation meds.  I soon found out two things.  The first was that just giving an injection without education or counseling only had about a 40% one month success rate.  The second was that the original Bachynsky shot of Atropine/scopolamine/thorazine had too many side effects.  This lead to the development of the SMART Shot ®.

 

How did you discover the SMART Shot ®? 

From primate data (Nature 1970) I knew that scopolamine was the main active ingredient.  Scopolamine has good penetration of the blood brain barrier so it can get into the CNS (central nervous system).  It also effects peripheral muscarinic receptors and can cause restless legs.  By adding the antihistamine hydroxyzine, there is an additional anticholinergic effect and it decreased the restless legs on the night of the shot.  After trying this combination, I was convinced that the side effect profile was significantly better than the original shot.  Thus the origin of the Scopolamine Mediated Anticholinergic Receptor Treatment (SMART Shot ®)

 

What is the mechanism of action?

The short answer is “I don’t know.” 

The long answer… excuse me because it is really long and I may ramble a little.  Here it goes:

Bachynsky’s initial paper in The International Journal of Addiction in 1986, suggested that there was competitive inhibition between nicotine and acetylcholine for the nicotinic receptors.  This lead to an increase in acetylcholine stores in the brain.  When the patient quit smoking, this excess of acetylcholine in the brain caused some of the physical effects of withdrawal.  Bachynsky suggested that it took about 7-10 days for these acetylcholine stores to get back to normal.  Thus the “hump” of physical withdrawal was in the first 7-10 days.

 

Is this what you believe?

I have found no data to confirm or refute this assertion, however in the last 30 years, we have learned much about the neurobiology of nicotine addiction.  We now know that the nicotinic acetylcholine receptors (nAChR) have an alpha subunit consisting of nine isoforms (α2-10) and the neuronal Beta subunit consists of three forms (β2-4).  Based upon radioligand studies, we have divided these receptors into three categories the high affinity receptors (of which the α4β2 are the most abundant) those with high affinity for α bungarotoxin (of which the α7 receptors are the most common) and those with a high affinity for neuronal bungerotoxin (α3 receptors).

There is a natural herbal extract called Cytisine that has been used for smoking cessation in Eastern Europe for 40 years (see Dr Etter’s article in Archives of Internal Med for an excellent discussion on cytisine http://www.stop-tabac.ch/cytisine/ or www.cytisine.org).  Cytisine acts on the α4β2 receptors,acting as a mixed agonist-antagonist.  Cytisine is the basis of the new stop smoking medication varenicline (Chantix).  We have Pfizer to thank for much of the research centered on the effects of the α4β2 receptors in the nucleus acumbens of the brain.  However, we also understand that there is a complex interaction of neurosubstrates of nicotine reinforcement involving the ventral trigeminal area, nucleus acumbens and ventral striatum of the frontal cortex involving other receptors than the α4β2 receptors such as the α7 receptors. It is the delicate interaction of these receptors in these areas of the brain that lead to nicotine addiction (figure 1 and 2).

Just when we start to think that we are pinning down the origin of nicotine addiction, we find out that a stroke or injury to the insula may cause people to quit smoking.   Clearly there is much more to be discovered about this addiction. 

 

And your point?  What does this have to do with scopolamine?

Sorry, I told you that I may ramble…  My point is that the more we know, the more we don’t know.  It is O.K. to say “I don’t know”. Back to scopolamine…

If you look at the structure of nicotine and the major nicotine analogs that are known to act on the nicotinic receptors; mecamylamine, anabaseine, cytisine, varenicline you can see the similarity of scopolamine (figure 3).  I think that scopolamine has good blood brain barrier penetration and probably acts on the nicotinic receptors in some fashion.  I can’t tell you if it is the α4β2 receptors or the α7 receptors or another subset of nAChR.

 

Do you think that research will eventually prove you right?

I don’t know if it ever will.  Since scopolamine is a cheap generic medication, there is not much interest in this area of research, at least not in the private sector.

 

What are the biggest challenges in smoking cessation today?

Recidivism! Utilizing tools available (Chantix, Zyban, SMART Shot ®), we can get people stop smoking with a one month success rate of up to 86%.  Unfortunately, at the end of the year more than half of these patients go back to smoking.  If you look at the recidivism rates of any of the smoking cessation studies, you will see the same sharp curve.  This is fairly independent of how long we keep people on these meds.  The way I see it is that we can ease the physical withdrawal with medications and “get them over the hump” however, there is no medication in the world that will prevent a patient from doing something stupid like lighting up “just one” cigarette six weeks, six months or six years after quitting.  Only education and support can help with that.

 

How does education and support help?

Over the last three years of listening to thousands of smokers whom have come through my clinic, I have learned that there are basically two reasons that people go back to smoking.  1) They do not respect the addiction and think that they are “the exception” and can smoke one cigarette.  2) They have a stressor and mistakenly believe that the only way to handle the stress is by being self destructive and smoking.  It is only through education and counseling that you can correct these fundamental errors in thinking.

 

How is your support different?

How many programs have the actual physician call the patients at home for follow up?  I personally call all of my patients initially.  Then our trained counselors call and get them through the process.  If they are struggling, our counselors let me know and I will call them again.  They also have access to leave a message on my cell phone if they need me.  I do not know of any other program that has that degree of support.

 

How good is the SMART Shot ® compared to other medications available?

We are having good success with the SMART Shot ®.  Our one month success rates are ranging from 70-86% across the board.  But it is just a tool to help ease the physical withdrawal. We often use it in conjunction with other tools such as Chantix and Zyban.  Again these are just tools to get smokers “over the hump” of physical addiction.  I can not stress the importance of education and counseling, which are the true cornerstone of our Quit Doc program.  I think without the education and counseling, our success rates would be about half of what they currently are.

 

What are your goals for the future?

Wow! There are so many goals that my partners and I have for Quit Doc… research, improving recidivism rates, prevention at the school level, inpatient smoking cessation… it just goes on.  I am lucky to have two partners, Dr Barry Hummel who is a pediatrician and the real creative mastermind behind Quit Doc and most of our prevention program, and Dr Andres Sasson who has the organizational and business savvy to keep us afloat.  We call Andres “the guy who lit a fire under our butts to make this concept materialize.”

Our quest reminds me a little of Schindler’s List.  We know that we literally save one life for every two people that we can help quit smoking.  I currently see about 1000 patients a year with a 35-40% 1year quit rate.  That is 175-200 lives saved each year by only one doc.  We have currently grown our Quit Doc Network to 10 clinics in three states. That will eventually translate to almost 2000 lives saved each year.  Imagine what we could do with 100 clinics? 

 

Do you have any other research interest?

Yes,  I am still very involved in interventional bronchoscopy and am currently involved with two FDA trials on bronchoscopic endobronchial volume reduction in severe COPD, as well as a sub investigator on about a half dozen other FDA trials.