Drugs from Gas Stations and Other Notes from the Field...

 

The Food and Drug Administration has not approved tianeptine for use in the United States; however, it is readily purchased in elixir formulations online or at gas stations informally referred to as “gas station heroin”  - from reference 1

 I shot the photo at the top of this post at my local gas station.  A couple of months ago they installed this neon sign advertising Kratom for sale and another selling Delta-10 THC.  Both compounds are intoxicants and are a part of the multigenerational drug epidemic that the United States finds itself in.   Depending on how you are reading about it that epidemic may seem restricted to fentanyl or in some cases amphetamines – but make no mistake about it there is a general trend in making all intoxicants more easily accessible and even making it seem like they are a legitimate business. Even the fentanyl story is only partially told.  The backdrop of excessive prescription opioid prescribing is rarely told – apart from a dramatized version.  The only good that has come of this is that all the hype about medicinal cannabis seems to be rapidly dwindling along with the lack of medical evidence that it has any such properties.

That brings me to the latest gas station intoxicant – tianeptine. It was originally intended to be an antidepressant based on a very general tricyclic structure.  I made the graphic below for a rapid structural comparison with standard tricyclic antidepressants (nortriptyline) and selective serotonin reuptake inhibitors (escitalopram). It is obviously not structurally like either class of compounds and has a unique moiety – the 5,5 dioxo structure on the central cycloheptane ring.

In terms of receptor affinities, the first property that jumped out at me was that tianeptine had none of the usual receptor or transporter affinities expected of typical antidepressants in the PDSP database.  The only affinity in that data set was for the mu opioid receptor (MOR). 

 

	NET	SERT	DAT	5-HT2A	5-HT1A	MOR
tianeptine	-	>10,000	>10,000	>10,000	>10,000	383 nM
nortriptyline	1.8 nM	15 nM	1,140 nM	294 nM	5 nM
escitalopram	6,514 nM	1.1 nM	>10,000	>10,000	>10,000

A recent CDC report (1) describes a spike in tianeptine ingestions and complications due to contamination from synthetic cannabinoid receptor agonists (SCRAs) between June and November 2023.  Fourteen of the 17 exposure calls involved patients drinking an elixir called Neptune’s Fix – a mixture of tianeptine and kavain or Piper methysticum root.  Six of the patients ingested other compounds including benzodiazepines, Kratom, trazodone, tramadol, and gabapentin.  Nine had previously used tianeptine. Thirteen of the 17 patients were admitted to intensive care units (ICU) and 7 required intubation and ventilatory support.  There were cardiovascular complications including conduction abnormalities, hypotension, tachycardia, and a cardiac arrest. All the patients had altered mental status.

Six samples of the Neptune’s Fix preparation from 2 of the patients were analyzed by gas chromatography-(GS-MS) and compared with a standard database of compounds of interest.  All of the bottles were labelled tianeptine and kavain. Two of the samples contained THC and CBD.  Two of the samples contained the SCRAs ADB-4en-PINACA and MDMB-4en-PINACA. 

The overall message of the report is that tianeptine preparations available as unregulated preparations can potentially be addictive and may contain adulterants that can produce severe adverse effects requiring resuscitation or ICU admission.  This has been noted in previous literature about SCRAs including severe psychiatric effects.  There have been 144 synthetic cannabinoids identified since 2014.  In some circles these compounds are referred to as JWH compounds after the organic chemist who first synthesized and researched them.

The way that tianeptine is described in the literature seems to parallel the interests of the authors.  The FDA references are uniformly negative because they are focused on severe side effects including death and addiction. Authors who are interested in the opioidergic system in depression will describe how it is a legal antidepressant in several countries and minimize both potential addiction and severe side effects. Either way it maps well onto the current American pro-drug culture. The sheer number of new intoxicants and widespread access to these intoxicants is staggering. Hundreds of new compounds in the past ten years.  Addictive compounds readily available at gas stations?  Those compounds laced with additional problematic intoxicants?  The so-called War on Drugs is obviously non-existent at this time. 

One of the questions I always get from people in response to posts about contaminated, adulterated, and counterfeit intoxicants is why?  Why would drug dealers or semi-legitimate businesses want to kill off or injure their customers?  What is their motivation? The most obvious one is that they don’t care.  There always seems to be a significant number of people out there interested in a new or higher high so demand is never a problem.  The second is marketing.  In a previous post I described a case where fentanyl was being pressed into tablets that looked like Xanax bars and the purchasers were not only aware of that but preferred to purchase those tablets even after directly observing them being made. A third possibility is ignorance. People looking to find intoxicants and sell them on the street are not medicinal chemists – even though they may talk like it. Some of these compounds vary in potency by a factor of a hundred or a thousand.  The fourth is a lack of accountability.  Even the most cynical conceptualization of the pharmaceutical industry recognizes the fact that the products are approved, manufactured, and monitored according to standards. Manufacturers are subject to regulatory bodies, criminal and civil liability, and accountability at the business level from a board of directors and at the shareholder level. It is fairly easy to find that the industry has paid tens of billions of dollars in civil and criminal penalties over the past 30 years. None of these incentives applies at the level of small companies marketing unapproved but unregulated drugs or street sales of illicit drugs. For that matter it probably also does not apply at the level of legal cannabis dispensaries. Even though legally prescribed and regulated medications have risks – unregulated and street drug risk is much higher.  As demonstrated in this post that risk starts with what is really in the bottle complicated by even higher risk adulterants. 

I always think of the former President of Mexico Vincente Fox in these situations.  When asked about the American drug problem and the involvement of Mexico he characterized the problem as “America’s insatiable appetite for drugs.”  When I think about people going into a gas station and buying Neptune’s Fix or Kratom or Delta-10 THC and not really knowing what they are getting in the bottle – he can’t be wrong.

George Dawson, MD, DFAPA

Supplementary:  On not caring that I mentioned in the above post.  I think there is a case to be made that the same attitude can fuel legitimate retail sales of drugs that reinforce their own used including alcohol, cannabis, and tobacco. Increasing liquor stores will increase alcohol consumption by increasing access.  That increased access comes with smaller distances to liquor stores, home delivery, placing liquor stores in proximity to other retail stores and supermarkets, and the commoditization of alcohol – you will always be able to find a cheaper drink. Since a significant portion of any population are problematic drinkers all this increased access directly impacts them. The people that create all this access, typically argue that the intoxicants are legal, they run a legitimate business, and not creating all this access puts them at a disadvantage compared to other sellers.  That argument leaves out the significant morbidity and mortality associated with alcohol and ironically that argument is typically used when advocates are trying to legalize another intoxicant as in:  “Our new intoxicant is not as dangerous or lethal as alcohol.”

 

References:

1:  Counts CJ, Spadaro AV, Cerbini TA, et al. Notes from the Field: Cluster of Severe Illness from Neptune’s Fix Tianeptine Linked to Synthetic Cannabinoids — New Jersey, June–November 2023. MMWR Morb Mortal Wkly Rep 2024;73:89–90. DOI: http://dx.doi.org/10.15585/mmwr.mm7304a5.

2:  El Zahran T, Schier J, Glidden E, et al. Characteristics of Tianeptine Exposures Reported to the National Poison Data System — United States, 2000–2017. MMWR Morb Mortal Wkly Rep 2018;67:815–818. DOI: http://dx.doi.org/10.15585/mmwr.mm6730a2

3:  Samuels BA, Nautiyal KM, Kruegel AC, Levinstein MR, Magalong VM, Gassaway MM, Grinnell SG, Han J, Ansonoff MA, Pintar JE, Javitch JA, Sames D, Hen R. The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor. Neuropsychopharmacology. 2017 Sep;42(10):2052-2063. doi: 10.1038/npp.2017.60. Epub 2017 Mar 17. PMID: 28303899; PMCID: PMC5561344.

4:  Nobile B, Ramoz N, Jaussent I, Gorwood P, Olié E, Castroman JL, Guillaume S, Courtet P. Polymorphism A118G of opioid receptor mu 1 (OPRM1) is associated with emergence of suicidal ideation at antidepressant onset in a large naturalistic cohort of depressed outpatients. Sci Rep. 2019 Feb 22;9(1):2569. doi: 10.1038/s41598-019-39622-3. PMID: 30796320; PMCID: PMC6385304.

5: Wikipedia contributors. Nortriptyline. Wikipedia, The Free Encyclopedia. December 20, 2023, 17:01 UTC. Available at: https://en.wikipedia.org/w/index.php?title=Nortriptyline&oldid=1190922632

Accessed February 4, 2024.  Wikipedia table was used for nortriptyline because the PDSP database was no longer working.

6:  Jelen LA, Stone JM, Young AH, Mehta MA. The opioid system in depression. Neurosci Biobehav Rev. 2022 Sep;140:104800. doi: 10.1016/j.neubiorev.2022.104800. Epub 2022 Jul 30. PMID: 35914624; PMCID: PMC10166717.

7:  FDA.  Tianeptine Products Linked to Serious Harm, Overdoses, Death.  https://www.fda.gov/consumers/consumer-updates/tianeptine-products-linked-serious-harm-overdoses-death

8:  FDA.  Tianeptine in Dietary Supplements.  https://www.fda.gov/food/dietary-supplement-ingredient-directory/tianeptine-dietary-supplements

9:  FDA.  FDA warns consumers not to purchase or use Neptune’s Fix or any tianeptine product due to serious risks.  https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-neptunes-fix-or-any-tianeptine-product-due-serious-risks

Incident Atrial Fibrillation and Intoxicants

I remain very interested in the cardiac and brain complications of medications and substances that are commonly used to get high or create altered states.  I am also very interested in the popular trend to characterize cannabis as some previously undiscovered medication that can cure everything ranging from anxiety to obstructive sleep apnea.  I was naturally interested when I saw this paper (1) looking at the issue of incident atrial fibrillation and common intoxicants.

The authors examine a very large database in California that included anyone who had been seen in an emergency department, ambulatory surgery center, or hospital over a period of 10 years (2005-2015).  After they eliminate minors, subjects with persistent atrial fibrillation, and subjects with missing data they had a total of 23,561,884 people. 998,747 of those people had incident atrial fibrillation (defined as the first encounter for atrial fibrillation).  Since their study design is a retrospective observational study they also recorded substance use was considered present if Substance use was considered present if there was coding for any indication of use of methamphetamine, cocaine, opiates, or cannabis.  Knowing the atrial fibrillation and substance use diagnoses – the authors calculate the hazard ratio for each of the substances of interest.

Hazard ratios are basically the ratio of the people exposed to intoxicants who developed atrial fibrillation over the unexposed who developed atrial fibrillation.  So any number greater than 1 means that the population exposed to intoxicants had greater risk.  The corrected hazard ratios were noted to be 1.86 (methamphetamine), 1.74 (opioids), 1.61 (cocaine), and 1.35 cannabis. The authors adjusted for common atrial fibrillation risk factors and ran an additional negative control analysis and looked at the scatter of data pints for these 4 substances and hazard ratios of developing appendicitis, connective and soft tissue sarcoma, and renal cell carcinoma and showed no consistent pattern for these illnesses.

There are a couple of interesting considerations relevant to this study.  The first is the mechanism of action in each case. With stimulants there is a direct hyperadrenergic effects and depending on the individual and dose of the drug varying degrees of tachycardia, palpitations, and hypertension.  Long term users frequently end up with cardiomyopathy from these effects and in some cases ventricular arrhythmias and congestive heart failure. There can also be acute vascular effects like ischemia either due to the increased cardiac demand or pre-existing arteriosclerosis. Atrial fibrillation has not typically been placed in that group of morbidities from stimulant use. Patient with atrial fibrillation often notice emotional precipitants for discrete episodes or atrial fibrillation although a recent study showed that the only reliable precipitant was alcohol use (2). There were significant limitations with that study with attrition and length of the study although I generally agree that alcohol is a clear participant.  Precipitants need to be carefully approached and I suspect that attentive physicians have noted variable phenomenology on an individual basis. 

The high hazard ratio for opioids is a little puzzling. Hyperadrenergic states can occur with the euphorigenic effects and withdrawal effects as well. Direct comparison with stimulants may be difficult due to rapid dose escalation and some degree of tachyphylaxis.  Cannabis is not surprising to me at all. Many initial cannabis smokers notice that their heart is pounding and don’t know why.  They find it unexpected given the conventional wisdom that cannabis is supposed to be a benign substance. Many initial users also get increased anxiety and, in some cases, have a panic attack that may be due to the cardiac sensations. The primary heart pounding sensation is because cannabis causes hypotension and they are experiencing reflex tachycardia. The effects may be less predictable because cannabis use can affect both sympathetic and parasympathetic pathways that can potentiate arrhythmias. A case report of cannabis induced atrial flutter (3) was described as occurring in a woman with a history of hypertension that eventually had to be terminated by an intravenous antiarrhythmic.   

Atrial fibrillation and other cardiac arrhythmias are another good reason for avoiding intoxicants including alcohol (in the supplementary analysis alcohol had a Hazard Ratio of 2.37).  It could be argued that it is basically a numbers game – since most people who use these intoxicants do not develop incident atrial fibrillation.  As of this moment, even if you have had your DNA analyzed for what are known about atrial fibrillation genes – you can’t be certain that you are not susceptible to the problem. And as outlined above there are many additional cardiac problems and that are possible from using these compounds.  The safest path is to avoid these intoxicants all together.

 

George Dawson, MD, DFAPA

 

 

References:

1:  Lin AL, Nah G, Tang JJ, Vittinghoff E, Dewland TA, Marcus GM. Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation. Eur Heart J. 2022 Oct 18:ehac558. doi: 10.1093/eurheartj/ehac558. Epub ahead of print. PMID: 36257330.

2: Marcus GM, Modrow MF, Schmid CH, Sigona K, Nah G, Yang J, Chu TC, Joyce S, Gettabecha S, Ogomori K, Yang V, Butcher X, Hills MT, McCall D, Sciarappa K, Sim I, Pletcher MJ, Olgin JE. Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial. JAMA Cardiol. 2022 Feb 1;7(2):167-174. doi: 10.1001/jamacardio.2021.5010. PMID: 34775507; PMCID: PMC8591553.

3: Fisher BA, Ghuran A, Vadamalai V, Antonios TF. Cardiovascular complications induced by cannabis smoking: a case report and review of the literature. Emerg Med J. 2005 Sep;22(9):679-80. doi: 10.1136/emj.2004.014969. PMID: 16113206; PMCID: PMC1726916. [full text] 

The Most Important Decision In Your Life......

See Complete Reference Below

I thought a while about how to write this.   There are a lot of opinions out there about how a decision like this one should be philosophical or religious.  After practicing psychiatry for over 30 years I have to come down on the side of practical.  The most practical decision I think that anybody can make is to stop using intoxicants, at least to the point of intoxication.  I don't really care what your current intoxicant is.  It could be alcohol or cannabis or heroin.  Deciding to stop it will only improve your life and the lives of your family and friends for any number of reasons.  At this point I am a witness to the thousands of people who have stopped and seen those improvements.  I am also a witness to the unfortunate thousands of people who did not stop and ended up dead, incarcerated, homeless, chronically mentally ill, in nursing homes, or leading miserable lives.  I am not naive enough to think that my little argument here is going to make that much of a difference and will elaborate on that in the paragraphs that follow.

One counter issue that I want to address as early as possible because it is often used to short circuit arguments against intoxicants is what I consider an American pro-intoxicants argument.  It certainly can exist in other cultures, but I am restricting my comments to Americans because of the pervasive attitudes about intoxicants.  The most obvious attitude is alcohol and drug use as a rite of passage to adulthood.  This is a well documented phenomenon rationalized at several levels.  Common examples include: "If one is old enough to vote or go to war they are old enough to drink."  There is abundant current evidence that 18-21 year olds if anything are exposing brains that are neurodevelopmentally immature to the effects of alcohol and street drugs - often at toxic levels.  Rational arguments against exposure are not likely to have much of an impact on a population segment in the throes of the invulnerability of youth.  Even apart from the brain based argument, the driving and risk taking behavior of this group is well documented.  Adding intoxicants to the mix is not likely to alter those decisions in a positive way.

An extension of the rite of passage argument is the rights argument as in "Alcohol and tobacco are legal substances and therefore I have a right to use them."  There is no doubt that is true, but the right is limited.  Only people of a certain age can use these compounds and in the case of intoxicants that can affect public safety - their use is even more limited.  People who I have seen invoke the rights argument are generally not talking about limited rights.  The modern version of the rights argument is that "no one should have the right to tell me what I can put in my body.  On that basis all drugs should be legal and easily accessible".  A complementary argument is: "Alcohol and tobacco kill more people every year than (fill in favorite intoxicant here) and therefore I should be able to use it."  Another complementary argument that often gets more support is: "The War on Drugs is a complete failure.  All drugs should be legal and that way we can tax it and make a profit from it.  We can put the cartels out of business."  The rights argument frames an idyllic drug consuming society immune to the medical problems of acute intoxication and addiction as well as all of the associated social and legal problems.  Extreme arguments like this suggest to me that they are driven in part by desperation.  Of course intoxicants need to be regulated - we already have ample evidence of what happens when they are not.  The basic problem that they reinforce their own use at increasing levels cannot be ignored.  Tax on intoxicants is generally an unreliable revenue source when the total cost to the taxpayers for that intoxicant and the fact that revenue is diverted away from covering those costs.
  
A second cultural phenomenon is the use of intoxicants for celebrations.  Weddings, funerals, and various parties often result in the excessive consumption of alcohol. I attended a funeral where the clergyman addressed half of the audience and suggested that an AA meeting might be in order afterwards.  The deceased was probably a victim of excessive alcohol use.  Although alcohol remains predominant in many of these settings, since the 1970s second and third intoxicants are also common.  The relevant consideration is whether these celebrations can occur without the intoxicants.  Interestingly, that decision may come down to the cost of having an "open bar" versus less expensive alcohol on tap. 

A third consideration is the subculture of extreme use.  Many states are notorious for per capita alcohol consumption, binge drinking, and driving after drinking too much.  I don't think that the problem has been well studied, but growing up in a heavy drinking or using culture exposes anyone to early use and reinforcement that are both precursors to problematic use. 

There are several arguments in the popular media that seek to minimize the potential impact of drugs on your life.  Think about the counterarguments:



1.  If I don't have a diagnosis of alcoholism or drug addiction my pattern of using intoxicants is not a problem:

The most absurd presentation of this argument was the idea that a significant number of binge drinkers do not meet diagnostic criteria for alcohol use disorder.  I can't count the number of people who I know that have had their lives ruined or ended by a single drinking binge.  Many high schools in the US started a senior party strategy because so many students were killed around the time of graduation parties due to acute alcohol intoxication.  The drivers in these cases were not alcoholics.  They were high school seniors many of whom had limited exposure to alcohol before the fatal accident.  Binge drinking and acute intoxication is associated with a long line of accidental deaths, alcohol poisoning deaths, suicides, homicides, intimate partner violence, rapes, and other crimes.  All preventable by not binge drinking or more importantly getting intoxicated in the first place.  The same pattern follows every other intoxicant.  If you put yourself in a mentally compromised state in practically any setting - bad things will happen whether you have been diagnosed with a substance use disorder or not.

2.  Alcohol is a heart healthy beverage:

The CDC and the American Heart Association both recommend moderate intakes of alcohol and they define that as one standard drink of alcohol per day for women and one or two standard drinks for men.  This is based on data that shows that these amounts of alcohol may confer reduced risk for heart disease but that higher amounts increase risk.

3.  Intoxicants can be good for your health - some are natural medicines:

The great natural argument leaves a lot to be desired. It's like listening to that guy in a bar tell you that his doctor told him he could drink as much wine as he wanted because it was a natural beverage and then realizing that he is standing in a puddle of his own urine. Peak alcohol consumption in the US occurred at time when it was considered a medication in the early part of the 19th century.  The current best example is cannabis, a substance that has been around for at least 10 centuries and suddenly it is a miracle cure for everything.  The obvious question is why that wasn't noticed in that last 1,000 years. 

4.  Alcohol and drug use disorders are not diseases - it is a question of choice and therefore I have nothing to worry about:

Despite what you may read on some online blog, in opinion polls most people consider alcoholism and addictions to be diseases.  Almost everyone has had some contact with people who have these problems and they see that the usual negative consequences that cause most people to correct their behavior - have no effect on the addicted.  There is no or at least limited capacity for self correction.

5.  I am a libertarian and I believe that all intoxicants and drugs should be legal - I should be the only person deciding what goes into my body:

A familiar argument that ignores human history. The reason that there are controls on addictive drugs is because a significant part of the population will use them in an uncontrolled manner and that generally leads to a chaotic society with all of the costs of that chaos. The more free access there is - the more addiction and chaos.

This argument implies that everyone is the best judge of "what I put in my body" based on political beliefs. There is no evidence that is true.

6.  I am an adult and if I want to have a drink - I will have a drink:

That is a minor variation of the libertarian argument for non-libertarians.  It is basically a truism - yes of course unless you are prohibited by law (and some people are) you can have a drink.  Doing something basically because you can strikes me as a shallow argument. Looking at what happened during Prohibition, I think it is safe to say that the right to drink was preserved by a relatively vocal minority of people who want to drink.  They want to drink for the previously cited cultural reasons and in fact there were some famous exceptions to Prohibition that were based on purported religious ceremony and requirements for alcohol. 

A similar argument is that if a person wants to feel high "there is nothing wrong with that."  At a superficial level and strictly speaking that is true as long as the level of intoxication doesn't lead to medical, safety, or interpersonal problems. The larger question is whether there is something better to do. Let's define better as another recreation that leaves you better off than using intoxicants.  In that case walking around the block is better than getting stoned.

7.  It is part of my creative process:  

There are reviews and books written about how creative people have used drugs and alcohol to enhance their creative process.  These works are by their nature anecdotal.  I am unaware of any controlled sober group and their creative process but it is likely that they exist in large numbers.

8. I am self -medicating and need it to treat insomnia, anxiety, depression, and/or pain:

Self medication implies that intoxicants are actual treatments for these problems. If you talk to any person who uses this strategy - the amount of relief lasts for a few hours.  People tell me: "Look doc - if you can't get rid of this anxiety - I know how to get rid of it for a few hours."  Using alcohol, street drugs, or diverted prescription medications is usually a recipe for worsening symptoms and tolerance.  In that setting people often have the idea that more drugs will bring back the few hours of relief and there are always examples of associated catastrophes in the news. 

9.  The political argument that by allowing universal access to drugs - the cartels will be out out of business - 

Very common to hear that all drugs should be legalized and hear this argument in the next breath.  Most of the people making this argument seem naive to fact that black markets still exist with legal intoxicants.  In the WHO Global status report on alcohol and health 2014, 24.8% of the alcohol consumed was outside of government control.  In the US, it was 0.5 liters of a total of 9.2 liters per capita.  For tobacco the black market is somewhere between 8.5 and 21% of sales. In Colorado there is currently mixed concern about the possibility that drug traffickers are in plain sight, continuing to grow cannabis in remote areas and transport to other states, but reliable information is not available. In the case of heroin, the current impetus for its use is that it is 25% the cost of diverted pharmaceutical opioids.  In the worst case scenario of legalized opioids with no control is it realistic to consider governments regulating heroin at that low cost to consumers?  If not it is a recipe for continued uncontrolled black markets. 

10.  The "You are an prohibitionist" counterargument:

Whenever I present any of my arguments for avoiding intoxicants in the list above, there is the inevitably that some very angry guy accuses me of being a prohibitionist.  I don't know how much weight that ad hominem carries but I always find it amusing. If prohibition worked, I would not need to make these arguments.  My blog is one of the few places where you can see a graphic of how things went during prohibition and it obviously wasn't good.
 
Believe me - you can go through life without ever taking a drink, smoking a joint, snorting cocaine, or injecting heroin and not miss it.  The best case scenario is that it adds nothing to your quality of life.  It is also tempting to think that you have plenty of time to quit later.  With that plan many people either never quit or realize when they are 40 years old that they have been in a fog for 20 years.  Addictions sneak up on you and steal what should be your most productive years.

In fact none of the people with addictions who I talk to ever started out believing that one day they would end up with an alcohol or drug use problem.  Recognizing all of the defective arguments listed above is a good first step.  The most important ability to prevent addictions is self correcting abstinence.  If you wake up one day and realize you dodged a bullet when you were intoxicated, think long and hard about avoiding that situation again.

If you can't - you may have a serious problem.


George Dawson, MD, DFAPA



Supplementary:

Graphic at the top is from:

Lavallee RA, Yi H.  Surveillance Report #92: Apparent per capita alcohol consumption: national, state, and regional trends, 1977-2009.  US Department of Health and Human Services. Public Health Service.  August 2011.  Link.