What Does the DEA Drug Trafficking Report Really Mean?

 

The DEA just published a significant report on the drug threat in the United States. I read the entire document and will review a few of the high spots here highlighting why it is not too relevant for most parts of the country.  I am on record in several places on this blog making similar comments. My basic argument has not changed significantly and that is that the demand for illegal and often fatal drugs is driven by the culture in the US and I would not expect law enforcement to make much of a difference. The case in point is Prohibition and the ban on alcohol.  Of course it was not a real ban.  Criminals still bootlegged alcohol into the country, religious groups found a way to circumvent the law, and there are always people producing illegal alcohol as a significant percentage of alcohol consumed every year.

These facts are most often distorted into the argument that Prohibition or any War on Drugs is doomed from the outset. That argument is most frequently used to implicitly suggest that any attempt to legally restrict intoxicants will be righteously overcome by people with a natural right to pursue intoxication.  That is extrapolated to practically any scenario short of negligent homicide due to intoxication or drug dealing. But even the drug dealing scenarios are being rapidly modified to allow possession of certain amount of cannabis or in some cases legitimizing drug dealing as a useful occupation. The direct and indirect costs of drug use to both individuals and society are typically ignored by anyone without a medical or public health interest. Intoxication is a cultural right, a right of passage, and every effort of being made to expand the availability of intoxicants to everyone in the US.

The DEA (1) states their role is to expand awareness, preserves lives, and provide intelligence to law enforcement that might be useful for resource allocation and prioritization.   Synthetic opioids and stimulants are described as the biggest threats.  Both can be easily mass-produced by the cartels in Mexico.  Fentanyl alone has accounted for a massive increase in mortality due to its potency and low therapeutic index – accounting for 74,225 deaths in 2022.  China is implicated as the main source of precursor drugs to produce fentanyl.

The report clearly states that two Mexican cartels are responsible for the drug flow into the US and the most significant drug crisis in the history of the US.  Further – the cartels have penetrated most states in the US to varying degrees.  The Internet has facilitated drug sales in the US and made these transactions more difficult to track.  The cartels are also producing methamphetamine leading to an increase in stimulant associated deaths.  There is also a China connection.  Chinese criminal operations supply precursors for the synthesis of opioids and methamphetamine as well as money laundering operations to make the money from illegal drugs sales useable. 

One of the strategies these criminal enterprises are using is adding additional intoxicants to the drug that users are purchasing.  This has the effect enhancing the intoxicating effects but with a much higher risk of overdose and death – especially if the user is naïve to that drug or the seller is ignorant about the potency of the additional intoxicant.  I became aware of this phenomenon about a decade ago when I was being told that users witnessed fentanyl being pressed into alprazolam tablets and sold as alprazolam.  A secondary phenomenon was that many people were not averse to fentanyl but actively sought it out to enhance the period of intoxication.  The DEA report describes the following combinations:  

Fentanyl plus:

Heroin, cocaine, methamphetamine, xylazine, Counterfeit prescription drugs: (oxycodone (M30, Percocet); hydrocodone (Vicodin); or alprazolam (Xanax)

 

The DEA report addresses many of the logistics of the substance use problem and it does raise awareness – especially of the dangers of getting adulterated drugs and the severe side effects including death. It also highlights drug counterfeiting and it gives a great example of an Adderall tablet counterfeited from methamphetamine (see below).  That is especially problematic during a time of Adderall shortages from legitimate suppliers.

 

The unaddressed problem is American culture.  I don’t want to suggest that large groups of sociopaths intent on making money no matter how many people they kill don’t bear some responsibility. I also don’t want to suggest that reducing the availability of these drugs by any means is not a good idea.  But one of the takeaways from reading this report is that law enforcement is clearly not winning and it is a huge burden on them in both the US and Mexico.  Former President of Mexico Vincente Fox characterized the problem well as “America’s insatiable appetite for drugs.”  Right now, it is a multigenerational chronic problem. People can get effective treatment and recover but too many die and too many become chronic users. There needs to be an effective strategy for primary prevention or preventing use in the first place. Suggestions along these lines typically end up caricatured as the 1980s “just say no” public service ads or the "failed war on drugs", but this strategy was clearly effective in reducing cigarette consumption and decreasing the population of smokers. It has had the expected effects of decreasing smoking related mortality in both the general population and in smokers who quit.  The same population-wide benefits would be expected from any public health measure that effectively reduced the use of alcohol, stimulants, opioids, cannabis, or any other intoxicants.  What are the cultural factors that keep this drug epidemic going?  Here are a few:

1:  Cultural acceptance of substance use as a rite of passage:  The stories are endless. Fraternity and sorority hazing involving excessive alcohol use.  High school graduation parties associated with multiple driving while intoxicated deaths. Incarceration from assaults and homicides from barroom fights. Consumption of alcohol and other intoxicants in high school well before the legal age for consumption has been reached. Much of this has to do with immaturity.  The Decade of the Brain did inform us that just on a biological basis human brains do not mature until the mid 20s and in the case of men possibly even later. Immersing an immature brain in intoxicants is generally not a recipe for success and may be a developmental risk for substance use disorders and mental illnesses.

2:  Consumerism and the selling of intoxicants:  This is a widespread phenomenon in the US.  Alcohol commercials typically suggest success, sexual attractiveness, popularity, sophistication, and glamour.  Identification with Hollywood A-listers is a plus and many of them are marketing their own brands to capitalize on that fact. The expensive packaging is often more significant than any difference in taste or quality. The only downsides are a very brief allusion to the Surgeon General’s warning about alcohol use in pregnancy or a disclaimer to “use responsibly.”  Not much about alcohol poisoning, cancer, cirrhosis, pancreatitis, cardiac problems, dementia risk, or substance induced psychiatric disorders. For a long time alcohol was hyped as a heart health beverage.

3:  Your right to intoxicants:  The subculture of users has a mixed agenda in promoting this idea.  There are a few people who believe that their lives are better by using drugs or alcohol, that they are using these substances in a controlled manner and “not hurting anybody.” And therefore, anyone should have the right to use them under these conditions.  On the face of it – few people would argue that point – even though it does assume that self-report about use and its consequences are always accurate.  A subgroup is promoting widespread intoxicant use as a business.  Many in this group see it as a get rich quick scheme. Many see it as a diversity equity inclusion (DEI) issue.  That is – minority groups sustained harm from excessive legal penalties against cannabis and other drug possession and therefore they should be given advantages in setting up businesses that profit from legalization.  Many want to extend cannabis law changes to include all drugs and legalize access to everything. The DEA report stands in contrast to mass legalization because it estimates how much the country would be awash in fentanyl if it was legal. It also ignores why substances were controlled in the first place and what happened when physicians started to prescribe more opioids both as "dope doctors" in the early 20th century maintaining people in addiction and in the late 1990s leading to the beginning of the current opioid epidemic.

4:  Cannabis misinformation:  There has not been much reflection of the medical cannabis period of the early 21^st century.  Cannabis was touted as a miracle drug whose benefit was being neglected due to archaic drug laws and the lack of modern research. Nothing was said about cannabis being around for over 700 years and having no clear cut indications for use or the fact that earlier cannabis compounds fell into disuse with modern therapeutics. That led to a patchwork of state-level medical cannabis laws, making each of those states a Mini-FDA with their own indications for use and in some cases limited forms of cannabis that could be dispensed for those indications.  Just as it became apparent that cannabis really was not much good for medical applications or even pain – the real motivation for the medical cannabis Trojan Horse became apparent.  That was of course recreational use. The Biden administration is currently considering rescheduling cannabis from a Schedule I to a Schedule III substance. That takes it off the experimental/no medical application category but still suggests that it will be prescribed and supervised by a physician.

5:  Widespread promotion of hallucinogens and psychedelics as miracle drugs: Building on the success of promoting cannabis as a medicine – we are now seeing frequent hype about the wonderful effects of psychedelics along with practically no discussion of the side effects. MDMA and LSD are being seen as wonder drugs that successfully treat depression, anxiety, PTSD, and substance use disorders. The cannabis promoters successfully promoted cannabis as a nearly completely benign substance and the hallucinogen/psychedelic promoters have used the same tactic.  I only recently read an account where the following side effects during a clinical trial of an LSD based drug were listed: illusion, nausea, euphoric mood, headache, visual hallucination, mydriasis, altered state of consciousness, anxiety, blood pressure increase, and abnormal thinking (all in significant numbers). In my clinical experience I have treated people with permanent side effects from this drug class after a single dose.

6:  Better living through chemistry:  There is a current wave of euphoria in the popular culture about GLP-1 agonists like Ozempic and Monjauro. It has been accompanied by FDA approved indications but also a very public reexamination of the usual prescriptions of diet and exercise for weight loss. The pendulum seems to have swung to the point that all excessive weight is a disease state that can only be approached with a powerful drug that has potentially powerful side effects.  From a cultural perspective this class of drugs reinforces the American dream that we can tune our bodies like we tune our cars and if we have the right drugs – we can have whatever kind of body or mind that we want. More longstanding evidence of this attitude is evident from anabolic androgenic steroid use and stimulant use for - both for performance enhancement.  All three are grand illusions. Hominid biology has evolved to incredible complexity over the past 2 millions years.  Any group of people may look alike but there are hidden differences in physiology and pharmacological response. One person’s medication is another person’s poison. As a result there are very few miracle drugs and some intoxicants have been around for centuries making it even less likely.

7:  Sobriety as a subculture:  In most societies certain religions and life philosophies are the most likely promoters of sobriety.   Most sobriety in the US is not thought about too much.  There are about 60% of people who never drink. There is a group of people in active recovery who had a problem with intoxicants and were successful in discontinuing them.  There is a small movement right now of young people who are not in recovery promoting sobriety.  The cultural resistance against substance use in the US seems trivial compared with the promotions.

8:  Treatment is secondary prevention: A standard political approach to the drug epidemic these days is to suggest that more availability of treatment centers and providers is a needed approach.  This is correct in so far as treatment for these conditions has always been deficient. Treatment has had a role in terminating localized drug epidemics in both Chicago and Washington DC.  There is a question about how well it will work now that just about every county in the US is awash with opioids and methamphetamine.   A logical approach may be to prevent new users from entering this cycle – in other words decreasing the incidence of the problem. Unfortunately there are fewer resources to address this problem and a lot of pessimism about that approach.  

9: Intoxicant use is a choice: Even though there is obvious evidence out there that a significant percentage of the population develops uncontrolled use of drugs and/or alcohol denial and rationalizations about this continues to persist. It has to in order to maintain the myth that people with substance abuse disorders really have a moral defect rather than a biological propensity.  In other words – repeatedly telling them to stop and blaming them for the problem is all that is required. That approach ignores the real problem that if you are biologically disposed – all it takes is access to substances to keep that process going. The moral approach also allows for a legalization position by simply stating that the people who cannot control their use are irresponsible.  

10:  Deaths of despair: This concept was popularized by Dean and Case (2) to explain increased mortality due to intentional injury and drug overdoses caused by hopelessness due to economic problems and the associated stress. Deaths due to alcohol and drug use were seen because of economic stress rather than a consequence of excessive use for other reasons including the cultural factors that have been specified. The concept minimizes the fact that severe alcohol and drug problems exist in populations that have no economic stress and that most of the people with severe economic stress do not have drug and alcohol problems. It also minimizes the fact that we are still in the midst of a multi-decade drug epidemic and there is no end in sight.  

11:  Legalizing drugs will put the cartels out of business:  This has always been an extremely naïve argument.  Alcohol and tobacco sales are legal and taxed but that does not prevent their illegal sales.  Prescribing opioids, stimulants, and benzodiazepines does not prevent their illegal sales.  The DEA report highlights continued involvement by organized crime in cannabis production and sales - even after it has been legalized. Illegal production has led to violent crime and adverse environmental impact.  These same organizations are currently producing counterfeit name brand pharmaceuticals.  There is no reason to expect that legalizing very high risk drugs will stop criminals from producing or selling them.

12:  No education about who may be at higher risk:  To an addiction psychiatrist seeing people after acute events the risks are obvious.  People who use intoxicants and get extremely euphoric or aggressive to the point that it impairs their judgment are clearly at high risk and should consider not using them at all. Unfortunately that self examination often does not happen until there has been a life changing event.  People with a strong family history of substance related problems are another high risk group.  Some individuals come to the conclusion that intoxicants are too risky for them to use.  I have heard this in many psychiatric evaluations: "My father and his father were alcoholics.  I knew I should probably not drink on that basis."  But this knowledge does not seem to be widely disseminated.  

Where does all of this leave us?  Not in a very good place. The DEA is describing its efforts to intercede in what is a massive effort originating from several countries to import highly dangerous substances into the United States. Although it is never overtly discussed this is clearly a national security problem. The immediate problems of deaths and morbidity from drug addiction seem to depend very little on how successful the DEA is in its efforts. The reason for that is the massive promotion of drugs at the cultural level both in direct advertising and false political philosophy equating drug use with freedom. It parallels the use of the Second Amendment to promote the widespread dissemination of firearms – even though there is no similar amendment for drug use. All the popular myths about drug use need to be actively countered and the advantages of a sober life need to be promoted. Those myths are a more subtle but equally dangerous threat to what the DEA is describing in this report.   

 

George Dawson, MD, DFAPA

 

References:

1:  Drug Enforcement Administration. National Drug Threat Assessment.  US Department of Justice.  May 2024.  57p.

2:  Case A, Deaton A. Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century. Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):15078-83. doi: 10.1073/pnas.1518393112. Epub 2015 Nov 2. PMID: 26575631; PMCID: PMC4679063

Abuse Deterrent Opioids - Are They The Solution?

I have a significant interest in opioids, specifically opioid use disorders or addiction to opioids.  We have seen an opioid epidemic in this country largely due to a naïve approach to chronic pain and exposing people unnecessarily to the risk of addiction.  At one level this is a failure of regulators who adopted the idea that chronic noncancer pain is best treated on a mass basis with opioids.  At another level it is a failure of American culture.  Americans are focused on abusable medications and they always have been.  This is not a recent phenomenon.  The reason that addictive drugs are regulated in the first place is that they were widely abused when they could be purchased over the counter from any pharmacy.  Advocates of legalizing drugs almost universally ignore that fact.  It is common to find people hoarding opioid prescriptions, giving them to their neighbors, and taking them for indications other than pain like insomnia, depression, or anxiety.  At the cultural level, opioids are generally regarded as magical pills that will cure whatever ails you.  But there is no such pill.

Physicians are not blameless in this process.  Around the turn of the 19th century, some physicians were maintaining large numbers of people in addiction as part of their medical practice.  At the turn of the 20th century, some physicians advocated “pain as the fifth vital sign” and the widespread practice of recording a patient’s pain rating in routine clinic visits with their vital signs.  In some cases this rating was mischaracterized as an “objective” measure like the other vital signs.  Any physician who is told that the pain rating is a “14” on a scale of 1-10, knows that little objectivity is involved.  The opioid epidemic is often viewed as a problem in physician education or a cognitive deficiency. I doubt that is the problem.  Every physician knows the basics about prescribing opioids by the time they leave medical school.  I can recall working in a clinic of chronic pain patients while I was a medical student in the 1980s.   In that clinic we prescribed hundreds of opioid prescriptions per month.  I also recall that none of those patients was ever asked about addiction or why they still wanted to take the medications even though their pain never seemed to improve.

This problem has also led to significant insights into the real function of the US Food and Drug Administration (FDA).  The FDA web site has three paragraphs on “What we do.”  The first paragraph highlights what I always thought was the main function of the agency:

“FDA is responsible for protecting the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation.”

That seems like a straightforward definition.  In practice it is more complicated.  The best example I can think of to illustrate that is the FDA approval of the sustained release, high-dose hydrocodone product Norco.  The FDA’s own scientific committee overwhelmingly recommended against approving this product in the midst of an opioid epidemic.  They were overruled and the product was approved based solely on the manufacturer meeting regulatory requirements.  Despite concern about getting medications to market fast enough it seems like there are few obstacle to opioid preparations that are basically old medications repacked in a new form.

The financial considerations in this field are significant.  Several years ago speculation was that any successful abuse-deterrent opioid formulation would be a billion dollar a year drug for that manufacturer.  That is highlighted by the number of recent approvals for these drugs noted in the table below.

The current market for abuse-deterrent opioids is estimated to be about $7 billion.  The global pain market is estimated to be worth about $50 billion growing at a rate of 10% annually.  From the table above it is apparent that this is basically a patent extension market.  All of the main ingredients in these medications are generic opioids that are very inexpensive on their own.  By putting them in a special formulation or combining them with opioid antagonists (naltrexone or naloxone) the manufacturers claim they are producing a medication that is less likely to be abused. Whether or not that ultimately happens is anybody’s guess.  I tried to pull up one of the more notable prodrug use web sites and have not seen those compounds and so far no suggestion on how to defeat the abuse deterrence.  There are historical precedents.   Abusable drugs generally follow a predictable course of oral use to smoking or insufflation (snorting) to intravenous use.  Breaking up that chain of events is one strategy that may lead to less severe drug use, but the fact remains that the original oral formulation is still a potent medication that can lead to addiction.  The original case in point was the reformulation of Oxycontin in 2013.  The original capsule could be breached and the contents snorted, smoked, or injected.  The reformulation put the oxycodone in a hydrogel making it less available for snorting, smoking or injecting.  The detailed package insert still says that this formulation and the original formulation place the user at risk for addiction.

What can be learned about the proliferation of abuse deterrent formulations?  There is a strong incentive both in terms of market size and low production costs.  All of the medications in the table are very inexpensive generics that are reformulated with an inexpensive antagonist or a different pill matrix.  The main safeguard is the FDA in terms of the total number of these medications on the market.  The FDA has the potential to decrease the incidence of opioid use disorders.  There is no evidence that is their strategy because they are approving medications over the objections of their own Scientific Committee.  In some cases they discuss post marketing surveillance as being a measure of whether the abuse deterrent medication is working.  Neither of those strategies would seem to be very likely to me.  It is well known that reports of signifiant medication related events are probably very low relative to the actual incidence of these events.  I have previously advocated for a pharmacosurveillance/data-mining solution that would produce results before the expected complications of opioid dependence and unintentional overdoses.  The FDA’s current approach seems to be that further education of physicians will solve the problem.  This is not a problem of physician education.

As the formulations of opioids continue to propagate, there needs to be an awareness that the FDA is not attempting to contain the number of new opioid products released and that a preventive approach is necessary and is more likely to save lives than waiting for people to report complications or waiting for the Drug Enforcement Agency to make arrests.  It is also time to consider what can be done at the level of American culture and focusing on some basic misperceptions that result in the overvaluation of opioids.  The idea that opioids can alleviate chronic pain, that they are the best treatment for chronic pain and that everyone can take them safely are primary among them.

There also needs to be a better understanding of opioid use disorders.  Recent stories in the popular press make it seem like addictions are easy problems to get over.  Just make a decision to stop and most people are able to.  Tell the old story about returning Vietnam vets and how easy it was for most of them to stop using heroin.  These are not the people who are seen in acute care settings or who are treated for drug overdoses.  Many of those people will say that they knew they were using a lot of the drug, that they were not thinking about suicide but they did not care if they lived or died because: "All I wanted to do was get high."

That is a powerful incentive for defeating abuse deterrent pills.



George Dawson, MD, DFAPA   


Supplementary 1: What is an New Drug Application (NDA)? This is the formal application to the FDA where the sponsor (usually a pharmaceutical company) proposes that a new drug be approved for sale and marketing in the United States. For detailed information from the FDA web site follow this link.   

  

Did The FDA Forget About America's First Amphetamine Epidemic?

That was the first thought I had when I read through the FDA release on the approval of Vyvanse for "binge-eating disorder".  I thought of the rotation I did on the Eating Disorder service at the University of Minnesota with some of the top experts in anorexia nervosa and bulimia.  In those days the residents admitted the patients and also rotated through the outpatient clinic where they saw new cases of eating disorders and developed treatment plans with the supervision of the attendings.  We talked about a lot of binge eating, since binge eating was a critical aspect of bulimic behavior.  ""Do you ever consume an amount of food large enough that it might be embarrassing if someone else found out?" and getting the details of that specific behavior was one of my standard interview questions.  It was clear that the binge eating of bulimia was a volume and rate task.  I would hear about large amounts of diet soda and popcorn being consumed in order to complete the cycle.

In the intervening 2 decades the only real changes was the addition of bulimia nervosa a composite of bulimic and anorexic behaviors.  That is until the advent of Binge-Eating Disorder in DSM-5.  In addition to a binge definition not much different from the one I used in 1984 eating an amount of food that is "definitely larger than what most people would ingest in the same period and similar circumstances" there is loss of control, and behavioral specifiers for rapidity, physical sensations, appetite, and psychological reactions to the binge eating.  Marked distress needs to occur and it cannot be part of another eating disorder.  The time specifier is that it needs to occur at least once a week for 3 months.  A summary of the FDA release about the indication states:

 “Binge eating can cause serious health problems and difficulties with work, home, and social life,” said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “The approval of Vyvanse provides physicians and patients with an effective option to help curb episodes of binge eating."   

The DSM-5 has a point prevalence estimate of 1-1.5% in women with a peak in late adolescence and early adulthood.  That same section in the DSM-5 suggests that the course is variable:

"However, over longer-term follow-up, the symptoms of many individuals appear to diminish with or without treatment, although treatment clearly impacts outcome. Periods of remission longer than 1 year are associated with better long-term outcome." (DSM-5 p 351-352)

As far as I can tell, the evidence supporting the fast tracked application for Vyvanse is a typical 8 week clinical trial that looked at remission and reduction in binge eating rates in a multicenter study of 255 individuals (1).  Both the 50 and 70 mg doses were effective.  The publication of the research coincides fairly closely with the FDA release.  Searching through the FDA web site reveals no information about the opinion of a Scientific Committee and whether there was any consensus on the decision or concerns about the addictive potential of the drug.  

The pharmacology of the Vyvanse is interesting.  It is a prodrug - lisdexamfetamine that is a conjugate of lysine and amphetamine.  After it is absorbed into the circulation it is hydrolyzed to lysine and amphetamine.  There has always been some debate about whether this prodrug approach confers a decreased likelihood that the compound can be abused or used in an addictive manner.  Most addiction psychiatrists will tell you that it can and  the FDA approved package insert confirms the fact that it has significant abuse potential.   It is a Schedule II drug according to the DEA.

The lesson of the first amphetamine epidemic is that these drugs will be prescribed, to the point that there is very high demand and production of the drug.  Widespread health consequences were noted from overprescribing stimulants for questionable indications (weight loss, nasal congestion, depression, anxiety, psychosomatic complaints).  During the peak of this epidemic (1969) the total number of 10 mg amphetamine doses was about 25 million.  This was not exceeded until about 2005 and then only as a combination of amphetamine and methylphenidate.  As a psychiatry resident in the 1980s, I was still seeing obese people who had not lost a pound using very high doses of amphetamines.  The weight loss indication was subsequently banned in order to establish some limits on the overprescription of these compounds.  In other words, they were taking the drug because of an addiction rather than using it for any therapeutic effect.  It is clear that the prescription of controlled substances for diagnoses that are based on subjective findings is a recipe for epidemics of addictive drugs both in terms of total prescriptions, escalating use, and diversion.  Stimulant medications have the additional allure as possible performance enhancing drugs and are widely diverted for that purpose.

In that context, it would seem that the FDA would need to come up with a clear rationale for using a Schedule II drug to treat what may be a time limited disorder or a disorder that responds to non-medical therapies.  The complex nature of medications that have addictive potential needs to be recognized.  The prescription of these compounds takes more than rote knowledge. At the minimum there needs to be strict pharmacosurveillance on how this drug is prescribed and flags need to be in place for trends indicating that the prescriptions are starting to exceed the known prevalence of the disorder or the dose ranges are higher than recommended and/or combined with short acting stimulants.  These are all common problems seen in the overprescription of controlled substances.

Passive post marketing surveillance can no longer be considered a viable option for stopping the overprescription of controlled substances.   Waiting for intervention by law enforcement when problems have already begun is an approach from the 1960s.  In an era when data mining is commonplace, the FDA can do a lot more than get drugs out into the marketplace and wait to see what happens.         

George Dawson, MD, DFAPA

1: McElroy SL, Hudson JI, Mitchell JE, Wilfley D, Ferreira-Cornwell MC, Gao J, Wang J, Whitaker T, Jonas J, Gasior M. Efficacy and Safety of Lisdexamfetamine for Treatment of Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Jan 14. doi: 10.1001/jamapsychiatry.2014.2162. [Epub ahead of print] PubMed PMID: 25587645.

2: Nutt, David, Leslie A King, William Saulsbury, Colin Blakemore. Development of a rational scale to assess the harm of drugs of potential misuse. The Lancet 2007; 369:1047-1053. PMID 17382831;doi:10.1016/S0140-6736(07)60464-4

Supplementary 1:  The following graph is from Wikimedia Commons and it is public domain.  It is a derivative work of reference 2 above and a complete description is available at this link.  I could find no author to cite.

Supplementary 2:  Almost on cue I noticed the first banner ads for Binge-Eating Disorder today (2/12/2015).  It is advertised as a "real medical disorder" and is a brief informational film.  It has a spokesperson who talks about her experience with the disorder and refers the interested viewer to the company web site at BingeEatingDisorder.com.  It carefully coaches people in how to talk with their doctor.  The pharmaceutical company and manufacturer is listed at the bottom on the page.  The graphic of a pizza slice over a drawing of a brain varies in different views.  I don't know exactly what that means.  It suggests psychological therapies for B.E.D. and does not mention Vyvanse.  But let's face it - when people read there is a pill for their eating problem and it is an amphetamine - how many people will be asking for the psychological therapies?