Xylazine – Another Dangerous Street Drug

Xylazine is the latest veterinary tranquilizer to be sold as a street drug. It has no approved human uses.  It is used as both a light and general anesthetic for horses depending on the extent of the surgery. Xylazine is a presynaptic alpha-2 adrenoceptor agonist inhibiting the release of norepinephrine from synaptic vesicles. This leads to decreased postsynaptic activation of adrenoceptors, inhibited sympathetic activity, leading to analgesia, sedation and anxiolysis.  This mechanism of action is also seen with clonidine and dexmedetomidine.  Xylazine has low potency and affinity for Alpha-2 receptor adrenergic receptors. It has been demonstrated by the use of a knock out genetic mouse model that the clinical effects are mediated through the alpha-2A receptor subtype (5).

Alpha-2 receptor adrenergic receptor (AR) profiles are complicated by the fact that there are 4 subtypes with central, peripheral and behavioral effects but very little seems to be written about the D subtype so I have not included it here.  The general associated mechanisms include a decrease in adenyl cyclase activity, suppressed voltage gated calcium currents, increased potassium currents and increased mitogen-activated protein kinase (MAP kinase) activity. At steady state the α-2A and α-2B receptor types are at the cell surface and the α-2C type is at the cell surface and intracellular.  Some drugs like clonidine and guanfacine promote α-2A internalization. The author (3) of the review suggests that this may account for the unique duration of signaling. α-2AR trafficking and signaling also undergoes complex regulation by a number of factors including protein kinases, G protein coupled receptors (GPCRs), and scaffolding proteins.  A table of receptor affinities for various drugs are listed below. These affinities are primarily from reference 2 and generally represent results for human cloned receptors of the averages of several experiments. Please note the very low affinities for xylazine. I have tried to corroborate these numbers from outside sources and have not been successful. If you have better affinities for xylazine please email me or post them here in the comments section.  

From a pharmacodynamic standpoint there are several relevant Alpha-2 AR polymorphisms that have been tentatively linked disease states like ADHD and hypertension. They have also been studied in heart rate, heart rate variability, blood pressure control, obesity and insulin resistance (4). As expected, these polymorphisms also effect drug response.  

Although Xylazine is approved only for veterinary uses, reports of human use and accidental or inadvertent overdoses began to appear in the 1980s.  A review of initial reports looking at the compound as an adulterant that was done in 2014 (7) and concluded that half of the human overdoses resulted in death.  

Central effects of alpha 2 agonists, results in decreased sympathetic output and resulting imbalances in the peripheral autonomic nervous system.  Decreased sympathetic output leads to the expected effects of bradycardia, hypotension, sedation and decreased level of consciousness. Unopposed vagal parasympathetic effects can lead to increasing heart block and arrhythmias.  

In addition to the central effects of α-2 agonists there are also peripheral effects.  A common α-1 and α-2 agonist used peripherally is oxymetazoline that is used as a topical nasal decongestant. It exhibits very high affinity for both receptors and the following K_is  α-2A (7.24 nM), α-2B (483.5 nM), α-2C (144.07 nM), α-1 (402.75 nM).  Peripheral α-2 adrenergic effects can lead to increased systemic vascular resistance due to effects at the level of arterioles. This is important from a toxicological perspective because it can cause hypertension and is probably the mechanism leading to soft tissue necrosis at injection sites.

The epidemiology of xylazine use is discussed in a few studies at this point (7,12,13). The original paper suggested it may have started in Puerto Rico and spread Philadelphia with the highest prevalence of overdoses in eastern states.  It is well described at this point both in terms of overdoses and as an adulterant when it is added to heroin, fentanyl, cocaine, methamphetamine, alcohol or combinations like heroin + cocaine. There are expected synergies with opioids including a depressed level of consciousness, and decreased respiratory drive. Synergies with stimulants would include increased likelihood of cardiac arrhythmias, hypertension, and tissue necrosis.

The CDC recently published a study of xylazine in Cook County, IL (Chicago area) in MMWR (12).  The study ran from January 2017 to October 2021.  Xylazine associated deaths were defined as positive post-mortem toxicology in any substance related death where the intent was unintentional, undetermined or pending. The authors identified 236 xylazine associated deaths that increased over the study period and are graphed below. The graph on the right is the percentage of fentanyl associated deaths involving xylazine by month. That graph peaks at 11.4% in October. Overall, fentanyl or its metabolites was present in 99.2% of xylazine associated deaths. The authors point out that naloxone does not reverse the effects of xylazine but it should be administered for any suspected opioid use in a polypharmacy toxidrome. They also state that better surveillance for this compound is probably indicated.  

 

The toxidromes from these drug combinations can be complex so that on a clinical basis it will be hard to tell if the patient you are seeing has used xylazine. I was fortunate enough to attend a Hennepin County Medical Center Addiction Medicine Journal Club on 4/5/2022. In that presentation the pharmacology, clinical effects and toxicology of xylazine were discussed. The cases presented all had xylazine combined with other substances and severe necrosis of the lower extremities in two cases and hand and wrist in the other. In one case the patient no longer had venous access and was injecting into the area of necrosis.  All of these patients required skin grafting wanted to leave the hospital after the acute phase of intoxication had passed. In these cases, the transition to detoxification and maintenance medications is complicated because of the possible synergy between opioids and α-2 adrenergic agonists and the question of rebound or withdrawal from preadmission use of xylazine. The question of Takotsubo cardiomyopathy was discussed because some patients the literature were described as using xylazine. Rebound or withdrawal from xylazine and the associated rapid increase in catecholamines was discussed as a potential mechanism. A toxicologist attending the meeting also pointed out that with overdoses the α-2 adrenergic agonists can cause hypertension by peripheral effects and this has caused some acute cardiac problems. That toxicologist was also familiar with local testing for xylazine and it was not currently being done. He pointed out that a half life of 5 hours was determined in humans as contrasted with a few minutes in several animal species.   He suggested that in the case of a patient unresponsive to high dose naloxone, without hypercapnia via arterial blood gases, and normal brain imaging it would be reasonable to request xylazine toxicology.

In an interesting development, the FDA recently approved a dexmedetomidine sublingual film for the treatment of acute agitation in schizophrenia and bipolar disorder (14).  Dexmedetomidine has been available for intravenous use for 20 years with the indication “sedation of non-intubated patients prior to and/or during surgical and other procedures” (15).  It also has a place in critical care medicine – addressing all three aspects of the ICU triad of pain, agitation, and delirium (16). The film comes in 120 mcg and 180 mcg doses with a schedule in the package insert with dosing for adults and geriatric patients with and without varying degrees of hepatic impairment.  The clinical trials in the package insert describe the medication as effective for this indication. As a psychiatrist who spent most of his career in acute care there are fairly frequent situations where medications that are typically used to treat agitation (antipsychotics and benzodiazepines) do not work – even at high doses. It will be interesting to see if acute care psychiatrists find dexmedetomidine preparation useful. When I ran into that situation it was typically cases of severe mania with agitation or delirious mania with catatonia and the only available option was conscious sedation by anesthesiology. The other unknown at this point is how effective this medication will be over time.  The package insert specifies a maximum of two or three doses.  Clinicians will be on their own after that. It reminds me of how another α-2 adrenergic agonist – clonidine is currently used for anxiety, agitation, and insomnia. Many patients experience it as transiently effective until a more sustained preparation (typically a transdermal patch) is used.  

The appearance and gradual increase in xylazine as a street drug is not good news.  It is clearly used as an adulterant in both opioids and stimulants.  Its use can result in severe complications and death. The surveillance for this compound is not good at this time and clinicians have to have a high index of suspicion to request toxicology for it. People with substance use disorders need to be educated about this compound and its use as an adulterant and that deciding to use it with an opioid or other CNS depressants (including alcohol) is very dangerous and needs to be avoided. Using it with stimulants can also have significant negative effects.  At this point it is also an unknown danger because like fentanyl - it can be sold as anything.

 

George Dawson, MD, DFAPA

 

References:

 

1:  Törneke K, Bergström U, Neil A. Interactions of xylazine and detomidine with alpha2-adrenoceptors in brain tissue from cattle, swine and rats. J Vet Pharmacol Ther. 2003 Jun;26(3):205-11. doi: 10.1046/j.1365-2885.2003.00466.x. PMID: 12755905.

2:  PDSP Ki Database referenced as The Multiplicity of Serotonin Receptors: Uselessly diverse molecules or an embarrassment of riches? BL Roth, WK Kroeze, S Patel and E Lopez: The Neuroscientist, 6:252-262, 2000

3:  Wang Q.  α2-Adrenergic Receptors. In: Primer on the Autonomic Nervous System, Third Edition.  Robertson D, Biaggioni I, Burnstock G, Low PA, Paton JFR. 2012. Elsevier, Amsterdam. 55-58.

4:  Matušková L, Javorka M. Adrenergic receptors gene polymorphisms and autonomic nervous control of heart and vascular tone. Physiol Res. 2021 Dec 30;70(Suppl4):S495-S510. doi: 10.33549/physiolres.934799. PMID: 35199539.

5:  Kitano T, Kobayashi T, Yamaguchi S, Otsuguro K. The α_2A -adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine. J Vet Pharmacol Ther. 2019 Mar;42(2):243-247. doi: 10.1111/jvp.12724. Epub 2018 Nov 11. PMID: 30417462.

6:  Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017 Aug;56(8):893-913. doi: 10.1007/s40262-017-0507-7. PMID: 28105598; PMCID: PMC5511603.

7:  Ruiz-Colón K, Chavez-Arias C, Díaz-Alcalá JE, Martínez MA. Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature. Forensic Sci Int. 2014 Jul;240:1-8. doi: 10.1016/j.forsciint.2014.03.015. Epub 2014 Mar 26. PMID: 24769343.

8:  Sinclair MD. A review of the physiological effects of alpha 2-agonists related to the clinical use of medetomidine in small animal practice. Can Vet J. 2003 Nov;44(11):885-97. PMID: 14664351; PMCID: PMC385445.

9:  Giovannitti JA Jr, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. 2015 Spring;62(1):31-9. doi: 10.2344/0003-3006-62.1.31. PMID: 25849473; PMCID: PMC4389556.

10:  Kanagy NL. Alpha(2)-adrenergic receptor signalling in hypertension. Clin Sci (Lond). 2005 Nov;109(5):431-7. doi: 10.1042/CS20050101. PMID: 16232127.

Activation of alpha(2A)-ARs in cardiovascular control centres of the brain lowers blood pressure and decreases plasma noradrenaline (norepinephrine), activation of peripheral alpha(2B)-ARs causes sodium retention and vasoconstriction, whereas activation of peripheral alpha(2C)-ARs causes cold-induced vasoconstriction

11:  Talke P, Lobo E, Brown R. Systemically administered alpha2-agonist-induced peripheral vasoconstriction in humans. Anesthesiology. 2003 Jul;99(1):65-70. doi: 10.1097/00000542-200307000-00014. PMID: 12826844.

12:  Chhabra N, Mir M, Hua MJ, et al. Notes From the Field: Xylazine-Related Deaths — Cook County, Illinois, 2017–2021. MMWR Morb Mortal Wkly Rep 2022;71:503–504. DOI: http://dx.doi.org/10.15585/mmwr.mm7113a3

13:  Friedman J, Montero F, Bourgois P, Wahbi R, Dye D, Goodman-Meza D, Shover C. Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis. Drug Alcohol Depend. 2022 Apr 1;233:109380. doi: 10.1016/j.drugalcdep.2022.109380. Epub 2022 Feb 26. PMID: 35247724.

14:  FDA Package Insert. IGALMITM (dexmedetomidine) sublingual film, for sublingual or buccal use.  April 5, 2022.  https://www.igalmihcp.com/igalmi-pi.pdf

15:  FDA Package Insert.  Dexmedetomidine hydrochloride injection. 1999. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206628s000lbl.pdf

16:  Reade MC, Finfer S. Sedation and delirium in the intensive care unit. N Engl J Med. 2014 Jan 30;370(5):444-54. doi: 10.1056/NEJMra1208705. PMID: 24476433.

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