Upon conclusion of this course, students will be able to:
Understand the scope of alcohol and cocaine use and their effects on ED visits;
Comprehend the various routes of administration and effects of alcohol ingestion;
Demonstrate knowledge of cocaine use and overdose interventions;
Understand recent ‘designer drugs’ and chemically modified narcotics.
Drug overdoses are routinely seen in trauma bays and emergency departments worldwide. The increasingly complex methods employed to develop and consume drugs make detection of side effects and potential interactions with other drugs difficult. Common substances of abuse are now being ingested in alternative, more hazardous ways, while designer drugs are being chemically modified to enhance their euphoric effects. These various modifications have rendered modern drug screening tests almost obsolete, placing medical professionals in a formidable position.
The purpose of this two-part review is to educate emergency medical personnel on trends in drug use and provide an overview of the physiologic effects associated with these substances, as well as touch on some potential adverse drug-drug interactions in order to allow for proper identification and treatment when patients present to the ED. This first part will cover alcohol, cocaine, and chemically modified/“designer” drugs; the second, next month, will look at prescription drugs and drug interactions.
According to the World Health Organization’s 2019 World Drug Report, 270 million people have used drugs in the previous year, and 35 million are estimated to be suffering from drug use dsorders.1 The 1984 death of New York teen Libby Zion, notwithstanding its legacy on medical education reform, was at its core a failure to recognize the potential of significant drug interactions, resulting in a fatal outcome.2
Never has this danger been more imminent than in the present day, when drugs of abuse are readily available, highly varied, and often unknown to medical professionals. It behooves clinicians, especially medical personnel at the frontiers, to familiarize themselves with some of the substances they are likely to encounter and recognize potentially lethal reactions and interactions with other drugs.
Alcohol and cocaine have long been mainstays of ED visits and may appear pedestrian to seasoned practitioners. However, they may be consumed in alternative and dangerous forms that can result in serious and unanticipated clinical outcomes.
Alcohol ingestion, while legal in the U.S., is responsible for nearly 88,000 deaths a year and is the fourth-leading cause of preventable death.3 The dangers of alcohol-related injuries, diseases, and deaths are increasing with the onset of observable trends in nontraditional consumption. These modified mechanisms of ingestion allow alcohol to be absorbed directly into the bloodstream, resulting in a quicker and more intense intoxication.
For instance, alcohol inhalation is a dangerous trend where vaporized alcohol can be created by pouring over dry ice or freebasing over a flame and inhaling the vapors directly.4 Direct inhalation into lungs eliminates first-pass hepatic metabolism, leading to a more rapid and potent intoxication.4 In addition to respiratory tract damage, it significantly increases the risk of alcohol poisoning.
Compounding the issue with inhalation is the mistaken belief that this method of consumption does not involve caloric intake, which inadvertently makes it an attractive alternative for certain populations.4 Similar trends to lower caloric intake involve sublingual absorption, where alcohol is held in the mouth for an extended period of time, then spit out.
Other reported trends in alcohol consumption are “butt chugging” (enemas), “tamponing” (vaginal or anal), “boofing” (insertion into the anus with syringe), “vodka eyeballing,” and snorting through straws—all of which result in alcohol and drugs entering the bloodstream rapidly, resulting in potent intoxication.5 Risks include alcohol poisoning, along with drying, bleeding, burning, and infections of the vaginal and anal canals. Vodka eyeballing irrefutably results in intense pain, corneal damage, and can lead to permanent blindness; it warrants an urgent ophthalmologic consult.6
The aforementioned methods of absorption make it challenging to track the intake amount. Treatment for acute toxicity is mostly supportive care and involves ensuring adequate hydration.7
It has become an increasing fad to combine alcohol with other substances. A current trend is blending it with caffeinated beverages to raise drinking stamina by increasing stimulation and decreasing sedation.8 This can lead to overconsumption of alcohol due to underestimation of intoxication level.
Researchers evaluated if mixing alcohol with energy drinks had a potentially lethal priming effect.9 In a subsequent study they concluded that consumption of an energy drink and alcohol cocktail may increase the desire to continue drinking, and that subjects drank at a faster pace than their counterparts who drank solely alcohol.10 Caffeine is an adenosine receptor antagonist and works primarily by blocking the A2A receptor that stimulates GABA neurons. It also serves as a stimulant due to being an indirect agonist of noradrenaline.8 Alcohol in combination with caffeine has a clinical presentation of tachycardia, dehydration, tremors, high blood pressure, and agitation, along with elevated blood alcohol concentration levels and increased possibility of acute alcohol poisoning.9
There are trends to permeate food substances with alcohol, including pizza, gummy candies, whipped cream, cupcakes, and popsicles. Substitutes are also still being consumed and may include cough syrup, mouthwash, hand sanitizer, and acetone (nail polish remover).11
Of note, an increasing number of case studies describe patients presenting with dizziness, slurred speech, and significant blood alcohol levels following consumption of carbohydrate-rich meals. Evaluation for auto-brewery syndrome, gut fermentation, is warranted in these unique cases.12–14
Another street drug readily recognized for its abuse potential is cocaine, which was once utilized by the medical profession for its anesthetic effects but has since been abused for the euphoria it induces.
Exacerbating the issue is the adulteration of the drug with unknown “cutting” agents added to make its sale more profitable. Cocaine cut with levamisole, an anthelmintic medication known to cause agranulocytosis, vasculitis, and skin necrosis, is of particular concern.15 In 2009 the DEA reported 69% of cocaine entering the country contained levamisole at a concentration of nearly 10%, compared to less than 1% concentration in 2001.15
Another alarming aspect of cocaine consumption is a trend that combines cocaine with other harmful drugs, notably heroin. Termed a “speedball,” the cocaine/heroin combination creates a euphoric high and feeling of relaxation without the side effects of drowsiness and sedation usually associated with depressants. This can be deadly, as the combination of the stimulant/depressant can cause the user to feel less high, leading to an increase in consumption. Death is most commonly caused by a delayed overdose response to the stimulant, since the stimulant is shorter-lasting. This causes the user to take further doses, leading to a fatal opioid overdose.16
Acute toxicity warrants urgent medical attention, and management is based on presentation. Psychomotor agitation and cardiovascular involvement including hypertension require benzodiazepine administration, along with nitroglycerin, nitroprusside, or phentolamine in refractory cases.17 Withdrawal symptoms can manifest after abrupt cessation following prolonged cocaine use as depression, anhedonia, fatigue, tremors, and chills, but they are rarely serious enough to warrant medical treatment.18
Currently no approved pharmacologic agents exist for the management of chronic cocaine addiction, though inpatient and outpatient rehabilitation programs have been helpful in treatment.
Substances of abuse are becoming more sophisticated and dangerous due to the constant modification of their chemical makeup as a means to both increase the intensity of intoxication and evade legal prohibitions. This has added danger of regularly rendering medical knowledge obsolete.
Synthetic marijuana, known colloquially as spice or K2, is a synthetic cannabinoid that is becoming an escalating problem among the homeless and mentally ill population. In contrast to partial agonist properties found in marijuana, spice acts as a full CB1 and CB2 agonist, increasing toxicity.19 Clinical effects of smoking spice include diaphoresis, anxiety, delusions, agitation, and paranoia that may become severe enough to induce suicide.20
Synthetic marijuana is not detected on traditional urine drug panels, as the metabolites do not react with THC, the active component of regular marijuana. Evidence has shown that synthetic cannabinoids can be detected by gas chromatography-mass spectrophotometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS), but these techniques are rarely employed in the clinical setting and do not dictate management.20 Treatment is mainly supportive and predicated on clinical manifestations, with potential administration of benzodiazepines for agitation and/or seizures.
MDMA (3,4-methylenedioxy-N-hydroxy-N-methylamphetamine), also known as ecstasy or molly, has increased in prevalence on the streets while its molecular purity has decreased. Originally intended as an appetite depressant,21 it is now desirable for its intoxicating effects.22 On a molecular level MDMA induces the release of many excitatory neurotransmitters (serotonin, norepinephrine, dopamine) while simultaneously inhibiting serotonin reuptake.21,22 It is a familiar presence at raves and is typically sold in powdered or tablet formulations but can be ingested nasally, orally, or intravenously.
MDMA can be laced with other substances, notably LSD, cocaine, ketamine, and methamphetamine. The pleasurable effects of MDMA include feelings of euphoria, hypersexual tendencies, and increased energy. The desired effects are typically felt within 30 minutes of consumption and last for 4–6 hours.22
Minor adverse reactions include tachycardia, anxiety, bruxism, ataxia, and hypertension with normal doses. The vital signs of patients with MDMA intoxication can include hypertension, tachycardia, and hyperthermia. MDMA can be detected in urine and blood samples with specific assays, but testing is not recommended, as management should be dictated by clinical presentation.23 If a recent exposure (under an hour) and the patient has an adequately protect airway, decontamination with activated charcoal may be attempted.23
More severe side effects include hyperthermia and hypertension, organ failure, brain damage, and death. Manage severely hypertensive patients with benzodiazepines, taking care to avoid beta blockers to prevent unopposed alpha-adrenergic stimulation. Benzodiazepines can also be administered for agitation, while any cardiovascular complaints warrant an ECG. Hyperthermia can lead to rhabdomyolysis and should be treated by submergence in an ice bath.23
Serotonin syndrome, the cause of Libby Zion’s death,2 is a potential serious side effect of MDMA intoxication. Serotonin syndrome is caused when there is increased serotonergic activity in the CNS caused by inadvertent drug interactions. Drugs that metabolize through the same enzyme (CYP2D6) as MDMA, such as codeine, hydrocodone, dextromethorphan (known as DXM), and dimethyltryptamine (DMT), pose the most significant overdose threat, particularly those with low overdose thresholds. Of note, tamoxifen, which is traditionally prescribed to treat breast cancer and has been used in the bodybuilding community, is a known CYP2D6 substrate.24,25
The common symptoms include a triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities.26 Hyperthermia caused by serotonin syndrome can be fatal and should be first treated by using benzodiazepines and cooling the patient if necessary. If this fails, intubation and paralysis should be the next step to combat hyperthermia.26 Besides MDMA, many other current synthetic street drugs also have serotonergic effects.
Methylenedioxypyrovalerone (MDPV), better known as bath salts or synthetic cathinone, is a psychoactive drug first noted for its abuse potential in 2010.27 It may be snorted, injected, inhaled, or swallowed as a replacement for cocaine or methamphetamine. While the mechanism of intoxication is not fully understood, the main physiologic effects occur due to inhibition of norepinephrine-dopamine reuptake.20 The desired high causes a sense of euphoria and sexual stimulation, along with increased energy, concentration, alertness, and sociability. Negative side effects include tachycardia, bruxism, hypertension, paranoia, suicidal thoughts, violent behavior, hallucinations, and death.20
As with other drugs, the original formula has been modified to result in dangerous sequelae, including documented brain damage and life-threatening hyperthermia, with recorded temperatures climbing past 42.2ºC. Most dangerous of all, bath salts have the allure of, and are marketed as, legal highs due to the limited ability of current standard urine and blood drug screens in detecting MDPV (although specialized kits can).20 Similar to MDMA intoxication and other sympathomimetic drugs of abuse, supportive care is the cornerstone of therapy, with concurrent administration of benzodiazepines for hypertensive control and agitation as needed. The treatment of hyperthermia and other serotonergic effects is similar to MDMA.
Another synthetic drug with a molecular structure similar to MDPV is Alpha-PVP (flakka or gravel). The low cost (reportedly only $5 a hit), coupled with ready availability via bulk purchasing, is a recipe for serious abuse.27 Flakka can be snorted, smoked, injected, or swallowed with a high similar to bath salts but stronger. The euphoric high poses a powerful attraction but does not prevent negative side effects, including delusions, psychosis, and agitated delirium.28 Agitated delirium is caused by an increased influx of sympathetic activation. Flakka is known to flood the brain with dopamine. Similar to MDPV, flakka is only identified via use of specialized GC-MS and LC-MS techniques. Clinical management is aggressive use of benzodiazepines and antipsychotics. Some patients may incur permanent damage.28
Krokodil, first reported in Russia with alleged appearances in the United States, is yet another synthetic version of a natural compound: opioids.29 The primary component is desomorphine, a derivative of morphine with higher addictive potential, which produces a substance that acts as a replacement for heroin due to its elevated potency and low cost. Desomorphine is combined with common household entities such as lighter fluid, red phosphorus, iodine, and cleaning oil.29 The resulting product is a highly contaminated intravenous/subcutaneous injection that can cause damage to the vasculature and multi-organ failure.29
Though desomorphine can be detected in the blood within hours and in urine within a couple of days after initial exposure, testing is specialized and often not available. Diagnosis depends on clinical presentation and patient history of substance use. Clinical presentation includes ulcers, cellulitis, greenish skin scales secondary to chronic infections, and skin necrosis. Management often involves wound care, intravenous antibiotics, surgical debridement, and amputation. Given its high addictive potential, krokodil withdrawal can be severe, requiring medical supervision and intense pain management. Mean survival time in chronic users is estimated around two years after first use of krokodil.29
The latest designer drug, known as NBOMe, is a synthetic phenethylamine advertised as a legal high. NBOMe has an affinity 10 times greater than serotonin for the 5-HT2A receptor, resulting in serotoninlike syndrome.30 It is typically administered onto blotting paper and taken sublingually but can be ingested via smoking or snorting as well. The desired high typically lasts for 4–6 hours and is similar to other classic hallucinogens with reports of euphoria, hallucinations, and dissociations with reality.30 Patients typically present to the ED with symptoms of serotonergic and sympathomimetic activations, including hypertension, tachycardia, confusion, agitation, and hallucinations.31 No routine testing for NBOMe is available, and diagnosis relies on maintaining a high index of suspicion. While no specific antidote exists for NBOMe poisoning, treatment includes supportive care and management of agitation with benzodiazepines.31
Dimethyltryptamine (DMT, dimitri, or businessman’s special) spiked in popularity among young American adults in the middle of the last decade.32 It is a naturally occurring compound with hallucinogenic properties found in South American plants. Users experience intense visual hallucinations, depersonalization, and auditory distortions. Physical presentation may include hypertension, increased heart rate, agitation, seizures, and dilated pupils. Historically it was ingested as a tea, ayahuasca (colloquially known as aya, yagé, hoasca), during tribal ceremonies in the Amazonian rainforest, where DMT is brewed in combination with caapi. Caapi acts as an MAO inhibitor and enhances serotoninergic activity. In addition, DMT can be smoked, snorted, ingested, or injected.
The effects of DMT when taken alone are short-acting; the onset of symptoms begins 1.5–2 minutes after injection or inhalation, and effects are completely resolved at the 30-minute mark.33 A typical dose of DMT is 60 mg, and a dose 91 times greater than that would be required to overdose.34 Treat overdoses by managing agitation and anxiety and monitoring vital signs, including core temperature, for possible serotonin syndrome. Consider activated charcoal if the drug was ingested orally. It is not detected in standard urine toxicology screen, and there is no known antidote.3
1. World Drug Report 2019, https://wdr.unodc.org/wdr2019/
2. Lerner BH. A Case That Shook Medicine. Washington Post, 2006 Nov 28, www.washingtonpost.com/wp-dyn/content/article/2006/11/24/AR2006112400985.html.
3. National Institute on Alcohol Abuse and Alcoholism. Alcohol facts and statistics, www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics.
4. Glatter R. The dangers of “smoking” alcohol. Forbes, 2013. www.forbes.com/sites/robertglatter/2013/06/21/the-dangers-of-smoking-alcohol/.
5. Rose B. Seven insane ways to get drunk without drinking. Gizmodo, 2012 Jul 6, http://gizmodo.com/5923902/seven-insane-ways-to-get-drunk-without-drinking.
6. Bosmia AN, Griessenauer CJ, Tubbs RS. Vodka eyeballing: A potential cause of ocular injuries. J Inj Violence Res, 2014; 6(2): 93–4.
7. UpToDate. Ethanol Intoxication in Adults, www.uptodate.com/contents/ethanol-intoxication-in-adults.
8. Marczinski CA, Fillmore MT. Clubgoers and their trendy cocktails: Implications of mixing caffeine into alcohol on information processing and subjective reports of intoxication. Exper Clin Psychopharm, 2006; 14(4): 450–8.
9. Cleary K, Levine DA, Hoffman RS. Adolescents and young adults presenting to the emergency department intoxicated from a caffeinated alcoholic beverage: A case series. Ann Emerg Med, 2012; 59(1): 67–9.
10. Marczinski CA, Fillmore MT, Maloney SF, Stamates AL. Faster self-paced rate of drinking for alcohol mixed with energy drinks versus alcohol alone. Psychol Addict Behav, 2017; 31(2): 154–61.
11. McKeever A. 13 Ways to Get Drunk Without Actually Drinking. Eater, www.eater.com/2012/11/27/6531095/13-ways-to-get-drunk-without-actually-drinking.
12. Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisole-contaminated cocaine: An emerging public health challenge. Mayo Clin Proc, 2012; 87(6): 581–6.
13. RehabCenter.net. The Dangers of Using Heroin with Cocaine (Speedball), www.rehabcenter.net/dangers-heroin-cocaine-speedball/.
15. UpToDate. Cocaine Use Disorder in Adults: Epidemiology, Pharmacology, Clinical Manifestations, Medical Consequences, and Diagnosis, www.uptodate.com/contents/cocaine-use-disorder-in-adults-epidemiology-pharmacology-clinical-manifestations-medical-consequences-and-diagnosis.
16. Fantegrossi WE, Moran JH, Radominska-Pandya A, Prather PL. Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ9-THC: Mechanism underlying greater toxicity? Life Sciences, 2014; 97(1): 45–54.
17. Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, spice), synthetic cathinones (bath salts), Kratom, salvia divinorum, methoxetamine, and piperazines. J Med Toxicol, 2012; 8(1): 15–32.
18. Burgess C, O’Donohoe A, Gill M. Agony and ecstasy: A review of MDMA effects and toxicity. Eur Psychiatry, 2000; 15(5): 287–94.
19. Hall AP, Henry JA. Acute toxic effects of ‘ecstasy’ (MDMA) and related compounds: Overview of pathophysiology and clinical management. Br J Anaesth, 2006; 96(6): 678–85.
22. Spiller HA, Ryan ML, Weston RG, Jansen J. Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. Clin Toxicol (Phila), 2011; 49(6): 499–505.
23. Crespi C. Flakka-Induced prolonged psychosis. Case Rep Psychiatry, 2016; 3460849.
24. California Poison Control System. Krokodil, https://calpoison.org/news/krokodil.
25. Lawn W, Barratt M, Williams M, Horne A, Winstock A. The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample. J Psychopharmacol, 2014; 28(8): 780–8.
26. Palamar JJ, Le A. Trends in DMT and other tryptamine use among young adults in the United States. Am J Addict, 2018; 27(7): 578–85.
27. Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry, 1994 Feb; 51(2): 98–108.
28. Strassman RJ. Human psychopharmacology of N,N-dimethyltryptamine. Behav Brain Res, 1996; 73(1-2): 121–4.
29. Toxicology Data Network. N,N-dimethyltryptamine Human Health Effects, https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+8017.
30. Madsen GR, Petersen TS, Dalhoff KP. NBOMe hallucinogenic drug exposures reported to the Danish Poison Information Centre. Dan Med J, 2017; 64(6): A5386.
31. Keilman J. Chronic pain patients say opioid crackdown is hurting them. Chicago Tribune, 2017 Jun 5; www.chicagotribune.com/lifestyles/health/ct-opioid-patients-backlash-met-20170603-story.html.
32. National Institute on Drug Abuse. Opioid overdose crisis, www.drugabuse.gov/drugs-abuse/opioids/opioid-crisis.
33. Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin use in the United States: A retrospective analysis of the past 50 years. JAMA Psychiatry, 2014; 71(7): 821–6.
34. Carlson RG, Nahhas RW, Martins SS, Daniulaityte R. Predictors of transition to heroin use among initially non-opioid dependent illicit pharmaceutical opioid users: A natural history study. Drug Alcohol Depend, 2016; 160: 127–34.
Michael J. Reihart, DO, FACEP, is a physician in the Department of Emergency Medicine at Penn Medicine Lancaster General Health, Lancaster, Pa.
Madison Morgan, BS, works in trauma services at Penn Medicine Lancaster General Health, Lancaster, Pa.
Tawnya M. Vernon, BA, is with the Penn Medicine Lancaster General Health Research Institute, Lancaster, Pa.
Shreya Jammula, MD, is a surgical resident with the Geisinger Health System, Danville, Pa.
Brian W. Gross, BS, is with the Robert Larner, MD, College of Medicine at the University of Vermont, Burlington, Vt.
Eric H. Bradburn, DO, MS, FACS, works in trauma services at Penn Medicine Lancaster General Health, Lancaster, Pa.
Frederick B. Rogers, MD, MS, FACS, works in trauma services at Penn Medicine Lancaster General Health, Lancaster, Pa. Contact him at firstname.lastname@example.org.