Epidemiology

Recreational abuse of hallucinogens and other drugs is common among patients in the emergency department (ED) and is directly responsible for many ED visits. Although the exact prevalence of drug abuse in patients in the ED is unknown because so much drug abuse goes undetected, various surveillance studies all indicate that ED visits related to drug use continue to rise yearly.^1–3

Patients who present to an ED immediately after using a drug do so for various reasons: an unfavorable or unanticipated reaction to the drug, an unintentional overdose, a traumatic injury, altered mental status, or suicidal and other dangerous behavior. In addition to the acute complications directly related to drug use, many cardiovascular, neurologic, infectious, psychiatric, and social health problems treated in the ED are linked to chronic drug abuse. Because drug abuse is often not declared by the patient at the time of arrival, recognition and optimal treatment require vigilance from the emergency physician, as well as attention to historical, clinical, and laboratory clues.

Recreational drug use today knows no demographic, age, or socioeconomic boundaries. Drug use is just as common (although perhaps less frequently suspected) in white, employed, and insured individuals as in patients who are nonwhite, unemployed, or homeless.^1,4 In the last 2 decades, first-time drug use has become more common among adolescents, and the variety of drugs used has exploded.^5,6 Drug use is no longer limited to what can be identified on a standard hospital toxicology screen, and many of the drugs people abuse to become high are not illegal, such as cough and cold products and prescription medications.^7–10 The rampant growth of drug use is likely linked to the proliferation of the Internet and the wide availability of unregulated partisan drug sites that enable potential users to learn about drugs, to order the raw ingredients and supplies to manufacture their own drugs, or simply to purchase drugs online in the safety of their own homes.⁶

Pathophysiology

The drugs available for recreational abuse are countless and are constantly evolving. In the past, recreational drugs were categorized, for the purposes of discussion, identification, and treatment, somewhat arbitrarily on the basis of structural class, predominant biochemical or neurotransmitter activity (e.g., dopaminergic versus serotonergic versus gamma-aminobutyric acid [GABA]–ergic), or expected clinical effect (e.g., hallucinogen versus stimulant versus entactogen). In reality, most drugs exhibit multiple biochemical effects of varying intensity that are not limited to a particular structural class, and clinical findings vary widely among different individuals even when these persons are exposed to the same drug. Physicians now recognize that clinical variability depends not only on the specific type of drug but also on the dose used, the form of drug (e.g., crystal versus powder versus liquid), the purity of the drug, the route of delivery (e.g., intranasal versus ingestion versus injection), the concomitant use of coingestants, individual genetic polymorphisms, and individual biochemical and physiologic adaptations from long-term exposure.

Most recreational drugs are highly lipophilic and easily cross the blood-brain barrier, so most result in some euphoria; otherwise, patients would have little reason to abuse them.³ Although the exact mechanisms are still incompletely understood, modulation of central dopaminergic activity, which is responsible for pleasure seeking and reward reinforcement, is an important factor in the euphoric response and the development of drug addiction.³ Recreational drugs also affect, to variable extents, peripheral and central norepinephrine, serotonin (5-HT), N-methyl-D aspartate (NMDA), and GABA activity.

Presenting Signs and Symptoms

The most common presenting feature in all patients with recreational drug use is some degree of altered mental status. It may range from seemingly benign giddiness to life-threatening agitation or obtundation. Drug-associated altered mental status may be associated with any kind of vital sign abnormalities or evidence of end-organ damage. Cardiovascular, neurologic, infectious, and psychiatric complaints are also common (Table 150.1). Because the predominant drugs seen in a particular ED vary depending on local geographic preferences and because the types of drugs abused change far more quickly than published medical literature can keep up with, optimal treatment depends on symptom-based (rather than drug-based) diagnostic strategies and interventions.

Table 150.1 Signs and Symptoms of Recreational Drug Use

Amphetamine

Commonly referred to as “crank” or “speed,” amphetamine is a specific drug first synthesized in 1887 and initially marketed as a decongestant and appetite suppressant. Many other drugs with a similar chemical structure, such as methylenedioxymethamphetamine (MDMA) and methamphetamine, are collectively called amphetamines, even though their clinical effects vary. More precisely, these drugs are all derived from a phenylethylamine core and should be collectively called phenylethylamines (MDMA and methamphetamine are discussed separately). Amphetamines are currently available as tablets in the form of a prescription (e.g., methylphenidate [Ritalin], proprietary mixture of amphetamine salts [Adderall]) or in a designer form produced in a clandestine laboratory.¹¹ The onset of symptoms occurs within 15 minutes of ingestion, and symptoms last 6 to 12 hours. The effects are primarily stimulant because of amphetamine’s activity at peripheral and central norepinephrine and dopamine sites.³ Varying levels of tachycardia, hypertension, hyperthermia, diaphoresis, and agitation are commonly seen in the ED in a patient who has ingested an amphetamine, and cardiac and central nervous system (CNS) complications have been frequently reported.

Cocaine

Cocaine is also discussed in Chapter 149, Sympathomimetics. Derived from Erythroxylon coca, a shrub indigenous to South America, cocaine is well absorbed by any mucosal route and thus is abused when snorted, smoked (crack), or injected intravenously. Effects typically occur within 5 to 15 minutes and last 1 to 4 hours. The effects are primarily stimulant and are related to its effects on the sympathetic nervous system: increasing the release of norepinephrine and blocking its reuptake.^3,12 Concomitant use of cocaine with alcohol results in cocaethylene, a by-product with a clinical effect lasting longer than cocaine’s and with direct myocardial depressant effects. After cocaine use, patients may present with chest pain, focal weakness, or altered mental status, and they typically exhibit tachycardia, hypertension, hyperthermia, diaphoresis, and agitation. Because of the intensity of the sympathomimetic stimulation, medical complications such as acute coronary syndrome, seizures, cerebral vascular accidents, intracranial hemorrhage, renal failure, and rhabdomyolysis are common.^12,13 Cocaine washout syndrome occurs after cocaine binging. Affected patients typically have a depressed mental status ranging from lethargy to obtundation that lasts up to 24 hours until depleted neurotransmitters are regenerated.

Dextromethorphan

Also known as DXM, dextromethorphan is a common antitussive agent found in over-the-counter and prescription medications in liquid or tablet form. It is a synthetic analogue of codeine but does not have the same analgesic effect because its activity is primarily at NMDA and 5-HT receptors.^7,10 Hallucinations are commonly reported, and in addition to some opioid features, patients may exhibit ataxia, slurred speech, nystagmus, tachycardia, hypertension, dystonia, and seizures.

Gamma-Hydroxybutyrate

Gamma-hydroxybutyrate (GHB), also known as “Georgia Home Boy” and “liquid G,” has been variously used as an exercise supplement, for treatment of narcolepsy, for obtaining chemical submission of victims, and for euphoria. GHB works primarily at GABA receptors and the still poorly defined GHB receptor.^14,15 The analogues gamma-butyrolactone (GBL), 1.4-butanediol (1,4-BD), gamma-hydroxyvalerate methyl-GHB (GHV), and gamma-valerolactone 4-pentanolide (GVL) work similarly because they are all converted to GHB through various pathways after ingestion. GHB easily crosses the blood-brain barrier and produces loss of consciousness within 15 to 30 minutes of ingestion. Bradycardia, vomiting, myoclonic jerks, and hypothermia are commonly associated. Duration of unconsciousness lasts 2 to 6 hours in most cases.¹⁶

Jimsonweed

Jimsonweed is the common name of plants in the Datura genera. Intoxication with jimsonweed was first reported in 1676. The plants grow throughout the United States, and all parts of it—the fruit, flower, and seeds—can be abused for their hallucinogenic properties. Because these plants contains the alkaloids atropine, scopolamine, and hyoscyamine, clinical effects associated with jimsonweed hallucinations include anticholinergic findings such as dilated pupils, dry mouth, warm and flushed skin, diminished bowel sounds, and urinary retention. Cardiovascular instability, hyperthermia, and seizures have been reported after large ingestions.¹⁷

Ketamine

Also known as “Special K,” “kitty Valium,” and “kiddie Valium,” ketamine is a structural and functional analogue of phencyclidine (PCP) and also works primarily at NMDA receptors.¹⁸ Ketamine can be ingested or injected. Patients with ketamine abuse have symptoms similar to those of PCP intoxication, including rotatory nystagmus, excessive salivation, muscle rigidity, tachycardia, and hypertension, although the effects tend to last a shorter time.^5,18

LSD

D-Lysergic acid diethylamide (LSD) was first synthesized in 1938. It is available in tablets, liquid, powder, and gelatin squares, although the most commonly abused form of LSD is “blotter” acid (sheets of paper sprayed with LSD, dried, and then perforated into small squares). Effects occur within 30 minutes, can last for 16 to 24 hours, and cause powerful hallucinations from serotonergic (5-HT) and dopaminergic activity. Time is distorted, and visual hallucinations of bright colors are common. Tachycardia, hypertension, anxiety, and paranoia are frequently seen in patients who seek treatment in the ED as a result of LSD use. Significant medical complications are uncommon.¹⁸

Marijuana

Also known as “grass,” “weed,” or “pot,” marijuana is considered the most commonly used illegal substance in the United States. Marijuana is primarily smoked; its effects occur within 15 minutes and can last up to 4 hours. The psychoactive substance, delta-9-tetrahydrocannabinol, is derived from the plant Cannabis sativa.³ Clinical effects are variable and seem to occur as a result of cannabinoid receptor activity in the brain. Inappropriate laughter, excessive hunger, anxiety, paranoia, ataxia, and tachycardia are commonly seen. Various synthetic cannabinoids (known by names such as Spice, K2, and Sky Incense) have become available to users in herb shops.¹⁹ The duration of symptoms has reportedly been longer than for naturally growing marijuana. Medical complications associated with cannabinoid abuse alone are uncommon.

Methylenedioxymethamphetamine

MDMA is better known as “Ecstasy,” “X,” “XTC,” and “ADAM” and is also discussed in Chapter 149, Sympathomimetics. It was first synthesized in 1914 but became wildly popular at rave parties and on college campuses in the 1980s and 1990s.^4,5 Although it is a phenylethylamine like amphetamine, MDMA’s strong serotonergic activity has clinical effects that are primarily hallucinogenic and entactogenic.³ Variable tachycardia and hypertension can also occur from some stimulant activity. Hyperthermia has been reported as a complication of excessive dancing in warm rave clubs without adequate hydration, although other individual variabilities and drug contaminants are also likely responsible.⁵ Hyponatremia, another common occurrence with MDMA use, results from excessive ingestion of water or from MDMA-induced syndrome of inappropriate antidiuretic hormone secretion.

Methamphetamine

Also known as “meth,” “crystal,” “chicken feed,” and “white man’s crank,” methamphetamine has become one of the most popular drugs of abuse in the twenty-first century.^20,21 Its popularity is related to its multiple forms (crystal, powder, liquid, and tablet), its ease of manufacture from decongestants such as pseudoephedrine, and its low street cost (less than one third the cost of cocaine). Methamphetamine has strong norepinephrine activity and, of all the phenylethylamines, is the most quickly addictive because of its strong dopaminergic action.³ It can be ingested, snorted, smoked, injected, or administered rectally. Clinical findings are similar to those associated with other stimulant intoxications, and acute coronary syndrome and cerebrovascular accident have been reported. Other hallmark features of methamphetamine are poor dentition, known as “meth mouth,” from poor hygiene and bruxism and dermatologic lesions called “crank bugs” or “meth mites,” from compulsive scratching that is likely delusional in origin.

Opioids

Naturally occurring or synthetic drugs with opium-like or morphine-like activity have always been popular. The poppy plant, Papaver somniferum, is the source of opium and contains the alkaloids morphine and codeine. Opioid effects are primarily modulated throughout the peripheral and CNS by interacting at three main opioid receptors: µ, κ, and δ.³ The classic opioid toxidrome comprises CNS depression, respiratory depression, and miosis, although the intensity of each of those features varies among the different synthetic opioids. Prehospital deaths typically occur from untreated apnea.²² Abuse of prescription opioids continues to rise, especially abuse of methadone and fentanyl patches. Data indicate that the abuse of combination acetaminophen-opioid analgesics is directly related to rising rates of acetaminophen-induced hepatic failure.²³

Other Natural Products

Naturally found herbs, plants, and other related products have become especially popular during the Internet drug era. Adolescents and young adults have been reported to use morning glory seeds for LSD-like effects, nutmeg for myristicin-associated hallucinogenic effects, and the plant Salvia divinorum (known also as “Sally D” and “diviner’s mint”) for κ-opioid–mediated hallucinogenic effects.²⁴ Naturally occurring recreational drugs are popular because they are considered “naturally” safe and can be used in various ways by users, including ingestion, insufflation, smoking, injection, and even tea consumption. Effects typically last 2 to 6 hours, and medical complications are uncommon, although long-term effects are still unknown.

Prescription Medications

Nonmedical abuse of prescription drugs has been identified as a national epidemic. In 2005, nearly 15 million U.S. residents abused prescription drugs, including prescribed opioids, sedatives, antidepressants, and stimulants.¹ One of the reasons for the rapid rise of prescription drug abuse is the perception that these agents are safer than traditional street drugs. The growing rates of prescriptions written for analgesia, for mood disorders, and for attention-deficit hyperactivity disorder have resulted in experimentation with easily available tablets by the family members or friends of the person for whom the agents were prescribed.^9,11