The term hallucinogen is misleading. Hallucinogenic compounds rarely produce true hallucinations—but rather, users experience profound distortions in body image, sensory perception, and time perception, in addition to rapid, intense alterations in mood, increased intensity of any emotions, and heightened suggestibility. Hallucinogen is sometimes used interchangeably with the term psychedelic.

Hallucinogens are widely perceived as safe by the public. However, these substances can cause dangerous physiologic effects resulting in serious health consequences.^1,2,3 The identity, purity, and amount of hallucinogenic compound is usually uncertain, and individual response can be unpredictable.

Hallucinogens in current use consist of both natural and synthetic compounds.⁴ The proliferation of “designer drugs”—chemical analogs or derivatives of illicit drugs marketed to circumvent existing drug laws—is a growing problem. Manufacturers of designer drugs try to circumvent U.S. federal drug laws by stamping their product with advisories such as “not intended for human consumption” or by identifying the products as plant food, bath salts, or potpourri. Prosecution through the Federal Analog Act, a section of the Controlled Substance Abuse Act, can occur only if the drug is “intended for human consumption.” Because of this limitation in federal law, some states have moved to ban the sale of such drugs.

Conditions that mimic hallucinogen intoxication include alcohol or benzodiazepine withdrawal, anticholinergic poisoning, thyrotoxicosis, central nervous system infections, structural brain lesions, acute psychosis, hypoglycemia, and hypoxia.⁵ Some prescription and nonprescription medications can cause hallucinations. The identity of street drugs is often misrepresented, and substitutions or adulteration of product is common.^6,7

Drug-induced psychosis may be difficult to distinguish from primary psychotic disorders.^8,9 A patient with substance-induced psychosis is more likely to have a diagnosis of dependence on any drug, report visual hallucinations, and have a history of parental drug abuse.⁹

Start by assessing the patient’s general medical condition and stabilizing the vital signs. Identify and correct hypoxia and hypoglycemia. Obtain a core temperature to recognize hyperthermia. Obtain serum chemistries and if the patient is agitated, obtain creatine phosphokinase to identify rhabdomyolysis. Obtain an electrocardiogram to identify QT interval prolongation.

Gastric decontamination is not needed in most cases because most hallucinogens are rapidly absorbed and because most patients with adverse effects do not present until several hours after the drug was taken. However, consider administration of oral activated charcoal for ingestions occurring within the previous hour or longer when gastric emptying is delayed, such as with anticholinergic poisonings (e.g., nutmeg ingestion).

Reassurance and a calm, supportive environment can often sufficiently soothe the agitated patient. Pharmacologic sedation and possibly physical restraints may be necessary in order to ensure the safety of the patient and the ED staff and to facilitate evaluation and treatment. Benzodiazepines are the preferred agents for the treatment of hallucinogenic-induced agitation and delirium because they possess no significant drug interactions, have no dystonic or anticholinergic adverse effects, do not prolong the QT interval or promote arrhythmias, and are reversible by flumazenil if over sedation occurs. Start with diazepam 5 to 10 milligrams PO or IV, or lorazepam 1 to 2 milligrams PO, IM, or IV. Give repeated doses as needed, and monitor blood pressure and respiration. Tachycardia and hypertension often respond to sedation with benzodiazepines alone. Severe hypertension can be treated with IV nitroprusside. Correct electrolyte abnormalities and treat dehydration and hypovolemia with normal saline infusion. Treat symptomatic arrhythmias using standard antiarrhythmic protocols. Active cooling measures should be initiated for patients with significant hyperthermia. Treatment of severe agitation, hyperthermia, or seizures may require neuromuscular paralysis and endotracheal intubation. Seizures are treated with benzodiazepines or propofol. Patients with rhabdomyolysis require aggressive IV hydration to maintain urine output.

DISPOSITION AND FOLLOW-UP

Compared with other abused psychoactive agents, hallucinogens have some of the largest acute safety ratios when lethal doses are measured against the doses customarily used to produce the desired hallucinogenic effects.¹⁰ Most patients seen in the ED due to adverse reactions from hallucinogen use can be discharged into the custody of family or friends if they are lucid and in medically sTable condition after a period of observation. Patients with persistent psychotic symptoms or comorbid psychiatric illnesses require psychiatric evaluation.

Common hallucinogens are listed in Table 188-1.

LYSERGIC ACID DIETHYLAMIDE

Lysergic acid diethylamide is a potent psychoactive drug. As little as 25 micrograms produces psychedelic effects. The hallucinogenic effects are believed to be mediated through agonism at the serotonin type 2 (5-HT₂) receptor.^11,12

Lysergic acid diethylamide is a colorless, tasteless, odorless, water-soluble substance that is sold in various forms, but most commonly as small squares of dried blotter paper printed with colorful graphics and cartoons that have been perforated and soaked in liquid lysergic acid diethylamide solution. Each square typically delivers a dose of 20 to 80 micrograms. Other forms include “microdots” (tiny tablets), “windowpane” (gelatin sheets), impregnated sugar cubes or candy, and small bottles of “breath drops” (the drug in solution).

The psychedelic effects begin within 30 minutes of ingestion, peak within 4 hours, and last between 8 to 12 hours.^13,14 Sympathomimetic stimulation with mydriasis and elevations of pulse, blood pressure, and temperature usually precede the psychedelic effects.^13,14 Marked facial flushing, mild gastric distress, piloerection, increased muscle tension, and hyperreflexia may occur. In massive overdoses, coagulopathy, hyperthermia, seizure, coma, and respiratory arrest have been reported.¹⁵

The psychedelic effects of lysergic acid diethylamide depend on the user’s prevailing mood, expectations, and surrounding environment. Effects may be perceived as pleasurable or horrifying. Profound distortions in perception of sensory stimuli, time, emotions, and memories occur and may cause users to experience paranoia, depression, extreme panic, or an acute psychotic reaction known as a dysphoric reaction or “bad trip.” Dangerous and impulsive behavior is possible, resulting in serious physical trauma or suicide. Prolonged and sometimes permanent psychosis, known as “flashbacks” or “hallucinogen persisting perception disorder,” can result.¹⁶

The typical user is usually conscious, alert, and able to provide history of the drug ingestion.¹³ Diagnosis is based on history of use, the presence of sympathomimetic signs, and reported psychedelic effects. Lysergic acid diethylamide can be detected in the urine for several days after ingestion using specific radioimmunoassay and enzyme immunoassay techniques. Reassurance and observation in a quiet, safe environment are generally the only interventions required to manage a dysphoric reaction. Oral or parenteral benzodiazepines are indicated for patients with extreme agitation or signs of excessive sympathomimetic stimulation. Patients with paranoid or psychotic symptoms lasting longer than 8 to 12 hours may require hospital admission. Medical complications due to massive overdose are rare, and recovery is usually rapid and requires only supportive care.^13,14,15

PSILOCYBIN

Psilocybin is a naturally occurring hallucinogenic compound found in at least six genera of mushrooms, but most notably the Psilocybe genus. Psilocybin is an indolalkylamine that is metabolized to the pharmacologically active compound psilocin. Both psilocybin and psilocin are believed to act as serotonin type 2 receptor agonists similar to lysergic acid diethylamide.

Psilocybin-containing mushrooms grow naturally in the southern United States and Europe but can also be grown from kits sold over the Internet.¹⁷ Most species of psilocybin-containing mushrooms turn bluish when bruised, but this is not a definitive method of identification or determination of potency. Psilocybin-containing mushrooms may be dried or cooked without losing potency. Hallucinogenic mushrooms sold on the street are often nonpsychoactive mushrooms that have been adulterated with lysergic acid diethylamide or phencyclidine.⁶ Because of the variation in mushroom size and concentration of psychoactive compounds, there is little correlation between the number of mushrooms ingested and the hallucinogenic effects. A user may ingest as few as five or as many as 100 mushrooms for a single “dose.”

Hallucinogenic effects begin within 30 minutes of ingestion and last 4 to 6 hours.^18,19 The hallucinogenic effects are similar to, although less powerful than, those produced by lysergic acid diethylamide. Other common effects include mydriasis, tachycardia, nausea, and vomiting. Serious medical complications are extremely rare but include seizures, hyperthermia, rhabdomyolysis, and renal failure.²⁰ Mistaken identity and ingestion of highly toxic mushrooms is possible and can lead to serious outcomes.²¹

Management is supportive. There is no routinely available screening test for psilocybin or psilocin in the urine. If the patient’s symptoms are not consistent with psilocybin ingestion, consider the possibility that a toxic mushroom (see Chapter 219, Mushroom Poisoning) or other psychoactive substances were ingested.²¹

MESCALINE AND PEYOTE

Mescaline is found in many cacti, most notably the Mexican Peyote cactus (Lophophora williamsii) and the Peruvian San Pedro cactus (Trichocereus pachanoi). Peyote is used in Native American religious ceremonies, and its legal use is restricted to the Native American Church. Mescaline is a phenylethylamine, structurally related to amphetamines, making it chemically distinct from lysergic acid diethylamide.²² Mescaline is believed to act as a serotonin type 2 receptor agonist, but is much less potent than lysergic acid diethylamide.

Peyote is most commonly sold as raw cactus or “buttons,” 2- to 3-cm discs sliced off of the top of the cactus. Each button contains approximately 45 milligrams of mescaline. A typical hallucinogenic dose is 200 to 500 milligrams. Pills or capsules sold on the street as “mescaline” are unlikely to be genuine and may instead contain lysergic acid diethylamide or phencyclidine.⁶

Peyote is bitter tasting and causes uncomforTable physical side effects within an hour of ingestion—including nausea, vomiting, abdominal discomfort, diaphoresis, dizziness, nystagmus, ataxia, and headache—that generally resolve after about 2 hours. Adrenergic stimulation causes mydriasis and mild elevations in pulse, blood pressure, and temperature. Hallucinogenic effects begin several hours after ingestion and persist for 6 to 12 hours. Significant morbidity or mortality caused by the physiologic effects of mescaline has not been observed, but death can result from aberrant behavior while under the influence of the drug.²³ Mescaline-intoxicated patients are managed supportively. Routine urine drug screens do not detect mescaline.

HALLUCINOGENIC AMPHETAMINES

More than 50 “designer” amphetamines have been created for their hallucinogenic properties. Best known is methylenedioxymethamphetamine, a synthetic phenylethylamine derivative structurally related to both amphetamines and mescaline and commonly known by the street name “Ecstasy.” Other designer amphetamines include methylenedioxyamphetamine and methylenedioxyethamphetamine (“Eve“). Methylenedioxymethamphetamine is known for both its psychedelic properties and unique effects on mood and intimacy, which has led to its reputation as a “love drug” popular in dance clubs.²⁴ Methylenedioxymethamphetamine has complex effects, interacting with dopamine, norepinephrine, acetylcholine, and β₂-adrenergic and serotonin type 2A receptors, and affecting the release of several hormones, including prolactin, oxytocin, adrenocorticotrophic hormone, dehydroepiandrosterone, and antidiuretic hormone.²⁵

Methylenedioxymethamphetamine is usually ingested as tablets in doses of 50 to 200 milligrams. The drug is colorless and tasteless—-properties lending to its use as a date-rape drug.²⁶ Symptoms occur within 30 minutes of ingestion and last about 4 to 6 hours. These include feelings of euphoria, inner peace, enhanced sociability, verbosity, and heightened sexual interest. The drug rarely causes actual hallucinations but can produce sensory effects such as alterations in the intensity of colors or sensation of textures. Other common effects include mydriasis, tachycardia, and elevated blood pressure, as well as nausea, jaw tension, bruxism, dry mouth, muscle aches, and ataxia. Current urinary amphetamine immunoassays incorporate a specific monoclonal antibody for methylenedioxymethamphetamine and should routinely detect this drug.

Methylenedioxymethamphetamine and related amphetamines can produce serious complications and death.^27,28,29,30 As with other amphetamines, large-quantity overdoses can cause severe hypertension, intracranial hemorrhage, and ischemia in the heart or brain.²⁷ Fatal arrhythmias and sudden cardiac death have been reported, both with and without underlying cardiac disease.^27,28 The most frequently cited causes of death are hyperthermia and hyponatremia.^31,32,33,34 A syndrome of methylenedioxymethamphetamine toxicity manifested by hyperthermia, seizures, disseminated intravascular coagulation, rhabdomyolysis, and hepatotoxicity has been described.³⁵ This pattern shares many features of the serotonin syndrome, and combining methylenedioxymethamphetamine with selective serotonin reuptake inhibitors (see Chapter 178, Atypical and Serotonergic Antidepressants) or monoamine oxidase inhibitors (see Chapter 179, Monoamine Oxidase Inhibitors) can precipitate serotonin syndrome.³⁶

Hyponatremia is predominantly due to excessive water consumption and inappropriate antidiuretic hormone secretion.^31,32 Excessive water drinking from thirst can occur if the drug is taken at hot and crowded club venues, with vigorous dancing and profuse sweating.^31,33 Persistent neurotoxic effects are possible from chronic methylenedioxymethamphetamine use. Neuropsychiatric studies of habitual users demonstrate long-lasting cognitive impairment and mood dysfunction, including memory impairment, diminished learning ability, and depression.³⁷