Intoxication from LSD and other common hallucinogens

INTRODUCTION — "Hallucinogen" describes substances whose primary effects include the alteration of sensory perception, mood, and thought patterns. Naturally occurring hallucinogens have been used for millennia as part of ritual and religious activities. The first synthetic hallucinogen, lysergic acid diethylamide (LSD), was synthesized in 1938 by the chemist Albert Hofmann. Its hallucinogenic properties were recognized by accident in 1943 when Dr. Hofmann was inadvertently exposed to LSD while working in his laboratory [1]. LSD was initially marketed as an anesthetic agent and touted as an adjunct for psychoanalysis. In the 1960s, LSD emerged as a recreational drug. Its popularity peaked in the late 1960s and early 1970s and has been declining since. The drug was banned under United States federal law in 1966. There is some renewed interest in therapeutic applications for LSD, including management of treatment-resistant depression, substance use disorders, and severe depression and anxiety related to terminal illness [2].

Hallucinogens are used for their so-called psychedelic effects. These desired effects involve heightening or distortion of sensory stimuli and enhancement of feelings and introspection. Most hallucinogens produce sympathomimetic effects, including tachycardia, hypertension, mydriasis, hyperthermia, and diaphoresis, but these are generally mild [3]. Nausea and vomiting are common and often precede the onset of hallucinogenic effects.

The clinical features, diagnosis, and management of intoxication from LSD and other prototypical hallucinogens (including dextromethorphan, some phenethylamines (mescaline, 2C-B, 2C-T-7), psilocybin and other tryptamines, and Salvia divinorum) are reviewed here (table 1). Amphetamines, methamphetamines, MDMA, ketamine, and phencyclidine (PCP) are discussed separately. (See "Methamphetamine: Acute intoxication" and "MDMA (ecstasy) intoxication" and "Ketamine poisoning" and "Phencyclidine (PCP) intoxication in adults".)

EPIDEMIOLOGY — Lysergic acid diethylamide (LSD) remains the prototypical hallucinogen and the most extensively studied of such drugs. Approximately 1.7 million persons in the United States aged 12 or older are categorized as current hallucinogen users [4]. Hallucinogen use occurs worldwide, although the prevalence is generally considered to be low relative to other drugs of abuse [5]. In some parts of the world, LSD has been supplanted as the most common hallucinogen by the so-called new psychoactive substances, such as synthetic cannabinoids (eg, K2, spice) and "club drugs," and naturally occurring hallucinogens, such as psilocybin and Salvia divinorum [5-7]. This is thought to be related to a number of factors, including the decreased supply of LSD, the rapid emergence of new psychoactive substances, and the ready availability of other hallucinogens via the internet [8,9].

HALLUCINOGEN-ASSOCIATED TERMS — A hallucination occurs when a person experiences sensory perceptions in the absence of external stimuli. True hallucinations can occur with recreational hallucinogen use. However, the alterations in perception commonly caused by these drugs are more accurately termed illusions because there is often a basis in reality for the sensory perception.

A "trip" refers to the effects experienced from acute intoxication. A "bad trip" is an acute intoxication reaction in which dysphoria, fear, agitation, or other unwanted effects are the predominant symptoms.

A "flashback" is a recurrence of symptoms associated with hallucinogen intoxication after the effects of acute intoxication have worn off. These may occur months to even years after the person's last use of a drug, although they tend to decrease in intensity and frequency over time. Flashbacks are not distressing and generally pleasant. Flashbacks stand in contrast to hallucinogen persisting perception disorder (HPPD), in which patients experience symptoms that are distressing, intrusive, and may affect daily function [10].

PHARMACOLOGY — The neurobiology of hallucinogenic compounds is complex and involves the interaction of numerous neurotransmitters, including serotonin (5-HT), dopamine, and glutamate. The exact mechanism underlying hallucinations is not known, but a property common to most of the drugs in this class is their ability to bind 5-HT2A receptors, especially those expressed in neocortical pyramidal cells [11,12]. This serotonergic activity may cause serotonin syndrome, which has been associated with LSD and a number of other hallucinogens [13]. (See "Serotonin syndrome (serotonin toxicity)".)

Salvinorin A, the active ingredient of Salvia divinorum, is unique among common hallucinogens in that it is a kappa opioid agonist [14]. (See 'Salvia divinorum' below.)

In addition to their neurocognitive effects, many hallucinogens have sympathomimetic effects, including mydriasis, tachycardia, hypertension, and hyperthermia. Other effects specific to each drug or class are discussed separately below. (See 'Specific hallucinogens' below.)

KINETICS — A table describing the pharmacokinetic profile of common hallucinogens is provided (table 2). Kinetics vary by drug and route of administration. Most hallucinogens are consumed orally and rapidly absorbed from the gastrointestinal (GI) tract.

GENERAL CLINICAL FEATURES OF INTOXICATION

Neuropsychiatric effects — Neuropsychiatric effects occur with every hallucinogen. Commonly reported effects include a heightened perception of sensory input, a distorted sense of time, euphoria, and a sense of well-being; a perception of being a passive observer of events or being outside one's body, feelings of expansiveness, and enhanced mystical or spiritual experiences. A peculiar phenomenon described with the use of these drugs is synesthesia (ie, a blending of the senses), where users report "hearing" colors or "seeing" sounds.

Unwanted neuropsychiatric effects include fear, panic reactions, dysphoria, frightening imagery, and an overwhelming sense of dread. Frank psychosis may occur and occasionally persists for days. Hallucinogens are not thought to induce psychotic disorders, but may unmask latent psychiatric illness [15].

Short-term tolerance may develop. Cross-tolerance has been reported for lysergic acid diethylamide (LSD), mescaline, and psilocybin, and likely occurs for other drugs in this class.

Vital sign abnormalities — Severe vital sign abnormalities are uncommon with hallucinogens and should prompt consideration of another toxin, such as phencyclidine (PCP), amphetamines, or cocaine. Hypertension and tachycardia are often seen with acute hallucinogen intoxication but generally do not require specific therapy. (See 'Agitation and dysphoria' below and "Methamphetamine: Acute intoxication" and "Cocaine: Acute intoxication".)

Hyperthermia seldom occurs with isolated hallucinogen intoxication, but denotes severe toxicity that requires aggressive management in a critical care setting. When hyperthermia does occur, psychomotor agitation is the most common cause [16]. Less common causes include central stimulation and serotonin syndrome. Complications from severe hyperthermia may include rhabdomyolysis, renal failure, hepatic injury, disseminated intravascular coagulation, and multiorgan failure. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults" and "Serotonin syndrome (serotonin toxicity)".)

Serotonin syndrome — Serotonin syndrome is characterized by the clinical triad of altered mental status, neuromuscular abnormalities, and autonomic hyperactivity. LSD, MDMA (ecstasy), and 5-MeO-DIPT ("Foxy Methoxy") are recognized causes of serotonin syndrome. Many hallucinogens increase serotonin activity and may interact with other serotonergic agents, such as selective serotonin reuptake inhibitors, meperidine, lithium, tryptophan, or monoamine oxidase inhibitors, to cause serotonin syndrome. Serotonin syndrome is discussed elsewhere. (See "Serotonin syndrome (serotonin toxicity)".)

Dependence — Physical dependence is not thought to occur for the majority of the hallucinogens, although psychological dependence is reported.

SPECIFIC HALLUCINOGENS — The source, basic pharmacology, and clinical features of several common hallucinogens, including lysergic acid diethylamide (LSD) and mescaline, are described below. The presentation, diagnosis, and management of several other drugs commonly categorized as hallucinogens are reviewed elsewhere. (See "Methamphetamine: Acute intoxication" and "MDMA (ecstasy) intoxication" and "Ketamine poisoning" and "Synthetic cannabinoids: Acute intoxication".)

LSD and other lysergic acid derivatives

Sources and dosing — LSD is a potent hallucinogen available in capsule, pill, and liquid form. As a liquid, it is most often added to blotter paper in colorful shapes, with each individual shape normally equivalent to one dose. Typical recreational doses are 25 to 80 mcg, but can range up to 250 mcg, and produce psychedelic effects lasting 6 to 12 hours [17].

Lysergic acid derivatives also occur naturally and are found in several species of morning glory (Ipomoea violacea, Rivea corymbosa) and Hawaiian baby woodrose (Argyreia nervosa) [18,19]. Both are available legally in plant nurseries and over the internet. Typical recreational doses are 200 to 300 seeds for morning glory and 5 to 10 seeds for woodrose.

Clinical features — LSD users report a wide variety of neuropsychiatric symptoms. These include distortions of time perception, visual illusions where objects appear unusually vivid or distorted and colors are perceived as being very intense; euphoria and feelings of expansiveness; depersonalization, and a "blending" of the senses (synesthesia). While intoxicated, most individuals remain oriented and aware that their experiences are drug-induced.

Severe symptoms from recreational use are uncommon [20]. Life-threatening toxicity, including cardiovascular collapse and hyperthermia, is only reported in the setting of a large ingestion (approximately >400 mcg) [21]. Severe toxicity or death more commonly occur as a result of impaired judgment while intoxicated (eg, drowning or trauma) or from co-ingestants.

General adverse effects tend to occur with higher doses and inexperienced users, but are not entirely predictable. Such effects may include dysphoria, an overwhelming sense of dread, and panic reactions. Disorientation and hallucinations may occur with high doses. Signs of sympathetic stimulation are common, but generally mild, and may include tachycardia, hypertension, mydriasis, piloerection, and diaphoresis. Vasospasm leading to strokes and peripheral ischemia has been reported, but is rare [22,23].

Dextromethorphan — Dextromethorphan (DXM) is the dextroisomer of the codeine analogue levorphanol. Dextromethorphan poisoning is discussed in detail elsewhere. (See "Dextromethorphan poisoning: Management" and "Dextromethorphan misuse and poisoning: Clinical features and diagnosis".)

DXM is easily available over the counter in numerous cough and cold preparations. Abuse is most common among adolescents. Typical recreational doses (100 to 200 mg) are 5 to 10 times the therapeutic dose. Users report experiencing an out-of-body dream-like state. Common effects include tachycardia, hypertension, lethargy, mydriasis, agitation, and vomiting. Higher doses (>2.5 mg/kg) can produce hallucinations and coma. Anticholinergic delirium and acetaminophen toxicity have occurred in adolescents who ingested DXM-containing cough and cold preparations. Effects usually last three to six hours and are typically mild. (See "Anticholinergic poisoning" and "Acetaminophen (paracetamol) poisoning: Management in adults and children".)

Mescaline, NBOMes, and other phenylethylamines — Mescaline (3,4,5-trimethoxy-phenethylamine) is the active ingredient of the peyote cactus (Lophophora williamsii), a small, spineless cactus found in the southwestern United States and northern Mexico. It is ingested as dried buttons, which are the round fleshy tops of the cactus. The buttons can also be crushed into a powder and prepared as a tea. The typical dose is 6 to 12 buttons. Mescaline produces effects similar to LSD, but is not as potent. Peyote may be used legally in the United States by members of the Native American Church [24]. Its use is otherwise restricted under the United States Controlled Substances Act.

Mescaline is a phenethylamine, a class of compounds that includes amphetamines, methamphetamines, MDMA, and other so-called designer drugs, such as the 2C series and the related NBOMes: 25B-NBOMe, a derivative of 2C-B; 25C-NBOMe, a derivative of 2C-T-7; and 25I-NBOMe, a derivative of 2C-I. All the NBOMes are synthetic phenethylamines that were initially marketed as alternatives to scheduled amphetamines and are most often obtained via the internet [25]. (See "Methamphetamine: Acute intoxication" and "MDMA (ecstasy) intoxication".)

Mescaline alters sensory perceptions in a similar way to LSD. Users report that it enhances and distorts images and light. Nausea and vomiting frequently precede the onset of psychedelic effects. While symptoms of sympathetic activation can occur, they are generally mild.

Users describe the effects of NBOMes as similar to LSD. Prior to 2011, abuse of these drugs was virtually unknown but subsequent reports document a sharp increase in prevalence in the United States and Europe [26,27]. Fatalities associated with 25B-, 25C-, and 25I-NBOMe use have been reported [25,26,28].

Phencyclidine (PCP) — PCP is a dissociative anesthetic with pharmacologic properties similar to ketamine. It was initially developed as an anesthetic agent, but abandoned for this use due to its side effects. PCP is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors. Like LSD, it emerged as a drug of abuse during the 1960s and 70s. Overall, PCP's popularity has waned since then, although there has been a resurgence in use in certain cities [17,29]. (See "Phencyclidine (PCP) intoxication in adults" and "Phencyclidine (PCP) intoxication in children and adolescents".)

PCP may be insufflated (ie, snorted), smoked, ingested, or injected. It is available as capsules, tablets, and powder, and is commonly added to cigarettes, marijuana, or other herbs for smoking. Typical doses are 1 to 3 mg when injected, insufflated, or smoked, and 2 to 6 mg when ingested.

Distinguishing features of PCP intoxication include bizarre or violent behavior, nystagmus (vertical and horizontal), and incoordination [30]. Low doses typically result in dissociative effects, such as feelings of detachment from one's surroundings or body, and social withdrawal. Distortions of sound and vision are common in low to moderate doses. Disorientation, severe agitation, violent behavior, auditory hallucinations, and catatonic stupor occur at higher doses. The usual duration of action is four to six hours, but effects can be prolonged following large ingestions. Coma lasting days may occur following the excitatory phase of the intoxication [31].

Like other hallucinogens, PCP has sympathomimetic properties, but most fatalities occur as a result of trauma rather than directly from pharmacological effects. PCP is unique in its ability to produce amnesia and analgesia in typical recreational doses.

Psilocybin and other tryptamines — Psilocybin is found in dozens of species of mushrooms, including members of the genus Psilocybe [32]. These are commonly known as "magic mushrooms" or "shrooms" and may be consumed fresh or dried. Some mushrooms purported to contain psilocybin are actually edible, nonpsilocybin mushrooms laced with LSD or other hallucinogens. Psilocybin-containing mushrooms grow in the Pacific Northwest and southern regions of the United States. The typical recreational dose of psilocybin is 10 to 50 mg, which corresponds to 20 to 30 g of fresh mushrooms or 1 to 2 g of dried mushroom powder. Psilocybin has been studied for the treatment of cancer-related anxiety in doses of 0.2 mg/kg [33].

Other tryptamines (indolealkylamines) include alpha-methyltryptamine (AMT), N,N-dimethyltryptamine (DMT), and 5-methoxydimethyltryptamine (5-MeO-DIPT). AMT is a synthetic tryptamine initially developed as an antidepressant in the 1960s. DMT is a naturally occurring, short-acting tryptamine that is usually smoked, but can be insufflated (ie, snorted) or ingested. It is present in thousands of plants and is the active ingredient in Ayahuasca, a traditional South American drink [18]. 5-MeO-DIPT ("foxy" or "foxy methoxy") was first synthesized in 1980 but became popular in the late 1990s due to internet sales and its availability in clubs and rave parties, where it was popularized as an erotic enhancer.

Hallucinogenic tryptamines produce neuropsychiatric effects similar to LSD. They may also cause prominent gastrointestinal symptoms, such as nausea, vomiting, and diarrhea. Tryptamines are structurally related to serotonin, and therefore, serotonin syndrome is a particular concern. A table describing the typical recreational doses and duration of effects of select tryptamines is provided (table 2). (See "Serotonin syndrome (serotonin toxicity)".)

Salvia divinorum — Salvia divinorum is a perennial herb of the mint family that has gained popularity among adolescents and young adults because of its easy availability [9]. Plants, leaves, and extracts are available for purchase over the internet, where it is marketed as a legal and safe hallucinogen on many websites [8,34].

The active ingredient is salvinorin A, a diterpene alkaloid and kappa opioid agonist, that is poorly absorbed from the gastrointestinal (GI) tract [14]. The usual dose is 10 to 20 fresh leaves chewed or 2 to 5 dried leaves smoked [35]. Although Salvia divinorum is not a federally controlled substance in the United States, the United States Drug Enforcement Agency has listed it as a Drug of Concern, and it is categorized as a controlled substance in Australia and several European countries [17].

The hallucinogenic effects of Salvia divinorum normally last one to two hours, but less when it is smoked. Like other drugs in this class, it can produce sensory distortions including synesthesia, but abusers more commonly report a sense of calm, elevated mood, and introspection. Sympathomimetic symptoms are mild, and no deaths or cases of severe toxicity have been reported.

DIFFERENTIAL DIAGNOSIS — Many patients who are intoxicated with a hallucinogen are awake, aware that their symptoms are drug-induced, and able to provide a history of recreational hallucinogen use. Confusion, overt psychosis, severe agitation, or markedly abnormal vital signs should prompt a search for alternative diagnoses.

A table describing differential diagnosis considerations is provided (table 3). Stimulant (eg, cocaine, amphetamines, MDMA) intoxication may produce signs and symptoms similar to hallucinogen intoxication. Differentiation may be possible based upon the character of the hallucinations: stimulant-induced hallucinations are usually auditory, whereas hallucinogen-induced hallucinations are usually visual. Also, stimulants tend to be associated with more severe tachycardia and hypertension. (See "Cocaine: Acute intoxication" and "Methamphetamine: Acute intoxication" and "MDMA (ecstasy) intoxication".)

Medical causes of altered mental status that should be ruled out immediately include hypoglycemia, hypoxia, and head trauma. Other considerations include withdrawal from ethanol or sedative-hypnotics, infection of the central nervous system, serotonin syndrome and neuroleptic malignant syndrome (NMS), and primary psychiatric disorders. (See "Management of moderate and severe alcohol withdrawal syndromes" and "Serotonin syndrome (serotonin toxicity)".)

Anticholinergic delirium produces tachycardia, mydriasis, and altered mental status, but affected individuals are usually confused with garbled speech. Individuals intoxicated with the common hallucinogens described above tend to be oriented and to speak clearly. (See "Anticholinergic poisoning" and 'Specific hallucinogens' above.)

LABORATORY AND RADIOGRAPHIC EVALUATION — Routine laboratory tests are generally NOT helpful in the evaluation or treatment of patients acutely intoxicated with hallucinogens, if they do not have severe symptoms and can provide a history of recreational drug use, which most can. Common hallucinogens are not detected by standard drugs-of-abuse screens.

In cases where there is no clear history of recreational hallucinogen use, diagnostic testing is indicated depending upon the type and severity of symptoms. Routine laboratory evaluation of the poisoned patient should include the following:

●Fingerstick glucose, to rule out hypoglycemia as the cause of any alteration in mental status

●Acetaminophen and salicylate levels, to rule out these common co-ingestions

●Electrocardiogram (ECG), to rule out conduction system poisoning by drugs that affect the QRS or QTc intervals

●Pregnancy test in women of childbearing age

Clinicians should obtain additional tests based upon clinical findings. Severe agitation from a drug intoxication increases the risk for rhabdomyolysis. In such cases, creatine kinase and urine myoglobin should be measured, along with a basic metabolic panel, to evaluate for electrolyte abnormalities and acute kidney injury. Altered mental status in association with fever raises concern for meningitis or other infections and warrants a thorough evaluation, including assessment of the cerebral spinal fluid. A head computed tomography scan should be obtained if there is external evidence or concern for head trauma.

MANAGEMENT

Basic measures — In most cases, supportive care is sufficient to manage patients acutely intoxicated with hallucinogens. The signs and symptoms of such intoxications are self-limited and not usually severe; a conservative approach is preferred unless there is evidence of severe toxicity (eg, hyperthermia and severe agitation).

Patients should be placed in a calm, quiet environment until symptoms of intoxication abate. The rationale for this recommendation is that hallucinogens distort and augment sensory input, and symptoms are minimized by limiting sensory input. This approach has not been evaluated in prospective trials, but has been used successfully for decades and is widely recommended [36,37].

Patients with normal vital signs on presentation are monitored with serial vital signs and observation. It is reasonable to measure vital signs every 10 to 15 minutes initially and decrease the frequency as symptoms subside. Patients who are tachycardic or hypertensive on presentation should be observed more closely, have IV access established, and be placed on a cardiac monitor. If agitation or vital sign abnormalities worsen, benzodiazepines and intravenous (IV) fluids should be given as described below.

Severe symptoms, such as hyperthermia and severe agitation, seldom occur, but may represent life-threatening illness and require emergent evaluation. In such patients, the clinician's first responsibility is to assess and stabilize the patient's airway, breathing, and circulation. In patients with a depressed mental status, life-threatening causes, such as hypoglycemia, hypoxia, infection, and head trauma, should be investigated.

Acute agitation and dysphoria should be managed with benzodiazepines as described in the next section [36,37]. If psychotic features (eg, auditory hallucinations, persecutory delusions) persist despite supportive care and adequate sedation, adjunctive treatment with neuroleptic medications is reasonable.

Agitation and dysphoria — Benzodiazepines represent first-line therapy in patients with agitation presumed to be caused by hallucinogen intoxication. Neuroleptics are a reasonable adjunct. The use of benzodiazepines and neuroleptics for this purpose will be reviewed here. General management of the acutely agitated or violent patient is discussed elsewhere. (See "Assessment and emergency management of the acutely agitated or violent adult".)

Benzodiazepines — Few randomized trials have been performed to assess the safety and efficacy of benzodiazepines for achieving rapid control of agitated patients, and none has been performed in the setting of hallucinogen-induced agitation [38-40]. Nevertheless, based upon observational data and broad clinical experience, we believe benzodiazepines provide a safe and effective means to control agitation in the patient with acute hallucinogen intoxication.

A number of benzodiazepines may be used. Midazolam is an attractive choice because its rapid onset and short half-life make it easily titratable [38,39]. We generally give midazolam in doses of 1 to 2 mg intravenously (IV). Acceptable alternatives include lorazepam (1 to 2 mg IV) or diazepam (2 to 5 mg IV). For patients with severe agitation or hypertension, these starting doses may be doubled.

The choice of benzodiazepine is less important than the route of administration. Benzodiazepines should be given IV and titrated as often as every three to five minutes until the patient is calm. Continuous monitoring and frequent clinical reassessment is required for agitated patients. While it may be necessary to give the initial benzodiazepine dose by intramuscular injection (IM), IV access should be established as soon as possible so that further doses can be titrated quickly and accurately. If IM use is required, we prefer midazolam 2 to 5 mg IM over other benzodiazepines because of its predictable pharmacokinetics.

Neuroleptics — Adjunctive treatment with neuroleptics is reasonable if psychotic features persist despite appropriate supportive care and aggressive treatment with benzodiazepines as described in the preceding section. This is particularly true when agitation has resolved and psychotic symptoms persist beyond the expected duration based upon the substance abused (table 2). In such instances, we suggest treatment with haloperidol (2 to 5 mg IV) or droperidol (1.25 to 2.5 mg IV). Administration of neuroleptics should be carefully titrated for the minimum effective dose, preferably after an electrocardiogram has been obtained.

Patients should be carefully monitored for adverse effects. Concerns about neuroleptic medications include adverse drug reactions (eg, akathisia, neuroleptic malignant syndrome) that may be difficult to differentiate from intoxication, or may exacerbate the signs and symptoms of intoxication; possible lowering of the seizure threshold; interference with heat dissipation in agitated patients, and cardiac dysrhythmias secondary to QT interval prolongation. (See "First-generation antipsychotic medications: Pharmacology, administration, and comparative side effects" and "Second-generation antipsychotic medications: Pharmacology, administration, and side effects".)

Hyperthermia — Hyperthermia seldom occurs as a result of acute intoxication with most hallucinogens. Should it occur, hyperthermia is managed in similar fashion to hyperthermia caused by stimulants. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults" and "Methamphetamine: Acute intoxication" and "Cocaine: Acute intoxication".)

Gastrointestinal decontamination — Gastrointestinal (GI) decontamination is NOT necessary in the vast majority of cases involving hallucinogen intoxication. Hallucinogens are rapidly absorbed and symptoms from intoxication are generally mild. The possible small benefit of decreased drug absorption rarely outweighs the risk of charcoal aspiration.

We suggest giving activated charcoal (1 g/kg, maximum 50 g) only to patients who meet one or both of the following criteria:

●Known large ingestion less than one hour prior to presentation

●Suicidal patients who ingested (or are suspected of having ingested) other drugs or medications less than one hour prior to presentation

Charcoal should be withheld in patients who are sedated and may not be able to protect their airway, unless endotracheal intubation is performed first. However, endotracheal intubation should not be performed solely for the purpose of giving charcoal.

Antidotal therapy — No specific antidote exists for any of the hallucinogens. Because they distort and augment sensory input, the main therapeutic strategy is to limit sensory input as much as possible and control agitation with benzodiazepines.

Avoid urinary acidification — Urinary acidification was once used because it was thought to increase the fractional excretion of LSD and PCP, which are weak bases. However, the effect is small, does not alter the course of clinical intoxication, and is associated with potential harm. Therefore, we recommend that urinary acidification NOT be performed.

Disposition — Patients may be discharged when their symptoms have abated and their vital signs have normalized. The expected duration of symptoms from particular intoxicants is summarized in the accompanying table (table 2). Patients with persistent, severe tachycardia or hypertension, severe agitation, or hyperthermia should be managed in a critical care setting.

PEDIATRIC CONSIDERATIONS — Pediatric hallucinogen exposure can be categorized according to the patient's age. Recreational use in adolescents is managed similarly to adults. Exposure in infants, toddlers, and young children is usually unintentional and most often occurs as a result of exploratory behavior. Establishing the diagnosis can be difficult, especially in preverbal children, because the caretaker may not be forthcoming about a history of exposure and because the signs of intoxication are nonspecific.

Common findings in young children include tachycardia, fright, and inconsolable crying, and generally resolve over several hours [41,42]. Rarely, movement disorders that imitate seizure activity have been described with phencyclidine (PCP) poisoning. Significant symptoms should be treated with benzodiazepines [43]. Children with known or suspected exposure to hallucinogens should be admitted for observation and referral to social services. (See "Phencyclidine (PCP) intoxication in children and adolescents".)

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use".)

SUMMARY AND RECOMMENDATIONS

●Definition and pharmacology – "Hallucinogen" describes substances whose primary effects include the alteration of sensory perception, mood, and thought patterns. Lysergic acid diethylamide (LSD) remains the prototypical and best-studied hallucinogen. The mechanisms of these agents remain poorly understood. Pharmacology and kinetics vary by agent (table 2). (See 'Pharmacology' above and 'Kinetics' above.)

●Intoxication effects – Commonly reported effects include a heightened perception of sensory input, a distorted sense of time, euphoria, a perception of being outside one's body, feelings of expansiveness, and synesthesia (a blending of the senses wherein users report "hearing" colors or "seeing" sounds). Unwanted neuropsychiatric effects can include fear, panic reactions, dysphoria, and frightening imagery. The effects of specific agents are described in the text. (See 'General clinical features of intoxication' above and 'Specific hallucinogens' above.)

●Differential diagnosis – Many patients who are intoxicated with a hallucinogen are awake, aware that their symptoms are drug-induced, and able to provide a history of recreational hallucinogen use. Confusion, overt psychosis, severe agitation, or markedly abnormal vital signs should prompt a search for alternative diagnoses (table 3). (See 'Differential diagnosis' above.)

●Laboratory testing – Routine laboratory tests are generally not helpful in the evaluation or treatment of patients acutely intoxicated with hallucinogens, especially if they do not have severe symptoms and can provide a history of recreational drug use. Common hallucinogens are not detected by standard drugs-of-abuse screens. In cases where there is no clear history of recreational hallucinogen use, diagnostic testing is indicated depending upon the type and severity of symptoms. (See 'Laboratory and radiographic evaluation' above and "Testing for drugs of abuse (DOAs)".)

●Supportive care – In most cases, supportive care is sufficient to manage patients acutely intoxicated with hallucinogens. The signs and symptoms of such intoxications are self-limited and not usually severe. Patients should be placed in a calm, quiet environment until symptoms abate. (See 'Basic measures' above.)

●Treatment of agitation, psychosis, and other severe features – We suggest that acute agitation and dysphoria from acute hallucinogen intoxication be managed with benzodiazepines (Grade 2C). Treatment options include midazolam (1 to 2 mg IV), lorazepam (1 to 2 mg IV), or diazepam (2 to 5 mg IV). For patients with severe agitation or hypertension, these starting doses may be doubled. (See 'Agitation and dysphoria' above.)

If psychotic features persist despite appropriate supportive care, including aggressive treatment with benzodiazepines, we suggest treatment with haloperidol (2 to 5 mg IV) (Grade 2C).

Gastrointestinal (GI) decontamination is not necessary in the vast majority of cases. (See 'Gastrointestinal decontamination' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Stephen J Traub, MD, former section editor of the toxicology program, for 20 years of dedicated service.