LSD Toxicity

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Practice Essentials

Lysergic acid diethylamide (LSD), a hallucinogen that is also known as an entactogen (“to touch within”[1] ) is one of the most potent psychoactive compounds known (said to be more than 3000 times more potent than mescaline). Doses as small as 1-1.5 mcg/kg can produce psychoactive effects; an oral dose of 25 µg is capable of producing potential deleterious psychedelic effects.[2, 3]  

The drug is odorless, colorless, and slightly bitter tasting. It is usually taken by mouth and is rapidly absorbed by the gastrointestinal (GI) tract. The image below depicts LSD in several different pill forms.



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Lysergic acid diethylamide (LSD) in assorted pill forms.

While LSD usage reached epidemic proportions in the 1960s, there has been a reduction of abuse owing to constraints on the manufacture and distribution of the drug. It is classified as a Schedule I drug by the US Food and Drug Administration, meaning it is considered a narcotic drug with no known acceptable medical use that has a high potential for abuse, and the possession of any amount of LSD is illegal.

There has also been a concerted effort to educate the public that the psychedelic experiences are a health hazard. Nevertheless, LSD continues to be used. Pockets of continued abuse have been documented across the country.[4]  

LSD toxicity can lead to respiratory arrest, coma, emesis, hyperthermia, autonomic instability, and bleeding disorders. In some cases, the patient's altered perceptions can result in behavioral toxicity, in which an individual fails to appreciate dangers in the environment and may be injured. 

Signs and symptoms

Psychomimetic symptoms

Adverse effects of LSD use can include the following:

Somatic symptoms

Somatic symptoms of LSD toxicity, which are usually due to sympathomimetic effects, include the following:

Massive overdoses can lead to the following[1, 2] :

LSD has been found to be responsible for triggering serotonin syndrome in patients already using precipitating drug combinations (serotonin precursors or agonists, serotonin-release stimulators, selective serotonin reuptake inhibitors [SSRIs], nonselective serotonin-reuptake inhibitors, nonspecific inhibitors of 5-HT metabolism).[5]

HPPD and flashbacks

In hallucinogen persisting perception disorder (HPPD), patients who are not intoxicated experience symptoms (flashbacks) that initially arose during LSD use. HPPD can last from months to years. According to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), all of the following criteria must be met for a diagnosis of HPPD[6] : 

Perceptual symptoms include the following[6] :

See Clinical Presentation for more detail.

Diagnosis

Although LSD toxicity is diagnosed primarily by way of history and physical examination, LSD can be detected by radioimmunoassay. levels from 1.5-5.5 ng/mL may be found within 24 hours after the patient has taken a 300-mcg dose of the drug. However, high-performance liquid chromatography or gas chromatography is required for confirmation.

Diagnostic testing should be directed at identification of complications or exclusion of comorbidities. Coagulation, total creatine phosphokinase, or serum electrolyte studies may be indicated in patients with seizures, coma, or a neuroleptic malignant syndrome–like presentation to identify coagulopathy or rhabdomyolysis or to exclude other diagnoses.

See Workup for more detail.

Management

The basic tenet of caring for patients who have ingested hallucinogens such as LSD is reassurance in a calm, stress-free environment that is safe for both patient and healthcare professionals. Rarely, patients need to be either sedated or physically restrained. Benzodiazepines can safely be given to treat agitation.[1, 2] Butyrophenones such as haloperidol may be required, although there is a small theoretic risk of lowering the seizure threshold.[1]

Massive ingestions of LSD should be treated with supportive care, including respiratory support and endotracheal intubation if needed. The following should be treated symptomatically:

See Treatment and Medication for more detail.

Background

The prototype of the hallucinogen class, LSD was first developed in 1938, when the Swiss biochemist Albert Hofmann synthesized it from lysergic acid while researching the medical effects of ergot-derived synthetic molecules. However, the hallucinogenic properties of LSD were not discovered until 1943, when Hofmann unintentionally ingested the substance and experienced an “extremely stimulated experience."[7]

Hailed as a wonder drug in the field of psychoanalysis during the 1950s and 1960s, LSD was used in schizophrenia research to produce “experimental psychosis” (through alteration of neurotransmitter systems) and in so-called psycholytic and psychedelic therapies.[8] Multiple reports suggested beneficial effects from the use of LSD in the treatment of depression, obsessive-compulsive disorder, and sexual dysfunction.[9] For over a decade, it was also used to treat children with autism.

The American psychologist, writer, and futurist Timothy Leary popularized LSD and other hallucinogens in the 1960s based on their alleged therapeutic and spiritual benefits. This led to a psychedelic revolution, with large numbers of people using LSD as part of a counterculture movement. Because of the resulting public health concerns, however, restrictions were placed on LSD research and on its use in psychotherapy, and the drug was banned for recreational purposes by federal law in 1966.[10]

Currently, LSD is known for its use as a “club drug,” together with gamma-hydroxybutyric acid (GHB); 3,4 methylenedioxymethamphetamine (MDMA), also referred to as ecstasy; and ketamine. Other hallucinogens include mescaline, psilocybin, and ibogaine, which all possess a structural similarity to serotonin. (See DDx.)

Psychoactive effects

LSD causes changes in thought, mood, and perception, with minimal effects on memory and orientation. The drug primarily produces so-called pseudohallucinations, which are illusions derived from the misinterpretation of actual experiences. These include synesthesias, in which the transposition of certain sensory modes occurs, creating an experience known as sensory crossover . For example, the perception of a sound evoked by a visual image or the impression of hearing colors or feeling sounds would be considered a synesthesia. True hallucinations occur as well; visual hallucinations are the most common. 

Exposure to LSD causes pleasant and unpleasant emotions, but the overall effects are unpredictable and vary with the ingested amount, the user’s personality and mood, individual expectations, and surroundings. Users are typically aware that visual, auditory, and olfactorial perceptions are distorted and unreal; however, acute adverse drug effects can include panic reactions, psychoses, and major depression.[11]

One case report describes a young man under the influence of LSD and alcohol who amputated his testicles.[12]

Synthesis and preparation

LSD can be synthesized from easily obtainable chemicals or from naturally occurring substances. Ergotamine alkaloids produced from a fungus that grows on rye and other grains contain lysergic acid. Lysergic acid amide (LSA), a Schedule III substance, is found in the seeds of morning glories and Hawaiian baby woodrose. LSD is produced as a crystalline powder and then mixed with various binding agents.

Potency

According to the US Drug Enforcement Administration (DEA), the strength of samples obtained from illicit sources ranges from 20-80 mcg of LSD per dose. Although LSD possesses a wide margin of safety, single doses obtained over recent years were significantly less potent than those available during the 1960s and 1970s, when a dose contained 100-200 mcg or more of LSD.

Use and availability

Most LSD manufactured in the United States is intended for illegal use. Primary motivations given for the use of LSD are experimentation, a desire to feel good, and a perceived enhancement of social interactions. It is also inexpensive. Typically, a dose costs less than $15.[2] Although small amounts of the drug are used for research purposes, it has no known medical applications. (See Epidemiology.)

Most commonly, 20 to 80 µg of this colorless, tasteless, odorless, and water-soluble substance is ingested via a small square of dried "blotter" paper that has been saturated with a solution of the compound. With this method, the LDS is sprayed onto the small squares of decorative paper, creating the product known as blotter acid.The blotter paper is often imprinted with fanciful designs or cartoons (ie, trademarks for the manufacturer). Other forms of LSD administration include "microdots" (tiny tablets), "windowpane" (gelatin sheets), and liquid LSD.[2]  See the image below.



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Assorted lysergic acid diethylamide (LSD) blotter papers.

Most illegal laboratories making LSD are found on the West Coast. The drug is sold under more than 80 street names, including "A", acid, Adams, back breaker, battery acid, beast, blotter, blue chairs, blue cheers, blue mist, brown dot, buttons, California triple dip, cube, dose, dot, Elvis, flat blues, gelatin, green wedge, hawk, looney toons, Lucy in the sky with diamonds, M and Ms, mellow yellow, mescal, microdot, mighty Quinn, mind detergent, Owsley acid, Owsley blue dot, pane, pearly gates, pink wedge, pink Owsley, purple Owsley, Sandoz's, strawberries, sugar cube, sunshine, Superman, uncle, vacation, wedding bells, window pane, and Zen.

Pathophysiology and Etiology

Most hallucinogens belong to 1 of the following 2 structurally distinct classes:

The most common route of exposure to LSD is oral; the drug is absorbed rapidly from the GI tract. Dermal absorption has not been well documented. LSD can be aerosolized and is absorbed by the lungs if the particle diameter is 5 micrometers or less.

Disruption of the serotonin system

Because of their structural similarity to serotonin and their intrinsic potency, hallucinogens disrupt the balanced functioning of the serotonin system.[3, 7]

Hallucinogens have a high affinity for serotonin (5-HT) receptors, at which LSD exhibits agonist and antagonist properties.[13]

The 5-HT2A receptor plays a major role in the modulation of sensory signals and is predominantly found in pyramidal neurons of the prefrontal cerebral cortex, where hallucinogens have effects on cognition, mood, perception, and emotions ranging from fear to euphoria. These receptors are also thought to be responsible for the pathology and therapy of schizophrenia. Serotonin receptors found in the locus coeruleus are important for sensory modulation and are responsible for the sympathomimetic effects of the drug (hypertension, tachycardia, dizziness, loss of appetite, dry mouth, sweating, nausea, numbness, tremor).

Affinities to other serotonin receptors differ between the 2 hallucinogen classes, which makes attributing specific effects to a single 5-HT receptor subtype impossible. LSD also stimulates dopamine D2 receptors.[14] This leads to a biphasic pharmacologic pattern of early serotoninlike effects (15-30 min after administration) and late mediated dopaminelike effects (60-90 min after administration). The relationship between the dopaminergic and serotonergic systems is not fully understood.[15, 16]

After oral administration, the early drug effects of LSD appear after 30-60 minutes. More profound psychoactive effects peak at 2-4 hours and some effects may last as long as 12 hours.[2] A typical dose to obtain the desired effects ranges from 50-200 mcg. LSD is rapidly metabolized in the liver by N-demethylation, N-deethylation, and aromatic hydroxylation after oral ingestion. The LSD metabolites N-demethyl-LSD (nor-LSD), lysergic acid ethylamide (LAE), iso-LAE, mono-oxylated LSD, and hydroxylated LSD are excreted in the urine. The elimination half-life of LSD is 3-5 hours.

Although LSD does not cause physical or psychological addiction, users quickly develop a high degree of short-lived tolerance (tachyphylaxis), which is due to down-regulation of 5-HT2A receptors. Long-term effects of chronic use can result in persistent psychosis and hallucinogen persisting perception disorder (HPPD), so called “flashbacks." LSD remains one of the most potent mood-altering and perception-altering drugs.[11]

Epidemiology

In 2017, the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS) reported 594 single exposures to LSD and no deaths.[17]   

The overall prevalence of LSD use among adolescents and young adults ages 15 to 34 years in Europe is estimated to be under 1.0%, although higher prevalence has been reported in Finland (1.3%) and the Czech Republic (1.4%).[18]

While LSD is included in national drug trending reports, the accuracy of these for actual LSD use is complicated by novel non-lysergamide hallucinogenic compounds being marketed as LSD. For example, a new class of designer research chemicals includes highly potent hallucinogenic serotonin agonists. Of these, 25I-NBOMe and 25C-NBOMe are the most common type called "Bomb" or "N-Bomb" and are sold on blotter paper. The drug is taken via the buccal or sublingual route, just like LSD. NBOMes are commonly misrepresented as LSD because of their similar routes of administration and effects.[19]  

A survey of 682 adults (aged 18–25 years) in 2015 entering electronic dance music (EDM) events at nightclubs and festivals in New York City found 2.9% of respondents reported lifetime use of LSD. In addition, LSD use significantly increased the risk of novel psychoactive substance (NPS) use (adjusted odds ratio = 4.64, p = 0.004).[19]  Another study of self-reported NPS use in a US nationally representative sample found that 73.7% of NPS users reported lifetime LSD use.[20]  

In the United States, LSD is used predominantly by whites.[21] While use by blacks and Hispanics is less common, it has been reported in surveys of urban populations, being especially used in clubs and raves.[19]

Males use LSD more frequently than do females. The typical LSD user is a risk-taking, white male in high school or college. However, a survey of women attending university-based ambulatory reproductive health clinics revealed that 13% had used LSD in the past.[22] There was also an association between LSD and high-risk sexual behavior.

The 2017 AAPCC-NPDS reported that 58% of reported exposures to LSD were in adolescents aged 13-19 years.[17]  

Since 2000, there has been a considerable falloff in reported availability among middle- and high-school students, which is reflected in the significant decline in use among younger adolescents.[23]

Prognosis

The long-term prognosis for persons who use LSD is good provided that they stop using it, and most users voluntarily decrease or stop the use of the drug over time. LSD is not considered an addictive drug, because it does not produce compulsive drug-seeking behavior; however, LSD does produce a physiologic tolerance, requiring subsequent increased doses to achieve the same effect.

For those who use LSD chronically, there is the enhanced risk for schizophreniform psychosis and derangements in memory function, problem solving, and abstract thinking. Long-term complications from LSD use may include prolonged psychotic reactions, severe depression, or an exacerbation/unmasking of a preexisting psychiatric illness. LSD potentially may exacerbate comorbid conditions in elderly patients.

In 2017, AAPCC reported only 1 death related to LSD exposure.[17] Because of its large index of toxicity, patients must have access to unusually concentrated forms of LSD if they are to overdose. The lethal dose of LSD has been estimated to be 14,000 mcg. However, only a few cases of massive ingestions have been reported. For example, eight individuals who believed they had cocaine accidentally insufflated an extremely high dose of LSD. Their plasma LSD levels were reported as between 1000 and 7000 μg/100 ml. These individuals all became comatose, with hyperthermia, vomiting, light gastric bleeding, and respiratory problems. With hospital treatment, however, all were reported to have survived without apparent residual effects.[24]  

The patient's altered perceptions can lead to behavioral toxicity, in which the patient does not appreciate the dangers in the environment and may be injured. Users may believe that they are invincible or possess superpowers and may do things they would not normally consider, such as believing they can fly, jumping from buildings, or incurring severe ocular damage by prolonged staring at the sun.[24] Extreme agitation brought on by disturbing hallucinations has been known to lead to suicide or to unintentional death, as users have tried to flee from these drug-induced illusions.

Despite early reports of LSD-related fetal malformations, inadequate evidence exists to establish causality.

Hallucinogen persisting perception disorder (HPPD) has an estimated prevalence of 4.2%. With HPPD, individuals who are not intoxicated experience symptoms (flashbacks) that initially arose during the use of LSD. Flashbacks tend to occur during times of psychological stress and can last for minutes to hours. HPPD may last several months; however, some patients report these experiences for as long as 5 years, with many of these individuals having an underlying psychiatric illness.[25]  

 

Patient Education

Counsel patients on the potential dangers of LSD use, including driving automobiles while intoxicated or combining LSD ingestion with ethanol, marijuana, or other illicit drugs. Because the metabolism of LSD is not fully understood, HIV-positive patients on highly active antiretroviral therapy should be counseled to not use LSD, due to the possibility of adverse drug-drug interactions."Mind Over Matter," an educational tool, is designed to encourage young people in grades 5-9 to learn about the effects of drug abuse on the body and brain (see National Institute on Drug Abuse, Mind Over Matter).

For patient education information, see Substance Abuse.

History and Physical Examination

Although the use of hallucinogens, such as lysergic acid diethylamide (LSD), rarely results in presentation to health care facilities, patients who present to the emergency department for hallucinogen-related treatment typically do so after acute panic reactions (“bad trip”), massive ingestions, or unintentional ingestions (children or adults who have unknowingly ingested a hallucinogenic drug).[4] Altered perception can lead to behavioral toxicity, in which judgment is impaired and prevents an appreciation of the dangers in the environment, resulting in situations in which injury can occur.

Patients who present after recent hallucinogen abuse are often oriented and capable of providing a history of drug ingestion. The subjective effects of LSD use widely vary with the user's preconceived beliefs and expectations about the drug and the environment in which the ingestion occurred.

In general, hallucinogens can intensify the user’s current mood; pleasant feelings can be augmented to euphoric ones, with the achievement of new insights or an expanded consciousness. Negative feelings, personal flaws, or depressive symptoms can be amplified to a dysphoric experience. Changes produced in consciousness lead to loss of boundaries between the user and the environment. Users often report intensification or alterations of colors and sound (synesthesia) and the perception that common objects are novel, fascinating, or awe-inspiring.

Patients can also be agitated or withdrawn, with adverse reactions usually being seen in inexperienced users or in patients who have unknowingly taken the drug (although seasoned users can experience negative reactions as well). Children can appear agitated, withdrawn, or catatonic. In pediatric cases of known LSD intoxication, parental abuse or neglect must be assumed and investigated.

Drug-induced persistent psychosis manifests as distorted and disorganized thoughts, dramatic mood swings, mania, depression, vivid visual disturbances, and hallucinations that persist even after the drug effects have ended. Although rare, these symptoms may last for years.

Psychoactive/psychomimetic symptoms

Early effects from LSD, such as conflicting perceptual and mood changes, visual illusions, synesthesias, and extreme lability of mood, usually occur within 30 minutes after LSD intake. These effects may persist for up to 18 hours, even though the half-life of the drug is only 3 hours.[4]

More profound psychoactive effects peak at 2-4 hours.

The patient may perceive or experience the following[26] :

While the effects of LSD often are considered pleasurable to the user, at times they may be profoundly disturbing, resulting in a "bad trip." Novices, as well as seasoned users, can experience bad trips, common manifestations of which include the following:

Somatic symptoms

Patients who have taken LSD generally present with a combination of somatic and psychomimetic symptoms.[28] Somatic symptoms, which are usually due to sympathomimetic effects, include the following:

Manifestations such as tachycardia, hypertension, pupillary dilation, tremor, and hyperpyrexia can occur within minutes following oral administration of 0.5–2 µg/kg.[4]

As previously stated, massive overdoses can lead to respiratory arrest, coma (very rare), emesis, hyperthermia, autonomic instability, and bleeding disorders.

LSD has been found to be responsible for triggering serotonin syndrome in patients already using precipitating drug combinations (serotonin precursors or agonists, serotonin-release stimulators, selective serotonin reuptake inhibitors [SSRIs], nonselective serotonin-reuptake inhibitors, nonspecific inhibitors of 5-HT metabolism).[5] Moreover, patients taking SSRIs or lithium have greater potential for LSD-related complications, such as seizures and flashbacks.

Hallucinogen persisting perception disorder 

Hallucinogen persisting perception disorder (HPPD) describes spontaneous, repeated or continuous recurrences of sensory distortions (flashbacks). Patients can have a combination of perceptual and visual disturbances during flashbacks, including the following:

These perceptual symptoms remain unchanged for long periods and often last for years after initial drug use. Such patients often present after previous negative workup for brain damage or psychiatric disorders.[11, 29]

Ergotism

Ergotism related to LSD ingestion is a possible, but extremely rare, complication. It is thought to be caused by ergot-derived lysergic acid amide (LSA) containing ergotlike precursors. Eponymously termed “Saint Anthony’s fire,” ergotism refers to ergot-induced vasoconstriction that leads to burning pain from limb ischemia, dry gangrene of fingers and toes, tissue desquamation, peripheral pulselessness, sensation loss, and edema. Ergotism can also present with convulsive symptoms leading to headache, paresthesias, seizures, and other central nervous system (CNS) effects, which are often preceded by GI symptoms such as nausea, vomiting, and diarrhea. LSD-induced ergotism often presents as vasoconstrictive effects in combination with hallucinations, mania, or psychosis.[30]

Hyperthermia

In rare cases, increased morbidity, or even mortality, has been associated with complications of hyperthermia, such as rhabdomyolysis,[31] myoglobinuric renal failure, hepatic necrosis, and disseminated intravascular coagulopathy.

Approach Considerations

Lysergic acid diethylamide (LSD) toxicity is diagnosed primarily by way of history and physical examination. Most routine drug screens do not detect LSD. In the urine, it is excreted primarily as 2-oxy-lysergic acid diethylamide, which is pharmacologically inactive. Only small amounts of LSD are excreted unchanged in the urine.[32]

The drug can be detected by radioimmunoassay; levels from 1.5-5.5 ng/mL may be found within 24 hours after the patient has taken a 300-mcg dose of LSD. However, high-performance liquid chromatography or gas chromatography is required for confirmation. LSD levels in the urine do not correlate with severity of symptoms.[33, 34]

Although urine tests may be positive for LSD for as long as 120 hours after its ingestion, such studies are too complex to be clinically useful and are instead most often performed in forensic examination.[35]

Studies Related to Complications and Comorbidities

Diagnostic testing should be directed at identification of complications or exclusion of comorbidities. Coagulation, total creatine phosphokinase, or serum electrolyte studies may be indicated in patients with seizures, coma, or a neuroleptic malignant syndrome–like presentation to identify coagulopathy or rhabdomyolysis or to exclude other diagnoses. Platelet dysfunction and associated bleeding have been reported in patients with large LSD overdoses. Other studies that may prove useful include the following:

Approach Considerations

Prior to patient management considerations, the clinician must first assess the entire situation in terms of scene safety. Is there an actual or potential threat of violence not only to himself or herself but also to the healthcare team? If the answer to that question is in the affirmative, then it is incumbent upon the team to approach the patient in an expeditious manner while limiting harmful exposure to the team. Developing guidelines, teaching those guidelines, and table-topping or exercising those guidelines helps to ensure that this type of patient is addressed in a calm, measured, and safe fashion—safe not only for the patient but also for the staff.[36, 37]

Otherwise, the basic tenet of caring for patients who have ingested hallucinogens such as lysergic acid diethylamide (LSD) is supportive reassurance in a calm, stress-free environment (“talking down”).[4] Rarely, as mentioned above, patients need to be either sedated or physically restrained. Benzodiazepines can safely be given to treat agitation, but neuroleptic medications, such as haloperidol (Haldol), may have adverse psychomimetic effects and thus are not indicated in LSD intoxication.

Excessive physical restraint should be avoided because of potential complications of LSD intoxication, such as hyperthermia and/or rhabdomyolysis.

Guidelines for detoxification and substance abuse treatment, including as they apply to LSD and other hallucinogens, have been established by the Substance Abuse and Mental Health Services Administration.[38]

Gastrointestinal decontamination (eg, activated charcoal) is rarely required, with the possible exception of ingesting huge amounts in a matter of 30-60 minutes prior to presentation. Enhanced elimination measure, likewise, may be counterproductive.[1]

Supportive care

Massive ingestions of LSD should be treated with supportive care, including respiratory support and endotracheal intubation if needed. Hypertension, tachycardia, and hyperthermia should be treated symptomatically. Hypotension should be treated initially with fluids and subsequently with pressors if required.

Ergotism therapy

Ergotism is treated with discontinuation of any inciting drugs and supportive care. Intravenous administration of anticoagulants, vasodilators, and sympatholytics may be useful. The use of balloon percutaneous transluminal angioplasty in severe cases has been reported.[30]

Consultations

Simple hallucinogen intoxication can usually be managed without consultation. Patients with a history of substance abuse should be referred for drug treatment, while patients who require admission should have consultation with a medical toxicologist or regional poison control center.

Prehospital and Emergency Department Care

Prehospital care

Prehospital care for LSD toxicity should be directed toward supporting the patient’s vital signs. Obtaining vascular access, administering oxygen, and monitoring cardiac function may be appropriate in severely intoxicated patients. Make an attempt to provide a quiet environment. Prehospital providers should obtain as thorough a history as possible and examine the patient for signs of coingestion.

Emergency department care

Most patients evaluated by medical personnel for LSD use are experiencing a "bad trip." Patients who have only minor agitation can usually be treated safely in the emergency department with observation and supportive care until symptoms have resolved.

Management priorities include searching for other causes of altered mental status, attending to the patient's safety, and achieving adequate sedation to prevent complications such as rhabdomyolysis or hyperthermia.[31] Patients with a history of psychedelic ingestion may have coingested other substances, so the care provider must be aware of other toxidromes.

Because LSD is rapidly absorbed through the GI tract, activated charcoal administration and gastric emptying are of little clinical value by the time a patient presents to the emergency department. These procedures may even cause the patient to become more frightened and agitated and can increase the risk of vomiting with aspiration. Activated charcoal may be indicated, however, to treat coingestants.

The patient should be placed in a quiet room to minimize sensory input. In many cases, establishing verbal rapport with patients makes it possible to "talk them down," eliminating the need for pharmacologic intervention. The clinician should attempt to define reality for the patient, making it clear that the patient's hallucinations are from the drug and are not real.

Inpatient Care

Admission should be considered if the etiology for the patient's abnormal behavior is unclear or if toxic coingestions are suspected. Patients with persistent or unexplained psychotic symptoms should have a psychiatric evaluation.

Admission is also warranted if the patient is severely intoxicated, requires prolonged observation, or is suicidal.

Admitted patients may warrant continued administration of anxiolytics or other medications directed at specific symptoms. Outpatient medications rarely are necessary.

Medication Summary

If placing a patient who has used lysergic acid diethylamide (LSD) in a quiet environment with minimal stimuli is not effective, a benzodiazepine (lorazepam or diazepam) is the medication of choice, especially in patients with dysphoric reactions. Benzodiazepines decrease central and peripheral sympathomimetic drug effects.

As previously mentioned, neuroleptic medications, such as haloperidol (Haldol), may have adverse psychomimetic effects and thus are not indicated in LSD intoxication.

Diazepam (Valium, Diastat)

Clinical Context:  This agent depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. Although seizures may be promptly brought under control with diazepam, a significant proportion of patients experience a return to seizure activity, presumably because of the short-lived effect of the drug after intravenous administration.

Diazepam has been used successfully for decades to treat patients with signs and symptoms of severe LSD toxicity. However, no head-to-head study has compared the efficacy of diazepam with lorazepam in this setting, and both of these drugs are considered appropriate for such therapy.

Lorazepam (Ativan)

Clinical Context:  Lorazepam may depress all levels of the CNS (eg, limbic and reticular formation) by increasing the activity of GABA, a major inhibitory neurotransmitter in the brain. It is an effective alternative to diazepam for the treatment of patients with signs and symptoms of severe LSD toxicity.

Class Summary

These agents may be indicated for an extremely agitated patient in order to control behavior and other autonomic signs and symptoms refractory to a quiet environment and verbal attempts to calm the patient’s behavior. Unlike antipsychotics, benzodiazepines do not lower the seizure threshold, a theoretical advantage in patients manifesting severe LSD toxicity. Sedation should be titrated carefully by the physician at the bedside.

Clonidine (Catapres, Nexiclon XR, Kapvay)

Clinical Context:  Clonidine has been found to decrease the severity of flashbacks and hallucinogen persisting perception disorder (HPPD) and to attenuate increased sympathetic activity associated with LSD use.

Class Summary

The antihypertensive agent clonidine has been shown to attenuate some signs and symptoms of LSD toxicity.

Author

Paul P Rega, MD, FACEP, Assistant Professor, Department of Public Health and Preventive Medicine, Assistant Professor, Emergency Medicine Residency Program, Department of Emergency Medicine, The University of Toledo College of Medicine; Director of Emergency Medicine Education and Disaster Management, OMNI Health Services

Disclosure: Nothing to disclose.

Chief Editor

Stephen L Thornton, MD, Associate Clinical Professor, Department of Emergency Medicine (Medical Toxicology), University of Kansas Hospital; Medical Director, University of Kansas Hospital Poison Control Center; Staff Medical Toxicologist, Children’s Mercy Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Timothy E Corden, MD, Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Disclosure: Nothing to disclose.

Acknowledgements

Stephan Brenner, MD, MPH Resident Physician, Department of Emergency Medicine, Washington University in St Louis School of Medicine

Disclosure: Nothing to disclose.

Robert G Darling, MD, FACEP Adjunct Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Director, Center for Disaster and Humanitarian Assistance Medicine

Robert G Darling, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, American Telemedicine Association, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

William H Dribben, MD Assistant Professor, Division of Emergency Medicine, Washington University in St Louis School of Medicine

William H Dribben, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Alan H Hall, MD, FACEP Assistant Professor of Emergency Medicine, Division of Toxicology, Texas Tech University Health Sciences Center at El Paso; President, Chief Medical Toxicologist, Toxicology Consulting and Medical Translating Services, Inc

Disclosure: Nothing to disclose.

Halim Hennes, MD, MS Division Director, Pediatric Emergency Medicine, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director of Emergency Services, Children's Medical Center

Halim Hennes, MD, MS is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

C Crawford Mechem, MD, MS, FACEP Professor, Department of Emergency Medicine, University of Pennsylvania School of Medicine; Emergency Medical Services Medical Director, Philadelphia Fire Department

C Crawford Mechem, MD, MS, FACEP is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children's Medical Center

Disclosure: Merck Salary Employment

Suzanne White, MD Medical Director, Regional Poison Control Center at Children's Hospital, Program Director of Medical Toxicology, Associate Professor, Departments of Emergency Medicine and Pediatrics, Wayne State University School of Medicine

Suzanne White, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Clinical Toxicology, American College of Epidemiology, American College of Medical Toxicology, American Medical Association, and Michigan State Medical Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Amanda Wood, MD Resident Physician, Emergency Medicine Resident, Division of Emergency Medicine, Barnes Jewish and St Louis Children's Hospitals

Disclosure: Nothing to disclose.

References

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Lysergic acid diethylamide (LSD) in assorted pill forms.

Assorted lysergic acid diethylamide (LSD) blotter papers.

Assorted lysergic acid diethylamide (LSD) blotter papers.

Lysergic acid diethylamide (LSD) in assorted pill forms.