AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

LSD (lysergic acid diethylamide) is the primary drug that makes up the hallucinogen class. It was first synthesized in 1938 by the Swiss biochemist Albert Hofmann, but the hallucinogenic properties of LSD were not discovered until 1943, when he serendipitously became topically exposed to the substance. Timothy Leary popularized hallucinogens in the 1960s, and a psychedelic revolution followed, with large numbers of people using LSD as part of the counterculture movement. The drug was banned for recreational purposes by federal law in 1967 as a result of public health concerns.

LSD can produce changes in thought, mood, and perception, with minimal effects on memory and orientation. LSD primarily produces illusions (pseudohallucinations), which are impressions derived from the misinterpretation of an actual experience. One common type of illusion produced by these drugs is called synesthesia (ie, transposition of sensory modes, or sensory crossover). For example, a particular sight may cause the user to perceive a sound. True hallucinations also can occur, with visual hallucinations being the most common. Users typically have awareness that what they are seeing, hearing, or smelling is distorted or not real; however, acute adverse effects can include panic reactions, psychosis, and major depression.

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 can contain lysergic acid, and lysergic acid amide is found in morning glory seeds or Hawaiian Baby Woodrose.LSD is one of the most potent psychoactive drugs; it is 3000 times more potent than mescaline, and doses as small as 1-1.5 mcg/kg can produce psychoactive effects. The minimum effective dose is 25 mcg.

The drug is odorless, colorless, and slightly bitter tasting. It is usually taken by mouth and is absorbed rapidly by the gastrointestinal route. LSD is often added to absorbent paper, such as blotter paper, and divided into small decorated squares, with each square representing one dose. The US Drug Enforcement Administration (DEA) reports that the strength of LSD samples currently obtained from illicit sources ranges from 20-80 mcg of LSD per dose. LSD has a wide margin of safety, and the doses taken today are significantly less potent than the doses available during the 1960s and 1970s, when they were reported to range from 100-200 mcg or more of LSD per dose.

LSD is sold under more than 80 street names, including "A," acid, Adams, buttons, the beast, blotter, blue chairs, blue cheers, blue mist, brown dot, California triple dip, cube, dot, flat blues, gelatin, green wedge, hawk, Lucy in the sky with diamonds, M and Ms, mescal, microdot, mighty Quinn, mind detergent, Owsley acid, Owsley blue dot, pearly gates, pink wedge, pink Owsley, purple Owsley, Sandoz's, strawberries, sugar cube, sunshine, uncle, vacation, wedding bells, and window panes.

Pathophysiology

Most hallucinogens are of 2 structurally distinct classes: indoles (eg, psilocybin, DMT [N,N-dimethyltryptamine], LSD) and phenylethylamines (eg, mescaline, MDMA [3,4-methylenedioxymethamphetamine]). The serotonin (5-HT) receptor is implicated in the modulation of hallucinations and can be found predominantly in the cerebral cortex. The cerebral cortex is where hallucinogens have effects on cognition, perception, and mood. Serotonin receptors found in the locus caeruleus are important in producing the sympathomimetic effects of the drug. Hallucinogens have a high affinity for serotonin 5-HT2 receptors, and LSD exhibits both agonist and antagonist properties. The two classes of hallucinogens have differing affinities for other serotonin receptor subtypes, as well, and it is not possible to attribute their effects to any single 5-HT receptor subtype. LSD may also stimulate both D1 and D2 dopamine receptors, but the relationship between the dopaminergic and serotonergic systems is not well understood.

LSD is absorbed rapidly after oral administration, with effects beginning in 30-60 minutes. The most profound psychoactive effects peak at 2-4 hours. The drug is metabolized in the liver, and the elimination half-life of LSD is approximately 2.5 hours; however, the effects may last approximately 12 hours.

Frequency

United States

Emergency department (ED) visits from patients with adverse reactions to hallucinogens are uncommon. Highlights from the 2003 Drug Abuse Warning Network (DAWN) estimate that approximately 627,923 drug-related ED visits occurred nationwide in the third and fourth quarters of 2003. Of these, only 656 cases, or 0.1%, involved LSD, whereas cocaine was involved in 125,921, or 20%, of all drug-related ED visits.

Mortality/Morbidity

Deaths due to the primary effects of LSD have not been well documented. The lethal dose of LSD has been estimated to be 14,000 mcg. Few cases of massive ingestions have been reported; because of its large index of toxicity, patients must have access to unusually concentrated forms of LSD if they are to overdose. In massive overdoses, respiratory arrest, coma, emesis, hyperthermia, autonomic instability, and bleeding disorders can occur.

Age

Hallucinogens regained popularity in the 1990s with individuals of high-school and college age. Low cost (prices range from $2-5 per dosage unit, or hit, with wholesale lots often selling for $1 or less), easy availability, alleged mind-expanding properties, and attractive paper designs make LSD especially intriguing to junior-high and high-school students. However, the National Survey on Drug Use and Health (NSDUH) data show that the annual use of LSD decreased from 2002 to 2003. In 2003, 10.3% of Americans aged 12 years and older reported using LSD at least once in their lifetime, and 0.2% had used it in the past year, down from almost 0.4% in 2002. In those aged 12-17 years, 0.6% had used LSD in the past year, as compared to 0.7% of those aged 14-15 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

• Hallucinogen use rarely results in presentation to the ED. Patients who arrive to the ED typically do so because of acute panic reactions, massive ingestions, or accidental ingestions (ie, children or adults who have unknowingly ingested the drugs). The patient's altered perceptions of the world can lead to behavioral toxicity, in which the patient does not appreciate the dangers in the environment and may be injured.
• A patient who has recently used hallucinogens is often oriented and capable of providing a history of drug ingestion. The subjective effects of LSD use, or a "trip," vary enormously with the user's preconceived beliefs and expectations about the drug and the environment in which the ingestion occurred. In general, its effects can intensify the current mood the user is in when the drug is taken. If users are feeling pleasant, the drug can induce euphoric feelings and help them achieve new insights or an expanded consciousness. The drug can also amplify negative feelings and exaggerate personal flaws, causing a dysphoric experience, or "bad trip." 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). Also, a perception exists that usual objects appear novel, fascinating, or awe inspiring.

Physical

• Patients generally present with sympathomimetic signs, including mydriasis, hypertension, flushing, tachycardia, and, rarely, hyperthermia. Behavior can be agitated or withdrawn. Adverse reactions are usually seen in inexperienced users or in people who have taken the drug unknowingly. An unexpected stressful setting can cause an acute panic reaction, even in experienced users. Children can appear agitated, withdrawn, or catatonic. In pediatric cases of known LSD intoxication, parental abuse or neglect must be assumed and investigated.
• Rarely, morbidity or mortality may be associated with the complications of hyperthermia; such complications include rhabdomyolysis, myoglobinuric renal failure, hepatic necrosis, and disseminated intravascular coagulopathy. Generally, LSD-related deaths result from behavioral toxicity. One LSD user, for example, was killed when he attempted to stop a train bare-handed. The extreme agitation of a bad trip has been known to lead to suicide or to accidental death as users have tried to flee from their hallucinations.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Encephalitis
Meningitis, aseptic

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• Most routine drug screens do not detect LSD. It is excreted primarily in the urine as 2-oxy-lysergic acid diethylamide, which is pharmacologically inactive. Only small amounts of LSD are excreted unchanged in the urine. The drug can be detected by radioimmunoassay; however, high-performance liquid chromatography or gas chromatography is required for confirmation. Radioimmunoassay may detect levels from1.5-5.5 ng/mL within 24 hours after having taken a 300-mcg dose of LSD (Taunton-Rigby, 1973). Urine test results may be positive for LSD for up to 120 hours after ingestion of the drug. Because of the complexity of detecting LSD, testing for the agent is not clinically useful and is most often done in forensics.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

• The basic tenet of caring for patients who have ingested hallucinogens is reassurance in a calm, stress-free environment. Recent ingestion of an unknown mushroom or toxic co-ingestion should be treated with appropriate measures. Rarely, patients need to be either sedated or physically restrained. Excessive physical restraint should be avoided because of the potential complication of hyperthermia, rhabdomyolysis, or both.
• Benzodiazepines can safely be given to decrease agitation. Neuroleptic medications may have adverse psychomimetic effects and thus are not indicated in patients with LSD intoxication. Patients with a history of psychedelic ingestion may have co-ingested other substances, so the care provider must be aware of other toxidromes.
• Because LSD is rapidly absorbed through the GI tract, activated charcoal and gastric emptying are of little clinical value by the time a patient presents to the ED. These procedures may also cause the patient to become more frightened and agitated.
• Massive ingestions should be treated with supportive care, including respiratory support by 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.

Consultations

Management of simple hallucinogen intoxications can usually be accomplished without consultation.

Patients with a history of substance abuse should be referred for drug treatment.

Patients requiring admission should have consultation with a medical toxicologist or regional poison control center.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

If placing the patient in a quiet environment with minimal stimuli is not effective, a benzodiazepine (lorazepam or diazepam) is the medication of choice in patients with dysphoric reactions due to the use of LSD. Benzodiazepines decrease both the exogenous and endogenous sympathomimetic effects.

Drug Category: Benzodiazepines

These agents may be indicated for extremely agitated patients.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Further Inpatient Care

• Patients with minor agitation can usually be treated safely in the ED with observation and supportive care until symptoms have resolved.
• Patients with persistent or unexplained psychosis should have a psychiatric evaluation.
• Admission should be considered if the etiology for the patient's abnormal behavior is unclear or if toxic co-ingestions are suspected.

Complications

• In massive overdoses, respiratory arrest, coma, emesis, hyperthermia, autonomic overactivity, and bleeding disorders can occur.
• The patient's altered perceptions of the world can lead to behavioral toxicity, in which the patient does not appreciate the dangers in the environment and may be injured. The extreme agitation of a bad trip has been known to lead to suicide or to accidental deaths as users have tried to flee from their hallucinations.
• Long-term complications may include prolonged psychotic reactions, severe depression, or an exacerbation of a preexisting psychiatric illness. Hallucinogen Persisting Perception Disorder (HPPD) is a DSM-IV diagnosis, in which patients who are not intoxicated experience symptoms (or flashbacks) that occurred during their use of LSD. Patients can have both perceptual and visual disturbances during these brief episodes. HPPD may last several months; however, some patients report these experiences for up to 5 years and often have an underlying psychiatric illness.

Prognosis

• Most users of LSD voluntarily decrease or stop its use 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.

Patient Education

• For excellent patient education resources, visit eMedicine's Substance Abuse Center. Also, see eMedicine's patient education article Substance Abuse.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Assorted lysergic acid diethylamide (LSD) blotter paper.
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Media type:  Photo

Media file 2:  Lysergic acid diethylamide (LSD) in assorted pill forms.
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Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

• Brunton L L, Lazo JS, Parker KL. Goodman and Gillman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Professional;. 2006.
• Drug Abuse Warning Network 2003. Interim National Estimates of Drug-Related Emergency Department Visits. Substance Abuse and Mental Health Services Administration. US Department of Health and Human Services. Rockville, Md: SAMHSA's National Clearinghouse. for Alcohol and Drug Information;December 2004.
• Gold MS, Schuchard K, Gleaton T. LSD use among US high school students. JAMA. Feb 9 1994;271(6):426-7. [Medline].
• Goldfrank L, Flomenbaum N, Lewin N, Howland MA, et al. Goldfrank's Toxicologic Emergencies. 7th ed. New York, NY: McGraw-Hill Professional;. 2002.
• Klock JC, Boerner U, Becker CE. Coma, hyperthermia, and bleeding associated with massive LSD overdose, a report of eight cases. Clin Toxicol. 1975;8(2):191-203. [Medline].
• Martin TG. Serotonin syndrome. Ann Emerg Med. Nov 1996;28(5):520-6. [Medline].
• Myles JS, Willner P. Substance misuse and psychiatric comorbidity in children and adolescents. Current Opinion in Psychiatry. 1999;12(3):287-290. [Medline].
• NIDA InfoFacts. LSD. Bethesda, Md: National Institute on Drug Abuse. National Institutes of Health. US Department of Health and Human Services;. February 2005.
• Schwartz RH. LSD. Its rise, fall, and renewed popularity among high school students. Pediatr Clin North Am. Apr 1995;42(2):403-13. [Medline].
• Taunton-Rigby A, Sher SE, Kelley PR. Lysergic acid diethylamide: radioimmunoassay. Science. Jul 13 1973;181(95):165-6. [Medline].

Article Last Updated: Aug 17, 2006