AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

Lysergic acid diethylamide (LSD) is a synthetic hallucinogen derived from the naturally occurring alkaloid lysergic acid, which is produced by the rye fungus Claviceps purpurea. Other natural sources of lysergic acid include morning glory seeds and the Hawaiian baby woodrose. LSD is a white, odorless, crystalline material that first was synthesized by the Swiss chemist Albert Hofmann in 1938. During the 1950s and early 1960s, the US Army's Chemical Corps and the CIA investigated the use of LSD as an incapacitating agent, one that caused temporary behavioral changes of such magnitude that soldiers were unable to perform their regular duties for hours to days. However, it ultimately was felt to have no practical military application.

The same mind-altering and mind-expanding properties that made LSD appealing as an incapacitating agent led to its application to psychiatry from the 1950s to early 1970s. Because of its ability to produce a so-called model psychosis, it was used in a variety of experiments leading to a proposed biochemical basis for schizophrenia. It was also used as a psychotherapeutic agent to help patients overcome inhibitions and explore their subconscious mind. Finally, for over a decade, it was used to treat children with autism. However, its application in psychotherapy decreased as it became a popular drug of abuse in the 1960s. It currently is categorized as a schedule I drug, indicating high abuse potential, no known medical application, and questionable safety. LSD abuse is currently on the rise. Like methamphetamine, it has become a widely used rave party or club drug.

Pathophysiology

As a hallucinogen, LSD is 100 times more potent than psilocybin and 5000 times more potent than mescaline. It is believed to induce hallucinations by acting as a partial agonist at the serotonin (5'hydroxytryptamine or 5-HT) receptor 2A subtype in the cerebral cortex, especially on neocortical pyramidal cells. Activation of these receptors leads to increased cortical glutamate levels. LSD also has sympathomimetic properties.

The most common route of exposure is oral, and it is absorbed rapidly from the GI tract. Dermal absorption has not been well documented. LSD can be aerosolized and is absorbed by the lungs provided the particle diameter is 5 micrometers or less. Metabolism is primarily via hydroxylation and conjugation in the liver, with conjugates excreted in the stool. Tolerance develops after 3-4 daily doses. Full sensitivity returns after a similar drug-free interval. No physical dependence and no withdrawal occur.

Frequency

United States

According to the 2002 National Survey on Drug Use and Health, 24.2% of young adults aged 18-25 years had used some sort of hallucinogen at least once in their lifetime.¹ 

Furthermore, National Institute on Drug Abuse (NIDA) data for 2007 revealed that 3.4% of high school seniors had used LSD at least once in their life, with 2.1% having used it within the past year.² 

LSD is often used in clubs or raves. Primary motivations given for its use are experimentation, a desire to feel good, and a perceived enhancement of social interactions.

International

No data on international use are available.

Mortality/Morbidity

Very few deaths are attributed exclusively to the pharmacologic effects of LSD. Deaths associated with LSD use are often from trauma resulting from risk-taking behavior while intoxicated. There is also a strong association between accidental injuries and LSD, especially among young users.

Race

In the US, LSD is used predominantly by whites. While use by African Americans and Hispanics is less common, it has been reported in surveys of urban populations, especially in clubs and raves.

Sex

Males use LSD more frequently than females. The typical LSD user is a middle-class, risk-taking, white male in high school or college. However, a recent survey of women attending university-based ambulatory reproductive health clinics revealed that 13% had used LSD in the past.³ There was also an association between LSD and high-risk sexual behavior.

Age

Of LSD users seen in emergency departments, 50% are younger than 20 years.

CLINICAL

Section 3 of 10  

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

History

The most common route of exposure is oral. LSD frequently is sprayed onto small squares of paper (ie, "blotter acid") that are decorated with a variety of patterns. Both the drug and paper are eaten. Current street doses typically are 20-80 mcg, considerably less than those used in the 1960s and 1970s. LSD also is sold as tiny tablets (microdots), thin squares of gelatin (windowpanes), liquid, or powder. It may be insufflated, smoked, injected, used sublingually, or instilled into the conjunctiva.

• Mental effects develop in 30-90 minutes, peak in 3-5 hours, and last 8-12 hours. These include the following:
• • Feeling of inner tension, often relieved by laughing or crying
  • Multiple, simultaneous emotions, such as joy, rage, terror, or panic
  • Religiosity and a feeling of "oneness with the universe"
  • Possible distorted perception of the passage of time
  • Possible magnification or distortion of sounds
  • Illusions (or hallucinations with high doses)
  • • Moving patterns of bright colors on people and objects
    • Geometric images within larger images
    • Trails behind moving objects
    • Halos around objects
    • Shapes blending together or melting like wax
  • Synesthesia or the mixing of sensory perception such that the individual may see sounds or feel colors
• 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 include the following:
• • Panic reaction
  • Amplification of unconscious fears
  • Self-aggression
  • Suicidal or homicidal ideation
  • Fear of going insane or of the inability to return to normal
  • Perception of rapid aging of self or others
  • Profound depression

Physical

• Predominantly sympathomimetic effects develop within 5-10 minutes of ingestion. Findings include the following:
• • Profound mydriasis
  • Hyperactive reflexes
  • Tachycardia
  • Hypertension
  • Tremors
  • Vomiting
  • Diarrhea
  • Piloerection
  • Mild pyrexia
  • Seizures (rare and typically with doses >10 mcg/kg)
  • Intact orientation and cognition
• In massive overdose, additional signs include the following:
• • Coma (very rare)
  • Respiratory arrest
  • Hyperthermia
  • Coagulopathy

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Toxins
Other psychedelics or entactogens
N,N-dimethyltryptamine (DMT)
4-Methyl-2,5-dimethoxyamphetamine (STP, DOM, serenity, tranquility, peace)
3,4-Methylenedioxyamphetmine (MDA)
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, Adam)
3,4-Methylenedioxyethamphetamine (MDEA, Eve)
Mescaline
Psilocybin
Phencyclidine (PCP)
Anticholinergics (atropine, Jimsonweed)
Sympathomimetics (cocaine, amphetamines)
Others - Steroids, yohimbine, bufotenine (toads), nutmeg, or other hallucinogenic mushrooms
Sedative-hypnotic withdrawal (ethanol, benzodiazepines, barbiturates, gamma-hydroxybutyrate [GHB])
Metabolic causes
Hypoxia
Hypoglycemia
Electrolyte abnormalities
CNS structural lesions
Trauma
Neoplasms
Functional
Schizophrenia
Psychosis
Other
Heat-related illnesses
CNS Infection
Thyrotoxicosis

WORKUP

Section 5 of 10  

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

Lab Studies

• Diagnosis is made predominantly by history and physical examination. Direct diagnostic testing at identifying complications or excluding comorbidity.
• • Routine urine or serum drug screens do not detect LSD. Specialized methods for confirmation exist but are not performed in most hospital laboratories. A radioimmunoassay is available for detecting LSD and its major metabolite, 2-oxy-LSD, in the urine. Urine remains positive for LSD up to 24-36 hours after ingesting 200-400 mg. However, given an accurate history, laboratory confirmation of LSD intoxication rarely is necessary. Levels in the urine do not correlate with severity of symptoms.
  • Coagulation studies, total creatine phosphokinase, or serum electrolytes 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.

Imaging Studies

• Imaging studies such as radiographs or CT scans rarely are necessary. However, they may aid in identifying complications of LSD use or in excluding other diagnoses.

Other Tests

• ECG may be appropriate if co-ingestion is possible or to exclude other causes of tachycardia.

Procedures

• Lumbar puncture may be indicated to exclude meningitis or encephalitis.

TREATMENT

Section 6 of 10  

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

Prehospital Care

Direct prehospital care toward supporting the vital signs. Obtaining vascular access, administering oxygen, and cardiac monitoring 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 co-ingestion.

Emergency Department Care

Most patients evaluated by medical personnel after using LSD are experiencing a "bad trip." Emergency department care is primarily supportive and directed at alleviating the patient's symptoms.

• Specifically, 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.
• Gut decontamination rarely is appropriate, unless the patient presents early after co-ingesting a potentially life-threatening substance. Administration of activated charcoal may be indicated to treat co-ingestants.
• Place the patient 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. Attempt to define reality for the patient, making it clear that the patient's hallucinations are from the drug and are not real.

Consultations

The need for consultation is dictated by the clinical situation. Most patients can be treated supportively and discharged. In some situations, consultation with a medical toxicologist or regional poison control center may be appropriate.

MEDICATION

Section 7 of 10  

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

Pharmacologic intervention may be required when a quiet environment and reassurance cannot control the patient's behavior or symptoms.

Drug Category: Anxiolytics

Benzodiazepines are indicated to control behavior and other autonomic signs and symptoms refractory to a quiet environment and "talking the patient down." 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.

Drug Name	Lorazepam (Ativan)
Description	Effective alternative to diazepam for treatment of patients with signs and symptoms of severe LSD toxicity.
Adult Dose	1-2 mg IV/IM
Pediatric Dose	0.05 mg/kg IV/IM
Contraindications	Documented hypersensitivity, acute angle-closure glaucoma (theoretical issue; no documented cases exist), preexisting CNS depression, hypotension
Interactions	Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs; clearance increased by oral contraceptives
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Although pregnancy class D, no specific fetal malformations are attributed to diazepam (concern is primarily potential decreased alertness and floppiness in the neonate if given close to time of delivery); caution in respiratory insufficiency and hypotension

Drug Category: Antihypertensives

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

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

• Admission is warranted in the setting of serious comorbidity or if the patient is severely intoxicated, requires prolonged observation, or is suicidal.

Further Outpatient Care

• Most patients are discharged after a period of observation. Discharge patients into the care of a responsible adult. Carefully explain discharge instructions to the patient and accompanying friends or family members. In appropriate cases, refer patients for outpatient drug counseling.

In/Out Patient Meds

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

Transfer

• As most patients only require a period of observation, transfer rarely is necessary. However, transfer may be justified in situations of serious complications or comorbidity or when management of behavioral symptoms exceeds the capability of the facility.

Deterrence/Prevention

• The only feasible deterrence is abstinence.
• "Mind Over Matter," an educational tool 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).

Complications

• Complications include persistent or recurrent affective disorders (eg, depression), although these are usually reversible.
• LSD exacerbates preexisting psychiatric illness (eg, psychosis).
• The drug disrupts personality.
• Flashbacks and HPPD are reported in 15-77% of LSD users. Flashbacks and HPPD represent a continuum of severity of signs and symptoms, with flashbacks being the more short-term phenomenon. Flashbacks last minutes to hours and tend to occur during times of psychological stress. With cessation of LSD use, flashbacks tend to stop with time. However, in one study by Abraham, 50% of subjects experienced flashbacks 5 or more years after they stopped using LSD.⁴ Flashbacks are characterized by visual disturbances including the following:
• • Geometric hallucinations
  • Flashes of color
  • Moving light
  • Terrifying illusions of people decomposing, crawling bugs or skulls, Satan's face superimposed on the faces of friends, or objects melting
  • Impaired color perception
• HPPD is a more long-term condition that may or may not resolve with time.

Prognosis

• The long-term prognosis for LSD users is good, provided they stop using the drug.

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.
• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education article Chemical Warfare.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• In most patients, the diagnosis of LSD use is made on the basis of history and physical examination. However, if the clinical picture is unclear, seek other explanations for the patient's symptoms.

Special Concerns

• Pregnant patients: Despite early reports of LSD-related fetal malformations, inadequate evidence exists to establish causality.
• Pediatric patients: The relatively low cost of a dosage unit of LSD blotter paper ($5), its widespread availability, and the artful designs make it very popular with adolescents. However, LSD intoxication in very young children suggests the possibility of child abuse.
• Geriatric patients: LSD potentially may exacerbate comorbid conditions in elderly patients.
• Patients taking selective serotonin reuptake inhibitors or lithium have greater potential for LSD-related complications such as seizures or flashbacks.

REFERENCES

Section 10 of 10

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

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2. National Institute on Drug Abuse (NIDA). NIDA InfoFacts: High School and Youth Trends. Revised 12/07. National Institutes of Health. Available at http://www.drugabuse.gov/Infofacts/HSYouthtrends.html. Accessed March 25, 2008.
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Article Last Updated: Mar 27, 2008