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 also enhanced self-awareness and helped patients to elicit painful memories, making it a potentially useful therapeutic agent. Multiple reports suggested beneficial effects in the treatment of depression, obsessive-compulsive disorder, and sexual dysfunction.[1] For over a decade, it was also used to treat children with autism. However, as it became an increasing popular drug of abuse in the 1960s, restrictions were placed both on LSD research and on its use in psychotherapy.
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.
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. A serotonin-glutamate receptor complex may be involved.[2] Activation 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.
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.[3]
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.[4]
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.[5] 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.
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
Palinopsia (the persistence of a visual image in the brain long after the actual stimulus has gone)[6]
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
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 such as radiographs or CT scans rarely are necessary. However, they may aid in identifying complications of LSD use or in excluding other diagnoses.
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.
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.[7]
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.
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.
Clinical Context:
Successfully used for decades to treat patients with signs and symptoms of severe LSD toxicity; no head-to-head study has compared the efficacy of diazepam with lorazepam in this setting; either is considered an appropriate agent.
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.
Clinical Context:
Recently demonstrated to decrease severity of flashbacks and hallucinogen persistent perceptual disorder (HPPD) and attenuate increased sympathetic activity associated with LSD use.
Admission is warranted in the setting of serious comorbidity or if the patient is severely intoxicated, requires prolonged observation, or is suicidal.
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.
Admitted patients may warrant continued administration of anxiolytics or other medications directed at specific symptoms. Outpatient medications rarely are necessary.
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.
"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).
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.[8] 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.
C Crawford Mechem, MD, MS, FACEP, Associate Professor, Department of Emergency Medicine, University of Pennsylvania School of Medicine; Emergency Medical Services Medical Director, Philadelphia Fire Department
Disclosure: Nothing to disclose.
Coauthor(s)
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.
Specialty Editors
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
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
Rick Kulkarni, MD, Attending Physician, Department of Emergency Medicine, Cambridge Health Alliance, Division of Emergency Medicine, Harvard Medical School
Disclosure: WebMD Salary Employment
John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
Disclosure: Nothing to disclose.
Chief Editor
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
Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Results from the 2002 National Survey on Drug Use and Health: National Findings. US Department of Health and Human Services. Available at http://www.oas.samhsa.gov/nhsda/2k2nsduh/results/2k2Results.htm#HallLife. Accessed March 25, 2008.
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.
Johnston LD, O'Malley PM, Bachman JG. National survey results on drug use from the Monitoring the Future study, 1975-1993. Volume I: Secondary school students. Rockville, MD: National Institute on Drug Abuse; 1994.
Smart JK. History of chemical and biological warfare: An American perspective. In: Sidell FR, Takafuji ET, Franz DR, eds. Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General; 1997:9-86.
