eMedicine Specialties > Psychiatry > Addiction

Hallucinogens

Author: Michael E Richards, MD, MPA, FACEP, Assistant Professor, Department of Emergency Medicine, University of New Mexico School of Medicine, Director, Center for Disaster Medicine, University of New Mexico Health Sciences Center
Coauthor(s): Brooke S Parish, MD, Assistant Professor, Department of Psychiatry, University of New Mexico School of Medicine; Scott Cameron, MD, Consulting Staff, Department of Emergency Medicine, Regions Hospital
Contributor Information and Disclosures

Updated: Apr 17, 2006

Introduction

Background

Hallucinogens are a diverse group of drugs that cause an alteration in perception, thought, or mood. A rather heterogeneous group, these compounds have different chemical structures, different mechanisms of action, and different adverse effects. Despite their name, most hallucinogens do not consistently cause hallucinations, which are defined as false perceptions that have no basis in reality. Often, they are more likely to cause changes in mood or in thought than actual hallucinations.

Hallucinogens share a rich history. Many cultures have used hallucinogens for religious or mystical experiences. The Hindu holy book, Rig Veda, mentions soma, a sacred substance used to induce higher levels of consciousness. Soma is thought to have been derived from the juice of the hallucinogenic mushroom Amanita muscaria. The Aztecs in pre-Columbian Mexico described the ceremonial use of teotlaqualli, a paste made from the hallucinogenic flower, ololiuqui. Rubbed on the skin of Aztec priests and soldiers, it was thought to eliminate fear and place the user in a proper mental state to serve the Aztec gods. The Mexican Indians have a long history of using peyote, a mescaline-containing hallucinogen, in religious ceremonies. Hallucinogens have also been proposed as a cause of the "immoral and illicit" behavior of alleged witches in the Salem, Massachusetts witch trials.

The first synthetic hallucinogen, lysergic acid diethylamide (LSD) 25, was serendipitously discovered in 1938 by Sandoz laboratories while searching for a new ergot-derived analeptic agent. Its discoverer, a Swiss chemist named Albert Hoffman, began to experience hallucinations after an inadvertent percutaneous exposure to the drug. Sandoz began marketing the new drug in 1947. Delysid, as the drug was called, was used by psychiatrists who believed its use in psychotherapy could help the patient access repressed emotions. The US Central Intelligence Agency also conducted human experiments with LSD, testing its use as an interrogation tool and as a mind-control agent. Unfortunately, many of these studies were conducted without the consent or knowledge of the participant.

LSD use increased in the late 1950s and early 1960s. Popularized by the media and by people such as Timothy Leary, experimentation with psychedelics reached a peak in the mid 1960s. As use increased, adverse reactions began to be reported. In 1966, because of mounting public health concerns, the federal government banned LSD. Illicit manufacture and use of hallucinogens, of course, has continued.

Hallucinogen use declined in the 1970s and early 1980s. Recent studies show an increase in use during the 1990s, particularly in the high school and college-age population. LSD is presently classified as a schedule I drug, ie, an agent with high abuse potential and no documented medical indication.

Pathophysiology

Hallucinogens may be grouped by structural criteria. The main groups include lysergamides, phenylethylamines, piperidines, indolealkylamines, and cannabinols.

Drugs classified as hallucinogens (abbreviated)

• Lysergamides
• Lysergic acid diethylamide
• Lysergic acid hydroxyethylamide (in morning glory seeds and Hawaiian baby woodrose)
• Indolealkylamines
• Psilocybin
• Psilocin
• Bufotenin
• Dimethyltryptamine (DMT)
• 5-methoxy,-N,N-dimethyltryptamine (5-MeO-DMT)
• Phenylethylamines
• Mescaline
• Methamphetamines
• 3,4-methylenedioxymethamphetamine (MDMA)
• 3,4-methylenedioxyethamphetamine (MDEA)
• 3-methoxy-4,5-methylenedioxyamphetamine (MMDA)
• 4-methyl-2,5-dimethoxymethamphetamine (DOM)
• Piperidines
• Ketamine
• Phencyclidine (PCP)
• Cannabinols - Tetrahydrocannabinol (marijuana, hashish)

Lysergamides

The lysergamides include LSD and lysergic acid hydroxyethylamide, which is a naturally occurring psychedelic found in morning glory seeds. LSD was initially derived from the ergot alkaloids produced by the fungus Claviceps purpurea, a contaminant of wheat and rye flour. LSD is the most potent psychoactive drug, with doses as low as 1-1.5 mcg/kg capable of producing psychedelic effects. Despite its potency, LSD has a very large safety margin; no deaths associated with isolated LSD ingestion have been reported, despite ingestions of several thousand mcg.

A tasteless, colorless, odorless liquid, LSD is usually sold as liquid-impregnated blotter paper, gelatin squares (window panes), or tiny tablets (microdots). Although usually ingested in blotter form, LSD can also be taken via intranasal, sublingual, parenteral, inhalational, or even conjunctival (ie, eyedrops) routes. LSD has dozens of street names, many referring to the pattern printed on the blotter paper, including acid, 'cid, sorcerer's apprentice, paper acid, Lucy in the Sky with Diamonds, Beavis and Buttheads, Bart Simpsons, and Sandoz. Typical street doses are 20-80 mcg of LSD per dose. This is much less than the levels reported during the 1960s and early 1970s, when the doses ranged from 100-200 mcg or higher, per unit.

LSD acts on serotonin and dopamine receptors in the brain. The neurotransmitter serotonin modulates mood, pain, perception, personality, sexual activity, and other functions. The hallucinogenic activity of LSD is thought to be mediated by LSD's effect on serotonin-2 receptors. LSD acts postsynaptically to inhibit serotonin release and increase retention of serotonin at serotonin-2 receptors. Its net effect is that of a serotonin agonist.

The onset of psychological effects occurs approximately 30-60 minutes after ingestion of LSD, and they last for approximately 12 hours. Effect peaks at approximately 5 hours. The psychological effects vary both with the individual taking the drug and the physical environment surrounding the user.

Several common elements of the "trip" are recognized. Changes in mood and perception are uniform. Boundaries between users and their environment are blurred, time becomes distorted, stationary objects may seem to flow or pulsate, and color perception is heightened. Synesthesias, such as hearing color or seeing sounds, are commonly reported. A feeling of clarity of consciousness may be reported by the user, during which the importance of reality is diminished. Hallucinations may occur, although users are usually aware that they are hallucinating. Occasionally, a threatening or stressful environment may provoke feelings of severe anxiety and paranoia. This acute panic reaction is often referred to as a "bad trip" and is the most common reason for users to seek medical attention.

A transient depression may occur after LSD use. Acute psychosis after LSD use has been reported, and an underlying or undiagnosed schizophrenia may worsen. An unusual aspect of LSD use is the occurrence of "flashbacks," or hallucinogen persisting perception disorder (HPPD), months to years after LSD use. These are observed most commonly in persons who have used LSD more than 10 times. During a psychotic episode, danger of suicide and homicide exists.

In addition to the psychological effects, LSD also produces sympathomimetic effects. Increases in heart rate, blood pressure, and, occasionally, temperature may occur. Mydriasis usually occurs and appears to parallel the intensity of the trip, with pupils returning to normal when the patient returns to a non–drug-induced mental state. Rarely, LSD can produce life-threatening symptoms. Hyperthermia (particularly with monoamine oxidase [MAO] use), hypertension, coma, respiratory arrest, and bleeding have been reported. However, users remain more at risk from behavior-related trauma than they do from the toxic effects of the LSD.

Lysergamides are also found naturally in several species of morning glory (Rivea corymbosa, ololiuqui) and Hawaiian woodrose (Ipomoea violacea). The seeds of these plants contain lysergic acid hydroxyethylamide, which has approximately one tenth the potency of LSD.

Phenylethylamines

Phenylethylamine derivatives include mescaline and several hallucinogenic amphetamines. Mescaline is the psychogenic amphetamine found in the peyote cactus, Lophophora williamsii. Native Americans have used peyote for more than 8000 years. Use continues today; members of the Native American Church are still permitted to use the drug in religious ceremonies. Mescaline is thought to induce hallucinations by an amphetaminelike action, although the precise mechanism is unknown. After ingestion of 6-12 peyote buttons (the dried bitter fleshy tops of the cactus), the user first begins to feel effects in 30 minutes to 2 hours. Nausea, vomiting, diaphoresis, and ataxia precede the hallucinogenic effects, which may last 8-12 hours. Mescaline also may be sold as pills containing ground peyote or a synthetic congener, but the prohibitively high cost of the raw materials often leads many dealers to simply substitute PCP.

The hallucinogenic amphetamines, also known as enactogens (ie, enabling the user to "touch within"), are structural analogs of mescaline and amphetamine. Most were derived from their parent compounds in an effort to avoid US Drug Enforcement Agency prosecution (so-called designer drugs). They all have similar psychogenic effects and toxicity. They include MDMA, MDA, MDEA, and MMDA.

MDMA, also known as ecstasy, is perhaps the most well known of these compounds. First synthesized in 1914, MDMA is presently the drug of choice at "raves," ie, all-night dance parties popular in the United States and the United Kingdom. MDMA appears to affect serotonin neurotransmission at presynaptic and postsynaptic sites. Although it usually does not cause hallucinations, it causes changes in mood and the perception of music, reputedly increases interpersonal communication, and fosters feelings of intimacy and empathy. Despite these positive-sounding attributes, concern is growing that ecstasy use may cause permanent neural damage to its users. Animal and primate studies show significant degradation of serotonergic neurons following MDMA use. This degradation is cumulative and dose-related. This has led some experts to warn of the possibility of permanent mood disorders in individuals who use the drug regularly.

In terms of complications and overdoses, the hallucinogenic amphetamines do not seem as benign as other psychedelic drugs. Many of their toxicities are identical to those of amphetamines. Sympathomimetic effects predominate, with hypertension and tachycardia being quite common. Hyperthermia is a common and occasionally serious complication. The combination of sympathomimetic effect, strenuous physical activity, dehydration, and high ambient temperatures found at raves all contribute to severe hyperthermia. This also may be accompanied by rhabdomyolysis, myoglobinuric renal failure, and disseminated intravascular coagulation (DIC).

Several deaths have been reported with MDMA use. Media coverage of these deaths has resulted in the belief that water is the antidote to MDMA. Unfortunately, the consumption of large amounts of water, combined with an intrinsic SIADH-like (syndrome of inappropriate secretion of antidiuretic hormone) effect of the drug itself, often leads to hyponatremia and, occasionally, seizures. Other reported complications of MDMA use are MAO inhibitor–induced hypertensive crisis, serotonin syndrome, seizures, hepatotoxicity, and tachydysrhythmias. Frequent users rapidly develop tolerance to the drug, requiring higher doses for the same effect.

Piperidines

Piperidine derivatives include PCP and ketamine. PCP was developed in the late 1950s as a dissociative anesthetic/analgesic agent initially marketed under the brand name Sernylan. It was soon withdrawn from use because of severe adverse psychological reactions following its use; severe dysphoria, agitation, and psychotic behavior were all noted routinely. It was used in veterinary medicine in the 1960s and soon became a popular drug of abuse, first observed in San Francisco. During a psychotic episode, danger of suicide and homicide exists.

Dubbed the PeaCe Pill, or PCP for short (also known as angel dust), its dysphoric effects and erratic absorption initially limited its appeal. However, its popularity eventually increased as dealers misrepresented the cheap and easy-to-synthesize drug as delta-9-tetrahydrocannabinol (THC), mescaline, LSD, or amphetamines. PCP continues to be marketed in place of other harder-to-obtain drugs. Use peaked in the late 1970s, declined in the 1980s, but seems to have made a resurgence in the 1990s. PCP goes by several street names, including angel dust, killer weed, elephant tranquilizer, rocket fuel, and hog.

The onset of effects occurs in 2-5 minutes after ingestion or smoking of PCP (often it is sprinkled on marijuana cigarettes). Peak effect occurs by 15 minutes. The duration of action is as long as 16 hours (some users report effects persisting as long as 24-48 h). PCP antagonizes the action of glutamate at the N-methyl-D-aspartate receptor, blocking the influx of calcium and inhibiting neurotransmitter release. Depending on the dose, PCP may cause either CNS excitation or depression. Sympathomimetic effects are prominent.

The clinical manifestations of PCP use are extremely variable and unpredictable. The patient may appear calm or wild, disoriented, violent, stuporous, or comatose, depending on the ingested dose. Patients often have a blank stare. Ataxia, grimacing, bruxism, muscle rigidity, and myoclonus are common. Temperature, heart rate, and blood pressure are elevated. Bizarre and psychotic behaviors are often noted. PCP is associated with a much higher morbidity and mortality than other classes of hallucinogens. The combination of sympathetic effects, severe agitation, and muscle rigidity place these patients at high risk for the complications of severe hyperthermia, rhabdomyolysis, and subsequent myoglobinuric renal failure. Their violent and bizarre behavior places them at high risk for trauma. The dissociative nature of PCP allows users to do tremendous harm to their bodies with little or no perceived pain.

Ketamine, structurally similar to PCP, is currently a widely used dissociative anesthetic. Abused since the 1970s, ketamine is currently undergoing a resurgence in popularity. Called "Special K," it is a popular drug at raves.

Indolealkylamines

The indolealkylamine group includes the 2 mushroom-derived hallucinogens (ie, psilocybin, psilocin), DMT, and bufotenine. They all appear to cause their psychogenic effects through activity at the serotonin receptor. Psilocybin is found in the following 3 major genera of mushrooms: Psilocybin, Conocybe, and Panaeolus. Often growing on cow dung, they are found in most areas of the United States, with the exception of arid regions. Several drug-oriented magazines advertise home cultivation kits that include live mycelia. The effects of psilocybin last approximately 4-6 hours. Hallucinations are common. The mushrooms cause fewer adverse reactions than LSD, although cases of hyperthermia, seizures, and coma have been reported. Misidentification of the mushrooms in the wild and on the street is common; only one third of "magic mushrooms" bought on the street contain psilocybin. Many are simply store-bought mushrooms laced with PCP.

DMT is a potent psychedelic with a brief duration of action (15-60 min). This has earned it the nickname "businessman's trip." It is found naturally in the bark of trees of the genus Virola, which grows in the Amazon basin. DMT is only active when smoked or snorted. It causes more visual hallucinations and more sympathetic effects than LSD.

Several species of toads produce venom that has psychoactive properties. Members of the genus Bufo, particularly Bufo marinus and Bufo alvarius, contain bufotenine and 5-MeO-DMT. The compound 5-MeO-DMT is firmly established as a hallucinogen, whereas the role of bufotenine has not yet been established. The toads are either licked or milked for their venom, which may then be ingested or smoked. Their dried skin also may be smoked.

Cannabinols

Marijuana is the leaf or flower of the plant Cannabis sativa and is commonly known as pot, grass, or weed. It contains the psychoactive substance THC. Although usually grouped with other hallucinogens, marijuana rarely causes hallucinations. Acute effects from smoking marijuana include an alteration in perception or mood, laughing, increased appetite, conjunctival injection, tachycardia, and mild CNS depression.

Other hallucinogens

Several mushrooms of the genus Amanita possess hallucinogenic effects. These include Amanita muscaria, Amanita pantherina, and Amanita cothurnata. These are not to be confused with the deadly Amanita phalloides group. A muscaria, or fly agaric, has been used as a psychotropic by Siberians for centuries. The active substances in the mushroom, muscimol and ibotenic acid, are thought to act on GABA receptor sites. The drug is excreted unchanged in the urine, leading to the Siberian practice of drinking the urine of persons or reindeer that have eaten the mushroom. Effects begin approximately 20 minutes after ingestion and last for 6-12 hours. Visual hallucinations and mania alternate with periods of deep sleep. Despite its name, A muscaria contains only a small amount of muscarine and does not cause cholinergic toxicity. Treatment with atropine is contraindicated.

Frequency

United States

The 1996 National Household Survey on Drug Abuse reports a lifetime prevalence rate of LSD use of 7.7% in the population aged 12 years or older. This rate is an increase from 6% in 1988. Approximately 14% of high school seniors reported using LSD at least once. The National Institute on Drug Abuse High School Student Survey in 1996 found that 5% of seniors admitted to MDMA use. A 1990 survey of undergraduate students at Tulane University showed that 24% of students polled had used MDMA. Hallucinogens are the third most frequently abused class of drugs in high school students, after alcohol and marijuana.

International

Although hallucinogen use is found in almost all cultures, several particular hallucinogens bear special mention. Khat, the leaves and stems of the Catha edulis shrub, is an amphetaminelike compound used by millions of people in the Middle East and Africa. The leaves are chewed to produce a euphoriant effect and as a mood-altering agent. Methylcathinone, a derivative of the active agent in khat, has been abused in Russia since the 1970s and is responsible for several deaths. Reports indicate that it is the most popular drug of abuse in the former Soviet Union.

Sex

Hallucinogens are abused most frequently by white males.

Age

The highest rate of hallucinogen abuse occurs in persons aged 18-25 years.

Clinical

History

Most people who take hallucinogens never seek medical attention. Most who do seek attention do so because of a massive overdose, an acute panic reaction, or an accidental ingestion.

• A history of recent hallucinogen use can often be obtained from the patient or the patient's friends and family. Use all available resources.
• Organic causes for altered mental state, acute psychosis, and agitation should be sought aggressively.
• Consider ingestion of drugs that have the potential to cause hyperthermia if patients are in different stages of undress. These drugs include PCP, mescaline, MDMA, and Jimson weed (not discussed in this article). Users of PCP seem to be fond of swimming, probably as a result of this hyperthermia, and drownings have been reported.
• Persons who present following LSD ingestions most often do so because of a bad trip, characterized by disturbing visual hallucinations, anxiety, and paranoid delusions. An acute panic reaction is frequently observed. Behavior is usually agitated.
• Patients who ingest peyote often have pronounced GI effects (nausea and vomiting), diaphoresis, and ataxia before the onset of hallucinations.
• Users of hallucinogenic amphetamines, such as ecstasy, often give a history of rave attendance. Preoccupation with light is common. Bruxism is also a common finding; many users carry something to put in their mouth (eg, an 18-year-old person with a pacifier).
• PCP users are more likely to present in the custody of law enforcement officials. They often have a blank stare, may be extremely agitated or violent, and may show no regard for pain. This may occasionally be difficult to distinguish from cocaine toxicity.
• A history of mushroom ingestion, particularly in novices, should prompt a thorough attempt to identify the ingested mushroom and to differentiate it from more toxic varieties.

Physical

• A complete set of vital signs should be obtained. Hallucinogen use may manifest with tachycardia, hypertension, and hyperthermia. Hypotension, hypoxia, and marked tachycardia or bradycardia are strong clues that imply serious disease.
• Sympathomimetic effects are common and often precede the hallucinogenic effects. Findings may include mydriasis, tachycardia, sweating, hyperthermia, ataxia, and vomiting.
• Note pupil responses where appropriate.
• Perform a complete mental status examination on all patients. Affect, speech, appearance, presence of auditory/visual hallucinations, delusional thinking, and suicidal/homicidal ideation should be carefully assessed.
• Most persons experiencing the effects of a hallucinogen are awake, alert, and oriented. Obtunded patients or those with a focal neurologic examination should prompt an aggressive search for an organic etiology.
• Although nystagmus in any direction can occur with PCP use, rotatory nystagmus is a classic sign.
• Trauma resulting from drug-induced behavior is common.
• Conjunctival injection is commonly observed with marijuana use.
• Toad licking may cause profound drooling, seizures, and cyanosis.
• Severe hyperthermia may be observed with PCP or MDMA use.

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