Hallucinogens are a diverse group of drugs that can cause highly unpredictable, idiosyncratic reactions. Intoxication typically causes hallucinations, with altered perception, impaired judgment, ideas of reference, and depersonalization. There is no stereotypical withdrawal syndrome. Diagnosis is clinical. Treatment is supportive.

Traditional hallucinogens include lysergic acid diethylamide (LSD), psilocybin, and mescaline. All are derived from natural products:

• LSD from a fungus that often contaminates wheat and rye flour
• Psilocybin from several types of mushrooms
• Mescaline from the peyote cactus

Dozens of newer synthetic compounds (“designer drugs”) have been produced, usually based on tryptamine or phenylethylamine molecules. Tryptamines include N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT).

To complicate matters, many illicit drugs sold under one name actually contain another drug of abuse—often ketamineSome Trade Names
KETALAR
Click for Drug Monograph
or phencyclidineSome Trade Names
No US trade name

(PCP), anesthetic drugs, dextromethorphanSome Trade Names
BENYLIN DM
DELSYM
DEXALONE
Click for Drug Monograph
, or other drugs.

Some other drugs, including marijuana, also have hallucinogenic properties. The term hallucinogen persists, although use of these drugs may not cause hallucinations. Alternative terms, such as psychedelic and psychotomimetic, are even less appropriate.

Pathophysiology

LSD, psilocybin, and many designer hallucinogens are serotonin receptor agonists. For mescaline, a phenylethylamine similar to amphetamines, the exact mechanism has not been determined.

Mode of use and effects vary:

• LSD is taken orally from drug-impregnated blotter paper or as tablets. Onset of action is usually 30 to 60 min after ingestion; duration of effects can be 12 to 24 h.
• Psilocybin is taken orally; effects usually last about 4 to 6 h.
• Mescaline is taken orally as peyote buttons. Onset of effects is usually 30 to 90 min after ingestion; duration of effects is about 12 h.
• DMT, when smoked, has onset in 2 to 5 min; duration of effects is 20 to 60 min (accounting for its street name, “businessman's lunch”).

A high degree of tolerance for LSD develops and disappears rapidly. Users tolerant of any of these drugs are cross-tolerant of the other drugs. Psychologic dependence varies greatly; there is no evidence of physical dependence or a withdrawal syndrome.

Symptoms and Signs

Intoxication results in altered perceptions, including synesthesias (eg, seeing sounds, hearing colors), intensification of sensations, enhanced empathy, depersonalization (feeling the self is not real), a distorted sense of the environment's reality, and changes in mood (usually euphoric, sometimes depressive). Users often refer to the combination of these effects as a trip. Periods of intense psychologic effects may alternate with periods of lucidity. LSD may also have several physical effects, including mydriasis, blurred vision, sweating, palpitations, and impaired coordination. Many other hallucinogens cause nausea and vomiting. With all, judgment is impaired.

Responses to hallucinogens depend on several factors, including the user's expectations, ability to cope with perceptual distortions, and the setting. With LSD, delusions and true hallucinations occur but are rare, as are anxiety attacks, extreme apprehensiveness, and panic states. Psilocybin and mescaline are more likely to cause hallucinations. When hallucinogenic reactions occur, they usually subside quickly if treated appropriately in a secure setting. However, some people (especially after using LSD) remain disturbed and may have a persistent psychotic state. Whether drug use has precipitated or uncovered preexisting psychotic potential or can cause this state in previously stable people is unclear.

Some people, especially long-term or repeat users (particularly of LSD), experience apparent drug effects long after they have stopped drug use. These episodes (flashbacks) are usually visual illusions but can include distortions of virtually any sensation (including self-image or perceptions of time or space) and hallucinations. Flashbacks can be precipitated by use of marijuana, alcohol, or barbiturates or by stress or fatigue or can occur without apparent reason. Mechanisms are not known. Flashbacks tend to subside within 6 to 12 mo.

Diagnosis

• Clinical evaluation

Diagnosis is usually made clinically. Drug levels are not measured. Except for PCP, most hallucinogens are not included in routine urine drug screens (see Drug Use and Dependence: Drug Testing).

Treatment

• For acute intoxication, supportive measures and relief of anxiety
• For persistent psychosis, psychiatric care

A quiet, calming environment with reassurance that the bizarre thoughts, visions, and sounds are due to the drug and will go away soon usually suffices. Anxiolytics (eg, lorazepamSome Trade Names
ATIVAN
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, diazepamSome Trade Names
VALIUM
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) may help reduce severe anxiety.

Persistent psychotic states or other mental disorders require appropriate psychiatric care. Flashbacks that are transient or not unduly distressing to the patient require no special treatment. However, flashbacks associated with anxiety and depression may require anxiolytics as for acute adverse reactions.

Ketamine and Phencyclidine (PCP)

Ketamine and phencyclidine are related drugs that can cause intoxication, sometimes with confusion or a catatonic state. Overdose can cause coma and, rarely, death.

KetamineSome Trade Names
KETALAR
Click for Drug Monograph
and phencyclidineSome Trade Names
No US trade name

(PCP) are chemically related anesthetics. These drugs are often used to adulterate or pass for other hallucinogens such as LSD.

KetamineSome Trade Names
KETALAR
Click for Drug Monograph
is available in liquid or powder form. When used illicitly, the powder form is typically snorted but can be taken orally. The liquid form is taken IV, IM, or sc.

PCP, once common, is no longer being legally manufactured. It is illegally manufactured and sold on the street under names such as angel dust; it is sometimes sold in combination with marijuana.

Symptoms and Signs

Intoxication, characterized by a giddy euphoria, occurs with lower doses; euphoria is often followed by bursts of anxiety or mood lability. Overdose causes a withdrawn state of depersonalization and disassociation; when doses are higher still, disassociation can become severe (known as a k-hole), with combativeness, ataxia, dysarthria, muscular hypertonicity, nystagmus, hyperreflexia, and myoclonic jerks. With very high doses, acidosis, hyperthermia, tachycardia, severe hypertension, seizures, and coma may occur; deaths are unusual. Acute effects generally fade after 30 min.

Diagnosis

• Clinical evaluation

Diagnosis is usually clinical. KetamineSome Trade Names
KETALAR
Click for Drug Monograph
is not detected by routine urine drug screens; high-performance liquid chromatography testing must be requested when ketamineSome Trade Names
KETALAR
Click for Drug Monograph
use must be confirmed.

Treatment

• Supportive measures

Patients should be kept in a quiet, calming environment and closely observed. Benzodiazepines can be used to manage seizures. Further treatment is rarely needed.

Last full review/revision July 2008 by Patrick G. O'Connor, MD, MPH

Content last modified February 2012