Hallucinogens

(Lysergic Acid Diethylamide; LSD; Psilocybin; Mescaline)

ByGerald F. O’Malley, DO, Grand Strand Regional Medical Center;
Rika O’Malley, MD, Grand Strand Medical Center
Reviewed/Revised Dec 2022
View Patient Education

Hallucinogens are a diverse group of drugs that can cause 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

Many synthetic hallucinogens (“designer drugs”) are based on naturally occurring tryptamine or phenylethylamine molecules such as 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

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 of Hallucinogen Intoxication

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 commonly taken orally from drug-impregnated blotter paper or as tablets. Onset of action is usually 30 to 60 minutes after ingestion; duration of effects can be 12 to 24 hours.

  • Psilocybin is taken orally; effects usually last about 4 to 6 hours.

  • Mescaline is taken orally as peyote buttons. Onset of effects is usually 30 to 90 minutes after ingestion; duration of effects is about 12 hours.

  • DMT, when smoked, has onset in 2 to 5 minutes; duration of effects is 20 to 60 minutes (accounting for one of its street names, “businessman’s lunch”).

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

Symptoms and Signs of Hallucinogen Use

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.

Massive overdose of LSD may lead to cardiovascular collapse and life-threatening hyperthermia.

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.

Chronic effects

Some people, especially long-term or repeat users (particularly of LSD), experience hallucinogen persistent perception disorder (HPPD) or flashback long after they have stopped drug use. In HPPD, the same symptoms from the original drug use occur without the use of the drug. These recurrent episodes 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 stress, fatigue, or use of marijuana, alcohol, or barbiturates; or flashbacks can occur without apparent reason. Mechanisms are not known. Flashbacks tend to subside within 6 to 12 months, but can recur for years.

Diagnosis of Hallucinogen Use

  • Usually a clinical diagnosis

Diagnosis of hallucinogen use is usually made clinically. Drug levels are not measured. Except for PCP, most hallucinogens are not included in routine urine drug screens.

Treatment of Hallucinogen Use

  • For acute intoxication, supportive measures and relief of anxiety and agitation

  • For persistent psychosis, psychiatric care

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 severe anxiety and depression may require sedatives.

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

  1. Findtreatment.gov: Listing of licensed US providers of treatment for substance use disorders

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