Hallucinogens are a diverse group of drugs that can cause unpredictable, idiosyncratic reactions and are used by ingestion, injection, or smoking. Intoxication typically causes hallucinations, altered perception, impaired judgment, ideas of reference, and depersonalization. Toxicity may include nausea, vomiting, mydriasis, blurred vision, sweating, impaired coordination, and most seriously, hyperthermia and tachydysrhythmias. Diagnosis is by history and physical examination. Management is with monitoring, sometimes benzodiazepines for anxiety or tachydysrhythmias, and external cooling measures for hyperthermia. There is no stereotypical withdrawal syndrome.
The canonical hallucinogens are lysergic acid diethylamide (LSD), psilocybin, and mescaline. Lysergic acid is produced by a fungus (Claviceps purpurea) that contaminates wheat and rye flour. Psiloycbin is produced by certain types of mushrooms. Mescaline is produced by the peyote cactus. Another hallucinogen is ayahuasca, usually consumed as a tea made from the leaves of plants containing the chemical dimethyltryptamine (DMT).
The crucial pharmacologic distinction among hallucinogens is whether the drug is derived from tryptamine or phenethylamine. Toxicity from tryptamine derivatives is, in general, rarer and confined to cardiovascular complications such as myocardial ischemia or hypertension. Toxicity from phenethylamine derivatives can also include seizures, tachydysrhythmias, agitation, and electrolyte abnormalities. Synthetic hallucinogens are based off tryptamine backbones such as N,N-dimethyltryptamine (DMT), or phenylethylamine backbones such as 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT). Illicit drugs sold as a specific hallucinogen may contain additional substances, such as ketamine or phencyclidine (PCP), anesthetic medications, or dextromethorphan.
The term hallucinogen persists, although use of these drugs may not cause hallucinations and other drugs, such as marijuana, can cause hallucinations. Alternative terms, such as psychotomimetic drugs reflect an inaccurate earlier hypothesis that this group of drugs induced a psychotic state. The term psychedelic, originally meaning "manifesting the soul or consciousness," is also misleading because it implies that these chemicals allow access to "hidden" parts of the mind, which is not accurate and does not include the somatic effects of these drugs. The common classification of MDMA as a stimulant and not a hallucinogen despite it being and empathogen and entactogen demonstrates the incoherent taxonomy. We prefer the terms tryptamine derivative or phenethylamine derivative. We use the term hallucinogen throughout this chapter when referring to both tryptamine and phenethylamine derivatives so as to not obscure the current discussion with ontology.
Street names for lysergic acid diethylamide include LSD and Acid. Street names for mescaline include Buttons, Cactus, and Mesc. Street names for psilocybin include Magic Mushrooms and Shrooms.
Pathophysiology of Hallucinogen Intoxication
LSD, psilocybin, mescaline, and designer hallucinogens are serotonin receptor agonists. The term "designer hallucinogens" refers to any synthetic chemicals with hallucinogenic effects. It refers to substituted phenethylamines, like NBOMes or DOx series, such as DOM or DOC, and substituted tryptamines, like 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), or LSD derivatives.
The exact mechanism of mescaline, a phenylethylamine, has not been determined. As discussed in the section on amphetamines, derivatives with substitutions in the phenyl portion of the phenethylamine scaffold have more psychoactive, hallucinogenic, and mind-altering properties than phenethylamine derivatives with substitutions in the ethylamine portion.
Hallucinogenic effects of both tryptamine and phenethylaminne derivatives are mediated through the 5-HT2A receptor (1). Perhaps substitution at the phenyl ring yields a compound that structurally resembles the ethylamine and 5-membered ring in tryptamine.
Pharmacokinetics of agents vary by common routes of use and approximate timing of effects:
LSD: Oral, common forms are drug-impregnated blotter paper and tablets. Onset of effects, 30 to 60 minutes; duration of effects,12 to 24 hours.
Psilocybin: Oral. Onset of effects, 20 to 40 minutes; duration of effects, 4 to 6 hours.
Mescaline: Oral, in the form of peyote buttons. Onset of effects, 30 to 90 minutes; duration of effects, 12 hours.
DMT: Smoking is common, for this form, onset of effects, 2 to 5 minutes; duration of effects, 20 to 60 minutes (accounting for one of its street names, “businessman’s lunch”).
Pathophysiology reference
1. López-Giménez JF, González-Maeso J. Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways. Curr Top Behav Neurosci. 2018;36:45-73. doi:10.1007/7854_2017_478
Symptoms and Signs of Hallucinogen Use
The effects of use are altered perceptions, 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 psychological effects may alternate with periods of lucidity.
Judgment is impaired during hallucinogen use. 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 managed appropriately in a secure setting. However, some people (especially after LSD use) remain psychologically disturbed and may have a persistent psychotic state. It is unclear whether drug use has precipitated or uncovered preexisting psychotic potential or can cause this state without prior vulnerability to psychosis.
Signs of acute toxicity that require immediate intervention are hyperthermia and tachydysrhythmias.
Hallucinogens may also have other physical effects, including mydriasis, blurred vision, sweating, palpitations, and impaired coordination. Many other hallucinogens cause nausea and vomiting.
Diagnosis of Hallucinogen Use
History and physical examination
ECG
For psychosis, psychiatric evaluation
A presumptive diagnosis is made when a patient reports ingestion of what they believe to be a hallucinogen, reports typical effects of use, and has characteristic changes in vital signs and other physical examination findings.
Except for phencyclidine (PCP), most hallucinogens are not included in routine urine drug screening tests.
The evaluation is similar to other substance ingestions, and testing should include: serum glucose (use a rapid point-of-care test, if available); complete metabolic profile; concentrations of salicylate, acetaminophen, and ethanol; and concentrations of any current medications prescribed to the patient. A urine toxicological screen and a urinalysis should be performed.
Initial ECG is typically performed in all patients. In patients with chest pain or tachycardia, at least 2 ECGs should be obtained one hour apart to observe for changes in morphology or intervals and serial serum troponins are measured.
The definitive diagnosis of hallucinogen toxicity requires demonstrating that a toxic amount of the hallucinogen was present in the patient when the patient had concordant symptoms. In practice this level of certainty is difficult to achieve. The longer the interval between ingestion and collection of the sample, the more difficult it is to estimate the amount ingested. Quantitative serum testing is not available for all hallucinogens and for no hallucinogens in real time.
For patients who are hemodynamically unstable, clinicians should not presume this status is due to hallucinogen toxicity, unless the patient ingested a large ingestion of a phenethylamine derivative. In any hemodynamically unstable patient with poisoning or overdose, a medical toxicologist should be consulted.
If patient exhibit severe or persistent psychotic symptoms, a psychiatric evaluation should be performed.
Treatment of Hallucinogen Toxicity
For acute intoxication, observation and sometimes benzodiazepines to reduce anxiety and agitation
For persistent psychosis, psychiatric care
For acute intoxication from hallucinogens, 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. Benzodiazepines (eg, lorazepam, diazepam) may be helpful if the patient has severe anxiety. As a last resort, patients with severe persistent agitation may require chemical and physical restraints as a last resort.
If hyperthermia and tachydysrhythmias occur, these require immediate treatment with benzodiazepines and cooling measures, as discussed for treatment of amphetamine toxicity.
Patients who exhibit severe or persistent psychotic symptoms, require psychiatric consultation and care.
Chronic Hallucinogen Use
Complications
Habitual users, particularly of LSD, experience hallucinogen persistent perception disorder (HPPD), or flashbacks, long after they have discontinued 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. The mechanisms are not known. Flashbacks tend to subside within 6 to 12 months, but can recur for years. 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.
Persistent psychotic states or other psychiatric disorders require appropriate psychiatric care.
Tolerance and dependence
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. Psychological dependence varies greatly; there is no evidence of physical dependence or a withdrawal syndrome.
Key Points
Hallucinogens (eg, lysergic acid diethylamide [LSD], psilocybin, mescaline, ayahuasca) are a diverse group of drugs that can cause unpredictable, idiosyncratic reactions.
Diagnosis is by history and physical examination.
Intoxication typically causes hallucinations, altered perception, impaired judgment, ideas of reference, and depersonalization. Toxicity may include nausea, vomiting, mydriasis, blurred vision, sweating, impaired coordination, and most seriously, hyperthermia and tachydysrhythmias.
Diagnose with history and physical examination and excluding other drug use (eg, alcohol).
Manage with monitoring and sometimes benzodiazepines for anxiety or tachydysrhythmias or external cooling measures for hyperthermia.
There is no stereotypical withdrawal syndrome.
Drug Information for the Topic
