Hallucinogen Use Disorder

Hallucinogen use disorder is defined by the pathologic consumption of hallucinogenic substances that cause perceptual distortions (visual or auditory). Examples include psilocybin (mushrooms), lysergic acid diethylamide (LSD), and phencyclidine (PCP). These drugs are used for their psychedelic effects, i.e., a temporarily altered state of consciousness. Most hallucinogens produce nausea, vomiting, and mild sympathomimetic effects such as tachycardia, hypertension, mydriasis, hyperthermia, and diaphoresis. Although hallucinogens may cause hyperthermia in severe cases, they don’t result in dependence or withdrawal symptoms.

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Overview

Definition

Hallucinogen use disorder describes a chronic (> 12 months), problematic pattern of hallucinogen use that causes significant distress. Hallucinogens are natural or synthetic intoxicants that alter multiple sensory perceptions.

Classification

Intoxication:

Acute intoxication appears with agitation or aggression as well as psychotic symptoms such as perceptual disturbances or changes in mood.

Withdrawal:

  • Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
  • Patients experience physical (nausea, diarrhea, chills, and body aches) and/or psychological symptoms (compulsion or perceived need to use the substance). 
  • Hallucinogens don’t cause withdrawal syndromes.

Tolerance:

Tolerance is the need to increase the dose of the substance to achieve the desired effect (diminished effect if using the same amount of the substance).

Epidemiology

Prevalence:

  • 10% lifetime use in the United States
  • Higher prevalence of use among males

Hallucinogen use is linked with lower morbidity and mortality compared with other substances.

Pharmacology

Mechanism of action

  • The exact mechanism of action is not well known.
  • May involve the interaction of numerous neurotransmitters (serotonin, dopamine, and glutamate)
  • Modes of ingestion: mostly oral, but also smoking, inhalation, and IV injections
Table: Different types of hallucinogenic drugs
HallucinogenFeaturesExamples
Psychedelics
  • Work via activation of serotonin 2A (5-HT2A) receptors
  • Main effects include changes in thought, mood, and perception.
  • Minimal intellectual and memory impairment
  • No stupor or narcotic effects
  • Lysergic acid diethylamide (LSD; “acid”)
  • Phencyclidine (PCP; “angel dust”)
  • Psilocybin (“shrooms”)
  • N,N-dimethyltryptamine (DMT)
  • Mescaline
Empathogen
  • Work via combined serotonin and dopamine reuptake inhibition and release
  • Produce experiences of emotional empathy and pleasure
MDMA (”ecstasy”)
Dissociative drugs
  • Act through N-methyl-d-aspartate (NMDA receptor)
  • Produce analgesia, amnesia, derealization, and dissociative perception
  • Horizontal and vertical nystagmus, marked hypertension, and seizures
  • Ketamine (“special K”)
  • Dextromethorphan

Clinical Presentation and Diagnosis

Hallucinogen intoxication

Effects of acute intoxication may be referred to as a “trip.” “Bad trip” symptoms can include anxiety, panic, and psychotic symptoms (paranoia, hallucinations).

Four different phases can be distinguished:

  1. Initial phase (inner unrest, tachycardia, vertigo)
  2. Delirious phase (psychedelic effects; e.g., the feeling of being able to fly)
  3. Relaxation phase
  4. After-effect phase (exhaustion, anxiety, depressive state)

General symptoms:

  • Perceptual changes (illusions, hallucinations, body image distortions, synesthesia)
  • Labile affect
  • Dilated pupils
  • Tachycardia
  • Hypertension
  • Hyperthermia
  • Tremors
  • Incoordination
  • Sweating
  • Palpitations
  • Note: LSD may cause serotonin syndrome if combined with other drugs that increase serotonin.

Specific symptoms:

  • PCP:
    • Violent behavior, impulsivity, severe hyperthermia 
    • Nystagmus
    • Seizures
  • LSD: 
    • Visual hallucinations
    • Depersonalization

Hallucinogen withdrawal

A withdrawal syndrome does not usually occur.

Hallucinogen use disorder

  • Many people use inhalants temporarily without developing dependence or withdrawal symptoms.
  • People may develop psychological dependence on the sensory alterations produced by the drugs. 
  • Hallucinogen-persisting perception disorder: the continued perceptual disturbances experienced during hallucinogen intoxication while the patient is sober

Management

Hallucinogen intoxication

The management of hallucinogen intoxication depends on the symptoms with which an individual presents.

  • Severe agitation or psychosis: 
    • Isolation of patient in quiet room 
    • 1st-line: benzodiazepines and antipsychotics (e.g., haloperidol) for sedation
    • For medications, IV route is preferred due to its rapid onset. 
    • Symptomatic support (i.e., control of hypertension and arrhythmias)
    • Treating hyperthermia (ice bath, cooling blanket)
  • Hemodynamic changes: 
    • Supportive care 
    • Hydration and correction of electrolytes

Hallucinogen withdrawal

There is no FDA-approved pharmacotherapy for hallucinogen withdrawal as the symptoms are mild.

Hallucinogen use disorder

  • Physicians should try to build a rapport with patients to treat underlying mood disorders or personality disorders.
  • There are no specific psychotherapeutic interventions indicated for hallucinogen use disorders.

Differential Diagnosis

  • Serotonin syndrome: a life-threatening condition caused by large increases in serotonergic activity. The syndrome can be triggered by taking excessive doses of certain serotonergic medications or taking these medications in combination with other drugs that increase their activity. Serotonin syndrome is marked by autonomic hyperactivity, neuromuscular instability, and altered mental status. Spontaneous clonus and hyperreflexia are highly specific findings of serotonin syndrome that are not found in intoxication with hallucinogens. 
  • Amphetamine intoxication: amphetamines produce their effect by increasing the release and blocking the reuptake of neurotransmitters (dopamine, norepinephrine, serotonin). Intoxication results in euphoria, pupillary dilation, hypertension, skin excoriation, paranoia, and severe aggression. Fatal complications can arise from myocardial infarction and coma. Presenting findings are often similar to hallucinogen intoxication and management of either substance should consider the other.
  • Cocaine intoxication: cocaine is an indirect sympathomimetic that blocks the reuptake of dopamine, epinephrine, and norepinephrine from the synaptic cleft, causing a stimulant effect (euphoria, increased energy, irritability, psychosis, decreased appetite, weight loss) similar to that of amphetamines. Withdrawal symptoms include severe depression and fatigue. Treatment options are limited and include benzodiazepines for acute intoxication as well as psychotherapy for long-term treatment. Hallucinogens don’t result in dependence or withdrawal symptoms, unlike cocaine.

References

  1. First Aid for the Psychiatry Clerkship, 4th edition, chapter 7, Substance-related and addictive disorders, pages 80, 91–92.
  2. Le T, Bhusan V, Sochat M, et al. (Eds.) (2020). First Aid for the USMLE Step 1, 30th ed. (p. 559).
  3. Thompson, A. (2021). Clinical management of drug use disorders. DeckerMed Medicine.
  4. Sadock BJ, Sadock VA, Ruiz, P. (2014). Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.). Chapter 20, Substance use and addictive disorders, pages 656–659. Philadelphia, PA: Lippincott Williams and Wilkins.
  5. Leikin JB, Krantz AJ, Zell-Kanter M, Barkin RL, Hryhorczuk DO. (1989). Clinical features and management of intoxication due to hallucinogenic drugs. Medical toxicology and adverse drug experience, 4(5), 324–350. https://doi.org/10.1007/BF03259916

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