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 PCP Pneumocystis jiroveci is a yeast-like fungus causing pneumocystis pneumonia (PCP) in immunocompromised patients. Pneumocystis pneumonia is spread through airborne transmission and classically affects patients with AIDS, functioning as an AIDS-defining illness. Patients may present with insidious onset of fever, chills, dry cough, chest pain, and shortness of breath. Pneumocystis jiroveci/Pneumocystis Pneumonia (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 Sympathomimetic Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (α, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs effects such as tachycardia, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. 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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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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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 Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. 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
Hallucinogen Features Examples
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 PCP Pneumocystis jiroveci is a yeast-like fungus causing pneumocystis pneumonia (PCP) in immunocompromised patients. Pneumocystis pneumonia is spread through airborne transmission and classically affects patients with AIDS, functioning as an AIDS-defining illness. Patients may present with insidious onset of fever, chills, dry cough, chest pain, and shortness of breath. Pneumocystis jiroveci/Pneumocystis Pneumonia (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 Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. 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 Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. 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 Serotonin syndrome Serotonin syndrome is a life-threatening condition caused by large increases in serotonergic activity. This condition 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 if combined with other drugs that increase serotonin.

Specific symptoms:

  • PCP PCP Pneumocystis jiroveci is a yeast-like fungus causing pneumocystis pneumonia (PCP) in immunocompromised patients. Pneumocystis pneumonia is spread through airborne transmission and classically affects patients with AIDS, functioning as an AIDS-defining illness. Patients may present with insidious onset of fever, chills, dry cough, chest pain, and shortness of breath. Pneumocystis jiroveci/Pneumocystis Pneumonia (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 Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. 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 Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and arrhythmias)
    • Treating hyperthermia (ice bath, cooling blanket)
  • Hemodynamic changes: 
    • Supportive care 
    • Hydration and correction of electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. 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 Serotonin syndrome Serotonin syndrome is a life-threatening condition caused by large increases in serotonergic activity. This condition 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 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 Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin excoriation, paranoia, and severe aggression. Fatal complications can arise from myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction and coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. 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 Sympathomimetic Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (α, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs 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 Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines for acute intoxication as well as psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. 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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