Hallucinogen Use Disorder

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 Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology perceptions.

Classification

Intoxication:

Acute intoxication appears with agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus or aggression Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. Oppositional Defiant Disorder as well as psychotic symptoms Psychotic symptoms Brief Psychotic Disorder 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 Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship experience physical ( nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, 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 Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever, and body aches) and/or psychological symptoms (compulsion or perceived need to use the substance). 
• Hallucinogens don’t cause withdrawal syndromes.

Tolerance Tolerance Pharmacokinetics and Pharmacodynamics:

Tolerance Tolerance Pharmacokinetics and Pharmacodynamics 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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency:

• 10% lifetime use in the United States
• Higher prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of use among males

Hallucinogen use is linked with lower morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status 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 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS, dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS, and glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids)
• Modes of ingestion: mostly oral, but also smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, inhalation, and IV injections

Clinical Presentation and Diagnosis

Hallucinogen intoxication

Effects of acute intoxication may be referred to as a “trip.” “Bad trip” symptoms can include anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, panic, and psychotic symptoms Psychotic symptoms Brief Psychotic Disorder (paranoia, hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia).

Four different phases can be distinguished:

1. Initial phase Initial Phase Sepsis in Children:
   • Inner unrest
   • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
   • 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 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
   • Depressive state

General symptoms:

• Perceptual changes:
  • Illusions Illusions The misinterpretation of a real external, sensory experience. Schizophrenia
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Body-image distortions
  • Synesthesia
• Labile affect
• Dilated pupils
• Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
• 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
• Hyperthermia
• Tremors
• Incoordination
• Sweating
• Palpitations Palpitations Ebstein’s Anomaly
• Note: LSD may cause serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome if combined with other drugs that increase serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS.
  • Selective serotonin reuptake inhibitors Selective Serotonin Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants ( SSRIs SSRIs Serotonin Reuptake Inhibitors and Similar Antidepressants)
  • Serotonin-norepinephrine reuptake inhibitors Serotonin-Norepinephrine Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants ( SNRIs SNRIs Serotonin Reuptake Inhibitors and Similar Antidepressants)
  • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants ( TCAs TCAs Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants)
  • Tramadol Tramadol A narcotic analgesic proposed for severe pain. It may be habituating. Opioid Analgesics

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 jirovecii/Pneumocystis Pneumonia (PCP):
  • Violent behavior, impulsivity Impulsivity Attention Deficit Hyperactivity Disorder, severe hyperthermia 
  • Nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism
  • 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
• LSD:
  • Visual hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Depersonalization Depersonalization State in which an individual perceives or experiences a sensation of unreality concerning the self or the environment; it is seen in disorders such as schizophrenia, affection disorders, organic mental disorders, and personality disorders. Depersonalization/Derealization Disorder

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 Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology alterations produced by the drugs. 
• Hallucinogen-persisting perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment 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 Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus 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 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. First-Generation Antipsychotics) 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
  • 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 Physicians Individuals licensed to practice medicine. Clinician–Patient Relationship should try to build a rapport with patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship to treat underlying mood disorders or personality disorders Personality Disorders A major deviation from normal patterns of behavior. Cluster A Personality Disorders.
• There are no specific psychotherapeutic interventions indicated for hallucinogen use disorders.

Differential Diagnosis

• Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome: a life-threatening condition caused by large increases in serotonergic activity Serotonergic Activity Serotonin Syndrome. 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 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome is marked by autonomic hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder, neuromuscular instability, and altered mental status Altered Mental Status Sepsis in Children. Spontaneous clonus Clonus Ehrlichiosis and Anaplasmosis and hyperreflexia are highly specific findings of serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome that are not found in intoxication with hallucinogens. 
• Amphetamine intoxication Amphetamine intoxication Amphetamine Use Disorder: amphetamines Amphetamines Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. Stimulants produce their effect by increasing the release and blocking the reuptake of neurotransmitters ( dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS, norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS, serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS). Intoxication results in euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy, 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. Skin: Structure and Functions excoriation Excoriation Mastitis, paranoia, and severe aggression Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. Oppositional Defiant Disorder. 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 intoxication Cocaine Use Disorder: cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics 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 Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS, epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs, and norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS from the synaptic cleft Synaptic cleft Synapses and Neurotransmission, causing a stimulant effect ( euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy, increased energy, irritability, psychosis, decreased appetite, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery) similar to that of amphetamines Amphetamines Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. Stimulants. Withdrawal symptoms include severe depression and fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia. 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 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics.