Other Hallucinogen (LSD, MDMA) Use Disorder

Primer

Other Hallucinogen Use Disorder is a substance use disorder characterized by a problematic pattern of hallucinogen use (not phencyclidine or phencyclidine-like substances) use leading to clinically significant impairment or distress. Of the other hallucinogens, MDMA is thought to have the greatest risk in terms of withdrawal symptoms and neurological impairment.

Epidemiology
  • In the United States, the 12-month prevalence is estimated to be 0.5% among 12- to 17-year-olds, and 0.1% in adults.[1]
    • Rates are highest in those younger than 30 years, and a peak at ages 18 to 29 years (0.6%)
    • Use is extremely rare in adults age 45 and over.
Prognosis
  • The course of other hallucinogen use disorder is not well known.[2]
  • Generally there is thought to be low persistence and high rates of recovery.[3]
Comorbidity
  • Adolescents who use MDMA and other hallucinogens have a higher prevalence of other substance use disorders.
  • Adults and adolescents who use MDMA are more likely to be polysubstance drug users and to have other drug use disorders.
  • Individuals are at higher risk for non-substance mental disorders such as anxiety disorders, depressive disorders, and bipolar disorders, especially with use of MDMA and salvia.
Risk Factors
  • Other substance use disorders such as alcohol, tobacco, and cannabis are risk factors
  • Major depressive disorder is associated with higher rates of other hallucinogen use disorder.
Cultural
  • Historically, hallucinogens have been used in established religious practices (e.g. - peyote in Native American Church). Ritual psilocybin use by indigenous populations occurs in South America, Mexico, and some areas in the United States.
  • Ayahuasca is a hallucinogenic tea used in the Santo Daime and Uniäo de Vegetal sects.
  • Regular use of hallucinogens as part of religious rituals is not linked to neuropsychological or psychological deficits.

DSM-5 Diagnostic Criteria

Criterion A

A problematic pattern of hallucinogen (other than phencyclidine) use leading to clinically significant impairment or distress, as manifested by at least 2 of the following, occurring within a 12-month period:

  1. The hallucinogen is often taken in larger amounts or over a longer period than was intended.
  2. There is a persistent desire or unsuccessful efforts to cut down or control hallucinogen use.
  3. A great deal of time is spent in activities necessary to obtain the hallucinogen, use the hallucinogen, or recover from its effects.
  4. Craving, or a strong desire or urge to use the hallucinogen.
  5. Recurrent hallucinogen use resulting in a failure to fulfill major role obligations at work, school, or home (e.g. - repeated absences from work or poor work performance related to hallucinogen use; hallucinogen-related absences, suspensions, or expulsions from school; neglect of children or household).
  6. Continued hallucinogen use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the hallucinogen (e.g. - arguments with a spouse about consequences of intoxication; physical fights).
  7. Important social, occupational, or recreational activities are given up or reduced because of hallucinogen use.
  8. Recurrent hallucinogen use in situations in which it is physically hazardous (e.g. - driving an automobile or operating a machine when impaired by the hallucinogen).
  9. Hallucinogen use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the hallucinogen.
  10. Tolerance, as defined by either of the following:
    • A. A need for markedly increased amounts of the hallucinogen to achieve intoxication or desired effect.
    • B. A markedly diminished effect with continued use of the same amount of the hallucinogen.
Note: Withdrawal symptoms and signs are not established for hallucinogens, and so this criterion does not apply.

Specifiers

Hallucinogen Specifier

  • Specify: the particular hallucinogen

Remission Specifier

Specify if:

  • In early remission: After full criteria for other hallucinogen use disorder were previously met, none of the criteria for other hallucinogen use disorder have been met for at least 3 months but for less than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or urge to use the hallucinogen,” may be met).
  • In sustained remission: After full criteria for other hallucinogen use disorder were previously met, none of the criteria for other hallucinogen use disorder have been met at any time during a period of 12 months or longer (with the exception that Criterion A4, “Craving, or a strong desire or urge to use the hallucinogen,“ may be met).

Environment Specifier

Specify if:

  • In a controlled environment: This additional specifier is used if the individual is in an environment where access to hallucinogens is restricted.

Severity Specifier

Specify if:

  • Mild: Presence of 2 to 3 symptoms
  • Moderate: Presence of 4 to 5 symptoms
  • Severe: Presence of 6+ symptoms

Signs and Symptoms

  • Different specific signs and symptoms can result from different hallucinogens.
  • In MDMA use, there can be a significant post-use depression.[4]
    • Among the hallucinogens, MDMA users are more susceptible to withdrawal symptoms, and can be seen in over 60% of individuals.[5]
  • In LSD use, users may experience visual hallucinations that can be frightening.
  • Individuals intoxicated with hallucinogens may experience a temporary increase in suicidal ideation.[6]

Hallucinogens Types and Use

Common

  • Hallucinogens are a diverse group of substances with different chemical structures and molecular mechanisms that produce similar changes in perception, mood, and cognition.
  • Hallucinogens under the “Other Hallucinogen Use Disorder” diagnosis include:
    • Phenylalkylamines
      • Mescaline
      • 2,5-dimethoxy-4-methylamphetamine (DOM)
      • 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”)
    • Indoleamines
      • Psilocybin (psilocin)
      • Dimethyltryptamine (DMT)
    • Ergolines
      • Lysergic acid diethylamide (LSD)
      • Morning glory seeds
  • There are many other ethnobotanical compounds also referred to “hallucinogens,” (such as Salvia divinorum and jimsonweed).
  • Cannabis and its psychoactive compound delta-9-tetrahydrocannabinol (THC) can have hallucinogenic effects but are in a separate diagnostic category of cannabis-related disorders.

MDMA

  • 3,4-Methylenedioxymethamphetamine (commonly known as “MDMA,” “Ecstasy,” “E,” “XTC,” “X”) is a somewhat unique substance in that it is officially classified as a hallucinogen in the DSM-5, but actually has strong stimulant properties and also acts like an amphetamine.
    • Arguments have been made that MDMA should be in its own category of substances.[7]
  • Its effects include openness, empathy, energy, euphoria, enhanced colour perception, and a general sense of well-being.
  • Negative effects include restlessness, decreased appetite, altered focus/concentration, dyspnea, paresthesia, hyperhydrosis, and tachycardia.
  • At high doses, facial dystonia can develop (“gurning”)
  • Mechanism of action: release and re-uptake inhibition of serotonin, dopamine and norepinephrine, and binds to 5-HT2A and alpha-2 receptors
  • There is evidence for long-term neurotoxic effects of MDMA use, such as cognitive impairment, impairment in neuroendocrine function, serotonin system dysfunction, and sleep disturbance.
  • There many also be adverse effects on brain microvasculature, white matter maturation, and damage to axons.
  • Use of MDMA may also decrease functional connectivity between brain regions.[8]

Use

  • Hallucinogens are usually taken orally.
    • Some can be smoked (e.g. - DMT, salvia), or much rarely used intranasally or by injection (e.g. - MDMA).
  • LSD, MDMA in particular have a long half-life and users may spend hours to days using and/or recovering from their effects.
  • Other hallucinogens (e.g. - DMT, salvia) are much shorter acting.[9]

Tolerance

  • Tolerance to hallucinogens can develop with repeated use and have autonomic and psychological effects.
  • Cross-tolerance also exists between LSD and other hallucinogens.[10]

Screening and Rating Scales

  • Three three commonly used research questionnaires to assess the subjective effects of hallucinogens include:[11]
    • Hallucinogen Rating Scale (HRS)
    • Mystical Experience Questionnaire (MEQ)
    • Addiction Research Center Inventory (ARCI)
  • These are not used in routine clinical practice however.

Pathophysiology

  • Like with all substance use disorders, there is a complex interplay between biological, social, psychological, and cultural factors.

Differential Diagnosis

  • Other substance use disorders
    • The effects of hallucinogens should be distinguished from those of other substances (e.g. - amphetamines), especially because the risk of contamination of the hallucinogens with other drugs is high.
  • Schizophrenia
    • Individuals with schizophrenia may falsely attribute their symptoms to use of hallucinogens.
  • Other mental disorders or medical conditions
    • Other potential disorders or conditions to consider include panic disorder, depressive disorders, bipolar disorders, and alcohol or sedative withdrawal.
  • Other medical conditions
    • Hypoglycemia and other metabolic conditions, seizure disorder, stroke, ophthalmological disorders, and central nervous system tumours may also resemble the symptoms of a hallucinogen use disorder. A detailed clinical examination can help differentiate these cases.[12]

Investigations

  • As clinically indicated.

Physical Exam

  • As clinically indicated.

Treatment

  • There are no approved treatments to treat hallucinogen use disorder.[13]
  • Generally, routine clinical support and substance use disorder psychotherapies such as motivational interviewing are recommended.

Resources

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Research

References

1) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
2) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
3) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
4) Cohen, R. S. (1995). Subjective reports on the effects of the MDMA (" ecstasy") experience in humans. Progress in neuro-psychopharmacology & biological psychiatry.
5) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
6) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
7) Cottler, L. B., Leung, K. S., & Abdallah, A. B. (2009). Test–re‐test reliability of DSM‐IV adopted criteria for 3, 4‐methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross‐national study. Addiction, 104(10), 1679-1690.
8) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
9) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
10) Isbell, H., Wolbach, A. B., Wikler, A., & Miner, E. J. (1961). Cross tolerance between LSD and psilocybin. Psychopharmacologia, 2(3), 147-159.
11) Bouso, J. C., Pedrero‐Pérez, E. J., Gandy, S., & Alcázar‐Córcoles, M. Á. (2016). Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens. Human Psychopharmacology: Clinical and Experimental, 31(5), 356-372.
12) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
13) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.