Disorders due to use of hallucinogens

ICD-10F16	Mental and behavioral disorders due to use of hallucinogens
DSM-5-TRF16.20	Other Hallucinogen Use Disorder, Moderate or Severe

1. Definition and nosology

Disorders due to use of hallucinogens (ICD-11: 6C49; DSM-5-TR: F16.20 Hallucinogen Use Disorder) — disorders related to use of LSD, psilocybin, mescaline, DMT, ayahuasca, and similar substances. Dissociative drugs — ketamine and phencyclidine (PCP) — are coded separately in ICD-11 (6C4D).

2. History

• Hofmann A. (1943) — accidental discovery of LSD’s hallucinogenic effect.
• 1950s–1960s — clinical research (depression, schizophrenia).
• 1970 — Controlled Substances Act in the US, Schedule I.
• 2020+ — psilocybin and ketamine “psychedelic therapy” research renaissance.

3. Epidemiology

• Dependence is relatively rare (unlike other substances); typical use is episodic.
• Hallucinogen Persisting Perception Disorder (HPPD) — flashback-like experiences.

4. Etiology and pathogenesis

• Effect on serotonergic (5-HT2A) or NMDA (ketamine, PCP) receptors.
• Environment, peers, experimentation.

5. Clinical features

• Intoxication — visual hallucinations, synesthesia, time distortion, depersonalization, derealization, “bad trip” (panic, paranoia).
• In severe cases — psychosis, fatal accidents.
• “Hallucinogen persisting perception disorder” (HPPD) — persistent visual phenomena (flashbacks) after use.
• Ketamine — dissociation, “K-hole”; chronic use — ketamine-associated uropathy.
• PCP — aggressive behavior, analgesia, disorganized behavior.

6. Diagnosis

6.1 Unified diagnostic criteria

DSM-5-TR 11 criteria; HPPD is a separate diagnosis (DSM-5). Unlike DSM-5-TR, which uses a single severity scale, ICD-11 uses three separate categories: episode of harmful use, harmful pattern of use, and dependence. ICD-11 duration requirement: harmful pattern of use — at least 12 months if use is episodic, at least 1 month if continuous; dependence — at least 12 months, or at least 3 months if use is continuous (daily or almost daily).

6.2 Differences between sources

• NIDA, SAMHSA.

6.3 Diagnostic algorithm

1. Clinical interview.
2. Toxicology (LSD not in standard panels).
3. Comorbid psychosis, anxiety, MDD.

6.4 Differential diagnosis

7. Examination and assessment

• Toxicology.
• Comorbidity scales.

8. Treatment

1. Acute intoxication (“bad trip”) — calm environment, benzodiazepine (lorazepam); antipsychotic (haloperidol) only in severe psychotic state; caution.
2. Dependence rare; psychosocial intervention (MI, CBT).
3. HPPD — antipsychotics usually ineffective; clonazepam helps some patients; long-term monitoring.
4. Psilocybin and ketamine therapeutic research (refractory MDD, PTSD) — used under supervision in research protocols; approved protocols in standard clinical practice are still limited (FDA esketamine Spravato is an exception).

8.1 Treatment methods

1. “Bad trip” management — Calm environment, reassurance, benzodiazepine as needed.
2. Clonazepam for HPPD — Off-label; evidence base small.
3. Psychedelic-assisted therapy (research phase) — Psilocybin + psychotherapy, ketamine + psychotherapy; in clinical trial protocols.

8.2 Differences between sources

• NIDA — psychedelic research renaissance; clinical recommendation still pending.

9. Prognosis

• Most users do not develop dependence.
• Chronic course in patients with severe psychotic or HPPD complications.

10. Myths and misconceptions

Myth 1: “Hallucinogens are not addictive, they are completely safe”

Evidence: Physical dependence is rare, but psychological dependence and severe psychotic episodes are possible; HPPD is a long-term complication.

Myth 2: “Psilocybin therapy is an approved treatment for depression”

Evidence: still under research phase; not fully approved into standard clinical practice. FDA ‘Breakthrough Therapy’ status, but a broad recommendation is premature.

Myth 3: “Ayahuasca is safe for religious ritual”

Evidence: serotonin syndrome (interaction with SSRI), psychotic decompensation cases have been reported.

Myth 4: “Ketamine is only a ‘club drug’, it has no medical use”

Evidence: Ketamine has been used as an anesthetic for decades; intranasal esketamine (Spravato) FDA-approved in 2019 for treatment-resistant depression.

Myth 5: “LSD ‘flashback’ is a myth”

Evidence: HPPD DSM-5 official diagnosis; some patients have persistent visual disturbances.

11. Sources

1. WHO. ICD-11. 6C49 Disorders due to use of hallucinogens. 2024.
2. APA. DSM-5-TR. 2022.
3. NIDA. Hallucinogens DrugFacts. 2019.
4. Halpern J.H., Lerner A.G., Passie T. A review of Hallucinogen Persisting Perception Disorder (HPPD). Curr Top Behav Neurosci 2018;36:333–360.
5. Carhart-Harris R.L. et al. Trial of psilocybin versus escitalopram for depression. NEJM 2021;384(15):1402–1411.