Hallucinogen persisting perception disorder and the serotonergic system: a comprehensive review including new MDMA-related clinical cases.
Ruud P. W. Litjens, Tibor M Brunt, Gerard-Jan Alderliefste, Remco H S Westerink
European Neuropsychopharmacology August 2014 DOI: 10.1016/j.euroneuro.2014.05.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Sample size | 31 |
| Population | Individuals with hallucinogen persisting perception disorder, including 31 new cases linked to ecstasy (MDMA) use |
| Topics | LSD MDMA Serotonin |
| Keywords | Hppd Hallucinogen |
| Key findings | The authors argue that HPPD may result from a misbalance of inhibitory-excitatory activity in low-level visual processing, potentially involving GABA-releasing inhibitory interneurons, and that most cases are attributed to drugs acting on 5-HT2A receptors. They present 31 new cases suggesting that ecstasy (MDMA) use may also induce HPPD symptoms, though evidence remains sparse and co-morbidities complicate the etiology. |
Abstract
Hallucinogen persisting perception disorder (HPPD) is a drug-induced condition associated with inaccurate visual representations. Since the underlying mechanism(s) are largely unknown, this review aims to uncover aspects underlying its etiology. Available evidence on HPPD and drug-related altered visual processing was reviewed and the majority of HPPD cases were attributed to drugs with agonistic effects on serotonergic 5-HT₂A receptors. Moreover, we present 31 new HPPD cases that link HPPD to the use of ecstasy (MDMA), which is known to reverse serotonin reuptake and acts as agonist on 5-HT₂A receptors. The available evidence suggests that HPPD symptoms may be a result from a misbalance of inhibitory-excitatory activity in low-level visual processing and GABA-releasing inhibitory interneurons may be involved. However, high co-morbidities with anxiety, attention problems and derealization symptoms add complexity to the etiology of HPPD. Also, other perceptual disorders that show similarity to HPPD cannot be ruled out in presentations to clinical treatment. Taken together, evidence is still sparse, though low-level visual processing may play an important role. A novel finding of this review study, evidenced by our new cases, is that ecstasy (MDMA) use may also induce symptoms of HPPD.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |
Citations in the library
Cited by 37
- Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review Journal of Psychopharmacology August 26, 2022
- Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives Brain Sciences March 16, 2018
- Safety pharmacology of acute MDMA administration in healthy subjects Journal of Psychopharmacology February 21, 2017
- Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry February 2, 2018
- Substance-Induced Psychoses: An Updated Literature Review Frontiers in Psychiatry December 23, 2021
and 32 more in the library
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