Hallucinogen persisting perception disorder and the serotonergic system: A comprehensive review including new MDMA-related clinical cases
This review (2014) examines the role of serotonergic transmission in Hallucinogen persisting perception disorder (HPPD), a rare perceptual disorder caused by LSD, and other classical hallucinogens, as well as MDMA. The disorder may be a result of a misbalance of inhibitory-excitatory activity in low-level visual processing caused by interneurons expresses 5-HT2A receptors, whose activity would normally suppress afterimages through inhibitory GABA release.
Authors
- Litjens, R. P. W.
- Brunt, T. M.
- Alderliefste, G.
Published
Abstract
Introduction
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.
Methods
Available evidence on HPPD and drug-related altered visual processing was reviewed...
Results
... 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.
Discussion
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.
Research Summary of 'Hallucinogen persisting perception disorder and the serotonergic system: A comprehensive review including new MDMA-related clinical cases'
Introduction
Litjens and colleagues introduce Hallucinogen Persisting Perception Disorder (HPPD) as a drug‑induced, long‑lasting disturbance of perception that resembles a ‘‘persistent drug trip’’. The Introduction summarises that classical hallucinogens (for example LSD and psilocybin) produce acute visual distortions such as altered colours, geometric patterns and trailing, and that a minority of users report persistent recurrent perceptual symptoms severe enough to meet DSM IV‑TR criteria for HPPD. Prevalence estimates vary widely across populations and study methods; the authors note limited, heterogeneous epidemiological data and uncertainty about which drugs and neurobiological mechanisms are implicated in HPPD. The paper sets out to review the available evidence on HPPD and drug‑related alterations in visual processing, with particular attention to serotonergic mechanisms. In addition to the literature review, the authors report a series of 31 previously unpublished clinical cases from an addiction psychiatry service, many of which implicate ecstasy (MDMA) as a suspected precipitant. The stated aim is to integrate clinical, pharmacological and neurophysiological evidence to clarify possible etiological pathways for HPPD and to highlight gaps for future research.
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Study Details
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- APA Citation
Litjens, R. P., Brunt, T. M., Alderliefste, G., & Westerink, R. H. (2014). Hallucinogen persisting perception disorder and the serotonergic system: A comprehensive review including new MDMA-related clinical cases. European Neuropsychopharmacology, 24(8), 1309-1323. https://doi.org/10.1016/j.euroneuro.2014.05.008
References (9)
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Baggott, M. J., Coyle, J. R., Erowid, E. et al. · Drug and Alcohol Dependence (2011)
Carhart-Harris, R. L., Nutt, D. J. · Journal of Substance Use (2010)
Geyer, M. A., Vollenweider, F. X. · Trends in Pharmacological Sciences (2008)
Halpern, J. H., Pope Jr, H. G. · Drug and Alcohol Dependence (2003)
Johnson, M. W., Sewell, R. A., Griffiths, R. R. · Drug and Alcohol Dependence (2012)
Passie, T., Halpern, J. H., Stichtenoth, D. O. et al. · CNS Neuroscience and Therapeutics (2008)
Passie, T., Seifert, J., Schneider, U. et al. · Addiction Biology (2002)
Studerus, E., Gamma, A., Kometer, M. et al. · PLOS ONE (2012)
Winter, J. C. · Psychopharmacology (2008)
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