Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Suggested Etiologies
3.2. Substances That Induce HPPD
3.3. Clinical Features
3.4. Mental Illnesses Comorbid with HPPD
3.5. First-Line Medications
3.6. Second Line Medications
3.7. Brain Stimulation Treatments
4. Discussion
Author Contributions
Conflicts of Interest
References
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Authors | Cases (n) | Substances Inducing Perceptual Disturbances | Trigger Cues |
---|---|---|---|
Zobor, 2015 [29] | 1 | Cannabis | |
Gaillard, 2003 [46] | 2 | Cannabis | |
Lerner, 2014 [47] | 2 | Cannabis (Synthetic) | |
Anderson, 2017 [48] | 1 | Cannabis and MDMA | Stress |
Brodrick, 2016 [49] | 1 | Cannabis and LSD | |
Coppola, 2017 [50] | 1 | Cannabis (Synthetic, JWH-122) | Cannabis consumption |
Lerner, 2003 [51] | 16 | LSD | |
Lerner, 2002 [20] | 1 | LSD | |
Lerner, 2000 [52] | 8 | LSD | |
Gaillard, 2003 [46] | 1 | LSD | Alcohol intake |
Lev-Ran, 2017 [53] | 40 | LSD | Sexual intercourse or Intentional |
Hermle, 2012 [54] | 1 | LSD | Stress |
Lerner, 2014 [19] | 2 | LSD | |
Abraham, 2001 [35] | 38 | LSD | Dark environment |
Litjens, 2014 [26] | 31 | LSD | |
Lerner, 2015 [55] | 1 | LSD | |
Baggott, 2011 [56] | 104 | LSD | |
Lev-Ran, 2015 [57] | 37 | LSD | |
Lev-Ran, 2014 [58] | 12 | LSD | Situation and mental states |
Lerner, 1997 [59] | 2 | LSD | |
Abraham, 1996 [34] | 3 | LSD | |
Espiard, 2005 [21] | 1 | PCP | Cannabis consumption |
Lauterbach, 2000 [60] | 1 | Risperidone |
Symptom | Description |
---|---|
Symptom Reported by Diagnostic and Statistical Manual of Mental Disorder, fifth edition (DSM-5) | |
Visual hallucinations | Perceptions in the absence of the objects. False perceived objects are often geometric figures. |
Altered motion perception | False perceptions of movement in the peripheral visual fields |
Flashes of color | |
Color enhancement | Perception of intensified colors |
Trails or tracers | Lines, stripes or bands that could be observed after animate and inanimate objects have already moved from their previous location. According to DSM-5, images left suspended in the path of a moving object as seen in stroboscopic photography |
Palinopsia | Positive afterimages that continue to appear in one’s vision after the exposure to the original image has ceased. |
Halos | Colored light around a light source or an object |
Micropsia | Misperception of images as too small |
Macropsia | Misperception of images as too large |
Common Symptoms Not Reported by DSM-5 | |
Floaters | Spots that seem to drift in front of the eye |
Visualizations | Dots, points, particles, mottles or specks emerging in an obscure room |
Fractals | Self-similarity perception or small parts that are seen having an equal and identical shape or form as the whole |
Repetitions | Recurrence of inanimate or moving patterns or motives |
Keenness | Undimmed color contrasts |
Pareidolia | An image within an image like the imagery of objects or faces in a foggy arrangement |
Superimpositions | Superimposed or overlapped geometric patterns |
Distorted Perception of Distance | Objects were seen slightly closer or distant |
Monochromatic Vision | The visual perception of distinct colors as one unique color with different tinges and tonalities |
Intense fragmentation | The sense of disintegration of still or moving objects |
Recurrent Synesthesia | Stimulation of one sensory pathway leads to automatic, involuntary reactions or experiences in a second sensory pathway |
Geometric Phosphenes | Seeing light without light penetrating the eye. |
Imagistic Phosphenes | Casual and unplanned formed images like non-humans (zoopsia) and human faces without geometric patterns or figures provoked by closing an eye and pressing it with a finger |
Acquired Dyslexia | Difficulty with reading notwithstanding normal intelligence |
Aeropsia or Visual Snow | Virtually seeing particles of air |
Authors | Study | Number of Patients | Substances | Symptoms Description | Onset Perceptual Disorders | Recurrence of Perceptual Disorders | Treatment |
---|---|---|---|---|---|---|---|
Lev-Ran, 2015 [57] | Observational, cross-sectional, control study | 80 hospitalized SCZ patient with past use of LSD 43 SCZ (DSM-IV-TR) 37 SCZ+HPPD (DSM-IV-TR) Onset of illness: 22.9 SCZ, 23.4 SCZ+HPPD * | Cannabis: 100% SCZ, 92% SCZ+HPPD * MDMA: 60% SCZ, 46% SCZ+HPPD * Opioids: 26% SCZ, 30% SCZ+HPPD 30% * Cocaine: 16% SCZ, 14% SCZ+HPPD * LSD initiation use: SCZ 17.9y, SCZ+HPPD 19.3y * | Adversive LSD experience (bad trip): 28% SCZ, 89% SCZ+HPPD ** PANSS: Positive symptoms: SCZ = SCZ+HPPD ** Negative symptoms: SCZ > SCZ+HPPD ** General psychopathology: SCZ > SCZ+HPPD ** Total score: SCZ > SCZ+HPPD ** | Treatment ineffective in SCZ+HPPD | Antipsychotic medication | |
Lev-Ran, 2014 [58] | Observational | 26 patients 14 SCZ (DSM-IV-TR)12 SCZ+HPPD (DSM-IV-TR) Demographic characteristic did not differ between the two groups | Past use of :LSD (100%) cannabis (100%) MDMA (7%) No differences between the two groups in age at onset of drug use and in number of incidences of hallucinogen use | 67% SCZ+HPPD could distinguish HPPD symptoms from hallucination related to a psychotic state | 9 SCZ+HPPD patients recognized precursory cues for perceptual distortion (7 substance-induced, 5 situational, and 2 mental cues) | 12 patients experienced perceptual distortion (SCZ+HPPD) | Antipsychotic treatment. No significant differences in response to APS and adverse effects between the two groups |
Lauterbach, 2000 [60] | Case report | 1 psychotic patient | No reported substance abuse and hallucinogen exposure Risperidone Clonazepam Trazodone | HPPD-like symptoms: palinopsia, illusions, and visual disturbances | After risperidone treatment | Weekly recurrence. Remission in 48 h each time |
Authors | Study | Number of Patients | Substances | Symptoms Description | Onset Perceptual Disorders | Recurrence of Perceptual Disorders | Treatment |
---|---|---|---|---|---|---|---|
Lev-Ran, 2017 [53] | Observational cross-sectional study | 40 (27 males); HPPD (DSM-IV-TR) | Previous use of LSD; Lifetime use of Cannabis | HPPD I: mean age 25.5 (3.7), times of LSD consumption: 7.1 (4.3), use of alcohol; perceptual disorders triggered by sexual intercourse, dark environment, and looking at still or moving objects | None of the subjects included in the study received medications particularly targeted at treating HPPD | ||
HPPD II: mean age 22.1 (2.8), times of LSD consumption 24.6 (1.4), use of SCS, stimulants and inhalants; intentionally triggering perceptual disturbances | |||||||
Zobor, 2015 [29] | Observational, cross-sectional, control study | Male, 23-year-old | Cannabis, previous 4-year history of heavy consumption (16–20 years) | Visual distortion: visual snow, sperm-like whizzing dot, jittering lights, floaters, photophobia, visual discomfort, positive and negative afterimages, impaired night vision, halos, starburst around lights; | During cannabis use period | Persistence despite cannabis withdrawal | No |
Ophthalmological examination: reduction of phosphene threshold, alteration in the EOG | |||||||
4 healthy subjects, mean age 25.5 years | Cannabis: Heavy consumption | Not reported | Not reported | No | |||
Lerner, 2014 [19] | Case report | Male, 24-year-old | Cannabis: Three-year past history of social consumption; | Visual disturbances (halos, color intensification, flashes of colors, distorted perception of distance) | During LSD intoxication | Recurrence one week after completely stopping all substance use: daily visual distortion | Not accepted by the patients |
MDMA, LSD and cocaine (sporadically); | |||||||
Social Alcohol drinking | Disappearance after one year | ||||||
Female, 25-year-old | Cannabis: Three-year past history of social consumption; | Visual disturbances (positive afterimages, color intensification, flashes of colors, trailing phenomena) | During LSD intoxication | Recurrence four days after completely stopping all substance use: daily visual distortion | Not accepted by the patients | ||
MDMA, LSD (sporadically); | Improvement after one year; | ||||||
Social Alcohol drinking | Trailing phenomena continued to appear intermittently | ||||||
Gaillard, 2003 [46] | Case reports | Female, 18-year-old | Cannabis: Three-year past history of regular consumption | White dots when looking at a white wall or blue sky, “seeing shadows” on the left side, palinopsia, visual vibration upon awakening | During comatose episode following excessive use of cannabis | Recurrence after stopping all substance use: daily visual distortion | |
Male, 25-year-old | Cannabis: Two-year past history of regular and heavy consumption | Visual illusion and dyskinetopsia, difficult in depth perception | After two years of consumption | Symptoms persistence and increase after cannabis withdrawal + memory loss, and concentration deficits | |||
Abraham, 2001 [35] | Observational | 38 HPPD cases | LSD: first mean use 18.1 (6.0) years; lifetime use 16 times (median) | 7.11 (2.2) different types of visual hallucinations per subject | 21 months after first use | Duration of visual hallucinations: 9.67 (7.68) years | |
13.5% subjects experienced symptoms within the first month of use, three subjects after a single use | |||||||
The majority of subjects reported an intensification of visual hallucinations on emerging into a dark environment | |||||||
Litjens, 2014 [26] | Case series | 31 HPPD cases; Web-questionnaire | MDMA | At least 2 different visual phenomena (visual snow, afterimages, flashes, illusory movement, and increased observation of floaters) with a minimum of one episode of disturbed perception every week (100%); | After a single drug exposure | ||
Cannabis | |||||||
LSD | Anxiety or panic in the weeks before or following the use of drugs (71%) | ||||||
Depersonalization (32%) | |||||||
assessment | 80% serotonergic drugs | Derealization (39%) | After a period of extensive drug use | ||||
Lerner, 2015 [55] | Case report | Male, 26-year-old | Cannabis: a Five-year history of occasional consumption; | No distressing macropsia, micropsia, pelopsia and teleopsia, looking at still or moving objects and humans; | LSD intoxication | Recurrence two days after completely stopping all substance use: daily visual distortion | Not accepted by the patients |
Alcohol: Social Consumption; | |||||||
LSD: Recreational use | Longer and distressing visual distortion experience with anxiety | ||||||
Disappearance after one year | |||||||
Baggott, 2011 [56] | Observational Web-based questionnaire | 2679 subjects | Median of 5 different drugs used by a single subject | 224 subjects reported having at least one diagnosis associated with unusual visual experiences; | After exposure to LSD | The probability of experiencing constant or near-constant symptoms was predicted by greater past exposure to drugs and exposure to LSD | 104 individuals considered symptoms impairing enough to seek treatment |
89.5% male, aged 21.6 (3.7) years | 1487 individuals reported at least one abnormal visual experience; | ||||||
587 endorsed at least one experience on a constant or near-constant basis |
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Martinotti, G.; Santacroce, R.; Pettorruso, M.; Montemitro, C.; Spano, M.C.; Lorusso, M.; Di Giannantonio, M.; Lerner, A.G. Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives. Brain Sci. 2018, 8, 47. https://doi.org/10.3390/brainsci8030047
Martinotti G, Santacroce R, Pettorruso M, Montemitro C, Spano MC, Lorusso M, Di Giannantonio M, Lerner AG. Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives. Brain Sciences. 2018; 8(3):47. https://doi.org/10.3390/brainsci8030047
Chicago/Turabian StyleMartinotti, Giovanni, Rita Santacroce, Mauro Pettorruso, Chiara Montemitro, Maria Chiara Spano, Marco Lorusso, Massimo Di Giannantonio, and Arturo G. Lerner. 2018. "Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives" Brain Sciences 8, no. 3: 47. https://doi.org/10.3390/brainsci8030047
APA StyleMartinotti, G., Santacroce, R., Pettorruso, M., Montemitro, C., Spano, M. C., Lorusso, M., Di Giannantonio, M., & Lerner, A. G. (2018). Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives. Brain Sciences, 8(3), 47. https://doi.org/10.3390/brainsci8030047