Migraine prevalence in visual snow with prior illicit drug use (Hallucinogen Persisting Perception Disorder) versus without

This between-subjects cohort study (n=48) compared the prevalence of migraine in individuals with visual snow (continuously flickering dot hallucination) in a cohort diagnosed with Hallucinogen Persisting Perception Disorder (HPPD) versus visual snow cohort without prior use of illicit drugs. HPPD-related visual disturbances were primarily caused by ecstasy but weren’t accompanied by migraines, whereas visual snow disturbances were accompanied by migraines in over half of the control cohort.


Background/objective: To investigate migraine prevalence in persons with Hallucinogen Persisting Perception Disorder (HPPD) presenting as visual snow syndrome (VSS)

Methods: Persons with visual snow as persisting symptom after illicit drug use (HPPD) were recruited via a Dutch consulting clinic for recreational drug use. A structured interview on (visual) perceptual symptomatology, details of drugs use, medical and headache history was taken. As a control group, persons with visual snow who had never used illicit drugs prior to onset were included. The primary outcome was lifetime prevalence of migraine. Symptom severity was evaluated by the Visual Snow Handicap Inventory (VHI), a 25‐item questionnaire.

Results: None of the 24 HPPD participants had migraine, whereas 20/37 (54.1%) of controls had migraine (p < 0.001). VHI scores did not differ significantly between the two groups; in both groups median score were 38 out of 100. In most HPPD cases (17/24; 70.9%), visual snow had started after intake of ecstasy; other psychedelic drugs reported included cannabis, psilocybin mushrooms, amphetamine, 4‐FMP, 3‐MMC, 2C‐B, and nitrous oxide.

Discussion: While none of the HPPD participants had migraine, over half of the visual snow controls without prior use of illicit drugs had migraine. This suggests that at least partly different pathophysiological factors play a role in both disorders. Users of ecstasy and other hallucinogens should be warned of the risk of visual snow. Further studies are needed to enhance understanding of the underlying neurobiology of HPPD and VSS to come to better management of these conditions.

Authors: Robin M. van Dongen, Gerard J. Alderliefste, Gerrit L.J. Onderwater, Michel D. Ferrari & Gisela M. Terwindt



Patients with visual snow syndrome see countless small dots in the entire visual field, and often also experience palinopsia, enhanced entoptic phenomena, photophobia, and nyctalopia. The pathophysiology of visual snow syndrome is not known.

This study investigated migraine prevalence in persons with hallucinogen persisting perception disorder.


A group of persons with visual snow as a persisting symptom after illicit drug use were recruited via a Dutch consulting clinic for recreational drug use.

Results: None of the 24 HPPD participants had migraine, whereas 20 of 37 (54.1%) controls had migraine. In most cases, visual snow started after intake of ecstasy.

The study concluded that none of the participants with HPPD had migraine, but more than half of the controls had migraine without prior use of illicit drugs.

Little is known about the epidemiology of visual snow, but first case series suggest that migraine is an important comorbid condition, and that visual snow may share a pathophysiology with migraine with aura.

Visual snow has also been reported as a persistent symptom after the intake of recreational drugs, especially hallucinogens such as ecstasy, lysergic acid diethylamide (LSD), and hallucinogenic mushrooms. Migraine was prevalent in both groups, suggesting that migraine may be an important factor in developing visual snow. We studied patients with visual snow after illicit drug use and compared them with patients with visual snow who had never used illicit drugs prior to onset.


A national consulting clinic specific for illicit/recreational drug use recruited persons with visual snow after illicit drug use. The participants underwent a structured telephone interview on visual symptoms, details of illicit drug use, and medical history and headache history.

Controls were patients with visual snow who had never used illicit drugs prior to onset. They had to meet previously published visual snow criteria, but were not required to meet the additional symptom criterion.

Patients with visual snow who had not used illicit drugs in the 12 months prior to visual snow onset were included in a third group.

The Visual Snow Handicap Inventory (VHI) was developed by modifying the Tinnitus Handicap Inventory (THI), a 25- item questionnaire on the impact of tinnitus. The total score ranges from 0 to 100 (even numbers only).

This study looked at lifetime and 1-year migraine prevalence. The Mann- Whitney U test was used to compare numerical variables and the chi- squared test was used for categorical variables.

Clinical characteristics

In total, 24 patients with HPPD and 37 controls with VS(S) were included in this study. All three groups had similar clinical and demographic characteristics, and most patients had two or more additional visual symptoms.

Type of illicit drugs and temporal relationship with onset of symptoms

Most HPPD participants reported that visual snow started after intake of XTC pills. Two prior XTC users reported that they had temporarily experienced visual snow before after using XTC.

Migraine prevalence

None of the HPPD cases had migraine versus 20 of 37 (54.1%) in the VS(S) group (p 0.001), and only two additional cases were found when criteria for probable migraine were applied.


Patients with visual snow who used XTC reported that the onset of visual snow was triggered by intake of illicit drugs. Migraine was absent in all patients with HPPD.

The relationship between visual snow and HPPD has not been extensively investigated. In a recent web-based study, patients with HPPD and patients without visual snow after illicit drug use were compared, and their clinical characteristics did not differ.

In contrast to our results on migraine prevalence, 57% of HPPD patients reported having a time between intake of illicit drugs and onset of their visual snow.

In our study, we observed no migraine in patients with HPPD, whereas previous studies had observed a high prevalence of migraine in patients with VSS. We believe this may be due to different data collection methods, or because migraine patients avoid illicit drug use to avoid triggering an attack.

Although the clinical phenotype may be like VSS, different initiation mechanisms may play a role. If there was an important interaction with migraine, we would have expected more migraine cases in our HPPD group.

There are no studies investigating pathophysiological correlates in both VSS patients and HPPD patients. LSD users have the first report of persistent visual complaints after illicit drug intake, and they have increased electroencephalographic coherence in the occipital region with reduced VEP latency. Recent research has focused on MDMA, which may be toxic for serotonergic neurons and cause increased visual cortex activation. However, replication of these studies has shown heterogenous results, raising the question of whether activation would be stronger in persons with HPPD complaints. HPPD is a wide clinical spectrum that includes reexperiencing perceptual symptoms that were experienced while intoxicated with a hallucinogen, as well as continuous symptoms that started after the intoxication. Type 2 HPPD includes visual snow as a symptom.

Our study has several limitations, but the large number of individuals describing a clear temporal relationship between illicit drug use and onset of visual snow warrants attention to illicit drugs as a potential important risk factor for developing visual snow. The small sample size and younger age of HPPD cases limit our conclusion on migraine prevalence to males. Selection bias might have played a role in this study, as the patients were recruited via a neurology outpatient clinic that is a tertiary headache center as well. However, this bias would still not explain the absence of migraine diagnoses in the HPPD group.

Although data on migraine may be skewed by differences in sex between the two groups, we believe that different pathophysiological factors may play a role in visual snow.


Robin M. van Dongen: Conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, software, visualization, writing – original draft, writing – review & editing, Gisela M. Terwindt: Funding acquisition, supervision, writing – review & editing.