Hallucinogen-Induced Persisting Perception Disorder: A Case Report.

Hallucinogen-persisting perception disorder (HPPD), also known as acute hallucinogen-induced psychosis or informally known as "flashbacks," is an unusual condition experienced by patients due to the use of different hallucinogenic substances. Hallucinogen-persisting perception disorder causes many symptoms, predominantly persistent visual perception distortion instead of intermittent distortion. Although different hallucinogens could cause HPPD, lysergic acid diethylamide (LSD) and LSD-like properties seem to be the most common hallucinogens causing the symptoms. In our case report, the patient is a 28-year-old Caucasian male with a long psychiatric and social history of polysubstance use using LSD and cannabis. He started experiencing many of the classic symptoms of HPPD seven months after stopping LSD. The diagnosis is suspected by ruling out all other possible underlying causes with the help of several laboratory and imaging tests. Despite having an extensive psychiatric history of illnesses, the patient's symptoms failed to improve with antipsychotics, confirming that the symptoms were not only due to mental illness. Although supposedly the first-line treatment for HPPD is the use of alpha-2 adrenergic drugs such as clonidine and benzodiazepines, we started to witness improvement in patient's symptoms with the use of lamotrigine, which is the gold standard in treating perceptual disturbance in time and space.

Association of Hallucinogen Persisting Perception Disorder with Trait Neuroticism and Mental Health Symptoms.

Hallucinogen Persisting Perception Disorder (HPPD) is considered rare in hallucinogen users although there are conflicting reports about its incidence and prevalence. HPPD may be more common in those with trait neuroticism. In this study, we invited hallucinogen and other drug users to complete an online questionnaire about their use of hallucinogens, their experience of HPPD symptoms, and their trait neuroticism and mental health symptoms. We received 802 responses with 415 of these containing adequate data for further analysis. 39.7% of responders reported symptoms corresponding to Type I HPPD, and 4.3% reported symptoms corresponding to Type II HPPD. We found no significant difference between neuroticism scores for participants with or without HPPD. Individuals with Type II HPPD were more likely to report mental health symptoms including anxiety, obsessional thoughts, paranoia, hypochondria and panic attacks (p < .05). We also found that individuals with Type II HPPD were more likely to report the use of 25I-NBOMe, dextromethorphan, nitrous oxide and benzodiazepines (p < .05). 47.3% of participants had never tested their drugs, making the attribution of HPPD severity to specific drugs difficult. Further work into the development of HPPD is required, particularly with the rise of hallucinogens as potential treatments for depression and other mental illnesses.

Delta-8 gummies causing visual snow: a case report.

A 26-year-old man developed visual snow syndrome (VSS) after consuming a little less than half of a delta-8 gummy (estimated at 4 mg of delta-8 tetrahydrocannabinol). Secondary VSS and hallucinogen-persisting perception disorder (HPPD) are discussed, and clinicians who evaluate patients with VS and VSS should ask about delta-8 gummies as an etiology of secondary VSS.

Pathological Delta Oscillations in Hallucinogen Persisting Perception Disorder: A Case Report.

Background: Hallucinogen persisting perception disorder (HPPD) is characterized by spontaneous recurrence of visual hallucinations or disturbances after previous consumption of hallucinogens, such as lysergic acid diethylamide (LSD). The underlying physiological mechanisms are unknown and there is no standardized treatment strategy available. Case Presentation: A 33-year-old male patient presented with persistent visual distortions (halos around objects, intensified colors, positive after images, and trails following moving objects) that developed after repeated use of hallucinogenic drugs at the age of 18. Symptoms developed gradually and worsened several months later, resulting in various pharmacological and psychosocial treatment attempts that remained unsuccessful, however. At presentation, 32-channel electroencephalography (EEG) showed increased delta activity over the occipital brain regions, reminiscent of occipital intermittent rhythmic delta activity (OIRDA) usually seen in children. Two sessions of cathodal (inhibitory) transcranial direct current stimulation (tDCS) over 30 min attenuated visual hallucinations and occipital delta activity by approximately 60%. The response persisted for over four weeks. Conclusion: Pathological delta activity over occipital brain regions may play an important role in the development and perpetuation of HPPD and can be attenuated by non-invasive brain stimulation.

A retrospective analysis of the "Neverending Trip" after administration of a potent full agonist of 5-HT2A receptor - 25I-NBOMe.

BACKGROUND: 5-HT2A receptor (e.g. 25I-NBOMe) agonists not only pose risks of acute intoxication but also long-term effects and significant adverse reactions, e.g. hallucinogen persisting perception disorder (HPPD), derealization, and depersonalization. AIMS: We evaluated the risk associated with single and repeated use of 25I-NBOMe. We aimed to identify factors that may increase the risk of HPPD, increase its severity and determine the time when the first symptoms appear. Herein, we report the first extensive evaluation of 25I-NBOMe-induced HPPD. METHOD: We assessed all reports (58) collected by The Pomeranian Pharmacovigilance Centre (PPC) from 2013 to 2020. RESULTS: The study included a total of 58 reports of adverse reactions caused by 25I-NBOMe. In the case of 15 reports (in patients aged 19-26 years), symptoms persisted many months after the discontinuation of 25I-NBOMe. The most common were: pseudohallucinations, bizarre delusions, derealizations and in some cases development or worsening of depression has been diagnosed. HPPD-like symptoms were most common in patients who took the drug regularly (i.e., several times a month). The risk of HPPD-like symptoms is higher in patients who have severe visual pseudohallucinations, severe bizarre delusions, derealization and/or depersonalization onset immediately after taking the drug. Recurrence of HPPD symptoms may be provoked by many factors, however, there is some cases there is no apparent reason. HPPD after 25I-NBOMe use can last from 2 months up to 2 years. In some patients, pharmacological treatment was necessary due to 25I-NBOMe-induced HPPD and depression. CONCLUSIONS: The study showed long-lasting effects after 25I-NBOMe administration and allowed for the determination of HPPD risk factors.

Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants.

BACKGROUND: LSD and psilocybin are increasingly used in phase I trials and evaluated as therapeutic agents for mental disorders. The phenomenon of reoccurring drug-like experiences after the acute substance effects have worn off was described for both substances and especially attributed to LSD. According to the DSM-V, the persisting and distressing manifestation of these experiences is called hallucinogen-persisting perception disorder (HPPD). Data on both conditions is very limited. OBJECTIVE: This study aims to provide descriptive data on reoccurring drug-like experiences after the administration of LSD and psilocybin in controlled studies with healthy participants. METHODS AND MATERIALS: Data from 142 healthy subjects enrolled in six double-blinded, placebo-controlled, randomized cross-over studies were analyzed. In total, 60 subjects received LSD; 27 subjects received LSD, MDMA, and D-amphetamine; 31 subjects received LSD and psilocybin; and 25 subjects received psilocybin and escitalopram. At the end-of-study visit (mean 39.8 days after last study session, SD 37.2), subjects were asked for any reoccurring drug effects since the initial substance effects had worn off. Those reporting reoccurring perception changes more than 24 h after administration were contacted for follow-up (mean follow-up duration: 31.2 months, SD 28.6). RESULTS: Thirteen out of 142 subjects reported reoccurring drug-like experiences (LSD: seven, psilocybin: two, both: four). The reported phenomena were predominantly mild and perceived as neutral to pleasant. Flashbacks were mostly of visual nature, lasted for seconds to minutes, and occurred within a week after the last drug administration. Two subjects reported distressing experiences that subsided spontaneously. One subject reported brief and pleasant visual perception changes which reoccurred for 7 months. None of the subjects reported impairment in their daily lives. None of the cases met DSM-V criteria for HPPD. CONCLUSION: Reoccurring drug-like experiences after the administration of LSD and psilocybin are a common phenomenon occurring in up to 9.2% of healthy subjects (7.8% for LSD, 8.3% for psilocybin and 14.3% if both substances are administered). Additionally, our work suggests that flashback phenomena are not a clinically relevant problem in controlled studies with healthy participants.

Not All Cases of Visual Snows are Benign: Mimics of Visual Snow Syndrome.

Visual snow syndrome (VSS) is a clinical disorder characterized by pan-field visual disturbance. It is a diagnosis of exclusion since its pathophysiology remains unknown. Excluding other mimics is of great significance since some serious pathologies can have secondary visual snow (VS) as an initial presentation. Delayed or incorrect diagnosis of these VSS mimics may lead to permanent vision loss or even death. The purpose of this review is to help physicians distinguish VSS mimics promptly to avoid bad outcomes. The authors performed a PubMed literature search of articles, case reports, and reviews describing VS symptoms in patients with underlying diseases other than VSS. The red flags of secondary VS symptoms were highlighted, such as new-onset or intermittent VS, unilateral or quadrant VS, and accompanied ocular or neurological deficits. There are four main categories of VSS mimics, ie, including neurological disorders, ocular pathologies, drug-related VS, and other systemic diseases. The physicians could largely exclude most etiologies based on history taking, ophthalmologic and neurologic examinations, and neuroimaging. Further research in VS should carefully define and unify the inclusion and exclusion criteria of this disorder and investigate these secondary VS conditions and their pathogenesis.

Migraine prevalence in visual snow with prior illicit drug use (hallucinogen persisting perception disorder) versus without.

BACKGROUND AND PURPOSE: This study was undertaken to investigate migraine prevalence in persons with hallucinogen persisting perception disorder (HPPD) presenting as visual snow syndrome (VSS). METHODS: Persons with visual snow as a 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, and 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 of 37 (54.1%) controls had migraine (p < 0.001). VHI scores did not differ significantly between the two groups; in both groups, the median score was 38 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-fluoroamphetamine, 3-methylmethcathinone, 4-Bromo-2,5-dimethoxypenethylamine, and nitrous oxide. CONCLUSIONS: Whereas none of the HPPD participants had migraine, more than 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 these 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 enable better management of these conditions.

Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives.

Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD.

Hallucinogen persisting perception disorder: A literature review and three case reports.

The paper describes diagnostic criteria, clinical presentation and types of hallucinogen persisting perception disorder (HPPD), as well as current approaches to the treatment of this phenomenon using available scientific sources. Three case reports are also presented to demonstrate different types of this disorder. The first case report describes a 23-year old patient with a previous history of cannabis consumption who reported HPDD type I after the use of psilocybin mushrooms with small amounts of alcohol and hash. A month later, after cannabis use, the same visual and auditory distortions appeared again. During the following year, hallucinations recurred with the consumption of natural cannabinoids but not with alcohol intake. The symptoms have reduced within a year. Surprisingly, both other cases belonging to HPDD type II appeared in patients who consumed ecstasy, although MDMA is generally not considered a hallucinogen and hallucinations are not frequently reported after MDMA consumption. In both cases of HPPD type II after the use of ecstasy, the condition was very stressful and frightening. Both patients sought medical help and received tofisopam, lamotrigine and sertraline. After that, in both cases visual impairments have smoothed, but have not passed completely. Scientific sources suggest that HPPD may affect more than 50% of hallucinogen users and this disorder is often underdiagnosed. Therefore, patients suffering from HPPD can present in various clinical settings, and clinicians should be aware of this condition.

The "Endless Trip" among the NPS Users: Psychopathology and Psychopharmacology in the Hallucinogen-Persisting Perception Disorder. A Systematic Review.

Hallucinogen-persisting perception disorder (HPPD) is a syndrome characterized by prolonged or reoccurring perceptual symptoms, reminiscent of acute hallucinogen effects. HPPD was associated with a broader range of LSD (lysergic acid diethylamide)-like substances, cannabis, methylenedioxymethamphetamine (MDMA), psilocybin, mescaline, and psychostimulants. The recent emergence of novel psychoactive substances (NPS) posed a critical concern regarding the new onset of psychiatric symptoms/syndromes, including cases of HPPD. Symptomatology mainly comprises visual disorders (i.e., geometric pseudo-hallucinations, haloes, flashes of colors/lights, motion-perception deficits, afterimages, micropsia, more acute awareness of floaters, etc.), even though depressive symptoms and thought disorders may be comorbidly present. Although HPPD was first described in 1954, it was just established as a fully syndrome in 2000, with the revised fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). HPPD neural substrates, risk factors, and aetiopathogenesys still largely remain unknown and under investigation, and many questions about its pharmacological targets remain unanswered too. A critical mini review on psychopathological bases, etiological hypothesis, and psychopharmacological approaches toward HPPD, including the association with some novel substances, are provided here, by means of a literature search on PubMed/Medline, Google Scholar, and Scopus databases without time restrictions, by using a specific set of keywords. Pharmacological and clinical issues are considered, and practical psychopharmacological recommendations and clinical guidelines are suggested.

Palinopsia revamped: a systematic review of the literature.

Palinopsia, the persistence or recurrence of visual images after the stimulus has been removed, is a nonspecific term that describes multiple types of visual symptoms with a wide variety of etiologies. For example, palinopsia may be the presenting symptom of a potentially life-threatening posterior cortical lesion, yet it may also be a benign medication side effect. We comprehensively review all published cases and subdivide palinopsia into two clinically relevant categories: illusory palinopsia and hallucinatory palinopsia.

Clinical characteristics of individuals with schizophrenia and hallucinogen persisting perception disorder: a preliminary investigation.

OBJECTIVE: An unusual side effect of hallucinogen use is the appearance of hallucinogen persisting perception disorder (HPPD). Despite high rates of prior hallucinogen use among individuals with schizophrenia, there are insufficient data on the clinical characteristics of individuals with co-occurring schizophrenia and HPPD. METHODS: Twenty-six hospitalized patients with schizophrenia and prior LSD use (12 with HPPD and 14 without HPPD) were recruited. Participants were clinically assessed using validated tools, and details regarding hospitalizations were retrieved from their medical records. Those patients who also had HPPD completed a questionnaire addressing HPPD-associated perceptual disturbances. RESULTS: Participants were mostly male (n = 22, 84.6%) and had an average age of 32.3 (SD = 7.67). Nearly half (n = 12, 46.2%) met criteria for HPPD. No significant differences were found in sociodemographic and clinical characteristics (including response to antipsychotic medications and adverse effects) between the groups. Nine individuals (75%) in the schizophrenia and HPPD group reported the ability to identify specific precursory cues for the appearance of the HPPD-associated perceptual distortions, and 8 (67%) reported the ability to distinguish HPPD perceptual disturbances from those associated with their psychotic disorder. CONCLUSIONS: Very little is known about the co-occurrence of schizophrenia and HPPD or the associated clinical implications. Further research is needed to understand the clinical impact of this comorbidity.

Hallucinogen-persisting perception disorder.

A 33-year-old female patient developed a hallucinogen-persisting perception disorder (HPPD) after lysergic acid diethylamide (LSD) abuse for a year at the age of 18. Specifically, she reported after images, perception of movement in her peripheral visual fields, blurring of small patterns, halo effects, and macro- and micropsia. Previous treatment with antidepressants and risperidone failed to ameliorate these symptoms. Upon commencing drug therapy with lamotrigine, these complex visual disturbances receded almost completely. Based on its hypothesized neuroprotective and mood-stabilizing effects, the antiepileptic lamotrigine may offer a promising new approach in the treatment of HPPD.