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.

A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD.

Hallucinogen persisting perception disorder (HPPD) is rarely encountered in clinical settings. It is described as a re-experiencing of some perceptual distortions induced while intoxicated and suggested to subsequently cause functional impairment or anxiety. Two forms exist: Type 1, which are brief "flashbacks," and Type 2 claimed to be chronic, waxing, and waning over months to years. A review of HPPD is presented. In addition, data from a comprehensive survey of 20 subjects reporting Type-2 HPPD-like symptoms are presented and evaluated. Dissociative Symptoms are consistently associated with HPPD. Results of the survey suggest that HPPD is in most cases due to a subtle over-activation of predominantly neural visual pathways that worsens anxiety after ingestion of arousal-altering drugs, including non-hallucinogenic substances. Individual or family histories of anxiety and pre-drug use complaints of tinnitus, eye floaters, and concentration problems may predict vulnerability for HPPD. Future research should take a broader outlook as many perceptual symptoms reported were not first experienced while intoxicated and are partially associated with pre-existing psychiatric comorbidity.

Comparing triggers to visual disturbances among individuals with positive vs negative experiences of hallucinogen-persisting perception disorder (HPPD) following LSD use.

BACKGROUND AND OJECTIVE: Exploring differences in visual disturbances and triggers between Hallucinogen-Persisting-Perceptual-Disorder (HPPD) Type I ("positive/benign") and II ("negative/distressing"). METHODS: Forty individuals with HPPD and prior LSD use completed clinical questionnaires. RESULTS: The most common type of visual disturbances among individuals with HPPD I and II was slow movement of still objects and trailing phenomena, respectively. Those with HPPD I were more likely to report experiencing disturbances in dark environment, while looking at a still or moving object and during sexual intercourse. DISCUSSION AND CONCLUSIONS: HPPD I and II differ in terms of visual disturbances and triggers, possibly representing different phenomena existing on the same spectrum. SCIENTIFIC SIGNIFICANCE: Our study indicating differences in triggers to HPPD I and II adds to existing literature on differences in visual disturbances between the two subtypes. Further research elucidating additional differences between the subtypes of HPPD is needed. (Am J Addict 2017;26:568-571).

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.

Benign and time-limited visual disturbances (flashbacks) in recent abstinent high-potency heavy cannabis smokers: a case series study.

Eight high-potency heavy cannabis smokers who fulfilled DSM-IV-TR criteria for cannabis dependence sought treatment for outpatient detoxification. During routine psychiatric interview they reported the presence of visual disturbances when intoxicated and no prior history of LSD use. They all communicated the persistence of visual disturbances after ceasing cannabis use. Seven categories of visual disturbances were described when staring at stationary and moving objects: visual distortions, distorted perception of distance, illusions of movement of stationary and moving objects, color intensification of objects,dimmed color, dimensional distortion and blending of patterns and objects. Patients reported having 2-5 different categories of flashbacks up to 3-6 months after cessation of cannabis use. The described phenomena may be interpreted as a time-limited benign side effect of high-potency cannabis use in some individuals. A combination of vulnerability and use of large amounts of high potency cannabis seem to contribute to the appearance of this condition. Conclusions from uncontrolled case series should be taken with appropriate caution.

Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features.

An unique and intriguing characteristic of lysergic acid diethylamide (LSD) and LSD-like substances is the recurrence of some of the symptoms which appear during the intoxication, in the absence of recent intake of hallucinogens. Hallucinogen persisting perception disorder (HPPD) is a condition in which the re-experiencing of one or more perceptual symptoms causes significant distress or impairment in social, occupational or other important areas of functioning and may be extremely debilitating. Benzodiazepines are one of the recommended agents for the treatment of HPPD but it is unclear which of them may be more helpful. The goal of our investigation was to assess the efficacy of clonazepam in the treatment of LSD-induced HPPD. Sixteen patients fulfilled entrance criteria. All complained of HPPD with anxiety features for at least 3 months and were drug free at least 3 months. They received clonazepam 2 mg/day for 2 months. Follow-up was continued for 6 months. They were weekly evaluated during the 2 months of clonazepam administration and monthly during the follow-up period using the Clinical Global Impression Scale, a Self-report Scale and Hamilton Anxiety Rating Scale. Patients reported a significant relief and the presence of only mild symptomatology during the clonazepam administration. This improvement was clearly sustained and persisted during a 6-month follow-up period. This study suggests that high potency benzodiazepines like clonazepam, which has serotonergic properties, may be more effective than low-potency benzodiazepines in the treatment of some patients with LSD-induced HPPD.

LSD-induced Hallucinogen Persisting Perception Disorder with depressive features treated with reboxetine: case report.

We would like to present the case of a patient who had a prior history of cannabis, ecstasy (MDMA) and LSD abuse and who developed both Hallucinogen Persisting Perception Disorder (HPPD) and a major depressive episode. Following two unsuccessful SSRIs trials, reboxetine was prescribed. During a six-month follow-up period on reboxetine 6 mg./day, no exacerbation of the visual disturbance or recurrence of the depressive features were reported. Reboxetine may have an alpha 2 adrenoreceptor modulating effect on both noradrenaline and serotonin release, thus reboxetine's alpha 2 adrenoreceptor modulating effect on noradrenaline release may affect sympathetic activity and be involved in the recovery process.

Flashback and Hallucinogen Persisting Perception Disorder: clinical aspects and pharmacological treatment approach.

One unique characteristic of lysergic acid diethylamide (LSD) and LSD-like substances is the recurrence of some of the symptoms which appeared during the intoxication after the immediate effect of the hallucinogen has worn off. This recurring syndrome, mainly visual, has not been clearly understood, appreciated or distinguished from other clinical entities by clinicians. The terms Flashback and Hallucinogen Persisting Perception Disorder (HPPD) are used interchangeably in the professional literature. Flashback is a usually short-term, non-distressing, spontaneous, recurrent, reversible and benign condition accompanied by a pleasant affect. In contrast, HPPD is a generally long-term, distressing, spontaneous, recurrent, pervasive, either slowly reversible or irreversible, non-benign condition accompanied by an unpleasant dysphoric affect. Flashback and HPPD appear to be part of a vast and broad spectrum of non-psychopathological and psychopathological states reported by hallucinogen users. Pharmacological agents such as clonidine, perphenazine and clonazepan have been shown to ameliorate this syndrome in some of the individuals seeking treatment.

Risperidone-associated, benign transient visual disturbances in schizophrenic patients with a past history of LSD abuse.

Two schizophrenic patients, who had a prior history of LSD abuse and who had previously developed EPS with classic antipsychotics, were successfully treated with risperidone. They both reported short episodes of transient visual disturbances, which appeared immediately after starting treatment with risperidone. This imagery resembled visual disturbances previously experienced as "flashbacks" related to prior LSD consumption. Risperidone administration was continued and the visual disturbances gradually wore off. During a six-month follow-up period, there was no recurrence of visual disturbances. This phenomenon may be interpreted as a benign, short-term and self-limiting side effect which does not contraindicate the use of risperidone or interfere with treatment. Conclusions based on two case reports should be taken with appropriate caution.