OPEN Foundation

A. Lerner

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

Abstract

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.
Martinotti, G., Santacroce, R., Pettorruso, M., Montemitro, C., Spano, M. C., Lorusso, M., … & Lerner, A. G. (2018). Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives. Brain sciences8(3), 47. 10.3390/brainsci8030047
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LSD Flashbacks – The Appearance of New Visual Imagery Not Experienced During Initial Intoxication: Two Case Reports.

Abstract

A side effect associated with the use of synthetic hallucinogens such as lysergic acid diethylamide-(LSD) is the partial or total recurrence of perceptual disturbances which previously appeared during intoxication, despite absence of recent use. These are commonly referred to as “flashbacks” or Hallucinogen Persisting Perception Disorder (HPPD). Here we present two cases of patients with a prior history of LSD use who turned to psychiatric consultation following brief episodes of HPPD. Surprisingly, in both cases new visual imagery appeared during episodes of flashbacks which was not experienced during primary LSD use. Both subjects reported the ability to discern between LSD-associated visual disturbances and new visual imagery. This phenomenon did not cause functional impairment and in both cases caused gradual concern due to its persistence. Both patients refused medical treatment and continued psychiatric follow-up. At one year follow-up both patients reported almost complete spontaneous remission. To the best of our knowledge these are the first reported cases of LSD-related benign flashbacks in which new imagery is experienced. Reasons for this reversible and apparently harmless side effect are proposed. Conclusions from case reports should be taken with caution.

Lerner, A. G., Goodman, C., Rudinski, D., & Lev-Ran, S. (2014). LSD flashbacks–the appearance of new visual imagery not experienced during initial intoxication: Two case reports. Isr J Psychiatry Relat Sci, 51(4).
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Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features.

Abstract

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.

Lerner, A. G., Gelkopf, M., Skladman, I., Rudinski, D., Nachshon, H., & Bleich, A. (2003). Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features. International clinical psychopharmacology, 18(2), 101-105.
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Flashback and Hallucinogen Persisting Perception Disorder: clinical aspects and pharmacological treatment approach.

Abstract

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.

Lerner, A. G., Gelkopf, M., Skladman, I., & Oyffe, I. (2002). Flashback and hallucinogen persisting perception disorder: clinical aspects and pharmacological treatment approach. The Israel journal of psychiatry and related sciences, 39(2), 92.
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LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study.

Abstract

A pilot open study was conducted in order to evaluate the efficacy of clonidine in the treatment of LSD-induced hallucinogen persisting perception disorder (HPPD). Eight patients fulfilled entrance criteria. All complained of HPPD for at least 3 months and were drug free at least 3 months. They received fixed low doses of clonidine, 0.025 mg, three times a day for 2 months. They were evaluated by the Clinical Global Impression Scale (CGI) and a self-report scale on the severity of symptoms (graded 0-5). Patients scored an average of 5.25 (SD = 0.46) on the CGI and 4 on the self-report scale at baseline, indicating marked psychopathology. One patient dropped out at week 3 and a second patient dropped out at week 5. Of the six patients remaining at the end of 2 months, the average CGI score was 2.5 (SD = 0.55) and the self-report scale score was 2, indicating mild symptomatology. LSD-related flashbacks associated with excessive sympathetic nervous activity may be alleviated with clonidine in some patients.

Lerner, A. G., Gelkopf, M., Oyffe, I., Finkel, B., Katz, S., Sigal, M., & Weizman, A. (2000). LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study. International clinical psychopharmacology, 15(1), 35-37.
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