OPEN Foundation

HPPD

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

Abstract

Introduction: Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders.

Objective: To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients’ accounts, and elucidating how these affect the treatment process.

Methods: We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP).

Results: Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.

Conclusions: This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.

Breeksema, J. J., Niemeijer, A. R., Krediet, E., Vermetten, E., & Schoevers, R. A. (2020). Psychedelic treatments for psychiatric disorders: a systematic review and thematic synthesis of patient experiences in qualitative studies. CNS drugs, 1-22; 10.1007/s40263-020-00748-y

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Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid Dependence

Abstract

Abstract unavailable for this article.
Knuijver, T., Belgers, M., Markus, W., Verkes, R. J., van Oosteren, T., & Schellekens, A. (2018). Hallucinogen persisting perception disorder after ibogaine treatment for opioid dependence. Journal of clinical psychopharmacology38(6), 646-648., 10.1097/JCP.0000000000000966
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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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LSD-associated "Alice in Wonderland Syndrome"(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report.

Abstract

A side effect associated with the use of LSD is the return of perceptual disturbances which anteriorly emerged during intoxication, despite absence of present use. Here we present the case of a patient with a previous history of sporadic and recreational cannabis, alcohol and LSD consumption who reported LSD associated “Alice in Wonderland Syndrome” (AIWS) or Todd’s syndrome. AIWS is basically characterized by four frequent visual illusions: macropsia, micropsia, pelopsia and teleopsia. AIWS only appeared during LSD consumption and continued after LSD suspension, namely, Hallucinogen Persisting Perception Disorder (HPPD). This phenomenon did not cause a major functional impairment but provoked sufficient worry and concern due to its persistent continuation. The patient refused medical treatment and continued psychiatric follow-up. At the one year follow-up he reported complete remission. To the best of our knowledge this is the first reported case of AIWS which persist after LSD interruption (HPPD) in the professional literature. Reasons for this intriguing, benign, reversible and apparently harmless side effect are proposed.

Lev-Ran, S. (2014). LSD-associated” Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report. The Israel journal of psychiatry and related sciences, 52(1), 67-68.
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LSD-associated “Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report.

Abstract

A side effect associated with the use of LSD is the return of perceptual disturbances which anteriorly emerged during intoxication, despite absence of present use. Here we present the case of a patient with a previous history of sporadic and recreational cannabis, alcohol and LSD consumption who reported LSD associated “Alice in Wonderland Syndrome” (AIWS) or Todd’s syndrome. AIWS is basically characterized by four frequent visual illusions: macropsia, micropsia, pelopsia and teleopsia. AIWS only appeared during LSD consumption and continued after LSD suspension, namely, Hallucinogen Persisting Perception Disorder (HPPD). This phenomenon did not cause a major functional impairment but provoked sufficient worry and concern due to its persistent continuation. The patient refused medical treatment and continued psychiatric follow-up. At the one year follow-up he reported complete remission. To the best of our knowledge this is the first reported case of AIWS which persist after LSD interruption (HPPD) in the professional literature. Reasons for this intriguing, benign, reversible and apparently harmless side effect are proposed.

Lev-Ran, S. (2014). LSD-associated” Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report. The Israel journal of psychiatry and related sciences, 52(1), 67-68.
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Psychedelics not linked to mental health problems or suicidal behavior: A population study

Abstract

A recent large population study of 130,000 adults in the United States failed to find evidence for a link between psychedelic use (lysergic acid diethylamide, psilocybin or mescaline) and mental health problems. Using a new data set consisting of 135,095 randomly selected United States adults, including 19,299 psychedelic users, we examine the associations between psychedelic use and mental health. After adjusting for sociodemographics, other drug use and childhood depression, we found no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression and anxiety. We failed to find evidence that psychedelic use is an independent risk factor for mental health problems. Psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use; serious adverse events involving psychedelics are extremely rare. Overall, it is difficult to see how prohibition of psychedelics can be justified as a public health measure.

Johansen, P. Ø., & Krebs, T. S. (2015). Psychedelics not linked to mental health problems or suicidal behavior: A population study. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114568039
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Synesthesias in the context of hallucinogen-induced persistent perception disorder following the use of lsd

Abstract

The hallucinogen-induced persistent perception disorder (hppd) is a disturbing complication resulting from the use of hallucinogens. We report on a case-study in which an artist suffering from visual, auditory and olfactory hallucinations also experienced chromatic-phonemic synesthesias that had persisted for two years after he had stopped using lysergic acid diethylamide (lsd). The case described demonstrates that individuals suffering from hppd can also experience synesthesias that may in fact differ phenomenologically from ‘coloured hearing’, which is a symptom known to occur in the context of substance abuse.

Neven, A., & Blom, J. D. (2013). [Synesthesias in the context of hallucinogen-induced persistent perception disorder following the use of lsd]. Tijdschrift voor psychiatrie, 56(11), 748-752.
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Hallucinogen persisting perception disorder and the serotonergic system: A comprehensive review including new MDMA-related clinical cases

Abstract

Hallucinogen persisting perception disorder (HPPD) is a drug-induced condition associated with inaccurate visual representations. Since the underlying mechanism(s) are largely unknown, this review aims to uncover aspects underlying its etiology. Available evidence on HPPD and drug-related altered visual processing was reviewed and the majority of HPPD cases were attributed to drugs with agonistic effects on serotonergic 5-HT2A receptors. Moreover, we present 31 new HPPD cases that link HPPD to the use of ecstasy (MDMA), which is known to reverse serotonin reuptake and acts as agonist on 5-HT2A receptors. The available evidence suggests that HPPD symptoms may be a result from a misbalance of inhibitory-excitatory activity in low-level visual processing and GABA-releasing inhibitory interneurons may be involved. However, high co-morbidities with anxiety, attention problems and derealization symptoms add complexity to the etiology of HPPD. Also, other perceptual disorders that show similarity to HPPD cannot be ruled out in presentations to clinical treatment. Taken together, evidence is still sparse, though low-level visual processing may play an important role. A novel finding of this review study, evidenced by our new cases, is that ecstasy (MDMA) use may also induce symptoms of HPPD.

Litjens, R. P., Brunt, T. M., Alderliefste, G. J., & Westerink, R. H. (2014). Hallucinogen persisting perception disorder and the serotonergic system: A comprehensive review including new MDMA-related clinical cases. European Neuropsychopharmacology, 24(8), 1309-1323. https://dx.doi.org/10.1016/j.euroneuro.2014.05.008

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Flashbacks and HPPD: A Clinical-oriented Concise Review.

Abstract

A unique characteristic of LSD, LSD-like and substances with hallucinogenic properties is the recurrence of some or all the hallucinogenic symptoms which had appeared during the intoxication after the immediate effects of the substance had worn off. This recurring syndrome, mainly visual, is not clearly understood. The terms Flashback and Hallucinogen Persisting Perception Disorder (HPPD) have been used interchangeably in the professional literature. We have observed at least two different recurrent syndromes, the first Flashback Type we refer to as HPPD I, a generally short-term, non-distressing, benign and reversible state accompanied by a pleasant affect. In contrast, the second HPPD Type we refer to as HPPD II, a generally long-term, distressing, pervasive, either slowly reversible or irreversible, non-benign state accompanied by an unpleasant affect. HPPD I and II appear to be part of a broad spectrum of non-psychopathological and psychopathological states reported by hallucinogen users. HPPD I and II may be clinically characterized by prodromal symptoms, onset, content of visual imagery, precipitators, frequency, duration and intensity of perceptual recurrences, severity, course, differential diagnosis, accompanying mood and affect, insight and remission. Pharmacological therapy with or without preceding or following co-occurring psychiatric disorders have been shown to ameliorate this syndrome. A large variety of medications may be utilized to alleviate this condition, but with differential results suggesting several subtypes. The purpose of this manuscript is to provide a clinical-oriented, comprehensive and concise review to treating psychiatrists.

Rudinski, D., Bor, O., & Goodman, C. (2013). Flashbacks and HPPD: A Clinical-oriented Concise Review. The Israel journal of psychiatry and related sciences, 51(4), 296-301.
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30 April - Q&A with Rick Strassman

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