Hallucinogen persisting perceptual disorder: a scoping review covering frequency, risk factors, prevention, and treatment

ABSTRACT

Introduction

Hallucinogen persisting perception disorder (HPPD) affects a subset of persons who use hallucinogens and is defined as the repeated experience of hallucinations and other perceptual disturbances as a result of prior intoxications. As select hallucinogens are under development for the treatment of selectmental disorders, there is a need to better characterize this disorder.

Areas covered

A scoping review of the literature on HPPD was completed from inception to July 2021. Topics covered in the review herein include treatments for HPPD, prevalence or incidence data on HPPD among different classes of hallucinogens, risk factors for HPPD, and data pertaining to the pathophysiology of HPPD.

Expert opinion

Hallucinogen persisting perception disorder appears to be an uncommon yet serious event associated with prior hallucinogen exposure. The renewed interest in psychedelics as potential treatment options for select mental disorders, especially agents with hallucinogenic potential, provides the impetus to characterize HPPD in its frequency, risk and protective factors, key characteristics, as well as other clinical and treatment-related factors.

KEYWORDS:

• HPPD
• hallucinogens
• drug toxicity
• serotonergic
• GABAergic dysfunction
• adrenergic overactivation
• perceptual disorders
• adverse events

Article highlights

• Hallucinogen Persisting Perception Disorder (HPPD) occurs in an unknown proportion of hallucinogen users and is defined as repeatedly experiencing hallucinations from previous intoxications.

• Lysergic acid diethylamide (LSD) is the hallucinogen most frequently associated with HPPD.

• Several drug classes (i.e. benzodiazepines, α-2 adrenergic agonists, antidepressants, atypical antipsychotics, anticonvulsants, and opioid antagonists) have demonstrated limited success in treating HPPD.

• There are no known risk factors for HPPD.

Declaration of interests

LMW Lui is a contractor to Braxia Scientific Corp. KM Teopiz reported receiving personal fees from Braxia Scientific Corp. outside the submitted work. JD Rosenblat is the medical director of Braxia Health (formally known as the Canadian Rapid Treatment Center of Excellence and is a fully owned subsidiary of Braxia Scientific Corp), which provides ketamine and esketamine treatment for depression, and has received research grant support from the American Psychiatric Association, American Society of Psychopharmacology, Canadian Cancer Society, Canadian Psychiatric Association, Joseph M. West Family Memorial Fund, Timeposters Fellowship, University Health Network Centre for Mental Health, and University of Toronto and speaking, consultation, or research fees from Allergan, COMPASS, Janssen, Lundbeck, and Sunovion. RS McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora therapeutics, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, Atai Life Sciences. RS McIntyre is a CEO of Braxia Scientific Corp. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2022.2063273

Additional information

Notes on contributors

Roger S. McIntyre

Dr. Roger McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC); speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, and Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp.