The “Endless Trip”: Psychopathology and psychopharmacology in the Hallucinogen Persisting Perception Disorder (HPPD)

Hallucinogen Persisting Perception Disorder (HPPD) is a syndrome marked by prolonged or recurring perceptual symptoms similar to acute hallucinogen effects, associated with substances like LSD, cannabis, MDMA, psilocybin, and mescaline. Symptoms mainly involve visual disturbances such as geometric pseudo-hallucinations, halos, flashes of light, motion-perception deficits, afterimages, and micropsy, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally established as a syndrome in the DSM-IV-TR in 2000. The neuronal substrate, risk factors, etiology, and pathogenesis remain unknown and under investigation. This critical review covers psychopathological bases, etiological hypotheses, and psychopharmacological approaches, presenting a case report and offering practical clinical recommendations.

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Abstract

Introduction 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, including cannabis, MDMA (methylenedioxymethamphetamine), psilocybin, mescaline and other psychostimulants. Symptomatology mainly comprises visual disorders (i.e., geometric pseudo-hallucinations, halos, flashes of colours/lights, motion-perception deficits, afterimages, micropsy, more acute awareness of floaters, etc.), even though depressive symptoms and thought disorders may be comorbidly present. Objective Although HPPD was firstly described in 1954, it was definitely established as a syndrome in 2000 with the revised forth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). However, neuronal substrate, risk factors, aetiology and pathogenesis of HPPD remains still unknown and under investigation. Furthermore, there are still open questions about its pharmacological targets. Aims A critical review on psychopathological bases, etiological hypothesis and psychopharmacological approaches towards HPPD was here provided. Methods A systematic literature search on PubMed/Medline, GoogleScholar and Scopus databases without time restrictions, by using a specific set of keywords was here carried out. In addition, a case report was here described. Results and conclusions Pharmacological and clinical issues are here considered and practical psychopharmacological recommendations and clinical guidelines here suggested. Disclosure of interest The authors have not supplied their declaration of competing interest.