Understanding Hallucinogen-Persisting Perception Disorder (HPPD)

What is HPPD?

Hallucinogen-persisting perception disorder (HPPD) is characterized by the enduring recurrence of visual distortions, hallucinations, and other perceptual anomalies following the use of psychedelic substances. These effects can last from days to years after drug elimination. While traditionally viewed as a rare, visually confined disorder, recent research suggests a broader spectrum of sensory and cognitive disturbances with meaningful impacts on daily functioning and connections to non-visual disturbances.

One of the first possibly recorded associated symptoms of HPPD was recorded in 1898 by the English physician Havelock Ellis in an article titled "Mescal: A New Artificial Paradise." Ellis detailed his experience of taking three mescal buttons (derived from the peyote cactus). After the hallucinogenic effects wore off, Ellis reported a sustained change in his perception of the world. He wrote that the experience had enhanced his "sensitivity...to the more delicate phenomena of light and shade and colour," making him "more aesthetically sensitive" than before.

While not describing HPPD in the context of modern clinical descriptions, his accounts describe one of the core features of HPPD. Since its formal inclusion in the DSM-III-R (1987), the disorder has been categorized under “Substance/Medication-Induced Hallucinogen Persisting Perception Disorder,” yet its phenomenological and biological boundaries remain poorly defined.

Causes of HPPD

The etiology of HPPD remains uncertain. It is most often reported following the use of serotonergic hallucinogens such as LSD, psilocybin, and mescaline, though cases have also been documented after MDMA, cannabis, and novel psychoactives. Not all users develop HPPD, suggesting a complex interplay between pharmacological exposure and individual vulnerability.

Potential risk factors include high dosage, frequent use, polydrug combinations, and preexisting neurological or psychiatric sensitivities. Individuals with migraine, anxiety, or dissociative tendencies appear overrepresented among reported cases. Nevertheless, causation has not been established for any single factor, and HPPD has occasionally followed a single exposure (Halpern & Pope, 2003).

Phenomenology of HPPD

The DSM-5 lists three hallmark symptoms—geometric hallucinations, color flashes, and trailing phenomena—but empirical evidence indicates a far richer phenomenological spectrum. A systematic review by Vis et al. (2021) documented more than sixty symptom types, including metamorphopsias (macropsia, micropsia, distortions of contour), visual snow, entoptic effects, derealization, depersonalization, and temporal or somatic distortions reminiscent of Alice-in-Wonderland phenomena.

Crucially, HPPD does not involve global alterations of consciousness or mystical experience typical of acute psychedelic states. Instead, it reflects persistent alterations in content rather than level of consciousness—heightened salience of internally generated perceptual signals within an otherwise unimpaired cognitive field. McConnell et al. (2025) further observed that individuals with HPPD frequently exhibit heightened photosensitivity and phonosensitivity, implying dysregulation across multiple sensory modalities rather than a purely visual disorder.

In the clinical literature, two proposed types of HPPD exist, although they are not officially categorized in the DSM-5.

HPPD Type 1 is associated with reexperiencing one or more perceptual symptoms, is shorter acting, and does not significantly affect an individual's ability to function in social, career, or occupational areas of life.

HPPD Type 2 is the more severe of the two, with longer-acting symptoms, potentially lasting several months to years after a psychedelic experience, and affects an individual's ability to function in important social, occupational, or familial aspects of life (Lerner et al., 2014).

Pathophysiology and Associated Factors

Although no definitive pathological mechanism has been identified, several interlocking hypotheses exist. Psychedelics act primarily at the 5-HT2A receptor, modulating cortical excitation–inhibition balance and modulating sensory perception. Persistent dysregulation of this receptor system, altered thalamocortical oscillations, and disrupted GABAergic inhibition have each been proposed to explain sensory “disinhibition” and visual hyperexcitability (Martinotti et al., 2018; Neven & Blom, 2025). Research indicates that substance use can lead to a reduction in serotonin (5-HT) receptors, potentially disrupting normal visual information processing.

Evidence also suggests that alterations in GABAergic neurons may impair the brain’s ability to filter irrelevant sensory input. Furthermore, EEG findings reveal atypical activity in the visual cortex consistent with seizure-like disturbances (Neven & Blom, 2025). Psychiatric comorbidity appears to play a substantial modulatory role. Anxiety and depression correlate with greater symptom complexity, longer duration, and poorer outcomes. Because these conditions themselves influence sensory gating and attentional bias, they may interact with neurobiological vulnerabilities to produce HPPD symptoms.

Determining the pathologies of HPPD and other associations with psychedelic adverse effects should be approached with caution, as the landscape is already treading lightly in the hopes of destigmatization for clinical legalization and medical/therapeutic treatments. Therefore, interpretation of sex differences in HPPD warrants caution. Zhou et al. (2025) reported higher odds of HPPD-type symptoms in women and urged caution when enrolling female participants in psychedelic research. Yet their dataset was overwhelmingly male (≈ 74 %), producing unstable gender estimates for the smaller female subgroup, accounting for little variance.

Psychiatric history—more common among female respondents—was itself a significant predictor, suggesting confounding. Because the study lacked controlled dosing, independent verification of substance purity, or matched male–female subsamples, attributing risk to “female gender” is premature. The framing risks pathologizing women’s responses rather than recognizing the interplay of psychiatric vulnerability, sociocultural factors, and reporting differences that could underlie the apparent association. Without controlled dosing or matched subsamples, attributing biological vulnerability to sex is premature and risks reinforcing gendered bias rather than elucidating mechanism.

Clinical Implications

Current DSM-5 criteria may underrepresent the true clinical picture and be overly restrictive. A broadened diagnostic framework incorporating both visual and non-visual phenomena could improve recognition, accurate diagnosis, and treatment. A thorough clinical assessment should include a detailed history of substance use, a comprehensive psychiatric evaluation, and a careful assessment of perceptual symptoms beyond those currently included in diagnostic guidelines. Differential diagnosis should rule out migraine aura, visual snow syndrome, dissociative disorders, and temporal lobe epilepsy.

Management focuses on comorbid conditions and symptomatic relief. Treatment considerations should prioritize addressing co-occurring mental health conditions such as anxiety and depression. Pharmacological evidence remains limited to small case series: clonidine and benzodiazepines show partial benefit, whereas lamotrigine and levetiracetam have anecdotal support (Ayyub et al., 2023; Neven & Blom, 2025). Psychotherapeutic interventions—particularly CBT and mindfulness-based approaches—may reduce anxiety and distress but do not eliminate perceptual anomalies.

Psychoeducation, reassurance, and harm-reduction counseling are critical first steps. Public-health messaging should acknowledge that psychedelics, even in therapeutic contexts, can precipitate lasting perceptual disturbances in susceptible individuals. A harm-reduction stance—balancing enthusiasm for clinical potential with transparency risk—is essential for ethical progress in psychedelic science.

Progressing Psychedelic Science

HPPD represents a complex interaction between neurobiological sensitization, perceptual processing, and psychological context. Its study offers a unique window into consciousness and sensory integration but also exposes epistemic tensions at the intersection of neuroscience, psychiatry, and culture. As psychedelic therapies expand, a nuanced understanding of HPPD will be vital—to ensure informed consent, reduce stigma, and promote equitable participation in research. Continued investigation must integrate neuroimaging, longitudinal design, and sociocultural analysis to disentangle biology from context.

Only through such multidimensional inquiry can we clarify whether HPPD is a disorder of perception, attention, or adaptation—and design treatments that restore both perceptual stability and quality of life. The non-profit organization, Perception Restoration Foundation, has dedicated attention to the support of HPPD and assisting those struggling with the disorder, as well as contributing to the scientific understanding of the disorder. To advance our understanding of psychedelics and their associated adverse effects, attention to the understanding of HPPD poses an opportunity to further our knowledge as the field gains attention and bleeds into the medical, academic, and clinical settings.

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Resources

Ayyub, J., Nandennagari, S., Edelbaum, D., Agbo, J., Nagendran, D., & Tamayo, L. (2023). Hallucinogen-Induced Persisting Perception Disorder: A Case Report. Cureus, 15(9), e46262. https://doi.org/10.7759/cureus.46262

Ellis, Havelock (1898). Mescal: A new artificial paradise. Contemporary Review, 73 (1-6): 130–141

Halpern, J. H., & Pope, H. G., Jr (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and alcohol dependence, 69(2), 109–119. https://doi.org/10.1016/s0376-8716(02)00306-x

Lerner, A., Rudinski, D., Bor, O., & Goodman, C. (2014). Flashbacks and HPPD: A Clinical-oriented Concise Review. The Israel journal of psychiatry and related sciences, 51(4), 296–301

Martinotti, G., Santacroce, R., Pettorruso, M., Montemitro, C., Spano, M. C., Lorusso, M., di Giannantonio, M., & Lerner, A. G. (2018). Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives. Brain sciences, 8(3), 47. https://doi.org/10.3390/brainsci8030047

McConnell, A., He, W., McConnell, H., Sperandei, S., & Sowman, P. F. (2025). The neverending trip: Associations between Hallucinogen Persisting Perception Disorder (HPPD) and non-visual perceptual disturbances. Journal of Psychedelic Studies, 9(3), 212-220. https://doi.org/10.1556/2054.2024.00408

Neven, A., & Blom, J. D. (2025). Pharmacological Treatment of Hallucinogen Persisting Perception Disorder (HPPD): A Systematic Review. Harvard review of psychiatry, 33(5), 264–275. https://doi.org/10.1097/HRP.0000000000000439

Perception Restoration Foundation. (n.d.). The PRF helps people with HPPD through research, support and harm reduction. https://www.perception.foundation/ 

Vis, P. J., Goudriaan, A. E., Ter Meulen, B. C., & Blom, J. D. (2021). On Perception and Consciousness in HPPD: A Systematic Review. Frontiers in neuroscience, 15, 675768. https://doi.org/10.3389/fnins.2021.675768

Zhou, K., de Wied, D., Carhart-Harris, R. L., & Kettner, H. (2025). Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use. PNAS nexus, 4(4), pgae560. https://doi.org/10.1093/pnasnexus/pgae560