Post-Use Phenomena and Hallucinogen Persisting Perceptual Disorder

adverse effects hallucinogen hppd mental health May 23, 2023

Persisting Perceptual Phenomenon after Psychedelics

Psychedelic drug intoxication is hallmarked by changes to our sensory experience and hallucinatory type activity. In most cases, effects of psychedelics are transient and end as concentrations of drug in the body fall. However, this is not true in all cases of use. There has been much debate, controversy, and misinformation about post-use effects of psychedelic drugs. There’s also likely much more to be discovered about how these effects occur and how we could manage or prevent them. In this article we’ll aim to have a balanced conversation about post-use phenomenon of psychedelics as well as Hallucinogen Persisting Perceptual Disorder (HPPD).

Specifically I’d like to:

  • Describe potential types of post-use phenomenon
  • Define HPPD according to the DSM-5
  • Discuss phenomenology and criteria for HPPD
  • Discuss management and treatment strategies for persons experiencing distressing post-use phenomenon


What is Hallucinogen Persisting Perceptual Disorder (HPPD)?

Several cases of persistent and distressing psychedelic-like phenomena post-use has been reported in the past, most notoriously with Lysergic Acid Diethylamide (LSD) or phencyclidine (PCP). These cases led to the creation of the symptom clusters used to diagnose Hallucinogen Persisting Perceptual Disorder (HPPD) in the Diagnostic Statistical Manual (DSM).

It’s been proposed that there are a couple different types of HPPD. While prevalence estimates may be inaccurate, the first or type 1 (HPPD I) involves transient ‘flashbacks’ and is estimated to occur in about 5% of regular psychedelic users. The second or type 2 (HPPD II) involves chronic, intense, waxing and waning visual disturbances for months to years leading to significant distress or dysfunction. This form of HPPD has been estimated to occur in about 1 in 50,000 psychedelic users [1].

According to DSM-5, the following criteria must be met to diagnose HPPD:

(1) reexperiencing one or more of the perceptual symptoms that were experienced while intoxicated with the hallucinogens following cessation of hallucinogen use

(2) clinically significant distress due to (1), and

(3) symptoms are not better accounted for by another disorder (e.g., delirium, dementia, schizophrenia) or general medical conditions (brain lesions and infections), and hypnopompic hallucinations occurring during state transition between sleep and wakefulness can be excluded.


Phenomenon Experienced in Persons with HPPD

Several recent review articles have been published summarizing phenomenon reported by persons affected with HPPD and have observed several differences between symptoms listed in the DSM-5 and reported symptoms [2-4]. This had led authors to conclude that the criteria in the DSM-5 is not complete and would benefit from an expansive revision to more closely mimic clinical phenomenology.

The table below shows the symptoms listed in DSM-5 as well as other reported symptoms, some of which are also common, and others which are rarer. The criteria in DSM-5 are limited and primarily include selected types of perceptual changes to vision, whereas persons report broader visual perceptual changes, changes to other sensory perceptions, distortions of time, and distortions of their subjective experience in the world. Overall, it appears that visual changes are most common, yet it may be more accurate to conceive of HPPD as being able to affect a broad array of sensory perceptions [2, 4, 5].

There may be specific types of post-use phenomena that are more common or even unique to particular psychedelics that are not thought of as linked to HPPD. For example, tinnitus has been reported with inhaled DMT and ‘reactivations’ with 5-MeO-DMT (particularly high doses via an inhalation route) [6, 7]. There have also been other energetic phenomena reported with psychedelic use that western sciences does not recognize or have a good grasp upon (e.g. kundalini awakening). In sum, there can be broader phenomena experienced post-use than what’s described as HPPD and an open mind to alternative explanations and approaches is reasonable as purely pathological perspectives may increase distress over the situation.



How Common is Post-Use Phenomena?

While HPPD is rare, experiencing some type of post-use phenomenon appears to be relatively common and mostly benign.

For example, an online survey of over two thousand psychedelic users found that 24% reported at least one drug-free visual abnormality on a constant or near constant basis. In the same survey, 4% found the experiences distressing enough to consider treatment, yet only 1% sought treatment [8]. A review of post-use phenomenon in clinical trials of LSD, MDMA, or psilocybin involving a total of 142 participants found that 9.1% (n = 13) reported reoccurring drug-like experiences that were predominantly mild [9]. Two of the 13 that reported reoccurring drug-like experiences found them distressing although they subsided spontaneously. One reported pleasant reoccurring drug-like experiences for 7 months.

Therefore, it appears that post-use phenomenon is reasonably common and persons considering psychedelic use may be counseled that ~1/11 healthy persons in trials did experience post-use phenomenon and that when it has occurred it’s mostly perceived as neutral or pleasant, yet not always.

Persons can be counseled that distressing and persistent forms of post-use phenomenon (HPPD) appear more common with regular use of psychedelics or poly-psychedelic use. This is important since one aspect that may cause significant distress is lack of education that post-use phenomenon can occur and temptation to pathologize unexpected changes to perception if they arise. Unexpected post-use phenomenon, psychiatric comorbidity, and prevailing misinformation about HPPD may lead persons to negative beliefs about themselves or the course of post-use phenomenon that could compound or worsen the situation. It has been noted that no case meeting a diagnostic criterion for HPPD has been reported from a clinical trial to date [9, 10].


What Causes HPPD?

The pathophysiology and etiologic roots of HPPD are not known, yet there are several hypotheses which are not necessarily mutually exclusive. Changes in EEG patterns have been detected both with intoxication from psychedelics and in persons with HPPD, which may indicate CNS changes resulting in a more chronic form of cortical disinhibition or hyperexcitability [2, 5]. This could occur via destruction or dysfunction of inhibitory GABA interneurons and excessive glutamate release. Other hypotheses involve impairment of the Lateral Geniculate Nucleus (LGN), which is located in the thalamus and involved in pathways of visual perception [2]. According to reports in medical literature HPPD is most often caused by LSD or PCP, although can also be caused by psilocybin, MDMA, cannabinoids, and other psychedelic substances [11, 12].

HPPD as Psychedelic PTSD

A study of 19 individuals who developed HPPD found that all recalled anxiety and/or panic reactions during the triggering episode [1]. Thus, HPPD symptoms could potentially be conceived as a form of trauma response, similar to PTSD, or a form of health anxiety evoked by residual symptoms of the original experience.

Psychiatric Comorbidity

It appears that persons with psychiatric comorbidity like depression, anxiety, or a substance use disorder are more likely to present with complex type of symptoms [5]. Other reviews have hypothesized that psychiatric comorbidity may be a risk factor for HPPD [1]. However, HPPD can occur in persons without psychiatric comorbidity. Symptoms of HPPD may accompany or be worsened by symptoms of anxiety or depression.

Neuroplasticity Gone Wrong?

Psychedelics can produce neuroplastic effects and these properties are being intensively studied for therapeutic potential. It is conceivable that there could be ways in which set and setting interact with neuroplastic responses of psychedelics to produce unwanted outcomes that involve sensory perception.


Management of HPPD


There is no known specific cure for HPPD and treatment may focus on a combination of therapy, medication, and lifestyle adjustment. Therapy can be helpful in teaching people how to change their thought patterns and reaction to experienced perceptual disturbances. Use of Cognitive Behavioral Therapy (CBT), exposure therapy, or mindfulness-based therapies have all demonstrated some improvements in particular cases. Simply providing a safe space to talk about what they experience and receive validation and emotional support can be helpful.

Lifestyle Modification

The development of HPPD if oftentimes linked with polysubstance use and many psychoactive substances that are not hallucinogenic have been reported to worsen or exacerbate HPPD at times. Avoidance of psychedelics, cannabis, alcohol, and stimulants while focusing on balanced nutrition and sleep can provide some relief and reduce intensity of perceptual disturbances.


Several types of medications have been trialed in cases of HPPD, at times with partial or full improvements, and at times without noticing any benefit or even worsening symptoms. First line medications may include pre-synaptic α2 agonists such as clonidine or lofexidine. These medications act as sympatholytic and can also increase GABA neurotransmission, both which could provide calming effects to key parts of the brain involved in responses to psychedelics (amygdala, cortex).  Other first line medications include benzodiazepines such as clonazepam or alprazolam. While evidence is not comprehensive, there is more data supporting benefit of clonazepam in cases of HPPD than other medications. The habit forming and addictive nature of benzodiazepines are obvious disadvantages and may need carefully considered in persons with histories of using multiple substances or having substance use disorders.

Medications such as antipsychotics or antidepressants with activity at serotonergic neurons are characterized by mixed reports, with some cases showing improvements and other cases worsening with use. Particularly, the atypical antipsychotic risperidone has been flagged in several cases as worsening symptoms of HPPD and should be avoided. Generally, medications such as antipsychotics or antidepressants may be more beneficial when there’s an underlying indication for their use that is separate or pre-dates development of HPPD (e.g. generalized anxiety disorder).

Other medications, particularly anticonvulsants such as gabapentin, lamotrigine, valproic acid, topiramate, and carbamazepine have been trialed with some benefit, particularly with sudden onset or paroxysmal visual disturbances, which could be viewed as a type of ‘visual seizure’. Alternative sympatholytic such as beta blockers or calcium channel blockers have also been prescribed with some benefit when other medications fail.

Transcranial Direct Current Stimulation (tDCS)

A newer case report described successful treatment of HPPD using transcranial direct current stimulation (tDCS) which has been shown to reduce cortical excitability. After a decade of misdiagnosis and treatment with various medications, a 33 y/o was diagnosed with HPPD and found to have an (EEG) with increased delta activity over the occipital brain regions. After the first session with tDCS symptoms improved greatly and persisted for 10 days. On a second session, symptoms reduced further and the increased delta activity originally observed was gone. The patient reported alleviation of HPPD as well as depression, anxiety, and agitation. Their HPPD did not completely resolve and remained ~3-4 on a VAS scale of illness severity, however they experienced great relief knowing that there is a tool that can help symptoms [13].


Research and Support

Persons experiencing distressing post-use phenomenon or suffering from HPPD can feel isolated or that support for their condition is lacking. The Perception Restoration Foundation is a non-profit organization that promotes and funds research, support and awareness-raising around HPPD. There is a large social media group dedicated to supporting persons with HPPD here. There is a survey through Johns Hopkins researching HPPD that is currently active. I'm also more than happy to consult with any person experiencing distressing post-use phenomena. 


High Notes

Post-use phenomena after psychedelic use is relatively common and mostly transient, benign, and limited in nature [9]. However, there are people that experience distressing and persistent post-use phenomenon. Distressing post-use phenomenon appears linked with traumatic psychedelic experiences, use of several psychedelics, cortical disinhibition, and pre-existing psychiatric illness. These cases have classically been diagnosed as either HPPD I or HPPD II, however the existing diagnostic criteria does not adequately capture the range of post-use phenomena reported [2]. First line treatments may use of medications or other interventions (tDCS) that reduce cortical excitability as well as therapy and lifestyle adjustments [2, 13].



  1. Halpern, J.H., A.G. Lerner, and T. Passie, A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD. Curr Top Behav Neurosci, 2018. 36: p. 333-360.
  2. Martinotti, G., et al., Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives. Brain Sci, 2018. 8(3).
  3. Doyle, M.A., et al., Hallucinogen persisting perceptual disorder: a scoping review covering frequency, risk factors, prevention, and treatment. Expert Opin Drug Saf, 2022. 21(6): p. 733-743.
  4. Ford, H., et al., Hallucinogenic Persisting Perception Disorder: A Case Series and Review of the Literature. Front Neurol, 2022. 13: p. 878609.
  5. Vis, P.J., et al., On Perception and Consciousness in HPPD: A Systematic Review. Front Neurosci, 2021. 15: p. 675768.
  6. Diab, H. and B. Malcolm, Persistent Tinnitus after Inhaled N,N-dimethyltryptamine (DMT). J Psychoactive Drugs, 2020: p. 1-6.
  7. Uthaug, M.V., et al., A comparison of reactivation experiences following vaporization and intramuscular injection (IM) of synthetic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting. Journal of Psychedelic Studies, 2020. 4(2): p. 104-113.
  8. Baggott, M.J., et al., Abnormal visual experiences in individuals with histories of hallucinogen use: a Web-based questionnaire. Drug Alcohol Depend, 2011. 114(1): p. 61-7.
  9. Müller, F., et al., Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants. Psychopharmacology (Berl), 2022. 239(6): p. 1933-1943.
  10. Schlag, A.K., et al., Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. J Psychopharmacol, 2022. 36(3): p. 258-272.
  11. Orsolini, L., et al., The "Endless Trip" among the NPS Users: Psychopathology and Psychopharmacology in the Hallucinogen-Persisting Perception Disorder. A Systematic Review. Front Psychiatry, 2017. 8: p. 240.
  12. Schetz, D., A. Schetz, and I. Kocić, A retrospective analysis of the "Neverending Trip" after administration of a potent full agonist of 5-HT2A receptor - 25I-NBOMe. Biomed Pharmacother, 2022. 146: p. 112295.
  13. Haslacher, D., et al., Pathological Delta Oscillations in Hallucinogen Persisting Perception Disorder: A Case Report. Front Psychiatry, 2022. 13: p. 867314.

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