Hallucinogen persisting perception disorder (HPPD) is a non-psychotic disorder in which a person experiences lasting or persistent visual hallucinations or perceptual distortions after using drugs such as psychedelics, dissociatives, deliriants, entactogens, and cannabinoids.
Symptoms may include visual snow, trails and after images (palinopsia), light fractals on flat surfaces, intensified colors, altered motion perception, pareidolia, micropsia, and macropsia. Floaters and visual snow may occur in other conditions.
For the diagnosis, other psychological, psychiatric, and neurological conditions must be ruled out, and they must cause distress in everyday life. In the DSM-5 it is diagnostic code 292.89 (F16.983). In the ICD-10, the diagnosis code F16.7 corresponds most closely. It is rarely recognized by hallucinogen users and psychiatrists, and is differentiated from hallucinogen-induced psychotic disorder in that it does not involve paranoia, insomnia, changes in thinking, or delusions, and relates to lasting visual changes only.
It is divided into two types, HPPD I and HPPD II. The more drastic cases, as seen in HPPD II, are believed to be caused by the use of psychedelics as well as associated mental disorders. Some people report symptoms after their first use of drugs (most notably LSD). There is little information on effective treatments.
The underlying mechanisms are not well understood. One hypothesis suggests that anxiety may amplify existing visual disturbances and potentially trigger these visual phenomena. Many report that their visual distortions become more pronounced or even emerge during periods of heightened anxiety or stress.
Symptoms Typical symptoms of the disorder include halos or auras surrounding objects, trails following objects in motion, difficulty distinguishing between colors, apparent shifts in the hue of a given item, the illusion of movement in a static setting, visual snow, distortions in the dimensions of a perceived object, intensified hypnagogic and hypnopompic hallucinations, monocular double vision, seeing an excessive amount of eye floaters, the morphing of multiple objects into one texture, and blue field entoptic phenomenon. The visual alterations experienced by those with HPPD are not homogeneous, and there appear to be individual differences in both the number and intensity of symptoms.
Visual aberrations can occur periodically in healthy individuals – e.g., afterimages after staring at a light, noticing floaters inside the eye, blue field entoptic phenomenon, or seeing specks of light in a darkened room. However, in people with HPPD, symptoms seem typically to be worse, but complications come from the additional roles played by anxiety and fixation. Indeed, anxiety has been implicated in visual perceptual effects similar to HPPD, and authors have recognized the crucial role of attending to underlying anxiety and panic in recovering from the disorder.
There is some uncertainty about to what degree visual snow constitutes a true HPPD symptom. There are individuals who have never used a drug which could have caused the onset, but yet experience the same grainy vision reported by those with HPPD, like people with the closely-linked neurological disorder known as visual snow syndrome. There are a few potential reasons for this, the most obvious of which is the theory that the drug usage may exaggerate the intensity of visual snow. At the same time, beyond the characteristic visual snow symptom, there is considerable overlap between the conditions, including after-images, palinopsia, tinnitus, dissociation, and free-floating anxiety, leading some to suggest that HPPD shares a strong relationship with visual snow syndrome. Visual snow syndrome is defined as lacking any known cause and is specifically distinguished from HPPD in its nosology, yet further research may clarify the relationship. HPPD usually has a visual manifestation, but some hallucinogenic and psychiatric drugs affect the auditory sense and can produce tinnitus-like symptoms as a side effect, and there are many anecdotal reports of people getting tinnitus with their HPPD.
A significant number of those reporting HPPD also describe comorbid depersonalization-derealization and anxiety disorders. Anxiety, PTSD and panic can promote depersonalization-derealization and visual disturbances, and vice versa, so these features may run in multidirectional relationships. Abraham suggested that all three can arise from a broader mechanism of disinhibition in sensory perception, affect and sense-of-self occasioned by psychedelic experience. It is not uncommon for depersonalization-derealization to be the most distressing symptom of the condition.
According to a 2016 review, there are two theorized subtypes of the condition. Type 1 HPPD is where people experience random, brief flashbacks. Type 2 HPPD entails experiencing persistent changes to vision, which may vary in intensity. This model has faced scrutiny, however, due to "flashbacks" often being considered a separate condition and not always a perceptual one.
Causes
A vast list of psychoactive substances have been linked with the development of this condition, including lysergamides like LSD and LSA, tryptamines like psilocybin and DMT, phenethylamines like 2C-B, MDMA, MDA and mescaline. Dissociatives such as ketamine and dextromethorphan as well as cannabis and synthetic cannabinoids, salvia divinorum, datura and iboga are also known to trigger HPPD. HPPD is not strictly associated with psychedelic consumption, as a number of hallucination-inducing substances may be correlated with its arising. For some, the dosage and how frequently one uses these substances does not seem to matter in the development of this condition, as there are several reports in the literature where patients were diagnosed after a single use. HPPD is more often seen in people with a history of previous psychological issues or substance misuse.
Which drugs are most prone to causing HPPD is not entirely known. While LSD has been described as the leading cause of HPPD, this may be a function of LSD's historically higher relative popularity as a recreational psychedelic drug. Popularity effects may explain the high proportion of cases precipitated by cannabis. A 2022 clinical review found no significant difference in the induction of subclinical visual phenomena between MDMA, LSD and psilocybin. Curiously, lasting visual effects have also occurred as complications of benzodiazepine withdrawal syndrome.
HPPD is more common among those with preexisting mental illness such as anxiety, depression, bipolar disorder, or schizophrenia.
Pathophysiology The exact pathophysiologic mechanism underlying HPPD is poorly understood. The primary neurobiological hypothesis is that persistent hallucinations are the result of chronic disinhibition of visual processors and subsequent dysfunction in the central nervous system following consumption of hallucinogens. Chronic disinhibition may occur from destruction and/or dysfunction of cortical serotonergic inhibitory interneurons involving the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). This ultimately can cause disruption of the normal neurological mechanisms that are responsible for filtration of unnecessary stimuli in the brain. On a macroscopic level, the lateral geniculate nucleus (LGN) of the thalamus, which is important in visual processing, has also been implicated in the pathophysiology of HPPD.
Other researchers have suggested HPPD may be related to drug-induced elevations in neuroplasticity – an effect also noted to occur for SSRIs. Reverse neuroplasticity effects may account for anecdotal reports of individuals treating their HPPD symptoms with further psychedelic drug use, while others report significant deterioriations in their symptoms.
Being characterized by clinical distress and impairment, however, HPPD is also shaped by psychosocial factors. There is tentative evidence that those who develop distressing HPPD have higher trait anxiety, or experienced elevations in baseline anxiety from possibly negative psychedelic experiences. Elevations in anxiety, and anxious responses to visual and related symptoms, may provoke direct elevations in symptom intensity and fuel the distress that defines HPPD as a clinical entity. Certain core beliefs and automatic thoughts are observed to occur among those reporting HPPD: fears of brain damage, a 'never-ending trip', the development of schizophrenia or a related psychosis spectrum disorder, a more generalized concern surrounding insanity, and destructive thoughts concerning the loss of one's previous self or a new identity centred on brokenness and alienation from others. Being a drug-related disorder, HPPD is therefore vulnerable to internalized anti-drug stigma, specifically around 'flashbacks' and 'brain frying', which were heavily propagandized in prohibitionist campaigns in the 20th-century.
Diagnosis Disorders with similar symptoms
Individuals without HPPD will sometimes notice similar visual abnormalities. These include floaters (material floating in the eye fluid that appears as black/dark objects floating in front of the eyes and are particularly visible when looking at the bright sky or on a white wall) and the white blood cells of the retinal blood vessels (seen as tiny, fast-moving, and quickly disappearing white specks). Likewise, bright lights in an otherwise dark environment may generate trails and halos. Most people don't notice these effects because they are so used to them. A person fearful of having acquired HPPD may be much more conscious about any visual disturbance, including those that are normal. In addition, visual problems can be caused by brain infections or lesions, epilepsy, and a number of mental disorders (e.g., anxiety, delirium, dementia, schizophrenia, Parkinson's disease). For an individual to be diagnosed with HPPD, these other potential causes must be ruled out.
Hallucinogen-induced psychotic disorder (HIPD)
Substance-induced psychosis from hallucinogens, also known as hallucinogen-induced psychotic disorder (HIPD), occurs when an individual experiences hallucinations, delusions, paranoia, or a reduced ability to communicate that continue beyond the initial effects of the hallucinogenic drug. Hallucinogen-induced psychotic disorder is a medical emergency. It is a psychotic reaction to a hallucinogenic drug that may indicate underlying bipolar disorder or schizophrenia. The specific treatment for hallucinogen-induced psychotic disorder is atypical antipsychotics, which includes both second and third-generation antipsychotics. Third-generation antipsychotics such as aripiprazole, brexpiprazole, cariprazine, and lurasidone, are increasingly used to treat substance-induced psychosis.
Treatment A variety of medications have been reported to be effective in treating HPPD. Essential to the treatment of HPPD is discontinuing all recreational drug use. In addition to HPPD symptoms, common comorbidities of anxiety, depression, psychosis, or sleep problems should be treated as well. Because anxiety exacerbates HPPD symptoms, studies have shown that both individual and group therapy can be effective in lowering anxiety and establishing a support network if those with HPPD are socially isolated.
Medication Case studies indicate full or partial recovery from HPPD using a variety of medications. Recent literature reviews recommend combining agents to treat HPPD symptoms, including comorbid anxiety, depression, psychosis, and insomnia.
Antipsychotics