Recent research published in translational psychiatry We provide evidence that people who experience persistent visual distortions after using psychedelic drugs tend to have higher rates of anxiety and physical health conditions. The findings suggest that this phenomenon is not a simple response to substance use, but is part of a complex interaction between mental and physical health.
When you take a psychedelic substance like lysergic acid diethylamide, commonly known as LSD, you typically expect the visual and perceptual changes to disappear once the drug leaves your body. Some people experience these visual distortions that persist long after the initial intoxication has ended. This condition is diagnosed as hallucinogen persistent sensory disorder.
People with this condition may see halos, trailing images, or static-like dots around objects in their vision. These visual phenomena are also colloquially referred to as flashbacks. Recent research tends to classify this condition into two different subtypes based on how symptoms manifest over time.
Type I is characterized by sudden, short-term changes in perception that can be experienced as positive, neutral, or negative. Type II involves chronic, persistent visual abnormalities and usually causes significant distress. The constant intrusion of these visual distortions can make people feel trapped and disconnected from reality.
Scientists have not yet identified the exact biological mechanisms behind the perceptual disturbances that psychedelics persist. An older theory proposed that psychedelics cause toxic damage to the brain’s visual processing pathways. Recent research tends to cast doubt on the idea of permanent deleterious brain damage.
Matt Butler, specialist registrar in psychiatry and postdoctoral clinical research fellow at King’s College London, wanted to investigate the condition on a larger scale. “HPPD is recognized to affect some people who use psychedelics and is rarely reported as a side effect in clinical trials of psychedelics,” Butler said. “This can be a debilitating disorder, but the factors that lead to its development are not fully understood and previous studies have tended to have small sample sizes.”
Butler noted that patients often struggle to find understanding within the medical community. “People with HPPD can be torn between the dismissal that it’s all in their head and the persistent stigma that the disease is caused by irreversible brain damage caused by psychedelics,” he says. “We wanted to use a very large clinical dataset to understand the clinical relevance of HPPD, which could lead to further hypotheses about how and why HPPD occurs.”
Current thinking suggests that this condition may be associated with subtle overactivation of the visual processing system. This condition appears to share overlapping features with visual snow syndrome. Visual snow syndrome is a neurological condition in which a person constantly sees small flickering dots in their field of vision, similar to the static on an old TV.
To conduct the study, the researchers accessed the TriNetX database. It is a global network of electronic medical records containing de-identified medical data from more than 150 million patients. By analyzing these medical records, researchers were able to look back and compare different patient groups.
The authors identified a specific sample of 25,778 people with a formal diagnosis of hallucinogen persistent sensory disorder. “We were pleasantly surprised by the numbers we could pull from the clinical database,” Butler said. “With over 25,000 cases, this is by far the largest study of HPPD and suggests that although relatively rare, HPPD should not be ignored as a clinically important factor.”
To provide proper context, the researchers created three separate control groups for comparison. The first control group consisted of the general population who participated in regular health checkups. The second control group consisted of people who had used psychedelic drugs but did not develop persistent sensory problems. The third control group includes people diagnosed with common visual impairments, serving as a proxy for people with conditions such as visual snow syndrome.
The researchers used advanced statistical models to compare the medical histories of these groups. They used propensity score matching to ensure that the groups were mathematically similar in age, gender, and other basic demographics. They calculated the cumulative incidence of various psychiatric and medical illnesses before patients received their primary diagnosis.
Medical records revealed a high proportion of pre-existing health conditions in the group with persistent hallucinogen perception impairment. Before being diagnosed, 29.2 percent of these people had experienced a depressive episode and 26.2 percent had been diagnosed with an anxiety disorder. Researchers also found that 15.9% had chronic pain, 14.7% had headache syndromes and 12.3% had post-viral fatigue.
Additionally, 6.6 percent of the group had been diagnosed with attention-deficit/hyperactivity disorder, and 6.7 percent had fibromyalgia, which is characterized by widespread musculoskeletal pain. When compared to a control group of people who used psychedelics without developing persistent visual impairment, the group with visual impairment had significantly higher rates of anxiety and functional somatic syndromes. Functional somatic syndromes are physical illnesses in which patients experience chronic symptoms, such as pain and fatigue, that cannot be fully explained by standard medical tests or structural damage to the body.
“This is the largest study of HPPD to date, and we found strong associations between HPPD and psychiatric disorders, particularly anxiety, as well as functional and somatoform disorders,” Butler said. “This suggests that symptom complexity may be a burden in a group of patients who may require advanced treatment.”
Butler explained that this association provides insight into the nature of the symptoms. “The association with anxiety and functional impairment caused by changes in the way the brain processes information, rather than by any identifiable structural damage, may provide clues about the underlying disease process in HPPD,” he said. “While further research is needed to confirm this, the results are consistent with a model of the disease where symptoms may be reversible, giving reason for optimism regarding treatment and recovery.”
Butler added that recognizing this link could lead to real benefits for patients. “Further development of targeted interventions could benefit this often neglected group of patients,” he said.
The researchers also wanted to know whether certain pre-existing symptoms predicted the development of hallucinogen persistent perception disorder in psychedelic users. To do this, they used a statistical method known as the Cox proportional hazards model. They found that psychedelic users with a history of anxiety were 1.5 times more likely to develop visual impairment.
Those previously diagnosed with post-viral fatigue were 1.9 times more likely to develop persistent visual symptoms. Looking at the period since diagnosis, scientists have found that people with visual impairments face increased health risks. Compared to a psychedelic-using control group, they were twice as likely to develop a new functional somatic syndrome.
The affected group was also 1.4 times more likely to be diagnosed with a new mental illness. The researchers created an exploratory composite to group similar diseases. They found that the visually impaired group had a slightly higher risk of neurodegenerative disorders such as Parkinson’s disease compared to a general population control group.
The absolute risk of developing a neurodegenerative disease remained very small, affecting only about 2.3 percent of the sample. The researchers noted that this small increase may be explained by the higher rate of antipsychotic medication prescribed to this patient group. Antipsychotic drugs are known to cause side effects similar to those of Parkinson’s disease.
Additionally, those with persistent visual symptoms were more likely to develop visual degenerative diseases such as glaucoma than psychedelic users. They were no more likely to suffer from these eye conditions when compared to a control group from the general population.
The authors noted that their approach has some limitations that require context. “Many of the connections we identified were substantial,” Butler said. “Nevertheless, this is an associative study, so although we are relatively confident in our results given the large sample, we cannot draw any conclusions about causality.”
Because this study relied on electronic medical records, it relied on the accuracy of clinical coding by medical professionals. Databases also tend to be overrepresented with individuals who have complex medical needs and frequently see their doctors. “In this context, the suggestions we make about the underlying causes of HPPD are speculative and will certainly need to be confirmed through future studies that address these hypotheses more directly,” Butler said.
Medical billing codes used to identify psychedelic use lack specific details. Researchers were unable to determine the exact type of drug used, the dosage, or whether the substance was taken recreationally or in a clinical setting. Scientists were also unable to distinguish between short-term, transient and chronic, permanent subtypes of the disease because of the broad diagnostic codes.
One potential misinterpretation of these findings is the assumption that hallucinogen persistent sensory disturbances are imaginary illnesses. “The relationship between HPPD and mental and functional disorders in no way suggests that HPPD is ‘all in the mind,'” Butler said. “Like all dysfunctions, this is real and can be debilitating, and a lack of understanding can alienate some patients.”
Butler emphasized the physical reality of this condition. “Although dysfunction causes symptoms in a different way than other diseases, it is equally important to understand and treat it,” he said. “Again, our findings established an association rather than a cause.”
Future research should investigate the overlapping mechanisms linking persistent visual impairment, anxiety, and physical symptoms. “An important question may be whether the same factors associated with HPPD in this study can predict who will develop symptoms after psychedelic exposure, so what are the risk factors for developing HPPD?” Butler said. “Prospective, long-term studies are needed to answer this question.”
A better understanding of how the brain’s attention networks contribute to the maintenance of symptoms could lead to new treatments. “As we have seen, future research that more directly investigates the question of the underlying biopsychosocial causes of HPPD will also be extremely beneficial,” Butler said. “In addition to this, we hope to one day participate in efforts to develop new treatments for HPPD, which may incorporate interventions designed to correct processing errors that may underlie HPPD.”
The study, Characterizing the Clinical Relevance of Hallucinogen Persistent Perceptual Disorders: A Retrospective Cohort Study, was authored by Matt Butler, Ellen Moore, James J. Rucker, Katherine Lynch-Kelly, Denmark Hafeez, Ed Prideaux, Timothy R. Nicholson, Mark Edwards, and Thomas A. Pollack.
