Psychedelics linked to lingering visual disturbances resembling early psychosis

Every night, as he fell asleep, a 25-year-old man saw an eye in his ceiling. It was huge and unblinking, and it felt as if the whole world was being sucked into it.

He didn't have psychosis, and he wasn't on drugs. But he had taken psychedelics in the past, and he was worried enough to contact Max Greenwald, an MD-PhD student at Yale School of Medicine, with a question: Was he developing psychosis?

"It's truly unclear whether this guy is at greater risk for psychosis," Greenwald says. But his experience would raise his score on the scale clinicians use to identify people at high risk.

That uncertainty is at the heart of a new study in Scientific Reports by Greenwald and Albert Powers, MD, PhD, medical director of Yale's PRIME Psychosis Risk Clinic for young people at high risk of psychosis. The study examines the lingering visual effects some people experience after psychedelics-which the researchers refer to as persisting perceptual abnormalities (PPAs)-and whether they work like the hallucinations of psychosis.

A common side effect, rarely studied

Now being tested as treatments for mental health disorders, psychedelics like psilocybin or LSD can leave behind PPAs, and researchers suspect this links to changes in how the brain receives, interprets, and organizes information. In the study's sample of 186 psychedelic users, recruited largely through online forums, more than half said they had experienced PPAs that started after psychedelic use.

"The rate of persisting perceptual abnormalities is much higher than I think most people appreciate," Greenwald says. He notes that visual abnormalities after psychedelic use have been recognized for decades as Hallucinogen Persisting Perception Disorder (HPPD), but this condition is not commonly diagnosed because it requires clinically meaningful distress and impairment.

PPAs were common in this study because Greenwald and Powers excluded the requirement for distress, and more than 90% of participants reported no distress.

The most common side effect they found in psychedelic users "is literally just colors being brighter," which, Greenwald says, is not necessarily distressing to users.

Moreover, people who started using psychedelics at a younger age were more likely to report having had these effects, the researchers found. "We saw evidence that suggests that using a psychedelic while the brain is still developing increases the probability of having experienced these effects," Greenwald says.

This corroborates previous studies where adolescent psychedelic users had a much higher rate of experiencing PPAs compared to adults.

Early stages of psychosis are hard to study because no one knows exactly when they begin. But psychotic illness rarely arrives all at once. "An average of about 22 months prior to the first episode of psychosis," says Powers, associate professor of psychiatry at Yale School of Medicine, "people start hearing buzzes or pops or footsteps, or might just see that their lights are brighter or sounds are louder."

Greenwald says that psychedelics rarely trigger psychosis in healthy, screened people. A psychosis diagnosis is typically preceded by a period of what's known as "prodromal psychosis," or the gradual onset of non-specific symptoms like irritability, difficulty focusing, or even PPAs such a color intensity. Greenwald says the perceptual abnormalities seen in prodromal psychosis resemble those that persist after psychedelic use.

The risk for those already vulnerable to psychotic illness remains inadequately understood. When someone develops psychosis after taking a psychedelic, "what's hard to know is whether or not that person would develop psychotic illness anyway, and the psychedelic use was a stress test," he says.

Training the brain to see what isn't there

For this new research, the team used a task Powers developed. A tone plays as faint stripes appear in visual static. The brain learns that the tone means stripes, like Pavlov's dogs learning that a bell means food. Later, when the tone plays but the stripes are missing, many people see them anyway.

"I think it's tapping into this mechanism that we all have," Powers says, comparing it to the feeling that your phone just buzzed when it didn't. Powers' earlier work has shown that people with psychosis are especially prone to "conditioned hallucinations" because their brains trust their expectations over what their eyes and ears report.

Greenwald expected psychedelic users to show the opposite pattern since leading theory holds that psychedelics loosen the brain's grip on its expectations. "We were expecting that a hallucinogen would actually cause fewer conditioned hallucinations," he says, "and people would be seeing the world more accurately."

That isn't what they found. People with lingering effects saw more phantom stripes, felt more confident about them, and were worse at telling real stripes from static. But the model didn't show them leaning harder on their expectations. Instead, the results suggested a noisy visual system that is quick to say "yes, I see it."

By "noise," the researchers mean random errors in perception: moments when the visual system misses something that's there, or registers something that isn't.

Powers compares it to static on a phone line. "On a really noisy phone line, it's simultaneously easier to miss something the other person says while also being likely to think they said something when they didn't.

"It was this interesting kind of dance," he adds. "An interplay between what seemed to be bottom-up, persisting noise and this top-down expectation." In a noisy system, they propose, expectations can act as a template, turning static into the expected image.

Looking back in time

The study can't show that psychedelics cause these changes, and its online volunteers may not represent all users. But the findings may matter for prodromal psychosis research. Through this work, Powers and Greenwald hope to build a model of abnormal representations of reality-one where they could discern the underlying brain processes from similar symptoms or experiences.

Powers says this study could lead to a better understanding of the mechanism behind the symptoms of prodromal psychosis. "In this case, we have an exposure that might mimic the same kinds of symptoms," he says.

"When somebody has a psychotic episode, the clock starts to get them treated," Greenwald adds, "Outcomes are worse the longer you wait. This is something that could be prevented, or at least could be intervened upon to drastically improve someone's quality of life."

Source:

Yale School of Medicine