The acute effects of psilocybin slow human reaction times and mildly impair the parts of cognition that regulate behavior. These short-term effects vary depending on the dose of the drug, highlighting the need for monitoring and safety measures while the substance is active in the body. The findings were recently published in the journal Psychopharmacology.
Psychedelic substances are increasingly being evaluated for their therapeutic potential in treating conditions such as anxiety and depression. As these drugs move toward wider clinical acceptance, researchers are attempting to understand exactly how these drugs alter immediate thought processes. Cognitive functions, especially executive functions, are essential mental skills that help people plan, focus attention, remember instructions, and multitask.
Executive function functions as a type of traffic control system for the brain, coordinating basic abilities to achieve specific goals. Disturbances in this system are common in a variety of mental illnesses. Observing how psychedelics temporarily alter these areas can help scientists assess the basic safety and potential side effects of future clinical treatments.
Leiden University researcher P. Yousefi and University of Freiburg researcher Morten P. Lietz led a group that quantified the acute cognitive effects of psilocybin. The acute phase refers to the period when a person is actively experiencing the direct physiological and psychological effects of the drug. The researchers wanted to see how executive functions responded to different doses of psilocybin, and how the timing of drug administration affected mental performance.
To assess these details, the research group conducted a systematic review and multilevel meta-analysis. Meta-analysis is a statistical method that combines data from multiple independent studies to identify broader and more reliable trends. The researchers pooled data from 13 empirical studies that included a total of 42 separate measures of cognitive ability.
These separate studies assessed different components of executive function. The researchers evaluated a task that measures discrepancy monitoring, the brain’s ability to process contradictory information. A common way to test this is the Stroop task. In this task, participants see the word “green” printed in red ink and have to say the color of the ink rather than reading the word.
They also assessed working memory. Working memory is often tested by asking participants to remember a series of numbers or locations that are continually updated as the test progresses. Finally, the analysis includes the study of response inhibition, the ability to suppress habitual responses. Attention span and cognitive flexibility were also assessed.
By combining the data collected, the scientists assessed how psilocybin affected two key outcomes during these cognitive tests. They focused on reaction times, which show how quickly participants respond to prompts. We also measured accuracy, which is the percentage of correct answers provided during a particular test session.
The researchers categorized the data by the dose given to the volunteers, treating anything less than 5 milligrams as a microdose and anything more than 30 milligrams as a high dose. They also grouped the data by the specific cognitive functions being tested. Finally, we evaluated the timing of the test compared to when the drug typically peaks in the bloodstream, typically between 90 and 180 minutes after ingestion.
The results showed that when participants took the drug, it took them longer to respond to a cognitive task than when they were given an inactive placebo. The researchers found that there was a linear relationship between drug dose and delayed reaction time. Microdosing produced a slight, barely measurable, delay effect, while low and moderate doses produced mild to moderate delays.
The highest doses caused extreme delays in processing speed. A notable finding from the pooled data was that working memory appeared to be slightly more resilient to these delays than basic attention, showing a severe decline only at high doses. In contrast, basic attention tasks experienced delays even in the lower dose range.
The change in accuracy was less pronounced. Although there was a slight trend toward decreased accuracy across studies, the results were not statistically significant. This means that the observed decrease in correct response rates was small enough that it could have been caused by statistical noise or random chance rather than the drug itself.
A general decrease in reaction time occurred. The researchers did not find that psilocybin impaired certain areas of executive function more than others. Delays were relatively uniform regardless of whether participants were inhibiting reflexes, updating memories, or switching between conflicting rules.
Timing of testing within the acute window did not alter the results. Response times were consistently delayed both during the peak period of drug effect and at times before and after the peak. This finding demonstrates that cognitive decline is an enduring feature of the entire acute psychedelic experience.
Analysts investigated how the design of the tasks affected these results. Some cognitive tests attempt to isolate purely mental tasks by subtracting baseline reaction speed from the final score, while others rely on raw scores that require a wide combination of sensory, motor, and attentional skills. The analysis revealed that common tests requiring multiple cognitive skills showed greater delays compared to tasks designed to isolate purely mental processes.
The authors propose several explanations for this uniform pattern of delayed responses. First, psilocybin can directly affect basic sensory and motor systems. There can be delays in how the visual cortex processes incoming light and how the motor cortex tells the hand to press a button, which can reduce performance on any physical exam.
Second, this drug is known to alter baseline alertness. Attention serves as the underlying building block for all higher-level mental operations. People who have difficulty concentrating on simple instructions will end up executing demanding rules at a slower pace and logically.
The third mechanism involves dual-task interference. As people navigate the intense subjective experience of psychedelic travel, their brains spend a great deal of effort processing emotional and sensory distortions. Asking participants to perform clinical tests simultaneously divides mental resources, leading to cognitive fatigue and slow performance.
There are some caveats to consider regarding the underlying data. The researchers noted a moderate to high risk of bias across the studies they analyzed. This was primarily because the physical effects of the active drug were so pronounced that it was difficult to tell participants whether they were given a psychedelic drug or a placebo.
The team also detected clear signs of publication bias in the data on reaction times. Publication bias occurs when studies with dramatic results are more likely to be published than studies with modest effects. As a result, the existing scientific literature may slightly overestimate the true extent to which psilocybin slows cognitive processing.
The available data focus only on the acute phase of the drug. Few studies have tracked cognitive performance days, weeks, or months after the drug leaves the body. Several recent independent studies have suggested the possibility of long-term cognitive effects after psychedelic use, but the mechanisms bridging acute impairment and long-term effects remain unclear.
Future research could benefit from moving to tasks that better mimic real-world activities. Traditional clinical testing can feel isolating and abstract, and while participants are actively experiencing an altered state, it can reduce participant motivation. Testing attention and memory in a more natural environment may help distinguish true cognitive impairment from a simple lack of motivation to complete boring computer tests.
Because psilocybin consistently slows reaction times during its active phase, researchers emphasize the need for close supervision in medical settings. Patients should avoid situations requiring rapid processing speed, such as driving or operating heavy machinery, until the immediate effects of the drug have completely resolved. Clinical guidelines require that patients remain in a safe environment for the duration of the drug’s effectiveness.
The study, “Acute Effects of Psilocybin on Attention and Executive Function in Healthy Volunteers: A Systematic Review and Multilevel Meta-Analysis,” was authored by P. Yousefi, Morten P. Lietz, FJ O’Higgins, RCA Rippe, G. Hasler, M. van Elk, and S. Enriquez-Geppert.
