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Home Exclusive Neuroimaging

Regular psychedelic users exhibit different brain responses to self-related thoughts, study finds

by Eric W. Dolan
June 28, 2025
in Neuroimaging, Psychedelic Drugs
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People who use psychedelic substances may think about themselves in a different way — not just psychologically, but also neurologically. A new study published in Progress in Neuropsychopharmacology & Biological Psychiatry suggests that individuals who regularly use psychedelics in real-world settings show altered patterns of brain activity when reflecting on themselves.

Psychedelic drugs such as LSD, psilocybin, and DMT are known for their ability to shift perception, mood, and sense of self. In recent years, researchers have become increasingly interested in how these substances may support mental health by changing how people relate to their thoughts and emotions. Clinical trials have shown that psychedelic-assisted therapy can reduce symptoms of depression, anxiety, and addiction, often with effects that last for months.

However, most of this research takes place in controlled laboratory environments with strict protocols. In contrast, millions of people use psychedelics in naturalistic, unsupervised settings. While large surveys have shown that such users tend to report lower psychological distress and better emotional well-being, much less is known about how psychedelics affect their brain function. The current study aimed to fill that gap by comparing how regular psychedelic users and non-users respond to self-reflective thoughts — both in terms of reported experience and brain activity measured through electroencephalography, or EEG.

To reduce the chance that personality differences would skew the results, the researchers compared regular users to individuals who had never taken psychedelics but said they intended to do so in the future. This design allowed the researchers to focus more precisely on the effects of actual psychedelic use, rather than differences in lifestyle or mindset that might come from being generally open to such experiences.

Participants were recruited through Polish organizations associated with drug policy and harm reduction. After completing a screening questionnaire, they were invited to take part in an EEG study that recorded their brain activity while they engaged in a task designed to prompt self-related thinking. In total, the researchers collected two independent datasets: one from 70 people tested in Warsaw, and a second from 38 people tested in Krakow. Each site included both psychedelic users and non-users, matched by age, gender, and education.

Before the EEG task, participants completed several psychological questionnaires. These measured their levels of rumination (repetitive negative thinking), reflection (thoughtful self-examination), depression, anxiety, and prior experiences with meditation and substance use. The results showed that, in one dataset, psychedelic users scored lower on measures of anxiety, depression, and rumination, and higher on reflection — suggesting more adaptive self-processing. These differences were not found in the second, smaller dataset.

During the EEG session, participants completed a “self-related thoughts induction” task. In this task, they were asked to think about prompts such as “why you react the way you do” or “what kind of person you think you should be.” These were compared to distraction prompts unrelated to the self, such as “why you like the books you do.” After each prompt, participants rated how much they had focused on the topic, how much they had focused on themselves, and how sad they felt.

Both users and non-users showed more self-focus and sadness during self-related prompts, as expected. In one dataset, psychedelic users reported feeling less sadness than non-users, but again, this difference did not appear in the second group.

The most distinctive part of the study involved analyzing EEG data. EEG records the brain’s electrical activity across different frequency bands. The researchers focused on alpha (7–12 Hz) and beta (14–30 Hz) frequencies, which have previously been linked to the brain’s default mode network — a system involved in internal thought, including rumination and self-reflection. In past studies, psychedelics have been found to reduce activity in this network during the drug’s acute effects, which some researchers believe may help explain their therapeutic potential.

EEG analysis revealed that during self-related thought, non-users showed greater increases in alpha and beta power in brain regions commonly associated with self-processing — especially the posterior cingulate cortex, a key hub of the default mode network. Psychedelic users, by contrast, showed weaker increases in these same regions. These differences suggest that the brain dynamics involved in self-reflection may function differently in those who have repeatedly used psychedelics.

However, this pattern appeared only in the first dataset. The second dataset, collected in a different lab with fewer participants, did not replicate the between-group differences. When the researchers combined data from both sites, some effects persisted but were smaller in size. This inconsistency led the authors to urge caution in interpreting the results.

One possible reason for the differences between datasets is sample size. The second group was smaller and may have lacked the statistical power to detect effects. Another factor is the technical setup. Only the first lab had access to detailed individual MRI scans and precise tracking of electrode placement, which improves the spatial accuracy of EEG results.

Importantly, the researchers also looked at whether other variables — such as lifetime meditation or cannabis use — might explain the observed brain activity patterns. After accounting for these factors in statistical models, the differences between psychedelic users and non-users became less clear. This suggests that at least some of the effects initially attributed to psychedelics could also be influenced by related lifestyle habits, like meditation, which is known to alter self-related thought and brain activity.

When the team examined how brain activity correlated with behavioral measures like depression or rumination, no strong relationships emerged after correcting for multiple comparisons. Some brain patterns showed modest associations with lifetime psychedelic use, but these did not hold up statistically. This lack of consistent correlation suggests that brain activity patterns alone may not directly explain differences in mood or thought style — or at least not in a simple, linear way.

The researchers were transparent about the limitations of their work. Since the study was cross-sectional, it cannot establish cause and effect. That is, we don’t know whether psychedelics changed participants’ brains, or whether people with different brain function were more likely to use psychedelics in the first place. The study also relied on participants’ self-reports about their drug use, and did not control for the specific substances, doses, or contexts involved.

Despite these challenges, the study is one of the most detailed attempts to examine the long-term psychological and brain-based differences in naturalistic psychedelic users. It raises questions about how these substances may influence how people process their own thoughts, particularly those involving self-reflection, emotion, and personal meaning.

The authors recommend that future studies include larger and more diverse samples, and that they continue to explore the connections between brain function, subjective experience, and mental health outcomes. In particular, they call for better ways to account for self-selection bias and the cultural narratives that may influence how psychedelic users interpret and report their experiences.

The study, “Processing of self-related thoughts in experienced users of classic psychedelics: A source localisation EEG study,” was authored by Anastasia Ruban, Mikołaj Magnuski, Justyna Hobot, Paweł Orłowski, Aleksandra Kołodziej, Michał Bola, and Aneta Brzezicka.

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