Psilocybin

Acute effects of psilocybin on the dynamics of gaze fixations during visual aesthetic perception

This double-blind study (n=23) using eye-tracking found that high doses of psilocybin mushrooms (0.5-3g dried) caused more localised visual exploration of paintings and less entropic fixation patterns compared to low doses, while increasing subjective emotional intensity without affecting aesthetic ratings of the artworks.

Authors

  • Enzo Tagliazucchi

Published

Scientific Reports
individual Study

Abstract

Serotonergic psychedelics are remarkable for their capacity to induce variable yet reproducible modifications to human consciousness. The acute effects of these compounds include perceptual alterations, predominantly in the visual domain, yet these alterations have been mostly documented only by subjective reports. We used eye-tracking to quantify the effects of low vs. high doses of psilocybin mushrooms on eye movements during the exploration of complex visual stimuli under semi-naturalistic conditions, focusing on the case of aesthetic perception. The experimental condition (high vs. low dose) was a priori unknown to participants and experimenters. High doses resulted in a more local visual exploration of paintings, and a less entropic distribution of fixations. While psilocybin altered gaze behavior and increased subjective emotional intensity and feelings of flow, it did not affect the aesthetic ratings of the stimuli, suggesting a dissociation between perceptual and evaluative aspects of aesthetic experience. These findings suggest that psilocybin may influence gaze fixation by altering the perception of low-level visual features, including textures, shapes, and colors. Our work highlights the possibility of investigating psychedelics by addressing their effect on behavior under complex naturalistic conditions, contributing to maintaining subject engagement while also increasing the ecological validity of the findings.

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Research Summary of 'Acute effects of psilocybin on the dynamics of gaze fixations during visual aesthetic perception'

Introduction

Earlier research documents robust subjective visual alterations produced by serotonergic psychedelics, but objective behavioural metrics of sensory engagement under these drugs remain underexplored. Muller and colleagues note that eye-tracking provides a quantitative window on how attention is allocated across visual scenes, allowing tests of theoretical proposals about psychedelic action such as the Relaxed Brain Under Psychedelics (REBUS) model. REBUS predicts that psychedelics relax high‑level priors and thus should increase entropy in how visual information is sampled, yet empirical tests using naturalistic stimuli are scarce. This study set out to quantify how an acute high dose of psilocybin mushrooms alters the spatiotemporal dynamics of gaze fixations during free viewing of classical paintings, compared with an active low‑dose control. Using a semi‑naturalistic, self‑blinded design intended to balance ecological validity and experimental control, the investigators combined eye tracking with self‑report measures of acute perceptual intensity, aesthetic experience and altered states to test whether high dose psilocybin increases the entropy and spatial spread of fixations as predicted by REBUS.

Methods

Twenty‑three adults (four females; mean age 31 ± 4 years; mean weight 72 ± 15 kg) with prior experience of serotonergic psychedelics were recruited. Eligibility required at least two prior experiences with doses ≥ 3 g dried psilocybin mushrooms and excluded recent psychedelic or other psychoactive use, current psychiatric disorders by DSM‑5 criteria, pregnancy and ongoing psychiatric medication. After psychiatric screening and informed consent, participants scheduled two sessions separated by ≈ one month. Due to poor eye‑tracking data quality six participants were excluded from eye‑tracking analyses and two participants stopped the task during the high dose session, yielding a final sample of 15 participants for eye‑movement analysis. A priori power calculations had targeted 23 participants for an expected effect size of d = 0.6. The experiment used a self‑blinded, within‑subject design with an active control. Participants prepared and randomised two capsule types themselves: a high dose condition (~3 g ground dried Psilocybe cubensis in gel capsules) and an active control (~0.5 g ground active mushroom mixed with edible mushrooms to match capsule weight). Experimenters and participants were kept unaware of condition identity prior to analysis; sessions took place in homes chosen by participants with researchers present. The eye‑tracking task began about one hour after ingestion, following EEG setup and a 30–45 min acclimation. Each of 30 paintings (selected randomly from a curated BBC set) was presented for 30 s, preceded by a 2 s fixation cross; after each image participants provided two trial‑wise visual analogue scale (VAS) ratings for emotional valence and perceived beauty. Calibration was repeated every five blocks. The full experimental session included additional tasks and lasted approximately 3.5–5 h. Eye movements were recorded with a Gazepoint GP3 HD portable eye‑tracker (150 Hz temporal resolution, visual angle accuracy 0.5–1.0°). Fixations were detected using the device's velocity‑based algorithm with a minimum duration of 150 ms. Fixation coordinates were standardised to a common 1280 × 768 pixel frame. For each image, participant and condition the investigators computed: total number of fixations (N), mean distance between consecutive fixations (ds), mean time between fixations (dt), mean distance between all pairs of fixations (ds2) and their standard deviations. Spatial entropy of the 2D fixation probability distribution was estimated using Shannon entropy on discretised fixation histograms with four bin sizes (40×40, 60×60, 80×80 and 100×100 pixels) to assess robustness across spatial resolutions. Subjective measures comprised repeated VAS items capturing perceptual effects during the acute window (one hour after ingestion and then hourly), the Aesthetic Experience Questionnaire (AEQ) administered immediately after the eye‑tracking task during dosing, and other trait/state scales collected before and after dosing (e.g. STAI, PANAS, MEQ, 5D‑ASC). Statistical comparisons used paired Student's t‑tests for questionnaire totals, Wilcoxon signed‑rank tests for eye‑tracking and trial‑wise VAS data, linear mixed effects models to examine order effects, and Bayesian factors (BF10) to quantify evidence for alternative vs null hypotheses. Multiple comparisons were controlled using Benjamini‑Hochberg FDR where appropriate; effect sizes were reported (Cohen's d, rank‑biserial correlation) and supplementary tables contained additional model results.

Results

Participants correctly identified condition (high vs low dose) on 42 of 46 measurement days (91% accuracy), indicating a substantial unblinding rate. As expected, the high dose produced robust subjective effects: all four total VAS scores (summed perceptual intensity items) were significantly higher under the high dose than the active control, with peak effects between 2 and 3 hours after ingestion. The high dose also yielded significant increases on the 5D‑ASC and MEQ30 scales. Many comparisons that were null showed BF10 values < 1/3, interpreted by the authors as evidence favouring the absence of an effect in those measures. On the AEQ, two subscales differed between conditions: the emotional response factor and the flow of experience factor scored significantly higher during the high dose. By contrast, trial‑wise VAS ratings of emotional valence and perceived beauty averaged across images did not differ between dosing conditions. The authors note that the AEQ captures a global emotional engagement across the session, whereas the VAS reflected immediate reactions to individual paintings. Eye‑tracking analyses (n = 15) revealed that the high dose led to more local visual exploration. Specifically, mean distance between consecutive fixations (ds) and mean distance between all fixation pairs (ds2) were significantly lower in the high dose condition, indicating shorter saccadic spans and a narrower spatial spread of fixations. The standard deviations of both ds and ds2 were also significantly reduced under the high dose, showing decreased variability in fixation distances. Shannon entropy computed for the 2D fixation probability distribution was significantly lower for the high dose across all tested bin widths, consistent with a less entropic, more spatially confined fixation distribution. No significant differences were reported for the number of removed fixations between conditions. Correlation analyses between total VAS scores and eye‑tracking metrics or aesthetic ratings did not yield significant associations after FDR correction. Repeated measures and Pearson correlations between fixation metrics and AEQ dimensions revealed four significant correlations in the low dose (control) condition and none in the high dose; the only significant difference between conditions in correlation strength was for ds versus the AEQ emotional response subscale (low dose r = 0.71, high dose r ≈ 0.08), indicating a decorrelation under the high dose. Linear mixed models including order as a factor found no significant order × condition interactions after FDR correction.

Discussion

Muller and colleagues interpret their findings as indicating that acute high‑dose psilocybin alters the spatial dynamics of visual exploration during aesthetic perception, producing shorter, less variable fixation distances and a lower entropy of fixation distributions. Behaviourally, this pattern suggests a shift toward more local, spatially confined attention under the high dose. At the same time, participants reported greater overall emotional engagement and flow on the AEQ, while immediate trial‑by‑trial beauty and valence ratings were unchanged, pointing to a dissociation between global affective engagement and momentary evaluative judgements. These results contrast with a simple prediction derived from REBUS that relaxing high‑level priors should increase entropy of visual sampling. The authors propose alternative reconciliations: increased bottom‑up information flow or relaxed priors might heighten processing demands on low‑level features, provoking slower or more local inspection of stimuli, or cause attention to dwell on texture and form at the expense of global semantic sampling. Such a mode of perception aligns with historical anecdotal reports of intensified attention to low‑level detail. The observed loss of correlation between global emotional engagement and global sampling (ds) under the high dose suggests that increased emotional experience under psilocybin does not arise from broader semantic sampling of the artwork. The authors acknowledge several limitations. The self‑blinded, semi‑naturalistic design improved ecological validity but allowed a high unblinding rate and variable implementation of the blinding procedure. Natural settings and longer, diverse task batteries increased the risk of missing data, which led to the exclusion of six participants from eye‑tracking analyses and two participants voluntarily stopping the task in the high dose. Stimulus familiarity was not systematically assessed, stimuli were relatively short in presentation (30 s) and exclusively classical paintings were used, so it remains unclear whether effects generalise to non‑artistic scenes. The sample was predominantly male, and the study was exploratory and not pre‑registered, increasing degrees of analytical freedom. The authors also note that placebo or expectation effects cannot be fully ruled out, though they suggest behavioural measures may be less sensitive to placebo than self‑reports. For future research the investigators recommend pre‑registered, hypothesis‑driven studies, inclusion of non‑artistic control stimuli, varied stimulus durations, and replication under tighter lab control to disentangle low‑level perceptual from top‑down attentional contributions. They consider this study a first quantitative characterisation of how psilocybin modulates fixation statistics during aesthetic perception and a basis for hypothesis generation in subsequent confirmatory work.

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RESULTS

Due to insufficient data quality (more than 30% of stimuli presenting more than 30% of the fixations missing or outside the screen, suggestive of lack of engagement with the task) the data of 6 participants were excluded from the analysis presented in this and the following section. This threshold excluded all subjects who failed to engage with the task (i.e. subjects with a majority of off-screen fixations), while simultaneously resulting in a final number of participants that was adequate for statistical analysis. Fixations outside the images were removed from the subsequent analysis. We did not find a significant difference in the number of removed fixations between conditions (see Figureof the supplementary material). After recording the coordinates of the gaze position, fixations were detected automatically using the built-in velocity-based algorithm provided by the Gazepoint GP3 HD software, accessed through the iohub module in PsychoPywith minimum fixation durations of 150 ms. This resulted in the average horizontal and vertical positions ( xi, yi), as well as the time of the i-th fixation ( ti), with the positions recorded in pixels and the time in seconds. Since the dimensions of the selected paintings varied, all fixations were standardized to a common dimension of 1280 × 768 pixels to allow straightforward comparison of distances. For each image, participant and condition, the following measures were calculated: the total number of fixations within the image ( N ), the Fig.. Outline of the eye tracking task. After an initial calibration, the first block (T1) begins. Each block consists of the following steps: a fixation cross is displayed for 2 s, followed by the presentation of the stimulus for 30 s, during which participants freely explore the painting while their gaze is being recorded by the eye tracker. Emotional valence and beauty ratings were assessed after each painting. This procedure was repeated for the 30 paintings, with intermediate eye tracker calibration every 5 blocks. mean distance between fixations ( ds), the mean time between fixations ( dt) and the mean distance between all pairs of fixations ( ds 2 ). These metrics are outlined in Fig., and are computed as follows: Additionally, the standard deviation was also calculated for each image for the distances between consecutive fixations ( ds) and the distances between all pairs of fixations ( ds 2 ), as follows: These measures were then averaged across images, resulting in a mean value for each participant and dosing condition.

CONCLUSION

Following a self-blinded paradigm under semi-naturalistic conditions with an active control (low dose), we investigated the modulation of perception by psilocybin, a natural serotonergic psychedelic of major contemporary interest in basic and clinical neuroscience. The experiment was designed to be self-blinded, with the experimental condition a priori unknown to participants and researchers. Nevertheless, there was a considerable unblinding rate in the participants. Instead of focusing solely on the measurement and analysis of subjective reports, we used eye tracking to quantify the behavior of participants regarding the statistics of their visual fixations when presented paintings from different art periods. These stimuli are naturally engaging and diverge from everyday visual scenes, thus factoring in an element of uncertainty in the experiment; moreover, their use represents an opportunity to further our knowledge of how psychedelic compounds influence aesthetic perception, a long-standing field of research which has gained attention recently. Our results suggest that participants under the high dose acquire information through a more local visual exploration, with shorter distances between all fixation pairs, as well as between consecutive fixations. Psilocybin also reduced the variability in these two metrics, while decreasing the entropy of the fixation probability distribution, which is consistent with narrower spatial distribution of attention under the high dose condition. Finally, we found that psilocybin induced a decorrelation between the consecutive fixation distance and the emotional response dimension of the aesthetic experience, as measured with the AEQ. With regards to the aesthetic experience itself, participants reported heightened emotional response and state of flow under the influence of the high dose relative to the control condition. Ample anecdotal evidence suggests a link between the output of successful artists and the use of psilocybin, LSD and other serotonergic psychedelics, contributing to the emergence of the movement known as "psychedelic art". However, few rigorous studies attempted to clarify the relationship between the acute effects of psychedelics, artistic perception and expression, and creativity. A recent naturalistic study addressed the effects of psychedelic microdosing on aesthetic perceptionfailing to find an effect of drug intake on feelings of awe elicited by paintings, thus partially contradicting anecdotal reports of a deeper and more profound aesthetic Fig.. Scatter plot of the fixation metrics vs. the emotional sub-scale of the AEQ, including the best linear fit in the least squares sense for the active control condition (AC) and high dose (PSI) conditions. The correlation coefficient obtained for the high dose condition was r = 0.079, while the value for the low dose condition was r = 0.71, resulting in a significant increase of the Pearson correlation from the low to the high dose condition. perception caused by these substances. Even though we did not explicitly address the construct of awe, we found increased scores of the emotional response dimension of the AEQ during the high dose condition. Interestingly, we did not find differences in the VAS item assessing the emotional valence of each individual painting. This discrepancy suggests that individuals may have experienced a heightened emotional response to the artworks overall in the high dose condition, however, this heightened emotional response may not necessarily translate into consistently more positive or negative evaluations of individual artworks, as reflected by the VAS scores. This interpretation implies that while the overall emotional experience may be intensified under the high dose condition, it may not significantly alter the valence of emotional responses to specific individual artworks. We also found a marginally significant effect of psilocybin on the flow of experience dimension. Interestingly, previous work suggests some degree of overlap between the constructs of flow and absorptionthe latter being originally defined as "a disposition for having episodes of total attention that fully engage one's representational resources". It is known that trait absorption and the acute effects of psychedelics can exert mutual influencesand that absorption plays an important role in the processing of aesthetic stimuli from different modalities. However, the lack of studies using eye tracking hinders a direct comparison between these studies and our findings. Our results show a discrepancy in how participants evaluate their general predisposition towards aesthetic perception (indicated by the AEQ questionnaire) and how they perceive and judge the aesthetic content of specific stimuli (indicated by the VAS). Previous work has addressed the effects of psychedelics on affective states and feelings of flow, showing acute and long-term increases of positive emotionsenhanced emotional response to musicand a state characterized by heightened abstract flow. Thus, the ratings from the AEQ questionnaire may reflect general aspects of the psychedelic experience that are not specifically related to aesthetic perception. Recent work from Aday and colleaguesinvestigated changes in aesthetic experiences elicited by ayahuasca, adopting an open label naturalistic design. Measured with the AEQ, participants reported increased levels of aesthetic experience in two follow-up sessions (one week and one month after the ayahuasca retreat). These changes occurred for all dimensions of the questionnaire, while in our study we only found differences for two facets. This discrepancy could be attributed to expectation effects in the study conducted by Aday et al., given the lack of a control condition, or due to the more intense and sustained nature of psychedelic use in that study, which consisted of retreats totaling between 2 and 7 ayahuasca sessions. It is possible that the use of an active control in our experiments could have resulted in alterations to aesthetic perception, thus reducing the difference between conditions. However, van Elk and colleagues did not find any significant effect of a comparable dose of psilocybinsuggesting that our results were related to the effects of the high dose. Another factor to be considered is a possible effect of the setting on aesthetic perception, as natural environments could favor aesthetic experiences more than urban contexts. In contrast to the experiment by Aday et al., we administered the AEQ during the acute effects of the drug and we did not investigate whether the psilocybin resulted in longterm modifications. This choice was also motivated by the possibility of false beliefs during the acute effectsand by the potential interference with the formation of memorieswhich could be triggered by the drug and thus diminish the confidence in the questionnaire scores. Finally, neither our experiment nor the one conducted by Aday and colleagues revealed significant correlations between acute effects (e.g. mystical type experiences) and the changes in the AEQ scores. Further research is required to understand how aesthetic perception relates to other idiosyncratic aspects of the psychedelic experience. The reported changes in fixation metrics could stem from the effects of psilocybin on low-level visual perception, top-bottom attentional processes, or a combination of both. According to a model proposed by Chatterjeethe first stage of aesthetic perception corresponds to the identification of lower-level variables (color, form, texture, etc.), which are subsequently integrated to form a holistic view, directing visual attention to specific areas of interest depending on visual composition and complexity. The well-established effects of psychedelics on low-level visual perception 2 could influence the first stage of this process, while the acute effects on attention could influence the second stage. Previous studies established that more global fixation distributions are characteristic of the judgment of aesthetic appeal, while more local distributions relate to the processing of visual complexity in the paintingsuggesting that our findings could stem from the interaction between psychedelics and the perception of low-level visual features in the stimuli. The positive correlation between ds and the AEQ sub-scale assessing the emotional aspect of the aesthetic experience suggests that semantic content is gathered by exploring the painting more globally when the participant is more emotionally engaged with the painting. Conversely, the decorrelation between these variables observed for the high dose condition could indicate that the emotional involvement with the artwork, which is overall greater in this condition, does not affect the way it is explored, suggesting that the increase in emotional engagement is not directly related to the semantic content gathered during visual exploration. However, it must be noted that the immediate VAS scales administered after each painting included a rating of subjective aesthetic appeal, yet no significant effects of psilocybin were found on this variable. Also, the exclusive use of classical paintings as visual stimuli in our study raises the question of whether the observed effects on gaze dynamics are specific to aesthetic experiences or reflect a more general alteration in visual exploration under psilocybin. Future studies could consider including non-artistic stimuli (e.g., natural scenes, geometric patterns, or everyday objects) to determine whether the reduction in fixation entropy and increased local exploration observed under psilocybin are specific to the aesthetic context or represent a broader change in visual attention mechanisms. Although we attempted to minimize prior familiarity by selecting paintings from a curated set that aimed to avoid overly recognizable artworks, some of the selected paintings may still have been well known to participants. Familiarity with a given artwork could influence patterns of gaze or subjective evaluation. We did not systematically assess participants' prior knowledge of the stimuli, which constitutes a limitation of the study. Nevertheless, since the same stimuli were used for both conditions of the experiment, it is unlikely that familiarity affected the results of the high vs. low dose comparison. Also, familiarity with the paintings is expected to increase in the second condition of the experiment; however, we did not find any effects of the order in which conditions were completed by participants. According to the REBUS theory proposed by Carhart-Harris and Friston, psychedelics act by relaxing the precision of high-level priors or beliefs, thereby liberating bottom-up information flow. In visual perception, this relaxation could manifest as a more entropic exploration of the visual scene, as the priors fail to inform gaze direction to regions where most of the relevant semantic information is represented. To date, this hypothesis has received evidence from multiple experiments, including complex tasks such as the production of natural speech. In contrast, our findings indicate a less entropic and more confined distribution of fixations. The liberation of bottom-up information flow could increase demands on cognitive processing, resulting in a slower and/or more local exploration of the visual scene. The relaxed priors might also lead to fixations failing to target relevant regions of the stimuli, increasing attention to low-level visual features and causing an exaggerated interest in this aspect of the paintings at the expense of a more global appreciation. In "The Doors of Perception", Aldous Huxley famously narrated how his attention was lost at seemingly insignificant details of the visual scene: "I looked down by chance, and went on passionately staring by choice, at my own crossed legs. Those folds in the trousers-what a labyrinth of endlessly significant complexity! And the texture of the grey flannel-how rich, how deeply, mysteriously sumptuous!". Such mode of perception seems compatible with the more local exploration revealed by our analysis of the eye tracking data. The interpretation of our results faces some limitations, mainly due to specific choices concerning the experimental design. In this study, we prioritized the inclusion of tasks which are either natural and/or spontaneous (e.g. production of language), or capable of engaging the participants for relatively long periods of time, as is the case for the visual perception and the aesthetic appreciation of artworks. We also opted to pursue this experiment under conditions that are less constrained and more natural than those of a typical lab-based study. The merits and drawbacks of this approach have been discussed with detail elsewhere, yet here it is important to highlight that distractions during an eye tracking task can easily introduce a large amount of missing data points, potentially rendering the gathered data useless for further analysis. This issue could be expected to become more problematic in settings where subjects can develop feelings of fear and/or anxiety, including research laboratories and hospital settings. Another characteristic of our study is the inclusion of a large variety of paintings, as opposed to presenting a reduced repertoire for a longer duration. This choice could have limited the processing of the stimuli to that of low-level features, as discussed above. We decided to present paintings for comparatively short durations to maintain the attention and engagement of the participants. A potential limitation could arise due to the large unblinding rate of the conditions, compatible with previous studieseven when adopting an active condition as control (i.e. the low dose). While it is impossible to rule out a contribution of placebo effects to the eye tracking metrics, previous studies suggest that self-reported measures are typically more sensitive to placebo effects than behavioral or physiological measures. Another limitation to the generalizability of our findings is the predominantly male group of participants, which may represent a source of bias as gender could influence aesthetic perception. Finally, a major limitation of our study is its exploratory nature and the lack of pre-registration of the experimental design, hypothesis and analysis methodology. In this regard, we consider that exploratory studies are necessary when previous literature is scarce -in this case, due to the lack of reports addressing the sensitivity of eye tracking to capture behavioral changes elicited by psychedelics. A drawback of exploratory studies is the increased number of degrees of freedom, which can undermine the statistical significance of the findings. However, we attempted to minimize the degrees of freedom by focusing only on the basic statistical descriptors of the eye movement time series, and on the entropy of the fixation probability distribution, motivated by the entropic brain hypothesis and other related theories of psychedelic action. Future work by our group and others should build upon this first effort, capitalizing the present results for hypothesis generation in a pre-registered study. In conclusion, we achieved a quantitative description of fixation statistics during aesthetic perception and their modulation by mushrooms of the Psilocybe genus, while also shedding light on the interaction between acute psychedelic effects and the aesthetic experience elicited by a selection of paintings. Guided by theoretical efforts positing a relaxation of priors during the acute effects of serotonergic psychedelics, we first hypothesized a more entropic distribution of fixations. However, we found the opposite result, which could be compatible with the idiosyncratic effects of psilocybin on the perception of low-level visual information. Future studies are required to address this and other possibilities raised by our work, a first attempt to quantify the acute effects of psychedelics on the complex eye movement behaviors underlying visual perception.

Study Details

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