Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans

Binocular rivalry is a visual phenomenon in which two different images presented separately to each eye produce alternating conscious percepts: observers typically report seeing one image at a time, with intermittent mixed or transitional percepts. Earlier research has used rivalry to probe neural correlates of consciousness and perceptual grouping, and several studies have reported associations between rivalry switch rate and global changes in conscious state such as clinical psychosis, drug-induced altered states, and meditation. Standard mutual-inhibition models explain switching by local cortical interactions and neural fatigue, but they do not account well for links between switch rate and broader state variables such as arousal or attention. An alternative model posits that large fluctuations in brainstem nuclei (raphe, ventral tegmental area, locus coeruleus) and their neuromodulator release (serotonin, dopamine, noradrenaline) drive perceptual alternations. This study used the serotonergic hallucinogen psilocybin to test whether pharmacologically altering serotonin-mediated brain states changes binocular rivalry dynamics and whether those changes depend on 5-HT2A receptor activation. Carter and colleagues administered psilocybin (215 μg/kg) alone and after pretreatment with the selective 5-HT2A antagonist ketanserin (50 mg) in ten healthy volunteers, and compared these conditions with ketanserin alone and placebo. Binocular rivalry switching, the proportion of mixed percepts, and subjective measures of mood, arousal and altered states were measured at multiple time points to test whether psilocybin would slow switching and whether ketanserin would block that effect.

The study received ethics approval and regulatory authorisation for psilocybin. Ten healthy volunteers (six men, four women; mean age 26.0±2.3 years) with normal or corrected vision and no personal or first-degree family history of major psychiatric disorder participated. Five participants had prior psilocybin experience; five were psilocybin-naïve. Treatments were given in gelatin capsules that looked identical: psilocybin 215 μg/kg, ketanserin 50 mg, and lactose placebo. The four experimental conditions (placebo; psilocybin; ketanserin; psilocybin plus ketanserin) were administered in a double-blind, counter-balanced within-subjects design, with sessions at least 14 days apart. Binocular rivalry stimuli were stationary green vertical and horizontal gratings delivered dichoptically via liquid crystal goggles, subtending 4° of visual angle with a spatial frequency of 1.5 cycles/degree and a duty cycle of 0.33. Subjects reported perceptual dominance using three keyboard buttons (vertical, horizontal, mixed); they were explicitly instructed to report mixed percepts, including extended transitional periods. Each rivalry session comprised four 60-s trials with 30-s breaks, and a 1-min simulated 'catch trial' movie was used before each session to familiarise subjects and assess response time and accuracy. The ketanserin or placebo capsule was given first and psilocybin or placebo 90 min later to ensure ketanserin receptor occupancy; rivalry was tested 45 min before and at several points after psilocybin/placebo intake (measures noted at 60–420 min depending on the test). The active metabolite psilocin peaks around 105±37 min after intake, and the 5D-ASC was administered to capture retrospective experience over 0–180 min, while the AMRS was completed at pretest and at 90 min. Attentional tracking and spatial working memory tests were performed at pretest and 120 min, but results from those tasks were reported elsewhere. Primary outcome measures included mean phase duration (average uninterrupted dominance time in seconds) and proportion of mixed percept reported. Subjective outcomes were assessed with the German AMRS (grouped into seven factors such as performance-related activity, general inactivity, dreaminess) and the 5D-ASC (five dimensions including oceanic boundlessness and reduced vigilance). The extracted text reports that analysis involved repeated-measures ANOVA to test drug and time effects and post hoc comparisons; response accuracy and reaction time on catch trials were also examined.

Psilocybin produced a robust slowing of binocular rivalry switching. Mean phase duration showed significant main effects of drug [F(3,27)=6.87; p<0.01] and time [F(10,90)=11.71; p<0.001]. Post hoc tests indicated that psilocybin, both alone and following ketanserin pretreatment, significantly increased phase duration at 60, 90 and 135 min (p<0.001). At 180 min, only the psilocybin-alone condition remained significantly greater than placebo (p<0.001). There was no significant difference between psilocybin alone and psilocybin plus ketanserin at any time point, and ketanserin alone did not differ from placebo. The proportion of mixed/transitional percepts also changed under psilocybin. A significant main effect of time [F(10,90)=5.24; p<0.001] and a time-by-dose interaction [F(30,270)=1.97; p<0.01] were reported. Post hoc comparisons showed that psilocybin increased the proportion of mixed percept at 90 and 240 min (p<0.01), while the psilocybin-plus-ketanserin condition showed a significant increase at 135 min (p<0.05). Performance on the catch-trial movie indicated that response accuracy was not affected by drug. Reaction times were significantly slower under psilocybin compared to placebo only at the 60-min time point (p<0.01). The combination of psilocybin and ketanserin produced slower response times at multiple time points (60, 90, 180, and 300 min; p<0.01). No differences between placebo and ketanserin alone were observed. Subjective measures showed a dissociation between classical hallucinogenic effects and reduced vigilance. Using AMRS difference scores (pretest to 90 min), repeated-measures ANOVA found main effects of drug [F(3,27)=10.28; p<0.001] and factor [F(6,54)=11.85; p<0.001]. Tukey post hoc tests indicated that psilocybin increased dreaminess (DR) markedly (p<0.0001); after ketanserin pretreatment, three AMRS factors changed significantly (performance-related activity PRA: p<0.01; general inactivity GI: p<0.0001; dreaminess DR: p<0.0001). Comparisons between psilocybin alone and psilocybin plus ketanserin found significant differences for GI (p<0.05) and general positive mood GPM (p<0.05). On the 5D-ASC, repeated-measures ANOVA yielded main effects for drug (F≈18.15; p<0.001) and factor [F(4,28)=11.22; p<0.001]. Psilocybin increased oceanic boundlessness, anxious ego dissolution and visionary restructuralization (all p<0.001) and also increased reduced vigilance (RV; p<0.05). Ketanserin pretreatment largely blocked the subjective effects of psilocybin except for RV, which remained significantly elevated (p<0.001). Ketanserin alone produced no significant subjective effects. At the individual level, slowing of binocular rivalry phase duration under psilocybin (relative to placebo at 90 min) correlated with increases in reduced vigilance scores (r2=0.61, p<0.05, df=8). A similar but non-significant relationship was observed in the psilocybin-plus-ketanserin condition (r2=0.27).

Carter and colleagues interpret their findings as demonstrating that psilocybin substantially prolongs perceptual dominance periods and increases mixed percepts during binocular rivalry. Crucially, these effects were not reversed by pretreatment with the selective 5-HT2A antagonist ketanserin, even though ketanserin blocked most of psilocybin's classical hallucinogenic or "positive" psychosis-like subjective effects (oceanic boundlessness, anxious ego dissolution, visionary restructuralization). The persistence of rivalry slowing despite 5-HT2A blockade led the investigators to conclude that the effect on switch rate is unlikely to be mediated by the cortical 5-HT2A receptor population responsible for those positive subjective phenomena. The authors highlight a dissociation between "positive" hallucinogenic effects and "negative" symptoms related to reduced arousal and attention. In their data, reduced vigilance (the RV dimension of the 5D-ASC) remained elevated after ketanserin pretreatment and correlated with the degree of rivalry slowing across individuals. This pattern suggests that changes in rivalry rate may be more closely linked to arousal and attentional state than to the hallucinogenic sensory distortions commonly attributed to 5-HT2A activation. The discussion suggests the 5-HT1A receptor as a plausible alternative mediator because psilocin also activates 5-HT1A, and 5-HT1A‑mediated reductions in raphe firing could alter cortical 5‑HT release and brainstem timing mechanisms implicated in switching. The authors emphasise, however, that direct tests using selective agonists or antagonists are required before firm conclusions can be drawn and that multiple receptors or downstream processes may contribute. Limitations acknowledged by the investigators include the absence of urine drug screens on test days and the possibility that ketanserin might interact with psilocybin in ways not yet understood; they note that ketanserin sometimes appeared to potentiate certain questionnaire scores. The authors argue that the results are unlikely to be artefacts of missed button presses or gross motor slowing because catch-trial accuracy was unchanged and reaction time changes were minimal and limited to a single time point. Finally, they propose that future work combining pharmacological manipulations (including testing compounds such as (S)-ketamine) with psychological manipulations of attention may clarify how attentional systems and neuromodulatory brainstem circuits influence conscious perception and rivalry dynamics.