Biology subjects

Ramaekers, J. G.

Publications and source records attributed to Ramaekers, J. G..

8 recordsLinked to original sources

bioRxiv2026

Psilocybin acutely dissociates cognitive and affective empathy, with empathic concern predicting persisting positive psychological effects

BackgroundPsychedelics have been proposed to enhance empathy and social connectedness, but it remains unclear whether these effects reflect global increases in empathic ability, whether they persist beyond the acute drug state, and whether they contribute to later psychological outcomes. MethodsIn a randomized, double-blind, placebo-controlled, parallel-group study, healthy participants received psilocybin (0.17 mg/kg) or placebo. Three dissociable components of empathy were assessed using the Multifaceted Empathy Test at baseline, during the acute drug state, and 7 days later: cognitive empathy (accuracy of emotion identification), emotional arousal (affective activation in response to anothers emotional state) and empathic concern (other-oriented compassion toward the depicted person. Persisting positive psychological effects were assessed at follow-up. Circulating oxytocin was measured, and spectral dynamic causal modeling was applied to resting-state fMRI data acquired during the acute drug state to examine effective connectivity within an empathy-relevant network. ResultsCompared with placebo, psilocybin acutely reduced cognitive empathy selectively for positive stimuli, while increasing emotional arousal for positive stimuli and empathic concern across valences. These empathy-related effects did not persist 7 days later. However, acute increases in empathic concern mediated later positive psychological changes, including improved attitudes about life and self, mood, and relationships. Psilocybin also increased circulating oxytocin compared to baseline, but oxytocin changes were not associated with empathy changes. Effective-connectivity analyses showed that empathic responding under psilocybin was associated with altered directional coupling among superior temporal and parahippocampal regions. ConclusionsPsilocybin does not simply enhance empathy, rather it impairs the identification of positive emotional states while heightening affective engagement and concern. Although these effects do not persist, acute empathic concern may contribute to later positive psychological change.

neuroscience↗

bioRxiv2026

Sex Differences in Acute Responses to Psychedelics: Evidence for Greater Subjective Intensity and Impairment in Female Participants

Serotonergic psychedelics are advancing as psychiatric treatments, yet acute responses vary between individuals and the contribution of sex, a fundamental biological variable, remains largely unexamined. We pooled two double-blind, placebo-controlled randomized studies in healthy volunteers (N = 94 drug observations; 43 male, 51 female) comparing psilocybin 15 mg, 2C-B 20 mg, and LSD 50 ug. Linear mixed models tested sex differences in acute subjective effects (visual analogue scales), retrospective altered-states ratings (5D- and 11-ASC), empathy (Multifaceted Empathy Test), and peak (Cmax) and total (AUC) drug exposure, with treatment and sex as fixed factors and age as a covariate. Female participants reported numerically higher subjective ratings than male participants on most measures. After adjustment for age, sex differences were significant on five measures, most robustly for feeling under the drugs influence, reduced vigilance, and impaired control and cognition, with medium-to-large effects. These effects were largely consistent across the three drugs. No sex differences emerged on any empathy measure or in peak drug concentrations, indicating that female's stronger responses occurred at equivalent drug exposure. Female participants may experience more intense acute subjective effects and greater perceived impairment under psychedelics, independent of age and not explained by drug exposure. These preliminary findings, implicating pharmacodynamic rather than pharmacokinetic mechanisms, have implications for dosing, informed consent, and safety monitoring, and underscore the need to treat sex as a biological variable in adequately powered psychedelic trials.

neuroscience↗

bioRxiv2024

The forgotten psychedelic: Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin

As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite its popularity among recreational users and distinct pharmacodynamics, the neural correlates of 2C-B remain unexplored. Using 7T resting-state functional MRI in 22 healthy volunteers, we mapped out the acute effects of matched doses of 20 mg 2C-B, 15 mg psilocybin and placebo across spatiotemporal benchmarks of functional brain organisation. In a within-subjects, double-blind, placebo-controlled crossover design, we evaluated the neuropharmacological and neurobehavioural correlates of an array of connectivity measures - including static (sFC) and global connectivity (gFC), dynamic connectivity variability (dFC), and spontaneous brain complexity. Compared to placebo, 2C-B and psilocybin selectively reduced intra-network sFC, while broadly increasing between-network and subcortical-cortical connectivity. Compared to psilocybin, 2C-B exhibited less pronounced reductions in between-network FC but elicited elevations in transmodal sFC. Both compounds yielded spatially divergent increases in gFC yet produced similar increases in brain complexity. Using PET density modelling, the spatial distribution of neural effects aligned with documented differences in monoaminergic transporter and serotonergic receptor binding affinity beyond 5-HT2A, highlighting the role of pharmacology in shaping functional dynamics. Lastly, we show behavioural markers of psychedelic effects are non-linearly reflected by the desynchronisation of the transmodal axis of functional brain organisation. Together, our findings highlight 2C-B as a useful new addition to the study of psychedelic neuroscience and may motivate new pharmacotherapy strategies.

neuroscience↗

bioRxiv2024

A virtual clinical trial of psychedelics to treat patients with disorders of consciousness

Disorders of consciousness (DoC), including the unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), have limited treatment options. Recent research suggests that psychedelic drugs, known for their complexity-enhancing properties, could be promising treatments for DoC. This study uses whole-brain computational models to explore this potential. We created individualised models for DoC patients, optimised with empirical fMRI and diffusion-weighted imaging (DWI) data, and simulated the administration of LSD and psilocybin. We used an in-silico perturbation protocol to distinguish between different states of consciousness, including DoC, anaesthesia, and the psychedelic state, and assess the dynamical stability of the brains of DoC patients pre- and post-psychedelic simulation. Our findings indicate that LSD and psilocybin shift DoC patients brains closer to criticality, with a greater effect in MCS patients. In UWS patients, the treatment response correlates with structural connectivity, while in MCS patients, it aligns with baseline functional connectivity. This virtual clinical trial lays a computational foundation for using psychedelics in DoC treatment and highlights the future role of computational modelling in drug discovery and personalised medicine.

neuroscience↗

bioRxiv2023

Altered subjective experience after psilocybin intake associates with a dynamic pattern of hyperconnected functional connectivity

To provide insights into neurophenomenological richness after psilocybin intake, we investigated the link between dynamical brain patterns and the ensuing phenomenological pattern after psilocybin intake. Healthy participants received either psilocybin (n=22) or placebo (n=27) while in ultra-high field 7T MRI scanning. Changes in the phenomenological patterns were quantified using the 5-Dimensional Altered States of Consciousness (5D-ASC) Rating Scale, revealing alterations across all dimensions under psilocybin. Changes in the neurobiological patterns displayed that psilocybin induced widespread increases in averaged functional connectivity. Time-varying connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low BOLD signal amplitude, suggesting heightened cortical arousal. In terms of neurophenomenology, canonical correlation analysis primarily linked the transition probabilities of the hyperconnected pattern with feelings of oceanic boundlessness (OBN), and secondly with visionary restructuralization. We suggest that the brains tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. For the first time, these findings link brain dynamics with phenomenological alterations, providing new insights into the neurophenomenology and neurophysiology of the psychedelic state.

neuroscience↗

bioRxiv2023

Assessment of the acute effects of 2C-B vs psilocybin on subjective experience, mood and cognition

2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, its acute effects and distinctions from classical progenitors have yet to be characterised in a controlled study. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C-B (20 mg) in comparison to psilocybin (15mg) and placebo in a within-subjects, double-blind, placebo-controlled study of 22 healthy psychedelic-experienced participants. 2C-B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared to placebo, as indexed by the Digit Symbol Substitution Test (DSST), Tower of London (TOL) and Spatial Memory Task (SMT). Neither compound produced empathogenic effects on the Multifaceted Empathy Test (MET). 2C-B induced transient pressor effects to a similar degree as psilocybin. The duration of self-reported effects of 2C-B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorisation of 2C-B as a subjectively "lighter" psychedelic. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-Bs experiential overlaps.

pharmacology and toxicology↗

bioRxiv2022

Ritualistic use of ayahuasca enhances a shared functional connectome identity with others.

The knowledge that brain functional connectomes are both unique and reliable has enabled behaviourally relevant inferences at a subject level. However, it is unknown whether such "fingerprints" persist under altered states of consciousness. Ayahuasca is a potent serotonergic psychedelic which elicits a widespread dysregulation of functional connectivity. Used communally in religious ceremonies, its shared use may highlight relevant novel interactions between mental state and FC inherency. Using 7T fMRI, we assessed resting-state static and dynamic FCs for 21 Santo Daime members after collective ayahuasca intake in an acute, within-subject study. Here, connectome fingerprinting revealed a shared functional space, accompanied by a spatiotemporal reallocation of keypoint edges. Importantly, we show that interindividual differences in higher-order FCs motifs are relevant to experiential phenotypes, given that they can predict perceptual drug effects. Collectively, our findings offer an example as to how individualised connectivity markers can be used to trace a subjects functional connectome across altered states of consciousness.

neuroscience↗

bioRxiv2019

Reduced responsiveness of the reward system underlies tolerance to cannabis impairment in chronic users

Cannabis is the most commonly used illicit drug in the world. However due to a changing legal landscape, and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly, cannabis impairment. Importantly, a growing body of evidence suggests regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo controlled, cross-over study assessed the acute influence of cannabis on brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional (OUs) and 12 chronic (CUs) cannabis users received acute doses of cannabis (300 g/kg THC) and placebo, and underwent ultra-high field functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS). In OUs, cannabis induced significant neurometabolic alterations in reward circuitry, namely decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in CUs. The finding that cannabis altered circuitry and distorted behavior in OUs, but not CUs, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment.

neuroscience↗