October 19, 2022
Stefan Baumann, Robin Carhart-Harris, David Nutt et al.
2 citations
preprint
In a placebo-controlled citizen science trial with 240 participants, microdosing tolerance was assessed by tracking whether correct guesses of receiving a microdose decreased with more doses taken. Correct guess probability declined overall, indicating tolerance developed. This tolerance was specific to LSD and LSD-analogue microdoses, not psilocybin microdoses. The findings suggest that microdosers may need to periodically suspend their routine to avoid tolerance and that psilocybin may be better suited for long-term protocols.
Research Square
April 28, 2022
David Wyndham Lawrence, Robin Carhart-Harris, Roland R. Griffiths et al.
2 citations
An analysis of 3,778 inhaled DMT experiences posted to Reddit over a decade found that entity encounters occurred in 45.5% of experiences, most commonly with a feminine phenotype (24.2%), aliens (16.3%), deities (13.8%), and jesters (6.5%). Interactions were predominantly positive (34.9%) or pedagogical (32.4%). Common visual phenomena included fractals and vivid colors, while somatic effects like auditory ringing were frequent. Mystical features and reduced fear of death were reported, with 6.1% of experiences described as profoundly beautiful. Challenging responses were less common.
PsyArXiv
June 25, 2021
Christopher Timmermann, Hannes Kettner, Chris Letheby et al.
2 citations
preprint
Psychedelic use can shift metaphysical beliefs away from materialism and toward panpsychism and fatalism, and these changes persist for at least six months. In a large prospective online survey, participants reported significant belief changes after using psychedelics, with shifts linked to the extent of past use and improved mental health. The belief shifts were moderated by baseline impressionability and mediated by perceived emotional synchrony with others during the experience. Findings were confirmed in an independent controlled clinical trial, suggesting psychedelics causally influence metaphysical beliefs.
bioRxiv (Cold Spring Harbor Laboratory)
June 16, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Gorka Zamora-López et al.
1 citation
Psilocybin and the conventional antidepressant escitalopram produce opposite changes in the brain's hierarchical non-equilibrium dynamics when treating major depressive disorder. Using resting-state fMRI before and after treatment, researchers built whole-brain models and measured how much each patient's brain activity deviated from the fluctuation-dissipation theorem. Baseline measures distinguished treatment responders from non-responders within each group. The deviation from the fluctuation-dissipation theorem may serve as a marker to differentiate the brain effects of psilocybin and escitalopram, contributing to understanding how these treatments work for depression.
bioRxiv (Cold Spring Harbor Laboratory)
January 29, 2026
Venkatesh Subramani, Timothy Nest, Annalisa Pascarella et al.
1 citation
LSD alters brain activity by increasing alpha and beta brain-wave frequencies while genuinely reducing oscillatory power, with these effects showing distinct cortical patterns. The drug also flattens the aperiodic 1/f spectral slope and increases neural signal fractality and complexity, particularly in sensory, language, emotion, and imagery-related networks, while sparing motor cortex. Machine learning identified peak-frequency shifts, aperiodic parameters, and complexity measures as key discriminators of the psychedelic state. Music did not amplify these neural signatures and showed a trend toward attenuation. These findings provide a comprehensive account of how LSD reorganizes large-scale human brain dynamics.
PsyArXiv
September 4, 2025
Jacob S. Aday, Robin Carhart-Harris, Kevin F. Boehnke
1 citation
preprint
Classic psychedelic drugs such as psilocybin, LSD, and ayahuasca are being explored as treatments for many health conditions, but predicting how individuals will respond is difficult. Age may be an important but underappreciated factor that moderates these responses. Older adults have unique disease processes for neuropsychiatric disorders and require special treatment considerations. Differences in life circumstances, body physiology, use of multiple medications, weight, and brain biology may create distinct risks and opportunities for older adults. A consistent trend in the literature is that psychedelic drug effects become blunted across the lifespan, a finding that has been overlooked.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 23, 2025
Jessica S. Henry, Bruna Giribaldi, David Nutt et al.
1 citation
In patients with major depressive disorder, two high-dose psilocybin therapy sessions produced large increases in optimism and improvements in all three domains of dysfunctional attitudes (achievement, dependency, self-control) at six weeks, while a six-week daily course of escitalopram improved only the achievement domain and did not change optimism. Psilocybin also made patients more optimistic about desirable life events, whereas escitalopram reduced pessimism about negative life events. The findings suggest psilocybin therapy is superior to escitalopram for remediating negative cognitive biases in depression.
Imaging Neuroscience
April 16, 2025
Lorenzo Pasquini, Alexander J. Simon, Courtney L. Gallen et al.
1 citation
DMT rapidly induces a short-lasting altered state of consciousness marked by physical transcendence, vivid auditory distortions, and visual imagery. Using simultaneous fMRI and EKG data from 14 healthy volunteers before, during, and after intravenous DMT or placebo, a brain substate emerged immediately after DMT injection, characterized by deactivations in the hippocampus and medial parietal cortex and increased activity in the superior temporal lobe. Hippocampal and medial parietal deactivations correlated with altered sense of time, space, and self-referential processes, reflecting a deconstruction of ordinary consciousness. Superior temporal lobe activations correlated with audio/visual hallucinations and the experience of "entities.
PLoS One
February 12, 2025
Zishan Jiwani, Simon B. Goldberg, Jack Stroud et al.
1 citation
Most meditators who also use psychedelics report that the drugs improve their meditation practice. In a survey of 863 regular meditators who had used psychedelics, 73.5% said psychedelics positively influenced the quality of their meditation. Machine learning analysis of 53 variables identified the strongest predictors of this perceived benefit: greater frequency of psychedelic use, setting intentions before taking psychedelics, having an agreeable personality, and having used N,N-Dimethyltryptamine (N,N-DMT). The results suggest that individual traits and patterns of use shape whether psychedelics are seen as helpful for meditation, but causality cannot be established from this cross-sectional data.
bioRxiv
February 8, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
1 citation
preprint
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region central to reward and motivation—communicates with other areas. In a resting-state fMRI study, neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connectivity between the limbic striatum and the amygdala, while LSD increased connectivity between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, suggesting the drugs reduce the brain's usual network segregation, which may help explain their therapeutic potential for conditions like addiction, mood disorders, and PTSD.
bioRxiv (Cold Spring Harbor Laboratory)
December 22, 2024
Jakub Vohryzek, Morten L. Kringelbach, Edmundo Lopez-Sola et al.
1 citation
preprint
Both psychedelic states and reduced states of consciousness flatten the brain's functional hierarchy, yet their behavioral and phenomenological profiles differ. To resolve this paradox, researchers defined hierarchy by the brain's proximity to thermodynamic equilibrium and examined changes induced by three serotonergic psychedelics: psilocybin, LSD, and DMT. All three consistently reduced the functional hierarchy globally. Unlike loss of consciousness, psychedelics moved the brain toward equilibrium while increasing neural activity complexity, indicating a distinct mechanism involving altered configuration and differentiation of resting-state networks. This work demonstrates how statistical mechanics metrics can characterize different global brain states, advancing understanding of consciousness as an emergent collective process.
bioRxiv Preprint Server
December 9, 2024
Clayton R. Coleman, Kenneth Shinozuka, Robert Tromm et al.
1 citation
preprint
Lysergic acid diethylamide (LSD) alters consciousness by affecting brain connectivity, particularly in the dorsolateral prefrontal cortex (DLPFC). Using fMRI and MEG data from healthy participants, the study found that ego dissolution—a hallmark of the psychedelic experience—was positively correlated with increased functional connectivity between the left and right DLPFC, thalamus, and fusiform face area. Emotional arousal was linked to stronger connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory analysis supported these findings. MEG data showed that LSD increased directed information flow from the thalamus to the DLPFC in the theta band, suggesting disrupted thalamic gating contributes to ego dissolution. These results indicate a key role for the DLPFC in LSD-induced states of consciousness.
Elife
July 18, 2024
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
1 citation
Loss of consciousness significantly disrupts the brain's ability to integrate information. In a study involving functional MRI analysis, it was revealed that gateway regions in a 'synergistic global workspace' correspond to the default mode network, while broadcaster regions align with the executive control network. This integration breakdown occurs during general anaesthesia or disorders of consciousness, with recovery restoring functionality. The findings enhance understanding of consciousness by bridging Global Neuronal Workspace and Integrated Information Theory, highlighting the critical role of brain networks in maintaining conscious experience.
PsyArXiv
February 13, 2024
Michael Angyus, Sarah Osborn, Eline Haijen et al.
1 citation
preprint
A new 9-item scale called the Imperial Psychedelic Predictor Scale (IPPS) predicts key features of the acute psychedelic experience. Analyzing four independent datasets (two online surveys with 741 and 836 participants, and two controlled administration studies with 30 and 28 participants), the scale showed good internal consistency and three factors: set, rapport, and intention. The IPPS significantly predicted mystical, challenging, and emotional breakthrough experiences. In one controlled dataset, set and rapport explained 40% of variance in mystical experience, and set alone explained 16% of variance in challenging experience. In another, rapport explained 9% of variance in emotional breakthrough. The scale may improve safety and therapeutic outcomes by forecasting response variability.
CPT: pharmacometrics & systems pharmacology
October 1, 2023
Emma Eckernäs, Jeroen Koomen, Christopher Timmermann et al.
1 citation
A modeling study designed an infusion protocol for the psychedelic compound DMT, aiming to maintain a specific level of psychedelic intensity. Using computer simulations based on pharmacokinetic/pharmacodynamic models, optimal doses to achieve intensity ratings between 7 and 9 on a 0-10 scale were a bolus of 14-16 mg DMT fumarate followed by an infusion rate of 1.2-1.4 mg/min. However, the proportion of simulated individuals achieving the target intensity was low (below 53%), indicating that individual dose adjustments would be necessary. Differences between the models were observed, particularly at scale boundaries, with bounded integer models predicting more cases exceeding the target than the continuous variable model.
Psychological Medicine
July 19, 2023
Brandon Weiss, Induni Ginige, Lu Shannon et al.
1 citation
No Summary
Neuroscience Applied
January 1, 2023
Hannah Douglass, Merle Spriggs, Kate Godfrey et al.
1 citation
No Summary
June 30, 2022
Sandeep M. Nayak, Bilal A. Bari, David B. Yaden et al.
1 citation
preprint
A Bayesian reanalysis of a trial comparing psilocybin (COMP360) to escitalopram for major depressive disorder found that psilocybin outperformed escitalopram, but not by a clinically meaningful amount. The analysis also found extremely strong evidence that psilocybin is non-inferior to escitalopram. Evidence for psilocybin's superiority varied by depression scale: indeterminate for one, strong for two, and extremely strong for another. For a clinically meaningful difference, evidence was moderate against it on one scale, indeterminate on two, and moderate supporting it on one. These results provide a more nuanced interpretation and support further research.
March 24, 2021
Pedro J. Teixeira, Matthew W. Johnson, Christopher Timmermann et al.
1 citation
preprint
Unhealthy behaviors like poor diet, inactivity, and smoking are major contributors to cancer, diabetes, and cardiovascular disease, causing substantial suffering and public health costs. Interventions to promote healthy behaviors increasingly draw on psychobiological models. This article explores the potential of psilocybin, a psychedelic with low toxicity and no addictive properties, to assist positive lifestyle change. Psilocybin has shown favorable effects in patients with depression, anxiety, and substance misuse, conditions marked by rigid behavioral patterns. The authors describe proposed mechanisms and research findings linking psychedelics to health behavior change, noting that therapeutic models combining psychedelic experiences with methods like Cognitive Behavior Therapy and Motivational Interviewing are already being tested for addiction and eating disorders. They suggest this research may extend to promoting diet, exercise, nature exposure, and mindfulness.
December 11, 2020
Balázs Szigeti, Laura Kärtner, Allan Blemings et al.
1 citation
A self-blinding citizen science study tested whether psychedelic microdosing improves well-being and cognition beyond placebo. 191 participants who already planned to microdose were randomly assigned to receive four weeks of microdoses, placebos, or a mix. All psychological outcomes—including well-being, mindfulness, and life satisfaction—improved from baseline in the microdose group, but the placebo group also improved, and no significant differences emerged between groups. Small acute differences in mood, energy, and creativity were observed, but these could be explained by participants correctly guessing whether they took a microdose. The findings suggest that the anecdotal benefits of microdosing are likely due to the placebo effect.
UNC Libraries
April 22, 2020
Peter J. Hellyer, Luke T. J. Williams, Ben Sessa et al.
1 citation
Lysergic acid diethylamide (LSD) in microgram doses produces profound, sometimes life-changing experiences and is a uniquely powerful psychoactive substance. In the first modern neuroimaging study of LSD, marked changes in brain blood flow, electrical activity, and network communication patterns were observed. These changes correlated strongly with the drug's hallucinatory and consciousness-altering properties. The findings have implications for understanding the neurobiology of consciousness and for potential applications of LSD in psychological research.
Lancet Psychiatry
September 1, 2016
Robin Carhart-Harris, David Nutt
1 citation
No Summary
bioRxiv (Cold Spring Harbor Laboratory)
Hanna M. Tolle, Andrea I. Luppi, Timothy Lawn et al.
1 citation
preprint
A geometric deep learning model called graphTRIP predicts post-treatment depression severity from pretreatment clinical and brain imaging data. Trained on a clinical trial comparing psilocybin and escitalopram, it achieves strong predictive accuracy (r = 0.75) and generalizes to an independent dataset. The model links better outcomes to reduced functional coupling within serotonin systems and broader serotonergic integration with sensory-motor networks. Causal analysis shows a group-level advantage of psilocybin over escitalopram but identifies individuals with specific stress-related neuromodulatory profiles who may benefit more from escitalopram, advancing precision medicine and biomarker discovery in depression.
Br J Psychiatry
July 8, 2026
Hannah Douglass, Meg J. Spriggs, Kate Godfrey et al.
In a small pilot study, 21 women with anorexia nervosa received three doses of psilocybin (COMP360) over six weeks, combined with talk therapy and usual care. The treatment was well tolerated; common side effects were headache, nausea, and dizziness. Two serious adverse events (suicide attempts) occurred in one participant during the 6–12 month period. Eating disorder symptoms significantly improved at six months, and motivation to change improved at twelve months, though individual responses varied widely. The findings provide preliminary support for the feasibility and safety of psilocybin therapy in this population, but larger, more rigorous studies are needed.
Hum Brain Mapp
July 1, 2026
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
A computational model predicts that a single dose of psilocybin can produce lasting changes in the dynamic activity and effective connectivity of fronto-striatal-thalamic brain circuits. The modeling suggests that psilocybin may strengthen connectivity between the prefrontal cortex and striatum while altering thalamic gating, effects that persist beyond the acute drug experience. These changes could underlie the sustained therapeutic benefits observed in clinical settings, such as reduced depressive symptoms and increased psychological flexibility. The findings provide a mechanistic framework for understanding how psilocybin induces long-term neural plasticity and highlight potential circuit targets for treating psychiatric disorders.