Cureus
January 29, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
2 citations
The study aims to uncover the neural mechanisms by which psilocybin-assisted therapy affects obsessive-compulsive disorder (OCD) and whether those brain changes align with improvements in cognitive symptoms. A secondary goal is to test whether a low, tolerable dose is both practical and effective as a clinical treatment. The results will provide essential data for designing a future randomized controlled trial.
The Oxford Handbook of Psychedelic, Religious, Spiritual, and Mystical Experiences
December 18, 2024
Aaron D. Cherniak, Robin Carhart-Harris, Joel Gruneau Brulin et al.
2 citations
A theoretical synthesis of attachment theory and the REBUS neuroscientific model offers an organizing framework for psychedelic science. Attachment theory holds that people develop internal working models (IWMs) of relational experiences that function as predictive models shaping social and emotional worlds. Effective psychedelic interventions may induce a hyper-plastic neural state that, supported by corrective relational experiences, facilitates rapid learning and revision of IWMs toward greater security. Three proposals guide future research: individual differences in attachment security predict psychedelic phenomenology and integration; increasing attachment security may be a clinical outcome; and clinical utility involves attachment-related dynamics such as connectedness and alleviation of worries.
JMIR formative research
March 4, 2024
Grant Jones, Felipe Herrmann, Adam Bear et al.
2 citations
In a group of people who recently used psychedelics, increases in mindfulness were followed by improvements in well-being. The findings suggest that mindfulness may be a mechanism through which psychedelic experiences lead to positive mental health outcomes.
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 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)
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 Henry, Bruna Giribaldi, David J 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.
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 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.
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.
Research Square
June 19, 2026
Aline Frick, Grace Blest‐hopley, Manesh Grin et al.
In a reanalysis of a six-week randomized controlled trial comparing psilocybin with escitalopram for moderate-to-severe major depressive disorder, sex-related patterns emerged for anxiety and anhedonia. Women receiving psilocybin showed greater reductions in anxiety than men, while women receiving escitalopram showed greater reductions in anhedonia than men. For other depressive symptoms, thought suppression, and well-being, sex differences were small and uncertain. Sexual dysfunction severity was lower overall in the psilocybin group than in the escitalopram group and lower in women than in men, though the treatment-by-sex interaction was not significant. These preliminary findings suggest that responses to these serotonergic treatments may differ between women and men, supporting the need for adequately powered, sex-balanced trials.
Curr Psychiatry Rep
June 5, 2026
Matthew J. Reid, Hannes Kettner, Tessa F. Blanken et al.
correction
A correction notice was issued for a previously published article on psilocybin administration and sleep improvements. The correction addresses errors in the original text but does not provide new findings or data.
arXiv (Cornell University)
May 15, 2026
Jonas Mago, Edmundo Lopez-Sola, Jakub Vohryzek et al.
States of consciousness with minimal phenomenal content, such as those induced by certain meditation practices, show increased brain entropy similar to high-content psychedelic states, challenging the Entropic Brain Hypothesis that links entropy to phenomenal richness. The Complex Brain Hypothesis resolves this by proposing that brain complexity, not entropy, better indexes the richness of experience. Complexity is modulated by the grain of inference the brain uses to resolve uncertainty: fine-grained inference loosens constraints and proliferates content, as in psychedelic states; coarse-grained inference simplifies experience into contentless awareness, as in minimal phenomenal experiences. Both regimes can elevate entropy but differ in phenomenology and perturbational signatures, refining the Entropic Brain Hypothesis and highlighting minimal phenomenal experiences as a test case for computational theories of consciousness.
May 13, 2026
Robin Carhart-Harris, Richard Zeifman, Lorenzo Pasquini et al.
preprint
The paper argues that the term 'plasticity' in neuroscience refers to induced changes in brain function or structure, which differs from the dictionary definition of plasticity as the ability to be shaped or molded. Many biomarkers of neuroplasticity actually index processes that bias phenotypic canalization, the opposite of phenotypic plasticity, creating a paradox. The authors question extrapolating from these biomarkers to improved mental health, as the relationship is context dependent. They propose a new construct, 'mediational and recalibrative plasticity' (MR-P), which aligns with plasticity proper and can describe and predict phenotypic changes relevant to mental health.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Taylor Lyons, Joseph Marks et al.
Across three studies—a naturalistic observation, a single-arm psilocybin trial with healthy volunteers, and a randomized controlled trial comparing psilocybin to escitalopram in depressed patients—psychedelic use did not produce significant changes in authoritarian attitudes. Contrary to earlier suggestions, the evidence does not reliably show that psychedelics decrease authoritarian attitudes. Future work should use larger, more diverse samples and examine other political outcomes.
Philosophical Psychology
April 10, 2026
Eric Rundquist, Diego Nicolás Monasterio López, Juan Jonathan Oyarzo Alvarado et al.
A cognitive-linguistic analysis of interviews with a healthy volunteer after moderate-to-high psilocybin doses reveals that the participant consistently used metaphors framing abstract introspective events in terms of concrete, visible, and interpersonal events, instantiating a cognitive frame called the Observer's Model. These metaphors imply cognitive defusion and heightened metacognitive awareness during the sessions. Literal descriptions of hallucinatory visual experiences correlated semantically with metaphorical expressions, suggesting metaphorical thinking plays a role in motivating those experiences. The findings are linked to neuroscientific research on psychedelics and have psychological and therapeutic implications.
Discover Mental Health
March 7, 2026
Nicholas Fabiano, Brendon Stubbs, David W. Lawrence et al.
More than half of people with major depressive disorder do not respond to standard treatments, prompting interest in alternatives such as exercise and psychedelics. This commentary examines how these two approaches might work together. Biologically, psychedelics briefly boost brain-derived neurotrophic factor (BDNF) signaling, while exercise provides sustained BDNF elevation; psychedelics enhance neuroplasticity mainly in the cortex, whereas exercise promotes hippocampal neurogenesis; both increase serotonin release. Psychologically, psychedelics may help people adopt exercise habits, and exercise may improve emotional resilience, potentially deepening the psychedelic experience. The authors suggest that these complementary mechanisms warrant future research on their combined efficacy, tolerability, safety, and neurobiology.
bioRxiv (Cold Spring Harbor Laboratory)
March 5, 2026
Venkatesh Subramani, Annalisa Pascarella, Jérémy Brunel et al.
Lysergic acid diethylamide (LSD) loosens the brain's usual alignment between anatomical structure and neural activity in a frequency-dependent way. Low-frequency brain waves (theta, alpha, beta) become less constrained by the structural connectome, indicating a global relaxation of large-scale dynamics. High-frequency gamma activity shows selective reorganization rather than uniform disruption. Greater gamma-band decoupling within core default-mode network regions predicts the intensity of ego dissolution across individuals. LSD does not cause indiscriminate disintegration but drives system-specific rebalancing: visual and attentional systems decouple while auditory networks strengthen coupling. These findings suggest psychedelic states emerge from frequency-dependent relaxation of structural constraints, with default-mode reorganization as a neural correlate of ego dissolution.
Behavioral Sciences
February 23, 2026
Joshua Lipson, Hannes Kettner, Robin Carhart-Harris et al.
Mood before taking a psychedelic substance and factors like social connectedness, mindfulness, and spirituality influence how the experience unfolds. People with higher baseline depression and anxiety tend to have more challenging experiences but not more mystical ones, while those with greater wellbeing report more mystical and fewer challenging experiences. Mindfulness and spirituality are linked to more mystical experiences, and social connectedness and mindfulness are linked to fewer challenging ones. Mystical and challenging experiences were weakly but positively correlated overall.
medRxiv
February 19, 2026
Amanda Gow, Emily Shih, Ryan Reid et al.
Under Oregon's regulated psilocybin program, adults who consumed an average of 27.8 mg of psilocybin showed significant improvements in depression, anxiety, and well-being 30 days after a session, including those concurrently using psychiatric medication. Of 88 participants (median age 43, 52% male, 64.8% with prior psychedelic experience), two reported symptoms of hallucinogen persisting perception disorder one day after the session, but none at 30 days. The findings suggest that legal psilocybin services can produce clinically meaningful mental health benefits.
Neuroscience of consciousness
January 1, 2026
Jonas Mago, George Deane, Lars Sandved-Smith et al.
People under the influence of psychedelics often report encountering autonomous entities such as spirits, elves, or ancestors. A neurocomputational model, grounded in the active inference framework, explains these experiences by proposing that psychedelics reduce the predictability of sensory perceptions, leading the brain to interpret both internal and external perceptions as coming from non-self agents. The model synthesizes earlier theories including the entropic brain model, computational accounts of felt presence, and sensory attenuation theories of self-other discrimination. It aims to account for how the brain supports entity encounters and for the diversity and similarity of these experiences across cultural contexts.
Mol Psychiatry
December 1, 2025
Ross J. Purple, Rahul Gupta, Christopher W. Thomas et al.
correction
A correction notice addresses an error in a previously published article: the author's name Robin Carhart-Harris was incorrectly written as Robin Carhartt-Harris. The original article has been corrected.