Neuroimage
January 29, 2021
Beatrice M. Jobst, Selen Atasoy, Adrián Ponce-Alvarez et al.
37 citations
After taking LSD, the brain's dynamics become less stable and more diverse in response to perturbations. Using a whole-brain computational model fitted to fMRI data from individuals under LSD or placebo, researchers simulated external disruptions to different brain regions. They measured recovery time with the Perturbational Integration Latency Index (PILI). Globally, LSD caused consistently higher PILI values, indicating a shift further from stable equilibrium. Locally, the largest differences appeared in the limbic, visual, and default mode networks. LSD also increased variability of PILI across brain regions, suggesting greater response diversity. These findings reveal brain-wide dynamical changes underlying the psychedelic state and suggest potential clinical applications for psychiatric disorders.
Journal of affective disorders
March 1, 2025
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
35 citations
In treatment-resistant depression, a single dose of 25 mg of psilocybin produced stronger correlations between certain psychedelic experiences and depression improvement three weeks later than lower doses. The intensity of psychedelic effects was dose-related, but scores for different doses overlapped considerably. At the 25 mg dose, dimensions of oceanic boundlessness and visual restructuralization, along with emotional breakthrough, showed the strongest correlations with reduced depression scores. The study does not establish causation and requires replication. The overlap in experience intensity across doses suggests unblinding to dose is less likely. Correlations between psychedelic experience and outcome indicate specificity in psilocybin's mechanism of action.
J Palliat Med
April 13, 2021
Yvan Beaussant, James Tulsky, Benjamin Guérin et al.
34 citations
Researchers from palliative care, psychosocial oncology, spiritual care, oncology, and psychedelic-assisted therapies identified seven key opportunities for advancing research on psychedelic-assisted therapy for people with serious illness. Four opportunities relate to science and design: clarifying which conditions the therapy is indicated for, developing and refining therapeutic protocols, investigating how set and setting affect outcomes, and understanding mechanisms of action. Three opportunities concern institutional and societal drivers: education and certification for therapists, regulations and funding, and diversity and inclusion. Participants also noted epistemological limitations of the medical model for understanding psychedelics' therapeutic value.
Conscious Cogn
December 8, 2020
Camila Sanz, Carla Pallavicini, Facundo Carrillo et al.
34 citations
Language produced under the influence of LSD shows increased entropy and reduced semantic coherence, consistent with a state of heightened neural entropy. Non-semantic analysis of speech organization revealed increased verbosity and a reduced lexicon, changes more similar to manic psychoses than to schizophrenia, as confirmed by direct comparison with reference samples. Features related to language organization allowed machine learning classifiers to identify speech under LSD with accuracy comparable to that obtained by examining semantic content. These results provide a quantitative characterization of disorganized natural speech as a landmark feature of the psychedelic state.
Sci Rep
July 26, 2023
Balázs Szigeti, David Nutt, Robin Carhart-Harris et al.
33 citations
Blinding in medical trials aims to evenly distribute expectancy effects between treatment groups, but it often fails. Using computational modeling, this work shows that weak blinding combined with positive treatment expectancy creates an 'activated expectancy bias' (AEB), which can inflate treatment effect estimates and produce false positive results. The authors introduce the Correct Guess Rate Curve (CGRC) to estimate outcomes of a perfectly blinded trial from imperfectly blinded data. Re-analyzing a self-blinding psychedelic microdose trial dataset, they find that observed placebo-microdose differences are susceptible to AEB and may be false positives, suggesting microdosing acts as an active placebo. The findings highlight the distinction between trials with a placebo control group and genuinely placebo-controlled trials.
J Affect Disord
February 27, 2024
Debora Copa, David Erritzøe, Bruna Giribaldi et al.
31 citations
Brain connectivity patterns measured before psilocybin treatment can predict how much depression symptoms will improve. In people with treatment-resistant depression given two doses of psilocybin (25 mg each, one week apart), baseline resting-state functional MRI scans showed that connectivity within visual, default mode, and executive networks predicted early symptom improvement, while salience network connectivity predicted who would respond up to 24 weeks later, with about 90% accuracy. Similar patterns appeared in a separate trial comparing psilocybin to escitalopram. Fronto-occipital and fronto-temporal connections predicted early and late symptom reduction, respectively. Small sample sizes and differences between datasets limit generalizability, and the lack of a placebo arm limits specificity.
J Psychopharmacol
January 27, 2024
Jessica Barbut Siva, Tommaso Barba, Hannes Kettner et al.
29 citations
A prospective survey study examined how serotonergic antidepressants affect the acute subjective experience of classic psychedelics and subsequent well-being and depressive symptoms. People taking antidepressants reported less intense mystical-type experiences and greater anxiety during psychedelic sessions compared to those not on antidepressants. Despite this blunting, both groups showed similar improvements in well-being and reductions in depressive symptoms after the session. The findings suggest that while antidepressants may dampen the acute psychedelic experience, they do not necessarily hinder long-term mental health benefits.
PLoS computational biology
February 1, 2023
Giulio Ruffini, Giada Damiani, Diego Lozano-Soldevilla et al.
28 citations
Brain dynamics under LSD become more disordered and complex, moving further from the critical point that characterizes healthy brain function. Using Ising spin models fitted to fMRI data from fifteen participants, the authors show that LSD reduces interhemispheric connectivity, especially between corresponding regions in opposite hemispheres. Ising temperatures were significantly higher under LSD than placebo, indicating a shift into a more disordered (paramagnetic) state. Algorithmic complexity of brain activity, measured by block decomposition, correlated with both Ising temperature and condition, supporting the entropic brain hypothesis that psychedelics increase neural disorder.
Psychiatry Research
July 23, 2023
Otto Simonsson, Per Carlbring, Robin Carhart-Harris et al.
24 citations
In a meta-analysis of three psilocybin trials for depression involving 102 participants, clinically significant symptom worsening occurred for a minority of those receiving psilocybin or escitalopram (about 10%) and for a majority of those in the waitlist condition (63.6%). The psilocybin arm showed a lower likelihood of symptom worsening compared to waitlist and no difference compared to escitalopram. The authors note the limitation of a relatively small sample size.
Psychopharmacology
December 11, 2023
Haley Maria Dourron, Charles D Nichols, Otto Simonsson et al.
23 citations
5-MeO-DMT, a tryptamine being developed as an antidepressant, may work through a mechanism distinct from typical psychedelics. This review compares the acute and post-acute effects of 5-MeO-DMT to epileptiform activity, particularly in temporal lobe epileptogenic zones. The authors note that 5-MeO-DMT has notable 5-HT1A receptor agonist properties and that aberrant 5-HT1A receptor functioning occurs in epilepsy. They suggest that 5-MeO-DMT's therapeutic mechanism might be partly mediated by evoking temporary epileptiform activity, similar to electroconvulsive therapy. The phenomenon of 'reactivations'—sudden re-experiencing of drug effects common after 5-MeO-DMT but not typical psychedelics—may indicate recurrent epileptiform activity. The review concludes that further evaluation of 5-MeO-DMT's unique mechanisms is warranted.
Scientific reports
July 17, 2024
Sara de la Salle, Hannes Kettner, Julien Thibault Lévesque et al.
21 citations
A prospective longitudinal survey of eight Canadians with cancer who received legal psilocybin-assisted psychotherapy under Section 56 exemptions found significant improvements in anxiety, depression, pain, fear of COVID-19, quality of life, and spiritual well-being two weeks after the session. Attitudes toward death, medical assistance in dying, and desire for hastened death remained unchanged. Most participants found the sessions highly meaningful, though one reported a substantial decrease in well-being. These preliminary data suggest that real-world psilocybin-assisted psychotherapy can produce psychiatric benefits similar to those in clinical trials, but limited enrollment and negative experiences indicate a need for formal real-world evaluation programs.
J Pharm Biomed Anal
February 3, 2022
Emma Eckernäs, Adam Bendrioua, Chiara Cancellerini et al.
18 citations
A highly sensitive LC-MS/MS method was developed and applied to simultaneously quantify N,N-dimethyltryptamine (DMT) and two of its metabolites in human plasma. This new method accurately and precisely measures DMT and its breakdown products, providing a robust tool for studying how DMT behaves in the body, its metabolism, and its effects.
Comprehensive psychiatry
July 1, 2025
Luca Pellegrini, Naomi A Fineberg, Sorcha O'Connor et al.
17 citations
A 10 mg dose of psilocybin produced a rapid, moderate-to-large reduction in compulsive symptoms in people with obsessive-compulsive disorder (OCD), lasting up to one week after dosing. In a blinded pharmacological challenge study, 18 adults with at least moderate OCD received a 1 mg and then a 10 mg dose of oral psilocybin, separated by four weeks. One week after the 10 mg dose, scores on the compulsion subscale of the Yale-Brown Obsessive Compulsive Scale showed a significant improvement compared to the 1 mg dose (Cohen's d = 0.74). No effect on depression was detected. The drug was well tolerated with no serious adverse events.
Translational psychiatry
December 4, 2024
Kenneth Shinozuka, Katarina Jerotic, Pedro Mediano et al.
17 citations
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and may help treat depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—subjective experience, neuroimaging, and molecular pharmacology—reveals that medium and high doses of LSD produce stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences exist in receptor selectivity among the drugs. The analysis finds high heterogeneity and risk of bias, calling for standardized methods and more research.
Journal of Psychopharmacology
April 12, 2024
Joseph Peill, Miriam Marguilho, David Erritzøe et al.
16 citations
In a double-blind randomized controlled trial, 59 patients with depression received either a high (25 mg) or placebo (1 mg) dose of psilocybin. Those given the high dose reported stronger perceived 'inner healing' effects, and within that group, higher inner healer scores predicted greater improvement in depressive symptoms two weeks later. The findings suggest that the concept of an intrinsic healing mechanism activated by psychedelics merits further scientific investigation, though the idea remains scientifically nascent.
CPT Pharmacometrics & Systems Pharmacology
February 10, 2023
Emma Eckernäs, Christopher Timmermann, Robin Carhart-Harris et al.
15 citations
A single intravenous dose of DMT fully suppresses alpha brain wave power, partially suppresses beta power, and increases signal diversity (Lempel-Ziv complexity) in the EEG of 13 healthy volunteers. The concentration needed to reach half of the maximum effect (EC50) was 71 nM for alpha suppression, 137 nM for beta suppression, and 54 nM for increased complexity. Alpha suppression showed the least variability between individuals (29%), while beta suppression and complexity varied widely (75% and 77%). These quantified relationships between DMT blood levels and brain activity may help select appropriate doses and response markers in future clinical research.
Commun Psychol
April 13, 2025
Martha N. Havenith, Max Leidenberger, Jelena Brasanac et al.
14 citations
Altered states of consciousness (ASCs) similar to those induced by psychedelics can be achieved through circular breathwork, a non-pharmacological practice. During breathwork sessions, deliberate hyperventilation reduces end-tidal CO2 pressure, which is significantly correlated with the onset of ASCs. The depth of these ASCs predicted subsequent improvements in well-being and reductions in depressive symptoms. Two forms of breathwork, Holotropic and Conscious-Connected, produced highly similar outcomes. The findings identify physiological conditions for ASCs outside of drug use, suggesting breathwork's potential as an accessible psychotherapeutic tool.
July 13, 2022
Inês Hipólito, Jonas Mago, Fernando Rosas et al.
13 citations
preprint
Psychedelics may help treat mental health conditions by acting as psychological and neurophysiological destabilizers. Drawing on the entropic brain hypothesis and the REBUS model, this theoretical paper proposes that psychedelics break reinforced patterns of thinking and behaving by destabilizing fixed attractors in the brain. The resulting increase in brain entropy disrupts neurophysiological set-points, allowing for new conceptualizations of psychedelic psychotherapy. These insights have implications for risk mitigation and treatment optimization, both during the peak psychedelic experience and the sub-acute recovery period.
Eur Neuropsychopharmacol
November 7, 2025
Mikkel Højlund, Helin Y. Kafali, Begüm Kırmızı et al.
12 citations
A living systematic review with meta-analysis examined the efficacy, safety, and all-cause discontinuation of serotonergic psychedelics and MDMA for treating mental disorders. The review found that these substances show promise in reducing symptoms of conditions such as depression, anxiety, and post-traumatic stress disorder, with some evidence supporting their therapeutic potential. However, the authors note that the overall quality of evidence is limited by small sample sizes, short follow-up periods, and methodological concerns. Safety profiles varied, with most adverse events being mild to moderate, though serious adverse events were reported in some studies. The review emphasizes the need for larger, more rigorous trials to confirm these findings.
Journal of affective disorders
February 1, 2025
Grant Jones, Matthew X Lowe, Sandeep Nayak et al.
12 citations
Psilocybin, the psychoactive compound in magic mushrooms, is linked to improved mental wellbeing on average, but few studies examine how effects differ by race. In a large online longitudinal study of 2,833 people planning naturalistic psilocybin use, race/ethnicity moderated changes in spiritual wellbeing, cognitive flexibility, and emotion regulation (expressive suppression) at 2–3 months post-experience, but not at 2–4 weeks. Participants of Color reported minor differences in context and subjective effects, such as being more likely to set an intention before use. Both groups showed comparable reductions in anxiety and depression, with no significant moderation by race.
JAMA Netw Open
July 1, 2024
Leor Roseman, David Erritzøe, David Nutt et al.
12 citations
Interruptions during psychedelic therapy sessions are associated with lower ratings of the intensity of the experience. This quality improvement study examined how breaks or disruptions affect the subjective depth of the psychedelic session, suggesting that maintaining a continuous, uninterrupted setting may be important for achieving a more intense experiential state.
Frontiers in Psychiatry
June 4, 2024
Julia Bornemann, James B Close, Kirran Ahmad et al.
11 citations
Psilocybin-assisted therapy may help treat fibromyalgia, a chronic widespread pain condition with limited treatment options. A protocol describes a mechanistic study with 20 participants who will attend 8 visits over 8 weeks, including two dosing sessions where psilocybin is given at least once, with doses up to 25 mg. The primary focus is on brain mechanisms, measured via electroencephalography during the acute psychedelic state and magnetic resonance imaging before and after treatment. Primary outcomes are Lempel-Ziv complexity from EEG and experiential avoidance via questionnaire. Secondary measures include pain, physical and mental function, and additional neuroimaging. Results aim to clarify how psilocybin-therapy works in the brain and inform a future randomized controlled trial.
Psychol Med
September 27, 2024
Michael Angyus, Sarah Osborn, Eline Haijen et al.
10 citations
A 9-item scale called the Imperial Psychedelic Predictor Scale (IPPS) can predict key features of the acute psychedelic experience. The scale has three factors: set (mindset), rapport (relationship with the guide or setting), and intention. In a controlled administration dataset, set and rapport together explained 40% of the variance in mystical experiences, while set alone explained 16% of the variance in challenging experiences. In another controlled dataset, rapport explained 9% of the variance in emotional breakthrough. The scale shows good internal consistency and predicts mystical, challenging, and emotional breakthrough experiences across naturalistic and controlled settings.
Imaging Neurosci (Camb)
January 3, 2025
Kenneth Shinozuka, Prejaas K.b. Tewarie, Andrea Luppi et al.
9 citations
LSD weakens the brain's usual hierarchy of information flow by making neural communication more balanced between sending and receiving signals. Using magnetoencephalography (MEG) data from 16 healthy adults given 75 micrograms of LSD intravenously, researchers measured directed functional connectivity under four conditions (eyes-closed with or without music, eyes-open with or without video). Across the whole brain, LSD reduced the asymmetry of directed connectivity over time. Machine learning classifiers distinguished LSD from placebo more accurately using hierarchy metrics than traditional connectivity measures. These results indicate that LSD flattens the brain's hierarchical information processing by increasing the balance between senders and receivers of neural signals.
Neuroscience of Consciousness
January 1, 2024
Charlotte Martial, Robin Carhart-Harris, Christopher Timmermann
9 citations
People who have had both a near-death experience (NDE) and a psychedelic experience (PE) report overlapping mystical-like effects, such as feelings of unity and transcendence, and similar attributions of reality, psychological insights, and lasting changes. However, low-level sensory phenomena differ: NDEs involve stronger disembodiment, while psychedelics produce more visual imagery. The study used an online survey of 31 adults who had experienced both an NDE (scoring ≥27 on the NDE-C scale) and a PE with classic psychedelics. Bayesian and frequentist analyses confirmed these overlaps and differences, suggesting psychedelics can model the mystical aspects of NDEs but not their sensory features.