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.
Journal of Psychopharmacology
November 14, 2022
Meg J. Spriggs, Bruna Giribaldi, Taylor Lyons et al.
15 citations
A fixed 25 mg dose of psilocybin produces similar acute psychedelic effects and improvements in well-being regardless of body mass index (BMI). Pooling data from three therapeutic studies, results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes, or emotional breakthroughs. There was weak evidence that lower BMI participants reported greater 'dread of ego dissolution,' but BMI did not meaningfully add to predictions beyond age, sex, and study. Mystical-type experiences and emotional breakthroughs strongly predicted well-being improvements, but BMI did not. These findings suggest body weight-adjusted dosing may be unnecessary, supporting fixed dosing to reduce practical and financial burdens on psychedelic therapy scalability.
Psychedelic Medicine
October 28, 2022
Bruna Giribaldi, Sandeep M. Nayak, Bilal A. Bari et al.
15 citations
A Bayesian reanalysis of a trial comparing psilocybin (25 mg) to escitalopram (20 mg) over 6 weeks in 59 patients with major depressive disorder found that psilocybin outperformed escitalopram on three of four depression scales, though evidence was not uniformly clinically meaningful. Using skeptical priors that bias results toward zero, the analysis showed strong to extremely strong evidence favoring psilocybin on the BDI-1A, MADRS, and HAMD-17, while evidence on the primary outcome (QIDS SR-16) was indeterminate. For clinically meaningful superiority, evidence was moderate against it for the QIDS SR-16 but moderate to strong for the MADRS and HAMD-17. Psilocybin showed extremely strong evidence of noninferiority to escitalopram across all scales. The findings support further research on psilocybin's relative efficacy.
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.
bioRxiv (Cold Spring Harbor Laboratory)
November 9, 2023
Fernando E. Rosas, Pedro A. M. Mediano, Christopher Timmermann et al.
14 citations
preprint
Autonomic signals can reveal aspects of subjective and neural states. A Bayesian framework estimated heart rate entropy under psychedelics. Across four drugs—LSD, DMT, psilocybin, and ketamine—mean heart rate, high-frequency heart rate variability, and heart rate entropy consistently increased during the psychedelic experience. These changes predicted various dimensions of the experience. Heart rate entropy increases correlated with brain entropy increases, while other autonomic markers did not. Cost-efficient autonomic measures can reveal detail about subjective and brain states, opening new research avenues in neuroscience.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
bioRxiv (Cold Spring Harbor Laboratory)
December 9, 2020
Jonathan W. Kanen, Qiang Luo, Mojtaba Rostami Kandroodi et al.
14 citations
preprint
Lysergic acid diethylamide (LSD) increases the speed at which the brain updates the value of actions following feedback, particularly after rewards, and makes behavior more exploratory. In a within-subjects experiment, healthy volunteers received intravenous LSD or placebo and performed a probabilistic reversal learning task where they learned which of three stimuli was most often rewarded, with contingencies later reversing. Computational modeling showed LSD enhanced the reward learning rate and also elevated the punishment learning rate, while reducing stimulus stickiness—a measure of choice repetition regardless of outcomes. Conventional measures of immediate feedback sensitivity were unaffected. These findings suggest LSD induces a state of heightened plasticity that may help revise maladaptive associations in clinical settings.
National Science Review
May 1, 2024
Jakub Vohryzek, Joana Cabral, Christopher Timmermann et al.
13 citations
The human brain's activity constantly reorganizes across space and time, and decomposing whole-brain recordings into harmonic modes reveals gradient-like patterns linked to different functions. Using the HADES framework, researchers analyzed brain activity in healthy participants after taking the serotonergic psychedelic DMT. They found significant decreases in contributions across most low-frequency harmonic modes during the DMT state. Specifically, the second functional harmonic, which represents the uni- to transmodal functional hierarchy, decreased, supporting the hypothesis that psychedelics alter this hierarchy. Dynamic measures of fractional occupancy, lifetime, and latent space precisely described the changes in the brain's spacetime hierarchical organization during the psychedelic state.
July 13, 2022
Inês Hipólito, Jonas Mago, Fernando E. 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.
July 7, 2022
Richard J. Zeifman, Meg J. Spriggs, Hannes Kettner et al.
13 citations
preprint
The Relaxed Beliefs Under pSychedelics (REBUS) model suggests that psychedelics reduce the strength of deeply held beliefs. In a preliminary test of this idea, 11 healthy adults received a low (1 mg) and a high (25 mg) dose of psilocybin four weeks apart. Confidence in negative self-beliefs decreased after the high dose but not after the low dose. Greater brain signal entropy and stronger subjective effects during the high dose correlated with larger decreases in negative belief confidence, both during the session and four weeks later. Reduced confidence in negative beliefs was strongly linked to improved well-being at the four-week follow-up. These findings provide initial psychological support for the REBUS model, though replication in larger and clinical samples is needed.
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 M. 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.
April 12, 2023
Rebecka Bremler, Nancy Katati, Parvinder Shergill et al.
12 citations
preprint
Negative psychological responses to psychedelics, lasting at least 72 hours, are real and can include new psychiatric diagnoses or worsened symptoms, particularly anxiety. In a sample of 32 individuals who reported such experiences, 37.5% received a new psychiatric diagnosis after psychedelic use, and 87% experienced new or worsened anxiety. In-depth interviews with 15 of the most severe cases suggested that contributing factors include unsafe environments, unpleasant acute experiences, prior psychological vulnerabilities, high or unknown drug doses, and young age. The study's small, self-selected sample means these findings cannot estimate how common such harms are.
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.
Research Square
May 20, 2021
Richard E. Daws, Christopher Timmerman, Bruna Giribaldi et al.
11 citations
Across two clinical trials, psilocybin therapy produced robust antidepressant effects that were linked to a decrease in brain network modularity measured by resting-state fMRI. In an open-label study of 16 adults with treatment-resistant depression, Beck Depression Inventory scores dropped sharply at one week and six months, and the reduction in network modularity one day after treatment correlated with clinical improvement at six months. In a double-blind randomized trial of 43 adults with major depressive disorder, the psilocybin arm showed superior antidepressant effects at two and six weeks compared with escitalopram, and improvements correlated with decreased modularity. These convergent findings suggest that psilocybin therapy may work by reducing the brain's network modularity.
Nature Medicine
February 6, 2026
Joshua S. Siegel, Conor Liston, Ginger E. Nicol et al.
10 citations
Classic psychedelics, acting at the serotonin 5-HT2A receptor, alter brain function and consciousness. Research converges on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. Evidence of therapeutic response across neuropsychiatric indications is reviewed, integrating mechanistic findings. Challenges include discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms and clinical evidence linking subjective experience to therapeutic response, risks of enhanced neuroplasticity, and questions about trial design, scalability, and regulatory approval. The growth of psychedelic science may compel a rethinking of the relationship between subjective experience and biological change in psychiatry.
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.
N Engl J Med
February 1, 2023
Robin Carhart-Harris
10 citations
A compound described as a 'nonpsychedelic psychedelic' reduced anxiety and depression in mice. This commentary questions whether findings from mouse models can reliably predict effects in humans, highlighting potential limitations in translating preclinical results to clinical treatments.
Research Square
September 20, 2022
Jakub Vohryzek, Joana Cabral, Louis-David Lord et al.
10 citations
Psilocybin therapy for depression shows promise, but how it works is unclear. By comparing responders (those with >50% reduction in symptoms) to non-responders after 10mg and 25mg doses, whole-brain modeling identified specific brain regions whose dynamics shift from a depressive to a healthy state. These regions overlap with maps of serotonin 5-HT2A and 5-HT1A receptors, which psilocin—the active metabolite of psilocybin—activates. The findings provide causal evidence linking serotonergic transmission and recovery from depression via psilocybin.
bioRxiv (Cold Spring Harbor Laboratory)
July 16, 2019
Lionel Barnett, Suresh Muthukumaraswamy, Robin Carhart-Harris et al.
10 citations
preprint
Psychedelic drugs such as LSD, psilocybin, and low-dose ketamine reduce directed functional connectivity—the flow of information—across the brain, as measured by Granger causality in source-localised MEG recordings. This breakdown in organised information flow supports the idea that the psychedelic state disrupts normal patterns of neural communication. With LSD specifically, directed connectivity decreased while undirected connectivity (measured by correlation and coherence) increased, an opposite movement that highlights the importance of using multiple connectivity measures when analyzing time-resolved neuroimaging data. The non-psychedelic anticonvulsant tiagabine was included for comparison.
bioRxiv (Cold Spring Harbor Laboratory)
July 25, 2018
Louis-David Lord, Paul Expert, Selen Atasoy et al.
10 citations
preprint
Brain activity can be viewed as exploring a landscape of different activity patterns over time, shifting between stable states of functional connectivity that support various mental processes. In a study using fMRI data from healthy participants given intravenous psilocybin (the active compound in magic mushrooms), researchers analyzed how this dynamical landscape changes during the psychedelic state. They found that a connectivity state linked to the fronto-parietal control system became strongly destabilized, while transitions toward a globally synchronized state increased. These changes suggest the psychedelic state biases the brain toward global integration at the cost of local network segregation, offering a mechanistic perspective on the subjective psychedelic experience and potential guidance for pharmacological interventions in neuropsychiatric disorders.
Pedro A. M. Mediano, Fernando E. Rosas, Andrea I. Luppi et al.
10 citations
A new method called Complexity via State-space Entropy Rate (CSER) estimates neural signal complexity with better temporal resolution and spectral decomposition than the standard Lempel-Ziv complexity (LZ) approach. CSER matches LZ in distinguishing conscious states but offers two key advantages: it can break complexity down by frequency bands, and it provides temporal resolution about 100 times finer. Using MEG, EEG, and ECoG data from humans and monkeys, CSER revealed that gamma-band activity primarily drives complexity changes across states of consciousness. In an auditory mismatch negativity experiment, CSER detected early entropy increases roughly 20 milliseconds before the standard event-related potential. This method enables finer-grained study of how signal complexity relates to cognitive processes and conscious states.
Drug Science Policy and Law
September 1, 2025
David Nutt, David Erritzøe, Anne Katrin Schlag et al.
9 citations
The field of psychedelic research lacks standardized terminology for clinical development, dosing, safety monitoring, and regulatory classification. A comprehensive framework is proposed that classifies psychedelics by pharmacology (serotonergic, glutamatergic, kappaergic, GABAergic, and atypical), introduces dose-dependent categories (microdose, minidose, mididose, macrodose), and standardizes terms like “short-acting” with specific pharmacokinetic parameters. Safety considerations include cardiovascular and psychological effects, with risk mitigation protocols for higher-risk compounds like ibogaine. A three-phase treatment model—preparation, dosing, and integration—is recommended as a minimum standard. The lack of comparative research on psychotherapy modalities is identified as a critical gap.
PNAS Nexus
April 1, 2025
Katie Zhou, David de Wied, Robin Carhart-Harris et al.
9 citations
Delusional ideation decreased one month after a planned psychedelic experience, while magical thinking showed no change. Over 30% of participants reported hallucinogen persisting perception disorder (HPPD)-type effects at four weeks, though fewer than 1% found them distressing. Younger age, female gender, a history of psychiatric diagnosis, and baseline trait absorption predicted HPPD-like effects. Lifetime psychedelic use at baseline correlated positively with both magical thinking and delusional ideation, suggesting these traits may correlate with psychedelic use rather than being caused by it.