bioRxiv (Cold Spring Harbor Laboratory)
June 25, 2017
Mendel Kaelen, Romy Lorenz, Frederick S. Barrett et al.
20 citations
preprint
Lysergic acid diethylamide (LSD) alters how the brain processes music, particularly by enhancing activity and connectivity in networks linked to music perception and emotion. Sixteen healthy volunteers listened to a 7-minute music piece during fMRI after taking either 75 mcg of LSD or a placebo. The acoustic feature of timbral complexity—the richness of the music's spectral distribution—drove the most pronounced changes in brain activity and connectivity under LSD. These changes correlated with increased feelings of wonder evoked by the music. The results suggest a neurobiological basis for why music is useful in psychedelic therapy.
Palliative & Supportive Care
November 3, 2022
Lisa Reynolds, Brian S. Barnett, Jeremy Weleff et al.
19 citations
Cancer health-care practitioners in New Zealand and the USA perceive psychedelic-assisted therapy as potentially beneficial for cancer patients, especially those with advanced disease no longer receiving curative treatment. They consider research in this area important and express willingness to refer patients to trials, though they emphasize that work should incorporate spiritual and indigenous perspectives of health. US practitioners had greater awareness of psychedelics, while New Zealand practitioners more strongly believed that spiritual and indigenous factors should be considered. The findings suggest that practitioners may be more open to studies beginning in palliative and end-of-life contexts.
Human Brain Mapping
December 6, 2019
Anna Forsyth, Rebecca McMillan, Doug Campbell et al.
19 citations
The validity of fMRI functional connectivity as a drug biomarker was tested by comparing seven preprocessing pipelines and by simultaneously measuring EEG and fMRI in a placebo-controlled, three-way crossover study with ketamine and midazolam. Independent components analysis (ICA)-denoising produced stronger reductions in connectivity after ketamine and weaker increases after midazolam than pipelines using physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This indicates that pipeline decisions should match a drug's unique noise structure; when unknown, extensive ICA denoising may sacrifice some signal but increase confidence in remaining results. No significant relationship was found between changes in electrophysiological and hemodynamic correlation structures, cautioning against cross-modal comparisons of pharmacologically-modulated functional connectivity.
NeuroImage
November 29, 2019
David T. J. Liley, Suresh Muthukumaraswamy
18 citations
The reduction in alpha-band brain wave power when people open their eyes is explained by increased damping of oscillatory activity, not by changes in neuronal population synchrony as commonly believed. Using time series modeling of EEG data, the authors found that the NMDA antagonist ketamine modifies these damping changes through glutamatergic neurotransmission. The results challenge the prevailing view that thalamus and neuronal population synchronization drive alpha rhythm generation and modulation, suggesting instead that physiological damping dynamics play a key role.
BMC neuroscience
February 5, 2024
Robin J Murphy, Kate Godfrey, Alexander D Shaw et al.
16 citations
Microdosing psychedelics is claimed to improve cognition, but clinical evidence is limited. In a placebo-controlled trial, 80 healthy adult males took 10 µg of LSD or placebo every third day for six weeks. A visual long-term potentiation (LTP) EEG paradigm measured neural plasticity indirectly. Standard event-related potential (ERP) analyses of N1b and P2 components showed no evidence of changes in LTP from LSD, either acutely or after six weeks. However, dynamic causal modeling of the ERP timecourse using a thalamocortical model revealed changes in laminar connectivity in primary visual cortex, including acute changes to self-gain and inhibitory input parameters and differences in excitatory connectivity from layer 2/3 to layer 5 between...
March 8, 2021
Suresh Muthukumaraswamy, Anna Forsyth, Thomas Lumley
16 citations
preprint
Effect sizes reported in randomized controlled trials of psychedelic drugs such as psilocybin, LSD, and ketamine for mental health disorders are likely overestimated because participants often become unblinded and develop strong expectations of improvement. Systematic reviews of these trials show that researchers have not measured or reported expectancy or de-blinding. To obtain accurate estimates, future trials should routinely measure these confounds and adjust effect sizes accordingly. Caution is urged when interpreting existing results.
Translational psychiatry
April 15, 2024
Nathan Allen, Aron Jeremiah, Robin Murphy et al.
15 citations
Microdosing LSD (10 µg every third day for six weeks) increased sleep duration in healthy adult male volunteers. On nights after dosing, the LSD group slept an extra 24.3 minutes per night compared to placebo, with no change in sleep on dosing days. Sleep stage proportions and physical activity remained unchanged. The findings indicate that microdosing LSD modifies physiological sleep requirements, and the objective changes are unlikely to be a placebo effect.
Anesthesiology
February 6, 2020
Andria Pelentritou, Levin Kuhlmann, John Cormack et al.
15 citations
Xenon and nitrous oxide produce different patterns of brain oscillatory power changes, depending on the gas and the recording method. Xenon increased low-frequency delta and theta power only at loss of responsiveness (delta: 208.3%, theta: 107.4% in MEG; delta: 260.3%, theta: 116.3% in EEG). Nitrous oxide increased high-frequency gamma power (low gamma: 46.3%, high gamma: 45.7% in MEG) and reduced frontal alpha power at 0.75 MACawake in MEG (44.4% reduction) and at 0.50 MACawake in EEG (44.0% reduction). The findings show no clear universal features of action for these two gaseous anesthetics, and differences between MEG and EEG must be considered for accurate brain state monitoring during anesthesia.
Trials
August 24, 2024
Dimitri Daldegan-Bueno, Carina Joy Donegan, Anna Forsyth et al.
14 citations
A phase 2b randomized controlled trial will test whether repeated low doses of LSD (4 to 20 micrograms, taken twice weekly for 8 weeks at home) reduce depressive symptoms in people with major depressive disorder, compared to an active placebo. The trial is triple-blind and includes measures of mood, personality, sleep, brain activity, blood biomarkers, and safety. This is the first controlled trial to test microdosed LSD in patients' natural environment. Results will help determine whether psychedelic microdosing is a viable additional treatment for depression and guide future research.
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.
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.
Psychopharmacology
February 1, 2025
Robin J Murphy, Rachael L Sumner, Kate Godfrey et al.
9 citations
A randomized controlled trial gave 80 healthy adult males 10 µg doses of LSD or placebo every third day for six weeks and tested creativity with the Alternate Uses Test, Remote Associates Task, Consensual Assessment Technique, and an Everyday Problem-Solving Questionnaire. No drug effect was found on any creativity measure at the first dose or after six weeks, despite participants reporting feeling more creative on dose days. Baseline vocabulary skill significantly influenced scores on two tests. The null findings may reflect that laboratory testing misses naturalistic creative differences, available tests do not capture the facets of creativity anecdotally affected, or reported enhancements are placebo effects.
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.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Suresh Muthukumaraswamy, Matthew J. Baggott, Eduardo Ekman Schenberg et al.
8 citations
Psychedelic-assisted therapy (PAT) is a complex intervention combining pharmacological, psychotherapeutic, and contextual elements that interact dynamically with patient experiences and healthcare settings. Conventional randomized controlled trials may fail to capture these complexities. This position paper advocates applying the UK Medical Research Council's framework for complex interventions to PAT development and evaluation, emphasizing the need to articulate the theory of therapeutic change, structure intervention development into phases, account for contextual interactions, and incorporate stakeholder perspectives.
Journal of Psychedelic Studies
May 16, 2025
Anna-Leigh Hodge, Anna Forsyth, Tehseen Noorani et al.
6 citations
A Māori-led project called Tū Wairua aims to integrate traditional Māori healing practices (rongoā Māori) with psychedelic-assisted therapy to address problematic methamphetamine use in Māori communities. Based at Rangiwaho Marae in Te Tairāwhiti (Gisborne), the project will use Kaupapa Māori methodology and biomedical psychedelic science to develop a decolonized, culturally appropriate approach to psilocybin treatment. It seeks to challenge colonial dynamics in current Western psychedelic therapy models, build a skilled Māori workforce, and challenge legislation restricting Indigenous psychedelic medicines, creating sustainable pathways for collective healing.
bioRxiv (Cold Spring Harbor Laboratory)
April 28, 2024
Kenneth Shinozuka, Prejaas Tewarie, Andrea I. Luppi et al.
5 citations
preprint
LSD weakens the brain's directed connectivity hierarchy by increasing the balance between senders and receivers of neural signals. This finding supports the REBUS theory, which proposes that psychedelics flatten the hierarchy of information flow in the brain. Analyzing magnetoencephalography data from 16 healthy participants given 75 micrograms of intravenous LSD, the study found that LSD diminishes the asymmetry of directed connectivity averaged over time. Machine learning classifiers distinguished LSD from placebo more accurately when trained on hierarchy metrics than on traditional functional connectivity measures.
bioRxiv
February 1, 2022
Hardik Rajpal, Pedro A.M. Mediano, Fernando E. Rosas et al.
5 citations
preprint
Schizophrenia and drug-induced states from LSD and ketamine both increase neural signal diversity, but they differ in how information flows in the brain. In schizophrenia, transfer entropy from the front to the back of the brain is increased, whereas under both drugs it is reduced overall. These differences can be modeled by altering Bayesian inference within a predictive processing framework: drug effects correspond to reduced precision of prior beliefs, while schizophrenia corresponds to increased precision of sensory information. The findings clarify similarities and differences between these altered states, with potential implications for understanding consciousness and developing mental health treatments.
Neuropharmacology
December 1, 2025
Carina Joy Donegan, Dimitri Daldegan-Bueno, Tehseen Noorani et al.
4 citations
Before starting a low-dose LSD regimen, people with major depression held varied expectations shaped largely by media and personal experience. Over half had tried other treatments that failed. Many expected subtle effects or had no specific expectations, while some anticipated changes in consciousness or neural rewiring. Hope served both as a motivator and a buffer against disappointment. The findings underscore how media influences expectations and suggest that current expectancy measures miss important factors specific to psychedelic therapy.
Neuropharmacology
November 5, 2025
Dimitri Daldegan‐bueno, C Donegan, Rachael L. Sumner et al.
4 citations
In an open-label phase 2A trial, 19 participants with major depressive disorder, most of whom were taking antidepressants, took microdoses of LSD twice weekly for eight weeks. No serious adverse events occurred, and one participant withdrew due to anxiety. Depression scores on the Montgomery-Åsberg Depression Rating Scale dropped by 59.5% at the end of the intervention, with improvements sustained for up to six months. Anxiety, rumination, stress, and quality of life also improved. The results provide preliminary evidence that microdosed LSD is safe and feasible for treating moderate depression, but randomized controlled trials are needed.
Human brain mapping
April 1, 2025
Clayton R Coleman, Kenneth Shinozuka, Robert Tromm et al.
4 citations
LSD alters consciousness by changing connectivity between the dorsolateral prefrontal cortex (DLPFC), thalamus, and visual areas. In healthy participants, stronger functional connectivity between the left and right DLPFC, thalamus, and fusiform face area correlated with greater ego dissolution. Emotional arousal was linked to increased connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory reverse analysis supported these findings. Magnetoencephalography data showed that LSD increased theta-band information flow from the thalamus to the DLPFC, supporting the idea that disrupted thalamic gating underlies ego dissolution. The results clarify the DLPFC's role in LSD-induced altered states.
bioRxiv
July 18, 2019
Christopher Timmermann, Leor Roseman, Michael Schartner et al.
4 citations
preprint
Intravenous DMT, a fast-acting psychedelic, markedly alters human brain activity. Compared with a placebo, DMT reduced oscillatory power in alpha and beta brainwaves and increased spontaneous signal diversity. Time-referenced analyses linked changes in subjective experience to changes in brain activity. Emergence of delta and theta frequency oscillations correlated with the peak of the experience, particularly its eyes-closed visual component. These findings advance understanding of the neurobiological underpinnings of immersive states of consciousness.
bioRxiv
March 24, 2025
Kenneth Shinozuka, Mattia Rosso, Clayton R. Coleman et al.
3 citations
preprint
LSD profoundly alters consciousness by reorganizing brain networks in specific frequency bands. Analyzing MEG data from 14 healthy participants, the substance enhances high alpha (12.1, 13.3 Hz) activity across all conditions and high beta (25.3 Hz) in three conditions, while suppressing low beta (18.1, 19.3 Hz) and low alpha (8.5 Hz). LSD also shifts network spatial distributions: low alpha moves anteriorly toward the motor cortex, high alpha becomes more localized to the visual cortex, and low beta expands over temporal and occipital cortices. These frequency- and region-specific changes add nuance to theories of network disintegration under psychedelics.
PsyArXiv
February 23, 2025
Suresh Muthukumaraswamy, Matthew Baggott, Eduardo Ekman Schenberg et al.
3 citations
preprint
Psychedelic-assisted therapy (PAT) is a complex, multi-component intervention, yet most clinical trials evaluate it as a simple pharmaceutical treatment, limiting real-world validity. This position piece advocates applying the UK Medical Research Council's complex intervention framework to PAT, emphasizing theory of change, structured development, context, and stakeholder input. Pragmatic randomized controlled trials, informed by the PRECIS-2 tool, are proposed to align trial designs with real-world healthcare settings. The authors contrast drug-centric and psychotherapy-augmented views of PAT's efficacy, and recommend integrating qualitative data, adaptive designs, and comparative effectiveness research. A pluralistic evidentiary model is suggested to advance psychedelic medicine while avoiding past developmental pitfalls.
bioRxiv
June 11, 2021
Daniel Toker, Ioannis Pappas, Janna D. Lendner et al.
3 citations
preprint
During conscious states, the cortex's electrical activity operates near the edge-of-chaos critical point—the boundary between stability and chaos. Applying a new chaos test to ECoG and MEG recordings from humans and macaques across waking, seizure, anesthesia, and psychedelic states shows that unconsciousness shifts cortical dynamics away from this critical point, disrupting information processing. Psychedelics may enhance information-richness by tuning activity closer to this point. Analysis of EEG from patients with disorders of consciousness suggests that measuring proximity to the edge-of-chaos critical point could serve as a clinical biomarker of consciousness.
JAMA psychiatry
June 1, 2026
Ben Deverett, Duan Li, Theresa R Lii et al.
1 citation
Ketamine produces distinct brain-wave patterns that may be linked to its therapeutic effects. General anesthesia selectively blocks one of these patterns—theta oscillations—while leaving another pattern, beta-gamma oscillations, intact. In 52 participants, ketamine given during anesthesia preserved beta-gamma power increases but eliminated the characteristic theta augmentation seen during awake administration. This suggests that different neurophysiologic effects of ketamine can be separated, offering a way to investigate which brain-wave changes underlie its antidepressant, analgesic, or dissociative properties.