Journal of Neuroscience
September 18, 2013
Matthew J. Brookes, David Errtizoe, Ben Sessa et al.
501 citations
Psychedelic drugs like psilocybin produce profound changes in consciousness by desynchronizing ongoing oscillatory rhythms in the cortex. Using magnetoencephalography in healthy participants, psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 Hz in posterior association cortices and from 8 to 100 Hz in frontal association cortices, with large decreases in default-mode network areas. Low-level visually induced and motor-induced gamma-band oscillations were unaffected, suggesting some basic oscillatory activity is preserved. Dynamic causal modeling indicated that posterior cingulate cortex desynchronization results from increased excitability of deep-layer pyramidal neurons rich in 5-HT 2A receptors.
Scientific Reports
April 19, 2017
Michael Schartner, Robin Carhart‐Harris, Adam B. Barrett et al.
450 citations
Measures of neural signal diversity, such as entropy and Lempel-Ziv complexity, are higher during wakeful rest than during anesthesia. In this study, these measures were computed for spontaneous magnetoencephalographic signals from humans under psilocybin, ketamine, and LSD. All three psychedelics produced reliably higher signal diversity, even after controlling for spectral changes, with the most pronounced increase in temporal (single-channel LZ complexity) rather than spatial diversity. Selective correlations emerged between changes in signal diversity and the intensity of psychedelic experience. This is the first time these measures have been applied to the psychedelic state and have yielded values exceeding normal waking consciousness, suggesting that psychedelic phenomenology constitutes an elevated level of consciousness.
Expert Review of Clinical Pharmacology
May 26, 2021
Suresh Muthukumaraswamy, Anna Forsyth, Thomas Lumley
312 citations
Psychedelic drugs like psilocybin, LSD, and ketamine show promise for treating mental health disorders, but their effectiveness in randomized controlled trials may be overstated. Previous research indicates that participants in psychedelic trials often become unblinded—they can tell whether they received the drug or a placebo—and may have strong expectations of improvement. A systematic review of trials from 1990 to 2020 found that most did not measure pre-trial expectancy or check whether blinding was successful. The authors argue that reported treatment effect sizes are likely overestimated due to these confounds. They recommend routine measurement of de-blinding and expectancy, careful trial design, and caution when interpreting existing effect size estimates.
Journal of Neuroscience
August 19, 2015
Suresh Muthukumaraswamy, Alexander D. Shaw, Laura E. Jackson et al.
244 citations
Subanesthetic doses of ketamine, similar to those used in antidepressant studies, increase anterior theta and gamma power but decrease posterior theta, delta, and alpha power, as shown by magnetoencephalographic recordings. Dynamic causal modeling revealed a decrease in NMDA and AMPA-mediated frontal-to-parietal connectivity, with AMPA-mediated changes persisting up to 50 minutes after infusion ceased, even after perceptual distortions had ended. A decrease in gain of parietal pyramidal cells correlated with participants' self-reports of blissful state. These alterations in frontoparietal connectivity patterns may be important in generating the antidepressant response to ketamine.
PLoS ONE
September 30, 2015
Eduardo Ekman Schenberg, João Felipe Morel Alexandre, Renato Filev et al.
115 citations
Ayahuasca, an Amazonian plant-based brew used ritually in Brazil and increasingly worldwide, produces a two-phase brain effect. Electroencephalogram recordings and blood measurements of the brew's compounds (DMT, harmine, harmaline, tetrahydroharmine, and their metabolites) showed that 50 minutes after ingestion, alpha brainwave power (8–13 Hz) decreased, mostly in the left parieto-occipital cortex. Between 75 and 125 minutes, slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) increased across multiple cortical regions, including left centro-parieto-occipital, left fronto-temporal, and right frontal areas. These brain changes were significantly linked to circulating levels of ayahuasca's active chemicals. The authors interpret these effects within cognitive and emotional frameworks relevant to ritual use and potential therapeutic applications.
Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.
Biological psychiatry
September 15, 2023
Robin J Murphy, Rachael Sumner, William Evans et al.
69 citations
Microdosing LSD (10 μg every three days for six weeks) in healthy adult men produced transient improvements in creativity, connectedness, energy, happiness, irritability, and wellness on dose days compared with nondose days, even after controlling for preintervention expectancy. However, no enduring changes in overall mood or cognition were observed between baseline and six-week assessments. The most notable adverse event was treatment-related anxiety, which led four participants in the LSD group to withdraw. Microdosing appears relatively safe in this population but does not support claims of lasting mood or cognitive benefits.
ACS chemical neuroscience
February 7, 2024
Pedro A M Mediano, Fernando E Rosas, Christopher Timmermann et al.
60 citations
LSD increases brain entropy (neural signal diversity) across all conditions, but the effect is strongest when eyes are closed. Brain entropy changes correlate with subjective psychedelic experience ratings, except when viewing a video, possibly because external stimuli compete with LSD-induced imagery. This shows context modulates neural dynamics during psychedelic experiences, highlighting the importance of environment in psychedelic psychotherapy.
Psychological Medicine
July 19, 2023
Tehseen Noorani, Gillinder Bedi, Suresh Muthukumaraswamy
49 citations
When a medical research program overlaps with a social movement, new forms of sociality—termed 'chemosociality'—emerge from shared chemical exposure. In psychedelic-assisted therapy (PAT) clinical trials, this chemosociality creates 'dark loops': unrecorded social interactions that breach assumptions underlying causal inference used to establish treatment efficacy. These loops affect participant experiences but are not incorporated into trial data interpretation. Three researcher responses are proposed: chemosocial minimization (designing trials to reduce dark loops), chemosocial description (openly documenting them), and chemosocial valorization (actively leveraging them for positive outcomes). The hype surrounding psychedelic research continues to shape the phenomena under study, even as trials grow larger and more rigorous.
bioRxiv (Cold Spring Harbor Laboratory)
November 2, 2020
Pedro A. M. Mediano, Fernando E. Rosas, Christopher Timmermann et al.
39 citations
preprint
Psychedelics reliably increase brain entropy (neural signal diversity), an effect linked to psychological changes and opposite to the decrease seen during loss of consciousness. This study investigated how context—specifically stimulus manipulation—modulates that entropy increase. Participants under LSD or placebo experienced eyes-closed versus eyes-open conditions, or no stimulus, music, or video. Brain entropy rose with LSD across all conditions but was largest with eyes closed. Entropy changes consistently matched subjective ratings of the psychedelic experience, except during video viewing, suggesting competition between external stimuli and internal LSD-induced imagery. The findings provide quantitative evidence that context shapes neural dynamics during psychedelic experiences, supporting the practice of eyes-closed psychedelic psychotherapy, and challenge simplistic views of brain entropy as a direct measure of conscious level.
International Journal of Environmental Research and Public Health
August 2, 2021
Lisa Reynolds, Amelia Akroyd, Frederick Sundram et al.
33 citations
Cancer healthcare professionals—doctors, nurses, psychologists, and social workers—show openness to psychedelic-assisted therapy for advanced cancer patients, driven by a desire to alleviate suffering and a lack of effective current treatments. However, this openness is tempered by concerns about patient safety and the need for rigorous, well-designed trials. The study identified four themes: beneficence (alleviating suffering), non-maleficence (keeping vulnerable patients safe), viewing psychedelic-assisted therapy as a transformative approach with real potential, and recognizing that new frontiers carry risks. These findings offer a foundation for engaging healthcare professionals in future research and clinical applications.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Robin J Murphy, Suresh Muthukumaraswamy, Harriet de Wit
31 citations
Taking regular low doses of psychedelic drugs (microdosing) has drawn attention for potential psychotherapeutic effects, but controlled studies have lagged. A review of 14 rigorous double-blind placebo-controlled studies using investigator-supplied lysergic acid diethylamide (LSD) at 5-20 micrograms found that acute microdoses dose-dependently altered blood pressure, sleep, neural connectivity, social cognition, mood, and perception of pain and time. Perceptible drug effects occurred at 10-20 micrograms but not 5 micrograms. No serious adverse effects were reported. Repeated doses did not alter mood or cognition on any measures. Low doses of LSD appear safe and produce acute behavioral and neural effects in healthy adults, warranting further study in patient samples and with other psychedelics.
Pilot and feasibility studies
October 5, 2023
Carina Joy Donegan, Dimitri Daldegan-Bueno, Rachael Sumner et al.
23 citations
An estimated 260 million people worldwide have depression, and many self-treat with microdoses of psychedelics like LSD and psilocybin despite limited clinical evidence. A prior phase 1 study in healthy volunteers found LSD microdosing safe, well tolerated, and feasible with good adherence. This open-label pilot trial (LSDDEP1) will test tolerability and feasibility of an 8-week LSD microdosing regimen in 20 patients with major depressive disorder. Participants receive a sublingual LSD formulation (MB-22001) twice weekly at 5–15 µg. Tolerability is measured by withdrawal due to adverse events; feasibility by clinic visit attendance. Antidepressant response will be assessed with MADRS scores over 8 weeks. Results will inform a future randomized controlled trial.
NeuroImage
November 1, 2022
Hardik Rajpal, Pedro A M Mediano, Fernando E Rosas et al.
23 citations
Schizophrenia and drug-induced states from LSD and ketamine both increase neural signal diversity, but they differ in brain connectivity: schizophrenia shows increased information flow from front to back of the brain, while the drugs reduce it. These differences can be modeled by altering Bayesian inference in a predictive processing framework: drug effects correspond to reduced precision of prior beliefs, whereas schizophrenia involves increased precision of sensory information. The findings clarify similarities and differences between these altered states, with implications for understanding consciousness and developing mental health treatments.
Trials
April 23, 2021
Robin J. Murphy, Rachael L. Sumner, William J. Evans et al.
23 citations
A proposed study will test whether regular low doses of LSD, known as microdosing, produce the cognitive and emotional benefits reported anecdotally. Eighty healthy men will receive either a placebo or 10 micrograms of LSD every third day for six weeks. The study will measure personality, creativity, mood, cognition, brain plasticity, and brain imaging at baseline and after the protocol, with additional acute measures after the first dose. Daily functioning will be tracked via questionnaires and a wearable device. The goal is to rigorously evaluate microdosing claims using objective measures, with potential future applications for treating depression, addiction, and other conditions.
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.
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.
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.
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.