New England Journal of Medicine
April 14, 2021
Robin Carhart‐Harris, Bruna Giribaldi, Rosalind Watts et al.
1,372 citations
In a selected group of patients, psilocybin did not show a significantly greater antidepressant effect than escitalopram based on depression scores at week 6. Secondary outcomes generally favored psilocybin, but these analyses were not corrected for multiple comparisons. The authors call for larger and longer trials to compare psilocybin with established antidepressants.
Frontiers in Human Neuroscience
January 1, 2014
Robin Carhart‐Harris, Robert Leech, Peter J. Hellyer et al.
1,289 citations
Entropy, a measure of uncertainty or disorder, is applied to brain function and consciousness, focusing on the psychedelic state induced by psilocybin. The psychedelic state is considered a primary or primitive state of consciousness, characterized by elevated entropy in brain function, including a greater repertoire of functional connectivity motifs that form and fragment over time. This suggests primary states may exhibit criticality, a transition zone between order and disorder. Normal waking consciousness suppresses entropy, operating just below criticality, which constrains cognition and enables metacognitive functions like reality-testing and self-awareness. Entry into primary states involves collapse of default-mode network activity and decoupling from medial temporal lobes. These hypotheses can be tested by comparing brain activity in REM sleep, early psychosis, normal waking consciousness, and anesthesia.
Proceedings of the National Academy of Sciences
January 23, 2012
Alessandro Colasanti, Robin J. Tyacke, Robert Leech et al.
1,191 citations
Psychedelic drugs like psilocybin, found in magic mushrooms, produce profound changes in consciousness by decreasing activity and connectivity in key brain hub regions. Using functional MRI, researchers observed that psilocybin reduced cerebral blood flow and BOLD signal, especially in the thalamus, anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC). Decreased activity in the ACC and medial prefrontal cortex (mPFC) predicted the intensity of subjective psychedelic effects. Psilocybin also reduced positive coupling between the mPFC and PCC. These findings suggest that psychedelics work by dampening the brain's connector hubs, leading to a state of unconstrained cognition.
Frontiers in Pharmacology
January 17, 2018
Leor Roseman, David Nutt, Robin Carhart‐Harris
814 citations
In patients with treatment-resistant depression given psilocybin, the quality of the acute psychedelic experience—specifically the intensity of oceanic boundlessness (a mystical-type experience) and dread of ego dissolution (anxiety-like experience)—predicted improvements in depressive symptoms at 5 weeks. Sensory perceptual effects had negligible predictive value. The findings support the view that the subjective quality of the psychedelic experience is a key mediator of long-term mental health changes, suggesting that therapeutic approaches should aim to enhance mystical-type experiences and reduce anxiety.
Journal of The Royal Society Interface
October 29, 2014
Giovanni Petri, Paul Expert, Federico Turkheimer et al.
689 citations
Functional brain networks can be studied through homological cycles—topological objects that capture mesoscopic structure in weighted correlation networks. A new method, homological scaffolds, compactly represents these cycles and makes them amenable to standard network analysis. Applied to resting-state fMRI data from 15 healthy volunteers given placebo or psilocybin, the homological structure of brain activity changed dramatically after psilocybin, producing many transient, low-stability cycles and a few persistent ones absent under placebo.
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.
Frontiers in Human Neuroscience
June 14, 2016
Matthew M. Nour, Lisa Evans, David Nutt et al.
476 citations
A new questionnaire, the Ego-Dissolution Inventory (EDI), reliably measures the experience of ego-dissolution—a temporary loss of the sense of self—during psychedelic drug use. The EDI shows strong psychometric properties, including internal consistency and construct validity, and its scores closely relate to the subjective psychedelic experience. This tool enables researchers to investigate the brain mechanisms underlying ego-dissolution, which may inform psychedelic-assisted psychotherapy and improve understanding of psychosis.
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.
Human Brain Mapping
July 3, 2014
Enzo Tagliazucchi, Robin Carhart‐Harris, Robert Leech et al.
423 citations
Psilocybin, the active compound in magic mushrooms, increases the variability and range of brain activity and connectivity. Using fMRI, fifteen healthy volunteers were scanned before, during, and after receiving psilocybin or a placebo. Psilocybin raised the variability of blood-oxygen-level-dependent signals in the hippocampi and anterior cingulate cortex. Changes in the spectral behavior of brain signals were limited to higher-order networks, including the default mode, executive control, and dorsal attention networks. The brain also explored a wider repertoire of connectivity states after psilocybin than under control conditions. These findings help explain the unconstrained, hyper-associative quality of consciousness in the psychedelic state.
Frontiers in Psychology
September 4, 2018
Raphaël Millière, Robin Carhart‐Harris, Leor Roseman et al.
402 citations
Both meditation and psychedelic drugs like psilocybin and LSD can disrupt the sense of self, but these disruptions are not uniform. Meditation traditions aim to dissolve the self through altered states, while psychedelics produce drug-induced ego dissolution via serotonin receptor agonism. The authors argue that self-consciousness is a multidimensional construct, with narrative aspects (autobiographical memory, self-related thoughts) and embodied aspects (multisensory processes) being differently affected by each. They caution against conflating temporary self-loss with long-term selflessness as a trait, though preliminary evidence suggests possible correlations. The article calls for nuanced understanding of these phenomena.
Acta Psychiatrica Scandinavica
October 30, 2020
Kristoffer Andreas Aamodt Andersen, Robin Carhart‐Harris, David Nutt et al.
352 citations
A systematic review of 16 papers from 10 clinical trials (7 with psilocybin, 2 with ayahuasca, 1 with LSD) found that serotonergic psychedelics show promise for treating depression, anxiety, obsessive-compulsive disorder, and substance use disorders. Across 188 patients with cancer- or illness-related anxiety and depression, major depressive disorder, OCD, or substance use disorder, the therapy appeared safe, with no severe adverse events reported. Therapeutic effects often lasted weeks to months after only 1 to 3 treatment sessions. The evidence supports feasibility and early efficacy, though larger trials are needed.
Human Brain Mapping
May 22, 2015
Alexander V. Lebedev, Martin Lövdén, Gidon Rosenthal et al.
347 citations
Psilocybin, the active compound in magic mushrooms, produces ego-dissolution—a feeling that the self is disintegrating or that the boundary between self and world is dissolving—similar to ego-disturbances seen in schizophrenia. In a placebo-controlled study of 15 healthy volunteers, functional MRI scans showed that psilocybin-induced ego-dissolution was linked to decreased connectivity between the medial temporal lobe and high-level cortical regions, disintegration of the salience network, and reduced communication between brain hemispheres. Individuals with lower diversity of executive network nodes at baseline were more likely to experience ego-dissolution. These findings suggest that maintaining a coherent sense of self depends on normal functioning of these brain systems.
Proceedings of the National Academy of Sciences
April 13, 2020
Morten L. Kringelbach, Josephine Cruzat, Joana Cabral et al.
326 citations
By combining multimodal neuroimaging data, a framework was developed that demonstrates the fundamental principles of bidirectional coupling between neuronal and neurotransmitter dynamical systems. The work causally explains the functional effects of stimulating specific serotoninergic receptors (5-HT2AR) with psilocybin in healthy humans. This could lead to a better understanding of why psilocybin shows promise as a therapeutic intervention for neuropsychiatric disorders such as depression, anxiety, and addiction.
Psychological Medicine
February 5, 2016
Robin Carhart‐Harris, Mendel Kaelen, Mark Bolstridge et al.
301 citations
A single intravenous dose of LSD (75 µg) in 20 healthy volunteers produced robust acute psychological effects, including heightened mood and elevated scores on a measure of psychosis-like symptoms. Two weeks later, participants showed increased optimism and trait openness compared to after placebo, with no changes in delusional thinking. The findings suggest that psychedelics can acutely induce psychosis-like symptoms yet improve psychological wellbeing in the mid to long term. The authors propose that acute mood changes stem from a more fundamental modulation of cognition, and that increased cognitive flexibility from serotonin 2A receptor stimulation promotes emotional lability during intoxication and leaves a lasting loosened cognition conducive to improved wellbeing.
Frontiers in Human Neuroscience
May 27, 2014
Leor Roseman, Robert Leech, Amanda Feilding et al.
293 citations
Psychedelic drugs like psilocybin and MDMA perturb consciousness in distinct ways, offering a tool to study brain mechanisms underlying conscious states. In placebo-controlled studies, psilocybin increased resting-state functional connectivity between brain networks, making them less differentiated, while decreasing connectivity between visual and sensorimotor networks. MDMA produced less marked changes in between-network connectivity, suggesting that the extensive network alterations under psilocybin may be unique to classic psychedelics and relate to their profound effects on consciousness. This analytical approach could help characterize other altered conscious states.
Psychopharmacology
February 1, 2018
Mendel Kaelen, Bruna Giribaldi, Jordan Raine et al.
274 citations
Music plays a central therapeutic role in psychedelic therapy with psilocybin for treatment-resistant depression. In interviews with 19 patients, music had both welcome influences—evoking meaningful emotion, mental imagery, guidance, openness, calm, and safety—and unwelcome influences, such as unpleasant emotion, imagery, and resistance. Patients' experience of the music correlated with mystical experiences and insightfulness. Critically, the nature of the music experience significantly predicted reductions in depression one week after psilocybin, whereas general drug intensity did not.
Acta Psychiatrica Scandinavica
June 19, 2018
David Erritzøe, Leor Roseman, Matthew M. Nour et al.
268 citations
In patients with treatment-resistant depression, psilocybin therapy was associated with a decrease in neuroticism and increases in extraversion and openness three months later. These personality shifts moved toward normative population averages and were predicted by the degree of insight experienced during the psilocybin session. Conscientiousness showed trend-level increases, while agreeableness did not change. The pattern partly resembles changes seen with conventional antidepressants, but the pronounced rises in extraversion and openness may be more specific to psychedelic therapy.
Schizophrenia Bulletin
October 6, 2012
Robin Carhart‐Harris, Robert Leech, David Erritzøe et al.
267 citations
Psilocybin, a classic psychedelic, increases functional connectivity between the default-mode network (DMN) and task-positive network (TPN), reducing the normal orthogonality between these networks. In 15 healthy volunteers, intravenous psilocybin (vs placebo) during resting-state fMRI scans led to greater DMN-TPN connectivity, a pattern also seen in psychosis and meditative states. Thalamocortical connectivity remained unchanged, suggesting it relates to arousal rather than the separateness of internal versus external focus. The findings support psilocybin as a model for early psychosis, where compromised DMN-TPN orthogonality may explain phenomenological overlaps.
The British Journal of Psychiatry
January 27, 2012
Robin Carhart‐Harris, Robert Leech, Tom A. Williams et al.
241 citations
Psilocybin, a classic psychedelic drug, may enhance the vividness and visual imagery of positive autobiographical memories. In a small study of ten healthy participants, functional magnetic resonance imaging scans showed that under psilocybin, compared to placebo, recollection of positive memories produced additional visual and sensory cortical activations in the late phase of recall. Participants also rated memories as more vivid and visually rich after psilocybin, and higher vividness correlated with greater subjective wellbeing at follow-up. These findings suggest psilocybin could be useful in psychotherapy for facilitating recall of salient memories or reversing negative cognitive biases.
Frontiers in Psychology
August 15, 2018
Christopher Timmermann, Leor Roseman, L. Williams et al.
228 citations
Near-death experiences (NDEs) share striking phenomenological similarities with the effects of the psychedelic drug DMT. In a placebo-controlled, within-subjects study, 13 healthy participants received DMT and placebo, then completed a standard NDE measure. DMT significantly increased NDE-like features compared to placebo. NDE scores were linked to DMT-induced ego-dissolution and mystical experiences, as well as baseline traits of absorption and delusional ideation. Nearly all NDE features overlapped between DMT-induced experiences and a matched group of actual NDE experiencers. These results indicate a remarkable similarity between the DMT state and NDEs, warranting further research.
Journal of Psychopharmacology
January 16, 2020
Lea J. Mertens, Matthew B. Wall, Leor Roseman et al.
211 citations
After a single 25 mg dose of psilocybin, patients with treatment-resistant depression showed decreased functional connectivity between the ventromedial prefrontal cortex and the right amygdala while viewing faces, particularly fearful and neutral ones. This decrease was linked to lower rumination levels one week later. Increased connectivity between these regions and occipital-parietal cortices also emerged. The findings suggest psilocybin therapy may revive emotional responsiveness at both neural and psychological levels, offering a potential treatment mechanism. Placebo-controlled studies are needed to confirm these results.
Biological Psychiatry
January 10, 2014
Robin Carhart‐Harris, Kevin Murphy, Robert Leech et al.
182 citations
The medial temporal lobes (MTLs) are specifically involved in how MDMA works in the brain, though more research is needed to understand how the drug's characteristic subjective effects emerge from its modulation of spontaneous brain activity.
Journal of Psychopharmacology
January 17, 2018
Taylor Lyons, Robin Carhart‐Harris
176 citations
In patients with moderate to severe treatment-resistant depression, psilocybin given in two oral doses (10 mg and 25 mg one week apart) was associated with increased nature relatedness and decreased authoritarianism one week after dosing. Nature relatedness remained significantly higher 7–12 months later, while the reduction in authoritarianism persisted only at a trend level. No changes occurred in healthy control subjects. The findings suggest that psilocybin combined with psychological support may produce lasting shifts in attitudes and beliefs, though the small sample size precludes causal conclusions.
Scientific Reports
January 21, 2021
Laura Kaertner, Michael B. Steinborn, Hannes Kettner et al.
152 citations
A prospective study of weekly psychedelic microdosing found that participants reported improved well-being, emotional stability, and reduced anxiety and depressive symptoms over four weeks. However, baseline positive expectancy scores predicted these improvements, suggesting a significant placebo response. The findings caution against overinterpreting the therapeutic value of microdosing.
Psychopharmacology
December 18, 2019
Neiloufar Family, Émeline L. Maillet, Luke T. J. Williams et al.
142 citations
Repeated low doses of LSD are safe and well tolerated in older adults. In a double-blind, placebo-controlled trial, 48 healthy volunteers aged around 63 received either 5, 10, or 20 micrograms of LSD or a placebo every four days for three weeks. LSD was undetectable in the blood at the 5 microgram dose, while peak levels for higher doses occurred within 30 minutes. Adverse events were no more frequent than with placebo, and tests of cognition, balance, and proprioception showed no impairment. These results support further clinical development of low-dose LSD for treating or preventing Alzheimer's disease.