The New England journal of medicine
November 3, 2022
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
Journal of Humanistic Psychology
June 19, 2017
Rosalind Watts, Camilla Day, Jacob Krzanowski et al.
582 citations
In an open-label trial, 20 patients with treatment-resistant depression described their experiences six months after psilocybin treatment. They reported two main shifts: from feeling disconnected from themselves, others, and the world to feeling connected, and from avoiding emotions to accepting them. Patients contrasted psilocybin with conventional treatments like medications and short-term talking therapies, which they said reinforced disconnection and avoidance, whereas psilocybin encouraged connection and acceptance. The findings suggest psilocybin may work through a novel mechanism opposite to standard antidepressants and some therapies.
Curr Biol
April 13, 2016
Enzo Tagliazucchi, Leor Roseman, Mendel Kaelen et al.
531 citations
Lysergic acid diethylamide (LSD) increases global functional connectivity in the brain, and this neural change correlates with the experience of ego dissolution—a temporary loss of the sense of self. The more the brain's networks became globally interconnected under LSD, the more participants reported a diminished or dissolved sense of self. This suggests that the subjective feeling of ego dissolution is linked to a breakdown of the normal modular organization of brain connectivity.
Nat Med
April 11, 2022
Richard E. Daws, Christopher Timmermann, Bruna Giribaldi et al.
432 citations
A single dose of psilocybin therapy increased global brain integration in people with depression, with effects lasting for weeks. The brain's regions communicated more broadly and flexibly after treatment, a pattern linked to reduced depressive symptoms. This neural change suggests psilocybin may help reorganize brain networks that become rigid in depression.
J Psychopharmacol
July 11, 2019
Leor Roseman, Eline Haijen, Kelvin Idialu-Ikato et al.
415 citations
Emotional breakthrough—a sudden release or shift in emotion during a psychedelic experience—is a distinct and important component that predicts long-term psychological changes, separate from mystical-type experiences. A six-item Emotional Breakthrough Inventory was validated in 379 participants who completed surveys before and after a planned psychedelic experience. Emotional breakthrough scores were dose-dependent and higher when the psychedelic was taken with therapeutic intent. In a subsample of 75 participants with low baseline well-being, emotional breakthrough, mystical experience, and challenging experience scores together significantly predicted changes in well-being (r=0.45). Emotional breakthrough and mystical experience scores predicted increases in well-being, while challenging experience scores predicted smaller increases.
Cell
April 1, 2020
David Nutt, David Erritzøe, Robin Carhart-Harris
330 citations
The paper argues that psychedelic psychiatry is entering a new era, characterized by a shift from prohibition to clinical investigation and therapeutic use. It describes how substances like psilocybin and MDMA are being studied for treating mental health conditions such as depression, PTSD, and anxiety, often in guided sessions with therapeutic support. The author contends that this emerging paradigm may transform mental healthcare by facilitating psychological breakthroughs and healing, though it also raises ethical and regulatory challenges. The work presents a historical and theoretical analysis of this transition, emphasizing the need for careful integration into clinical practice.
Nature
August 1, 2024
Joshua S Siegel, Subha Subramanian, Demetrius Perry et al.
241 citations
A single high dose of psilocybin (25 mg) massively disrupts functional connectivity in the human brain, causing more than threefold greater change than methylphenidate (40 mg). These changes are driven by desynchronization across spatial scales, dissolving network distinctions by reducing correlations within and anticorrelations between networks. The strongest effects occur in the default mode network, which is connected to the anterior hippocampus and is thought to create the sense of space, time, and self. Individual differences in connectivity changes are strongly linked to the subjective psychedelic experience. A persistent decrease in connectivity between the anterior hippocampus and default mode network lasts for weeks, suggesting a neuroanatomical correlate of the therapeutic and proplasticity effects of psychedelics.
JAMA Psychiatry
February 1, 2021
David Nutt, Robin Carhart-Harris
233 citations
No Summary
Frontiers in Pharmacology
March 31, 2022
Roberta Murphy, Roberta Murphy, Hannes Kettner et al.
229 citations
In a trial comparing psilocybin-assisted therapy to escitalopram for moderate-to-severe depression, a stronger therapeutic alliance with the therapist predicted greater emotional breakthrough and mystical-type experiences during psilocybin sessions, and these experiences in turn predicted larger reductions in depression symptoms six weeks after treatment. Emotional breakthrough during the first session strengthened the alliance before the second session, while a weaker alliance before the second session directly predicted higher depression scores at the endpoint, independent of the acute psychedelic experience. The findings suggest the therapeutic relationship plays a key role in shaping both the quality of the psychedelic experience and clinical outcomes.
Frontiers in Pharmacology
March 31, 2022
Roberta Murphy, Roberta Murphy, Hannes Kettner et al.
229 citations
In a trial comparing psilocybin-assisted therapy to escitalopram for moderate-to-severe depression, a stronger therapeutic alliance with the therapist predicted greater emotional breakthrough and mystical-type experiences during psilocybin sessions, and these experiences in turn predicted larger reductions in depression symptoms six weeks after treatment. Emotional breakthrough during the first session strengthened the alliance before the second session, while a weaker alliance before the second session directly predicted higher depression scores at the endpoint, independent of the acute psychedelic experience. The findings suggest the therapeutic relationship plays a key role in shaping both the quality of the psychedelic experience and clinical outcomes.
Psychopharmacology
August 8, 2022
Rosalind Watts, Hannes Kettner, Dana Geerts et al.
159 citations
A new scale, the Watts Connectedness Scale (WCS), measures a three-dimensional sense of connectedness to self, others, and the wider world. Analysis of data from 1,226 participants in online surveys and a randomized controlled trial of 52 people with major depressive disorder showed the scale has good internal consistency and construct validity. After psychedelic use, total connectedness scores increased significantly, and acute experiences of mystical experience, emotional breakthrough, and communitas correlated with these changes. In the trial, psilocybin-assisted therapy produced greater increases in WCS scores than daily escitalopram. The WCS may sensitively capture therapeutically relevant psychological changes.
Proc Natl Acad Sci U S A
February 1, 2022
Daniel Toker, Ioannis Pappas, Janna D. Lendner et al.
148 citations
During conscious states, the cortex operates near a mathematically specific critical point called the edge-of-chaos, the boundary between stability and chaos. Applying a modified 0-1 chaos test to ECoG and MEG recordings from humans and macaques, evidence suggests that unconscious states—such as generalized seizure and anesthesia—involve a shift of low-frequency cortical oscillations away from this critical point, disrupting information processing. Psychedelic states tune these oscillations closer to the critical point, potentially increasing information richness. Analysis of clinical EEG from patients with disorders of consciousness indicates that measuring proximity to this critical point may serve as a clinical index of consciousness.
Eur Neuropsychopharmacol
April 12, 2016
Mendel Kaelen, Leor Roseman, Joshua Kahan et al.
143 citations
Lysergic acid diethylamide (LSD) alters how the brain processes music-induced mental imagery by changing connectivity in the parahippocampal region. This suggests that psychedelics can enhance or modify the subjective experience of music through specific neural mechanisms, potentially linking sensory perception and imagination.
Neuroimage
April 25, 2022
Manesh Girn, Leor Roseman, Boris Bernhardt et al.
112 citations
LSD and psilocybin flatten the brain's normal hierarchical organization, reducing the functional separation between sensory and higher-order networks and increasing cross-talk between them. Analyzing two resting-state fMRI datasets, the principal gradient of cortical connectivity—which normally runs from basic sensory areas to complex association regions—was significantly compressed under both drugs compared to placebo. This flattening was driven by decreased specialization at both ends of the hierarchy: default mode and frontoparietal networks at the top, and somatomotor networks at the bottom. The findings support a proposed mechanistic model of the psychedelic state and demonstrate that macroscale connectivity gradients can be acutely altered by a pharmacological intervention.
J Psychopharmacol
February 28, 2019
David Erritzøe, James Smith, Patrick M Fisher et al.
95 citations
People who use psychedelics recreationally tend to score higher on the personality trait openness, which involves being open-minded, curious, and receptive to new experiences. This study examined whether this link might be explained by differences in the brain's serotonin system, a key chemical system affected by psychedelics. Using brain imaging, the researchers measured serotonin markers in recreational users and non-users. The findings suggest that higher openness in psychedelic users is not directly tied to these serotonin markers, indicating that other factors may underlie the personality differences.
Psychological medicine
June 1, 2024
Balázs Szigeti, Brandon Weiss, Fernando E Rosas et al.
74 citations
In a double-blind trial comparing escitalopram and COMP360 psilocybin for major depressive disorder, patients held higher expectations for psilocybin than for escitalopram. Higher pre-trial expectancy for escitalopram predicted better outcomes with escitalopram, but expectancy for psilocybin did not predict response to psilocybin. Pre-treatment trait suggestibility was linked to therapeutic response in the psilocybin arm but not the escitalopram arm. These findings suggest that psychedelic therapy may be less influenced by expectancy biases than previously thought, and that highly suggestible individuals may be especially responsive to psilocybin treatment.
J Psychopharmacol
February 10, 2021
Carla Pallavicini, Federico Cavanna, Federico Zamberlán et al.
73 citations
Inhaled N,N-dimethyltryptamine (DMT) in natural settings reduces alpha brainwave power (8-12 Hz) across the scalp while increasing delta (1-4 Hz) and gamma (30-40 Hz) power. Gamma power increases correlate with reports of mystical-type experiences. DMT also raises global synchrony and metastability in the gamma band and lowers them in the alpha band. These findings align with prior lab-based psychedelic research and suggest EEG markers for mystical experiences in real-world contexts, underscoring the value of studying psychedelics in natural settings.
Neuroimage
June 24, 2019
Carla Pallavicini, Martina G. Vilas, Mirta Villarreal et al.
66 citations
The work examines the distinct brainwave patterns produced by two classes of psychoactive drugs: serotonergic psychedelics (such as psilocybin or LSD) and glutamatergic dissociatives (such as ketamine). The authors describe how each drug class generates unique spectral signatures in EEG recordings, reflecting different underlying neural mechanisms. Serotonergic psychedelics are associated with increased gamma power and reduced alpha power, while glutamatergic dissociatives produce increased theta and gamma power. These distinct patterns may serve as biomarkers for the drugs' effects on brain function and consciousness.
Scientific reports
May 24, 2022
David Wyndham Lawrence, Robin Carhart-Harris, Roland Griffiths et al.
64 citations
An analysis of over 3,700 naturalistic experiences with inhaled N,N-DMT posted to Reddit over a decade reveals common themes. Somatic effects like body sensations (37.5%) and auditory ringing (15.4%) were frequent, while visualizations often involved fractals, shapes, and vivid colors. Entity encounters occurred in 45.5% of experiences, most commonly with a feminine phenotype, deities, aliens, and creature-based beings. Interactions were predominantly positive or pedagogical. Descriptions of alternate dimensions, rooms including a 'waiting room,' and tunnels were common. Mystical and ego-dissolution features were frequent, along with rewarding aspects like reduced fear of death. Challenging responses were less common.
Scientific reports
April 17, 2023
Rubén Herzog, Pedro A M Mediano, Fernando E Rosas et al.
51 citations
Psychedelic drugs such as LSD, which activate the serotonin 2A receptor, produce profound changes in consciousness and are linked to increased entropy in spontaneous brain activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonin neuromodulation. The model reproduced the overall rise in neural entropy seen in prior experiments. Entropy increased across all brain regions, with the largest effects in visuo-occipital areas. At the whole-brain level, this reconfiguration was not well explained by the density of serotonin 2A receptors but was closely related to the topological properties of the brain's anatomical connectivity.
EClinicalMedicine
September 23, 2024
David Erritzøe, Tommaso Barba, Kyle T Greenway et al.
46 citations
In a clinical trial, psilocybin therapy showed comparable effectiveness to a common SSRI antidepressant for treating depression, with both treatments leading to significant reductions in depressive symptoms over a follow-up period. The findings suggest psilocybin may offer a viable alternative to standard antidepressant medication, though the study's design and sample size limit the strength of conclusions.
Neuropsychologia
April 5, 2016
Devin B. Terhune, David P. Luke, Mendel Kaelen et al.
45 citations
In a placebo-controlled experiment, LSD reliably induced synaesthesia-like experiences where sensory modalities blended, such as seeing sounds or tasting shapes. Participants reported significantly more cross-sensory perceptions under LSD than placebo, with the effect strongest for sound-to-vision and vision-to-touch pairings. The findings suggest that LSD can temporarily produce sensory blending similar to developmental synaesthesia, likely by altering neural connectivity and sensory integration processes.
Frontiers in Psychology
April 4, 2014
Robin Carhart-Harris, David Nutt
42 citations
A commentary argues that dreaming is not a unique state of consciousness but rather a form of imaginative experience that shares core features with waking imagination. The author contends that dreams and waking fantasies are both products of the same cognitive processes, specifically the default mode network and memory consolidation mechanisms. The piece suggests that the vividness and narrative structure of dreams arise from the same neural dynamics that generate daydreams and creative thought, challenging the traditional view of dreaming as a separate or altered state of consciousness.
Frontiers in pharmacology
January 1, 2021
Leor Roseman, Yiftach Ron, Antwan Saca et al.
39 citations
Ayahuasca ceremonies involving Palestinians and Israelis can foster peacebuilding through intersubjective and intercultural relational processes. Analysis of 31 in-depth interviews identified three types of shared experiences: unity-based connection, where participants felt a sense of shared humanity that dissolved national and religious identities; recognition and difference-based connection, where awe and reverence arose from encountering the other culture's music or prayers; and conflict-related revelations, where personal or historical traumatic elements of the conflict emerged in visions triggered by the presence of the other. These findings suggest that psychedelic ceremonies may contribute to peacebuilding not only by dissolving identities but also by enabling shared spiritual experiences and revealing links between personal psychological states and the broader sociopolitical context.
Brain sciences
July 14, 2021
Charlotte Martial, Géraldine Fontaine, Olivia Gosseries et al.
37 citations
People who have had a near-death experience often report a disturbed sense of having a distinct self. In a survey of 100 individuals who scored 27 or higher out of 80 on the Near-Death-Experience Content scale, 80 had their experience in a life-threatening situation and 20 did not. Participants completed inventories measuring ego dissolution and ego inflation during their NDE, as well as a scale of nature-relatedness. Ego-dissolution scores were higher than ego-inflation scores. Total NDE intensity positively correlated with ego dissolution and, more weakly, with ego inflation and nature-relatedness. Ego dissolution also correlated with the intensity of out-of-body experiences and a sense of unity. The findings suggest that dissolved ego-boundaries are a common feature of NDEs.