Journal of Psychopharmacology
April 15, 2010
Ben Sessa, Amanda Feilding, Robin Carhart-Harris et al.
53 citations
Up to 2 mg of psilocybin administered as a slow intravenous injection to healthy, hallucinogen-experienced volunteers in a mock-MRI environment produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. The pilot work supports the viability of using functional magnetic resonance imaging to investigate psilocybin's effects on cerebral blood flow and activity.
J Psychopharmacol
March 4, 2024
Alessia Marrocu, Hannes Kettner, Brandon Weiss et al.
51 citations
About 16% of people who used psychedelics in naturalistic settings showed a clinically meaningful decline in psychological well-being four weeks later. Those with a prior diagnosis of a personality disorder were disproportionately affected: 31% were negative responders, and multivariate regression indicated a greater than four-fold elevated risk of adverse psychological responses. The findings suggest that personality disorders may represent an elevated risk for psychedelic use, and that psychological support and a good therapeutic alliance may be especially important for this population.
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.
Neuropsychopharmacology
September 20, 2021
Andre Zamani, Kalina Christoff, Robin Carhart-Harris
50 citations
The prefrontal cortex contains multiple subregions linked to different large-scale brain networks, supporting a wide range of mental phenomena from goal-directed thought and executive functions to mind-wandering and psychedelic experiences. A key dimension distinguishing conscious experiences is the stability or variability of mental states over time, which is central to the dynamic framework of thought (DFT) and the relaxed beliefs under psychedelics (REBUS) model. This review synthesizes these frameworks to explain how prefrontal subregions may differentially contribute to the stability and variability of thought and conscious experience, and suggests future research directions.
Neuropsychopharmacology
February 14, 2017
Ishan C Walpola, Timothy Nest, Leor Roseman et al.
50 citations
MDMA (100 mg) reduces functional connectivity between the right insula and the salience network in the brain, indicating a disintegration of this network. This decrease in connectivity correlates with higher baseline trait anxiety and more intense acute experiences of altered bodily sensations under the drug. The findings suggest that insular disintegration is a neurobiological signature of the MDMA experience, linking the drug's effects on brain activity to individual differences in anxiety and bodily awareness.
bioRxiv
November 26, 2020
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
49 citations
preprint
The brain coordinates information from many sources to create a unified conscious experience. Combining network science and information theory, the authors identify a “synergistic global workspace” where gateway regions gather synergistic information from specialized brain modules, integrate it, and then broadcast it widely via broadcaster regions. Functional MRI shows that gateway regions correspond to the default mode network and broadcasters to the executive control network. Loss of consciousness from general anesthesia or disorders of consciousness reduces the workspace’s ability to integrate information, which is restored upon recovery. This work reconciles aspects of the Global Neuronal Workspace and Integrated Information Theory.
World Psychiatry
September 7, 2018
Robin Carhart-Harris
49 citations
Serotonin is a complex neuromodulator involved in brain development, perception, cognition, and mood, but no unified theory of its function exists, partly due to its 14+ receptors. While SSRIs are the dominant depression treatment, their widespread use has not reduced depression prevalence, and questions about safety and efficacy persist. Evidence suggests serotonergic processes mediate sensitivity to context, with genetic and pharmacological factors interacting with environment to affect mental health.
JAMA Psychiatry
June 1, 2023
Jacob S. Aday, Robin Carhart-Harris, Joshua Woolley
48 citations
The abstract discusses emerging challenges for psychedelic therapy, highlighting obstacles such as regulatory hurdles, accessibility issues, equity concerns, and the need for practitioner training. It underscores difficulties in integrating psychedelic treatments into mainstream healthcare, including governance, legal frameworks, and developing accessible and equitable treatment models. The text suggests that responsible integration requires addressing these barriers to ensure safe and effective mental health care.
Current Drug Abuse Reviews
January 9, 2015
Samuel Turton, D.j. Nutt, Robin Carhart-Harris
48 citations
An analysis of the subjective experiences of psilocybin administered intravenously in an MRI scanner found effects consistent with prior reports on psilocybin's subjective effects. The article documents these phenomena and suggests further research is needed to explore the identified experiences.
Frontiers in Psychology
November 25, 2021
Brandon Weiss, Victoria Amalie Nygart, Lis Marie Pommerencke et al.
47 citations
In an online volunteer sample, naturalistic use of psychedelic compounds was associated with reductions in Neuroticism and increases in Agreeableness and perceived social connectedness over four weeks. These changes covaried, suggesting shared emotion-regulation processes. Preliminary evidence pointed to a specific decrease in critical and quarrelsome interpersonal style, a component of Agreeableness. Baseline levels of Neuroticism, perspective taking, and social connectedness tentatively amplified adaptive changes in those respective traits. Demographic characteristics, social setting, and acute subjective factors showed limited moderating effects. The findings suggest psychedelics might help address interpersonal aspects of personality pathology and loneliness.
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 Luke, Mendel Kaelen et al.
45 citations
Lysergic acid diethylamide (LSD) induces synaesthesia-like experiences in non-synaesthetes, but these experiences do not meet two key criteria for genuine synaesthesia: consistency of stimulus-colour associations over time and inducer specificity. In a placebo-controlled pilot study, participants reported more spontaneous synaesthesia-like experiences under LSD compared to placebo, yet their colour responses to standardized graphemes and sounds did not differ across conditions in consistency or specificity. Individual differences in absorption propensity were linked to some effects. The findings suggest that LSD-induced synaesthesia-like experiences are not equivalent to genuine synaesthesia.
Psychological Medicine
October 1, 2023
Jonathan W. Kanen, Qiang Luo, Mojtaba Rostami Kandroodi et al.
44 citations
LSD increases the rate at which people learn from both rewards and punishments during a probabilistic reversal learning task, suggesting a state of heightened learning plasticity. Healthy volunteers given intravenous LSD or placebo completed a task where they had to learn which of three stimuli was most often rewarded, with the reward contingencies later reversing. Computational modeling of reinforcement learning showed that LSD primarily enhanced the reward learning rate and also elevated the punishment learning rate, while decreasing stimulus stickiness (a measure of choice repetition), indicating increased exploration. These effects point to a potential mechanism by which LSD could help revise maladaptive associations in clinical treatment.
Frontiers in Psychiatry
November 12, 2021
Julia Bornemann, James B. Close, Meg J. Spriggs et al.
43 citations
Eleven individuals with chronic pain who self-medicate with psychedelic drugs described their experiences in a group discussion. Pain scores improved substantially during and after psychedelic experiences across a range of substances and doses. Two processes—Positive Reframing and Somatic Presence—were reliably identified as contributing to improvements in mental wellbeing, relationship with pain, and physical (dis)comfort. Additional strategies such as mindfulness, breathwork, and movement were also widely reported. The authors note that due to the subjective nature of the data, no claims on causality or generalisability can be made. These results will inform the design of a forthcoming controlled trial testing psychedelic therapy for chronic pain.
Neuroscience of Consciousness
November 1, 2021
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
42 citations
Consciousness can be better understood by decomposing it into distinct information-theoretic elements rather than measuring it as a single quantity of integrated information. The authors propose Integrated Information Decomposition (ΦID), which provides a formal argument that whether consciousness is an emergent phenomenon depends on its information-theoretic composition. Two organisms may have the same amount of integrated information yet differ in composition. A new measure, ΦR, and the ΦR-ing ratio quantify how efficiently information is used for conscious processing. This approach enables identification of qualitatively different 'modes of consciousness' and mapping them to phenomenology, starting with selfhood. ΦID offers new ways to explore the relationship between information, consciousness, and neural dynamics.
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.
Journal of psychopharmacology (Oxford, England)
January 1, 2024
Lisa Luan, Emma Eckernäs, Michael Ashton et al.
41 citations
A novel method of administering the psychedelic DMT via a bolus injection followed by a constant-rate infusion safely extends the experience to 30 minutes in a stable and tolerable fashion. In eleven healthy volunteers, subjective effects plateaued into a steady state while plasma DMT concentrations continued to rise, indicating acute psychological tolerance. Anxiety ratings remained low and heart rate habituated within 15 minutes, demonstrating psychological and physiological safety. This continuous intravenous administration method lays groundwork for further basic and clinical research into DMT's potential for treating mental health conditions and studying consciousness.
Nature Mental Health
August 5, 2024
Gustavo Deco, Yonatan Sanz Perl, Samuel Johnson et al.
39 citations
Two serotonergic interventions—psilocybin therapy and the antidepressant escitalopram—rebalance brain dynamics in major depressive disorder through opposite hierarchical reconfigurations. In a double-blind phase II trial, 22 patients received two 25 mg doses of psilocybin plus daily placebo, while 20 patients received two 1 mg doses of psilocybin plus daily escitalopram. Resting-state fMRI scans before and after treatment, analyzed with generative effective connectivity models, showed that the two treatments produced significantly different and opposite changes in whole-brain hierarchy. Machine learning predicted treatment response with 85% accuracy. The findings suggest that depression may involve disrupted function of brain regions that orchestrate dynamics from the top of the hierarchy.
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.
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.
Psychological Medicine
January 1, 2024
Brandon Weiss, Induni Ginige, Lu Shannon et al.
38 citations
In a trial comparing psilocybin therapy with the antidepressant escitalopram for moderate-to-severe major depressive disorder, both treatments led to personality changes in a direction consistent with improved mental health. Psilocybin was linked to decreases in neuroticism, introversion, disagreeableness, and impulsivity, and increases in absorption, conscientiousness, and openness at six weeks, with some changes lasting six months. Escitalopram was linked to decreases in neuroticism, disagreeableness, and impulsivity, and increases in openness at six weeks, with neuroticism remaining decreased at six months. No significant differences between the two treatments were observed, except that patients' pre-trial positive expectations for escitalopram moderated personality changes after that treatment, but not after psilocybin.
Journal of Psychopharmacology
November 26, 2022
Melissa Shukuroglou, Leor Roseman, David Nutt et al.
38 citations
Listening to music after psilocybin therapy for treatment-resistant depression increases the pleasure people feel from music, and this increase correlates with a reduction in anhedonia (loss of pleasure). Nineteen patients received a low dose (10 mg) and then a high dose (25 mg) of psilocybin one week apart. Functional MRI scans before and after treatment showed that during music listening, functional connectivity between the nucleus accumbens (a brain reward region) and areas resembling the default mode network decreased after treatment. The findings suggest psilocybin therapy enhances music-evoked pleasure and point to a possible brain mechanism involving reduced connectivity in the default mode network.
Scientific Reports
February 7, 2024
Christopher Timmermann, Richard J. Zeifman, David Erritzøe et al.
37 citations
Intravenous DMT, a fast-acting psychedelic, improved depression scores in healthy volunteers one to two weeks after administration. In a placebo-controlled comparison (13 participants) and a prospective dataset (17 participants), depression severity decreased significantly. Reductions in trait neuroticism appeared only in the placebo-controlled sample. Changes in depression and anxiety correlated with the intensity of acute peak experiences, suggesting that DMT may reduce depressive symptoms by inducing such experiences. The short half-life and flexible dosing of intravenous DMT make it a practical candidate for psychedelic medicine, though further research in clinical samples is needed.
Psychopharmacology (Berl)
November 4, 2021
Joanna Kuć, Hannes Kettner, Fernando E. Rosas et al.
37 citations
People who use cannabis at the same time as a classic psychedelic report more intense subjective effects, with higher cannabis doses linked to stronger mystical, visual, and ego-dissolution experiences. The relationship between cannabis dose and challenging experiences followed a U-shaped pattern, while emotional breakthrough showed no connection to cannabis dose. The findings suggest an interaction between cannabis and psychedelics, but the study's design cannot establish cause or clinical implications.
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.