The International Journal of Neuropsychopharmacology
December 17, 2013
Robin Carhart‐Harris, Matthew B. Wall, David Erritzøe et al.
110 citations
MDMA (ecstasy) makes recalling favorite autobiographical memories feel more vivid, emotionally intense, and positive, while making recall of worst memories feel less negative. In a double-blind, placebo-controlled fMRI study with 19 participants who had prior MDMA experience, 100 mg of MDMA altered brain activity during memory recall: it increased activation in the fusiform gyrus and somatosensory cortex for favorite memories and decreased activation in the left anterior temporal cortex for worst memories. These neural changes suggest MDMA creates a positive emotional bias, which may explain why it helps patients revisit traumatic memories during psychotherapy for PTSD.
Neuropharmacology
December 27, 2022
Robin Carhart‐Harris, Shamil Chandaria, David Erritzøe et al.
106 citations
A theoretical model proposes that psychopathology arises from a defensive process called canalization, which narrows an individual's range of thoughts, feelings, and behaviors by increasing precision or reducing variance in neural responses. This contrasts with an early form of plasticity, TEMP (Temperature or Entropy Mediated Plasticity), which increases variance and learning rate. Canalization entrenches pathology as the agent develops expertise in their disorder, while TEMP, combined with gentle psychological support, may counter this entrenchment. The model distinguishes adaptive from maladaptive canalization and suggests concrete experiments to test its hypotheses.
Frontiers in Psychiatry
August 7, 2020
Richard J. Zeifman, Anne Catherine Wagner, Ros Watts et al.
104 citations
In two prospective studies with convenience samples of people planning to use a psychedelic (total N=358), participants completed questionnaires before use and at 2 and 4 weeks afterward. Across both studies, significant decreases occurred in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may reduce experiential avoidance, depression severity, and suicidal ideation, and that reduced experiential avoidance may be a transdiagnostic mechanism in psychedelic therapy. Integrating psychedelics with therapies targeting experiential avoidance, such as acceptance and commitment therapy, may enhance outcomes.
Scientific Reports
September 25, 2023
Rebecka Bremler, Nancy Katati, Parvinder Shergill et al.
102 citations
Negative psychological responses to psychedelics lasting more than 72 hours are real and can include new psychiatric diagnoses or worsened symptoms. In a sample of 32 individuals who completed an online questionnaire, 37.5% received a new psychiatric diagnosis after their psychedelic experience, and 87% experienced anxiety symptoms. Deeper interviews with 15 of the most severe cases revealed potential causes: unsafe environments, unpleasant acute experiences, prior psychological vulnerabilities, high or unknown drug doses, and young age. The findings cannot estimate how common such harms are due to the small, selective sample and study design focused only on negative outcomes.
Frontiers in Psychiatry
July 19, 2021
Rita Kočárová, Jiřı́ Horáček, Robin Carhart‐Harris
95 citations
Psychedelic therapy may work across many psychiatric disorders by increasing neuronal and mental plasticity, which enhances the potential for change. Combined with psychotherapy, this plasticity can promote healthy adaptability and resilience, protecting long-term well-being. The authors propose that psychedelics' core action is transdiagnostic, offering prophylactic benefits beyond current treatments. They link candidate neurological and psychological markers to a predictive processing model, suggesting broad public health impact.
NeuroImage
June 30, 2020
Thomas F. Varley, Robin Carhart‐Harris, Leor Roseman et al.
91 citations
Psychedelic drugs like psilocybin and LSD increase the fractal dimension of brain activity, suggesting that the brain moves toward a critical state between order and disorder. Using fMRI data from volunteers, the study tested two fractal measures: one for functional connectivity networks and one for BOLD time-series. Both drugs significantly increased the fractal dimension of functional connectivity networks. LSD also significantly increased the fractal dimension of BOLD signals, while psilocybin showed a non-significant trend in the same direction. Changes in the fractal dimension of BOLD signals were localized to brain areas in the dorsal attention network. These results indicate that psychedelic-induced changes in consciousness are associated with evolution toward a critical zone.
The British Journal of Psychiatry
March 1, 2017
Matthew M. Nour, Robin Carhart‐Harris
90 citations
Altered self-experiences, which occur in some psychiatric conditions and can be induced by psychoactive drugs or spiritual practices, are now being studied through a neuroscience framework that combines functional neuroimaging with altered states from psychedelic drugs. This emerging understanding may significantly benefit psychiatry.
Schizophrenia Bulletin
August 5, 2020
Pantelis Leptourgos, Martin Fortier-Davy, Robin Carhart‐Harris et al.
88 citations
A multidisciplinary working group reviewed evidence on the similarities and differences between hallucinations induced by psychedelics and those occurring in schizophrenia-spectrum disorders, examining data from pharmacology, brain imaging, phenomenology, and anthropology. The authors highlight both shared features and distinct characteristics across these scales, and attempt to integrate findings using computational approaches. They conclude with recommendations for future research, emphasizing the need for further study to clarify the relationship between these types of hallucinations.
Journal of Psychopharmacology
May 29, 2021
Pedro J. Teixeira, Matthew W. Johnson, Christopher Timmermann et al.
87 citations
Healthy behaviors like diet, exercise, and not smoking greatly reduce risks for cancer, diabetes, and cardiovascular disease, but lifestyle diseases remain a major burden. Psychedelic substances, particularly psilocybin, are being explored as tools to promote positive lifestyle change. Psilocybin has low toxicity, is non-addictive, and has shown favorable changes in patients with depression, anxiety, and substance misuse. The article describes proposed mechanisms of action and research linking psychedelics to health behavior change, suggesting that combining psychedelic experiences with methods like Cognitive Behaviour Therapy and Motivational Interviewing may help improve diet, exercise, nature exposure, and mindfulness.
Frontiers in Psychiatry
October 20, 2021
Meg J. Spriggs, Hannah Douglass, Rebecca J. Park et al.
78 citations
Anorexia nervosa is a severe psychiatric condition with few approved treatments. This paper describes how individuals with lived experience of anorexia nervosa helped shape a pilot study of psilocybin-assisted therapy through two online focus groups involving eleven people, and presents the protocol for that study at Imperial College London. Twenty female participants aged 21–65 with a body mass index of 15 kg/m² or above will receive three oral doses of psilocybin (up to 25 mg) over six weeks, supported by psychological preparation and integration, with a 12-month remote follow-up.
Frontiers in Psychology
October 12, 2018
Taylor Lyons, Robin Carhart‐Harris
78 citations
Patients with treatment-resistant depression showed a significant pessimism bias when predicting future life events, which was linked to the severity of their depressive symptoms. One week after receiving two doses of psilocybin (10 and 25 mg) with psychological support, this pessimism bias decreased significantly, depressive symptoms greatly improved, and patients became more accurate at predicting future events. No such change occurred in non-depressed controls. The findings suggest that psilocybin with psychological support might correct pessimism biases in treatment-resistant depression, enabling a more positive and accurate outlook.
Neuroscience of Consciousness
January 1, 2019
Gregory Scott, Robin Carhart‐Harris
72 citations
The classic psychedelic psilocybin may increase conscious awareness in patients with disorders of consciousness, based on its ability to increase brain complexity—a reliable index of conscious level. The authors propose testing this hypothesis but also confront the considerable ethical and practical challenges that must be addressed for direct assessment.
Science Advances
June 14, 2023
Leor Roseman, Christopher Timmermann, Daniel Golkowski et al.
65 citations
The effects of mind-altering drugs on brain function arise from complex interactions with multiple neurotransmitter systems, not just one. By linking the distribution of 19 neurotransmitter receptors and transporters (measured with PET) to changes in functional connectivity (measured with fMRI) caused by 10 drugs—anesthetics (propofol, sevoflurane, ketamine), psychedelics (LSD, psilocybin, DMT, ayahuasca), and others (MDMA, modafinil, methylphenidate)—the work shows a many-to-many mapping between drug effects and neurotransmitter systems. The drugs' impacts follow hierarchical gradients of brain structure and function, and regional susceptibility to drug-induced changes mirrors susceptibility to structural alterations from brain disorders.
Frontiers in Psychiatry
June 29, 2021
Keri Mans, Hannes Kettner, David Erritzøe et al.
65 citations
Psychedelic substances like LSD and psilocybin have regained legitimacy in clinical research. In this naturalistic observational study of volunteers intending to take a psychedelic, well-being was assessed using fourteen measures at four time points: 1 week before and 2 weeks, 4 weeks, and 2 years after the experience (sample sizes 654, 315, 212, and 64, respectively). Changes clustered into three factors: 'Being well,' 'Staying well,' and 'Spirituality.' Repeated measures analysis showed improvements in Being Well and Staying Well in the weeks following the experience, and mixed model analyses indicated these improvements remained statistically significant up to 2 years, despite high attrition. Spirituality did not show significant change.
Neuroscience of Consciousness
January 1, 2023
Inês Hipólito, Jonas Mago, Fernando E. Rosas et al.
60 citations
Psychedelic therapy shows promise for mental health, but the psychological mechanisms behind its benefits are unclear. This paper proposes that psychedelics act as destabilizers, both psychologically and neurophysiologically, drawing on the 'entropic brain' hypothesis and the 'RElaxed Beliefs Under pSychedelics' model. Using complex systems theory, it suggests that psychedelics disrupt fixed points or attractors, breaking reinforced patterns of thinking and behavior. The approach explains how increased brain entropy destabilizes neurophysiological set points, leading to new understandings of psychedelic psychotherapy. These insights have implications for reducing risks and optimizing treatment during both the peak experience and the subacute recovery period.
Scientific Reports
October 20, 2020
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
60 citations
Psychedelic drugs such as lysergic acid diethylamide, which activate the serotonin 2A receptor, produce profound changes in consciousness and increase entropy in spontaneous neural activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonergic neuromodulation. The model reproduced the overall entropy rise seen in previous experiments. Entropy changes were not uniform: some brain regions showed increased entropy while others showed decreases, indicating a topographical reconfiguration driven by receptor activation. At the whole-brain level, this reconfiguration was not well explained by receptor density but was closely related to the brain's anatomical connectivity topology.
BJPsych Open
September 1, 2022
Tommaso Barba, Sarah Buehler, Hannes Kettner et al.
57 citations
Psilocybin, but not the antidepressant escitalopram, reduced rumination and thought suppression in people with major depressive disorder six weeks after treatment. In a randomized trial of 59 participants, only those given psilocybin showed significant decreases in both maladaptive coping strategies. Among treatment responders, thought suppression decreased exclusively in psilocybin responders, while rumination decreased in both psilocybin and escitalopram responders. Reductions in rumination and thought suppression correlated with ego dissolution and psychological insight during psilocybin sessions, suggesting distinct therapeutic mechanisms for the two treatments.
Scientific Reports
July 13, 2021
Otto Simonsson, Walter Osika, Robin Carhart‐Harris et al.
54 citations
Lifetime use of classic psychedelics is associated with lower odds of heart disease and diabetes. Analyzing data from the National Survey on Drug Use and Health (2005–2014), people who had ever tried a classic psychedelic had 23% lower odds of past-year heart disease and 12% lower odds of past-year diabetes. The associations persisted after adjusting for other factors. The authors suggest classic psychedelic use might benefit cardiometabolic health but call for more research on causal pathways.
Language Cognition and Neuroscience
August 11, 2016
Neiloufar Family, David Vinson, Gabriella Vigliocco et al.
53 citations
LSD alters cognition by expanding the breadth of semantic activation. In a picture-naming task with ten participants, LSD reduced accuracy and altered error correction patterns compared to placebo, consistent with an increased spread of semantic activation. These effects align with a generalized entropic effect on the mind. The authors recommend future studies include direct neuroimaging and more naturalistic measures of semantic processing.
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.
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.
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.
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.
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.