Nat Med
April 11, 2022
Richard E. Daws, Christopher Timmermann, Bruna Giribaldi et al.
432 citations
Psilocybin therapy produces rapid and sustained antidepressant effects that correlate with a global increase in brain network integration. In two clinical trials, one open-label in treatment-resistant depression and one double-blind randomized controlled trial comparing psilocybin with escitalopram in major depressive disorder, functional MRI showed that psilocybin reduced brain network modularity, making higher-order functional networks more interconnected and flexible. The antidepressant response to escitalopram was milder, with no changes in brain network organization. These consistent efficacy-related brain changes across both studies suggest that psilocybin's antidepressant mechanism involves global increases in brain network integration.
Frontiers in Pharmacology
November 2, 2018
Adam D. G. Hampshire, Christopher Timmermann, Christopher Timmermann et al.
422 citations
Psychological well-being increased two weeks after a psychedelic experience and remained elevated at four weeks. Higher ratings of a 'mystical-type experience' positively influenced this change in well-being, while 'challenging experience' and 'visual effects' did not. Having 'clear intentions' for the experience fostered mystical-type experiences. A positive 'set' and recreational intentions reduced the likelihood of a challenging experience. The trait 'absorption' and higher drug doses amplified all aspects of the acute experience. Baseline traits had the strongest effect on well-being change, underscoring the importance of extra-pharmacological factors in shaping responses to psychedelics.
Frontiers in Pharmacology
November 2, 2018
Adam D. G. Hampshire, Christopher Timmermann, Christopher Timmermann et al.
422 citations
Psychological well-being increased two weeks after a psychedelic experience and remained elevated at four weeks. Higher ratings of a 'mystical-type experience' positively influenced this change in well-being, while 'challenging experience' and 'visual effects' did not. Having 'clear intentions' for the experience fostered mystical-type experiences. A positive 'set' and recreational intentions reduced the likelihood of a challenging experience. The trait 'absorption' and higher drug doses amplified all aspects of the acute experience. Baseline traits had the strongest effect on well-being change, underscoring the importance of extra-pharmacological factors in shaping responses to psychedelics.
Sci Rep
November 19, 2019
Christopher Timmermann, Leor Roseman, Michael Schartner et al.
325 citations
Intravenous DMT, a fast-acting psychedelic, markedly reduces alpha and beta brain wave power and increases spontaneous signal diversity in the human brain, as measured by EEG. The emergence of delta and theta oscillatory activity correlates with the peak of the subjective experience, especially its eyes-closed visual component. Relationships between changes in subjective experience and brain activity were observed across time, linking specific brain changes to specific aspects of the experience.
The International Journal of Neuropsychopharmacology
October 21, 2022
James J Gattuso, Daniel Perkins, Simon Ruffell et al.
233 citations
Classical psychedelics like LSD, psilocybin, and ayahuasca consistently disrupt resting-state connectivity within the Default Mode Network (DMN) and increase functional connectivity between canonical resting-state networks. The DMN, a set of brain regions active during self-referencing and mind wandering, is altered in various neuropsychiatric conditions. While DMN modulation is central to some cognitive models of psychedelics, its role in their therapeutic potential remains unclear. This systematic review provides a comprehensive overview to guide future research on the neurocognitive mechanisms of these agents.
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.
Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
Scientific reports
November 23, 2021
Christopher Timmermann, Hannes Kettner, Chris Letheby et al.
208 citations
People who use psychedelic drugs often shift away from materialist views of reality and consciousness toward panpsychism and fatalism, with most changes lasting at least six months. In a large prospective online survey, these belief shifts correlated with greater past psychedelic use and improved mental health. Emotional synchrony with others during the experience mediated the changes, and baseline impressionability moderated them. An independent clinical trial confirmed the direction of belief change, suggesting psychedelics may causally influence metaphysical beliefs away from hard materialism, though contextual independence remains uncertain.
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.
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.
Trends in Cognitive Sciences
December 22, 2022
Christopher Timmermann, Prisca R. Bauer, Olivia Gosseries et al.
145 citations
A neurophenomenological framework is proposed for studying non-ordinary states of consciousness (NSCs) such as hypnosis, meditation, and psychedelics. NSCs involve shifts in what appears to the experiencer or how it appears, enabling investigation of the plastic and dynamic nature of experience across mind, brain, body, and context. The approach highlights NSCs as catalysts of transformation in clinical practice by refining understanding of relationships between subjective experience and neural dynamics. Ethical implications for standard conceptions of health and pathology are outlined, along with the crucial role of experience-based know-how in NSC research and application.
J Psychopharmacol
January 5, 2022
Joseph M Peill, Katie E Trinci, Hannes Kettner et al.
135 citations
A new self-report questionnaire, the Psychological Insight Scale, was developed and validated to measure the degree of psychological insight people gain from a psychedelic experience. The scale was tested in a large online sample and showed strong reliability and validity, capturing a distinct aspect of psychedelic-induced change not measured by existing tools. Higher scores on the scale were associated with greater improvements in well-being and reductions in psychological distress, suggesting that psychological insight may be a key mechanism underlying the therapeutic potential of psychedelics.
Transcultural psychiatry
October 1, 2022
Christopher Timmermann, Rosalind Watts, David Dupuis
112 citations
Psychedelics can make experiences feel profoundly true and meaningful, effects that may outlast the drug. This double-edged sword can drive therapeutic benefits but also risks validating false beliefs, worldviews, or memories, potentially causing harm like false memory syndrome. As psychedelic therapy goes mainstream with strong commercial interests, these ethical challenges grow. Using examples from therapy, neo-shamanic, and research settings, the authors argue that current preparation and integration methods are insufficient. They propose a pragmatic framework centered on 'psychedelic apprenticeship,' which emphasizes validation through empathic resonance by an experienced guide or therapist, embedding the experience in historical and cultural context, and recognizing its intersubjective nature.
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.
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.
Elife
October 12, 2020
Andrea Alamia, Christopher Timmermann, David J Nutt et al.
86 citations
The psychedelic drug DMT rapidly induces a highly immersive state of consciousness with vivid visual imagery. In a study of participants who received DMT or placebo (saline) while keeping their eyes closed, brain electrical activity showed a pattern of cortical travelling waves similar to that normally seen during visual stimulation. The typical alpha-brainwave rhythms of eyes-closed rest were significantly reduced, while forward-directed waves from lower to higher brain regions increased. These findings support the idea that psychedelics reduce the brain's reliance on prior expectations, shifting the balance from top-down to bottom-up information processing, which may be a key mechanism underlying altered states of consciousness.
Neuropharmacology
November 20, 2017
Christopher Timmermann, Meg J. Spriggs, Mendel Kaelen et al.
83 citations
LSD reduces the brain's automatic neural adaptation to familiar sounds and blunts the neural 'surprise' response to unexpected sounds. Using magnetoencephalography and dynamic causal modeling, the authors found that LSD modulates backward (top-down) connectivity within a fronto-temporal network and intrinsic connectivity in the primary auditory cortex. These patterns resemble those seen in schizophrenia, ketamine states, and reduced consciousness, suggesting that backward connectivity may reflect altered perceptual learning common to multiple altered states rather than a direct marker of conscious level. The findings challenge top-down hypotheses of consciousness and indicate that several altered states may share this biophysical mechanism.
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.
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.
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.
Journal of psychopharmacology (Oxford, England)
March 1, 2022
Malin Vedøy Uthaug, Alan K Davis, Trevor Forrest Haas et al.
64 citations
Mescaline, a naturally occurring psychoactive compound found in cacti such as Peyote and San Pedro, is used infrequently (once a year or less) by most English-speaking adults, primarily for spiritual exploration or connection with nature (74%). In a web-based survey of 452 respondents, very few reported drug craving (9%), legal problems (1%), or psychological problems (1%), and none sought medical attention. Acute mystical-type effects were rated as moderate, ego-dissolution and insight as slight, and challenging effects as very slight. About half of the sample had a psychiatric condition, and most (over 67%) reported improvements in these conditions after their most memorable mescaline experience. The findings suggest that mescaline may produce a psychedelic experience with spiritual significance and mental health benefits and has low abuse potential.
Health Psychol Open
July 1, 2020
Sam Gandy, Matthias Forstmann, Robin Lester Carhart-Harris et al.
64 citations
Contact with nature and psychedelic administration may work together to improve mental health. The authors suggest that these two experiences share psychological mechanisms—such as awe, connectedness, and reduced ego—that could amplify each other's positive effects. The paper reviews existing evidence and proposes that combining psychedelic therapy with nature-based interventions might enhance therapeutic outcomes. This synergistic approach could offer new avenues for treating mental health conditions, though the authors call for further empirical research to test these ideas directly.
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.
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.
Journal of psychopharmacology (Oxford, England)
January 1, 2024
Lisa X 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.