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.
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.
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.
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.
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 Erritzoe, 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.
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.
Scientific Reports
February 7, 2024
Christopher Timmermann, Richard J Zeifman, David Erritzoe 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.
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.
Network Neuroscience
January 1, 2022
Josephine Cruzat, Yonatan Sanz Perl, Anira Escrichs et al.
28 citations
Psychedelic drugs like LSD and psilocybin may treat neuropsychiatric disorders by dose-dependently altering the brain's functional hierarchy—the organization of neural activity across regions. Using a turbulence framework that measures local synchronization (vorticity) in both space and time, researchers found that both drugs produce consistent and distinct effects, particularly compressing the default mode network, a higher-level network. These findings support the hypothesis that psychedelics modulate the functional hierarchy and provide a quantitative comparison of how LSD and psilocybin change brain dynamics, with implications for therapeutic use.
NeuroImage
December 1, 2023
Stefano Delli Pizzi, Piero Chiacchiaretta, Carlo Sestieri et al.
27 citations
LSD selectively alters the functional connectivity between specific thalamic nuclei and sensory and associative cortical areas. Using structural and resting-state functional MRI in healthy volunteers under acute LSD administration, researchers found increased coupling of the ventral complex, pulvinar, and non-specific thalamic nuclei with somatosensory and auditory cortices, as well as with associative cortex regions rich in serotonin 2A receptors. At subcortical levels, LSD increased connectivity among these thalamic nuclei but decreased striatal-thalamic connectivity. These nucleus-specific changes help explain LSD's modulation of subcortical-cortical circuits and associated behavioral effects.
December 30, 2020
Christopher Timmermann, Rosalind Watts, David Dupuis
27 citations
preprint
Psychedelics can make people feel that specific thoughts or ideas are profoundly true and meaningful, a feeling that can last long after the drug wears off. This double-edged feature may drive therapeutic benefits but also risks validating false beliefs, memories, or worldviews, potentially leading to iatrogenic complications like false memory syndrome. The paper discusses these risks through examples in therapy, neo-shamanic rituals, and research. It proposes a pragmatic ethical framework that emphasizes embedding psychedelic experiences in historical and cultural contexts, their intersubjective nature, and a form of psychedelic apprenticeship—going beyond standard preparation and integration by centering validation through empathic resonance with an experienced guide.
bioRxiv (Cold Spring Harbor Laboratory)
May 8, 2020
Andrea Alamia, Christopher Timmermann, Rufin Vanrullen et al.
25 citations
preprint
The psychedelic drug DMT rapidly induces an immersive conscious state with vivid visual imagery. EEG recordings showed that DMT alters cortical traveling waves: the typical alpha-band backward wave of eyes-closed rest decreased, while a forward wave similar to that seen during visual stimulation increased. This supports a model where psychedelics reduce the precision-weighting of prior expectations, shifting the balance from top-down to bottom-up information flow. The findings suggest that backward traveling waves are correlates of precision weighting and that reduced backward and increased forward waves are a mechanistic principle of psychedelic-induced altered states.
Clinical and Translational Science
September 11, 2022
Emma Eckernäs, Christopher Timmermann, Daniel Röshammar et al.
22 citations
The psychedelic compound DMT is cleared from the body at a very high rate—26 L/min—indicating its elimination is independent of blood flow. Plasma concentrations follow a two-compartment model, with DMT metabolized to indole 3-acetic acid. The intensity of the psychedelic experience is linked to DMT concentration at an effect site, with half-maximal effect at 95 nM. Simulated median intensity ratings after doses of 1, 4, 7, 14, and 20 mg were zero, 2, 4, 8, and 9 on a 0–10 scale. The model can help predict suitable doses for clinical studies based on desired subjective experience intensity.