Neuroscience of consciousness
January 1, 2025
Christopher Timmermann, James W Sanders, David Reydellet et al.
19 citations
The psychedelic 5-MeO-DMT can, in its most extreme cases, produce a complete absence of self-experience and other perceptual content while preserving a quality of aroused, waking awareness. In an exploratory observational study in naturalistic ceremonial settings, micro-phenomenological interviews, questionnaires, and EEG recordings revealed a dynamic progression of effects, including variable disruptions of bodily and narrative self, reduced phenomenal distinctions, and visual imagery. EEG showed global alpha and posterior beta power reductions, suggesting inhibition of top-down brain models. The findings indicate 5-MeO-DMT's potential as a pharmacological model for deconstructed consciousness, though retrospective questionnaires have limitations.
Biological psychiatry. Cognitive neuroscience and neuroimaging
July 1, 2023
Stefano Delli Pizzi, Piero Chiacchiaretta, Carlo Sestieri et al.
18 citations
LSD alters brain functional connectivity and local signal amplitude in opposite directions depending on the type of serotonin receptor involved. In healthy volunteers, LSD increased activity and connectivity in cortical regions of the default mode and attention networks, which have high densities of 5-HT2A receptors; these changes correlated with visual hallucinations. Conversely, LSD decreased activity and connectivity in limbic areas rich in 5-HT1A receptors. The spatial patterns of these functional changes overlapped with the distribution of the two serotonin receptor subtypes, suggesting distinct receptor-mediated mechanisms underlie LSD's reorganization of brain networks.
bioRxiv (Cold Spring Harbor Laboratory)
May 12, 2023
Christopher Timmermann, Emma Eckernäs, Leor Roseman et al.
17 citations
preprint
The serotonergic psychedelic DMT rapidly induces a profoundly immersive altered state lasting less than 20 minutes, allowing the entire drug experience to be captured during a single fMRI scan. Using network control theory, which quantifies the input needed to drive transitions between brain states, brain structure and function were integrated to map energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Global control energy was reduced following DMT compared to placebo. Longitudinal trajectories of global control energy correlated with EEG signal diversity and subjective drug intensity ratings. Regional effects correlated with serotonin 2a receptor density. Receptor distribution and pharmacokinetic information successfully recapitulated DMT's effects on global control energy trajectories.
bioRxiv (Cold Spring Harbor Laboratory)
August 20, 2020
Carla Pallavicini, Federico Cavanna, Federico Zamberlán et al.
17 citations
preprint
Inhaled DMT, a short-acting psychedelic found in plants and animals, was studied in 35 experienced participants in natural settings using wireless EEG and questionnaires. DMT reduced alpha brain waves (8-12 Hz) across the scalp while increasing delta (1-4 Hz) and gamma (30-40 Hz) waves. Increases in gamma power correlated with reports of mystical-type experiences. DMT also altered global synchrony and metastability in gamma and alpha bands and increased signal complexity. These findings align with prior psychedelic research and suggest EEG markers for mystical experiences in natural contexts, underscoring the value of studying these compounds in real-world settings.
Neuroscience of Consciousness
January 1, 2020
Michael Schartner, Christopher Timmermann
17 citations
The serotonergic system regulates the balance between prior expectations and sensory information in shaping conscious visual perception. Psychedelic drugs like N,N-Dimethyltryptamine can perturb this system, altering how the brain gates internal and external inputs. Two generative deep neural networks are discussed as tools to both illustrate the visual effects of psychedelics and to model the biological mechanisms of sensory gating. This approach offers a new medium, alongside paintings and verbal reports, for understanding how the brain constructs conscious experience.
Journal of psychopharmacology (Oxford, England)
October 1, 2024
Valerie Bonnelle, Amanda Feilding, Fernando E Rosas et al.
16 citations
The joint influence of the sympathetic and parasympathetic nervous systems over cardiac activity, known as sympathovagal coactivation, is positively related to ratings of spiritual experience and insightfulness during the DMT-induced peak experience, and also to improved well-being two weeks later. The balance between the two autonomic branches before DMT injection predicted insightfulness scores and subsequent coactivation. These findings demonstrate the autonomic nervous system's involvement in psychedelic-induced peak experiences.
Journal of Psychopharmacology
April 12, 2024
Joseph Peill, Miriam Marguilho, David Erritzoe et al.
16 citations
In a double-blind randomized controlled trial, 59 patients with depression received either a high (25 mg) or placebo (1 mg) dose of psilocybin. Those given the high dose reported stronger perceived 'inner healing' effects, and within that group, higher inner healer scores predicted greater improvement in depressive symptoms two weeks later. The findings suggest that the concept of an intrinsic healing mechanism activated by psychedelics merits further scientific investigation, though the idea remains scientifically nascent.
Frontiers in psychiatry
January 1, 2023
Ellen James, David Erritzoe, Tiffanie Benway et al.
16 citations
A phase 1 trial tested escalating intravenous doses of the psychedelic DMT (SPL026) in healthy volunteers who had never used psychedelics, to find a safe, tolerable dose for a future trial in people with major depressive disorder. Participants were randomly assigned to placebo or one of four doses (9, 12, 17, or 21.5 mg). The drug was well tolerated with no serious adverse events. Higher blood levels of DMT correlated with stronger ratings of mystical experience, ego dissolution, and intensity, though these trends need confirmation in larger studies. Based on safety and pharmacodynamic results, 21.5 mg given as a two-phase infusion was chosen for the patient trial.
CPT Pharmacometrics & Systems Pharmacology
February 10, 2023
Emma Eckernäs, Christopher Timmermann, Robin Carhart-Harris et al.
15 citations
A single intravenous dose of DMT fully suppresses alpha brain wave power, partially suppresses beta power, and increases signal diversity (Lempel-Ziv complexity) in the EEG of 13 healthy volunteers. The concentration needed to reach half of the maximum effect (EC50) was 71 nM for alpha suppression, 137 nM for beta suppression, and 54 nM for increased complexity. Alpha suppression showed the least variability between individuals (29%), while beta suppression and complexity varied widely (75% and 77%). These quantified relationships between DMT blood levels and brain activity may help select appropriate doses and response markers in future clinical research.
Journal of Psychopharmacology
November 14, 2022
Meg J Spriggs, Bruna Giribaldi, Taylor Lyons et al.
15 citations
A fixed 25 mg dose of psilocybin produces similar acute psychedelic effects and improvements in well-being regardless of body mass index (BMI). Pooling data from three therapeutic studies, results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes, or emotional breakthroughs. There was weak evidence that lower BMI participants reported greater 'dread of ego dissolution,' but BMI did not meaningfully add to predictions beyond age, sex, and study. Mystical-type experiences and emotional breakthroughs strongly predicted well-being improvements, but BMI did not. These findings suggest body weight-adjusted dosing may be unnecessary, supporting fixed dosing to reduce practical and financial burdens on psychedelic therapy scalability.
bioRxiv (Cold Spring Harbor Laboratory)
November 9, 2023
Fernando E. Rosas, Pedro A. M. Mediano, Christopher Timmermann et al.
14 citations
preprint
Autonomic signals can reveal aspects of subjective and neural states. A Bayesian framework estimated heart rate entropy under psychedelics. Across four drugs—LSD, DMT, psilocybin, and ketamine—mean heart rate, high-frequency heart rate variability, and heart rate entropy consistently increased during the psychedelic experience. These changes predicted various dimensions of the experience. Heart rate entropy increases correlated with brain entropy increases, while other autonomic markers did not. Cost-efficient autonomic measures can reveal detail about subjective and brain states, opening new research avenues in neuroscience.
National science review
May 1, 2024
Jakub Vohryzek, Joana Cabral, Christopher Timmermann et al.
13 citations
The human brain's activity constantly reorganizes across space and time, and decomposing whole-brain recordings into harmonic modes reveals gradient-like patterns linked to different functions. Using the HADES framework, researchers analyzed brain activity in healthy participants after taking the serotonergic psychedelic DMT. They found significant decreases in contributions across most low-frequency harmonic modes during the DMT state. Specifically, the second functional harmonic, which represents the uni- to transmodal functional hierarchy, decreased, supporting the hypothesis that psychedelics alter this hierarchy. Dynamic measures of fractional occupancy, lifetime, and latent space precisely described the changes in the brain's spacetime hierarchical organization during the psychedelic state.
July 3, 2023
Hugh McGovern, Hilary Jane Grimmer, Manoj K. Doss et al.
12 citations
preprint
Psychedelics can reorient beliefs, but they may also lead to false insights and false beliefs. A review of laboratory research on false insights and false memories is connected to belief formation under psychedelics through the active inference framework. Psychedelics increase both the quantity and subjective intensity of insights and beliefs, including false ones. Future research should aim to minimize the risk of false and potentially harmful beliefs arising from psychedelics. Understanding this risk is crucial for safely leveraging the therapeutic potential of psychedelics.
Neuroscience of Consciousness
January 1, 2024
Charlotte Martial, Robin Carhart-Harris, Christopher Timmermann
9 citations
People who have had both a near-death experience (NDE) and a psychedelic experience (PE) report overlapping mystical-like effects, such as feelings of unity and transcendence, and similar attributions of reality, psychological insights, and lasting changes. However, low-level sensory phenomena differ: NDEs involve stronger disembodiment, while psychedelics produce more visual imagery. The study used an online survey of 31 adults who had experienced both an NDE (scoring ≥27 on the NDE-C scale) and a PE with classic psychedelics. Bayesian and frequentist analyses confirmed these overlaps and differences, suggesting psychedelics can model the mystical aspects of NDEs but not their sensory features.
Psychopharmacology
May 1, 2018
Mendel Kaelen, Bruna Giribaldi, Jordan Raine et al.
9 citations
correction
Music plays a central role in psychedelic therapy by helping to guide and support the therapeutic process. The article synthesizes evidence that music can influence emotional states, facilitate psychological insights, and enhance the overall therapeutic outcome when combined with psychedelic substances. The authors argue that music acts as a "hidden therapist" by directing the trajectory of the psychedelic experience, promoting emotional release, and supporting the integration of the experience afterward. This suggests that careful selection and use of music is crucial for optimizing the therapeutic benefits of psychedelic therapy.
bioRxiv (Cold Spring Harbor Laboratory)
May 31, 2024
Jakub Vohryzek, Selen Atasoy, Gustavo Deco et al.
8 citations
preprint
Psychedelic substances like DMT, psilocybin, LSD, and ketamine alter brain function by reshaping the repertoire of connectome harmonics—patterns of neural activity that depend on the brain's structural network of white matter pathways. Under DMT, the entropy of these harmonics increases, indicating a more diverse range of brain states. For the first time, changes in the energy spectrum and entropy of connectome harmonics were shown to track the intensity of subjective experience in real time, suggesting a close link between the brain's harmonic activity and conscious experience.
Communications biology
April 18, 2025
S Parker Singleton, Christopher Timmermann, Andrea I Luppi et al.
7 citations
After DMT injection, the brain requires less control energy to transition between states compared to placebo, indicating a more flexible and less constrained brain dynamic. These energy changes track with EEG signal diversity and subjective intensity of the drug experience. The regional pattern of DMT's effects aligns with serotonin 2a receptor density, and a model using receptor distribution and pharmacokinetics can predict the drug's impact on brain energy trajectories.
Communications biology
March 11, 2025
Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini et al.
6 citations
The transition into a psychedelic brain state is often overlooked in favor of static descriptions of acute effects. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the work shows that a transient of heightened reactivity in fronto-parietal regions and visual cortices correlates with serotonin 5HT2a receptor density. Simulated perturbations suggest that minimal disturbances can achieve maximal effects during this brief period, and the temporal evolution of these features aligns with pharmacokinetics. These findings indicate a mechanism for how short psychedelic episodes may exert a lasting influence over time.
bioRxiv (Cold Spring Harbor Laboratory)
July 13, 2022
Andrea I. Luppi, Justine Y. Hansen, R. Adapa et al.
5 citations
preprint
Psychoactive drugs reshape brain function by engaging multiple neurotransmitter systems simultaneously. By mapping the distribution of 19 neurotransmitter receptors and transporters (via PET) and the connectivity changes caused by 10 drugs (anesthetics, psychedelics, and stimulants), the study shows that drug effects are organized along hierarchical gradients of brain structure and function. Additionally, brain regions susceptible to drug-induced changes are also vulnerable to structural alterations from brain disorders. These findings reveal systematic links between molecular neurochemistry and large-scale functional reorganization.
Journal of Psychedelic Studies
May 30, 2025
Esenia K. Cassidy, David Dupuis, Christopher Timmermann et al.
4 citations
Attachment patterns and psychedelic use jointly influence worldview transformations and enculturation processes. Both may operate through common mechanisms: heightened epistemic trust at the psychological level and heightened serotonin 2a receptor-binding with associated hyper-plastic states at the neural level. The synthesis draws on attachment-religion research, anthropological studies of Ayahuasca use in shamanic tourism, and preliminary attachment-psychedelics research. Future research directions and ethical considerations for psychedelic-assisted therapies and cross-cultural research are outlined.
bioRxiv : the preprint server for biology
August 12, 2024
Lorenzo Pasquini, Alexander J Simon, Courtney L Gallen et al.
4 citations
preprint
The psychedelic DMT rapidly alters consciousness, producing physical transcendence, vivid auditory distortions, and visual imagery. Using simultaneous fMRI and EKG data from 14 healthy volunteers before, during, and after intravenous DMT (versus placebo), a brain substate emerged immediately after injection characterized by deactivations in the hippocampus and medial parietal cortex alongside increased superior temporal lobe activity. Hippocampal and medial parietal deactivations correlated with disruptions in the sense of time, space, and self-referential processes, reflecting a deconstruction of ordinary consciousness. Superior temporal lobe activations correlated with audio/visual hallucinations and the experience of "entities.
Journal of Psychoactive Drugs
July 14, 2023
Christopher Timmermann, Aki Nikolaidis, Alan K. Davis et al.
4 citations
Spanish translations of three questionnaires measuring acute psychedelic effects—the Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ)—showed good psychometric properties in a sample of 442 native Spanish speakers. Confirmatory factor analysis confirmed that the factor structures matched the original English versions, and this consistency held across subgroups who had used LSD or psilocybin. Construct validity was supported by positive associations between the PIQ and MEQ and between these measures and changes in cognitive fusion, alongside negative associations with changes in prosocial behaviors. Predictive validity was indicated by strong relationships between persisting effects and scores on the MEQ and PIQ. The Spanish versions can be reliably used in research with Spanish-speaking populations.
Meghan Good, Tiffanie Benway, Zelah Joel et al.
4 citations
DMT (N,N-dimethyltryptamine) is being developed as a treatment for major depressive disorder. In a phase I trial, 24 healthy adults received escalating intravenous doses of DMT fumarate (SPL026) that were safe and well-tolerated. DMT exposure increased proportionally with dose over the 9–21.5 mg range. Peak plasma concentration occurred at about 10 minutes, and the mean elimination half-life was 9–12 minutes. In vitro experiments showed that DMT is cleared by monoamine oxidase A (MAO-A) and modified by the enzymes CYP2D6 and CYP2C19. The unbound fraction of DMT in plasma was approximately 70%. These findings support the development of DMT infusion regimens for treating major depressive disorder.
Journal of psychoactive drugs
January 1, 2024
David Wyndham Lawrence, Alex P DiBattista, Christopher Timmermann
3 citations
Among 227 naturalistic DMT experiences that felt familiar, the familiarity was not attributed to a prior psychedelic experience. Most (97.4%) included features of a mystical experience, 16.3% involved ego-dissolution, and 11.0% a profound sense of death. A new questionnaire identified five themes of familiarity: feeling or knowledge gained; place or environment; the act of going through the experience; transcendent features; and familiarity imparted by an entity encounter. Two stable participant classes emerged: one class more often reported familiarity from an entity encounter and from the feeling or knowledge gained. The sense of familiarity during DMT appears non-referential to past psychedelic use.
Neuroscience and biobehavioral reviews
July 1, 2026
Marcus J Glennon, Catherine I V Bird, Prateek Yadav et al.
2 citations
Setting up a psychedelic research study involves a long, arduous, and Kafkaesque process with many unstandardised challenges. These complexities challenge existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. This review brings together major UK psychedelic research teams to formalise these unique considerations, addressing sociocultural, political, legal, pharmacological, safety, study design, and experiential facets. It identifies continuing areas of debate and provides a practical, experience-based guide with recommendations for policymakers and future researchers intending to set up a psychedelic study or clinical trial.