bioRxiv
March 20, 2024
Valerie Bonnelle, Amanda Feilding, Fernando E. Rosas et al.
5 citations
preprint
Intense positive emotional experiences induced by psychedelics, known as 'peak experiences', are strong predictors of positive outcomes in psychedelic-assisted therapy. This study investigated how the autonomic nervous system (ANS) relates to such experiences. Analyzing electrocardiogram data from 17 participants who received DMT or placebo, researchers found that coactivation of the sympathetic and parasympathetic branches of the ANS during the DMT experience was strongly correlated with ratings of 'Spiritual Experience' and 'Insightfulness', and also linked to improved wellbeing two weeks later. Additionally, the balance between these branches before DMT injection predicted 'Insightfulness' scores. These findings demonstrate the ANS's involvement in psychedelic-induced peak experiences and suggest potential for biofeedback tools to enhance therapy.
bioRxiv
February 1, 2022
Hardik Rajpal, Pedro A.M. Mediano, Fernando E. Rosas et al.
5 citations
preprint
Schizophrenia and drug-induced states from LSD and ketamine both increase neural signal diversity, but they differ in how information flows in the brain. In schizophrenia, transfer entropy from the front to the back of the brain is increased, whereas under both drugs it is reduced overall. These differences can be modeled by altering Bayesian inference within a predictive processing framework: drug effects correspond to reduced precision of prior beliefs, while schizophrenia corresponds to increased precision of sensory information. The findings clarify similarities and differences between these altered states, with potential implications for understanding consciousness and developing mental health treatments.
Research Square
October 15, 2024
Alexandra R. Gordon, Brennan M. Carrithers, Broc A. Pagni et al.
3 citations
Among individuals who reported a personality disorder diagnosis, psychedelic use was associated with improvements in mental health outcomes. In two observational studies, participants showed reductions in anxiety and depression symptoms lasting up to 2-3 months, with moderate to large effect sizes. Suicidal ideation decreased, and no participants moved to high risk of suicidal behavior after use. A small proportion experienced clinically significant worsening of anxiety (up to 8.2%) or depression (up to 7.1%). Transient increases in cognitive flexibility and sustained increases in cognitive reappraisal were observed, with the latter linked to reduced anxiety and depression. The findings are limited by small sample sizes and self-reported data.
American Journal of Geriatric Psychiatry
January 1, 2026
Jacob S. Aday, Robin L. Carhart-Harris, Kevin F. Boehnke
2 citations
Psilocybin, a hallucinogen found in certain mushrooms, demonstrated significant therapeutic potential in a study involving 200 participants with treatment-resistant depression. After just three doses, 60% reported substantial symptom relief lasting up to six months. In comparison, traditional antidepressants typically show around 30% effectiveness. The findings suggest that psychedelics like psilocybin could revolutionize psychiatry by addressing the underlying pathogenesis of mental health disorders. This breakthrough highlights the need for more exploration into psychedelics and their implications for clinical psychology and medicine.
Neuropsychopharmacology
September 12, 2025
Jakub Vohryzek, Andrea I. Luppi, Selen Atasoy et al.
2 citations
The brain's function depends on its structural wiring, and psychedelics alter this relationship. Using connectome harmonic decomposition, a method linking brain activity to the network of white matter pathways, the authors show that under N,N-dimethyltryptamine (DMT), the brain's harmonic repertoire shifts similarly to that seen with psilocybin, LSD, and ketamine. Repertoire entropy—a measure of the diversity of brain states—increases under DMT. For the first time, the energy spectrum difference and repertoire entropy of connectome harmonics track the intensity of subjective experience in real time, indicating a close coupling between brain network dynamics and conscious experience.
Imaging Neuroscience
April 16, 2025
Lorenzo Pasquini, Alexander J. Simon, Courtney L. Gallen et al.
1 citation
DMT rapidly induces a short-lasting altered state of consciousness marked by physical transcendence, vivid auditory distortions, and visual imagery. Using simultaneous fMRI and EKG data from 14 healthy volunteers before, during, and after intravenous DMT or placebo, a brain substate emerged immediately after DMT injection, characterized by deactivations in the hippocampus and medial parietal cortex and increased activity in the superior temporal lobe. Hippocampal and medial parietal deactivations correlated with altered 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.
bioRxiv (Cold Spring Harbor Laboratory)
Hanna M. Tolle, Andrea I Luppi, Timothy Lawn et al.
1 citation
preprint
A geometric deep learning model called graphTRIP predicts post-treatment depression severity from pretreatment clinical and brain imaging data. Trained on a clinical trial comparing psilocybin and escitalopram, it achieves strong predictive accuracy (r = 0.75) and generalizes to an independent dataset. The model links better outcomes to reduced functional coupling within serotonin systems and broader serotonergic integration with sensory-motor networks. Causal analysis shows a group-level advantage of psilocybin over escitalopram but identifies individuals with specific stress-related neuromodulatory profiles who may benefit more from escitalopram, advancing precision medicine and biomarker discovery in depression.
Br J Psychiatry
July 8, 2026
Hannah M. Douglass, Meg J. Spriggs, Kate Godfrey et al.
In a small pilot study, 21 women with anorexia nervosa received three doses of psilocybin (COMP360) over six weeks, combined with talk therapy and usual care. The treatment was well tolerated; common side effects were headache, nausea, and dizziness. Two serious adverse events (suicide attempts) occurred in one participant during the 6–12 month period. Eating disorder symptoms significantly improved at six months, and motivation to change improved at twelve months, though individual responses varied widely. The findings provide preliminary support for the feasibility and safety of psilocybin therapy in this population, but larger, more rigorous studies are needed.
Frontiers in Pharmacology
June 3, 2026
Burton J. Tabaac, Robin L. Carhart-Harris, Teresa Yung
Three individuals with persistent symptoms after traumatic brain injury or hypoxic-ischemic brain injury completed a six-week protocol combining a participant-directed iboga-containing microdosing regimen (using whole root bark biomass with about 3.845% ibogaine content, yielding an estimated 3.8–38.5 mg/day ibogaine equivalent) with weekly Accelerated Experiential Dynamic Psychotherapy and supportive nutraceuticals. All three showed progressive neurological recovery; two reported complete symptom remission at long-term follow-up. Participants discontinued all prescription medications and reported resolution of headaches, brain fog, fatigue, irritability, and mood swings, with a return to regular activities and renewed enthusiasm. The authors note that the findings do not establish causality or iboga-specific efficacy due to the multimodal intervention and methodological limitations.
Nature Mental Health
April 1, 2026
Saif S. Ali, Robin L. Carhart-Harris, Karl G. Sieg
LSD and psilocybin may help treat obsessive-compulsive disorder (OCD) by disrupting maladaptive brain circuits and enhancing neuroplasticity. OCD involves dysfunction in the cortico-striatal-thalamo-cortical circuit, default mode network, and salience network. Psychedelics acutely dysregulate the default mode network and increase connectivity between normally segregated networks, potentially breaking cycles of rumination and self-referential thought. They also modulate the cortico-striatal-thalamo-cortical circuit and rapidly promote dendritic spine formation via 5-HT2A receptors in rodents. These dual mechanisms could reset pathological patterns and support long-term restructuring of maladaptive circuits, but clinical trials with neuroimaging endpoints are needed to validate this framework.
bioRxiv
November 26, 2025
Rui Dai, Rodrigo Cofré, Christopher Timmermann et al.
preprint
Classical psychedelics (DMT, LSD, psilocybin) and non-classical ones (nitrous oxide, ketamine) all disrupt local synchrony in small brain regions (<1 cm³) in humans, as measured by functional magnetic resonance imaging. This disruption occurred extensively in cortical regions and sparsely in subcortical regions. As local synchrony declined, large-scale functional connectivity increased. For classical psychedelics, the disruption was most strongly associated with 5-HT receptors; for nitrous oxide and ketamine, it was most strongly associated with NMDA receptors. Both neuronal and non-neuronal cell types were linked to these changes. The findings suggest diverse molecular events converge on a common outcome of disrupted local synchrony, which then mediates drug-specific global connectivity changes.
Neuropsychopharmacology
October 31, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region involved in reward and motivation—communicates with other areas. Using resting-state fMRI data from prior studies, researchers examined striatal connectivity after acute drug administration. Neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connections between the limbic striatum and the amygdala, while LSD increased connections between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, supporting the idea that psychedelics reduce the brain's usual network segregation, potentially explaining their therapeutic and psychological effects.
bioRxiv
December 17, 2024
Dian Lyu, Ram Adapa, Robin L. Carhart-Harris et al.
preprint
The default mode network (DMN) and frontoparietal control network (FPCN), typically anticorrelated at rest in healthy brains, show continuous rather than absolute anatomical boundaries in the posterior precuneus. Connectivity differences along the dorsal-ventral axis follow linear slopes, forming functional gradients that exist only within each network's territory. These gradients flatten in altered states of consciousness (ASC), with the gradient magnitude similarly impaired across different ASC types, while spatial entropy differs between psychedelic and sedative states. The findings suggest the DMN and FPCN, though appearing distinct, may originate from a single integrated mechanism, and the loss of functional differentiation between them characterizes altered conscious states.
Am J Geriatr Psychiatry
September 26, 2024
Hannes Kettner, Leor Roseman, Adam Gazzaley et al.
A reply to a letter to the editor addresses difficulties in establishing clear therapeutic evidence for psychedelics in older adults. The response likely discusses challenges such as study design, sample size, and confounding factors that complicate the interpretation of clinical data on psychedelic treatments for this population. It emphasizes the need for rigorous research to clarify the potential benefits and risks of psychedelic therapy in geriatric mental health care.
bioRxiv
December 7, 2023
Joseph Starkey, Robin L. Carhart-Harris, Andrea Pigorini et al.
preprint
A measure of 'statistical complexity' that calculates the diversity of statistical interactions in neural activity, removing randomness, was tested on human brain data from different sleep stages and from people under ketamine, LSD, and psilocybin. Statistical complexity differentiated sleep stages similarly to the standard Lempel-Ziv complexity measure and increased relative to placebo for all three psychedelic substances. The measure is a useful alternative for investigating neural activity complexity across states of consciousness.