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.
Nature medicine
February 6, 2026
Joshua S Siegel, Conor Liston, Ginger E Nicol et al.
10 citations
Classic psychedelics, acting at the serotonin 5-HT2A receptor, alter brain function and consciousness. Research converges on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. Evidence of therapeutic response across neuropsychiatric indications is reviewed, integrating mechanistic findings. Challenges include discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms and clinical evidence linking subjective experience to therapeutic response, risks of enhanced neuroplasticity, and questions about trial design, scalability, and regulatory approval. The growth of psychedelic science may compel a rethinking of the relationship between subjective experience and biological change in psychiatry.
PNAS nexus
April 1, 2025
Katie Zhou, David de Wied, Robin L Carhart-Harris et al.
9 citations
Delusional ideation decreased one month after a planned psychedelic experience, while magical thinking showed no change. Over 30% of participants reported hallucinogen persisting perception disorder (HPPD)-type effects at four weeks, though fewer than 1% found them distressing. Younger age, female gender, a history of psychiatric diagnosis, and baseline trait absorption predicted HPPD-like effects. Lifetime psychedelic use at baseline correlated positively with both magical thinking and delusional ideation, suggesting these traits may correlate with psychedelic use rather than being caused by it.
Frontiers in psychiatry
January 1, 2024
Matthew X Lowe, Hannes Kettner, Del R P Jolly et al.
9 citations
Ceremonial ayahuasca use is associated with significant improvements in mental health, well-being, and psychological functioning among Middle Eastern and North African (MENA) immigrants and refugees. In a longitudinal online survey of 15 primarily female participants, reductions in depression, anxiety, and shame were reported, along with increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced positive behavioral changes persisting months after ingestion. The findings suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during migration, though data are preliminary.
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.
Npj mental health research
February 7, 2025
Ari Brouwer, Joshua K Brown, Earth Erowid et al.
5 citations
Psychedelic therapy may work partly because of an overlooked temporal pattern: the initial 'come-up' phase often feels like an acute stress reaction, while the later 'come-down' phase brings positive feelings similar to recovery from illness or stress. A qualitative analysis of psilocybin experience reports from Erowid.org, using phenomenological, thematic content, and word frequency analysis, shows that negatively valenced states dominate the onset, and positively valenced states dominate the falling phase. This pattern helps explain how initially distressing altered states can ultimately resolve distress, with implications for therapeutic and theoretical understanding of psychedelic treatment.
Neuropharmacology
July 1, 2025
Brennan M Carrithers, Daniel E Roberts, Brandon M Weiss et al.
4 citations
Psychedelic therapy may hold potential for treating personality disorders by promoting adaptive changes in personality, though rigorous research is lacking. This review first examines research on psychedelics in individuals with personality disorders using the DSM-5-TR categorical model, then applies the dimensional DSM-AMPD framework to explore how psychedelics might affect self-functioning, interpersonal functioning, and pathological personality traits. The authors discuss clinical relevance, safety considerations, gaps, and recommendations for treating these complex populations.
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 psychiatric research
November 1, 2025
Felipe M Herrmann, Grant Jones, Daniel M Low et al.
Increases in meaning in life, agreeableness, mindfulness, and extraversion are the psychological changes most strongly linked to future improvements in well-being after naturalistic psychedelic use. Increases in mindfulness, emotional stability, and extraversion are most associated with later reductions in anxiety, while increased self-esteem is most tied to decreased depression. Mindfulness was the only variable ranking among the top three predictors for all three outcomes—well-being, anxiety, and depression. These differing psychological changes may explain the mental health benefits observed after psychedelic use.
International review of neurobiology
January 1, 2025
Matthew B Wall, Robin L Carhart-Harris
Functional MRI has been central to recent psychedelic research in healthy and clinical populations. Classic psychedelics such as psilocybin, LSD, and DMT acutely and profoundly disrupt normal resting-state brain connectivity, an effect likely linked to their subjective experiences and longer-term positive emotional impacts. This chapter outlines fMRI methodology and reviews current knowledge from task and resting-state studies in both non-clinical and clinical groups. Current limitations include small datasets and lack of standardization; future work should provide more data, standardize acquisition and analysis, conduct multi-modal imaging, and share data openly. fMRI remains a key tool for understanding psychedelic mechanisms and developing psychedelic-based treatments.