medRxiv
December 17, 2021
Anders S. Olsen, Anders Lykkebo-Valløe, Brice Ozenne et al.
4 citations
preprint
After a psychedelic dose of psilocybin, the occurrence and duration of two brain states involving lateral frontoparietal and medial fronto-parietal-cingulate coherence decrease, while a fully connected brain state increases. These changes are associated with both the level of psilocin in the blood and the intensity of the subjective drug experience. The findings suggest that the acute perceptual effects of psilocybin may arise from a shift away from specific frontoparietal connectivity motifs toward a more uniform connectivity structure. The study also proposes an improved method for modeling brain states from dynamic functional connectivity data.
Psychiatric Research and Clinical Practice
January 14, 2026
Celia Faye Jacobsen, Dea Siggaard Stenbæk, Stig Poulsen et al.
3 citations
The Compass Psychological Support Model (CPSM) used in psilocybin trials is arguably a form of bona fide psychotherapy, not merely psychological support. Its components—psychoeducation, trust, present-moment focus, and client autonomy—align with humanistic-experiential therapies like client-centered and emotion-focused therapy. These methods, such as building therapeutic alliance and reducing experiential avoidance, have established links to improved outcomes in both general psychotherapy and psilocybin treatments. Framing the CPSM as non-therapeutic undermines methodological transparency and may obscure its contribution to efficacy. Recognizing it as psychotherapy could enable optimization of therapist skills and client factors, enhancing treatment outcomes.
European Neuropsychopharmacology
January 1, 2019
M. Madsen, Daniel Burmester, Dea Siggaard Stenbæk et al.
3 citations
No Summary
Research Square
August 23, 2024
Mathias E. Jensen, Dea Siggaard Stenbæk, Catharina Messell et al.
1 citation
A single 25 mg dose of psilocybin, given with preparation and integration sessions, reduced alcohol consumption in ten adults with severe alcohol use disorder. Heavy drinking days dropped by 37.5 percentage points over 12 weeks, and drinks per day decreased by 3.4 units. Participants also reported rapid and lasting reductions in craving and increased self-efficacy. Blood levels of the active metabolite psilocin varied widely between individuals, peaking from 14 to 59 µg per liter. The open-label study, which lacked a placebo group, suggests that even a single psilocybin session may be safe and effective, but larger randomized controlled trials are needed.
Psychedelics
June 28, 2026
Joost J. Breeksema, Ulf Bremberg, Jens H. van Dalfsen et al.
Psychedelic therapies face layered complexity from interactions between pharmacological and extra-pharmacological factors, and their embeddedness in societal, legal, and regulatory systems. This is compounded by epistemic fragmentation: dominant biomedical paradigms often clash with knowledge from social sciences, humanities, or Indigenous traditions. Though interdisciplinary engagement is increasingly recognized as necessary, existing calls rarely specify structural or pedagogical conditions for operationalizing it. Addressing these complexities requires moving beyond superficial collaboration; genuine interdisciplinary progress needs researchers capable of productive friction across epistemic cultures. The authors propose cultivating T-shaped competencies and intersectoral training as a structural response to these systemic challenges.
Nature Communications
June 24, 2026
Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al.
A prominent theory holds that psychedelics increase brain entropy, but past studies have used many different entropy measures. This work analyzed 121 fMRI scans from 28 healthy adults before and after psilocybin, testing 14 entropy metrics with two brain-parcellation methods and seven denoising pipelines. Five metrics—including Shannon entropy of spatial eigendistribution, path-length, instantaneous correlations, brain-state switching, and sample entropy at short time-scales—consistently showed positive associations with psychedelic effects. However, eight metrics showed no significant effects, and Lempel-Ziv complexity gave inconsistent positive results. The entropy measures correlated poorly with each other, indicating that brain entropy is not a single, unified phenomenon.
BMC medical education
April 9, 2026
Nikita Sanati Morel, Dea Siggaard Stenbæk, Johan Lundberg et al.
Nine nurses completed a 15-week online and on-site training program to serve as facilitators in a trial of psilocybin treatment for depression in cancer patients. Subjective evaluations indicated the training supported knowledge and skill acquisition, but most nurses reported needing additional practical in-person training to feel adequately prepared. An objective assessment of verbal relational skills using role-plays showed a significant increase in only one of twelve measures, with medium to large effect sizes for six measures from pre- to post-training. The training model showed modest potential to improve outcomes, though effects were limited to role-play. The specific skills and qualifications needed for providing psychotherapeutic support in psilocybin treatment remain unclear.
Research Square
October 10, 2025
Gitte M. Knudsen, Annette Johansen, Pontus Plavén‐sigray et al.
A single dose of psilocybin increases synaptic density in the frontal cortex and hippocampus of healthy individuals, but the magnitude of this effect depends on the environment in which the experience occurs. Participants who took psilocybin in a therapeutic-like room reported more intense mystical-type experiences, longer-lasting psychological benefits, and showed greater increases in synaptic density compared to those dosed inside an MRI scanner. These findings indicate that psilocybin's neuroplastic effects are modulated by environmental context, with implications for psychedelic-assisted therapies.
medRxiv
June 18, 2025
Drummond E-Wen Mcculloch, K. M. Larsen, Annette Johansen et al.
preprint
Lysergic acid diethylamide (LSD) increases global cerebral blood flow and internal carotid artery flow without affecting artery diameter, effects opposite to those of psilocybin. Functional connectivity analyses show decreases in global connectivity (GCOR), which is negatively correlated with the increase in cerebral blood flow. An anticlockwise hysteresis loop between plasma drug levels and subjective effects suggests atypical pharmacodynamic mechanisms. These findings, derived from simultaneous PET-MRI in seven healthy volunteers, establish the dose-occupancy relation of LSD at cerebral serotonin 2A receptors and highlight neurophysiological differences from related psychedelics, providing insights for clinical development.
Frontiers in Psychology
January 24, 2023
Maria Beckman, Stig Poulsen, Manoj Doss et al.
This editorial introduces a Research Topic on the role of set and setting in psychedelic-assisted psychotherapy. It argues that the effects of psychedelic substances are profoundly shaped by the psychological state of the individual (set) and the physical, social, and cultural environment (setting), rather than being purely pharmacological. The editorial emphasizes that understanding and optimizing these contextual factors is crucial for both safe clinical practice and the design of future research. It calls for more systematic investigation into how set and setting influence therapeutic outcomes, and highlights the need to integrate these insights into training and clinical protocols to maximize the potential benefits and minimize risks of psychedelic-assisted therapy.