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Patrick M. Fisher

Copenhagen University Hospital, Rigshospitalet

38 papers in the library · 1,460 citations · publishing 2014-2026

Papers

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Serotonergic psychedelics induce distinct patterns of metabolic activity and covariance within biologically informed rat brain networks

Nature Communications August 3, 2026 Frederik Gudmundsen, Julia Czurylo, Daniel Ryskamp Rijsketic et al.

Serotonergic psychedelics show therapeutic potential across neuropsychiatric disorders despite transient acute effects. These compounds share serotonin 2 A receptor agonism but differ in broader pharmacology, motivating a systematic comparison of their neurobiological effects. Here, we use [18 F]FDG-PET in rats to assess acute and one-week effects of psilocybin, LSD, and 2C-B on brain metabolic...

Psilocybin's effect on human brain synaptic plasticity.

Translational Psychiatry July 15, 2026 Annette Johansen, Pontus Plavén-sigray, Martin K Madsen et al.

Psychedelics such as psilocybin have been linked to enhanced neuroplasticity and symptom relief in affective disorders, but the neurobiological mechanisms and impact of environmental context remain unclear. Here, we tested whether a single dose of psilocybin (0.3 mg/kg) alters synaptic density in healthy individuals and whether setting-dependent subjective experience shapes this effect. Fifteen...

Multi-metric evaluations of acute psychedelic effects on fMRI brain entropy

Nature Communications June 24, 2026 Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al.

A prominent theory of psychedelics is that they increase brain entropy. Thirteen studies have evaluated psychedelic effects on fMRI brain entropy, each applying a distinct measure. Here we evaluated these metrics in an independent 28-participant healthy cohort with 121 pre- and post-psilocybin fMRI scans. We assessed relations between brain entropy and objective and subjective psychedelic drug...

Effects of psilocybin on sleep quality and brain microstructure in chronic cluster headache.

Journal of psychopharmacology (Oxford, England) May 29, 2026 Kristoffer Brendstrup‐brix, Brice Ozenne, Patrick M. Fisher et al.

Patients with chronic cluster headache (CCH) suffer from poor sleep, which may impact their brain microstructure and parenchymal clearance of waste products. Psilocybin has shown promise for the treatment of CCH and has been linked to increased neuroplasticity with possible influences on brain microstructure. To investigate the effects of psilocybin on sleep, brain water diffusivity, and...

Psilocybin acutely reduces low-frequency BOLD power and frequency-specific connectivity

bioRxiv April 13, 2026 Anders S. Olsen, Kristian Larsen, Drummond E. Mcculloch et al.

Abstract Psilocybin and other serotonergic drugs acutely alter human brain function and large-scale connectivity as measured with BOLD fMRI, but whether these effects are frequency-specific remains unknown. We applied multitaper spectral and cross-spectral analyses to resting-state fMRI data from 28 healthy volunteers scanned multiple times acutely following oral psilocybin administration (0.2...

An international mega-analysis of psychedelic drug effects on brain circuit function

Nature Medicine April 1, 2026 Manesh Girn, Manoj K. Doss, Leor Roseman et al. 8 citations

Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented...

Psychedelics distinctly alter brain entropy and complexity compared to psychostimulants

medRxiv January 16, 2026 Kristian Larsen, Patrick M. Fisher, Drummond E. Mcculloch et al. 1 citation

Classical psychedelics have regained interest for their potential to treat psychiatric and neurological disorders, and explore neural mechanisms supporting perception, cognition, and mood. Acute psychedelic effects have been linked to increases in brain complexity and entropy, but it is unclear if these changes are specific to psychedelics or reflect more general psychoactive effects. Here, we...

Psilocybin’s effect on human brain synaptic plasticity

Research Square October 10, 2025 Gitte M. Knudsen, Annette Johansen, Pontus Plavén-sigray et al.

Abstract Psychedelics such as psilocybin have been linked to enhanced neuroplasticity and symptom relief in affective disorders, but the neurobiological mechanisms and impact of environmen-tal context remain unclear. Here, we tested whether a single dose of psilocybin alters synap-tic density in healthy individuals and whether setting-dependent subjective experience shapes this effect. Fifteen...

Molecular, haemodynamic and functional effects of LSD in the human brain

medRxiv June 18, 2025 Drummond E-Wen Mcculloch, Kristian Larsen, Annette Johansen et al. preprint

In this study, we provide the first study to integrate molecular and functional neuroimaging during psychedelic drug effects in humans. Using simultaneous PET-MRI technology, we describe multiple brain actions of lysergic acid diethylamide (LSD) in healthy volunteers. We quantify the occupancy of LSD at cerebral serotonin 2A receptors and show that LSD increases global cerebral blood flow and...

Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study

Journal of Psychopharmacology February 28, 2025 Dea Siggaard Stenbæk, Emil Deleuran Poulsen, Marie Katrine Klose Nielsen et al. 15 citations

Background: Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects of a single dose have not been investigated. Aims: To investigate the pharmacokinetics, feasibility, safety and efficacy of single-dose psilocybin therapy in AUD. Methods: This...

Acute psilocybin and ketanserin effects on cerebral blood flow: 5-HT2AR neuromodulation in healthy humans.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism February 26, 2025 Kristian Larsen, Ulrich Lindberg, Brice Ozenne et al. 9 citations

Psilocin, the active metabolite of psilocybin, is a psychedelic and agonist at the serotonin 2A receptor (5-HT2AR) that has shown positive therapeutic effects for brain disorders such as depression. To elucidate the brain effects of psilocybin, we directly compared the acute effects of 5-HT2AR agonist (psilocybin) and antagonist (ketanserin) on cerebral blood flow (CBF) using pseudo-continuous...

Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression

The British Journal of Psychiatry December 5, 2024 Emma S Høgsted, Vincent Beliveau, Brice Ozenne et al. 4 citations

Background Using [ 18 F]altanserin, a serotonin 2A receptor (5-HT 2A R) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT 2A R binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT 2A R agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms...

Neurochemical characterization of 5-HT 2A R partial agonists with simultaneous PET-MRI

Journal of Cerebral Blood Flow & Metabolism November 29, 2024 Frederick A. Bagdasarian, Kristian Larsen, Deng Hong et al. 1 citation

Understanding neuromodulatory effects of serotonin 2A receptor (5-HT 2A R) agonists with diverse pharmacological profiles is relevant to advancing psychedelic-related drug applications. We performed simultaneous positron emission tomography (PET) and pharmacological magnetic resonance imaging (phMRI) in anesthetized nonhuman primates (NHP; N = 3) to examine partial agonists with varying 5-HT 2A...

Neuroimaging of Serotonergic and Psychedelic Agonist Drug Challenges in Non-Human Primates

Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition November 26, 2024 Ande Bagdasarian, Kristian Larsen, Patrick M. Fisher et al.

Motivation: Acute effects of psychedelic drugs are under-reported in neuroimaging studies, warranting further investigation of their immediate pharmacology to explore the potential to monitor treatment response with imaging. Goal(s): Our goal was to assess acute impacts of serotonergic (psychedelic and non-psychedelic) agonists on hemodynamics in non-human primates (NHP). Approach:...

Single-Dose Psilocybin Therapy for Alcohol Use Disorder: Pharmacokinetics, Feasibility, Safety, and Efficacy in an Open-Label Study

Research Square August 23, 2024 Mathias E. Jensen, Dea Siggaard Stenbæk, Catharina Messell et al. 1 citation

Abstract Background Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects a single dose have not been investigated. Aims To investigate the pharmacokinetics, feasibility, safety, and efficacy of single-dose psilocybin therapy in AUD. Methods This...

Altered states of consciousness in Danish healthy volunteers and recreational users of psilocybin and the possible impact of setting and intention: Danish validation of the five-dimensional altered states of consciousness questionnaire

Journal of Psychopharmacology August 13, 2024 Oliver Rumle Hovmand, Dea Siggaard Stenbæk, M. Madsen et al. 9 citations

Background: Psychedelic substances reliably induce marked altered states of consciousness (ASC), which may be important for lasting effects and clinical outcomes of psychedelic intervention. Several instruments are available to measure the acute psychedelic experience, of which the Five Dimensional Altered States of Consciousness Questionnaire (5D-ASC) is commonly used. The questionnaire can be...

Ketanserin exhibits dose- and concentration-proportional serotonin 2A receptor occupancy in healthy individuals: Relevance for psychedelic research

European Neuropsychopharmacology August 9, 2024 Friederike Holze, M. Madsen, Claus Svarer et al. 16 citations

The serotonin 2A (5-HT2A) receptor is an important target for drug development and the main receptor through which classical psychedelics elucidate their hallucinogenic effects. The 5-HT2A receptor antagonist ketanserin has frequently been used as a tool to block the receptor. Here, we establish the dose-occupancy relation of ketanserin and the cerebral 5-HT2A receptor in healthy participants...

Not all serotonergic psychedelics are alike - they induce distinct patterns of altered metabolic activity and connectivity

May 28, 2024 Frederik Gudmundsen, Julia Czurylo, Camilla Trang Vo et al. 1 citation preprint

Serotonergic psychedelic drugs have shown promising benefits in trials for various neuropsychiatric disorders. While the acute effects of these psychedelics last only a few hours, the positive therapeutic effects can persist long after a single administration. Serotonergic psychedelics produce their psychedelic effects by activating serotonin 2A receptors, but they differ in other...

Validation of the Danish Translation of the Revised Mystical Experience Questionnaire (MEQ30) and Possible Impact of Setting, Dose and Intention

Journal of Psychoactive Drugs January 15, 2024 Oliver Rumle Hovmand, Mathias Ebbesen Jensen, Tobias Søgaard Juul et al. 6 citations

Research suggests positive changes in both well-being and psychiatric symptoms following a psychedelic experience. One explanation may be the ability of psychedelic compounds to occasion mystical-type experiences. The Revised Mystical Experiences Questionnaire (MEQ30) is designed to assess the intensity and quality of such experiences. We examined the validity, reliability, and factor structure...

CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity

Headache The Journal of Head and Face Pain 2024 Anja Sofie Petersen, Inger Marie Sørensen, Harald Schiønning et al. 29 citations

Abstract Objective To evaluate the feasibility and prophylactic effect of psilocybin as well as its effects on hypothalamic functional connectivity (FC) in patients with chronic cluster headache (CCH). Background CCH is an excruciating and difficult‐to‐treat disorder with incompletely understood pathophysiology, although hypothalamic dysfunction has been implicated. Psilocybin may have...

Amygdala response to emotional faces following acute administration of psilocybin in healthy individuals

Neuroscience Applied December 30, 2023 Sophia Armand, Kristian Larsen, Martin K Madsen et al. 7 citations

The serotonergic psychedelic psilocybin acutely induces changes in emotional states. However, it remains unresolved whether psilocybin acutely modulates amygdala reactivity to emotions, a brain region critically involved in emotion processing. Using functional magnetic resonance imaging (fMRI), we examined in 26 healthy individuals whether amygdala responses to angry, fearful and neutral faces...

Navigating the chaos of psychedelic fMRI brain-entropy via multi-metric evaluations of acute psilocybin effects

medRxiv July 3, 2023 Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne et al. 20 citations preprint

A prominent theory of psychedelics is that they increase brain entropy. Twelve studies have evaluated psychedelic effects on fMRI brain entropy quantifications, no findings have been replicated. Here we evaluated these metrics in an independent 28-participant healthy cohort with 121 pre- and post-psilocybin fMRI scans. We assessed relations between brain entropy and plasma psilocin, brain...

Psilocybin modulation of time-varying functional connectivity is associated with plasma psilocin and subjective effects

Neuroimage October 27, 2022 Anders Lykkebo-Valløe, Brice Ozenne, Sophia Armand et al. 44 citations

Our findings suggest that the acute perceptual psychedelic effects induced by psilocybin may stem from drug-level associated decreases in the occurrence and duration of lateral and medial frontoparietal connectivity motifs. We apply and argue for a modified approach to modeling eigenvectors produced by LEiDA that more fully acknowledges their underlying structure. Together these findings...

Lasting increases in trait mindfulness after psilocybin correlate positively with the mystical-type experience in healthy individuals

Frontiers in Psychology October 5, 2022 Anna Søndergaard, Brice Ozenne, Sophia Armand et al. 35 citations

Background Psilocybin-induced mystical-type experiences are associated with lasting positive psychological outcomes. Recent studies indicate that trait mindfulness is increased 3 months after psilocybin intake, preceded by decreases in neocortical serotonin 2A receptor (5-HT 2A R) binding. However, the association between psilocybin-induced mystical-type experiences and subsequent changes in...

Psilocybin-induced reduction in chronic cluster headache attack frequency correlates with changes in hypothalamic functional connectivity

medRxiv July 10, 2022 M. Madsen, Anja Sofie Petersen, Dea Siggaard Stenbæk et al. 5 citations preprint

Abstract Chronic cluster headache (CCH) is an excruciating disorder of unknown pathophysiology, but hypothalamic dysfunction has been implicated. CCH is difficult to treat but on a case-basis, the psychedelic compound psilocybin is said to have beneficial effects. In this first-ever clinical trial ( NCT04280055 ), we evaluate in a small open-label study of CCH patients the feasibility and...