Evaluation of the Effect of a Single Dose of Psilocybin on Neural Correlates of Cognitive Control in Patients With Psychogenic Nonepileptic Seizures

NCT06647056 | Completed

• 1 other identifier: NIMAO/2022-2/IC01
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Psychogenic non-epileptic seizures (PNES) are functional paroxysmal motor disorders that may be clinically suggestive of epilepsy but are not associated with the electroencephysiological and electroencephalographic changes of epilepsy. Thus, hyper-connectivity of the regions of the default mode network (DMN) linked to executive control could be involved in the impairment of cognitive control capacities in patients suffering from PNES. Also, the HYCORE study (NCT02329626), showed that dysregulation of frontal regions involved in attentional and emotional regulation is correlated with motor symptoms in patients with functional neurological disorders. The researchers of this study hypothesized that psilocybin would improve cognitive control in patients with PNES.

Conditions

Psychogenic Nonepileptic Seizures; Psilocybin

Outcome Measures

Primary Outcomes (2)

• Emotional distraction in PNES patients receiving psilocybin

  Fluctuation du signal BOLD (Blood-oxygen level dependence) during a Go-No Go test

  Three days before psilocybin treatment

• Emotional distraction in PNES patients receiving psilocybin

  Fluctuation du signal BOLD (Blood-oxygen level dependence) during a Go-No Go test

  Five days after psilocybin treatment

Secondary Outcomes (22)

• Resting-state activity in brain regions involved in cognitive control in PNES patients receiving psilocybin

  Three days before psilocybin treatment

• Resting-state activity in brain regions involved in cognitive control in PNES patients receiving psilocybin

  Five days after psilocybin treatment

• Resting-state activity in brain regions of the default mode network (DMN) in patients with PNES receiving psilocybin.

  Three days before psilocybin treatment

• Resting-state activity in brain regions of the default mode network (DMN) in patients with PNES receiving psilocybin.

  Five days after psilocybin treatment

• Cognitive control abilities in patients with PNES receiving psilocybin

  Three days before psilocybin treatment

Study Arms (1)

Patients with PNES

EXPERIMENTAL

Drug: Psilocybin; Other: MRI

Interventions

Psilocybin DRUG

Administration of psilocybin 25 mg

Patients with PNES

MRI OTHER

Two standard MRI + fMRI scans before (D-3) and after (D5) treatment

Patients with PNES

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Euthymic patient according to the MINI questionnaire.
• Diagnosis of PNES confirmed by video-EEG, progressing for more than 3 months, and meeting DSM5 criteria.
• Normal brain MRI during the assessment as part of routine care
• No contraindication to stopping any antidepressant treatment for a fortnight (or 5 weeks for fluoxetine) prior to the administration of psilocybin. Other psychotropic treatments will not be interrupted.
• Patient must have given their free and informed consent and signed the consent form
• Patient must be a member of beneficiary of a health insurance plan
• Patient available for a total of 6 months follow-up.
• Good physical health and absence of unstable medical pathology. These pathologies include cardiovascular co-morbidities: history of stroke, myocardial infarction, heart failure, arrhythmia, uncontrolled hypertension (greater than 165/95 mmHg at screening); organic epileptic syndrome and active neurological comorbidities; endocrine pathologies (dysthyroid and adrenal insufficiency, type 1 diabetes or insulin-requiring type II diabetes, history of severe hypoglycaemia requiring hospital treatment); considerable impairment of liver function; glaucoma; symptomatic prostatic hypertrophy or bladder neck obstruction.
• Ability to understand and speak French

You may not qualify if:

• Serious risk of suicide according to the clinician opinion.
• High risk of adverse emotional or behavioural reaction as clinically assessed by the investigator (e.g. severe personality disorder, antisocial behaviour, severe current stress factors, lack of consequent social support).
• Active dependence on a substance according to the MINI questionnaire (excluding tobacco).
• Psychotropic treatment (anxiolytics, antipsychotics, hypnotics) modified in the last month.
• Patient with intellectual disability.
• A lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder or psychosis not otherwise specified.
• Family history of schizophrenia, schizoaffective disorder or type 1 bipolar disorder in first or second degree relatives.
• Presence of neurological comorbidities.
• Medical conditions that would preclude safe participation in the trial; for example: considerable impairment of liver function, coronary artery disease, history of arrythmia, heart failure, uncontrolled hypertension (greater than 165/95 mmHg at screening). History of stroke, severe asthma, hyperthyroid, narrow angle glaucoma, uncontrolled type I or type II diabetes or history of ketoacidosis, hyperglycaemic coma or severe hypoglycaemia with loss of consciousness.
• Participants planning to donate sperm within three months of psilocybin administration.
• Participants having sexual intercourse that could lead to pregnancy and who do not agree to use a highly effective contraceptive method (contraceptive ring, surgical contraception, implant, patch, contraceptive pill, male and female condoms, IUD) throughout their participation in the study and for at least three months after administration of psilocybin.
• Contraindications to magnetic resonance imaging.
• Allergy, hypersensitivity or other adverse reaction to previous use of psilocybin or other hallucinogens.
• Consumption of hallucinogenic substances (excluding cannabis) more than 10 times in a lifetime or in the last 2 months, regardless of frequency.
• Use of medication likely to interfere with the effects of psychedelics.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

CHU de Nîmes, Hôpital Universitaire Carémeau

Nîmes, 30029, France

Location

MeSH Terms

Conditions

Psychogenic Nonepileptic Seizures

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Ismaël CONEJERO

  CHU Nimes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2024
• First Posted: October 17, 2024
• Study Start: December 19, 2024
• Primary Completion: January 3, 2025
• Study Completion: May 22, 2025
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)