Psilocybin in Functional Neurological Disorder

Study Overview
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Brief Summary
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The goal of this study is to learn about the brain network response in people who have functional neurological disorder who are administered with a single dose of the psychedelic psilocybin with therapeutic support. The main question it aims to answer is: Can the default mode network, a brain network thought to be relevent in FND, be modified by the administration of psilocybin based on functional magnetic resonance imaging before and after the dose?

Official Title
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Probing the Functional Magnetic Resonance Imaging Response to Psilocybin in Functional Neurological Disorder (PsiFUND)

Conditions
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Functional Neurological Disorder

Intervention / Treatment
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* Drug: Psilocybin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 25 - 60 years. Fluent in the English language A diagnosis of FND from a neurologist and/or neuropsychiatrist as per DSM-5 criteria Moderate or severe symptoms (≥4 on Clinical Global Impression Severity (CGI-S) scale) which have been present for >12 months and have failed to respond to best available treatment. Able to tolerate fMRI scanning procedures. Failed to respond is defined as an inadequate response to a full course of FND-specific therapy, including psychological therapy (cognitive behavioural therapy) or physiotherapy. Either therapy must have been undertaken by a suitably trained expert in FND and must have been specifically targeted at FND symptoms. Exclusion Criteria: Diagnosis of severe depression (defined as meeting DSM-5 criteria) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of bipolar affective disorder (defined as meeting DSM-5 criteria for bipolar I or bipolar II) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of a psychotic disorder (defined as meeting DSM-5 criteria) on the MINI 7.0, EXCEPT substance/medication induced psychotic disorder where the duration was limited to the acute period of direct intoxication with the substance/medication. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of drug or alcohol dependence disorder (defined as meeting DSM-5 criteria) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of a personality disorder (defined as meeting DSM-5 criteria) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of any dementia (defined as meeting DSM-5 criteria for any dementia disorder) based on clinical interview by a psychiatrist. Diagnosis of any autistic spectrum disorder (defined as meeting DSM-5 criteria for any dementia disorder) based on clinical interview by a psychiatrist. Diagnosis of any learning disability (defined as meeting DSM-5 criteria for any dementia disorder) based on clinical interview by a psychiatrist Significant suicidal behaviour in past 12-months defined using the Columbia-Suicide Severity Rating Scale (C-SSRS) and confirmation based on clinical interview by a psychiatrist Any other factor which would render the participant unsuitable for psilocybin and/or interfere with a supportive therapeutic relationship and/or preclude safe follow-up. Those unable to give informed consent Medical diagnosis incompatible with psilocybin treatment (see Section 8.2.1) Inability to provide a screening blood sample, urine sample or electrocardiogram. Biochemical abnormalities (defined as falling outside the normal reference range) as evaluated by a full blood count, full biochemistry profile and thyroid function tests. Biochemical abnormalities must also be determined as clinically significant by a medical doctor to fulfil the criterion for exclusion. Electrocardiographic abnormalities, defined as any abnormality that is not normal sinus rhythm and determined as clinically significant by a medical doctor. Women of childbearing potential not using contraception. Pregnant or breast-feeding women. Non-registration with a GP or failure to consent to sharing of the GP summary care record and any psychiatric assessments held. Those enrolled in another clinical or research study. Use of any psychedelic substances >2 times in past 12 months. Any factor which would exclude the participant from magnetic resonance imaging (e.g., presence of metal)

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study arm<br>Psilocybin with therapeutic support | Drug: Psilocybin<br>* Psilocybin 25mg PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in functional connectivity in default mode network |  | One week prior dosing versus one week post dosing (intra-subject) |