PsiloIMAGINE: A Psychedelic-augmented Mental Imagery-based Intervention for Young People With Self-harm

Early Phase 1

Not yet recruiting

• Conditions: Self Harm
• Interventions: Drug: Psilocybin 5 mg with cognitive behavioural therapy intervention; Drug: Placebo with cognitive behavioural therapy intervention

• Registration Number: NCT06798636
• Lead Sponsor: Imperial College London

Brief Summary

Approximately 20% of young people experience self-harm behaviour in their lives. Self-harm can occur across different mental health disorders, and lead to negative outcomes and risk of suicide. Current treatments are long, costly and do not suit all young people, making it essential to research alternative treatments. Therapy combined with psychedelic drugs has recently been shown to be helpful in a variety of mental health disorders, including depression. This research project will explore the mechanisms by which combining a low dose of psychedelic psilocybin with a cognitive technique may target self-harm behaviour in young people (aged 16-25).

Previous research has shown that mental images of self-harm are common among individuals who self-harm and can increase the urge to self-harm. Imagery Re-Scripting (ImRS) is a cognitive technique that guides an individual to replace mental imagery driving self-harm with an alternative image that will instead discourage self-harm and promote alternative coping strategies. However, during ImRS individuals may fear bringing negative mental images and emotions to mind, hindering the process. Psychedelic substances can increase the ability to tolerate difficult emotions, make thinking styles more flexible and individuals more open to change. Based on this, the aim is to test if enhancing a cognitive technique with a low dose psychedelic can modify the cognitive mechanisms maintaining self- harm behaviour.

The aim is to examine the effect of a sub-hallucinogenic dose of psilocybin in combination with ImRS on cognitive processes, such as experiencing vivid mental images, and whether it can reduce these mental images and associated negative emotions in young people with recent self-harm behaviour above the effects of ImRS alone.

The hypothesis is that psilocybin could facilitate confronting the emotions that arise during ImRS and make it easier to generate new helpful mental imagery.

These experimental data could lay the foundation for future treatment development targeting self-harm in young people.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-14
• Study First Submitted QC: 2025-01-22
• Last Update Submitted: 2025-01-22
• Study First Posted: 2025-01-29
• Last Update Posted: 2025-01-29
• Study Start: 2025-03-01
• Primary Completion: 2026-08-31
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• At least 2 lifetime episodes of self-harm measured using the Self-Injurious Thoughts and Behaviours Interview (Nock et al., 2007) and at least 1 self-harm episode in the past month
• Self-harm-associated mental imagery in the past 6-weeks measured using the Self-harm Imagery Interview (Hales et al., 2011)
• Any gender
• Age: 16-25 years old
• Good command of the English language
• Mental capacity to provide written informed consent
• Participant is willing to engage in tasks showing images of self-harm
• Participant is willing to talk about mental health and self-harm behaviour
• Normal ECG and blood pressure (determined by study medic)
• Psychedelic naïve
• No recreational drug use 7 days prior to the dosing visit
• Comfortable using a computer and smartphone app for data collection, access to the internet from home and willing to have some of the study visits via video-link

Exclusion Criteria

• Current or past history of psychosis or mania in themselves or a first-degree relative
• Current severe suicidal ideation that constitutes a risk for their participation
• Have a medically significant condition which renders them unsuitable for the psychedelic component of the study (e.g., hypertension, diabetes, severe cardiovascular disease, hepatic or renal failure etc.)
• Previous psychedelic use
• Current or chronic history of kidney or liver disease
• Have previously experienced a serious adverse response after psychedelic use
• Intoxication on any of the visits, as assessed by difficulty in walking, the slurring of speech, difficulty concentrating or drowsiness
• Clinically significant head injury (e.g., requiring medical or surgical intervention) that in the opinion of the investigators, contraindicates their participation
• Severe learning disability (including dyslexia/dyspraxia) that needs support to perform daily work/school tasks
• Unwillingness or inability to follow the procedures outlined in the protocol
• Are currently using a psychoactive medication
• History of psychosurgery
• In the opinion of the study team, they are unlikely to comply with the study protocol and lifestyle restrictions that it imposes
• Unstable physical illness
• Heavy smoker
• Those needing regular specified medication that might interact adversely with psilocybin e.g., selective serotonin reuptake inhibitor, 5HT1 agonists, mirtazapine, trazodone, analgesics that have serotonergic effects (tramadol), MAOI's, antipsychotics with significant 5-HT2A receptor antagonist actions (risperidone, olanzapine, and quetiapine)
• Those unwilling to allow their GP or involved mental health practitioners to be informed of their participation
• Women of childbearing age who are not using reliable contraceptive methods
• Women of childbearing age who are unable to comply with or produce a positive pregnancy urine test

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Psilocybin 5mg	Psilocybin 5 mg with cognitive behavioural therapy intervention	Participants will be given orally one 5mg psilocybin capsule.
Placebo	Placebo with cognitive behavioural therapy intervention	Participants will be given orally one 25mg MCC inert placebo capsule.

Primary Outcome Measures

Name	Time	Method
Frequency of mental imagery	Up to 3 months	Frequency scores on a 1-10 Likert scale related to self-harm and novel adaptive mental imagery
Vividness of mental imagery	Up to 3 months	Vividness scores on a 1-10 Likert scale related to self-harm and novel adaptive mental imagery
Intensity of emotions related to mental imagery	Up to 3 months	Emotions' intensity scores on a 1-10 Likert scale related to self-harm and novel adaptive mental imagery
Believability of cognitions related to mental imagery	Up to 3 months	Cognitions' believability scores on a 1-10 Likert scale related to self-harm and novel adaptive mental imagery
Schemas	Up to 3 months	Scores on Young Schema Questionnaire Short Form (Young et al., 1994)

Secondary Outcome Measures

Name	Time	Method
Attrition	Up to 5 months	Percentage of eligible enrolled participants completing outcome assessment
Approach Avoidance task	Up to 5 months	Performance (e.g., reaction time, accuracy) to self-harm vs neutral pictures and positive vs neutral pictures on the Approach Avoidance task (Loijen et al., 2020)
Probabilistic Reversal Learning Task	Up to 5 months	Performance (e.g., reaction time, accuracy, learning rate) on the Probabilistic Reversal Learning task (Dombrovski et al., 2010)
Self-harm Dot Probe Task	Up to 5 months	Performance (e.g., reaction time, accuracy, learning rate) on the Self-harm Dot Probe Task (Constantinou et al., 2010)
Difficulty in Emotional Regulation	Up to 5 months	Scores on the Difficulty in Emotional Regulation Scale (Hallion et al., 2018)
Self-compassion	Up to 5 months	Scores on the Self-compassion scale (Neff, 2003)
Motivation for Reducing Self-harm	Up to 5 months	Scores on the State Motivation for Reducing Self-harm scale (Robinson et al., 2016)
Mystical Experience	Up to 5 months	Scores on the Mystical Experience questionnaire (Barrett et al., 2015)
Challenging Psychedelic Experience	Up to 5 months	Scores on the Challenging Experience questionnaire (Barrett et al., 2016)
Emotional Breakthrough	Up to 5 months	Scores on the Emotional Breakthrough inventory (EBI; Roseman et al., 2019)