Clinical trial NCT06798636: PsiloIMAGINE: A Psychedelic-augmented Mental Imagery-based Intervention for Young People With Self-harm
Official title: Investigating the Effects of a Psychedelic-augmented Mental Imagery-based Intervention for Young People With Self-harm Behaviour: an Experimental Medicine Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Self Harm
Keywords: Psilocybin
Psychedelic
Self injury
Self-Injurious Behaviour
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2025-01-29
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Frequency of mental imagery
timeFrame: Up to 3 months
measure: Vividness of mental imagery
timeFrame: Up to 3 months
measure: Intensity of emotions related to mental imagery
timeFrame: Up to 3 months
measure: Believability of cognitions related to mental imagery
timeFrame: Up to 3 months
measure: Schemas
timeFrame: Up to 3 months
Secondary outcomes:
measure: Approach Avoidance task
timeFrame: Up to 5 months
measure: Probabilistic Reversal Learning Task
timeFrame: Up to 5 months
measure: Self-harm Dot Probe Task
timeFrame: Up to 5 months
measure: Difficulty in Emotional Regulation
timeFrame: Up to 5 months
measure: Self-compassion
timeFrame: Up to 5 months
measure: Motivation for Reducing Self-harm
timeFrame: Up to 5 months
measure: Mystical Experience
timeFrame: Up to 5 months
measure: Challenging Psychedelic Experience
timeFrame: Up to 5 months
measure: Emotional Breakthrough
timeFrame: Up to 5 months
measure: Attrition
timeFrame: Up to 5 months
Other outcomes:
Locations:
Study officials:
affiliation: Imperial College London
name: Martina Di Simplicio, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: David Nutt, Prof
role: PRINCIPAL_INVESTIGATOR
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