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

NCT06798636 | Recruiting Early Phase 1

• 2 other identifiers: 172441IRAS ID: 330839
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Self Harm

Keywords

Psilocybin; Psychedelic; Self injury; Self-Injurious Behaviour

Outcome Measures

Primary Outcomes (5)

• Frequency of mental imagery

  Frequency scores on a 1-10 Likert scale related to self-harm and novel adaptive mental imagery

  Up to 3 months

• Vividness of mental imagery

  Vividness scores on a 1-10 Likert scale related to self-harm and novel adaptive mental imagery

  Up to 3 months

• Intensity of emotions related to mental imagery

  Emotions' intensity scores on a 1-10 Likert scale related to self-harm and novel adaptive mental imagery

  Up to 3 months

• Believability of cognitions related to mental imagery

  Cognitions' believability scores on a 1-10 Likert scale related to self-harm and novel adaptive mental imagery

  Up to 3 months

• Schemas

  Scores on Young Schema Questionnaire Short Form (Young et al., 1994)

  Up to 3 months

Secondary Outcomes (10)

• Approach Avoidance task

  Up to 5 months

• Probabilistic Reversal Learning Task

  Up to 5 months

• Self-harm Dot Probe Task

  Up to 5 months

• Difficulty in Emotional Regulation

  Up to 5 months

• Self-compassion

  Up to 5 months

Study Arms (2)

Psilocybin 5mg

EXPERIMENTAL

Participants will be given orally one 5mg psilocybin capsule.

Drug: Psilocybin 5 mg with cognitive behavioural therapy intervention

Placebo

PLACEBO COMPARATOR

Participants will be given orally one 25mg MCC inert placebo capsule.

Drug: Placebo with cognitive behavioural therapy intervention

Interventions

Psilocybin 5 mg with cognitive behavioural therapy intervention DRUG

This is an oral 5mg psilocybin dose preceding a mental imagery rescripting procedure

Also known as: Psilocybin

Psilocybin 5mg

Placebo with cognitive behavioural therapy intervention DRUG

This is an oral placebo comparator preceding a mental imagery rescripting procedure

Placebo

Eligibility Criteria

• Age: 16 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College London

London, United Kingdom

RECRUITING

Related Publications (9)

• Passie T, Guss J, Krahenmann R. Lower-dose psycholytic therapy - A neglected approach. Front Psychiatry. 2022 Dec 2;13:1020505. doi: 10.3389/fpsyt.2022.1020505. eCollection 2022.

  PMID: 36532196 BACKGROUND

• Doss MK, Povazan M, Rosenberg MD, Sepeda ND, Davis AK, Finan PH, Smith GS, Pekar JJ, Barker PB, Griffiths RR, Barrett FS. Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Transl Psychiatry. 2021 Nov 8;11(1):574. doi: 10.1038/s41398-021-01706-y.

  PMID: 34750350 BACKGROUND

• Erritzoe D, Roseman L, Nour MM, MacLean K, Kaelen M, Nutt DJ, Carhart-Harris RL. Effects of psilocybin therapy on personality structure. Acta Psychiatr Scand. 2018 Nov;138(5):368-378. doi: 10.1111/acps.12904. Epub 2018 Jun 19.

  PMID: 29923178 BACKGROUND

• Roseman L, Demetriou L, Wall MB, Nutt DJ, Carhart-Harris RL. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology. 2018 Nov;142:263-269. doi: 10.1016/j.neuropharm.2017.12.041. Epub 2017 Dec 27.

  PMID: 29288686 BACKGROUND

• Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Palenicek T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443.

  PMID: 36322843 BACKGROUND

• Holmes EA, Arntz A, Smucker MR. Imagery rescripting in cognitive behaviour therapy: images, treatment techniques and outcomes. J Behav Ther Exp Psychiatry. 2007 Dec;38(4):297-305. doi: 10.1016/j.jbtep.2007.10.007. Epub 2007 Oct 26.

  PMID: 18035331 BACKGROUND

• Hasking PA, Di Simplicio M, McEvoy PM, Rees CS. Emotional cascade theory and non-suicidal self-injury: the importance of imagery and positive affect. Cogn Emot. 2018 Aug;32(5):941-952. doi: 10.1080/02699931.2017.1368456. Epub 2017 Aug 25.

  PMID: 28838289 BACKGROUND

• Di Simplicio M, Appiah-Kusi E, Wilkinson P, Watson P, Meiser-Stedman C, Kavanagh DJ, Holmes EA. Imaginator: A Proof-of-Concept Feasibility Trial of a Brief Imagery-Based Psychological Intervention for Young People Who Self-Harm. Suicide Life Threat Behav. 2020 Jun;50(3):724-740. doi: 10.1111/sltb.12620. Epub 2020 Feb 14.

  PMID: 32057131 BACKGROUND

• Ji JL, Kavanagh DJ, Holmes EA, MacLeod C, Di Simplicio M. Mental imagery in psychiatry: conceptual & clinical implications. CNS Spectr. 2019 Feb;24(1):114-126. doi: 10.1017/S1092852918001487. Epub 2019 Jan 28.

  PMID: 30688194 BACKGROUND

MeSH Terms

Conditions

Self-Injurious Behavior

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

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

Study Officials

• Martina Di Simplicio, Dr

  Imperial College London

  PRINCIPAL INVESTIGATOR

• David Nutt, Prof

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joanna Vamvakopoulou

CONTACT

+44 (0) 7942292199; imagine@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 29, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Access Criteria: Data will be publicly available on the OSF repository.

Locations

GB (1)