Effect of Psychedelic VR-augmented Therapy on Patients With Clinical Depression

Study Overview
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Brief Summary
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Research has demonstrated that psychedelic compounds possess significant therapeutic potential for a variety of disorders, including depression. Despite these findings, the underlying mechanisms driving the therapeutic efficacy of psychedelics remain elusive. Furthermore, there exists a debate over the contribution of the subjective psychedelic experience to their therapeutic benefits. In this study, virtual reality (VR) is utilized as a tool to replicate the subjective experiences induced by psychedelics, aiming to explore their impact on depressive symptoms within a clinical sample. The primary objective of this research is to examine the influence of psychedelic-like phenomenology, as simulated through VR, on depressive symptoms. The study is structured into two distinct arms: the experimental condition features 'Psyrreal,' a VR experience designed to emulate psychedelic effects and the control condition which includes 'Routine Realms,' an analogous VR experience devoid of psychedelic elements. A third waiting list condition may be included, dependent on the availability of sufficient participants and resources. Additionally, the study seeks to identify and analyze various potential mediators that might underpin the therapeutic outcomes observed.

Official Title
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Effect of Psychedelic VR-augmented Therapy on Patients With Clinical Depression

Conditions
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Depression

Intervention / Treatment
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* Other: Therapeutic Intervention with Psychedelic Virtual Reality
* Other: Therapeutic Intervention with Non-Psychedelic Virtual Reality


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persistent depressive symptoms observed during the initial screening and confirmed at baseline, as determined through a comprehensive psychiatric evaluation. Provision of written informed consent by the participant. Fluent in Estonian as a native language. Exclusion Criteria: Presence of significant impairments in vision, hearing, or balance. Active suicidal ideation or current engagement in self-harm behaviors. Note: Individuals meeting this criterion will be directed to suitable crisis intervention services. Established diagnosis of bipolar disorder. Manifestation of psychotic symptoms. History of schizophrenia, either personally or within two generations of the family lineage. Ongoing diagnosis of epilepsy, dementia, or any other neurological condition that could interfere with the effective utilization of virtual reality (VR) technology. Susceptibility to motion sickness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psyrreal<br>Psychedelic virtual reality experience. | Other: Therapeutic Intervention with Psychedelic Virtual Reality<br>* A 55-minute immersive psychedelic virtual reality experience is incorporated into a therapeutic intervention, comprising a preparatory phase and a subsequent integration session based on the individual's experience.<br>|
| Sham Comparator: Routine Realms<br>A non-psychedelic virtual reality experience that is largely analogous to Psyrreal. | Other: Therapeutic Intervention with Non-Psychedelic Virtual Reality<br>* A 55-minute immersive virtual reality experience is incorporated into a therapeutic intervention, comprising a preparatory phase and a subsequent integration session based on the individual's experience.<br>|
| No Intervention: No intervention<br>A conditional waiting list condition. This condition may be included, dependent on the availability of sufficient participants and resources. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Emotional State Questionnaire 2 depression subscale score from baseline to follow-up | Measurement of the intensity of depressive symptoms during a specified period (suitable for periods longer than a week). | Measured at 3 time-points - on the day 1 of intervention, and two weeks and two months after intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short mood questionnaire | A short questionnaire based on the Emotional State Questionnaire 2 to evaluate changes in mood on a short time-scale. | Measured at two time-points - baseline and on the day 1 of the intervention.. | 
| Emotional State Questionnaire 2 other subscales | These subscales measure symptoms of panic disorder, agoraphobia, generalized anxiety disorder, asthenia and sleeping disorder. | Measured at 3 time-points - on the day 1 of intervention and two weeks and two months after intervention. | 
| State Mindfulness Scale | Questionnaire for evaluating change in state mindfulness due to virtual reality experience. | Measured at two time-points -baseline and on the day 1 of the intervention | 
| Adapted short version of the questionnaire for the assessment of altered states of consciousness (11D-ASC) | Questionnaire to evaluate alterations in consciousness during the virtual reality experience. Some items are adapted for implementation in virtual reality and a subset of questions are omitted from the original 11D-ASC questionnaire. | Measured at one time-point - after the virtual reality experience on the day 1 of the intervention. | 
| Psychological Insight Questionnaire | Questionnaire for measuring psychological insight during acute (psychedelic) experiences. | Measured at one time-point - after the virtual reality experience on the day 1 of the intervention. | 
| Ego-Dissolution Inventory | Questionnaire for measuring the experience of ego-dissolution during the virtual reality experience. | Measured at one time-point - after the virtual reality experience on the day 1 of the intervention. | 
| Avoidance/Acceptance-Promoting Experience Questionnaire | Questionnaire for measuring changes in acceptance- and avoidance-related beliefs due to virtual reality experiences. | Measured at one time-point - after the virtual reality experience on the day 1 of the intervention. | 
| Awe Experience Scale | Questionnaire for measuring the experience of awe during the virtual reality experience. | Measured at one time-point - after the virtual reality experience on the day 1 of the intervention. |