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

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.

Study Overview

• Status: Recruiting
• Conditions: Depression
• Intervention / Treatment: Other: Therapeutic Intervention with Psychedelic Virtual Reality; Other: Therapeutic Intervention with Non-Psychedelic Virtual Reality

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karl Kristjan Kaup, MSc; Phone Number: +372 5342 8489; Email: kaup.kristjan@gmail.com
• Study Contact Backup: Name: Kadi Tulver, PhD; Phone Number: +372 522 9245; Email: kadi.tulver@gmail.com

Study Locations

• Estonia
  • Harjumaa
    • Tallinn, Harjumaa, Estonia, 10138
      • Recruiting
      • Confido Medical Centre
      • Contact: Helen Kadastik, Dr; Phone Number: +372 528 6278; Email: Helen.Kadastik@confido.ee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psyrreal; Psychedelic virtual reality experience.	Other: Therapeutic Intervention with Psychedelic Virtual Reality; 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.
Sham Comparator: Routine Realms; A non-psychedelic virtual reality experience that is largely analogous to Psyrreal.	Other: Therapeutic Intervention with Non-Psychedelic Virtual Reality; 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.
No Intervention: No intervention; A conditional waiting list condition. This condition may be included, dependent on the availability of sufficient participants and resources.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Custom background questionnaire part I	Contains items regarding demographic information and prior experiences with virtual reality.	Measured at one time-point - before the virtual reality experience on the day 1 of the intervention.
Custom background questionnaire part II	Contains items on prior experiences with psychedelics and spiritual practices, and the subjective impression of the intervention.	Measured at one time-point - at the two month follow-up.
Semi-structured interview transcriptions	If the participant agrees, the post-experience integration session will be recorded and transcribed.	Measured at one time-point - immediately after the virtual reality experience on the day 1 of the intervention.

Collaborators and Investigators

• Sponsor: University of Tartu
• Collaborators: Confido Medical Centre
• Investigators: Principal Investigator: Jaan Aru, PhD, University of Tartu

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: November 22, 2023
• First Submitted That Met QC Criteria: December 15, 2023
• First Posted (Actual): December 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens
• Other Study ID Numbers: DB-RCT-PSYRREAL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No