Psychedelic replications in virtual reality and their potential as a therapeutic instrument: an open-label feasibility study

Psychedelic-assisted therapies have seen a strong resurgence because of promising results across conditions such as depression, addiction and end-of-life distress. A central unresolved question in this literature is whether therapeutic benefit arises primarily from neurochemical action or from the subjective experiences psychedelics produce — for example mystical-type states, ego-dissolution and insight. If subjective phenomenology is a key mediator, then replicating those phenomenological elements without drugs might produce at least some therapeutic effects and offer a more accessible alternative for people who cannot, or prefer not to, take psychedelic compounds. Aday and colleagues designed a virtual reality (VR) experience called Psyrreal intended to mimic a broad set of audiovisual and narrative features of psychedelic, mystical and meditative states. This open-label feasibility study tested Psyrreal in a 2-day augmented therapeutic protocol for adults with mild-to-moderate depressive symptoms, with the main aim of assessing whether the intervention reduced depressive symptoms and whether psychedelic-like subjective factors (mystical experiences, ego-dissolution, insight) were elicited and measurable.

Study design and participants: The investigators conducted an open-label, one-group uncontrolled longitudinal feasibility study. Recruitment occurred via a public Estonian mental-health website between October and December 2021. Thirteen adults (8 women, 5 men), aged 20–58 (mean 33.8, SD 10.6), enrolled; exclusions included current depression therapy or medication, psychotic disorders, epilepsy, family history of schizophrenia, and hypersensitivity to motion sickness. After screening and re-evaluation on day 1, two participants were excluded (one on antidepressants, one whose depressive score fell below the inclusion cut-off), leaving a final analysed sample of 11; n = 10 for the primary depression follow-up measure because one participant missed the 2-week EST-Q2 questionnaire. Most participants (9/13) reported a prior diagnosis of depression. Intervention and hardware/software: Psyrreal is a purpose-built, somato-audiovisual VR application developed in Unreal Engine 4.27 and run on an HTC Vive Pro Eye headset. The experience comprises 19 distinct visual "levels" combining open-eye effects, closed-eye visuals (CEVs), large-scale vistas, and narrative elements, supported by a composed soundtrack designed to manipulate tempo and perceived time. The software is distributed on request under a Creative Commons Attribution-Non-Commercial licence. A small validation study with experienced psychedelic users (reportedly seven participants) rated similarity of some scenes and physical sensations to drug states. Procedure and psychological support: The protocol spanned two consecutive days. Day 1 comprised a 30–45 minute preparatory session with a clinical psychologist, a 15-minute demonstrative VR control (10 minutes guided meditation with eyes closed, then 5 minutes in a non-interactive living-room VR environment) and short discussion; questionnaires (EDI, PIQ, MEQ30) were administered referencing the 5-minute demo VR for baseline comparison. Day 2 began with a brief pre-session discussion, the same guided meditation, then a 45-minute Psyrreal session while the participant was seated; a psychologist was available nearby and a technician monitored equipment. After an integrative 20–30 minute session with the psychologist, EDI, PIQ and MEQ30 were re-administered. A follow-up EST-Q2 questionnaire was sent 2 weeks post-intervention. Participants were asked to abstain from alcohol/substances prior to sessions; informed consent and ethics approval (University of Tartu) were obtained. Measures and analysis: The primary symptom measure was the Emotional State Questionnaire (EST-Q2), with a depression subscale cut-off of ≥12 for inclusion. Secondary self-report measures included the Psychological Insight Questionnaire (PIQ), the Ego-Dissolution Inventory (EDI), and the Revised Mystical Experience Questionnaire (MEQ30). The Montgomery–Åsberg Depression Rating Scale (MADRS) was administered by the psychologist at baseline to validate depressive severity. Semi-structured integrative interviews were audio-recorded and thematically analysed. Quantitative before–after comparisons used paired-sample t-tests (two-tailed, α = 0.05); normality of difference scores was checked with Shapiro–Wilk. Analyses were performed in JASP. The authors also performed sensitivity analyses excluding two participants who reported seeking psychological counselling after the intervention, with results reported as similar in supplementary materials.

Sample and safety: All 13 registered participants completed the study procedures, but two were excluded from analyses as described above; the final analysed sample was 11 for most measures and 10 for the EST-Q2 follow-up. No serious adverse events were reported. Four participants (of the original 13) mentioned transient nausea during the VR session; otherwise participants were encouraged to report discomfort and none was recorded as a formal adverse event. Primary outcome — depressive symptoms: Baseline EST-Q2 depression subscale mean was 15.20 (SD = 2.66). At the 2-week follow-up (n = 10), EST-Q2 mean decreased to 11.00 (SD = 3.74). Paired-samples t-test indicated a statistically significant reduction: t(9) = 3.50, p = 0.007, Hedges' g = 1.046 (large effect). The response rate (≥50% reduction from baseline) was 18% and the remission rate (score below 12) was 60%. Baseline EST-Q2 scores correlated with clinician MADRS ratings (r = 0.66, p = 0.010). The authors note that the modest response but higher remission is partly explained by the mild-to-moderate baseline symptom levels. Secondary and subjective measures: Anxiety subscale scores of the EST-Q2 also decreased at follow-up, although baseline anxiety scores were generally low and only four participants had scores indicative of anxiety disorder (≥12). MEQ30 mean increased from 39.58 (SD = 19.57) after the demo VR to 42.73 (SD = 18.43) after Psyrreal; this change was not statistically significant, t(10) = 0.673, p = 0.520, g = 0.137. Changes in PIQ (insight) and EDI (ego-dissolution) likewise did not reach statistical significance. The authors emphasise high interindividual variability on these subjective questionnaires; one participant reported a complete mystical experience on day two, and another on day one only. Qualitative findings: Thematic analysis of integrative interviews identified several recurring themes. All participants reported some positive emotions during the experience: 55% reported calmness/peace and 55% reported joy/pleasure. Seven participants reported negative emotions (e.g., sadness, fear, anxiety), with four mentioning sadness. Forty-five per cent reported personally relevant thoughts during the session; examples included descriptions of engaging with previously inaccessible sadness and arriving at new understandings. Three participants described gaining new beneficial insights, and five reported perspective shifts. Alterations in sense of self were reported by six participants (three noting narrative self changes, four noting embodied self changes). Somatic effects during high-motion scenes were reported by 36% and described as impactful. Selected brief participant remarks illustrate these themes, e.g. participant P12: "From this place where I got in touch with this emotion [sadness] these other questions also started to unravel...".

Aday and colleagues interpret these preliminary findings as indicating that a psychedelic-inspired VR experience, delivered within a brief augmented therapeutic setting, may alleviate mild-to-moderate depressive symptoms in some people. The significant decrease in EST-Q2 scores at 2 weeks, together with a 60% remission rate, led the authors to suggest potential therapeutic utility for VR experiences tailored to mimic psychedelic phenomenology, while emphasising that causal inferences cannot be drawn from this uncontrolled feasibility design. The authors situate their results relative to prior work: effects were similar, though weaker, than those reported in psychedelic-assisted therapy and comparable to at least one earlier VR-based depression study. They highlight that measures of mystical experience, insight and ego-dissolution (MEQ30, PIQ, EDI) did not show statistically reliable group-level increases, but that qualitative interviews revealed instances of insight and self-alteration for some participants. From this pattern the investigators present tentative support for the hypothesis that subjective experience may mediate therapeutic effects, while acknowledging large interindividual variability and limited statistical power. Mechanistic considerations proposed by the authors include: amplification of emotional material by an intense VR experience that allows access to previously avoided feelings; facilitation of "letting go" and relaxation of rigid top-down beliefs (a putative mechanism in psychedelic therapy); and induction of awe or accommodation by unusual, vast, or surreal virtual stimuli which may promote psychological plasticity and new perspectives. The authors also note that purposely induced somatic sensations (e.g., strong visual motion leading to mild cybersickness) may function therapeutically when combined with preparation to surrender and integrate the experience. Limitations acknowledged by the study team are several and substantial. The intervention is an audiovisual approximation and cannot replicate all drug-induced phenomena such as full synesthesia or hyperdimensionality. The open-label, uncontrolled design, small sample size and potential expectancy effects (including the preparatory discussion, guided meditation and the demonstrative VR used as a control) limit attribution of effects to the psychedelic-like content. The authors also discuss measurement challenges: some participants reported unexpectedly high scores on MEQ30 and EDI after the short demo session, raising concerns about the suitability of these questionnaires for non-pharmacological VR contexts and the influence of prior experience and interpretation on responses. Blinding and development of appropriate placebo VR controls are noted as methodological hurdles for future trials. Finally, the investigators outline practical advantages of VR for research and therapy — greater accessibility, controllability, shorter and pausable sessions, and the ability to dissociate and test specific phenomenological components — and suggest future directions including increased interactivity, guided narration, componential experiments, better placebo controls, possible combination with sensory-deprivation or microdosing approaches, and adaptation or development of questionnaires suited to VR-induced altered states.

The authors conclude that Psyrreal, a somato-audiovisual VR experience modelled on psychedelic and mystical phenomenology, produced an alleviation of mild-to-moderate depressive symptoms in this small open-label feasibility study. They argue that VR may be a useful, controllable tool both as a potential therapeutic augmentation and as a method to investigate which subjective elements of psychedelic experiences mediate therapeutic effects. Further research — notably larger, randomised and controlled trials and development of VR-appropriate outcome measures — is recommended to evaluate efficacy and mechanisms more robustly.