The current version of Psyrreal is a stable release of the virtual reality experience which could already be applied in a therapeutic setting. The experience will run on most modern VR headsets, and HTC Vive Pro Eye was used for development and the experiments. Epic Games Unreal Engine (UE) 4.27 was used as the development platform and the experience was written fully in Blueprint visual scripting language. The final software is distributed as open source upon request¹, with the Creative Commons Attribution-Non-Commercial license.

Psyrreal imitates the audiovisual and narrative phenomenology reported during psychedelic experiences (57, 58, 64–74) (Figure 1). Certain elements were also included based on descriptions of pharmacologically induced and spontaneously occurring mystical experiences (29, 72, 75–81), deep meditative states (82–85), and awe-inducing experiences (86–89) as in some cases these offered more details about specific phenomena which also occur in psychedelic states. The phenomenological elements and concepts used in the experience (Table 1 and Supplementary material 7) were selected after careful study of the available literature on psychedelic (57, 58, 64–74), meditative (82–85), awe-inducing (86–89), and mystical (29, 72, 75–81) experiences, written reports (58, 59, 68, 76, 90–92) and visual replications (66, 68, 93) of such experiences.

The participants begin the experience in a virtual “real world” which starts to acquire psychedelic phenomenology and continues to progress through a total of 19 distinct visual levels incorporating and combining various psychedelic effects. The visuals for the most part consist of abstract shapes and geometric patterns that would allow participants to project their own meaning to the experience. The duration of levels varies from approximately 30 s to 2 min. A specific soundtrack was composed for Psyrreal implementing narrative (e.g., varying intensity) and perceptual (e.g., temporal alterations) aspects of psychedelic phenomenology matching the visual levels. Psyrreal was validated among participants with extensive psychedelic experiences who evaluated its similarity to psychedelic experiences (see Supplementary material 3 for more details). All participants had prior experiences with lysergic acid diethylamide (LSD) and psilocybin with five (out of seven) participants also having prior experiences with N,N-dimethyltryptamine (DMT) or Ayahuasca. Participants in the validation study were recruited via social media. Five people rated at least one scene from Psyrreal to be visually very similar (4 on a scale from 0 to 5) to psychedelic experiences. Though the experience is purely audiovisual and did not include any physical stimulation, six people also rated the physical sensations induced by Psyrreal to be very similar to those experienced under the effects of psychedelics.

Paired sample t-tests were conducted on the before and after scores of the questionnaires (EST-Q2, EDI, PIQ, and MEQ30). All tests were two-tailed with α = 0.05. Shapiro–Wilk test confirmed approximately normal distribution for the before-after differences of all datasets. All statistical analyses were conducted with JASP (98) (version 0.16.1.0).

One participant did not fill in the questionnaire at the 2-week follow-up and was therefore excluded from the analyses concerning the EST-Q2 measure. Additionally, two participants implied in their follow-up report that they had sought psychological counseling after the intervention. Because of this, we conducted an additional analysis on all questionnaires, excluding the two participants, yielding similar results which are reported in the Supplementary material 2.

We conducted an open-label feasibility study in adults (n = 11) with mild to moderate depressive symptoms. Note that n = 10 for the EST-Q2 measure, as one participant did not complete the follow up questionnaire. The experiments took place on two consecutive days with Psyrreal being implemented on the second day (see Figure 2). No adverse effects were reported during the administration of the VR experience, even though the participants were encouraged to express any discomfort. In the interviews afterward, four participants (out of 13) mentioned transient nausea during the VR experience.

Baseline EST-Q2 depression subscale results were M = 15.20 (SD = 2.66) and showed good consistency with the MADRS questionnaire results (r = 0.66, p = 0.010). There was a significant decrease in EST-Q2 scores at the 2 week follow-up (M = 11.00, SD = 3.74; paired samples t-test, t₍₉₎ = 3.50, p = 0.007, Hedges’ g = 1.046; Figure 3A). The response rate of the treatment was 18% and remission rate was 60%. The difference between the response and remission rate is largely due to the mild-to-moderate symptoms reported by the studied population. The anxiety scale results of the EST-Q2 showed a similar pattern, as scores decreased from baseline M = 10.10 (SD = 4.65) to M = 7.60 (SD = 4.14) after 2 weeks [t₍₉₎ = 3.73, p = 0.005, g = 0.459; Figure 3B].

PIQ score results were M = 24.74 (SD = 22.98) after the control condition and M = 29.09 (SD = 21.73) after the experimental condition. Paired samples t-test indicated that the change was not statistically significant [t₍₁₀₎ = 1.256, p = 0.238, g = 0.161].

EDI scores increased from M = 35.76 (SD = 21.14) after the control condition to M = 39.83 (SD = 27.77) post-experiment, but the change was not statistically significant [t₍₁₀₎ = 0.829, p = 0.426, g = 0.136]. Two participants (P2, P3) did show a large increase (>25 points) in EDI scores.

The MEQ30 average score increased from M = 39.58 (SD = 19.57) to 42.73 (σ = 18.43). The change was not statistically significant [t₍₁₀₎ = 0.673, p = 0.520, g = 0.137]. One participant (P3) reported a complete mystical experience (all MEQ30 subscales over 60) on day two. One participant (P7) reported a complete mystical experience on the first day, but not on the second.

While the changes of scores on PIQ, MEQ30 and EDI did not reach statistical significance, the results were highly varied. A thematic analysis (99) was conducted based on the transcripts of the integrative semi-structured interview sessions to investigate the effects of the intervention on individual participants. Extracts from the transcripts that were used in the thematic analysis can be found in Supplementary material 4. The analysis revealed certain themes that were often mentioned in the interviews (Table 2). All participants reported feeling some positive emotions during the experience with 55% of participants reporting calmness or peace and the same amount of people reporting feelings of joy, pleasure, or fun. Seven participants also reported negative emotions (sadness, fear, and anxiety) with four participants mentioning feeling sadness. A total of 45% of participants reported that they had personally relevant thoughts during the experience, for example, one participant mentioned: “From this place where I got in touch with this emotion [sadness] these other questions also started to unravel and I understood many of my [behavioural and cognitive] patterns,” (P12). Six participants mentioned that they did not reach any new understandings, while three did arrive at new beneficial understandings: “[.] this novel understanding that I can reprogram myself, that this essence of myself doesn’t exist—it’s very liberating. It gives me, in some sense, a vitality that I’m looking for,” (P7).

Three participants specifically highlighted a physical feeling of insight as illustrated by the following quote from participant seven: “It was a different kind of insight, like a new insight. Like a physical insight,” (P7). Five people reported changes in perspective: “[.] Like a shift in perspective - in the beginning, I was looking more at the details, afterward I was looking at the whole,” (P3). Six participants reported alterations in their sense of self with three reporting alterations in the narrative sense of self and four participants reporting alterations in the embodied sense of self. For example: “Did you experience any change or loss of your self-image or sense of self? Yes, like dissolution, yes. [.] The whole experience was so immersive that you melted into it,” (P2). A total of 36% of participants reported somatic effects during the experience: “Specifically the parts with strong motion, these almost physical experiences, those were the most impactful,” (P12).

Our augmented therapy intervention combined a therapeutic environment and discussion about one’s problems with an engaging VR experience. One potential mechanism how this intervention yields therapeutic benefits could be that the intense and different virtual experience amplifies the therapeutic process and provides an experiential route for the participant to get in touch with their emotions (102–106) as an alternative to cognitive therapies which emphasize the role of explicit verbal discussion and reasoning (107–109). According to current understandings of psychedelic therapy, psychedelic substances in contrast to conventional antidepressants serve to amplify mental content and thus help to address rather than avoid aversive memories and emotions (23, 59, 110). Some participants mentioned that they were able to access feelings that have otherwise stayed out of reach, for example one participant expressed to the psychologist: “When we met yesterday, [.] I said I could not feel sadness. We could have five more similar sessions and I still wouldn’t feel sadness. But thanks to this experience, as short as it was yesterday, suddenly this sadness arose (in me),” (P7).

A related possible mechanism is that the intensity of the experience can require relinquishing control which could result in some degree of relaxation of fixed cognitive constraints. The relaxation of top-down beliefs is suggested to be one of the possible mechanisms behind the therapeutic effects of psychedelics, wherein potentially pathological content can be accessed and overwritten (111). Letting go of control and allowing oneself to experience anything that comes up in a psychedelic experience could allow more difficult content to reach consciousness, shorten the challenging episodes and foster integration and healthy interpretation of difficult content (112, 113). This concept of “letting go” is a central element of psychedelic (59, 113, 114) and other forms of therapy (115, 116), ritual use of psychedelics (117) as well as an important part of meditative practices (84, 118–120) [see also (41)]. Psyrreal mimics the oscillating and overwhelming intensity of psychedelic experiences (68). For example, some sections of Psyrreal purposefully depict high-motion visual scenes without actual physical motion that induce quite strong physical sensations and mild symptoms of cybersickness that can be “let go” (e.g., Figure 1 “Tunnel”). Hence, this somatoaudiovisual intensity could also function as something that could be accepted or surrendered to. The beneficial effects of “letting go” were also remarked by some participants, for example: “[.] Then, at one moment, I let go, thinking that it doesn’t work like this [focusing on finding answers]. [.] Then it actually started to work, yes. [.] I think that the first half of the experience you kind of get into it or start going along with it and then the answers arrive very clearly somehow,” (P12). In our study, participants were explicitly instructed to accept and let go of any emotions that might arise during the experience. While Psyrreal does not include any explicitly affective visual stimuli (the music, however, varies in its emotional tone) most participants mentioned experiencing a wide range of emotions with some explicitly reporting “getting in touch” with their emotions (see above). Therefore, we suggest that another potential therapeutic mechanism for this type of therapy could be combining a virtual emotion-eliciting experience with the preparation of “letting go.” Somewhat similar ideas have been implemented in VR-augmented exposure therapy where people are exposed to aversive virtual stimuli to facilitate habituation, inhibition or cognitive reappraisal of the psychological reaction (121–123).

While the experience of being in virtual reality in itself might facilitate elements that could beneficially augment the therapeutic process, there could also be added value in implementing specific visual content from reports of subjective psychedelic and mystical experiences. Unusual, infinitely vast, and even surreal stimuli common to such experiences might result in emotions of surprise and awe, where the novel stimulus needs to be accommodated into existing cognitive structures (86). The necessity for accommodating vastly different and novel stimuli would require updating the existing mental framework (86, 124) and thereby lead to a state of plasticity or “insightfulness” (41). This could allow the subject to gain different perspectives, revise pathological beliefs, and come to new insights (105, 124, 125). Such effects have also been discussed in contemporary psychedelic science (111). In fact, awe has been suggested to be a central mediator of the beneficial effects of psychedelics (126) and a potential therapeutic asset for different mental health disorders, including depression (127). Psyrreal contains infinite abstract “worlds” as well as vast landscapes and cathedrals which could induce awe (87). Additionally, virtual environments which break the usual laws of physics might also require accommodation and induce states of relaxed beliefs (105, 128, 129).

Despite our efforts, we are far from claiming that Psyrreal is an exact replication of psychedelic experiences. Psychedelic experiences encompass many aspects of consciousness (32, 57, 58) that we tried to replicate within the audiovisually confined medium of virtual reality. Some elements of substance-induced psychedelic experiences are inherently impossible to be implemented in virtual reality (e.g., hyperdimensional spaces, many synesthetic elements). Also, compared to psychedelics, virtual reality has some additional aspects which could contribute to the loss of immersion in the experience. For example, people might lose their immersion due to interactive elements that fail to meet their expectations or due to the graphics not being realistic enough (130).

The open-label design, small sample size and lack of controls in our reported experiment do not allow us to make strong claims about such interventions yet. We were unable to reliably estimate the effect of the control condition on EST-Q2 scores due to the 2-day design, as such short term changes (or lack thereof) would be unlikely to reflect true effects. Hence, the main comparison in depression scores could only be evaluated at least 2 weeks after the intervention. The design was chosen after careful consideration of how to best optimize resources for the purpose of evaluating preliminary results and feasibility for conducting more expensive future studies – which we now hope to conduct. Therefore, it is also possible that an expectancy bias in the participants, initial discussion with the psychologist, guided meditation or even a brief experience of non-psychedelic virtual reality might be responsible for the decrease of depressive symptoms. This is highlighted by a few participants reporting quite high results on the Psychological Insight Questionnaire and Mystical Experience Questionnaire even on the first day. While the psychologist did not apply usual therapeutic techniques and assumed the role of an observer, simply an opportunity to discuss their problems could already have had a beneficial effect.

While MEQ30 has been validated for psychedelic compounds and it has seen some use in investigating non-pharmacological methods for inducing mystical experiences [e.g., (50, 51, 131–134)], we are not aware of any studies using non-pharmacological methods that have implemented a control/baseline measurement of MEQ30. Our results suggest some potential difficulties in using the MEQ30 with non-pharmacological methods, as multiple participants had confusing results with one participant reporting a complete mystical experience on day one and a further two participants who only very narrowly missed out on the threshold of a complete mystical experience. While it is not impossible that they actually had a real mystical experience on the first day, it is unlikely and they also did not describe their experience as such during their discussion with the psychologist. We speculate that certain inflated scores could be due to the subjective nature of the questionnaire, and/or difficulties in understanding the questions. As the MEQ30 instructions require people to compare a specific experience (in our case, the VR experience) to other previous experiences in their lives, the results are dependent on the intensity of similar experiences they have had in the past, as well as their previous experience with VR. This also relates to difficulties in understanding the questions: people with varying amounts of mystical experiences can have a very different understanding of the questionnaire items which is further exacerbated by the fact that mystical experiences are ineffable and hard to describe (35, 81). It is also possible that a VR experience by itself could incline some participants to report high scores on the MEQ30. Finally, it is possible that the participants scored higher due to not wanting to disappoint the experimenters, as the people conducting the experiment were friendly and supportive to create an environment where participants feel safe and comfortable. Though, due to the open-label design, participants were aware that the measurements on the first day served an introductory and demonstrative purpose.

The guided meditation and short demonstrative VR (used on the first day) could also be conducive to reporting high scores on the MEQ30, PIQ, and EDI. Additionally, the results of these questionnaires were compared between a 5 min long control VR and 45 min long Psyrreal, which limits the comparability of the conditions. The effects of meditation on inducing altered states of consciousness, insight, self-alterations and mystical experiences are well documented (82–84, 132), but even a short experience with VR could have some effect for a couple of reasons. First, for people who have not had much experience with VR, the experience might be something so different that it has a strong effect on them (135). Second, the content of VR might by chance be specifically relevant to the participant, as was the case for one participant (who was excluded from the analysis) who had been pondering whether they should go traveling to the mountains with their ex-spouse. As the demonstrative VR was in a small room with a balcony view onto a mountain range the participant felt it to be very personally meaningful. Third, one of the potential mediators of the beneficial effects of psychedelic experiences as well as a crucial element of mystical experiences (32, 38, 97) — ego-dissolution, might be induced to some degree in any VR experience with an altered image of the body (136, 137). While the EDI did not show a significant change from baseline, half of the participants showed relatively high (a score of over 40) results even after the demo experience on the first day and several participants mentioned alterations in their sense of self during the integrative sessions. Therefore, it can be difficult to disentangle the effects of VR and the specific psychedelic content of our designed experience. Also, blinding procedures for such methods are complicated by a bane common to psychedelic investigation — the active condition is easily distinguishable from the control condition (44, 138, 139). The issues of blinding and confounding are important to be addressed in future studies.

Although virtual reality is likely a less powerful tool than psychedelic substances (52) [but see (50)], using it to augment therapy could be beneficial for those who suffer from acute side effects of psychedelics or who prefer to avoid consuming these kinds of substances. Virtual reality could also work as a stepping stone before engaging in psychedelic therapy (101) and could be used in countries where psychedelics are not available for medical use. The duration of virtual reality experiences is also less constrained than psychedelic experiences, which (in the case of LSD) can last over 16 h (140). Virtual reality experiences can be stopped at any moment (e.g., in the case of challenging experiences) or paused if the participant would like to immediately discuss something. Virtual reality could also be a powerful tool for investigating the precise therapeutic factors of subjective (e.g., psychedelic) experiences (101) which are often confounded and contain multiple interfering interactions, as it allows to test and separate different elements and concepts that might mediate beneficial effects. In other words, virtual reality allows one to study in a controlled manner which specific subjective experiences (e.g., certain visual experiences, challenging experiences, ego-dissolution) might be beneficial for therapeutic success.

Forms of meditation, audiovisual media, engaging in physical activities (e.g., dancing and hiking) could also be used as therapeutic “amplifiers” (105), but virtual reality offers an especially powerful medium for such a tool. First, it can offer a strong sense of presence and immersion in a specific environment which might be beneficial for the efficacy of such augmentation (101). Second, virtual reality is adaptable and could be tailored to the needs and specific symptomatology of the participant as well as to different disorders (e.g., anxiety and post-traumatic stress disorder). For instance, in Psyrreal it is possible to remove and add specific parts of the experience to customize the virtual reality experience for the specific participant and the circumstances. Third, virtual reality could have some advantages in regard to inducing ego-dissolution (51, 105, 136, 141, 142) which could be one of the mechanisms behind the therapeutic effects of psychedelics (32, 38, 97). Fourth, virtual reality assisted therapeutic interventions have high satisfaction rates (143) and are often preferred by patients. This was also echoed by our participants who subjectively evaluated the potential effectiveness of such an intervention with a mean rating of 8.00 out of 10 (n = 12, SD = 2.30).

The current study highlights multiple important directions for further research. First, some participants in our study mentioned that the computer graphics and lack of interactivity led to a loss of immersion in the experience. Next iterations of Psyrreal might benefit from adding a guided narration to make certain implemented concepts (e.g., connectedness or ego-dissolution) clearer, and from incorporating more interactive elements which could be beneficial for increasing immersion in the experience (144). Technical developments in the growing field of virtual reality are likely to hugely enhance designing such therapeutic experiences and could be used to develop more immersive and ‘realistic’ experiences in the near future. Second, while Psyrreal implements a wide variety of different phenomenological aspects, it could also be interesting to investigate specific components separately to help elucidate the therapeutically beneficial factors of psychedelic experiences. Furthermore, implementing an appropriate control condition is a difficult task for VR methods which could be addressed in future research (i.e., developing suitable “placebo” VR experiences). Third, combining virtual or augmented reality with, for example, sensory deprivation methods or microdosing of psychedelics might also offer intriguing avenues of research (101, 145, 146). Fourth, the results of MEQ30 and EDI highlight some issues in using these questionnaires for VR experiences (see “Limitations”). The development of new questionnaires or adaptation of existing ones for VR could be useful to investigate the effects of similar VR-based methods more reliably.