Psychedelics and virtual reality: parallels and applications

Abstract

Psychedelic drugs and virtual reality (VR) each have the capacity to disrupt the rigidity and limitations of typical conscious experience. This article delineates the parallels among psychedelic and VR states as well as their potential synergistic applications in clinical and recreational settings. Findings indicate that, individually, psychedelics and VR are used in analogous ways to alter sensory experience and evoke awe. They are also both used in tandem with traditional therapies to treat a variety of mood disorders; their shared capacity to transiently alter perspective and disrupt rigid patterns of mental experience may underly their analogous and transdiagnostic therapeutic uses. In terms of their combined applications, a number of recreational users currently utilize psychedelics and VR together to enhance their experience. We propose that VR may be a useful tool for preparing hallucinogen-naïve participants in clinical trials for the sensory distortions experienced in psychedelic states. Given the critical role of “setting” in psychedelic treatment outcomes, we also detail how VR could be used to optimize the environment in psychedelic sessions. Finally, we provide considerations for future studies and detail how advancements in psychedelic and VR research can inform one another. Collectively, this article outlines a number of connections between psychedelics and VR, and, more broadly, is representative of growing scientific interest into the interactions among technology, psychopharmacology, and mental health.

Keywords

commentary cyberdelics perspective psychedelics virtual reality

Introduction

Psychedelic drugs and virtual reality (VR) are each used to disrupt the rigidity of sensory experience,^1,2 as well as enhance outcomes with mental health treatments.^3,4 Classic psychedelics include lysergic acid diethylamide (LSD), psilocybin, mescaline, and ayahuasca/N,N-dimethyltryptamine (DMT; Table 1), and they induce their acute effects primarily through serotonin 5-HT2A receptor activation.⁵ VR is defined as three-dimensional interactive environments, which users navigate via avatars.⁶ The early discourse surrounding VR was linked with psychedelic culture and the drugs’ capacity to markedly change mental experience – a reluctant connection for some in the technological community.⁷ Many in the psychedelic community, on the other hand, embraced these connections and saw VR as a socially accepted tool to introduce the public to altered states.⁸ Notably, Timothy Leary argued that cyberdelics – the fusion of psychedelic drugs and cyberculture – could reprogram the mind,⁹ and went so far as to change his popular catchphrase “turn on, tune in, drop out” to “turn on, boot up, and jack in.” Despite the early associations among psychedelics and VR, there has been a paucity of contemporary scholarly discussion in this area. This article addresses this gap by summarizing the parallels between psychedelics and VR, detailing their combined clinical and recreational applications, and discussing experimental considerations for future research.

Table 1.

Overview of the classic psychedelic drugs.

Hallucinogen	Chemical class	Potential therapeutic applications	Therapeutic mechanisms
Ayahuasca/DMT	Tryptamine	Anxiety,¹⁰ depression,¹¹ substance misuse¹²	Increased BDNF,¹¹ neurogenesis/plasticity,¹³ MAO Inhibition¹¹
LSD	Tryptamine	Anxiety,¹⁴ depression,¹⁵ substance misuse¹⁶	Amygdala and DMN alterations,¹⁷ mystical experience¹⁸
Mescaline	Phenethylamine	No clinical applications studied to-date
Psilocybin	Tryptamine	Anxiety,¹⁹ depression,²⁰ OCD,²¹ substance misuse²²	Amygdala and DMN alterations,²³ mystical experience,²² neurogenesis/plasticity²⁴

BDNF, brain-derived neurotrophic factor; DMT, N,N-dimethyltryptamine; LSD, lysergic acid diethylamide; MAO, monoamine oxidase inhibitor; OCD, obsessive-compulsive disorder.

Parallels

One connection between psychedelics and VR regards their ability to alter perceptual experience, notably visual processing. DMT, in particular, is a potent hallucinogen for immersing users into unique and vivid mental landscapes²⁵; “visions” are a characteristic effect of other classic psychedelics as well, but take on increased salience in DMT reports. At higher doses, DMT visions can “completely replace ongoing mental experience”,²⁶ and immerse individuals into what are subjectively described as “alternate universes”.²⁷ Curiosity in exploring this visual phenomenology can be a motive for usage.²⁸ Likewise, a signature feature of VR is to immerse individuals into visual environments that transcend the limitations of their physical self.²⁹ This quality has recreational and therapeutic implications. For example, visual attractiveness of virtual worlds has been shown to influence entertainment value,⁶ and virtual immersion into anxiety-provoking situations has been used in tandem with exposure therapy to enhance outcomes with anxiety disorders.³⁰ Altogether, research supports that immersion into new perceptual environments can be an important feature of psychedelic and VR experiences.

Another commonality among psychedelics and VR is their capacity to evoke awe in users, which can also have cognitive and therapeutic implications. For instance, awe has been linked to increased curiosity, better academic outcomes, and enhanced wellbeing.^31,32 When used with proper preparation, support, and integration, psychedelic experiences have been described as awe-provoking and incredibly personally meaningful: in one study in which participants were given psilocybin, two-thirds subsequently rated their session among the five most meaningful experiences of their entire lifetime.³³ Hendricks postulated that awe is an important mechanism underlying psychedelics’ therapeutic benefits, specifically by promoting unitive experiences as well as feelings of sacredness and gratitude.³⁴ In a qualitative analysis of participant accounts from a study examining psilocybin’s potential for smoking cessation, Noorani and colleagues found that the patients’ psilocybin sessions left an enduring sense of awe, and this diminished the relative importance of smoking in their lives.³⁵ Similarly, VR has emerged as a modern and accessible method of evoking awe.³⁶ One study found that awe-inducing VR environments were associated with an increased sense of perceived vastness, presence, and positive affect.³⁷ Quesnel and Riecke found that aesthetic beauty, themes of social connection, familiarity, and personalization of VR environments influenced the extent to which participants experienced awe.³⁸ Thus, psychedelics’ and VR’s potential to elicit awe is illustrative of another commonality between the two.

Researchers are also beginning to assess if, individually, psychedelics and VR can be incorporated into traditional mental health treatments to optimize therapeutic outcomes.^39,40 Indeed, in late 2018, psilocybin-assisted psychotherapy was designated to breakthrough therapy status for treatment-resistant depression by the United States Food and Drug Administration (FDA).⁴¹ Preliminary evidence from a number of recent studies suggests that, in carefully screened and monitored volunteers, psychedelic-assisted psychotherapy can potentiate remission of depression,^3,11 anxiety,^10,14,19 obsessive-compulsive disorder (OCD),²¹ end-of-life distress,²⁰ and substance misuse.^12,22 Mystical experiences,^18,42 emotional breakthrough,⁴³ ego dissolution,⁴⁴ neuroplasticity,⁴⁵ neurogenesis,^13,24,46 and decreases in default mode network (DMN) activity have each been theorized to underlie the therapeutic benefits linked to psychedelics.^17,47 It should be noted, however, that there are several limitations to much of the current research, including unstandardized dosages, homogenous samples, expectancy effects, and small sample sizes.²³ In addition, while psychedelics are non-toxic (i.e., do not damage mammalian organ systems)⁴⁸ and have low potential for abuse,⁴⁹ the drugs are not risk-free as they can lead to psychologically challenging experiences for some individuals.⁵⁰ Even with robust therapeutic support, up to a third of participants experience transient fear or panic at some point during high-dose sessions.³³ Given the potential for these intense emotional reactions, individuals with predispositions towards psychotic symptoms are generally excluded from current trials. Finally, psychedelics alone do not seem to induce serotonin syndrome⁵¹; however, the combination of a selective serotonin reuptake inhibitor (SSRI) with a monoamine oxidase inhibitor (MAOI; such as that found in ayahuasca) can produce severe serotonin syndrome. Because of this, ayahuasca retreats typically require attendees to abstain from their current medications for a month before taking the drug.

VR has been utilized in research and clinical settings to assist in treating a number of overlapping conditions as psychedelic treatment, including depression,⁴ anxiety,³⁰ OCD,⁵² and substance misuse⁵³; VR has also been incorporated into palliative care by simulating travel experiences for housebound individuals.⁵⁴ Potential risks linked to this treatment include nausea, dizziness, and seizures in epileptic patients.⁵⁵ VR has been argued to impart its therapeutic benefits through providing a benign, but vivid, setting, and to confront fears as well as by promoting memory reconsolidation completed through a safe environment and perspective.⁵⁶ Ratings of “immersion” and “presence” in virtual environments predict a number of positive outcomes when VR is combined with therapy,⁵⁷ suggesting that transcending one’s typical perspective is a critical mechanism underlying its therapeutic efficacy. Many psychiatric disorders can be characterized by rigid beliefs about one’s self and getting “stuck” in maladaptive narratives, moods, or habits.⁵⁸ Therefore, psychedelics’ and VR’s shared capacity to transiently alter perspective and disrupt rigid patterns of mental experience may be common mechanisms underlying their analogous and transdiagnostic therapeutic uses.

Next, it may be useful to directly compare the effect sizes between research integrating psychedelics or VR into therapy (Table 2). Aday et al.²³ compiled the effect sizes for long-term changes in depression after psychedelic-assisted psychotherapy, and found that η_p² ranged from 0.32 to 0.70, Hedges’ g from 0.7 to 3.2, and Cohen’s d from 0.82 to 2.3. Li and colleagues reviewed the research on VR therapy for depression and found an average Cohen’s d of 0.67,⁵⁹ but this average was derived from just two studies. A later experiment combining a self-compassion regimen and VR found an effect size of Cohen’s d = 1.11 for depression.⁴ Aday et al.’s review of the long-term effects of psychedelic drugs also assessed changes in anxiety after psychedelic treatment²³; these effect sizes ranged from η_p² = 0.27 to 0.28, Hedge’s g = 2.0–3.2 and Cohen’s d = 0.5–2.67. When reviewing the effects of VR therapy on anxiety, Opris et al. found a strong effect (i.e. Cohen’s d = 1.11) for VR compared with a waitlist control, but no effect when compared with traditional evidence-based treatments (i.e. Cohen’s d = 0.16).⁶⁰ The research on integrating psychedelics or VR into therapy for substance misuse, OCD, and end-of-life care is growing but still in its infancy, making it difficult to meaningfully compare data from the two paradigms. Nonetheless, this analysis suggests that incorporating psychedelics or VR may improve the efficacy of some therapeutic treatments, particularly in settings in which only small-to-moderate effects are achieved with traditional treatment approaches. Further research is needed to identify if incorporating both psychedelics and VR into a single therapeutic regimen would yield additive effects or if their overlapping mechanisms would limit further improvement. To inform this work, we will next address theoretical considerations of using psychedelics and VR together.

Table 2.

Effect sizes in therapy.

Authors	Drug	Dosage(s)	Study type	Measure(s)	Effect size(s)
Psychedelics
Depression (10 studies)
Agin-Liebes et al.⁶¹	Psilocybin	0.3 mg/kg	RCT	BDI; HADS-D	Cohen’s d = 1.27–1.97
Barrett et al.⁶²	Psilocybin	25 mg/70 kg	Open-label	POMS	η_p² = 0.32
Carhart-Harris et al.⁶³	Psilocybin	10, 25 mg	Open-label	BDI; HAM-D; QIDS	Hedges’ g = 2.0–3.2
Carhart-Harris et al.⁶⁴	Psilocybin	10, 25 mg	Open-label	QIDS-SR16	Cohen’s d = 2.3
Carhart-Harris et al.³	Psilocybin	10, 25 mg	Open-label	BDI; HAM-D; QIDS	Cohen’s d = 1.52–2.3
Griffiths et al.⁶⁵	Psilocybin	1 or 3 mg/70 kg, 22 or 30 mg/70 kg	RCT	BDI; HADS; HAM-D	Cohen’s d = 1.55
Lyons and Carhart-Harris⁶⁶	Psilocybin	10, 25 mg	Open-label	HAM-D; QIDS	Hedges’ g = 0.7
Roseman et al.⁶⁷	Psilocybin	10, 25 mg	Open-label	HAM-D; QIDS	Cohen’s d = 1.55
Ross et al.²⁰	Psilocybin	0.3 mg/kg	RCT	BDI; HADS	Cohen’s d = 0.82–1.32
Stroud et al.⁶⁸	Psilocybin	10, 25 mg	Open-label	QIDS	η_p² = 0.67–0.70
Anxiety (5 studies)
Agin-Liebes et al.⁶¹	Psilocybin	0.3 mg/kg	RCT	HADS-A; STAI	Cohen’s d = 0.86–2.67
Barrett et al.⁶²	Psilocybin	25 mg/70 kg	Open-label	STAI	η_p² = 0.27–0.28
Carhart-Harris et al.⁶³	Psilocybin	10, 25 mg	Open-label	STAI-T	Hedges’ g = 2.0–3.2
Carhart-Harris et al.³	Psilocybin	10, 25 mg	Open-label	STAI	Cohen’s d = 1.2–2.2
Ross et al.²⁰	Psilocybin	0.3 mg/kg	RCT	HADS-A; STAI	Cohen’s d = 0.8–1.49
VR
Authors	Study details			Measure(s)	Effect size(s)
Depression (4 studies)
Falconer et al.⁴	Combined self-compassion/VR therapy			PHQ-9; Zung SDS	Cohen’s d = 1.11
Gamito et al.⁶⁹	VR exposure therapy in war veterans			BDI	Cohen’s d = 1.16
Li et al.⁷⁰	VR games for children with cancer			CES-DC	η_p² = 0.06
Li et al.⁵⁹	Reviewed 2 VR therapy studies			BDI; HAM-D	Cohen’s d = 0.67
Anxiety (5 studies)
Botella et al.⁷¹	VR exposure therapy for panic disorder			ASI; PDSS	η_p² = 0.67–0.72
Krijn et al.⁷²	VR exposure therapy for fear of flying			FAM; FAS	Cohen’s d = 1.82–2.13
Opris et al.⁶⁰	Reviewed 23 VR exposure therapy studies			Varied	Cohen’s d = 1.11
Wallach et al.⁷³	VR CBT for public speaking anxiety			FNE; SSPS	Cohen’s d = 0.92–1.50

ASI, Anxiety Sensitivity Index; BDI, Beck Depression Inventory; CBT, cognitive behavioral therapy; CES-DC, The Center for Epidemiological Studies Depression Scale for Children; FAM, Flight Anxiety Modality questionnaire; FAS, Flight Anxiety Situations questionnaire; FNE, Fear of negative evaluation; HADS-A, Hospital Anxiety and Depression Scale (Anxiety); HADS-D, Hospital Anxiety and Depression Scale (Depression); HAM-A, Hamilton Anxiety Rating Scale; HAM-D, Hamilton Depression Rating Scale; PDSS, Panic Disorder Severity Scale; PHQ-9, Patient Health Questionnaire-9; QIDS, Quick Inventory of Depressive Symptomatology; QID-SR16, Quick Inventory of Depressive Symptomatology (Self-Report); RCT, randomized controlled trial; SSPS, Self-statements during public speaking; STAI, State-Trait Anxiety Inventory; STAI-T, State-Trait Anxiety Inventory (Trait); VR, virtual reality; Zung SDS, Zung Self Rating Depression Scale.

Combined applications

There are a number of ways psychedelics and VR can be combined to optimize the benefits of each. Already, a number of individuals use psychedelics and VR together for recreational enhancement. Entire online communities dedicated to the discussion of using VR while on psychedelics have emerged on popular websites such as Reddit. Indeed, at the time of writing, the psychedelics/VR Reddit forum had over 6000 members.⁷⁴ Members of these communities have anecdotally reported feeling greater presence and immersion into virtual worlds while on psychedelic drugs. Users have combined psychedelics with both competitive games as well as open world VR, which is less linear and allows players to explore virtual worlds more freely. While there has yet to be scientific inquiry into the use of VR with psychedelics, these naturalistic reports can be a valuable springboard for further research – Reddit and similar websites have been demonstrated as inexpensive sources for high-quality data and as cultural forums that can be facilitators of research ideas.^75,76

Combining psychedelics and VR could also have uses in therapeutic settings. For instance, simulating psychedelic hallucinations in VR may be a valuable method of preparing hallucinogen-naïve participants for the strong sensory distortions commonly experienced in psychedelic states. Suzuki et al. developed VR technology that produces visual phenomenology described as qualitatively comparable with the effects of classic psychedelic drugs, which could be co-opted for preparing participants.⁷⁷ This technology’s use as a tool to experimentally alter consciousness has the potential to open new avenues of psychological research. VR may also be useful during psychedelic sessions by optimizing the therapeutic setting, which is widely argued to be integral to the drugs’ benefits.^78,79 That is, psychedelics seem to be unique drugs in that the context they are taken in can dramatically alter their acute and long-term effects. As psychedelic research progresses, scientists may delineate which settings are most effective for therapeutic benefits, and these can be simulated in VR. In addition, it is not uncommon for individuals on psychedelic substances to want to immerse themselves into nature while under the influence of the drugs, and psychedelics have been shown to increase nature relatedness.⁶⁶ Currently, clinical trials are conducted in secured laboratories or hospitals, which do not allow for participants to be outside in natural environments. VR could synthetically circumvent this problem by simulating natural scenes that participants could explore and immerse themselves into.

Experimental considerations for future research

Although this synthesis of the literature revealed a number of connections and potential applications with psychedelic drugs and VR, there are additional ethical concerns, experimental limitations, and open questions that should be addressed. Delineation of these factors can inform future research combining psychedelics and VR. First, given the proverbial nature/technology dichotomy and divide, some in the psychedelic community may be resistant to incorporating artificial devices into psychedelic experiences that have been described as primitive, noetic, and sacred.⁸⁰ Many cultures around the world revere hallucinogenic plants for their spiritual and medicinal properties⁸¹; thus, researchers should proceed respectfully and be attendant to cultural concerns. In addition, an important distinction to keep in mind for future researchers considering combining psychedelic drugs and VR is that the perceptual changes are generated internally with psychedelics and externally with VR. While confounding internally and externally driven perceptual changes may be a transient and benign experience in healthy volunteers, it is conceivable that this could pose risk for patients with psychotic conditions characterized by pre-existing self/other and internal/external distortions. This distinction also has phenomenological – and potentially therapeutic – implications as internally driven changes by psychedelics may have a noetic quality, whereas changes triggered by VR could be perceived as artificial because they were generated by another person/technology. Speculatively, it is possible that psychedelic treatment could serve as an alternative or adjunct to VR therapy in cases where altered perspective is desired, but the virtual environment is perceived as too contrived for immersion.

A limitation to the current research is that, while VR technology can simulate some of the visual effects of psychedelic drugs, it is clear that further research and development is needed for VR to replicate the nuances of the drugs’ perceptual effects. In particular, refining VR-induced synesthesia is an area of study that is growing and can be coalesced with psychedelic research.⁸² Furthermore, future researchers should assess if these parallels and combined applications differ across various types of psychedelic drugs, as well as identify which virtual environments are most conducive to psychedelic therapy. VR offers a unique paradigm for testing the effects of environmental conditions on psychedelic experiences because researchers can systematically alter precise parameters of the environment and replicate them across experiments. Given the critical role of “setting” in psychedelic experiences and long-term outcomes,^23,77 VR could be a valuable tool for studying how to optimize treatment effects.

A final consideration concerns using theoretical advancements discovered in psychedelic research to shape VR research (and vice versa). For example, recent studies indicate that psychedelics alter an individual’s perspective and sense of self in part by inhibiting activity in the DMN – which is thought to be fundamentally involved in maintaining one’s sense of self.⁸³ Could it be, then, that VR might alter perspective through the same mechanism? If so, could VR be used to induce ego dissolution, which has been related to decreased DMN activity and positive changes in affect?⁸⁴ These remain open and intriguing empirical questions.

Conclusion

The findings presented here demonstrate numerous connections among psychedelic and VR states as well as several combined uses. Some of these parallels and applications date to the inception of VR technology but have received limited scholarly attention. Psychedelics and VR are both used to alter sensory experience, evoke awe, and are used in combination with traditional therapies to treat a variety of psychiatric conditions. VR can simulate the visual phenomenology of psychedelic states, which may be useful for preparing participants in clinical trials with the drugs. VR could also be used to optimize and tailor the therapeutic setting during psychedelic sessions. Finally, a number of recreational users currently utilize psychedelics and VR together to enhance their experience. Altogether, it is apparent that the connections between psychedelics and VR have important implications for psychological research. These findings are in line with recent increased scientific interest into the interactions among technology, psychopharmacology, and mental health.

Footnotes

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Jacob S. Aday

References

Kometer

Vollenweider

FX.

Serotonergic hallucinogen-induced visual perceptual alterations. In Halberstadt

Vollenweider

Nutt

(eds.) Behavioral neurobiology of psychedelic drugs. Springer, Berlin, Heidelberg, 2016, pp. 257–282.

Wright

WG.

Using virtual reality to augment perception, enhance sensorimotor adaptation, and change our minds. Front Syst Neurosci 2014; 8: 56.

Carhart-Harris

Bolstridge

Day

CMJ

, et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology 2018; 235: 399–408.

Falconer

Rovira

King

, et al. Embodying self-compassion within virtual reality and its effects on patients with depression. BJPsych Open 2016; 2: 74–80.

Vollenweider

Vollenweider-Scherpenhuyzen

MFI

Bäbler

, et al. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 1998; 9: 3897–3902.

Verhagen

Feldberg

van den Hooff

, et al. Understanding users’ motivations to engage in virtual worlds: a multipurpose model and empirical testing. Comput Human Behav 2012; 28: 484–495.

Chesher

Colonizing virtual reality: construction of the discourse of virtual reality, 1984–1992. Cultronix 1994; 1: 15–28.

Cranford

The social trajectory of virtual reality: substantive ethics in a world without constraints. Technol Soc 1996; 18: 79–92.

Leary

Horowitz

Marshall

Chaos & cyber culture. Berkeley, CA: Ronin, 1994.

10.

Bouso

González

Fondevila

, et al. Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of ayahuasca: a longitudinal study. PLoS One 2012; 7: e42421.

11.

Osório

Sanches

Macedo

, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Braz J Psychiatry 2015; 37: 13–20.

12.

Nunes

Dos Santos

Osório

, et al. Effects of ayahuasca and its alkaloids on drug dependence: a systematic literature review of quantitative studies in animals and humans. J Psychoactive Drugs 2016; 48: 195–205.

13.

Morales-García

de la Fuente Revenga

Alonso-Gil

, et al. The alkaloids of banisteriopsis caapi, the plant source of the Amazonian hallucinogen ayahuasca, stimulate adult neurogenesis in vitro. Sci Rep 2017; 7: 5309.

14.

Gasser

Kirchner

Passie

LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects. J Psychopharmacol 2015; 29: 57–68.

15.

Savage

Lysergic acid diethylamide (LSD-25): a clinical-psychological study. Am J Psychiatry 1952; 108: 896–900.

16.

Abramson

HA.

LSD in psychotherapy and alcoholism. Am J Psychother 1966; 20: 415–438.

17.

Muttoni

Ardissino

John

Classical psychedelics for the treatment of depression and anxiety: a systematic review. J Affect Disord 2019; 258: 11–24.

18.

Liechti

Dolder

Schmid

Alterations of consciousness and mystical-type experiences after acute LSD in humans. Psychopharmacology 2017; 234: 1499–1510.

19.

Grob

Danforth

Chopra

, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 2011; 68: 71–78.

20.

Ross

Bossis

Guss

, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol 2016; 30: 1165–1180.

21.

Moreno

Wiegand

Taitano

, et al. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry 2006; 67: 1735–1740.

22.

Garcia-Romeu

Griffiths

Johnson

MW.

Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev 2014; 7: 157–164.

23.

Aday

Mitzkovitz

Bloesch

, et al. Long-term effects of psychedelic drugs: a systematic review. Neurosci Biobehav Rev 2020; 113: 179–189.

24.

Catlow

Song

Paredes

, et al. Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Exp Brain Res 2013; 228: 481–491.

25.

Barker

SA.

N, N-dimethyltryptamine (DMT), an endogenous hallucinogen: past, present and future research to determine its role and function. Front Neurosci 2018; 12: 536.

26.

Strassman

RJ.

Human psychopharmacology of N, N-dimethyltryptamine. Behav Brain Res 1996; 73: 121–124.

27.

Gallimore

Strassman

RJ.

A model for the application of target-controlled intravenous infusion for a prolonged immersive DMT psychedelic experience. Front Pharmacol 2016; 7: 211.

28.

Metzner

Sacred vine of spirits: ayahuasca. Rochester, VT: Inner Traditions/Bear & Co., 2005.

29.

Guttentag

DA.

Virtual reality: applications and implications for tourism. Tour Manag 2010; 31: 637–651.

30.

Powers

Emmelkamp

PMG

. Virtual reality exposure therapy for anxiety disorders: a meta-analysis. J Anxiety Disord 2008; 22: 561–569.

31.

Anderson

Dixson

Monroy

, et al. Are awe-prone people more curious? The relationship between dispositional awe, curiosity, and academic outcomes. J Pers 2020; 88: 762–779.

32.

Rudd

Vohs

Aaker

Awe expands people’s perception of time, alters decision making, and enhances well-being. Psychol Sci 2012; 23: 1130–1136.

33.

Griffiths

Richards

McCann

, et al. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology 2006; 187: 268–283; discussion 284–292.

34.

Hendricks

PS.

Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy. Int Rev Psychiatry 2018; 30: 331–342.

35.

Noorani

Garcia-Romeu

Swift

, et al. Psychedelic therapy for smoking cessation: qualitative analysis of participant accounts. J Psychopharmacol 2018; 32: 756–769.

36.

Chirico

Cipresso

Yaden

, et al. Effectiveness of immersive videos in inducing awe: an experimental study. Sci Rep 2017; 7: 1218.

37.

Chirico

Ferrise

Cordella

, et al. Designing awe in virtual reality: an experimental study. Front Psychol 2018; 8: 2351.

38.

Quesnel

Riecke

BE.

Are you awed yet? How virtual reality gives us awe and goose bumps. Front Psychol 2018; 9: 2158.

39.

Aday

Davoli

Bloesch

EK.

2018: A watershed year for psychedelic science. Drug Sci Policy Law 2019; 5: 1–4.

40.

Carl

Stein

Levihn-Coon

, et al. Virtual reality exposure therapy for anxiety and related disorders: a meta-analysis of randomized controlled trials. J Anxiety Disord 2019; 61: 27–36.

41.

Aday

Bloesch

Davoli

CC.

Beyond LSD: a broader psychedelic zeitgeist during the early to mid–20th century. J Psychoactive Drugs 2019; 51: 210–217.

42.

Russ

Carhart-Harris

Maruyama

, et al. Replication and extension of a model predicting response to psilocybin. Psychopharmacology. Epub ahead of print 15 June 2019. DOI: 10.1007/s00213-019-05279-z.

43.

Roseman

Haijen

Idialu-Ikato

, et al. Emotional breakthrough and psychedelics: validation of the emotional breakthrough inventory. J Psychopharmacol 2019; 33: 1076–1087.

44.

Letheby

Gerrans

Self unbound: ego dissolution in psychedelic experience. Neurosci Conscious 2017; 2017: nix016.

45.

Greb

Cameron

, et al. Psychedelics promote structural and functional neural plasticity. Cell Rep 2018; 23: 3170–3182.

46.

da Cruz

RVL

Moulin

Petiz

, et al. A single dose of 5-MeO-DMT stimulates cell proliferation, neuronal survivability, morphological and functional changes in adult mice ventral dentate gyrus. Front Mol Neurosci 2018; 11: 312.

47.

Aday

Bloesch

Davoli

CC.

Can psychedelic drugs attenuate age-related changes in cognition and affect?

J Cogn Enhanc 2020; 4: 219–227.

48.

Nichols

DE.

Hallucinogens. Pharmacol Ther 2004; 101: 131–181.

49.

Johnson

Griffiths

Hendricks

, et al. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology 2018; 142: 143–166.

50.

Carbonaro

Bradstreet

Barrett

, et al. Survey study of challenging experiences after ingesting psilocybin mushrooms: acute and enduring positive and negative consequences. J Psychopharmacol 2016; 30: 1268–1278.

51.

Gillman

PK.

Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache 2010; 50: 264–272.

52.

Kim

, et al. Virtual reality for obsessive-compulsive disorder: past and the future. Psychiatry Investig 2009; 6: 115–121.

53.

Metcalf

Rossie

Stokes

, et al. Virtual Reality cue refusal video game for alcohol and cigarette recovery support: summative study. JMIR Serious Games 2018; 6: e7.

54.

Niki

Okamoto

Maeda

, et al. A novel palliative care approach using virtual reality for improving various symptoms of terminal cancer patients: a preliminary prospective, multicenter study. J Palliat Med 2019; 22: 702–707.

55.

Korolov

The real risks of virtual reality. Risk Manag 2014; 61: 20–24.

56.

Wilhelm

Pfaltz

Gross

, et al. Mechanisms of virtual reality exposure therapy: the role of the behavioral activation and behavioral inhibition systems. Appl Psychophysiol Biofeedback 2005; 30: 271–284.

57.

Mitrousia

Giotakos

Virtual reality therapy in anxiety disorders. Psychiatriki 2016; 27: 276–286.

58.

Holtzheimer

Mayberg

HS.

Stuck in a rut: rethinking depression and its treatment. Trends Neurosci 2011; 34: 1–9.

59.

Theng

Foo

Game-based digital interventions for depression therapy: a systematic review and meta-analysis. Cyberpsychol Behav Soc Netw 2014; 17: 519–527.

60.

Opriş

Pintea

García-Palacios

, et al. Virtual reality exposure therapy in anxiety disorders: a quantitative meta-analysis. Depress Anxiety 2012; 29: 85–93.

61.

Agin-Liebes

Malone

Yalch

, et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol 2020; 34: 155–166.

62.

Barrett

Doss

Sepeda

, et al. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci Rep 2020; 10: 2214.

63.

Carhart-Harris

Bolstridge

Rucker

, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 2016; 3: 619–627.

64.

Carhart-Harris

Roseman

Bolstridge

, et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep 2017; 7: 13187.

65.

Griffiths

Johnson

Carducci

, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol 2016; 30: 1181–1197.

66.

Lyons

Carhart-Harris

RL.

Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression. J Psychopharmacol 2018; 32: 811–819.

67.

Roseman

Demetriou

Wall

, et al. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology 2018; 142: 263–269.

68.

Stroud

Freeman

Leech

, et al. Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression. Psychopharmacology 2018; 235: 459–466.

69.

Gamito

Oliveira

Rosa

, et al. PTSD elderly war veterans: A clinical controlled pilot study. Cyberpsychology, Behavior, and Social Networking 2010; 3: 43–48.

70.

Theng

Foo

. Game-based digital interventions for depression therapy: a systematic review and meta-analysis. Cyberpsychology, Behavior, and Social Networking 2014; 17: 519–527.

71.

Botella

García-Palacios

Villa

, et al. Virtual reality exposure in the treatment of panic disorder and agoraphobia: a controlled study. Clin Psychol Psychother 2007; 14: 164–175.

72.

Krijn

Emmelkamp

PMG

Olafsson

, et al. Fear of flying treatment methods: virtual reality exposure vs. cognitive behavioral therapy. Aviat Space Environ Med 2007; 78: 121–128.

73.

Wallach

Safir

Bar-Zvi

Virtual reality cognitive behavior therapy for public speaking anxiety: a randomized clinical trial. Behav Modif 2009; 33: 314–338.

74.

Where psychedelics meet VR: /r/RiftintotheMind. (n.d.), https://www.reddit.com/r/RiftintotheMind/ (accessed 2 July 2020).

75.

Jamnik

Lane

DJ.

The use of Reddit as an inexpensive source for high-quality data. Pract Assess Res Evaluation 2017; 22: 1–10.

76.

Jensen

Helles

The internet as a cultural forum: implications for research. New Media Soc 2011; 13: 517–533.

77.

Suzuki

Roseboom

Schwartzman

, et al. A deep-dream virtual reality platform for studying altered perceptual phenomenology. Sci Rep 2017; 7: 15982.

78.

Carhart-Harris

Roseman

Haijen

, et al. Psychedelics and the essential importance of context. J Psychopharmacol 2018; 32: 725–731.

79.

Sepeda

Clifton

Doyle

, et al. Inhaled 5-methoxy-N, N-dimethyltryptamine: supportive context associated with positive acute and enduring effects. J Psychedelic Stud 2019; 1–9.

80.

Richards

WA.

Sacred knowledge: psychedelics and religious experiences. New York: Columbia University Press, 2015.

81.

Jay

Mescaline: a global history of the first psychedelic. New Haven, London: Yale University Press, 2019.

82.

Ross

Virtual reality’s new synesthetic possibilities. Telev New Media 2018; 21: 152747641880524.

83.

Lebedev

Lövdén

Rosenthal

, et al. Finding the self by losing the self: neural correlates of ego-dissolution under psilocybin. Hum Brain Mapp 2015; 36: 3137–3153.

84.

Uthaug

van Oorsouw

Kuypers

KPC

, et al. Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution. Psychopharmacology 2018; 235: 2979–2989.