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Employing Synergistic Interactions of Virtual Reality and Psychedelics in Neuropsychopharmacology

Authors:
Employing Synergistic Interactions of Virtual Reality and Psychedelics in
Neuropsychopharmacology
Matthew Moroz*
University of Nevada, Reno
Robin L. Carhart-Harris
Imperial College London
ABSTRACT
The increased prevalence of various psychiatric disorders continue
to concern [54, 71, 96]. Promising results are starting to emerge
from recent experimental interventions employing VR [32,81], and
psychedelics [14, 69] individually. We propose that for certain
pathologies researchers need not bother themselves as to which
medium offers greater hope. Instead, we hypothesize that the most
effective interventions shall necessarily come from a composite
approach utilizing both.
Traditional medicine adopts similar such synergistic strategies.
Combining codeine and acetaminophen increases the analgesic ef-
fect. While research into the therapeutic effects of novel interven-
tions using VR and psychedelics, independent of one another, is
still in its infancy, we believe that the increased utility of a dual
approach justifies closer examination without delay. We posit three
main benefits from this integrated intervention. Increases in the
efficacy of each individual paradigm due to synergistic coupling,
and increases in specificity due to the ability to tailor bespoke ther-
apies for particular individuals and groups, are achieved directly.
Such increases in efficacy consequently lead to the third benefit of
allowing a therapeutic effect to be achieved while using lower doses
of a given psychedelic compound [19].
Index Terms:
Human-centered computing—Human computer
interaction (HCI)—Interaction paradigms—Virtual reality; Applied
computing—Law, social and behavioral sciences—Psychology
1 INTRODUCTION
The dawn of highly immersive virtual reality (VR) has coincided
somewhat with a renewed acceptance of psychedelic medicine re-
search [94]. While VR promised much as far back as the 1980s,
psychedelic medicine offered similar promise in the 1950s and 1960s.
The labeling of lysergic acid diethylamide (LSD) and others as
“drugs of abuse” all but put an end to exploration into psychedelics
as possible alternative therapeutic choices. Some 50 or so years later
we see the use of psychedelics in medicine gradually shrugging off
the burden of taboo.
Compounds such as psilocybin, LSD, ketamine, and MDMA offer
renewed hope for those suffering from various psychiatric disorders
including treatment-resistant depression, anxiety, post-traumatic
stress disorder (PTSD), and addiction. The ability of VR to hijack
the human sensorimotor system creates a similar novel therapeutic
potential for applications in mental health. Among the pathologies
put forth as ideal candidates for VR applications are those very same
psychiatric disorders best suited to psychedelic medicine.
Rather than deciding which novel intervention holds the greatest
potential for treatment, we advance a theory that in many cases an
optimum solution necessarily incorporates both techniques. VR is
at its most useful when immersion, and consequently, the user’s
*mmoroz@nevada.unr.edu
r.carhart-harris@imperial.ac.uk
sense of presence, is maximized. This psychological perception
of ‘being in’ the virtual environment (VE) [82] can be increased
by employing psychedelics due to their inherent ability to heighten
suggestibility [11, 88]. The benefits of such mediation are two-fold.
While an elevation of presence is our primary goal, we may also
imagine increased usefulness of virtual avatars due to a leveling out
of the uncanny valley [17,61, 87].
As with VR, environmental setting and sensory stimuli are every-
thing [46, 89]. Minor changes in stimulus may profoundly alter a
users experience. Psychedelic treatments tend to take place within
extremely controlled environments. A sterile medical laboratory
setting provides the necessary safety required when employing such
compounds. Composite treatment solutions employing VR afford
similar control of surroundings while adding far greater opportuni-
ties to evoke specific cognitive and emotional responses [22].
The ability of psychedelics to increase presence, and the ability
of VR to provide controlled sensory stimuli creates the potential for
powerful bespoke treatment solutions. The individual interventions
not only complement each other but offer synergistic interactions
whereby each increases the efficacy of the other. Although ‘ab-
sorption’ (openness to absorbing and self-altering experiences) [93]
initially seems like a synonym for ‘presence’, they are not only differ-
ent but research has shown no significant correlation [67]. We may
argue that a composite intervention involving VR and psychedelics
has the potential to take patients beyond the usual sense of VR
presence and into the realm of absorption resulting in even greater
susceptibility [93].
Current upward trends in prevalence for various psychiatric disor-
ders [4, 21, 54, 71,96] are of great concern. Speculation continues as
to the underlying causes of these shifts while many posit the effects
of modern life [20, 37]. This position comes in different forms
such as increased social isolation and loneliness [50, 65], sedentary
lifestyles [25, 59], distractions of modern technologies [30, 31, 49],
and over prescription [97]. The prevalence of depression in the
U.S. increased from 6.6% to 7.3% from 2005 to 2015. Even more
worrying is the 8.7% to 12.7% change among 12 to 17 year olds [96].
Whatever the factors influencing such swings might be, we must
explore all therapeutic solutions, however novel, which offer hope
to those individuals and communities increasingly impacted.
2 TH E IMPORTANCE OF STIMULUS
Technology is finally at a level at which fully immersive VR sim-
ulations are possible. Successful evocation of immersion and the
resulting sense of presence is ultimately dependent upon the incom-
ing sensory stimuli. Visual, auditory, haptic, proprioceptive, and
motor cues in the form of efference copy, should closely match
expectations within the brain. When VR delivers with the neces-
sary fidelity the opportunity for sensory hijack and immersion is
maximized [43].
Incoming sensory stimuli possess an equivalent capacity to make
or break a user’s psychedelic experience. Switching out Black
Sabbath’s ’Paranoid’, for The Orb’s ’Slug Dub’ may go much further
than effecting the enjoyment of the soundtrack which accompanies
their trip. Visual perception, mood, and indeed the character of the
entire experience may be fundamentally altered for the better or
worse depending solely on audition [47, 48, 89].
3 MU TUA L INCREASES OF EFFIC AC Y
In defining VR as a technology which provides a space in
which immersive VEs are increasingly possible, we may describe
psychedelics as a catalyst which enhances sensitivity to this space.
Evolution of interactive technologies shall further boost immersion
and presence [63]. What technology lacks, however, is the ability to
directly suppress the brain’s natural reality-testing circuits [5,40, 44].
These circuits, which ordinarily serve to protect against immer-
sion, are desensitized by psychedelics. We may, therefore, label
psychedelics “pro-immersion” compounds able to increase the effi-
cacy of VR as a tool for good.
This increase in efficacy runs both ways. Treatments employing
psychedelics to reduce symptoms in the psychiatric disorders previ-
ously described have shown promising results. Treatments of this
nature tend to be restricted by location and setting due to concerns of
safety. The potency of such interventions may be improved for cer-
tain individuals using VR. The addition of VR simulations tailored
for a given pathology leads to no reduction in safety or control. We
maintain the physical setting of sterile medical laboratory together
with an accompanying psychiatrist/psychotherapist. The real world
set-up shall remain almost unchanged. By donning head mounted
displays, however, the patient may by taken to a far more effective
VE, and the therapist may join when necessary in the form of an
avatar.
A carefully constructed VR simulation enables us to strategically
guide the experience. In a similar way that music therapy may
be applied in order to induce immersive experiences [80] we may
strategically employ VR in order to evoke a specific cognitive re-
sponse. By targeting a given pathology in this way we may attempt
to alter perception in a precisely defined way. Current psychedelic
treatments delivered in a laboratory together with a mental health
professional have a non-trivial probability of evoking additional
anxiety due to increased feelings of self-consciousness. Immersing
a patient in VR helps mitigate the effect by decreasingly the overtly
clinical nature of their surroundings [64], and therefore enabling the
patient’s experience to develop in a more consistently positive way.
4 CA ND IDATE PATHOLOGIES
The improvements already described offer extra optimism for the
success of these promising novel treatment paradigms. Certain
psychiatric disorders may not require specific sensory stimulation.
Psychedelics alone may be enough to break a patient out of a spiral
of delusional or negative thoughts/behaviors. However, it is in those
pathologies most benefiting from specific sensory stimulation and
maximal immersion which we focus on. In such cases the synergistic
fusion of VR and psychedelics offers an optimal therapeutic solution
for breaking the delusion and evoking a psychological ‘reset’ [15].
Phobias can have a debilitating impact on the lives of sufferers [42,
78]. Body dismorphic disorder (BDD) holds a similar power to
cause extreme psychological distress [38, 74]. Both conditions offer
difficulties in daily functioning by focusing the sufferer in on a
specific anxiety inducing delusion [75, 76, 86]. It is the very fact
that the misappraisal relates to something concrete which advances
these conditions as prime candidates for the prescribed composite
intervention. Knowledge regarding the offending misconception
allows us to target it directly.
Thus far we have discussed VR and psychedelics in very general
terms. However, it is in the increased efficacy from specificity (analo-
gous to the improvements in therapeutic selectivity from synergistic
drug combinations) [57], which offers such hope for our candidate
pathologies.
5 BESPOKE INTERVENTIONS
Current research demonstrates promising results from the use of
different classes of psychedelics. Serotonergic psychedelics such
Figure 1: Synergistic interactions of composite VR and psychedelics
based therapeutic solutions.
as psilocybin have shown to reduce depressive symptoms and anxi-
ety [12, 13, 83], as have dissociatives such at ketamine [6, 41, 68, 79].
Empathogen-entactogens such as MDMA have shown similar im-
provements for sufferers of PTSD [8,16, 66,70].
Specific classes of psychedelics show greater potential as solu-
tions for specific classes of psychiatric disorder. Certain compounds
may instead prove extremely counterproductive if utilized for the
wrong condition. We have some flexibility regarding which com-
pound within a class, might suit a certain individual, and the level of
dosage. Combining with VR greatly increases our possible interven-
tions. As with psychedelics, specific types of VR simulation shall
naturally fit some disorders better than others.
In treating PTSD we expose patients to a VE which closely mim-
ics the trigger situation of their condition. Combat veterans are taken
virtually back to Vietnam, Afghanistan or Iraq [62,85]. Survivors of
the terrorist attacks of September 11, 2001 [23, 24] relive jets flying
into the World Trade Center and the ensuing aftermath.
Composite interventions of similar specificity can offer hope to
those otherwise unresponsive to treatment. Psilocybin only treat-
ments have already been shown to reduce symptoms in those with
treatment-resistant depression [15, 84, 95, 100]. Providing a tailored
sensory stimulus in order to guide the experience grants both pos-
sible symptom reduction in those still resistant to treatment, and
a potential temporal improvement in symptom reduction for all
patients. One such utility offering VE would include elements of
mindfulness meditation which displays potential as a therapeutic
solution in its own right.
Vipassana (mindfulness) meditation shows similar promise as a
therapeutic solution for alcohol and substance abuse [60], anxiety
and depression [1, 2, 26,52, 53], and stress [91]. For a given individ-
ual we may decide the most effective VE should include a virtual
one-to-one session with an expert Vipassana teacher, or shared group
session. Such a scenario might prove impossible for a patient in the
real world. As part of their bespoke treatment they can instead expe-
rience the meditation practice in a heightened state of suggestibility,
while enjoying the removal of any potentially counterproductive
social anxiety.
Such an intervention may include a pre-rendered VE featuring
a real-world Vipassana teacher such as Matthieu Ricard or Joseph
Goldstein. Alternatively, depending on the patient, we may decide
that a perfectly designed digital avatar exuding the same level of
calm, enlightened, reassuring presence would be preferable. In
either scenario we likely evoke a mystical-type experience in a
patient. Such quality of experience potentially facilitates yet further
long-term improvements in mental health [33,34, 58, 84]. Beneficial
mystical/spiritual experiences of this type are of course possible with
psychedics alone [33, 35]. Guiding in this way, however, increases
the reliability of inducing such experiences [10].
Figure 2: Vir tual environment flexibility enables absolute specificity
when tailoring bespoke therapeutic interventions.
Our candidate pathologies call for absolute specificity of VR sim-
ulation. Virtual reality exposure therapy (VRET) is well-established.
The technique has already been used extensively and has consis-
tently shown promising results when applied to phobias such as
agoraphobia, acrophobia, vehophobia, claustrophobia, aviophobia,
social phobia, and arachnophobia [72, 73]. Although this alternative
to traditional exposure therapy methods has shown to be somewhat
useful, the importance of maximizing immersion and presence has
been identified as key [9,39, 51].
Previous combined approaches to social phobia have included
supplementing exposure therapy with the selective serontonin re-
uptake inhibitor (SSRI) sertraline. While the combination showed
improved efficacy [7, 36], it also evoked adverse effects such as
nausea, malaise, and sexual dysfunction during the study [7], and
significant deterioration in self reported health 28 weeks after cessa-
tion of the treatment [36].
Psilocybin offers far more promise as a potential partner to VRET.
Unlike psilocybin, SSRIs such as sertraline are not direct 5-HT
2A
receptor agonists and so offer none of the associated benefits such as
improved cognitive flexibility, associative learning, and cortical neu-
ral plasticity [13]. These characteristics directly assist in a patient’s
reappraisal of their deluded belief. By allowing the unlearning and
replacement of inaccurate perspectives, with new less exaggerated
versions, a patient is able to break free of their pathology.
These same traits enable an openness to fresh perspectives for
those suffering from BDD. VR simulations might take a number of
different guises and shall depend on the individual patient. In general,
the benefit lies in the ability to provide patients with solid, therapist-
independent information about the misguided mental representation
of their body image [27]. One possible simulation could see a patient
inhabit a number of different avatars in a given VE. With the freedom
to inspect themselves by looking down or in a virtual mirror in a
variety of different virtual bodies (including a virtual version of
their own), we encourage a realization as to the erroneous nature
of their concerns. Additional therapeutic simulations may look to
harness the Proteus effect which has already shown an ability to alter
perception and behavior in VR users inhabiting avatars dissimilar to
their own self [98,99] .
BDD has been associated with incidences of abnormal connec-
tivity in the brain [3,28]. Although the primary aim of employing
a composite psychedelics/VR intervention to BDD sufferers would
be to evoke a perceptual change, we may additionally speculate a
possible mitigation of the effects of such abnormalities. Psychedelic
experience with compounds such as psilcybin and LSD not only in-
crease cortical neural plasticity, but also evoke changes in functional
connectivity [47, 55, 92].
6 CONSIDERATIONS, COUNTERPOINTS,AND MITIGATIONS
We must consider the infancy of the research which we discuss and
look to combine. A great deal remains to be completely established
and replicated scientifically and so we may be accused of multiplying
this uncertainty by bringing together two, as yet, unestablished
paradigms. When contemplating such arguments we must consider
the restrictions previously, and indeed currently, put upon such
research. Processing power has hindered the emergence of VR
while bureaucracy has done the same for psychedelic medicine.
Despite these obstacles we still see a growing literature of promising
findings.
Such is the potential power of combining VR and psychedelics
that we may cause concern by promoting this pairing of interventions.
Only by careful experimentation shall we truly know the effects of
this composite therapeutic treatment. We propose a non-linear sum-
mation relating to treatment benefits but it is difficult to accurately
predict. Perhaps something is lost in the combination which is not
currently obvious to us. Such concerns shall be mitigated by re-
stricting dosage of psychedelic compounds. This restriction shall
lie significantly below the levels currently used and detailed in the
accepted safety guide [45]. We implement such restriction not only
for safety reasons, but to facilitate immersion and presence in the
prescribed VE rather than one generated in the patient’s own mind.
Consequently, we shall hope to experience increased acceptance
from internal review boards when evaluating the research.
In order to maintain absolute safety we shall necessarily accom-
pany the patient with a psychiatrist or psychotherapist with whom
they are completely comfortable. In order to reduce instances of a
patient breaking presence by removing the head mounted display,
we shall introduce the therapist virtually as necessary using social
VR or similar.
One might argue that taking a patient out of the sterile medical
laboratory setting, and into a VE, risks a decrease of expectation and
subsequent loss of any associated placebo effect. We counter such
concerns by emphasizing the complexity of conducting safe inter-
ventions using psychedelics, which in turn may increase expectation.
Additionally, when conducting research with psychedelics we must
concern ourselves that an overly clinical environment, exhibiting
extraneous medical equipment and personnel in white lab coats, may
increase anxious reactions [90].
7 CONCLUSION
We propose a novel combined therapeutic approach for a wide range
of psychiatric disorders including depression, anxiety, PTSD, and
addiction. We encourage others to explore the usefulness of this
technique for such disorders while we focus our attention on provid-
ing solutions for sufferers of body dismorphic disorder and a variety
of phobias.
We begin by developing flexible simulations in order that patients
receive the most effective sensory stimulus. Screening phases in the
treatment process shall allow identification of VEs and avatars best
suited to the pathology, and most conducive to offering the patient
an optimally comfortable experience. Avatar design is crucial as this
entity shall offer guidance and support while the patient navigates
their psychedelic experience. Avatars have already shown their
utility in schizophenia treatments [29, 56].
In prescribing composite therapies we shall decide drug, dosage,
and simulation combinations in a similar way to drug-only combina-
tions using the Chou-Talalay method [18]. We may categorize simu-
lation settings according to pathology while rating the expected po-
tency using the German VR Simulation Realism Scale [77]. Testing
shall initially take place using healthy subjects in order to establish
tolerance and gauge the effects of various psychedelic compound
on the sense of presence. Phase 2 sees patients who previously
responded well to drug-only interventions receive the combined
treatment. Here we gain insight into the increased efficacy of com-
bining treatment paradigms. Phase 3 shall attempt to treat those
hard cases who previously exhibited little or no improvement from
drug-only therapies.
Follow up visits and feedback shall inform how to proceed re-
garding the future development of composite treatments. The ef-
fectiveness of each novel composite treatment shall be assessed by
evaluating patients in follow up discussions and will rely upon self
reporting and clinical assessment by a psychiatrist. Acceptance of
novel treatments of this nature is naturally slow. Psychedelics will
take time to become an established part of medicine due to an ar-
guably checkered history and the resulting popular misconceptions
surrounding such compounds.
Whether or not the adoption of psychedelic medicine proves
to be straightforward, now is not the time to resist progressing the
knowledge of such novel interventions. The prevalence of depression
and anxiety [96], PTSD [71], and addiction [54] are all increasing.
Effective composite treatments such as those described can raise
hope in the individuals and communities currently suffering these
pathologies.
REFERENCES
[1]
K. Adhikari. Study of effect of vipassana on anxiety and depres-
sion. International Journal of Psychology and Behavioral Sciences,
2(6):274–276, 2012.
[2]
A. S. AlaAldin Al-Hussaini, S. X. A. Dorvlo, J. D. Dhananjay Chavan,
S. A.-R. Vimal Purecha, and A.-A. Samir. Vipassana meditation:: A
naturalistic, preliminary observation in muscat. Journal for scientific
research. Medical sciences/Sultan Qaboos University, 3(2):87, 2001.
[3]
D. Arienzo, A. Leow, J. A. Brown, L. Zhan, J. GadElkarim, S. Hovav,
and J. D. Feusner. Abnormal brain network organization in body
dysmorphic disorder. Neuropsychopharmacology, 38(6):1130–1139,
2013.
[4]
H. O. Atladottir, D. Gyllenberg, A. Langridge, S. Sandin, S. N.
Hansen, H. Leonard, M. Gissler, A. Reichenberg, D. E. Schendel,
J. Bourke, et al. The increasing prevalence of reported diagnoses
of childhood psychiatric disorders: a descriptive multinational com-
parison. European child & adolescent psychiatry, 24(2):173–183,
2015.
[5]
R. P. Bentall, G. A. Baker, and S. Havers. Reality monitoring and
psychotic hallucinations. British Journal of Clinical Psychology,
30(3):213–222, 1991.
[6]
R. M. Berman, A. Cappiello, A. Anand, D. A. Oren, G. R. Heninger,
D. S. Charney, and J. H. Krystal. Antidepressant effects of ketamine
in depressed patients. Biological psychiatry, 47(4):351–354, 2000.
[7]
S. Blomhoff, T. T. Haug, K. Hellstr
¨
om, I. Holme, M. Humble, H. P.
Madsbu, and J. E. Wold. Randomised controlled general practice trial
of sertraline, exposure therapy and combined treatment in generalised
social phobia. The British Journal of Psychiatry, 179(1):23–30, 2001.
[8]
J. C. Bouso, R. Doblin, M. Farr
´
e, M.
´
A. Alc
´
azar, and G. G
´
omez-
Jarabo. Mdma-assisted psychotherapy using low doses in a small
sample of women with chronic posttraumatic stress disorder. Journal
of psychoactive drugs, 40(3):225–236, 2008.
[9]
B. Busscher, D. de Vliegher, Y. Ling, and W. Brinkman. Analy-
sis of physiological response to neutral virtual reality worlds. In
Proceedings of the ECCE2010 workshop–Cognitive engineering for
technology in mental health care and rehabilitation, pp. 978–994,
2010.
[10]
R. Carhart-Harris, S. Brugger, D. Nutt, and J. Stone. Psychiatrys
next top model: cause for a re-think on drug models of psychosis
and other psychiatric disorders. Journal of Psychopharmacology,
27(9):771–778, 2013.
[11]
R. Carhart-Harris, M. Kaelen, M. Whalley, M. Bolstridge, A. Feild-
ing, and D. Nutt. Lsd enhances suggestibility in healthy volunteers.
Psychopharmacology, 232(4):785–794, 2015.
[12]
R. L. Carhart-Harris, M. Bolstridge, C. M. J. Day, J. Rucker, R. Watts,
D. E. Erritzoe, M. Kaelen, B. Giribaldi, M. Bloomfield, S. Pilling,
J. A. Rickard, B. Forbes, A. Feilding, D. Taylor, H. V. Curran, and D. J.
Nutt. Psilocybin with psychological support for treatment-resistant
depression: six-month follow-up. Psychopharmacology, Nov 2017.
doi: 10.1007/s00213-017-4771-x
[13]
R. L. Carhart-Harris, M. Bolstridge, J. Rucker, C. M. Day, D. Erritzoe,
M. Kaelen, M. Bloomfield, J. A. Rickard, B. Forbes, A. Feilding,
et al. Psilocybin with psychological support for treatment-resistant
depression: an open-label feasibility study. The Lancet Psychiatry,
3(7):619–627, 2016.
[14]
R. L. Carhart-Harris and G. M. Goodwin. The therapeutic potential
of psychedelic drugs: Past, present, and future. Neuropsychopharma-
cology, 2017.
[15]
R. L. Carhart-Harris, L. Roseman, M. Bolstridge, L. Demetriou,
J. N. Pannekoek, M. B. Wall, M. Tanner, M. Kaelen, J. McGonigle,
K. Murphy, et al. Psilocybin for treatment-resistant depression: fmri-
measured brain mechanisms. Scientific reports, 7(1):13187, 2017.
[16]
H. Chabrol and P. Oehen. Mdma assisted psychotherapy found to
have a large effect for chronic post-traumatic stress disorder. Journal
of Psychopharmacology, 27(9):865–866, 2013.
[17]
M. Cheetham, P. Suter, and L. J
¨
ancke. The human likeness dimension
of the uncanny valley hypothesis: behavioral and functional mri
findings. Frontiers in human neuroscience, 5, 2011.
[18]
T.-C. Chou. Drug combination studies and their synergy quantification
using the chou-talalay method. Cancer research, 70(2):440–446,
2010.
[19]
M. Cokol, H. N. Chua, M. Tasan, B. Mutlu, Z. B. Weinstein, Y. Suzuki,
M. E. Nergiz, M. Costanzo, A. Baryshnikova, G. Giaever, et al. Sys-
tematic exploration of synergistic drug pairs. Molecular systems
biology, 7(1):544, 2011.
[20]
J. Colla, S. Buka, D. Harrington, and J. M. Murphy. Depression
and modernization. Social Psychiatry and Psychiatric Epidemiology,
41(4):271–279, 2006.
[21]
W. M. Compton, K. P. Conway, F. S. Stinson, and B. F. Grant. Changes
in the prevalence of major depression and comorbid substance use
disorders in the united states between 1991–1992 and 2001–2002.
American Journal of Psychiatry, 163(12):2141–2147, 2006.
[22]
J. Diemer, G. W. Alpers, H. M. Peperkorn, Y. Shiban, and
A. M
¨
uhlberger. The impact of perception and presence on emo-
tional reactions: a review of research in virtual reality. Frontiers in
psychology, 6, 2015.
[23]
J. Difede, J. Cukor, N. Jayasinghe, I. Patt, S. Jedel, L. Spielman,
C. Giosan, and H. G. Hoffman. Virtual reality exposure therapy for
the treatment of posttraumatic stress disorder following september 11,
2001. Journal of Clinical Psychiatry, 68(11):1639, 2007.
[24]
J. Difede and H. G. Hoffman. Virtual reality exposure therapy for
world trade center post-traumatic stress disorder: A case report. Cy-
berpsychology & behavior, 5(6):529–535, 2002.
[25]
A. L. Dunn and R. K. Dishman. 2 exercise and the neurobiology of
depression. Exercise and sport sciences reviews, 19(1):41–98, 1991.
[26]
S. J. Eisendrath, K. Delucchi, R. Bitner, P. Fenimore, M. Smit, and
M. McLane. Mindfulness-based cognitive therapy for treatment-
resistant depression: a pilot study. Psychotherapy and Psychosomat-
ics, 77(5):319–320, 2008.
[27]
M. Ferrer-Garc
´
ıa and J. Guti
´
errez-Maldonado. The use of virtual
reality in the study, assessment, and treatment of body image in eating
disorders and nonclinical samples: a review of the literature. Body
Image, 9(1):1–11, 2012.
[28]
J. D. Feusner, D. Arienzo, W. Li, L. Zhan, J. GadElkarim, P. M.
Thompson, and A. D. Leow. White matter microstructure in body
dysmorphic disorder and its clinicalcorrelates. Psychiatry Research:
Neuroimaging, 211(2):132–140, 2013.
[29]
D. Freeman. Studying and treating schizophrenia using virtual reality:
a new paradigm. Schizophrenia bulletin, 34(4):605–610, 2008.
[30]
S. Gibbs. Apple investors call for action over iphone ’addiction’
among children. Guardian Online, 2018.
[31]
P. S. Gill, A. Kamath, and T. S. Gill. Distraction: an assessment of
smartphone usage in health care work settings. Risk management and
healthcare policy, 5:105, 2012.
[32]
L. Gregg and N. Tarrier. Virtual reality in mental health. Social
psychiatry and psychiatric epidemiology, 42(5):343–354, 2007.
[33]
R. R. Griffiths, W. A. Richards, M. W. Johnson, U. D. McCann,
and R. Jesse. Mystical-type experiences occasioned by psilocybin
mediate the attribution of personal meaning and spiritual significance
14 months later. Journal of psychopharmacology, 22(6):621–632,
2008.
[34]
R. R. Griffiths, W. A. Richards, U. McCann, and R. Jesse. Psilocy-
bin can occasion mystical-type experiences having substantial and
sustained personal meaning and spiritual significance. Psychophar-
macology, 187(3):268–283, 2006.
[35]
C. S. Grob, A. L. Danforth, G. S. Chopra, M. Hagerty, C. R. McKay,
A. L. Halberstadt, and G. R. Greer. Pilot study of psilocybin treatment
for anxiety in patients with advanced-stage cancer. Archives of general
psychiatry, 68(1):71–78, 2011.
[36]
T. T. Haug, S. Blomhoff, K. Hellstrøm, I. Holme, M. Humble, H. P.
Madsbu, and J. E. Wold. Exposure therapy and sertraline in social
phobia: I-year follow-up of a randomised controlled trial. The British
Journal of Psychiatry, 182(4):312–318, 2003.
[37]
B. H. Hidaka. Depression as a disease of modernity: explanations for
increasing prevalence. Journal of affective disorders, 140(3):205–214,
2012.
[38]
E. Hollander, L. J. Cohen, and D. Simeon. Body dysmorphic disorder.
Psychiatric Annals, 23(7):359–364, 1993.
[39]
D. Horv
´
athov
´
a and V. Sil
´
adi. Creating virtual environments for phobia
treatment. Open Computer Science, 6(1), 2016.
[40]
M. Hurvich. On the concept of reality testing. The International
journal of psycho-analysis, 51:299, 1970.
[41]
S. A. Irwin, A. Iglewicz, R. A. Nelesen, J. Y. Lo, C. H. Carr, S. D.
Romero, and L. S. Lloyd. Daily oral ketamine for the treatment of
depression and anxiety in patients receiving hospice care: a 28-day
open-label proof-of-concept trial. Journal of palliative medicine,
16(8):958–965, 2013.
[42]
J. W. Jefferson. Social phobia: a pharmacologic treatment overview.
The Journal of clinical psychiatry, 56:18–24, 1995.
[43]
J. Jerald. The VR book: human-centered design for virtual reality.
Morgan & Claypool, 2015.
[44]
M. K. Johnson and C. L. Raye. Reality monitoring. Psychological
review, 88(1):67, 1981.
[45]
M. W. Johnson, W. A. Richards, and R. R. Griffiths. Human hallucino-
gen research: guidelines for safety. Journal of psychopharmacology,
22(6):603–620, 2008.
[46]
M. Kaelen, B. Giribaldi, J. Raine, L. Evans, C. Timmerman-Slater,
N. Rodriguez, L. Roseman, A. Feilding, D. Nutt, and R. Carhart-
Harris. The hidden therapist: Evidence for a central role of music in
psychedelic therapy. 2017.
[47]
M. Kaelen, L. Roseman, J. Kahan, A. Santos-Ribeiro, C. Orban,
R. Lorenz, F. S. Barrett, M. Bolstridge, T. Williams, L. Williams,
M. B. Wall, A. Feilding, S. Muthukumaraswamy, D. J. Nutt, and
R. Carhart-Harris. Lsd modulates music-induced imagery via changes
in parahippocampal connectivity. European Neuropsychopharmacol-
ogy, 26(7):1099 – 1109, 2016. doi: 10.1016/j. euroneuro.2016. 03.
018
[48]
M. Kaelen, L. Roseman, R. Lorenz, A. Simmonds, A. Santos-Ribeiro,
D. Nutt, and R. Carhart-Harris. Effects of lsd and music on brain
activity. European Neuropsychopharmacology, 26:S130, 2016.
[49]
M. A. Killingsworth and D. T. Gilbert. A wandering mind is an
unhappy mind. Science, 330(6006):932–932, 2010.
[50]
R. Kraut, M. Patterson, V. Lundmark, S. Kiesler, T. Mukophadhyay,
and W. Scherlis. Internet paradox: A social technology that reduces
social involvement and psychological well-being? American psychol-
ogist, 53(9):1017, 1998.
[51]
M. Krijn, P. M. Emmelkamp, R. P. Olafsson, and R. Biemond. Virtual
reality exposure therapy of anxiety disorders: A review. Clinical
psychology review, 24(3):259–281, 2004.
[52]
J. R. Krygier, J. A. Heathers, S. Shahrestani, M. Abbott, J. J. Gross,
and A. H. Kemp. Mindfulness meditation, well-being, and heart rate
variability: a preliminary investigation into the impact of intensive
vipassana meditation. International Journal of Psychophysiology,
89(3):305–313, 2013.
[53]
S. Kumar, G. Feldman, and A. Hayes. Changes in mindfulness
and emotion regulation in an exposure-based cognitive therapy for
depression. Cognitive Therapy and Research, 32(6):734, 2008.
[54]
M. Laxmaiah Manchikanti, I. Standiford Helm, and J. W. J. MA.
Opioid epidemic in the united states. Pain physician, 15:2150–1149,
2012.
[55]
A. V. Lebedev, M. Kaelen, M. L
¨
ovd
´
en, J. Nilsson, A. Feilding, D. J.
Nutt, and R. L. Carhart-Harris. Lsd-induced entropic brain activ-
ity predicts subsequent personality change. Human brain mapping,
37(9):3203–3213, 2016.
[56]
J. Leff, G. Williams, M. A. Huckvale, M. Arbuthnot, and A. P. Leff.
Computer-assisted therapy for medication-resistant auditory halluci-
nations: proof-of-concept study. The British Journal of Psychiatry,
202(6):428–433, 2013.
[57]
J. Leh
´
ar, A. S. Krueger, W. Avery, A. M. Heilbut, L. M. Johansen,
E. R. Price, R. J. Rickles, G. F. Short Iii, J. E. Staunton, X. Jin,
et al. Synergistic drug combinations tend to improve therapeutically
relevant selectivity. Nature biotechnology, 27(7):659–666, 2009.
[58]
C. Letheby. The epistemic innocence of psychedelic states. Con-
sciousness and cognition, 39:28–37, 2016.
[59]
Y. Liao, A. Shibata, K. Ishii, and K. Oka. Independent and com-
bined associations of physical activity and sedentary behavior with
depressive symptoms among japanese adults. International journal
of behavioral medicine, 23(4):402–409, 2016.
[60]
G. A. Marlatt, K. Witkiewitz, T. M. Dillworth, S. W. Bowen, G. A.
Parks, L. M. Macpherson, H. S. Lonczak, M. E. Larimer, T. Simpson,
A. W. Blume, et al. Vipassana meditation as a treatment for alcohol
and drug use disorders. Mindfulness and acceptance: Expanding the
cognitive-behavioral tradition, pp. 261–287, 2004.
[61]
R. McDonnell, M. Breidt, and H. H. B
¨
ulthoff. Render me real?:
investigating the effect of render style on the perception of animated
virtual humans. ACM Transactions on Graphics (TOG), 31(4):91,
2012.
[62]
R. N. McLay, D. P. Wood, J. A. Webb-Murphy, J. L. Spira, M. D.
Wiederhold, J. M. Pyne, and B. K. Wiederhold. A randomized,
controlled trial of virtual reality-graded exposure therapy for post-
traumatic stress disorder in active duty service members with combat-
related post-traumatic stress disorder. Cyberpsychology, behavior,
and social networking, 14(4):223–229, 2011.
[63]
D. Mestre, P. Fuchs, A. Berthoz, and J. Vercher. Immersion et
pr
´
esence. Le trait
´
e de la r
´
ealit
´
e virtuelle. Paris: Ecole des Mines de
Paris, pp. 309–38, 2006.
[64]
D. R. Mestre, C. Ma
¨
ıano, V. Dagonneau, and C.-S. Mercier. Does
virtual reality enhance exercise performance, enjoyment, and dissoci-
ation? an exploratory study on a stationary bike apparatus. Presence:
Teleoperators and Virtual Environments, 20(1):1–14, 2011.
[65]
E. D. Miller. The curse of the cursor? Narratives of Loneliness:
Multidisciplinary Perspectives from the 21st Century, 2017.
[66]
M. C. Mithoefer, M. T. Wagner, A. T. Mithoefer, L. Jerome, S. F. Mar-
tin, B. Yazar-Klosinski, Y. Michel, T. D. Brewerton, and R. Doblin.
Durability of improvement in post-traumatic stress disorder symp-
toms and absence of harmful effects or drug dependency after 3, 4-
methylenedioxymethamphetamine-assisted psychotherapy: a prospec-
tive long-term follow-up study. Journal of Psychopharmacology,
27(1):28–39, 2013.
[67]
C. D. Murray, J. Fox, and S. Pettifer. Absorption, dissociation, locus of
control and presence in virtual reality. Computers in Human Behavior,
23(3):1347–1354, 2007.
[68]
J. W. Murrough, D. V. Iosifescu, L. C. Chang, R. K. Al Jurdi, C. E.
Green, A. M. Perez, S. Iqbal, S. Pillemer, A. Foulkes, A. Shah, et al.
Antidepressant efficacy of ketamine in treatment-resistant major de-
pression: a two-site randomized controlled trial. American Journal of
Psychiatry, 170(10):1134–1142, 2013.
[69]
D. E. Nichols. Psychedelics. Pharmacological reviews, 68(2):264–
355, 2016.
[70]
P. Oehen, R. Traber, V. Widmer, and U. Schnyder. A
randomized, controlled pilot study of mdma (
±
3, 4-
methylenedioxymethamphetamine)-assisted psychotherapy for
treatment of resistant, chronic post-traumatic stress disorder (ptsd).
Journal of Psychopharmacology, 27(1):40–52, 2013.
[71]
N. I. of Health et al. Ptsd: A growing epidemic. NIH Medline Plus,
4(1):10–4, 2009.
[72]
I. Paliokas, A. Tsakiris, A. Vidalis, and D. Tzovaras. Sense of presence
and metacognition enhancement in virtual reality exposure therapy in
the treatment of social phobias and the fear of flying. In International
Conference on Virtual, Augmented and Mixed Reality, pp. 316–328.
Springer, 2014.
[73]
T. D. Parsons and A. A. Rizzo. Affective outcomes of virtual reality
exposure therapy for anxiety and specific phobias: A meta-analysis.
Journal of behavior therapy and experimental psychiatry, 39(3):250–
261, 2008.
[74]
K. A. Phillips and R. D. Crino. Body dysmorphic disorder. Current
Opinion in Psychiatry, 14(2):113–118, 2001.
[75]
K. A. Phillips, W. Menard, C. Fay, and M. E. Pagano. Psychosocial
functioning and quality of life in body dysmorphic disorder. Compre-
hensive psychiatry, 46(4):254–260, 2005.
[76]
K. A. Phillips, W. Menard, C. Fay, and R. Weisberg. Demographic
characteristics, phenomenology, comorbidity, and family history in
200 individuals with body dysmorphic disorder. Psychosomatics,
46(4):317–325, 2005.
[77]
S. Poeschl and N. Doering. The german vr simulation realism scale-
psychometric construction for virtual reality applications with virtual
humans., 2013.
[78]
D. H. Powell. Treating individuals with debilitating performance
anxiety: An introduction. Journal of clinical psychology, 60(8):801–
808, 2004.
[79]
R. B. Price, M. K. Nock, D. S. Charney, and S. J. Mathew. Effects of
intravenous ketamine on explicit and implicit measures of suicidality
in treatment-resistant depression. Biological psychiatry, 66(5):522–
526, 2009.
[80]
L. A. Rhodes, D. C. David, and A. L. Combs. Absorption and enjoy-
ment of music. Perceptual and Motor Skills, 66(3):737–738, 1988.
[81]
G. Riva. Virtual reality in psychotherapy. Cyberpsychology & behav-
ior, 8(3):220–230, 2005.
[82]
G. Riva, F. Davide, and W. IJsselsteijn. Being there: The experience
of presence in mediated environments. Being there: Concepts, effects
and measurement of user presence in synthetic environments, 5, 2003.
[83]
L. Roseman, L. Demetriou, M. B. Wall, D. J. Nutt, and R. L. Carhart-
Harris. Increased amygdala responses to emotional faces after psilo-
cybin for treatment-resistant depression. Neuropharmacology, pp. –,
2017. doi: 10. 1016/j.neuropharm.2017.12.041
[84]
L. Roseman, D. J. Nutt, and R. L. Carhart-Harris. Quality of acute
psychedelic experience predicts therapeutic efficacy of psilocybin for
treatment-resistant depression. Frontiers in Pharmacology, 8:974,
2017.
[85]
B. O. Rothbaum, L. Hodges, R. Alarcon, D. Ready, F. Shahar,
K. Graap, J. Pair, P. Hebert, D. Gotz, B. Wills, et al. Virtual reality
exposure therapy for ptsd vietnam veterans: A case study. Journal of
traumatic stress, 12(2):263–271, 1999.
[86]
F. R. Schneier, L. R. Heckelman, R. Garfinkel, R. Campeas, B. A.
Fallon, A. Gitow, L. Street, D. Del Bene, and M. R. Liebowitz. Func-
tional impairment in social phobia. The Journal of clinical psychiatry,
1994.
[87]
J. Seyama and R. S. Nagayama. The uncanny valley: Effect of realism
on the impression of artificial human faces. Presence: Teleoperators
and virtual environments, 16(4):337–351, 2007.
[88]
B. M. Sjoberg. The Effects of Lysergic Acid Diethylamide (LSD-25),
Mescaline, Psilocybin and a Combination of Three Drugs on Primary
Suggestibility. Department of Psychology, Stanford University., 1965.
[89] G. Stanislav. Realms of the human unconscious, 1975.
[90] R. Strassman. Dmt: The spirit molecule, 2001.
[91]
R. A. Szekeres and E. H. Wertheim. Evaluation of vipassana medi-
tation course effects on subjective stress, well-being, self-kindness
and mindfulness in a community sample: Post-course and 6-month
outcomes. Stress and Health, 31(5):373–381, 2015.
[92]
E. Tagliazucchi, L. Roseman, M. Kaelen, C. Orban, S. D. Muthuku-
maraswamy, K. Murphy, H. Laufs, R. Leech, J. McGonigle, N. Cross-
ley, et al. Increased global functional connectivity correlates with lsd-
induced ego dissolution. Current Biology, 26(8):1043–1050, 2016.
[93]
A. Tellegen and G. Atkinson. Openness to absorbing and self-altering
experiences (” absorption”), a trait related to hypnotic susceptibility.
Journal of abnormal psychology, 83(3):268, 1974.
[94]
K. W. Tupper, E. Wood, R. Yensen, and M. W. Johnson. Psychedelic
medicine: a re-emerging therapeutic paradigm. Canadian Medical
Association Journal, 187(14):1054–1059, 2015.
[95]
R. Watts, C. Day, J. Krzanowski, D. Nutt, and R. Carhart-Harris.
Patients accounts of increased connectedness and acceptance after
psilocybin for treatment-resistant depression. Journal of Humanistic
Psychology, 57(5):520–564, 2017.
[96]
A. Weinberger, M. Gbedemah, A. Martinez, D. Nash, S. Galea, and
R. Goodwin. Trends in depression prevalence in the usa from 2005
to 2015: widening disparities in vulnerable groups. Psychological
medicine, pp. 1–10, 2017.
[97]
R. Whitaker. The case against antipsychotic drugs: a 50-year record
of doing more harm than good. Medical hypotheses, 62(1):5–13,
2004.
[98]
N. Yee and J. Bailenson. The proteus effect: The effect of transformed
self-representation on behavior. Human communication research,
33(3):271–290, 2007.
[99]
N. Yee, J. N. Bailenson, and N. Ducheneaut. The proteus effect:
Implications of transformed digital self-representation on online and
offline behavior. Communication Research, 36(2):285–312, 2009.
[100]
S. N. Young. Single treatments that have lasting effects: some
thoughts on the antidepressant effects of ketamine and botulinum
toxin and the anxiolytic effect of psilocybin. Journal of psychiatry &
neuroscience: JPN, 38(2):78, 2013.
... Indeed, both psychedelics and Virtual Reality share effectiveness in treating disorders such as depression, anxiety, PTSD, and Eating Disorders [72,73]. Specifically, some authors highlight the potential of such combined treatment to alleviate the considerable psychological distress caused by phobias and Body Dysmorphic Disorder [74]. ...
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... 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"). ...
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Plant-based psychedelics such as psilocybin have an ancient history of medicinal use. After the first English-language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aides to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programmes. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and 3 separate clinical trials of psilocybin for depressive symptoms. In this Circumspective piece, Robin Carhart-Harris and Guy Goodwin share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.Neuropsychopharmacology accepted article preview online, 26 April 2017. doi:10.1038/npp.2017.84.
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Virtual reality (VR) can provide our minds with direct access to digital media in a way that seemingly has no limits. However, creating compelling VR experiences is an incredibly complex challenge. When VR is done well, the results are brilliant and pleasurable experiences that go beyond what we can do in the real world. When VR is done badly, not only is the system frustrating to use, but it can result in sickness. There are many causes of bad VR; some failures come from the limitations of technology, but many come from a lack of understanding perception, interaction, design principles, and real users. This book discusses these issues by emphasizing the human element of VR. The fact is, if we do not get the human element correct, then no amount of technology will make VR anything more than an interesting tool confined to research laboratories. Even when VR principles are fully understood, the first implementation is rarely novel and almost never ideal due to the complex nature of VR and the countless possibilities that can be created. The VR principles discussed in this book will enable readers to intelligently experiment with the rules and iteratively design towards innovative experiences.