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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.
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