Table 4.

Other Virtual Reality (VR) treatment studies.

Reference	Design	Population	Control Intervention	VR Intervention	Measurements	Clinical Outcome
Nicotine studies
Girard et al. (2009) [53]	VR2/3 study into preliminary effectiveness with a clinical population, not compared to golden standard, follow-up, no power-analysis, use of randomized controlled design	-NTS, FTND = 5.9–6.4 (n = 91)	-VR-embodied learning: find and grasp up to 60 virtual balls, embedded in broader psychosocial program (n = 45)	-VR-embodied learning, embedded in broader psychosocial program (n = 46) -Computer-generated, multisensory (visual + auditory), proximal VEs: (1) medieval castle/find and crush cigarettes -Interaction: Gamepad to control virtual arm -4 weekly, 30 min VR sessions in first 4 weeks of psychosocial program (whole program consisted of 8 sessions in week 1, 2, 3, 4, 6, 8, 10 and 12)	Pre-post-follow up: -Severity of ND a Post VR-post program: -Cigarettes/day + air expired CO Follow up: -Cigarettes/day	-Stronger reduction in experimental group (p < 0.05), most notably from week 4 onwards (p < 0.001) -Abstinence status: post VR 2% (experimental group) versus 9% (control group) (n.s.), post program increased to 15% (experimental group) versus 2% (control group) (p < 0.05) -Abstinence status (past week) 39% (experimental group) versus 20% (control group) (p < 0.05)
Bordnick et al. (2012) [58]	VR2 study into feasibility and preliminary effectiveness with pre-follow up and post-session evaluation and randomized controlled design	-TS, cigarettes/day = 24.5–26.4, FTND = 5.9–6.6 (n = 46, only completers included)	-NRT-only (n = 25)	-Progressive individualized exposure + coping skill training + NRT (n = 21) -Computer-generated, multisensory (visual, auditory, olfactory + haptics), complex VE: (1) party, (2) driving, (3) restaurant, (4) office building and courtyard, (5) convenience store, (6) airport smoking lounge and gate -Interaction: no/limited -10 weekly, 60 min sessions	Post (between-groups): -Cigarettes/week -Craving b -Self-efficacy c Pre-follow up: -Cigarettes/day -Confidence to resist smoking d	-Reduced (p < 0.05, ηp2 = 0.14) -Reduced (p < 0.05, ηp2 = 0.37) -Increased (p < 0.05, ηp2 = 0.13) -Reduced at 1, 2 (p < 0.05) + 6 months (p < 0.01) follow up -Increased at 1, (p < 0.05) 2, 3 (p < 0.01) and 6 (p < 0.001) months follow up
Caponnetto et al. (2018) [59]	VR2 study into feasibility and preliminary effectiveness with pre-post session evaluation	-NTS, cigarettes/day = 15, FTND = 5.3, not motivated to quit (n = 40)	-No control	-VR-covert sensitization (n = 40) -Shocking image, video and VR session are compared in randomized cross-over design -Computer-generated, multisensory (visual + auditory), proximal VE that changes over time from neutral to aversive: cigarettes and smoke -Interaction: full body (magic leap) -3 × 15–30 min, 2 days in between sessions	Pre-post: -Motivation to quit e	-Increase: image < video < VR (p < 0.01, η2 = 0.95)
Alcohol studies
Spagnoli et al. (2014) [57]	VR2 study into preliminary effectiveness with pre-post session evaluation	-TS alcohol drinkers (n = 50)	-Traditional assessment only (n = 25)	-VR + traditional assessment (n = 25) -Computer-generated, complex VEs (one neutral, two involving alcohol cues and one a performance task) -Interaction: interaction with gamepad -1 session	Pre-post: - Readiness to change f Precontemplation phase Contemplation phase Determination phase Termination phase Action phase Maintenance phase -Self-efficacy g	-n.s. -n.s. (p = 0.052) -n.s. -Increased (p = 0.009) -n.s. -n.s. -Increased (p = 0.002)
Choi & Lee (2015) [50]	VR2 study with focus on preliminary effectiveness with pre-post session evaluation, within-person controlled	-sup>- NTS male under-graduates, AUDIT HSD = 20.0, LD = 4.6 (n = 40)	-sup>- No control (HSD (n = 20) and LD (n = 20) are compared in cross-over design)	-VR-covert sensitization (n = 40) -Computer-generated, aversive, multisensory (visual + auditory), context environments: (1) virtual hospital, (2) virtual subway -Interaction: Keypad -1 × 20 min session	Pre-post: -Craving h -Implicit alcohol associations i -Implicit alcohol eye behavior j -Implicit alcohol attentional bias k	-HSD showed a greater reduction than LD group (p < 0.01) -HSD showed a weaker positive association than LD group (p < 0.01) -Reduced dwell time in both HSD and LD group (p < 0.05, η2 = 0.14) -Reduced reaction times in both HSD and LD group (p < 0.05, η2 = 0.14)
Methamphetamine studies
Wang et al. (2019) [22]	VR2 studies with focus on preliminary effectiveness with pre-post session evaluation and randomized controlled designs	-Study 1: TS males with MD (n = 61) -Study 2: abstaining methamphetamine abusers (n = 888, only completers included)	-Waiting list (n = 30) -Waiting list (n = 276)	-Study 1 (n = 31) + 2 (n = 612): -VR-covert sensitization -360°, aversive, multisensory (visual + auditory) complex VEs. Scene1: auditory cues with social interaction; Scene 2: drugs and drug-related paraphernalia; Scene 3: METH-use social context). In the second part of the videos, participants viewed that characters in the videos experienced a distinct adverse consequence caused by METH use, totaling six videos. -No interaction: exposure -5 × 6 min sessions, twice weekly	Study 1, pre-post: -Craving e -Liking e -Propensity to use e Study 2, pre-post: -ECG (HRV indexes)	-Reduced (p = 0.001) -Reduced (p = 0.002) -n.s. -SDNN, RMSSD, pNN50 reduced (p < 0.001), nLF, nHF, LF/HF n.s.
Gambling studies
Bouchard et al. (2017) [45]	VR2 studies with focus on integrating VR and CBT (study 2) and preliminary effectiveness (study 3) with pre-post session evaluation and randomized controlled design	-Study 2: TS inpatient pathological gamblers, SOGS = 11.5 (n = 34) -Study 3: TS pathological gamblers, CPGI = 20.0 (n = 25)	-2 imaginal exposure sessions embedded in 28-day CBT program (n = 14) -Imaginal exposure (4 sessions) (n = 11)	-VR-CBT: a hierarchy in exposure to a virtual bar or casino guides users progressively approaching machines where they can gamble. Users are invited to walk to each step of the hierarchy and apply various CBT techniques. The VR-CBT was embedded in 28-day CBT program. -Computer-generated, multisensory (visual, auditory, haptics), complex VEs: (1) generated virtual casino, (2) generated virtual bar, with fixed locations in the VEs to explore and the sound controlled by proximity or therapist. -Interaction: with agents and objects via mouse device (wireless mouse) and a box with pushbuttons replicating the interface panel of a real VLT. -Study 2: 2 VR-CBT sessions -(n = 20) -Study 3: 4 VR-CBT sessions -(n = 14)	Study 2, pre-post: -Craving l Study 3, pre-post: -Severity of problem gambling m -Number of diagnostic criteria o -Gambling related cognitions p	-Time p < 0.001, group + interaction n.s. (η2 = 0.006) -n.s. (ηp2 = 0.001) -n.s. (ηp2 = 0.07) -n.s. (ηp2 = 0.04)

Abbreviations: AUDIT = Alcohol Use Disorder Identification Test; CBT = Cognitive-Behavioral Therapy; CG = control group; CO = carbon monoxide; CPGI = Canadian Problem Gambling Index; FTND = Fagerstrom Test of Nicotine Dependence; IG = intervention group; MD = Methamphetamine Dependent (according to DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders, 4th edition)); ND = Nicotine Dependent; NRT = Nicotine Replacement Therapy; NTS = Non-Treatment Seeking; RCT = Randomized Clinical Trial; TS = Treatment Seeking; VEs = virtual environments; VLT = Video Lottery Terminal; Measurement instruments: ^a Fagerstrom Test of Nicotine Dependence (FTND); ^b Questionnaire of smoking Urges-Brief version (QSU-brief); ^c Smoking Abstinence Self-Efficacy (SASE); ^d modified Smoking Confidence Questionnaire (mSCQ); ^e Visual Analogue Scale (VAS); ^f Motivation Assessment of Change questionnaire-Alcoholism version (MAC2-A); ^g Generalized Self- Efficacy Questionnaire (GSE); ^h Alcohol Urge Questionnaire (AUQ); ⁱ Alcohol-Implicit Association Task (IAT); ^j Eye-tracking test; ^k Alcohol-Stroop test; ^l Gambling Craving Scale (GCS); ^m Canadian Problem Gambling Index (CPGI); ^o Diagnostic Interview for Gambling (DIG); ^p Gambling Related Cognition Scale (GRCS).