Smoking addiction is a worldwide [1] and costly [2] problem. Tobacco smoking has been linked to cardiovascular disease [3], various types of cancer [4-6] and respiratory problems [7], among other diseases, reducing the consumers’ quality of life [8], and lowering life expectancy by up to 4 years [9]. Approximately 30% of all cancer deaths in high-income countries are caused by cigarette smoking [10].

The Diagnostic and Statistical Manual of Mental Disorders lists nicotine dependency (rephrased as tobacco use disorder in a more recent edition) as a psychological disorder [11]; 55% of US smokers try to quit every year [12], but it has been estimated that between 60% and 90% of them relapse within the first year [12-14]. Smoking addiction has a strong psychological component [15,16] in addition to physiological dependence. Physiological craving may only take a few weeks to wane [17], but the habit and psychological link between smoking, socializing, relaxing, and rewarding are much harder to abandon [16]. Thus, different therapies and interventions have been developed to overcome this link.

Therapies and interventions are both care strategies, but their main difference is the scope. Interventions usually aim to motivate someone to commit to a specific action, such as a teenager saying no when their peers offer a cigarette or a smoker entering treatment. Therapies, on the other hand, address more comprehensive goals, such as maintaining abstinence and altering habits or attitudes. In practice, there is often no clear distinction between the two and they can be thought of as lying on a continuum rather than reflecting 2 dichotomous categories [18].

Cue exposure therapy (CET) uses a classical conditioning approach to unlearn a response (craving) to stimuli (smoking-related items and situations). During the therapy sessions, craving is elicited by exposing participants to smoking-related cues such as cigarette packages and images of situations in which the participant usually smoked. In daily life, participants would relieve cravings through smoking, which reinforces the craving response. During CET, typically no nicotine reward is provided [19] (however, see the study by Kotlyar et al [20] and De La Garza et al [21] that combines CET with nicotine replacement therapy [NRT]). Once the craving has receded, the participant is exposed to smoking cues again, with the aim of repeating this procedure until the association between smoking cues and reward is weakened and eventually extinguished [19,22].

The approach-avoidance task (AAT) adopts an operant conditioning approach. This task can be used to measure and influence subconscious bias [23,24]. During the AAT, participants have to either pull or push away a lever in response to visual cues. People tend to be quicker to pull when presented with cues that elicit a positive (approach) bias than when cues have a neutral or negative association, whereas they are quicker to push away (avoid) negative cues than positive or neutral ones [23]. Thus, AAT can be used to measure existing subconscious biases, as smokers will be quicker to pull when presented with smoking-related cues than nonsmokers. In addition, AAT can be used as an instrument to break or reverse subconscious biases by instructing participants to respond to smoking cues with avoidance behaviors (eg, pushing away) over a number of trials or sessions until smoking cues are automatically associated with avoidance and negative affect [24,25].

Cognitive behavioral therapy (CBT)–based interventions often take a multicomponent approach: teaching smokers to recognize the thought patterns they engage in before smoking and to identify triggering factors in the environment. Smokers are then trained in alternative strategies to cope with craving and temptation [26].

NRT aims to reduce cravings and by extension smoking behavior by replacing the source of nicotine [27]. It is an accessible standalone intervention for smokers who do not have the resources or motivation to commit to a more substantial intervention but will not target the psychological component of the smoking habit [27]. To this effect, NRT is often combined with CBT [28,29].

One particular form of NRT includes the use of Electronic Nicotine Delivery Systems (ENDS), more commonly known as electronic cigarettes, e-cigarettes, or vapes. Invented at the start of the 2000s, these devices heat a solution usually containing nicotine and flavoring agents and deliver the vapor (aerosol) to the user to be inhaled [30], although the amount of nicotine varies and nonnicotine liquids are available as well [31,32]. ENDS were originally introduced as a device to help reduce the number of cigarettes smoked or even quit (conventional) smoking altogether [30,33,34]. However, there has been an ongoing debate in the scientific and medical community on the health risks associated with ENDS [35,36] as well as the potential of ENDS to form an introduction to smoking for previous nonsmokers (the gateway hypothesis; [37]). Recent meta-analyses suggest that although far from harmless, ENDS may still pose a lower health risk than smoking cigarettes [37,38] and that they may be more effective than NRT for smoking cessation [39]. The question of whether this makes ENDS an eligible form of NRT has yet to be resolved [40,41].

Virtual reality technologies (VRTs) have been recognized as potentially helpful in increasing the effects of these and other interventions. These technologies provide an immersive interface that can be used to enhance (augmented reality [AR]) or even replace (virtual reality [VR]) reality with computer-generated simulations. AR is commonly used on a screen that combines the display of the real world with some added virtual features; a well-known example is the game Pokémon Go (Niantic Inc), which displayed the camera view on screen but added virtual Pokémon creatures to the scene, which the user could interact with. In contrast, in VR apps, users often wear a VR headset such as a stereoscopic head-mounted display that projects video images in 3D. Although the focus in VR and AR generally lies in visual simulation, the experience can be enhanced through haptic, olfactory, and audio feedback.

There are multiple potential benefits of using the VRT. First, training smokers to respond to a potentially tempting situation will be more effective if the therapy can mimic those situations more closely [42,43], and VR has been shown to create a stronger feeling of being immersed than 2D images [44-46]. Second, VR offers a safe environment for coping skills [47]. Finally, it can be easily tailored to the specific needs of individual smokers [22,42]. Therefore, over the last 15 years, the potential of VR for smoking cessation therapy has been extensively studied. Although AR has not yet been widely embraced, it was still included in the current search strategy.

In this paper, we systematically review and summarize the findings from the literature on the adoption of VRT in smoking cessation therapy.

This paper is centered around three main research questions:

The review will focus on the adult population (people aged ≥18 years) of smokers with no comorbidities. Randomized controlled trials, controlled trials, single group pre- and posttest studies, and case studies were all included, as well as protocols (to give an indication of future directions of research), meta-analyses (as those can detect effects with greater power than individual studies), and reviews (for the reference list search and to refer to as an overview for the interested reader). Intervention studies were included if they incorporated VRT in their intervention and measured either smoking cue reactivity or intervention effectiveness. With regard to the data extracted, the comparators were treatment, placebo, pre- and postcomparison, and waiting list. The outcomes were craving or smoking urge, nicotine dependence, number of cigarettes smoked, abstinence rates, and quit rates.

Some systematic review papers have been published [48-52], but their scopes only partially overlapped with that of this one; for example, some systematic reviews included nonadult subjects [50], focused exclusively on cue reactivity or CET [48-50,52], limited themselves to head-mounted display VR [51], studied a variety of addictions [48,50,51], or were simply published over 5 years ago, thus missing more recent publications [49,50]. This paper includes 15 papers that were not covered by the previous reviews and thus expands on previous findings by presenting a wider and updated overview of the potential of VRT in smoking cessation.

The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for review [53] were followed for the current review. The database search strategy was developed under the supervision of a trained subject librarian. After deliberation with the librarian, 5 databases (MEDLINE, Embase, Scopus, Cochrane, and EbscoHost) were identified to be searched using the following search terms: (Virtual reality, OR Augmented reality, OR Mixed Reality, OR Augmented Virtuality) AND (smoking OR vaping OR tobacco OR cigarette OR nicotine OR vape OR e-cigarette) AND (craving OR crave OR withdrawal OR cue exposure OR cue reactivity OR urge OR cessation OR desire). The reference lists of selected papers were also scanned for other relevant papers.

The search was completed in July 2020, resulting in a total of 299 papers: MEDLINE (n=51), Embase (n=51), Scopus (n=88), Cochrane (n=52), and EbscoHost (n=57). After removing duplicates, 137 papers remained. Three rounds of selection were completed: exclusion based on title, exclusion based on the abstract, and exclusion based on the entirety of the paper. Inclusion and exclusion criteria were determined beforehand [54], with the inclusion criteria being as follows: the paper had to discuss the (potential) use of VRT for smoking cessation treatment; the target population had to be adults, with no pre-existing psychological or physiological conditions; only tobacco smoking in the form of cigarettes, cigars, or pipe and the vaping of nicotine were included (ie, no smoking of crack, marijuana, or any other substance; smoking a nargile or bong; or vaping of tetrahydrocannabinol S containing liquids). After 3 rounds of selection, 42 papers remained. Furthermore, 8 papers that had been identified through the reference list search and met the inclusion and exclusion criteria were added to this selection, as well as 1 meta-review that was published after the search but recommended by the paper reviewer, resulting in a final set of 51 papers. However, because the 2 studies by Pericot-Valverde et al [42,55] are based on the same data set (Pericot-Valverde, personal communication, January 30, 2021), we counted them as 1 study, reducing the total number to 50. Paper selection and data extraction were completed by one of the authors. Figure 1 shows a flowchart overview of the review rounds (see Multimedia Appendix 1 [20,21,42-44,46, 48-52,55-95] for a list of the selected papers).

The timestamped literature selection plan, including search terms and inclusion and exclusion criteria, can be found [54], and the search terms, as well as the raw results from the individual databases, can be found [96] as well as in the Multimedia Appendix 1.

A few general observations were made using the data set of papers. Of the 51 selected papers, 26 (51%) introduced or tested an intervention, 17 (33%) studied cue reactivity, 5 (10%) were meta-reviews, and 3 (6%) were protocols for studies yet to be conducted. In addition, 77% (22/26) of the intervention papers described a multisession intervention, stretching out from 3 to 10 weekly sessions. Furthermore, 27% (6/22) of these multisession interventions reported at least 1 follow-up measure, ranging from 1 week to 12 months after the final session. Follow-up measurements are a great asset to intervention studies as initial effects might fade over time (for example, the results in the study by Pericot-Valverde et al [42]). Figure 2 shows a flowchart indicating the division of the papers.

In addition, 54% (14/26) of the interventions were compared with an alternative therapy; however, only 15% (4/26) included a placebo condition. Although not including an alternative intervention or placebo condition does not invalidate the overall findings of a study, it also does not provide any information on the efficacy of one therapy over the other or indeed the efficacy of one therapy over an optimistic mindset.

Furthermore, of the 42 papers examining the effect of an intervention on smoking craving or behavior, 7 (17%) used smokers unmotivated to quit as participants; the rest of the papers was roughly equally divided between smokers motivated to quit (17/42, 40%) and smokers with undisclosed motivation to stop (18/42, 43%). All but 3 papers [44,56,57] used VR in their interventions.

The prerequisite for VRT to have any (added) value in smoking interventions is whether or not these techniques can reliably induce craving through activation of smoking and smoking-related associations. Once these cravings have been elicited, any subsequent therapy can target the cravings. Cravings in non-VRT settings are usually elicited by using smoking-related paraphernalia [97], 2D images of cigarettes and scenes with people smoking [19], and imaginary procedures where participants are instructed to imagine themselves in a (personalized) high-risk situation [98]. VR can create a more immersive experience [44-46], which may add to the effectiveness of the therapy, and being virtual, it theoretically allows for tailoring specifically to the user’s needs [42,58].

A plethora of studies (n=17) set out to test whether VR could induce nicotine craving and confirmed that craving can be successfully induced in VR by exposing participants to smoking-related cues [46,58-72] (see the study by Pericot-Valverde [49] for a meta-analysis). Moreover, exposing nonsmokers to VR smoking cues did not elicit cravings [46].

Furthermore, craving can be elicited using minimal cues. No explicit mention of smoking is needed; simply presenting an environment where cigarettes are usually handled (eg, a bar or the checkout counter of a newspaper kiosk) or providing smoking-related cues in the background (such as ashtrays) was sufficient to elicit cravings. The addition of olfactory cues [60,73] or branded cigarette packages [66,67] did not increase the craving response. Ferrer-García et al [74] tested different potential moderators of cue-induced craving and found that the (sense of) presence in VR was positively linked to craving.

Whether VR-cue exposure (CE) elicits craving to a greater extent than the more traditional methods has been less extensively studied. Bordnick et al [70] found that a VR environment elicited greater craving in participants than exposure to a 2D image of the same environment. In contrast, Karelitz [52] conducted a meta-analysis on different factors that may influence cue reactivity and found that although VR cues increased craving, they did not do so to a greater degree than 2D pictorial images or scripted imagery.

It is noteworthy that the number of years that participants had been smoking correlated negatively with cue reactivity [52]. The majority (11/17, 65%) of the cue reactivity studies did not report measuring the number of years smoking; of the 6 that did, 5 did not use it as a control variable or to assess whether the experimental groups were similar before commencing the experiment, thus potentially allowing for bias. Related to this, only 6 of the papers on cue reactivity reported participants’ intention to quit. However, CE supposedly elicits craving in both types of cigarette smokers to an equal extent [62], so this lacuna in the data may not be problematic.

Given the underwhelming results that were achieved by VR-CET in terms of smoking cessation, future studies might want to explore the potential of alternative interventions. However, at present, the interest in VR-CET does not appear to have waned yet, as shown by the number of recent studies that attempt to obtain results by combining VR-CET with other therapies, such as CBT [42,89] and NRT [20,79]. It is possible that combining VR-CET with other interventions will result in a more successful intervention, as multiple aspects of nicotine addiction are addressed.

In contrast to VR-CET, interventions that used some form of behavioral intervention showed promising results. More work will be needed to solidify these findings, especially as a number of the studies reported were merely intended as pilot studies or proof of concept. One protocol study [43] laid out the design for a VR-AAT study, which would be timely as thus far only proof of concept has been reported for VR-AAT interventions. The results from the gamified interventions are promising and could lead to a lower attrition rate.

Possibly because of the ongoing controversy [38,40] surrounding ENDS, few studies to date have explored the potential use of ENDS in combination with VRT for smoking cessation therapy. However, ENDS and VRT both aim to mimic real life and allow for control over the surroundings as well as the amount of nicotine ingested, which could make them an alternative for therapy settings. De La Garza et al [21] reported a pilot study on the combination of VR-CET and ENDS as a form of NRT. The participants indicated that ENDS were not as satisfying as the conventional cigarette, even if it contained equal amounts of nicotine; at the same time, the placebo nicotine delivered in the study by Kotlyar et al [20] reduced craving in the same way as the actual nicotine treatment. These findings suggest that craving is a subjective experience and can be tweaked by participants’ beliefs of what relief they will feel. Capitalizing on this make-believe could be an interesting avenue for ENDS-based NRT.

The use of VRT could offer an alternative for, or addition to, smoking cessation interventions. VR can be used to recreate triggering situations in a more life-like and persuasive way than traditional methods. This may allow for the creation of an experience where both the environment and the triggers presented are tailored to the user’s circumstances, which may further enhance the effectiveness of the intervention.

Although VR-CET has been the most extensively researched of all interventions, the results have been mixed at best. VR CE reliably elicited cravings, and most VR-CET interventions found that by the end of the therapy, craving in response to smoking-related cues was reduced. However, the effectiveness of therapy above and beyond alternative interventions such as CBT is debatable. These findings echo the conclusions from earlier meta-reviews [48,50,51] and analysis [49]. This lack of results is disappointing but may not be unpredictable as regular CET has been shown to have very limited behavioral effectiveness in battling addictions [22,101]. In fact, this lack of results in conventional CET has been one of the larger motivations for the adoption of VR; extinction of cue reactivity has been shown to be highly context dependent [102], and it has been suggested [46,61] that the discrepancy between the controlled laboratory environment where people were conditioned and the real-world situations where their therapy was put to the test was too large. Introducing VR would supposedly reduce these problems with generalization but still does not yield a significant effect. This may be due to the quality of the virtual environments, as they are far from photorealistic. Addiction remains a multidimensional problem, and CET (in VR or a more traditional setting) may target a component that is too small to be effective as a standalone intervention. Alternatively, the lack of results may be a consequence of the quality of the virtual worlds. Since its introduction, VR has improved greatly, but even as graphics and technology have improved the environments (or at least the ones usually developed for academic studies, ie, on a budget) are far from photorealistic and rarely closely mimic the actual world of the users. Future studies with current VRT may be able to create more realistic and personalized virtual scenarios and thus potentially obtain more reliable results.

Three other types of intervention with a behavioral component emerged: AAT-based [79,80], gamified behavioral training [56,83-85], and skill training [86,87]. The proof of concept has been provided for VR-AAT [81,82], and the 2 immersive games based on AAT demonstrated some success [56,83,84]. Similarly, tentative initial findings suggest a potential for gamified interventions that combine behavioral therapy with psychological coaching [85]. Overall, the potential of gamified interventions as an (effective) treatment program is further enhanced through the addition of a gaming element. Well-designed games lead the user to play out of intrinsic rather than extrinsic motivation [103]; thus, designing an intervention in this format could elicit higher participant engagement, which would, in turn, lead to better therapy compliance and lower dropout rates than conventional interventions. Given the high dropout rates of smoking cessation therapies [104,105] and the importance of compliance in the effectiveness of an intervention [105], these would be major advantages over conventional (nongamified) therapies and interventions.

Only 1 paper was found that combined VR and ENDS in a smoking intervention, possibly because of the ongoing controversy surrounding ENDS [36,37]. Although no consensus has been reached yet on whether the downsides of ENDS outweigh the improvements over conventional cigarettes [38,39], implementing ENDS in future interventions as an NRT component may be explored more as a viable method for smoking cessation.

A final factor that needs consideration in the discussion of VR-based interventions is cost. With the gaming industry’s growing interest in the technology [51], VR has become increasingly accessible over the last few years, with a variety of affordable systems and VR template environments readily available. Nonetheless, developing VRT materials is far from cheap, and the technology thus ought to have a considerable benefit over conventional methods if it is to replace them. Considering this drawback, AR may prove to be an easier and more economical alternative, as it does not require an entire world to be created from scratch but rather uses the existing one as a template to be enhanced or altered.

The studies presented in this review suggest that VRT can be considered a promising addition to smoking cessation therapies. Although VR-CET by itself has not yielded consistent results, tentative initial findings on behavioral interventions as well as the combination of VR-CET with these interventions are promising. Moreover, the potential of ENDS in combination with VRT may offer an alternative for future research. More rigorous testing, especially in terms of larger sample sizes, the inclusion of control groups or placebo interventions, and follow-up measures, is still needed.