Will XR Become the Next Frontier in Healing Substance Use Disorders?

Leonardo Angelone^*Elena Koustova

• National Institute on Drug Abuse (NIH), Bethesda, United States

mental health therapeutics [5] signaling progress toward sustainable coverage models that could accelerate broader adoption.XR systems have been proposed across several clinical settings, including surgical planning, pain treatment, rehabilitation, and mental health [6]. Within mental health, XR systems have shown promise in both diagnosing [7] and treating [8] transdiagnostic processes such as cravings, stress reactivity, attentional bias, and emotional regulation, factors that play a central role in substance use trajectories. By enabling the controlled replication of real-world triggers within immersive environments, XR is particularly well suited for interventions such as cognitive behavioral therapy and cue-exposure therapy, where ecological validity is critical [9].Reflecting this potential, NIDA has funded innovative research targeting multiple SUD, with a portfolio that includes studies on XR applications for opioid use disorder [10,11], stimulant use [12], and vaping [13]. Together, these projects illustrate both the breadth of XR applications under investigation and the growing interest in immersive technologies for SUD treatment.While other digital health solutions (e.g., mobile apps and web-based platforms) have been proposed in SUD treatment, XR differs from conventional digital therapeutics in its reliance on immersive, multisensory environments that more effectively elicit craving and support in-context practice of coping skills [14]. At the same time, these features introduce distinct challenges, including heightened cybersecurity and data privacy risks associated with rich behavioral and biometric data capture [15], considerations for informed-consent related to psychological presence, and the potential for adverse effects such as dissociation or trigger intensification [16]. In addition, the cost of XR devices and the need for supporting technological infrastructure may exacerbate existing inequities, disproportionately limiting access for low-income, rural, and marginalized populations [16].The design of a successful XR platform must ensure integration into current clinical workflows, access and ease of use for patients and their caregivers, and affordable costs [6]. Successful implementation requires not only clinician training and technical support infrastructure, but also consideration of session duration, therapeutic space requirements, and protocols for managing potential adverse reactions within busy clinical environments, as studies have identified organizational and logistical barriers, including limited clinician time, inadequate training opportunities, lack of dedicated treatment space, and insufficient technical support, that hinder the real-world adoption of XR technologies in healthcare settings [17]. The demonstration of clinical necessity for reimbursement may also require comparison with current standard treatments and evidence-based development frameworks that guide real-world implementation [18]. These practical implementation challenges are as critical as the scientific evidence base, yet they remain underexplored in many development programs.Beyond these implementation and equity concerns, XR-based medical devices must also meet rigorous evidence standards for safety and effectiveness. As outlined by the FDA in the DeNovo approval of EaseVRx [1], safety evaluation of a complete system required multiple assessments, including biocompatibility testing to ensure the headset does not cause tissue reactions, as well as assessments of electromagnetic compatibility and electrical, mechanical, and thermal safety to prevent interference or risk of shock. Systems must also be evaluated for user discomfort, nausea, and motion sickness. Notably, these requirements pertain specifically to "virtual reality behavioral therapy device for pain relief" as specified in FDA regulation 890.5800. While this framework may not be directly applicable to all XR systems intended for other clinical uses, it provides valuable guidance on possible regulatory requirements [19].Demonstrating effectiveness typically requires rigorous clinical trial design that meets FDA expectations [20]. A critical challenge is the development of credible sham controls, namely, XR systems intentionally designed to have no therapeutic effect but that appear convincing enough to maintain participant blinding [21]. Because of the variation in specific interventions and peculiarities of intended use and indications for FDA-approved medical devices, the specific sham developed for one intended use may not be applicable to a study with different intended use and population. Two-dimensional visualizations delivered through the XR headset were accepted for early FDA-cleared applications [1]. However, an important open question remains as to whether such designs represent the best control for interventions that use XR to deliver behavioral therapies for substance use. For these applications, a fully immersive sham where the specific therapeutic component has been modified may be more appropriate [21]. This question highlights the complexity of establishing rigorous evidence standards for XR-based SUD interventions.Critical research gaps include the need for long-term outcome studies extending beyond initial treatment response to assess sustained abstinence, relapse prevention, and quality of life changes, as most current VR trials focus on proximal outcomes like craving and involve small, heterogeneous samples [22]. Comparative effectiveness trials against established interventions are scarce, and standardization of treatment parameters such as session duration and frequency remains underdeveloped [22].While XR holds substantial promise as a transformative tool in the prevention, diagnosis, and treatment of SUD, realizing this potential requires coordinated effort across multiple stakeholders. Researchers need to continue generating rigorous evidence while developing innovative trial designs appropriate for immersive technologies. Critical questions remain open, from optimal sham control design to accessibility and affordability. Advancement depends on regulatory pathways that balance innovation with patient safety, sustainable reimbursement models that recognize the value of these interventions, and sustained support for both foundational science and translational research that bridges the gap between laboratory findings and clinical implementation.Additional research is needed to evaluate XR interventions across diverse cultural contexts, healthcare systems with varying resource levels, and populations with different patterns of substance use. Globally, an estimated 296 million people (5.6% of the population aged 15 to 64) used drugs in 2022 [23], with substantial variation in SUD prevalence across countries, types of substances used, and demographic and socioeconomic characteristics [24]. Despite this global burden, only about 1 in 11 people with drug use disorders received treatment in 2022 [23], highlighting a critical treatment gap that disproportionately affects low-and middle-income countries [25]. The increasing availability of low-cost mobile VR platforms and the potential for asynchronous, self-guided interventions suggest that XR-based approaches could expand access to evidence-based SUD treatment in underserved settings [22,26]. However, realizing this potential will require culturally adapted therapeutic content validated in diverse populations, sustainable implementation models that address technology literacy and infrastructure barriers [27], standardization of VR methodologies and treatment parameters [22], and international research partnerships that prioritize local expertise and community engagement [28].