Extended reality (XR) technologies, including virtual reality (VR), augmented, and mixed reality, are rapidly emerging as therapeutic tools with strong potential to address the growing public health burden of SUDs. As the need for scalable, engaging, and evidence-based interventions increases, XR provides a unique opportunity to deliver personalized, immersive care, particularly for adolescents and young adults who may be underserved by traditional treatment models and are highly receptive to technology-enabled solutions.

Digital therapeutic products have already gained traction in the U.S. healthcare system. The National Institute on Drug Abuse (NIDA), as part of the National Institutes of Health, is the leading funding agency supporting scientific discoveries and their translation into effective treatment strategies for (SUD). NIDA provides programmatic assistance and support to academic investigators and small businesses to develop products that improve the lives of patients and caregivers affected by SUDs. NIDA has funded XR research for 20 years and was the first to recognize the translational and commercial potential of such applications, providing support for the first FDA-cleared XR as medical device for chronic pain (AppliedVR, 2021).

The regulatory landscape for XR-based therapeutics has evolved considerably. The U.S. Food and Drug Administration (FDA) cleared XR-enabled devices for chronic pain management (AppliedVR, 2021; Maddox et al., 2025), including pediatric applications (Smileyscope, 2023), demonstrating regulatory openness to innovative modalities. In parallel, the Centers for Medicare and Medicaid Services proposed reimbursement frameworks for virtual reality (VR) products as durable medical equipment (Centers for Medicare & Medicaid Services CMS, 2022) and, more recently, for digital mental health therapeutics (Centers for Medicare and Medicaid Services (CMS)) 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 (Morgan et al., 2025). Within mental health, XR systems have shown promise in both diagnosing (Kjærstad et al., 2025) and treating (Gardin et al., 2022) 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 (Kuntze et al., 2001).

Reflecting this potential, NIDA has funded innovative research targeting multiple SUDs, with a portfolio that includes studies on XR applications for opioid use disorder (National Institutes of Health, 2026a; National Institutes of Health, 2026b), stimulant use (National Institutes of Health, 2026c), and vaping (National Institutes of Health, 2026d). 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 (Segawa et al., 2020). At the same time, these features introduce distinct challenges, including heightened cybersecurity and data privacy risks associated with rich behavioral and biometric data capture (Lake et al., 2024), considerations for informed-consent related to psychological presence, and the potential for adverse effects such as dissociation or trigger intensification (Goulet et al., 2024). 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 (Goulet et al., 2024).

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 (Morgan et al., 2025). 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 (Kouijzer et al., 2023). 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 (Kim et al., 2024). 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 (AppliedVR, 2021), 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 (Beams et al., 2022).

Demonstrating effectiveness typically requires rigorous clinical trial design that meets FDA expectations (Food and Drug Administration FDA, 2013). 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 (Persky and Colloca, 2023). 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 (AppliedVR, 2021). 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 (Persky and Colloca, 2023). 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 XR trials focus on proximal outcomes like craving and involve small, heterogeneous samples (Glavak-Tkalić et al., 2025). Comparative effectiveness trials against established interventions are scarce, and standardization of treatment parameters such as session duration and frequency remains underdeveloped (Glavak-Tkalić et al., 2025).

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 15–64) used drugs in 2022 (United Nations Office on Drugs and Crime, 2024), with substantial variation in SUD prevalence across countries, types of substances used, and demographic and socioeconomic characteristics (Volkow and Blanco, 2023). Despite this global burden, only about 1 in 11 people with drug use disorders received treatment in 2022 (United Nations Office on Drugs and Crime, 2024), highlighting a critical treatment gap that disproportionately affects low- and middle-income countries (World Health Organization, 2022). The increasing availability of low-cost mobile XR 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 (Glavak-Tkalić et al., 2025; Freeman et al., 2017). However, realizing this potential will require culturally adapted therapeutic content validated in diverse populations, sustainable implementation models that address technology literacy and infrastructure barriers (Means et al., 2020), standardization of XR methodologies and treatment parameters (Glavak-Tkalić et al., 2025), and international research partnerships that prioritize local expertise and community engagement (Patel et al., 2018).