VR Retrieval–Extinction Training Shows Only Short-Lived Cue Reactivity Reductions in Methamphetamine Use Disorder

A randomized controlled trial of virtual reality-based retrieval–extinction training in methamphetamine use disorder has found that the approach produced only short-lived reductions in cue reactivity, and that the effects did not demonstrate the reconsolidation-specific mechanism the intervention was designed to exploit. The study, published in BMC Psychiatry, enrolled 53 male individuals with methamphetamine use disorder and randomly assigned them to three groups that differed in the timing and content of a brief VR retrieval session preceding extinction training. The final analytic sample comprised 48 participants after attrition.

Methamphetamine use disorder is characterized by a high relapse risk driven by persistent drug-associated memories. Retrieval–extinction training is grounded in memory reconsolidation theory, which holds that a retrieved memory enters a temporary unstable state during which it can be modified. The strategy tested in the trial was to reactivate drug-related memories with a virtual reality scene and then deliver extinction training within the reconsolidation window, in the hope of weakening the memory more durably than standard extinction alone. Virtual reality was chosen because it may enhance memory reactivation during retrieval, offering controlled, immersive drug-related cues that conventional cue exposure cannot easily replicate.

Participants were assigned to one of three conditions. The R–10 min–E group received methamphetamine-related VR retrieval followed by extinction training 10 minutes later, placing the extinction within the presumed reconsolidation window. The NR–10 min–E group received neutral VR retrieval followed by extinction 10 minutes later, serving as the comparison condition without drug-cue reactivation. The R–6 h–E group received methamphetamine-related VR retrieval followed by extinction 6 hours later, outside the reconsolidation window, allowing the researchers to test whether the timing of extinction relative to retrieval mattered. The intervention was delivered over two consecutive days.

Outcome measures captured both the subjective and physiological dimensions of cue reactivity. Cue-elicited self-reported craving was assessed alongside skin conductance responses and heart rate, recorded at pre-test and at 1-day, 1-week, 1-month, and 6-month follow-ups. Crucially, responses were measured to both the original methamphetamine-related VR scenes used in training and to novel methamphetamine-related scenes, allowing the researchers to test whether any reductions generalized beyond the specific cues encountered during the intervention. Groups were compared using baseline-adjusted analyses of covariance with false discovery rate correction for multiple comparisons.

The results showed that cue reactivity decreased in all three groups over time. Compared with the neutral-retrieval group, the methamphetamine-retrieval group that received extinction 10 minutes later reported lower craving at the 1-day follow-up and showed lower skin conductance responses and heart rate at 1 week. That group also showed lower heart rate than the group whose extinction came 6 hours after retrieval at 1 day, with a corrected significance value of q = 0.08.

Generalization to novel scenes was partial and confined to physiological measures. Skin conductance responses to novel methamphetamine-related scenes were lower in the R–10 min–E group at 1 day, and in both retrieval groups at 1 week, at q < 0.05. Heart rate responses to novel scenes were lower in the R–10 min–E group at 1 week, with q = 0.08. Craving in response to novel scenes did not differ between groups at any time point, indicating that the subjective component of cue reactivity did not generalize beyond the trained cues.

The durability findings were the study’s most consequential result. No group differences remained at the 1-month or 6-month follow-ups, meaning the observed advantages of retrieval–extinction training had dissipated within a month. An exploratory analysis of correlations between retrieval-phase craving and 6-month change did not survive false discovery rate correction, providing no support for the idea that the intensity of memory reactivation predicted longer-term outcomes.

The authors’ interpretation is notably cautious. Extinction after methamphetamine-related VR retrieval was followed by short-lived reductions in some indices of cue reactivity, with partial short-term generalization of physiological effects. However, because the effects did not depend on the timing of extinction, the pattern expected if reconsolidation were the operative mechanism was not observed. The researchers also note that the findings may partly reflect additional methamphetamine-cue exposure in the retrieval groups rather than a reconsolidation-specific process, since those participants encountered drug-related VR scenes that the neutral-retrieval group did not. Reconsolidation-specific effects were therefore not demonstrated.

The trial was registered with the Chinese Clinical Trial Registry as ChiCTR1800018899, registered on October 16, 2018. The authors conclude that larger trials with equated cue exposure across groups and no-treatment controls are needed to establish whether retrieval–extinction training offers benefits beyond those attributable to extra cue exposure. For a field in which relapse driven by persistent drug-associated memories remains a central clinical challenge, the study tempers expectations that a single two-day VR-based memory intervention can produce lasting reductions in cue reactivity, while leaving open the possibility that better-controlled designs might yet clarify the role of memory reconsolidation in addiction treatment.

Subject of Research: Virtual reality-based retrieval–extinction training and cue reactivity in methamphetamine use disorder

Article Title: Virtual reality-based retrieval–extinction training reduces cue reactivity in methamphetamine use disorder: a randomized controlled trial with 6-month follow-up

Article References: Liu, W., Mo, Y.-K., Qiao, S.-Y., Wang, X., & Li, Y.-H. (2026). Virtual reality-based retrieval–extinction training reduces cue reactivity in methamphetamine use disorder: a randomized controlled trial with 6-month follow-up. BMC Psychiatry. https://doi.org/10.1186/s12888-026-08826-z

Image Credits: AI Generated

DOI: 10.1186/s12888-026-08826-z

Keywords: methamphetamine use disorder, virtual reality, retrieval-extinction training, memory reconsolidation, cue reactivity, randomized controlled trial, craving, skin conductance response, heart rate, extinction training, BMC Psychiatry, Virtual