Ketamine, an interoceptive associative agent? Evidence from ketamine-assisted Mindfulness-Oriented Recovery Enhancement for opioid use disorder
Benjamin R. Lewis, Eric L Garland
Journal of Psychopharmacology November 5, 2026 DOI: 10.1177/02698811261495546 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary analysis of a randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 68 |
| Population | Adults with opioid use disorder receiving buprenorphine |
| Interventions | Ketamine-assisted psychotherapy Mindfulness-Oriented Recovery Enhancement (MORE) |
| Duration | 8 weeks of MORE with or without KAP; follow-up to 3 months |
| Measures | Ecological momentary assessment (EMA) of body awareness, Multidimensional Assessment of Interoceptive Awareness (MAIA) subscales |
| Topics | Addiction Esketamine Ketamine Meditation |
| Registration | NCT04892251 |
| Key findings | Adding ketamine-assisted psychotherapy to MORE was associated with a rapid, sustained increase in ecological momentary assessment body-awareness salience and with higher MAIA Self-Regulation and Body Listening scores. A composite of these interoceptive facets mediated reduced opioid craving at three months (indirect effect B = -11.27, 95% CI [-25.50, -0.25]). |
Abstract
Background: Relapse in opioid use disorder (OUD) remains common despite pharmacotherapy. Altered interoceptive processing may contribute to addiction, and ketamine-induced changes in salience and insula-related networks may facilitate mindfulness-based interoceptive learning.
Aims: This secondary analysis examined whether ketamine-assisted psychotherapy (KAP) added to Mindfulness-Oriented Recovery Enhancement (MORE) improved interoceptive awareness and whether these changes mediated reductions in opioid craving.
Methods: Sixty-eight adults with OUD receiving buprenorphine were randomized to 8 weeks of MORE with or without KAP. Assignment was unblinded, and outcomes were self-reported. Interoception was assessed using ecological momentary assessment (EMA) of body awareness and Multidimensional Assessment of Interoceptive Awareness (MAIA) subscales. Posttreatment EMA data were available for 18 MORE + KAP and 15 MORE participants. Mixed-effects models and path analysis were conducted.
Results: Piecewise modeling showed a greater increase in EMA-assessed body awareness salience in MORE + KAP during days 1–35, spanning the pre-dosing and first-ketamine-dose period ( B = 0.039, standard error (SE) = 0.005, p < 0.001). Slopes attenuated during days 36–90 (group × slope-change: B = −0.035, SE = 0.008, p < 0.001), although body awareness remained higher for MORE+KAP through follow-up. MORE + KAP increased MAIA Self-Regulation and Body Listening. A composite of these facets mediated reduced opioid craving at 3 months (indirect effect: B = −11.27, 95% bootstrap confidence interval (CI) [−25.50, −0.25], p = 0.044; κ 2 = 0.378).
Conclusions: Adjunctive ketamine was associated with rapid, sustained increases in body awareness salience. Improvements in interoceptive regulatory capacity mediated reduced opioid craving, supporting interoception as a potential mechanism and treatment target in ketamine-augmented mindfulness interventions for OUD. ClinicalTrials.gov: NCT04892251
Comparable studies
Other randomized controlled trials on ketamine for addiction, most cited first.