Cue-Induced Retrieval and Reconsolidation with Episodic Future Thinking for Craving and Delay Discounting in Opioid Use Disorder: A Pilot Randomized Controlled Trial
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Aims
To evaluate whether Cue-Induced Retrieval and Reconsolidation with Episodic Future Thinking (CIREF), which combines personalized drug-cue retrieval with structured future-oriented processing, produces greater changes in craving and delay discounting than a recent-past episodic active control in individuals with opioid use disorder receiving methadone maintenance treatment.
Design
Multicentre, two-arm, parallel-group randomized controlled pilot trial with per-protocol analyses.
Setting
Two outpatient addiction treatment and rehabilitation centres in Tehran, Iran.
Participants
Thirty participants with opioid use disorder receiving methadone maintenance treatment were randomized to CIREF or Episodic Recent Thinking (ERT; n = 15 per group). Twenty-eight completed the intervention and were included in the analyses (n = 14 per group).
Intervention and comparator
Participants completed one screening, baseline, and personalized cue-development session followed by three 75-minute intervention sessions. CIREF combined personalized drug-cue retrieval with future-oriented simulation, prediction, intention, and planning. ERT was structurally matched but anchored episodic processing to the recent past.
Measurements
Primary craving outcomes comprised the three Desire for Drug Questionnaire (DDQ) subscales assessing session-level phasic/current craving immediately before and after each intervention session and the four Obsessive–Compulsive Drug Use Scale (OCDUS) subscales assessing tonic craving before and after the intervention period. The secondary outcome was Monetary Choice Questionnaire (MCQ) log(k), with more negative values indicating less steep delay discounting.
Findings
After Holm correction across the three DDQ subscales, Group × Occasion interactions indicated greater reductions with CIREF for Desire and Intention to Drug Use, FGG(1.23, 32.09) = 24.37, pHolm < .001, η²p = .484, and Negative Reinforcement, FGG(1.35, 35.23) = 17.67, pHolm < .001, η²p = .405, but not Drug Abuse Control (pHolm = .172). After Holm correction across the four OCDUS subscales, only Desire and Mental Preoccupation with Drugs showed a significant Group × Time interaction, F(1, 26) = 12.35, pHolm = .007, η²p = .322; the remaining subscales were not significant (adjusted ps ≥ .177). MCQ log(k) showed a Group × Time interaction, F(1, 26) = 7.18, p = .013, η²p = .217; mean log(k) changed from −1.22 (0.36) to −1.80 (0.55) in CIREF and from −1.39 (0.32) to −1.44 (0.44) in ERT.
Conclusions
In this small pilot sample, the future-oriented retrieval-based intervention produced greater changes than the recent-past active control in two dimensions of session-level phasic craving, one dimension of tonic craving, and monetary delay discounting. The results are preliminary and do not establish memory reconsolidation or effects on relapse or longer-term clinical outcomes.
