Methadone Induced Memory Retrieval-extinction Procedure in Heroin Addicts

A Novel Methadone-induced Memory Retrieval-extinction Procedure to Prevent Heroin Craving and Relapse

The study assessed the efficacy of a methadone-induced memory retrieval-extinction procedure on heroin craving and relapse. Male participants aged 18-55 years old and prescribed MMT to treat heroin dependence were included in the present study, and randomly assigned to receive methadone, or receive methadone plus 10 minutes plus extinction, or receive methadone plus 6 hours plus extinction. The intervention persisted 3 times per week for 4 weeks. Then the subjects were followed up once a month for cue induced heroin craving and relapse.

Study Overview

• Status: Completed
• Conditions: Heroin Dependence
• Intervention / Treatment: Behavioral: methadone induced memory retrieval-extinction procedure

Detailed Description

In the present study, we explored the effect retrieval-extinction procedure on heroin craving and relapse in heroin addicts using the methadone (a commonly used µ-opioid receptor agonist) instead of heroin as the trigger to reactivate drug memories. The subjects were randomly divided into 3 groups, in which they received methadone alone or extinction sessions 10 min or 6 hours after methadone administration. The extinction sessions were given 3 times per week for 4 weeks, each lasted for 30 min. During the extinction procedure, the subjects were exposed to images, heroin paraphernalia and mimic heroin. Subjective craving, morphine urine test and physiological responses were recorded monthly for 4 months.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• met the diagnostic criteria of heroin dependence according to DSM-IV
• were prescribed methadone maintenance treatment (MMT) and took it regularly
• no change in city of residence for at least 1 year
• had normal blood pressure and heart rate
• had negative urine morphine screening test
• primary-school level education
• provide signed consent

Exclusion Criteria:

• other substance abuse(except nicotine)
• had a current or past history of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition（DSM-IV) AxisⅠdisorders
• had clinically evident physical disorders
• neurological signs and/or history of neurological disease
• noncompliance with the procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Methadone; The subjects take methadone as usual.
EXPERIMENTAL: Methadone-10min-Extinction; The subjects were given extinction training 10 min following methadone administration.	Behavioral: methadone induced memory retrieval-extinction procedure; Drug memory is not invariably stable and can be induced transiently labile again by drug-related cues or drug itself, which is termed as 'reconsolidation'. Previously we and other groups have demonstrated that extinction coincided with reconsolidation weakened the drug memory and decreased drug craving and relapse. In the present study, we tried to interfere the methadone-induced heroin addiction memory reconsolidation by extinction given at different times following methadone administration.
SHAM_COMPARATOR: Methadone-6h-Extinction; The subjects were given extinction training 6h following methadone administration.	Behavioral: methadone induced memory retrieval-extinction procedure; Drug memory is not invariably stable and can be induced transiently labile again by drug-related cues or drug itself, which is termed as 'reconsolidation'. Previously we and other groups have demonstrated that extinction coincided with reconsolidation weakened the drug memory and decreased drug craving and relapse. In the present study, we tried to interfere the methadone-induced heroin addiction memory reconsolidation by extinction given at different times following methadone administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of cue induced heroin craving	Heroin craving will be assessed using a visual analog scale (VAS), i.e., an undivided line marked at the left and right ends with 0 ("not at all") and 10 ("extremely high").	Baseline (Day 0 ), post-intervention (1 month), monthly during follow-up for 4 months (2, 3, 4 and 5 month)
change of negative urinary morphine test	All the participants will be required to have urine tests for morphine during screening, weekly during intervention and monthly during follow-up.	Baseline (Day 0), weekly during intervention(1, 2, 3 and 4 week) and monthly during follow-up for 4 months (2, 3, 4 and 5 month)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cue induced heart rate change	Heart rate will be monitored immediately before and after cue exposure	Baseline (Day 0 ), post-intervention (1 month), monthly during follow-up for 4 months (2, 3, 4 and 5 month)
cue induced blood pressure change	Blood pressure will be monitored immediately before and after cue exposure.	Baseline (Day 0 ), post-intervention (1 month), monthly during follow-up for 4 months (2, 3, 4 and 5 month)

Collaborators and Investigators

• Sponsor: National Institute on Drug Dependence, China

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 20, 2015
• Primary Completion (ACTUAL): April 23, 2017
• Study Completion (ACTUAL): April 20, 2019

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (ACTUAL): October 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Heroin Dependence; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Methadone
• Other Study ID Numbers: NIDD12035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No