Craving, Impulsivity, and Subsequent Methamphetamine Use With Naltrexone-Bupropion Versus Placebo: Findings From a Randomized Clinical Trial

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Craving, Impulsivity, and Subsequent Methamphetamine Use With Naltrexone-Bupropion Versus Placebo: Findings From a Randomized Clinical Trial

Published: March/April 2026
Journal Article

Overview

This one-hour, journal article–based activity explores key clinical predictors of treatment success for methamphetamine use disorder (MUD) by analyzing secondary data from the landmark ADAPT-2 trial. The article examines how patient levels of craving and impulsivity correlate with transitions between positive and negative urine drug screens (UDS) in individuals receiving a combination of injectable naltrexone and oral bupropion. These findings provide insights for clinicians aiming to optimize pharmacotherapy outcomes and tailor interventions for a high-risk population currently lacking FDA-approved medication options. 

The target audience for this intermediate continuing education activity includes physicians, nurse practitioners, physician assistants, and other clinicians, researchers, students, and policymakers. 

This activity addresses the following ACGME Core Competencies: Patient Care, Medical Knowledge, Practice-Based Learning and Improvement, and Systems-Based Practice 

Abstract

Aims 

The accelerated development of additive pharmacotherapy treatment (ADAPT-2) for methamphetamine use disorder (MUD) trial demonstrated the efficacy of extended-release injectable naltrexone (NTX) and oral bupropion (BUP). In this secondary analysis, we determined whether craving and impulsivity levels could predict subsequent use of methamphetamine.

Methods

Participants (N = 357) of the ADAPT-2 trial with at least one transition point [transition from positive-to-negative urine drug screen (UDS) or vice versa] during stage 1 (baseline through week-6) were included in this secondary analysis. Craving was assessed using the Visual Analog Scale (VAS). Impulsivity was assessed using the 2-item impulsivity factor of the Concise Health Risk Tracking (CHRT) Scale.

Results

A significant treatment by craving by time interaction was noted (P = 0.018), where higher craving levels were consistently associated with a lower likelihood positive-to-negative UDS transition at the next visit in both NTX-BUP and placebo groups. However, no such effect was present by week 6 of treatment in the placebo group. CHRT Impulsivity also had a significant effect on the probability of a positive-to-negative UDS transition (P = 0.019) in addition to the 3-way interaction of VAS, week, and treatment group. Individuals with lower craving levels but higher impulsivity exhibited a lower probability of transitioning to negative UDS at the next visit. Higher craving, but not impulsivity, was associated with a higher likelihood of negative-to-positive UDS transition at the next visit in both treatment groups.

Conclusion

Further investigations are necessary to optimize NTX-BUP treatment, focusing on the impact of craving and impulsivity on outcomes.

Learning Objectives

Upon completion of this activity, learners will be able to:

  1. Analyze the relationship between craving levels and achieving or maintaining negative urine drug screens during methamphetamine use disorder treatment.  
  2. Evaluate the independent and interactive effects of impulsivity and craving on treatment transitions, recognizing how high impulsivity may impede recovery even when craving levels are low.  
  3. Summarize the clinical significance of using the naltrexone-bupropion (NTX-BUP) combination for MUD and understanding behavioral phenotypes such as craving and impulsivity to inform personalized therapeutic approaches. 

Registration Rates

Rate DescriptionRate
ASAM Member$0
Non-Member$39
Associate Member$0
Resident Member*$0
Student Member*$0

*Residents, Fellows-in-training, Interns, and Students must join ASAM to receive a discounted registration rate. Click here to become an ASAM member. National and Chapter membership dues apply. There is no charge for Students to become a Member, but verification of student status is required.

Membership Question?  Call ASAM at 1.301.656.3920, email us, or view the ASAM website for more information.

Refunds & Cancellations

All ASAM eLearning Center refund requests must be made in writing to education@asam.org within 90 days of purchase. Those requesting refunds for courses that are in progress will receive partial refunds or eLearning Center credit. Automatic full refunds will be made for any course with a live-course component that has been canceled.

Open Registration: 03/19/2026 - 02/10/2029

Close Access Date: 02/10/2029

Course Instructions

  1. Click on the Contents tab to begin this activity.
  2. Click Download Journal Article in the box titled Journal Article and read the journal article in its entirety. 
  3. Click Complete Post-Test to answer multiple-choice questions. You will have 10 attempts to pass and must answer 2 out of 3 questions correctly.
  4. Click Complete Evaluation to provide valuable activity feedback. Scroll down on all questions, as there may be answer options that expand past the size of the window.
  5. Click the button Claim Medical Credits in the box titled Claim Credits & Certificate. Choose the type of credit and click submit. Click the button View/Print Certificate to save or print your certificate. You can view/print your certificate at any time by visiting the ASAM eLearning Center, clicking Dashboard, and clicking Transcript/Achievements.

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Accreditation & Credits

Joint Accreditation Statement

In support of improving patient care, the American Society of Addiction Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Credits Available
  • Physicians: 1.00 Credit
  • Nurses & NPs: 1.00 Nursing Contact Hour
  • PAs: 1.00 Credit
  • Pharmacology Hour: 1 Hour
  • Interprofessional Continuing Education: 1.00 Credit
  • Certified Counselors: NBCC Contact Hours Not Offered

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    American Society of Addiction Medicine has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 7062. Programs that do not qualify for NBCC credit are clearly identified. American Society of Addiction Medicine is solely responsible for all aspects of the programs.
  • Maintenance of Certification (MOC)/Continuing Certification Program (CCP)

    This activity is designed to meet the requirements for MOC/CCP for several primary physician boards and for state licensing CME requirements. MOC Credit is only reported and designated for ABA, ABP, ABIM, and ABS. By completing the online credit application and evaluation, the learner permits ASAM to report credits to the appropriate Board. Learn more.

    • ABIM MOC Points: 1.00 Medical Knowledge
    • ABP MOC: 1.00 Lifelong Learning & Self-Assessment
    • ABS Continuing Certification: 1.00 Accredited CME
    • ABA MOCA 2.0®*: 1.00 Lifelong Learning MOCA 2.0® is a trademark of the American Board of Anesthesiology®. This activity contributes to the CME requirement for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology's (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, https://www.theaba.org/, for a list of all MOCA 2.0 requirements.

    Additionally, this activity has been designed to satisfy the requirements of the following primary physician board certification requirements. Please confirm with your individual Board.

    • American Board of Addiction Medicine (ABAM)
    • American Board of Preventive Medicine (ABPM)
    • American Board of Psychiatry and Neurology (ABPN)
    • Royal College of Physicians and Surgeons of Canada (RCPSC)
    Certificates for other professions

    All participants may request a certificate of participation upon completion of the activity and an online evaluation confirming their participation. Learners are strongly advised to contact their professional licensing board or professional association to confirm this certificate will be accepted as evidence supporting continuing education requirements.

    California Association for Drug/Alcohol Educators (CAADE)

    This educational program is approved by CAADE: #CP40 999 1225.

    California Association of DUI Treatment Centers (CADTP)

    This educational program is approved by CADTP: #205.

    California Consortium of Addiction Programs and Professionals (CCAPP)

    This educational program is approved by CCAPP: #OS-20-330-0227.

    Disclosure Information

    In accordance with the disclosure policies of ASAM and Joint Accreditation, the effort is made to ensure balance, independence, objectivity, and scientific rigor in all accredited continuing education activities. These policies include identifying and mitigating all relevant financial relationships with ineligible companies for those involved in the creation and dissemination of accredited continuing education. 

    See the attached article and pdf for a list of disclosures


Key:

Complete
Failed
Available
Locked
Journal Article
Open to download resource.
Open to download resource. This article was published in the March/April 2026 issue of the Journal of Addiction Medicine.
Complete Post-Test
3 Questions  |  10 attempts  |  2/3 points to pass
3 Questions  |  10 attempts  |  2/3 points to pass To complete and receive credit for this CE activity, you must answer at least two out of the following three questions correctly.
Complete Evaluation
9 Questions
9 Questions Please scroll down to view questions that may extend beyond the visible window.
Claim Credit & Certificate
Up to 1.00 medical credits available  |  Certificate available
Up to 1.00 medical credits available  |  Certificate available Participants should claim only the credit commensurate with the extent of their participation in this activity.