Quality & Science

Ask the PCSS Expert: Does Evidence Show Naltrexone Reduces Cravings?

by The PCSS Expert | December 15, 2015

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A physician wrote the PCSS mentor network seeking advice on naltrexone. They asked three questions: 

1) Is there evidence that naltrexone reduces cravings? 
2) What is the supposed mechanism of action for naltrexone, a mu antagonist, to help patients eliminate cravings? 
3) Does the patients’ motivation to succeed in treatment correlate with diminished cravings? 

AnswerEmpirical evidence shows that naltrexone reduces cravings which can reduce the risk of relapse. While the exact mechanism in this case is unclear some would argue that this is the case of most of the medications used in psychiatry. Even though there is not a clear “mechanism” (link between the acute pharmacological effect to a behavior change), addiction specialists still use them clinically every day and empirical evidence suggests the importance of treating opioid use disorders with medication (see ASAM’s recently released guideline).  

There are a variety of theories as to why naltrexone works and which biological mechanism might be at play. Some propose that it is a behavioral mechanism, knowing that when opioid receptors are “permanently” blocked, the perceived availability of the drug and craving is decreased. This behavioral mechanism would not, however, explain why craving is lower in the active medication group versus the placebo group. 

What we do know is that craving goes substantially down in people that are on naltrexone, and that this craving reduction occurs pretty much from the beginning of treatment (first 2-3 weeks) and doesn’t seem to return after that. There are certainly people who continue to have cravings, but this is a rather small proportion and usually occurs only after coming off medication. Those who maintain treatment with naltrexone have no cravings, and some believe that combining naltrexone with personal recovery work in a 12-step based program is especially effective. 

• For more information about the Providers’ Clinical Support System for Medication Assisted Treatment (PCSS-MAT) visit  www.pcssmat.org
• To sign up for a mentor CLICK HERE
• Have a Question for PCSS-MAT Experts? CLICK HERE!


Providers’ Clinical Support System is a national training and mentoring project funded by the Substance and Mental Health Services Administration led by American Academy of Addiction Psychiatry in partnership with: American Osteopathic Academy of Addiction Medicine, American Psychiatric Association and ASAM. ASAM Magazine is republishing selected questions received by the PCSS mentors. Please note the Mentoring Program and Listserv discussion group and ASAM Magazine are NOT intended to provide clinical consults for specific patient questions and is offered only as a resource for education and overall guidance.

Funding for this initiative was made possible (in part) by Providers’ Clinical Support System for Medication Assisted Treatment (1U79TI024697) from SAMHSA. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.


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  1. Brady Jun 06, 2019 - 12:07 AM
    My girlfriend had been taking naltrexone and found she was having stronger cravings so she got off of it and found her cravings and mental state were off the charts and put herself in to be Bakeracted. She has been a 12 step program as have i. I have finished my steps and have a good amount of clean time. This change was sudden and profound. Ive heard that when coming off the medication that for a brief time afterwards stronger cravings may occur. Any feedback on this would grately appreciated
  2. werwaer Feb 14, 2019 - 04:50 AM
    It should be noted that the clinical connection between naltrexone's effect on dropping opioid craving in relation to preventing relapse is uniquely attributed in the literature to extended-release naltrexone only; not oral naltrexone - which generally has not been found to yield better clinical outcomes than placebo.  
  3. Mike McGrath Jun 28, 2018 - 02:58 PM

    The research I have seen on long acting naltrexone seems biased by patient self-selection and industry support.  I appreciate the above receptor science, but the underlying distress that defines addiction (anxiety, mood dysregulation, social isolation, etc) would be unlikely to be assuaged by an antagonist.

  4. Terri Marini Jun 13, 2018 - 02:47 PM

    I have read questions/comments regarding the benefits of naltrexone used to treat OUD, yet still lack clarity.  In the SAMHSA TIP 63 on page 1-3 under the heading Benefits, naltrexone is included as one of the medications that reduce or eliminate cravings to use opioids.

    So why in other places in the manual, is the statement of craving reduction or elimination omitted?  Such as on pages 3-5, exhibit 3A.1, and 3-36 under Pharmacology.

  5. asd Mar 10, 2016 - 04:02 PM
    Thank you.
  6. Stuart Wasser MD Dec 18, 2015 - 05:42 PM
    you will get a reduction of cravings with naltexone po when dosed BID.  Naltrexone acts as an inverse agonise slowing down tonically active mu receptors that are ligand free.  This may have effects on intracelleular G proteins, CREB and actylation of DNA which will effect overall nuclear and subsequent cellular function.  Mu receptor synthesis as well as subsequent anchoring of mu receptors to the g proteins are increased thereby increasing the cells responsiveness to endogenous endorphins.  This may be one reason cravings are reduced, pain modulation may be more efficient and many patients have an improved sense of well being
  7. Robert W. Mooney, MD Dec 18, 2015 - 12:30 PM

    Is the question of cravings related to alcohol or opioids? From a clinical perspective I have not been impressed with naltrexone's effects on drinking behavior. I have seen too many patients who say that naltrexone seemed to increase their desire to drink. The research is not overwhelming compared to placebo. Don't forget there will always be a number of patients that medications do not seem to benefit and may actually be harmful. What do you do with those? Clinical based evidence suggest that an abstinence approach is still a viable option.

  8. David R Gastfriend, MD Dec 18, 2015 - 11:41 AM

    It should be noted that the clinical connection between naltrexone's effect on dropping opioid craving in relation to preventing relapse is uniquely attributed in the literature to extended-release naltrexone only; not oral naltrexone - which generally has not been found to yield better clinical outcomes than placebo.  

    Also, there is indeed a neurobiological theory that likely underlies its actions: conditioned cues in the environment prompt dopamine priming (sudden physiologic dopamine releases in the brain's reward center) and endorphins enhance dopamine release.  A stable naltrexone blockade (e.g., with extended-release naltrexone) will prevent this - even with normal diurnal elevations of endorphins.  This protective mechanism is likely concurrent with the behavioral one mentioned in the article. (And even that one is neurobiological at its foundation.)

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