MAT for opioid use disorder: medication-assisted treatment, explained

Opioid Use Disorder (OUD) is increasingly recognised as a chronic neurobiological condition1, characterised by changes to the brain’s reward and stress systems. The primary pathology of OUD lies in the dysregulation of the mu-opioid receptor² and its downstream signalling pathways, which are essential for modulating pain, pleasure, and reward. 

When opioids are used chronically, they cause adaptive neuroplastic changes, which reinforce the compulsive seeking and consumption of these substances despite negative consequences.

The neurobiological hallmark of OUD³ is the development of tolerance, where increasing amounts of the drug are required to achieve the desired effect. As tolerance builds, withdrawal symptoms manifest when opioid use is reduced or ceased, leading to cravings and heightened vulnerability to relapse. This vicious cycle is driven by changes in the mesolimbic dopaminergic system, which controls reward processing, and the hypothalamic-pituitary-adrenal (HPA) axis, which regulates stress responses.

The condition often co-occurs with other mental health experiences, such as depression, anxiety, and PTSD, further complicating treatment. In the UK, opioid overdose deaths have surged in recent years⁴, underlining the urgent need for comprehensive, evidence-based interventions that consider both the neurobiological and psychosocial components of recovery.

Effective management of OUD necessitates a multifaceted approach, integrating pharmacological treatments – such as Medication-Assisted Treatment (MAT) with psychosocial therapies that address the underlying psychological and emotional drivers of addiction. 

What Is MAT? Definitions, frameworks, & evidence base

Medication-Assisted Treatment (MAT) refers to the use of FDA-approved medications in combination with counselling and behavioural therapies to treat opioid use disorder (OUD)⁵. The primary goal of MAT is to reduce opioid cravings, prevent withdrawal symptoms, and restore balance to the brain’s neurochemistry, all while supporting recovery⁶ through psychosocial interventions.

In the UK, MAT is commonly referred to as opioid substitution treatment (OST) and follows similar principles, using medications such as methadone or buprenorphine alongside structured psychological and social support. While terminology may vary, the core objective – supporting safe, long-term recovery – remains consistent.

The most commonly used medications in MAT include methadone, buprenorphine, and naltrexone⁷. Methadone and buprenorphine are opioid agonists or partial agonists that bind to the same receptors as opioids⁸, but in a controlled, less intense manner, alleviating cravings without producing the euphoria associated with illicit drug use. Naltrexone, on the other hand, is an opioid antagonist, blocking opioid receptors and preventing the reinforcing effects⁹ of opioid use.

MAT frameworks are rooted in a bio-psycho-social approach, addressing the neurobiological, psychological, and social aspects of addiction. The integration of pharmacotherapy with counselling and behavioural therapies (eg., Cognitive Behavioural Therapy, Contingency Management) helps individuals develop coping strategies, manage triggers, and build long-term recovery skills.

The scientific consensus

The evidence supporting MAT is robust. Numerous systematic reviews¹⁰ and clinical trials¹¹ demonstrate that MAT significantly improves retention in treatment, reduces the risk of opioid overdose, and enhances long-term recovery outcomes. 

MAT has been shown to decrease opioid misuse¹², reduce the transmission of infectious diseases like HIV and hepatitis C, and improve overall physical and mental health.

Emerging research highlights the role of extended-release formulations (eg., extended-release buprenorphine or injectable naltrexone) in improving treatment adherence¹³ and reducing the risk of relapse. 

As understanding of OUD advances, MAT continues to be recognised as the cornerstone of effective, evidence-based treatment for opioid addiction.

Adjunctive psychosocial interventions in MAT

While medications are central to the treatment of opioid use disorder (OUD), adjunctive psychosocial interventions are equally critical in ensuring long-term recovery. These interventions target the psychological and behavioural aspects of addiction, helping individuals address underlying issues and develop coping strategies. The most commonly used psychosocial approaches in MAT include:

• Cognitive Behavioral Therapy (CBT): CBT helps individuals identify and challenge negative thought patterns and behaviours associated with substance use. By developing healthier coping mechanisms, patients can better manage stress, triggers, and cravings.
• Contingency Management (CM): CM is a behavioural therapy that reinforces positive behaviours such as drug abstinence by providing tangible rewards. This strategy has shown efficacy in increasing treatment adherence and encouraging long-term recovery¹⁴.
• Motivational Interviewing (MI): MI enhances motivation by addressing ambivalence about recovery¹⁵. This client-centered, non-judgmental approach strengthens commitment to change and helps individuals navigate the stages of recovery.
• Family Therapy: Where appropriate, family therapy can address the impact of OUD on relationships, aiming to improve communication, rebuild trust, and foster a supportive home environment. This approach is crucial in enhancing treatment outcomes and preventing relapse.

MAT outcomes: retention, mortality, & relapse reduction

Medication-assisted treatment (MAT) is consistently associated with improved clinical outcomes across multiple domains16 in the management of opioid use disorder (OUD). 

A growing body of UK- and US-based research, including meta-analyses and systematic reviews, underscores MAT’s role in reducing harm, stabilising recovery, and supporting long-term behavioural change.

Treatment retention

Retention in care is a core metric of treatment success. Patients receiving MAT – particularly with methadone or buprenorphine – demonstrate significantly higher retention rates¹⁷ compared to non-pharmacological approaches. 

Prolonged engagement with services allows for sustained behavioural therapy, medical monitoring, and social reintegration, all of which contribute to lasting recovery.

Reduction in mortality

MAT dramatically reduces the risk of all-cause and opioid-specific mortality. 

Studies indicate that patients on methadone or buprenorphine maintenance experience a >50% reduction in overdose deaths¹⁸ compared to those who discontinue treatment. Mortality risk is especially elevated during the induction and discontinuation phases, reinforcing the importance of clinical oversight and continuity of care.

Relapse prevention

MAT mitigates the severity and frequency of relapse by stabilising neurochemical dysregulation within the brain’s reward and stress systems¹⁹. Cravings are reduced through mu-opioid receptor modulation, while the inclusion of psychosocial supports strengthens cognitive resilience and emotional regulation. 

Extended-release formulations, such as injectable buprenorphine or naltrexone, may further improve adherence and relapse outcomes.

Clinical considerations

Effective delivery of medication-assisted treatment for opioid use disorder (OUD) requires nuanced clinical judgement, and induction protocols differ by agent. 

Methadone requires cautious titration due to overdose risk²⁰, while buprenorphine permits flexible initiation²¹ based on withdrawal onset. Extended-release options may improve adherence in complex or high-risk presentations. 

Drug interactions – particularly with CNS depressants like benzodiazepines – must be closely monitored²², as must concurrent psychotropic regimens to avoid iatrogenic harm.

Moreover, prescribers must be licensed under UK controlled drug legislation, with diversion-resistant formulations such as buprenorphine/naloxone often preferred. Regular monitoring, including urine drug screening, liver function tests, and structured outcome measures, supports safe, adaptive care. 

Reframing MAT as evidence-based recovery – not substitution

Medication-assisted treatment (MAT) should not be misconstrued as mere pharmacological substitution²³. Rather, it is a rigorously evidence-based, clinically validated approach to managing opioid use disorder (OUD) as a chronic neurobiological disease. 

By stabilising neurochemical dysregulation, reducing all-cause mortality, and enhancing treatment retention, MAT forms the cornerstone of sustainable, whole-person recovery – especially when delivered alongside structured psychosocial support.

When implemented with clinical precision and compassionate care, MAT enables individuals to re-establish agency, rebuild cognitive and emotional function, and engage meaningfully with long-term therapeutic goals. Harbor London offers private, medically-led pathways grounded in both the science of neurobiology and the art of therapeutic alliance – supporting individuals and families in navigating the complex journey from dependency to enduring wellness.

If you’re a clinician or a healthcare professional, explore our referral options or contact us today to learn more about our integrated, specialist-led services.

References

1. https://onlinelibrary.wiley.com/doi/pdf/10.1111/add.15636#:~:text=Keywords%20Brain%2C%20cognition%2C%20neuroimaging%2C,treatment.&text=Opioid%20use%20disorder%20(OUD)%20is,repeated%20exposure%20to%20exogenous%20opioids.
2. https://www.ncbi.nlm.nih.gov/books/NBK546642/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC2851054/ 
4. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2023registrations#:~:text=Almost%20half%20of%20all%20drug,in%202022%20(2%2C261%20deaths).
5. https://www.azahcccs.gov/Members/BehavioralHealthServices/OpioidUseDisorderAndTreatment/MAT.html
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC2851054/
7. https://nida.nih.gov/research-topics/medications-opioid-use-disorder#:~:text=Medications%20to%20treat%20opioid%20use%20disorder&text=They%20may%20also%20help%20treat,methadone%2C%20buprenorphine%2C%20and%20naltrexone.
8. https://journals.sagepub.com/doi/10.1177/0963689718811060
9. https://academic.oup.com/alcalc/article/36/1/2/137995
10. https://www.ncbi.nlm.nih.gov/books/NBK553166/
11. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2760032
12. https://www.psychiatry.org/patients-families/opioid-use-disorder
13. https://pmc.ncbi.nlm.nih.gov/articles/PMC6980175/
14. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2782768
15. https://harborlondon.com/motivational-interviewing-drug-addiction/
16. https://www.ncbi.nlm.nih.gov/books/NBK534504/
17. https://pmc.ncbi.nlm.nih.gov/articles/PMC5312702/
18. https://www.bmj.com/content/357/bmj.j1550
19. https://pmc.ncbi.nlm.nih.gov/articles/PMC6165853/
20. https://www.ncbi.nlm.nih.gov/books/NBK562216/
21. https://intjem.biomedcentral.com/articles/10.1186/s12245-024-00593-6
22. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-withholding-opioid-addiction-medications
23. https://nida.nih.gov/research-topics/addiction-science/words-matter-preferred-language-talking-about-addiction