Substance Use Disorder (SUD) is a chronic, relapsing condition with devastating consequences, but it is also one of the most medically treatable behavioral health conditions we face today. Over the last 50 years, the field has evolved from “talk therapy only” to a growing arsenal of medications that can help reduce cravings, block euphoric effects, and support long-term recovery. Despite these tools, far too many people go untreated or drop out of care before achieving stability. This article examines the historical evolution of medication-assisted treatment (MAT), explores current options, breaks down barriers to access and compliance, and previews promising new pharmacotherapies that could redefine addiction treatment in the years ahead.
A Brief History: From Abstinence-Only to Evidence-Based Pharmacotherapy
The treatment of SUD has historically leaned heavily on abstinence and psychotherapy. For decades, “just say no” was a Nancy Reagan common catchphrase, yet relapse rates remained high. And, it wasn’t until the 1960s and 70s that pharmacological treatments began to gain traction, particularly for opioid use disorder (OUD). Methadone, first approved in 1972 for OUD, was the first major step forward. As a full opioid agonist, it helped stabilize individuals and reduce mortality, but strict regulations and stigma kept it out of reach for many. Naltrexone, approved in 1984, introduced a non-opioid antagonist that blocked the effects of opioids but required full detoxification before initiation, limiting its early use. In 2002, buprenorphine (Subutex/Suboxone) was a game-changer: as a partial agonist, it offered a safer, more flexible option that could be prescribed in outpatient settings and filled at the local pharmacy. These treatments all remain available today, and I will discuss them in greater detail below.
What Medications Are Available Today for SUD (and How They Work)
Treatment options for substance use disorders vary by substance, with differing levels of regulatory approval, efficacy, and patient suitability. For Opioid Use Disorder (OUD), several medications are considered the gold standard, each with unique benefits and limitations. Methadone, a full opioid agonist, has decades of evidence supporting its effectiveness, particularly in cases of high-severity opioid dependence. However, its use is restricted to certified opioid treatment programs (OTPs), and it carries a risk of misuse, requiring close supervision. Unfortunately, methadone has failed to change with the times. The tight regulations and requirements of a daily visit to a methadone clinic make long-term compliance difficult and lead people to seek alternative treatments based on convenience. Buprenorphine, a partial agonist available in formulations such as Suboxone (combined with naloxone), Sublocade, and Brixadi, presents a lower risk of overdose and has become a mainstay of outpatient care. Extended-release injectable forms of buprenorphine have been shown to significantly improve treatment adherence and reduce diversion. Naltrexone, available in oral form and as the extended-release injection Vivitrol, is an opioid antagonist with no abuse potential. However, it requires full detoxification prior to initiation, which can be a barrier for many patients.
For individuals with Alcohol Use Disorder (AUD), naltrexone is also commonly used to reduce the pleasurable effects of alcohol and decrease cravings. Acamprosate (Campral) works differently, by restoring neurotransmitter balance in the brain after withdrawal, which can help maintain abstinence. Disulfiram (Antabuse) operates through aversive conditioning: if alcohol is consumed while on the medication, it causes intense physical illness, which discourages use. While effective for some, adherence can be a challenge due to the nature of this mechanism.
In contrast, treatment for Stimulant Use Disorder remains an area of significant unmet need, as no FDA-approved medications currently exist. However, several off-label pharmacologic options are being explored. These include bupropion combined with naltrexone, mirtazapine, modafinil, and topiramate, each showing varying degrees of efficacy in early studies. While none have yet received official approval, ongoing clinical trials may pave the way for targeted treatments in the future.
The evolving medication landscape underscores the importance of individualized treatment planning, integrating both pharmacological and behavioral interventions to support long-term recovery across substance categories.
Barriers to Access and Adherence: Only 1 in 10 Receives MAT
Why do only about 1 in 10 people with OUD get MAT? Barriers to effective treatment include the persistent stigma that Medication-Assisted Treatment (MAT) is simply “trading one drug for another,” despite its reducing harm. Two camps remain: those who support a harm reduction model and those who believe that abstinence is the only way forward for recovery. Regulatory hurdles further complicate access, as requirements vary across state and federal levels. A lack of integration also plays a role, with poor screening for substance use disorders in both mental health and primary care settings, along with significant provider shortages in rural areas. Patients often experience mistrust due to concerns about side effects and fear of judgment. Lastly, cost and insurance barriers persist, particularly with limited coverage for injectable treatments like Sublocade and Vivitrol.
What’s Coming: The Future of SUD Pharmacotherapy
Emerging therapies for substance use disorder (SUD) are expanding beyond traditional medications, with early studies showing promise across several novel approaches. GLP-1 receptor agonists, such as semaglutide and liraglutide, originally developed for diabetes and weight loss, are now being investigated for their potential to reduce alcohol and cocaine use. These agents may work by modulating dopamine pathways, potentially dampening the brain’s reward response to substances. Preliminary findings in both animal models and small human studies suggest a reduction in craving and intake, sparking considerable interest in larger clinical trials.
Tesofensine, a triple monoamine reuptake inhibitor (SNDRI), is also being studied for its dual impact on stimulant use and obesity. By enhancing levels of dopamine, norepinephrine, and serotonin, tesofensine appears to suppress appetite and elevate mood, which may help mitigate some of the underlying drivers of stimulant misuse. Early-phase studies report reductions in food and substance cravings, though more research is needed to validate these outcomes in broader populations.
Meanwhile, ketamine and other psychedelics are gaining attention for their ability to promote neuroplasticity and disrupt compulsive use patterns. Trials examining ketamine-assisted psychotherapy and psilocybin for alcohol use disorder have shown promising early results, including sustained reductions in use and improvements in mood and motivation.
In tandem with pharmacologic innovations, digital therapeutics are also transforming the treatment landscape. When paired with medications, these tools can offer real-time coaching, behavioral tracking, and contingency management, in addition to psychoeducational curriculum and evidence-based therapies delivered immediately when a client most needs support. These digital therapeutics have shown great success in enhancing adherence, engagement, and outcomes. As evidence continues to build, these integrative strategies could represent the next frontier in personalized, technology-enhanced addiction care.
Beyond Traditional Medications: Peptides and Supplements in SUD Recovery
A growing body of research is exploring how peptides and targeted supplements may support recovery from substance use disorders (SUD) by addressing underlying neurological, psychological, and physiological imbalances. These agents, though not yet part of mainstream treatment guidelines, offer promising adjunctive strategies for individuals in early recovery and beyond.
Among the most studied peptides, Selank stands out for its anxiolytic effects, working through modulation of GABA, serotonin, and dopamine systems. Originally developed in Russia, early human and animal studies suggest that Selank may reduce anxiety and improve stress resilience, which are key factors that often contribute to relapse (Chaban et al., 2016). Similarly, Semax, a synthetic peptide with nootropic properties, has been shown to increase brain-derived neurotrophic factor (BDNF) and dopamine function, potentially improving cognitive flexibility and emotional regulation in individuals affected by long-term substance use (Myasoedov et al., 2013).
BPC-157, another peptide of interest, has demonstrated neuroprotective and anti-inflammatory properties in preclinical studies. It may help repair neuroinflammation and restore gut-brain axis balance, which are important considerations given the emerging link between gut health and mental health in addiction recovery (Sikiric et al, 2018). Additionally, Oxytocin, known as the “bonding hormone,” is being investigated for its ability to reduce drug cravings and promote prosocial behavior. Early trials suggest it may enhance trust, emotional connection, and therapeutic alliance, making it a compelling tool for relational repair during treatment (Lee et al., 2016).
Supplements are also playing an increasingly recognized role. N-acetylcysteine (NAC) has been one of the most studied in addiction contexts, especially for cocaine, cannabis, and alcohol use. It works by restoring glutamate and dopamine balance in the brain and has been associated with reduced cravings in several clinical trials (Dean et al., 2011). L-theanine, an amino acid derived from green tea, promotes a state of calm without sedation and may help regulate the nervous system in early recovery phases. Magnesium glycinate and magnesium threonate are often used to support stress regulation, improve sleep, and enhance cognitive recovery, all of which are critical in the post-acute withdrawal stage (Nathan et al., 2006).
Basic nutritional support also remains essential. Deficiencies in omega-3 fatty acids, vitamin D, B-complex vitamins, and zinc are common in individuals with SUD, and correcting these imbalances has been associated with improvements in mood, cognition, and immune function. As nutritional psychiatry gains traction, these supplements are becoming more integrated into holistic recovery programs.
Though further large-scale studies are needed, the early evidence supporting peptides and supplements is compelling, especially when these tools are used in conjunction with evidence-based treatments such as behavioral therapy and medication-assisted treatment. Their ability to support mood, cognition, and neural repair makes them a promising frontier in personalized, integrative care for substance use recovery (Koob & Volkow, 2016).
Final Thoughts
If we treated diabetes the way we treat addiction, we’d withhold insulin from patients who “weren’t ready.” That’s unacceptable, and it’s time we hold addiction medicine to the same standard. The science is here. The challenge now is willpower, funding, and compassion. Let’s meet the moment.
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Struggling with substance use or know someone who is? We can help. Call or text us at (877) 465-6650 to inquire about our no-cost services for individuals with Medicare and Medicaid.
References
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