Title : Emerging pharmacotherapies for substance use disorders: A narrative review of novel agents and clinical implications
Abstract:
Background: Substance use disorders (SUDs) represent a significant and growing public health burden, with alcohol use disorder (AUD), opioid use disorder (OUD), and stimulant use disorder (StUD) accounting for disproportionate rates of morbidity, mortality, and healthcare utilization. Despite the availability of FDA-approved pharmacotherapies—including methadone, buprenorphine, and naltrexone for OUD, and naltrexone and acamprosate for AUD—treatment engagement and long-term outcomes remain suboptimal. This gap has driven growing interest in novel pharmacological targets and repurposed agents with emerging evidence in SUD treatment.
Objective: This narrative review aims to synthesize current evidence on emerging and investigational pharmacotherapies across multiple substance use disorders, with attention to clinical applicability in outpatient psychiatric and addiction medicine settings.
Methods: A narrative review of peer-reviewed literature published between 2019 and 2025 was conducted using PubMed, PsycINFO, and ClinicalTrials.gov. Search terms included combinations of “substance use disorder,” “pharmacotherapy,” “emerging treatments,” and substance-specific terms. Clinical trials, systematic reviews, meta-analyses, and mechanistic studies were included.
Results: Several pharmacological agents demonstrate promising preliminary evidence. GLP-1 receptor agonists (e.g., semaglutide, liraglutide) have shown reductions in alcohol and opioid craving through dopaminergic and reward pathway modulation, with early clinical trial data supporting their investigation for AUD and OUD. Gabapentinoids, particularly gabapentin, show evidence in managing alcohol withdrawal and reducing craving, though concerns regarding misuse potential warrant careful clinical consideration. Psilocybin-assisted therapy has demonstrated significant reductions in alcohol and tobacco use in Phase II trials, with ongoing Phase III investigations. Sodium oxybate shows efficacy for AUD in European contexts, with renewed interest in its US clinical application. For stimulant use disorder, where no FDA-approved agents exist, mixed amphetamine salts, bupropion combined with naltrexone, and ibudilast show emerging phase II efficacy data.
Conclusions: The pharmacotherapy landscape for SUDs is rapidly evolving, with several novel agents demonstrating mechanistically distinct and clinically meaningful effects. Clinicians, particularly in outpatient behavioral health settings, should remain informed of emerging evidence to optimize individualized treatment planning. Integration of these agents into existing frameworks—including dual-diagnosis care—represents a critical pathway toward improving long-term recovery outcomes.
