PhD Scientific Days 2026

Mental Health Sciences 3.

Dopamine D2/D3 Partial Agonists Reduce Craving in Substance Use Disorders: A Systematic Review and Meta Analysis

Name of the presenter

Lucatz, Amit

Institute/workplace of the presenter

Centre for Translational Medicine, Semmelweis University, Budapest, Hungary

Authors

Amit Lucatz¹, Hasika Parthasarathy¹, Amir Makolli¹, Karen Fazekas¹, Anna Szűcs², János Réthelyi³
1: Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
2: Institute of Behavioural Sciences, Semmelweis University, Budapest, Hungary
3: Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction
Substance use disorders (SUD) affect approximately 200 million people globally and are associated with high relapse rates and poor adherence. Dopamine dysregulation, particularly at the D2 and D3 receptors, is a core neurobiological mechanism across addictions. Higher craving levels are associated with worse prognosis, making craving a relevant therapeutic target. D2/D3 partial agonists, including aripiprazole, brexpiprazole, and cariprazine, may function as dopamine stabilizers and have shown preliminary potential in reducing craving, especially in dual-diagnosis populations.
Aims
To investigate the efficacy of D2/D3 partial agonists in reducing craving in substance use disorders
Methods
This systematic review and meta-analysis followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420251232201). Eligibility followed the Population, Intervention, Comparator, Outcome (PICO) framework. A systematic search of 3 databases in November 2025 identified 5585 records. Duplicates were removed, titles and abstracts were screened independently by two reviewers (AL and HP) using a predefined protocol, followed by a full-text review. Inter-rater reliability was very high (κ = 0.84 and κ = 0.94, respectively). Discrepancies were resolved by consensus with a third party. Forward and backward citation chasing was performed.
Results
Twenty-five full-text articles were included in the systematic review. Of these, 12 were included in the meta-analysis for the primary outcome, change in Visual Analogue Scale (VAS) craving scores. The pooled analysis showed a mean decrease of 3.24 points in craving (95% CI, 2.06 to 4.42), based on 281 participants. Subgroup analysis by substance showed an even higher, significant reduction in craving in cannabis use disorder, with a mean decrease of 5.29 points on the VAS.
Conclusion
Current evidence suggests, with a low level of certainty, that D2/D3 partial agonists can reduce craving in the SUD population, with notable decreases in cannabis use disorder. Rigorous, blinded randomized controlled trials are needed in the future. Clinicians may consider these medications as a first-line option in schizophrenia spectrum disorder patients with concurrent SUD to target both pathologies simultaneously.
Funding
Supported by the Semmelweis University Research, Development and Innovation Fund.