Partial Dopamine Agonists May Treat Both Schizophrenia and Cannabis Addiction Simultaneously | Research

The takeaway

A preclinical review and modeling study suggests partial D2/D3 dopamine receptor agonists like cariprazine could treat both psychotic symptoms and cannabis use disorder simultaneously by stabilizing dysregulated dopamine signaling.

Psychiatrists treating dual diagnosis, psychopharmacology researchers, and patients with schizophrenia and co-occurring CUD.

What the researchers found

Partial D2/D3 agonists (aripiprazole, brexpiprazole, cariprazine) have unique pharmacology: they activate dopamine receptors enough to prevent withdrawal/craving but not enough to worsen psychosis. Computational modeling predicted cariprazine would best balance antipsychotic and anti-addiction properties due to its high D3 affinity. Preliminary clinical evidence supports reduced cannabis use in schizophrenia patients on partial agonists.

Why it matters

Cannabis use disorder co-occurs in 25-50% of schizophrenia patients and worsens outcomes. Current antipsychotics do not address the addiction. A medication that treats both could significantly improve outcomes for this dual-diagnosis population.

The numbers in context

25-50% CUD comorbidity in schizophrenia. Three partial agonists modeled. Cariprazine predicted optimal due to D3 preference. Preliminary clinical data supports reduced cannabis use.

How the study worked

Narrative review of preclinical and clinical evidence combined with computational receptor occupancy modeling for three partial D2/D3 agonists across dopamine signaling scenarios.

What this study cannot tell us

Primarily theoretical with computational modeling. Limited clinical evidence for anti-cannabis effects. Individual responses vary widely. D3 receptor role in cannabis addiction still debated.

How to read the evidence

Innovative computational approach with biological rationale, but primarily theoretical with limited clinical validation.

When this study was published

2025 review with receptor occupancy modeling for dual-diagnosis treatment.

The bigger picture

Treating co-occurring disorders with a single medication reduces pill burden, side effects, and treatment complexity. The partial agonist concept — not fully blocking or activating receptors — represents a paradigm shift in psychopharmacology.

Questions still open

Will randomized trials confirm cariprazine reduces cannabis use in schizophrenia?
Could partial agonists help cannabis use disorder in non-psychotic populations?

Common questions

Can one medication treat both schizophrenia and cannabis addiction?

This study suggests partial dopamine agonists, especially cariprazine, may address both by stabilizing dopamine signaling — reducing psychotic symptoms without worsening addiction.

Why do so many people with schizophrenia use cannabis?

25-50% of schizophrenia patients have cannabis use disorder. Dopamine dysregulation contributes to both conditions, which is why medications targeting dopamine balance may help both.

Read the original research

Partial Dopamine D2/3 Agonists and Dual Disorders: A Retrospective-Cohort Study in a Real-World Clinical Setting on Patients with Schizophrenia Spectrum Disorders and Cannabis Use Disorder.

Current neuropharmacology, 23(8), 996-1006

View on PubMed ↗Publisher’s paper ↗

Citation

Trovini, Giada; Lombardozzi, Ginevra; Kotzalidis, Georgios D; Pagano, Ilaria; Amici, Emanuela; Giovanetti, Valeria; Perrini, Filippo; Fagiolini, Andrea; De Filippis, Sergio. (2025). Partial Dopamine D2/3 Agonists and Dual Disorders: A Retrospective-Cohort Study in a Real-World Clinical Setting on Patients with Schizophrenia Spectrum Disorders and Cannabis Use Disorder.. Current neuropharmacology, 23(8), 996-1006. https://doi.org/10.2174/011570159X350599241214042724