Plant-derived Bioactive Compounds in Schizophrenia: Pharmacological Mechanisms and Emerging Drug Targets
Marta Raquel Costa Loureiro, João Paulo Fernandes, António ParanhosIntroduction:
Schizophrenia is a chronic and heterogeneous psychiatric disorder characterized by positive and negative symptoms, together with cognitive dysfunction. Because current antipsychotic-based treatment remains limited for negative and cognitive symptoms, adjunctive strategies targeting additional pathophysiological pathways are needed.
Methods:
This narrative review synthesized preclinical and clinical evidence on selected medicinal plants, standardized extracts and plant-derived bioactive compounds investigated as adjunctive approaches in schizophrenia. Evidence was organized according to plant source or compound, putative mechanisms of action, preclinical findings, clinical evidence, symptom domains, antipsychoticassociated adverse effects and pharmacological pathways.
Results:
The reviewed interventions targeted oxidative stress, neuroinflammation, glutamatergic and dopaminergic dysfunction, endocannabinoid modulation, mitochondrial function and neurotrophic signaling. Randomized clinical evidence was available for a limited subset of candidates, including cannabidiol, Withania somnifera, L-theanine, curcumin-based formulations, Ginkgo biloba and Panax quinquefolius. Most other agents remained supported mainly by preclinical, mechanistic or indirect clinical evidence. Potential benefits included improvement in positive, negative or cognitive symptom domains and attenuation of selected antipsychotic-associated adverse effects.
Discussion:
The evidence base remains heterogeneous, with substantial variation in formulations, doses, treatment duration, outcome measures and translational maturity. Bioavailability and standardization are major challenges for several compounds, particularly polyphenols.
Conclusion:
Plant-based interventions should be positioned as adjunctive, not alternative, approaches. Further adequately powered clinical trials using standardized preparations are required to clarify efficacy, safety, optimal dosing and clinical relevance in schizophrenia.